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Merge branch 'ocr-v2'

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LLLin000 2026-06-29 12:32:19 +08:00
commit d4b230dfe4
4 changed files with 123 additions and 134 deletions
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6
paperforge/worker/ocr_bio.py
View file

@ -87,12 +87,12 @@ def _bio_text_score(text: str) -> tuple[int, set[str]]:
"""Score 0-5 and return category set.
Category-weighted: each signal type contributes independently.
Returns (0, set()) for text too short (<5 words) or too long (>80 words).
Returns (0, set()) for text too short (<5 words) or too long (>200 words).
"""
if not text:
return 0, set()
words = text.split()
if len(words) < 5 or len(words) > 80:
if len(words) < 5 or len(words) > 200:
return 0, set()
categories: set[str] = set()
@ -462,7 +462,7 @@ def post_ref_bio_cleanup(
continue
role = block.get("role", "")
if role not in {"reference_item", "reference_heading", "figure_caption"}:
if role not in {"reference_item", "reference_heading", "figure_caption", "structured_insert_candidate"}:
continue
text = str(block.get("text", "") or "")

22
paperforge/worker/ocr_figures.py
View file

@ -4475,8 +4475,15 @@ def build_figure_inventory(structured_blocks: list[dict], page_width: float = 12
}
)
if unresolved_clusters:
consumed = {bid for uc in unresolved_clusters for bid in uc["media_block_ids"]}
unmatched_assets = [a for a in unmatched_assets if a.get("block_id", "") not in consumed]
consumed = {
(int(uc.get("page", 0) or 0), str(bid))
for uc in unresolved_clusters
for bid in uc["media_block_ids"]
}
unmatched_assets = [
a for a in unmatched_assets
if (int(a.get("page", 0) or 0), str(a.get("block_id", ""))) not in consumed
]
unmatched_assets = _recompute_final_unmatched_assets(assets, used_asset_page_ids, unresolved_clusters)
@ -4525,8 +4532,15 @@ def build_figure_inventory(structured_blocks: list[dict], page_width: float = 12
}
)
if unresolved_clusters:
consumed_dense = {bid for uc in unresolved_clusters for bid in uc["media_block_ids"]}
unmatched_assets = [a for a in unmatched_assets if a.get("block_id", "") not in consumed_dense]
consumed_dense = {
(int(uc.get("page", 0) or 0), str(bid))
for uc in unresolved_clusters
for bid in uc["media_block_ids"]
}
unmatched_assets = [
a for a in unmatched_assets
if (int(a.get("page", 0) or 0), str(a.get("block_id", ""))) not in consumed_dense
]
# --- P2: page-local caption grammar validation ---
local_pairing_hypotheses = _validate_page_local_caption_grammar(

16
paperforge/worker/ocr_rebuild.py
View file

@ -269,6 +269,22 @@ def run_derived_rebuild_for_keys(vault: Path, keys: list[str], progress_bar=None
figure_inventory = build_figure_inventory(structured)
write_back_figure_roles(figure_inventory, structured)
# Author bio passes (Pass B + Pass C)
from paperforge.worker.ocr_bio import (
residual_author_bio_pass,
post_ref_bio_cleanup,
prune_figure_inventory_after_bio,
_resolve_ref_start_page,
)
residual_author_bio_pass(
figure_inventory, structured,
include_ambiguous=False, include_weak_matched=False,
)
ref_start_page = _resolve_ref_start_page(structured)
if ref_start_page is not None:
post_ref_bio_cleanup(figure_inventory, structured, ref_start_page=ref_start_page)
prune_figure_inventory_after_bio(figure_inventory)
# Rebuild reader figures
from paperforge.worker.ocr_figure_reader import synthesize_reader_figures

213
tests/fixtures/ocr_real_papers/4AG67PBH/block_trace.csv vendored
View file

@ -33,35 +33,32 @@ Guimarães 4800-058, Portugal","[607, 1287, 942, 1343]",footnote,0.7,"[""footnot
1,19,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[687, 1479, 1097, 1499]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[92, 32, 311, 106]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_side_zone,support_like,none,False,False
2,1,header,small science,"[1008, 14, 1092, 81]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_side_zone,support_like,short_fragment,False,False
2,2,header,www.small-science-journal.com,"[878, 86, 1090, 106]",noise,0.9,"[""header label""]",noise,0.9,frontmatter_side_zone,support_like,none,False,False
www.advancedsciencenews.com","[92, 32, 311, 106]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
2,1,header,small science,"[1008, 14, 1092, 81]",noise,0.9,"[""header label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
2,2,header,www.small-science-journal.com,"[878, 86, 1090, 106]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
2,3,text,"electrical potentials generated in loaded bone: the piezoelectric effect (mainly on dry bone, and attributed to the crystalline micelle of collagen molecules) $ ^{[16,18,19]} $ and the streaming poten","[89, 139, 582, 402]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,4,text,Many researchers have explored the effects of electromagnetic fields on the tightly orchestrated bone remodeling process. $ ^{[30-32]} $ Several animal models have been used to test the efficacy of el,"[90, 402, 582, 843]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,5,text,"Three methods have been used to provide electromagnetic stimulation, which includes the delivery of electrical fields (EF) and magnetic fields (MF). Direct electric current (DC) stimulation, requiring","[90, 844, 583, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,text,"tissues. CMF stimulation combines these coil-generated PEMF
with an overlapping static MF provided by permanent
magnets.[47] Both CC and IC methods have been proposed as
therapeutic strategies to mini","[598, 138, 1092, 427]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,6,text,,"[598, 138, 1092, 427]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
2,7,text,"We here comprehensively overview the most relevant bone healing-related outcomes induced by IC in vivo, both in animal models and human patients, aiming to identify top-performer magnetic stimulation ","[598, 425, 1093, 1007]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,8,paragraph_title,2. Pre-Clinical Studies of IC Therapies 2.1. Overview of IC Pre-Clinical Designs,"[600, 1044, 973, 1107]",section_heading,0.85,"[""paragraph_title label with numbering: 2. Pre-Clinical Studies of IC Therapies 2.1. Overview of IC ""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
2,9,footer,,"[601, 1083, 911, 1107]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,empty,False,False
2,8,paragraph_title,2. Pre-Clinical Studies of IC Therapies,"[600, 1044, 973, 1071]",section_heading,0.85,"[""paragraph_title label with numbering: 2. Pre-Clinical Studies of IC Therapies""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
2,9,paragraph_title,2.1. Overview of IC Pre-Clinical Designs,"[601, 1083, 911, 1107]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.1. Overview of IC Pre-Clinical Designs""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
2,10,text,"Our search has retrieved 73 pre-clinical studies using IC stimulators to treat musculoskeletal conditions in animal models (Table S1, Supporting Information). PEMF was by far the most used IC stimulat","[599, 1127, 1092, 1372]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,11,text,"The pre-clinical therapeutic efficacy of IC stimulation has been tested for several musculoskeletal conditions, namely bone defects, implants' osseointegration, conditions of low bone","[599, 1371, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
2,12,footer,"Small Sci. 2024, 4, 2300303","[93, 1479, 261, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,13,footer,2300303 (2 of 25),"[400, 1476, 541, 1499]",noise,0.9,"[""footer label""]",noise,0.9,frontmatter_main_zone,reference_like,reference_numeric_dot,False,False
2,14,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[680, 1479, 1091, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
2,15,aside_text,"26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar","[1154, 23, 1171, 1542]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,frontmatter_side_zone,support_like,none,False,False
2,15,aside_text,"26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar","[1154, 23, 1171, 1542]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,body_zone,body_like,none,False,False
3,0,header,"ADVANCED
SCIENCE NEWS
www.advancedsciencenews.com","[98, 31, 316, 106]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,1,header,small science,"[1015, 14, 1098, 80]",noise,0.9,"[""header label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
3,2,header,www.small-science-journal.com,"[884, 86, 1097, 107]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
3,3,figure_title,A,"[174, 143, 194, 163]",figure_inner_text,0.9,"[""panel label / figure inner text: A""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
3,4,figure_title,IC stimulation methods in animal models,"[233, 158, 411, 203]",non_body_insert,0.85,"[""figure_title label: IC stimulation methods in animal models""]",figure_caption,0.85,body_zone,body_like,none,False,False
3,4,figure_title,IC stimulation methods in animal models,"[233, 158, 411, 203]",figure_caption,0.85,"[""figure_title label: IC stimulation methods in animal models""]",figure_caption,0.85,body_zone,body_like,none,True,True
3,5,chart,,"[223, 217, 480, 424]",media_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,body_like,empty,True,True
3,6,figure_title,B,"[537, 142, 555, 162]",figure_inner_text,0.9,"[""panel label / figure inner text: B""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
3,7,figure_title,Animal models receiving IC stimulation,"[622, 151, 921, 174]",non_body_insert,0.85,"[""figure_title label: Animal models receiving IC stimulation""]",figure_caption,0.85,body_zone,legend_like,none,False,False
3,7,figure_title,Animal models receiving IC stimulation,"[622, 151, 921, 174]",figure_caption_candidate,0.85,"[""figure_title label: Animal models receiving IC stimulation""]",figure_caption,0.85,body_zone,legend_like,none,False,False
3,8,chart,,"[517, 198, 1020, 487]",media_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,body_like,empty,True,True
3,9,figure_title,C,"[174, 506, 194, 527]",figure_inner_text,0.9,"[""panel label / figure inner text: C""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
3,10,figure_title,Musculoskeletal conditions assessed in animal models,"[382, 514, 849, 539]",figure_caption,0.85,"[""figure_title label: Musculoskeletal conditions assessed in animal models""]",figure_caption,0.85,body_zone,legend_like,none,True,True
@ -70,7 +67,7 @@ www.advancedsciencenews.com","[98, 31, 316, 106]",noise,0.9,"[""header label""]"
3,13,figure_title,E,"[621, 908, 639, 930]",figure_inner_text,0.9,"[""panel label / figure inner text: E""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True
3,14,image,,"[179, 920, 586, 1232]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,True,True
3,15,image,,"[623, 923, 963, 1239]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,True,True
3,16,figure_title,Figure 1. General trends of IC stimulation on pre-clinical studies with animal models of musculoskeletal disorders. A) IC stimulation methods applied; B) Type of animal models used; C) Musculoskeletal,"[97, 1255, 1098, 1418]",figure_caption,0.92,"[""figure_title label: Figure 1. General trends of IC stimulation on pre-clinical s""]",figure_caption,0.92,display_zone,support_like,figure_number,True,True
3,16,figure_title,Figure 1. General trends of IC stimulation on pre-clinical studies with animal models of musculoskeletal disorders. A) IC stimulation methods applied; B) Type of animal models used; C) Musculoskeletal,"[97, 1255, 1098, 1418]",figure_caption,0.92,"[""figure_title label: Figure 1. General trends of IC stimulation on pre-clinical s""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
3,17,footer,"Small Sci. 2024, 4, 2300303","[99, 1479, 267, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
3,18,number,2300303 (3 of 25),"[407, 1476, 547, 1499]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
3,19,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[687, 1479, 1096, 1499]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
@ -81,10 +78,7 @@ www.advancedsciencenews.com","[92, 31, 312, 107]",noise,0.9,"[""header label""]"
4,1,header,small science,"[1008, 13, 1091, 81]",noise,0.9,"[""header label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
4,2,header,www.small-science-journal.com,"[877, 86, 1091, 107]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
4,3,text,"mineral density (BMD), soft tissue healing, spine fusion, and osteoarthritis, as well as in healthy subjects. Bone defects $ ^{[59-81]} $ were the most assessed condition (in 27.4% of the studies; Fig","[89, 137, 582, 298]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,4,text,"in pre-clinical studies to deliver PEMF is schematically presented
in Figure 1D. Additionally, Figure 1E portrays a photograph of an
actual IC stimulation device used in a pre-clinical study here
revi","[599, 137, 1092, 226]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,4,text,,"[599, 137, 1092, 226]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
4,5,text,"The tested pulse frequencies ranged from 1 Hz $ ^{[73]} $–400 Hz, $ ^{[66]} $ with the most tested frequency being 15 Hz (in 36.5% of the tested frequencies, Figure 2A). Unless stated otherwise, all","[600, 224, 1093, 297]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
4,6,chart,,"[192, 337, 582, 844]",media_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,body_like,empty,True,True
4,7,chart,,"[615, 338, 993, 851]",media_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,body_like,empty,True,True
@ -105,11 +99,8 @@ www.advancedsciencenews.com","[98, 32, 317, 106]",noise,0.9,"[""header label""]"
5,5,paragraph_title,2.2. Effects of IC Stimulation on Small-Sized Animals,"[97, 593, 505, 616]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2. Effects of IC Stimulation on Small-Sized Animals""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,6,text,"Rats (Rattus norvegicus) were the most used animal models to test IC stimulation in vivo (Figure 1). Rats are anatomic and physiologically well-studied, have fast growth and reproductive rates and req","[96, 637, 588, 927]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,7,text,PEMF have been applied to determine whether bone tissues from healthy rats responded well to electromagnetic stimuli. These studies were focused on major macroscopical and micro-architectural effects ,"[94, 926, 589, 1441]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,8,text,"Increased expression levels of femur p-PKA and p-CREB, soluble
adenyl cyclase (sAC), and serum cAMP were also observed, indi-
cating osteogenic effects through the sAC/cAMP/PKA/CREB
signaling pathway.","[605, 137, 1097, 230]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,9,paragraph_title,2.2.1. Managing Bone Defects in Small-Sized Animals Through IC Stimulation,"[607, 258, 1006, 308]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.1. Managing Bone Defects in Small-Sized Animals Through ""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,8,text,,"[605, 137, 1097, 230]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
5,9,paragraph_title,2.2.1. Managing Bone Defects in Small-Sized Animals Through IC Stimulation,"[607, 258, 1006, 308]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.1. Managing Bone Defects in Small-Sized Animals Through ""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
5,10,text,"PEMF of rather different parameters were applied to heal rat bone defects (fractures and osteotomies) and consolidate bone fusions, with promising effects such as faster osseous bridging, assessed by ","[604, 327, 1099, 883]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,11,text,"Studies using PEMF of higher pulse frequencies, from 20 to 400 Hz, have mostly reported positive impacts on bone healing (Figure 2). For example, PEMF of 50 Hz and 1.5 mT, applied to rat tibial fractu","[605, 884, 1098, 1327]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
5,12,text,"An FDA-approved PEMF device, Physio-Stim, delivering pulses at the most commonly used frequency (15 Hz pulse), of triangular or sawtooth bursts at 3.85 kHz, and 2.0 mT with a daily exposure of 3 h day","[604, 1326, 1098, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
@ -123,14 +114,11 @@ www.advancedsciencenews.com","[92, 32, 312, 106]",noise,0.9,"[""header label""]"
6,1,header,small science,"[1008, 13, 1092, 80]",noise,0.9,"[""header label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
6,2,header,www.small-science-journal.com,"[878, 86, 1091, 106]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
6,3,text,"parameters over 3 and 5 weeks, and reported higher osteotomy gap filling and a 2-fold increase in hard callus formation rate and volume, and in bending strength.[69] Another study applied this stimula","[89, 139, 583, 406]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,4,paragraph_title,2.2.2. Studies of IC Stimulation for Soft Tissue Disorders in Small-Sized Animals,"[91, 432, 507, 480]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.2. Studies of IC Stimulation for Soft Tissue Disorders i""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
6,4,paragraph_title,2.2.2. Studies of IC Stimulation for Soft Tissue Disorders in Small-Sized Animals,"[91, 432, 507, 480]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.2. Studies of IC Stimulation for Soft Tissue Disorders i""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
6,5,text,"Physio-Stim was also used for soft tissue healing in rats $ ^{[107-109]} $ and PEMF of parameters similar to the ones described above (15 Hz; ≈2 mT) led to radiographical, biomechanical, and histologi","[89, 498, 582, 813]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,6,paragraph_title,2.2.3. Tackling Osteoporosis in Small-Sized Animals Through IC Stimulation,"[91, 839, 562, 885]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.3. Tackling Osteoporosis in Small-Sized Animals Through ""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
6,6,paragraph_title,2.2.3. Tackling Osteoporosis in Small-Sized Animals Through IC Stimulation,"[91, 839, 562, 885]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.3. Tackling Osteoporosis in Small-Sized Animals Through ""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
6,7,text,"Osteoporosis, a highly relevant musculoskeletal disorder, is usually studied in animal models by mimicking osteoporotic phenotypes of low BMD, either through ovariectomy (OVX; the most used osteoporos","[90, 905, 582, 1441]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,8,text,"www.small science journal.com
better results than if the treatment was initiated 12 weeks
post-OVX, highlighting that the timing of PEMF therapy initia-
tion is important to achieve optimal effects.[1","[597, 140, 1094, 953]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,8,text,,"[597, 140, 1094, 953]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
6,9,text,"For disuse osteoporosis models, PEMF of 10 Hz and 3.82 mT, for 40 min day $ ^{-1} $ over 12 weeks, improved bone microarchitecture (increased Tb.Area and Tb.N; reduced Tb.S) and increased serum OC by ","[598, 955, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
6,10,footer,"Small Sci. 2024, 4, 2300303","[93, 1479, 261, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
6,11,footer,2300303 (6 of 25),"[400, 1476, 541, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False
@ -144,13 +132,10 @@ www.advancedsciencenews.com","[98, 32, 316, 106]",noise,0.9,"[""header label""]"
7,3,text,"animals), and acted on bone remodeling pathways: +42.1% serum TGF-β1 and −21.7% serum IL-6.[111] PEMF of higher frequency (50 Hz) and lower MF strength (0.6 mT), applied for 1.5 h day−1 over 4 weeks, ","[95, 139, 588, 582]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,4,text,"In cases of drug-induced osteoporosis, PEMF of 7.3 Hz and 0.8 mT for 1 h day $ ^{-1} $ over 4 weeks reverted heparin-induced bone loss, increasing new bone area by 4-fold and reducing serum CTX ( $ -2","[95, 583, 588, 805]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,5,text,"Finally, in senile osteoporosis models, PEMF of 8 Hz and 3.82 mT (applied for 40 min day $ ^{-1} $) partially reverted aging-related bone deterioration, after 12 weeks of stimulation. Improved BMD, bo","[95, 805, 588, 1052]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,6,paragraph_title,2.2.4. IC Stimulation to Improve Implant Osseointegration in Small-Sized Animals,"[97, 1080, 548, 1127]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.4. IC Stimulation to Improve Implant Osseointegration in""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
7,6,paragraph_title,2.2.4. IC Stimulation to Improve Implant Osseointegration in Small-Sized Animals,"[97, 1080, 548, 1127]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.4. IC Stimulation to Improve Implant Osseointegration in""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
7,7,text,"IC stimulation was also tested on rat implants’ osseointegration. A study applying PEMF with the most common parameters (15 Hz, 1.0 mT), has compared the effectiveness of 1 vs 3 h day $ ^{-1} $ exposu","[95, 1148, 587, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,8,text,"increased peri-implant and osteotomy ossification were observed
in the group stimulated for 0.5 h twice-a-day with PEMF of 50 Hz
and high MF strength (72 mT), demonstrating that this IC ther-
apy can a","[604, 138, 1098, 497]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,9,paragraph_title,2.2.5. Handling Osteoarthritis in Small-Sized Animals with IC Stimulation,"[606, 525, 1064, 572]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.5. Handling Osteoarthritis in Small-Sized Animals with I""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
7,8,text,,"[604, 138, 1098, 497]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
7,9,paragraph_title,2.2.5. Handling Osteoarthritis in Small-Sized Animals with IC Stimulation,"[606, 525, 1064, 572]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.2.5. Handling Osteoarthritis in Small-Sized Animals with I""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
7,10,text,"In two studies of a rat model mimicking temporomandibular joint osteoarthritis, PEMF of 2 mT and 15 Hz pulses (bursts of 5 kHz), applied for 2 h day $ ^{-1} $ over 3 or 6 weeks, partially reversed mic","[604, 593, 1099, 1218]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,11,text,"Other animals used as osteoarthritis models are guinea pigs (Cavia porcellus) of the Dunkin-Hartley breed, that spontaneously develop degenerative joint diseases around 3 months old. $ ^{[104]} $ Impr","[605, 1216, 1099, 1441]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
7,12,footer,"Small Sci. 2024, 4, 2300303","[99, 1479, 267, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
@ -165,9 +150,9 @@ www.advancedsciencenews.com","[92, 32, 312, 106]",noise,0.9,"[""header label""]"
8,3,text,"two pulse frequencies: 3/ and 75 Hz. Both frequencies lowered Fibrillation Index (FI) and SBT, with the 75 Hz being more beneficial to cartilage (+20.6% thickness; −18.5% cartilage FI). Nevertheless, ","[90, 137, 582, 252]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,4,paragraph_title,2.3. Effects of IC Stimulation on Intermediate-Sized Animals,"[90, 285, 552, 307]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3. Effects of IC Stimulation on Intermediate-Sized Animals""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
8,5,text,"Rabbits (Oryctolagus cuniculus) are the second usual choice to study IC stimulation on bone remodeling and implants' osseointegration (Figure 1). Comparatively to smaller models, rabbits undergo more ","[90, 329, 582, 557]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,6,paragraph_title,2.3.1. Managing Bone Defects in Intermediate-Sized Animals Using IC Stimulation,"[91, 589, 539, 635]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3.1. Managing Bone Defects in Intermediate-Sized Animals U""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
8,6,paragraph_title,2.3.1. Managing Bone Defects in Intermediate-Sized Animals Using IC Stimulation,"[91, 589, 539, 635]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3.1. Managing Bone Defects in Intermediate-Sized Animals U""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
8,7,text,"Various studies investigated the IC stimulation impact on callus and bone formation in rabbits' bone defects (fractures/osteotomies).[67,68,71,72,76,79] Daily distracted tibial osteotomies, exposed to","[90, 658, 583, 1438]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,8,paragraph_title,2.3.2. IC Stimulation Effects on Implant Osseointegration in Intermediate-Sized Animals,"[601, 140, 1044, 187]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3.2. IC Stimulation Effects on Implant Osseointegration in""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
8,8,paragraph_title,2.3.2. IC Stimulation Effects on Implant Osseointegration in Intermediate-Sized Animals,"[601, 140, 1044, 187]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3.2. IC Stimulation Effects on Implant Osseointegration in""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
8,9,text,Bone replacement of rabbits' hindlimbs was commonly used to test IC-induced implant osseointegration. Matsumoto et al.[82] applied 100 Hz PEMF to improve osseointegration of dental implants in rabbits,"[598, 208, 1093, 589]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,10,text,"Another study using PEMF of similar MF strengths but at 1/10 of the pulse frequency and with increased exposure (10 Hz, 0.2–0.4 mT, 24 h day $ ^{-1} $) for up to 4 weeks, also improved osseointegratio","[599, 588, 1093, 1350]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
8,11,text,"In a study comparing tibial implants, PEMF of 1.5 Hz (quasi-square pulses), 0.18 mT, applied 8 h day $ ^{-1} $ for 6 weeks, accelerated bone formation and maturation (thicker trabeculae; most signific","[599, 1349, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
@ -182,18 +167,15 @@ www.advancedsciencenews.com","[98, 32, 318, 106]",noise,0.9,"[""header label""]"
9,2,header,www.small-science-journal.com,"[884, 86, 1097, 107]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
9,3,text,"hydroxyapatite (HA) but not around tricalcium phosphate (TCP) implants.[91] Moreover, HA tibial implants stimulated with PEMF of higher pulse frequency and MF strength (50 Hz, 8 mT), for 0.5 h twice-a","[95, 138, 588, 493]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,4,text,"Implant osseointegration was also evaluated in low BMD conditions, namely in type-1 diabetes mellitus (T1DM) rabbit models and in glucocorticoids-treated rabbits.[87,88] Both studies used the same por","[96, 494, 588, 1027]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,5,paragraph_title,2.3.3. Tackling Soft Tissue Disorders in Intermediate-Sized Animals via IC Stimulation,"[97, 1052, 587, 1099]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3.3. Tackling Soft Tissue Disorders in Intermediate-Sized ""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,5,paragraph_title,2.3.3. Tackling Soft Tissue Disorders in Intermediate-Sized Animals via IC Stimulation,"[97, 1052, 587, 1099]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.3.3. Tackling Soft Tissue Disorders in Intermediate-Sized ""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,6,text,"Regarding soft tissue healing applications, rabbits subjected to patellectomy and further exposed for 0.5 h day $ ^{-1} $ for 8–16 weeks to CMF (alternating stimuli of 76.6 Hz, 0.04 mT; constant stimu","[96, 1119, 589, 1301]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,7,paragraph_title,2.4. Effects of IC Stimulation on Medium-Sized Animals,"[96, 1327, 527, 1350]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4. Effects of IC Stimulation on Medium-Sized Animals""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,8,text,Dogs (Canis lupus familiaris) were not widely used to assess IC stimulation (Figure 1) but can offer some advantages when studying the bone response to injury and treatments. Their skeleton is similar,"[96, 1371, 588, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,9,text,"Their skeleton is similar to humans in bone weight, density,
organic and inorganic composition, water fraction, secondary
osteons, epiphyseal fusion after maturity, intracortical remodel-
ing activity","[604, 138, 1098, 362]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,10,paragraph_title,2.4.1. Managing Bone Defects in Medium-Sized Animals Through IC Stimulation,"[607, 388, 1091, 435]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4.1. Managing Bone Defects in Medium-Sized Animals Through""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,9,text,,"[604, 138, 1098, 362]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
9,10,paragraph_title,2.4.1. Managing Bone Defects in Medium-Sized Animals Through IC Stimulation,"[607, 388, 1091, 435]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4.1. Managing Bone Defects in Medium-Sized Animals Through""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,11,text,"The earliest evidence of PEMF effects on bone dates back to 1974 with a study on bone defects, when dog fibular osteotomies were stimulated for 24 h day $ ^{-1} $ with PEMF of 1 or 65 Hz over 4 weeks.","[604, 456, 1098, 678]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,12,text,"Other findings in dogs also support the use of PEMF to repair bone defects and improve the success rate of bone (spine) fusion. $ ^{[62,131]} $ Exposure of osteotomized tibiae for 1 h day $ ^{-1} $ to","[604, 678, 1098, 1011]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,13,paragraph_title,2.4.2. IC Stimulation of Medium-Sized Animals with Osteoporosis and Cartilage Defects,"[606, 1037, 1092, 1085]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4.2. IC Stimulation of Medium-Sized Animals with Osteoporo""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,13,paragraph_title,2.4.2. IC Stimulation of Medium-Sized Animals with Osteoporosis and Cartilage Defects,"[606, 1037, 1092, 1085]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4.2. IC Stimulation of Medium-Sized Animals with Osteoporo""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
9,14,text,"In OVX osteoporosis dog models, PEMF of 1.5 Hz for 1 h day $ ^{-1} $ during 12 weeks reduced bone loss from 23.1% to 9.5%, but had no effect on bone remodeling within the bone cortex. $ ^{[132]} $ For","[604, 1104, 1099, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
9,15,footer,"Small Sci. 2024, 4, 2300303","[98, 1479, 267, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
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@ -204,7 +186,7 @@ SCIENCE NEWS
www.advancedsciencenews.com","[92, 31, 311, 106]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
10,1,header,small science,"[1009, 13, 1092, 80]",noise,0.9,"[""header label""]",noise,0.9,body_zone,unknown_like,short_fragment,False,False
10,2,header,www.small-science-journal.com,"[878, 86, 1090, 106]",noise,0.9,"[""header label""]",noise,0.9,body_zone,body_like,none,False,False
10,3,paragraph_title,2.4.3. IC Musculoskeletal Studies on Medium-Sized Animals Showing No Improvement,"[91, 140, 534, 188]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4.3. IC Musculoskeletal Studies on Medium-Sized Animals Sh""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
10,3,paragraph_title,2.4.3. IC Musculoskeletal Studies on Medium-Sized Animals Showing No Improvement,"[91, 140, 534, 188]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 2.4.3. IC Musculoskeletal Studies on Medium-Sized Animals Sh""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
10,4,text,"Studies that did not report any IC-driven improvements in dogs' bone metabolism have tested the effects of i) a PEMF of 1.5 Hz, 0.1 mT, 0.5 or 1 h day $ ^{-1} $ for 12 weeks, on spine fusion rate and ","[90, 207, 583, 457]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
10,5,paragraph_title,2.5. Findings from IC Pre-Clinical Studies,"[601, 140, 920, 163]",subsection_heading,0.85,"[""paragraph_title label with numbering: 2.5. Findings from IC Pre-Clinical Studies""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
10,6,text,"Pre-clinical studies in non-human animal models have gathered evidence on the benefits of IC stimulation to treat bone and cartilage disorders, as illustrated in Figure 3. These included faster callus","[598, 183, 1093, 457]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
@ -213,7 +195,7 @@ www.advancedsciencenews.com","[92, 31, 311, 106]",noise,0.9,"[""header label""]"
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10,12,figure_title,Figure 3. Examples of biological outcomes commonly assessed in IC stimulation studies using animal models. A) Improved trabecular bone microarchitecture and cortical bone thickness of femurs of rats s,"[88, 1197, 1095, 1439]",figure_caption,0.92,"[""figure_title label: Figure 3. Examples of biological outcomes commonly assessed ""]",figure_caption,0.92,display_zone,support_like,figure_number,True,True
10,12,figure_title,Figure 3. Examples of biological outcomes commonly assessed in IC stimulation studies using animal models. A) Improved trabecular bone microarchitecture and cortical bone thickness of femurs of rats s,"[88, 1197, 1095, 1439]",figure_caption,0.92,"[""figure_title label: Figure 3. Examples of biological outcomes commonly assessed ""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
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10,15,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[681, 1479, 1090, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
@ -226,13 +208,10 @@ www.advancedsciencenews.com","[98, 32, 317, 106]",noise,0.9,"[""header label""]"
11,3,text,"properties, including bone bending stiffness, callus/bone elastic modulus, torque and load bearing, have also improved upon IC stimulation. At a molecular/biochemical level, IC stimulation activated o","[96, 139, 588, 315]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,4,text,"A general overview of IC stimulation efficacy in animal studies is presented in Figure 2, which presents improvements versus no improvements according to stimuli frequency, MF strength or exposure tim","[96, 316, 588, 756]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,5,text,"Overall, whenever biological outcomes were assessed, IC stimulation induced improvements in more than 75% of the assays, regardless of the assessed outcome (Figure 4A). Nevertheless, radiological and ","[96, 758, 588, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,6,text,"modalities that still require optimization, like RMF, or to the rel-
atively lower frequencies, field strengths, or exposure times used
(Table S1, Supporting Information). Of note, CMF and PEMF
were di","[605, 139, 1098, 293]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,6,text,,"[605, 139, 1098, 293]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
11,7,text,"In general, the studies applying IC stimulation to animal models revealed promising success rates, although radiological and biomechanical outcomes should be more thoroughly assessed. The available da","[605, 294, 1098, 518]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,8,paragraph_title,3. Clinical Studies of IC Therapies 3.1. Overview of IC Clinical Designs,"[606, 557, 942, 619]",section_heading,0.85,"[""paragraph_title label with numbering: 3. Clinical Studies of IC Therapies 3.1. Overview of IC Clin""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
11,9,footer,,"[606, 595, 888, 619]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,empty,False,False
11,8,paragraph_title,3. Clinical Studies of IC Therapies,"[607, 557, 942, 583]",section_heading,0.85,"[""paragraph_title label with numbering: 3. Clinical Studies of IC Therapies""]",section_heading,0.85,body_zone,reference_like,reference_numeric_dot,True,True
11,9,paragraph_title,3.1. Overview of IC Clinical Designs,"[606, 595, 888, 619]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.1. Overview of IC Clinical Designs""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
11,10,text,The clinical application of IC stimulation to treat multiple complications has been under development since the middle of the $ 20^{th} $ century. This therapeutic is gaining increasing popularity in,"[605, 639, 1098, 928]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,11,text,IC clinical studies mainly used devices delivering PEMF (in 88.6% of the studies) (Figure 5A). FDA-approved stimulators are the most used devices to test the efficacy of IC musculoskeletal therapy in ,"[604, 928, 1098, 1305]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
11,12,text,"Regarding the IC stimuli parameters applied in clinical studies (Figure 6A–D), there is first to highlight that the clinical studies reported less frequently the stimuli parameters applied than the pr","[604, 1305, 1098, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
@ -275,12 +254,9 @@ www.advancedsciencenews.com","[98, 31, 318, 106]",noise,0.9,"[""header label""]"
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13,16,figure_title,"Figure 5. General trends of IC clinical stimulation in clinical studies. Types of A) IC stimulation applied, and B) Stimulation devices used in human patients. ""Approved devices"" refer to stimulators ","[97, 1060, 1100, 1223]",figure_caption,0.92,"[""figure_title label: Figure 5. General trends of IC clinical stimulation in clini""]",figure_caption,0.92,display_zone,support_like,figure_number,True,True
13,16,figure_title,"Figure 5. General trends of IC clinical stimulation in clinical studies. Types of A) IC stimulation applied, and B) Stimulation devices used in human patients. ""Approved devices"" refer to stimulators ","[97, 1060, 1100, 1223]",figure_caption,0.92,"[""figure_title label: Figure 5. General trends of IC clinical stimulation in clini""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
13,17,text,"information. In the fewer clinical studies that could be analyzed here, the stimuli pulse frequencies ranged from 1.5–80 Hz, with a high prevalence of 15 Hz, the frequency used in 44.1% of the studies","[96, 1263, 588, 1423]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
13,18,text,"These highly varied from 6 μT to 5 mT (except for a higher MF
strength of 105 mT), although 45.4% (10 out of 22 studies)
applied MF strengths between 1.0 and 3.0 mT. The daily expo-
sure time ranged f","[604, 1263, 1098, 1422]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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13,21,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[687, 1479, 1097, 1499]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
@ -300,7 +276,7 @@ www.advancedsciencenews.com","[92, 31, 312, 106]",noise,0.9,"[""header label""]"
14,10,text,"durations varied from 6 days to 18 months, with a median of 3 months and an average of 5.4 months.","[90, 1076, 584, 1122]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,11,paragraph_title,3.2. Evidence of IC Clinical Efficacy in Humans,"[91, 1150, 454, 1172]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2. Evidence of IC Clinical Efficacy in Humans""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
14,12,text,"Regarding the type of non-invasive biological/clinical outcome measures used to assess the efficacy of IC stimulation, radiological imaging outcomes were the ones mainly assessed in almost all the cli","[90, 1194, 582, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,13,paragraph_title,3.2.1. Managing Bone Defects in Humans with IC Stimulation,"[602, 1079, 1063, 1101]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.1. Managing Bone Defects in Humans with IC Stimulation""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
14,13,paragraph_title,3.2.1. Managing Bone Defects in Humans with IC Stimulation,"[602, 1079, 1063, 1101]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.1. Managing Bone Defects in Humans with IC Stimulation""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
14,14,text,"Success when treating bone defects, like delayed unions and non-unions, was obtained upon stimulation with PEMF (and CMF) of 15, 23, or 80 Hz pulses, 0.01–2 mT, applied for 8–24 h day $ ^{-1} $, since","[599, 1123, 1093, 1438]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
14,15,footer,"Small Sci. 2024, 4, 2300303","[94, 1479, 261, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
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15,4,chart,,"[282, 143, 774, 491]",media_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,body_like,empty,True,True
15,5,chart,,"[244, 514, 954, 1106]",media_asset,0.85,"[""media label: chart""]",media_asset,0.85,body_zone,body_like,empty,True,True
15,6,figure_title,"Figure 7. Analysis of the efficacy of the IC in vivo stimulation parameters (magnetic field and frequency) on human patients, based on the reported bone-associated outcomes. A) Overview of the IC effi","[97, 1118, 1099, 1261]",figure_caption,0.92,"[""figure_title label: Figure 7. Analysis of the efficacy of the IC in vivo stimula""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
15,7,text,"1007 ununited fractures. Similar success rates were obtained when comparing PEMF against surgery with bone grafts, to treat ununited tibial fractures. Aaron et al. $ ^{[162]} $ (2004) concluded that b","[96, 1301, 588, 1437]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,body_zone,reference_like,reference_numeric_dot,True,True
15,8,text,"intervention could have evolved more over the last decades, still
highlighting the lack of setup optimization and/or personalized
medicine studies.","[605, 1300, 1097, 1367]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,7,text,"1007 ununited fractures. Similar success rates were obtained when comparing PEMF against surgery with bone grafts, to treat ununited tibial fractures. Aaron et al. $ ^{[162]} $ (2004) concluded that b","[96, 1301, 588, 1437]",body_paragraph,0.78,"[""default body_paragraph for text label"", ""late role resolution: non-body family 'reference_like' overrides body_paragraph"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,,reference_like,reference_numeric_dot,True,True
15,8,text,,"[605, 1300, 1097, 1367]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
15,9,text,"Examples of setups with positive osteogenic effects include the EBI Bone Healing System Model 420 (15 Hz pulses, 4.5 kHz bursts, 8–10 h day $ ^{-1} $) to treat scaphoid non-unions, which","[605, 1368, 1098, 1436]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
15,10,footer,"Small Sci. 2024, 4, 2300303","[99, 1479, 266, 1498]",noise,0.9,"[""footer label""]",noise,0.9,body_zone,body_like,none,False,False
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@ -332,13 +306,10 @@ www.advancedsciencenews.com","[92, 32, 311, 106]",noise,0.9,"[""header label""]"
16,3,text,"resulted in better grip and wrist motion unto 83% and 89% of normal levels, respectively.[141] However, in a follow-up study 6 years later, using the same settings, results slightly decreased to 77% a","[90, 137, 583, 622]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,4,text,"PEMF efficacy was also tested in acute bone fractures. PEMF of 40–72 Hz, 1 mT, applied 2–6 h day $ ^{-1} $ after mandibular fracture, complemented with maxillo-mandibular fixation, was able to return ","[90, 623, 583, 1130]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,5,text,"Regarding spine fusion, some studies state that both PEMF (4–8 h day $ ^{-1} $) and CMF (30 min day $ ^{-1} $) can improve the surgery's success rate by up to 48.8% $ ^{[145,175,176]} $. In contrast, ","[90, 1129, 582, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,6,text,"hypothesis, a recent multicenter study on the use of PEMF as
an adjuvant therapy to lumbar spine fusion in 142 patients at risk
for pseudarthrosis (Orthofix SpinalStim, 1.5 Hz pulses, 3.85 kHz
bursts, ","[598, 137, 1093, 473]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,7,paragraph_title,3.2.2. Tackling Osteoporosis in Humans Through IC Stimulation,"[602, 499, 1076, 523]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.2. Tackling Osteoporosis in Humans Through IC Stimulatio""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
16,6,text,,"[598, 137, 1093, 473]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True
16,7,paragraph_title,3.2.2. Tackling Osteoporosis in Humans Through IC Stimulation,"[602, 499, 1076, 523]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.2. Tackling Osteoporosis in Humans Through IC Stimulatio""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
16,8,text,"In post-menopausal women prone to osteoporosis and taking calcium and vitamin D supplements, a 40 min day $ ^{-1} $ thrice-a-week treatment with PEMF of 8 Hz pulses and 3.82 mT only slightly increased","[598, 543, 1093, 1187]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
16,9,paragraph_title,3.2.3. Enhancing Implant Osseointegration in Humans via IC Stimulation,"[601, 1215, 1055, 1261]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.3. Enhancing Implant Osseointegration in Humans via IC S""]",subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
16,9,paragraph_title,3.2.3. Enhancing Implant Osseointegration in Humans via IC Stimulation,"[601, 1215, 1055, 1261]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.3. Enhancing Implant Osseointegration in Humans via IC S""]",sub_subsection_heading,0.85,body_zone,body_like,heading_numbered,True,True
16,10,text,"To our knowledge, PEMF efficacy on implants’ osseointegration in humans was only tested in dental and hip prosthesis implants. $ ^{[142,184]} $ For dental implants, PEMF was implemented through caps t","[598, 1281, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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@ -349,25 +320,22 @@ SCIENCE NEWS
www.advancedsciencenews.com","[98, 32, 317, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False
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17,3,text,"prosthesis, BMD levels at 0 and 90 post-operative days, were measured on different zones following stimulation with PEMF of 75 Hz, 2.0 mT (6 h day $ ^{-1} $). Although no significant differences were ","[96, 139, 588, 361]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
17,4,paragraph_title,3.2.4. Handling Osteoarthritis in Humans Through IC Stimulation,"[97, 387, 585, 411]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.4. Handling Osteoarthritis in Humans Through IC Stimulat""]",subsection_heading,0.85,,unknown_like,heading_numbered,True,True
17,5,text,"Only two studies tested the efficacy of PEMF on (knee) osteoarthritis. One study used the FDA-approved MAGCELL ARTHRO device to deliver PEMF of 8 Hz, 105 mT for 5 min twice-a-day, for 15 days, and ati","[96, 431, 588, 742]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
17,6,paragraph_title,3.2.5. Addressing Soft Tissue Disorders in Humans with IC Stimulation,"[97, 767, 528, 815]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.5. Addressing Soft Tissue Disorders in Humans with IC St""]",subsection_heading,0.85,,unknown_like,heading_numbered,True,True
17,7,text,"In the only study on IC clinical application for soft tissues reported in the literature, PEMF stimuli of very high frequency (1 kHz pulses, with 27 MHz bursts) could improve soft tissue healing, pain","[96, 835, 588, 950]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
17,8,paragraph_title,3.3. Findings from IC Clinical Studies,"[97, 973, 387, 997]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.3. Findings from IC Clinical Studies""]",subsection_heading,0.85,,unknown_like,heading_numbered,True,True
17,9,text,"The relative efficacy of the IC clinical studies, according to the applied stimuli parameters, is presented in Figure 6 (global overview for each parameter) and Figure 7, which associates pairs of fre","[95, 1018, 587, 1129]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
17,10,text,"First, no clinical study has reported major adverse effects from the use of IC stimulation devices. Studies assessing radiographic outcomes (examples illustrated in Figure 8) have reported effects dri","[96, 1129, 589, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
17,11,text,"low efficacy for treating scaphoid non-unions and delayed unions
after foot and ankle arthrodesis, and effectiveness on bone frac-
tures highly varied. Indeed, various setups did not significantly
impro","[604, 137, 1098, 360]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
17,12,text,"Many authors did not report the IC parameters used in their studies, making it difficult to draw more assertive conclusions regarding effective magnetic stimuli settings. However, most of them used cl","[605, 360, 1098, 779]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
17,13,text,"Altogether, the use of IC stimulation seems clinically feasible to treat non-unions, to reduce its risk after fracture and accelerate healing when combined with standard procedures, and to increase th","[605, 778, 1098, 1066]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
17,14,text,"Overall, this study indicates that it would be desirable to develop more attractive devices for daily use, with the ability to provide personalized stimuli, and highlights the need to comprehensively ","[605, 1065, 1099, 1178]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
17,15,paragraph_title,4. The Potential Biomechanism Behind IC Therapeutic Effects,"[606, 1212, 1018, 1266]",unknown_structural,0.85,"[""paragraph_title label with numbering: 4. The Potential Biomechanism Behind IC Therapeutic Effects""]",section_heading,0.85,reference_zone,reference_like,reference_numeric_dot,False,True
17,16,text,"At the turn of the 21 $ ^{st} $ century, various groups started attempting to infer the biomechanisms underlying the IC effects on the musculoskeletal system, with this line of research accelerating i","[604, 1282, 1099, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
17,3,text,"prosthesis, BMD levels at 0 and 90 post-operative days, were measured on different zones following stimulation with PEMF of 75 Hz, 2.0 mT (6 h day $ ^{-1} $). Although no significant differences were ","[96, 139, 588, 361]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
17,4,paragraph_title,3.2.4. Handling Osteoarthritis in Humans Through IC Stimulation,"[97, 387, 585, 411]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.4. Handling Osteoarthritis in Humans Through IC Stimulat""]",sub_subsection_heading,0.85,body_zone,unknown_like,heading_numbered,True,True
17,5,text,"Only two studies tested the efficacy of PEMF on (knee) osteoarthritis. One study used the FDA-approved MAGCELL ARTHRO device to deliver PEMF of 8 Hz, 105 mT for 5 min twice-a-day, for 15 days, and ati","[96, 431, 588, 742]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
17,6,paragraph_title,3.2.5. Addressing Soft Tissue Disorders in Humans with IC Stimulation,"[97, 767, 528, 815]",sub_subsection_heading,0.85,"[""paragraph_title label with numbering: 3.2.5. Addressing Soft Tissue Disorders in Humans with IC St""]",sub_subsection_heading,0.85,body_zone,unknown_like,heading_numbered,True,True
17,7,text,"In the only study on IC clinical application for soft tissues reported in the literature, PEMF stimuli of very high frequency (1 kHz pulses, with 27 MHz bursts) could improve soft tissue healing, pain","[96, 835, 588, 950]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
17,8,paragraph_title,3.3. Findings from IC Clinical Studies,"[97, 973, 387, 997]",subsection_heading,0.85,"[""paragraph_title label with numbering: 3.3. Findings from IC Clinical Studies""]",subsection_heading,0.85,body_zone,unknown_like,heading_numbered,True,True
17,9,text,"The relative efficacy of the IC clinical studies, according to the applied stimuli parameters, is presented in Figure 6 (global overview for each parameter) and Figure 7, which associates pairs of fre","[95, 1018, 587, 1129]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
17,10,text,"First, no clinical study has reported major adverse effects from the use of IC stimulation devices. Studies assessing radiographic outcomes (examples illustrated in Figure 8) have reported effects dri","[96, 1129, 589, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,True,True
17,11,text,,"[604, 137, 1098, 360]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,,body_like,empty,False,True
17,12,text,"Many authors did not report the IC parameters used in their studies, making it difficult to draw more assertive conclusions regarding effective magnetic stimuli settings. However, most of them used cl","[605, 360, 1098, 779]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
17,13,text,"Altogether, the use of IC stimulation seems clinically feasible to treat non-unions, to reduce its risk after fracture and accelerate healing when combined with standard procedures, and to increase th","[605, 778, 1098, 1066]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
17,14,text,"Overall, this study indicates that it would be desirable to develop more attractive devices for daily use, with the ability to provide personalized stimuli, and highlights the need to comprehensively ","[605, 1065, 1099, 1178]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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17,16,text,"At the turn of the 21 $ ^{st} $ century, various groups started attempting to infer the biomechanisms underlying the IC effects on the musculoskeletal system, with this line of research accelerating i","[604, 1282, 1099, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
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17,20,aside_text,"26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar","[1153, 29, 1171, 1534]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
18,0,header,"ADVANCED
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18,4,figure_title,Figure 8. Examples of biological outcomes assessed in IC stimulation studies in humans. A) Anteroposterior and lateral radiographs of a distal tibial nonunion: i) 10 months after fracture; ii) after P,"[90, 1149, 1093, 1293]",figure_caption,0.92,"[""figure_title label: Figure 8. Examples of biological outcomes assessed in IC sti""]",figure_caption,0.92,display_zone,support_like,figure_number,True,True
18,5,text,"storages, increasing the cytosolic Ca²⁺ concentration. This potentially occurs through the activation of ryanodine-dependent Ca²⁺ channels (RyR) or inositol 1,4,5-triphosphate receptors (IP₃R) of the ","[90, 1326, 581, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
18,6,text,"coupled with the activation of voltage-sensitive enzymes,
the reorganization of the cytoskeleton, and the activation of
Ca2þ-dependent enzymes, including calmodulin (CaM).[190]
In osteoblasts, calcine","[599, 1326, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
18,4,figure_title,Figure 8. Examples of biological outcomes assessed in IC stimulation studies in humans. A) Anteroposterior and lateral radiographs of a distal tibial nonunion: i) 10 months after fracture; ii) after P,"[90, 1149, 1093, 1293]",figure_caption,0.92,"[""figure_title label: Figure 8. Examples of biological outcomes assessed in IC sti""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
18,5,text,"storages, increasing the cytosolic Ca²⁺ concentration. This potentially occurs through the activation of ryanodine-dependent Ca²⁺ channels (RyR) or inositol 1,4,5-triphosphate receptors (IP₃R) of the ","[90, 1326, 581, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
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18,10,aside_text,"26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smse.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar","[1154, 30, 1171, 1542]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False
19,0,header,"ADVANCED
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19,4,figure_title,Figure 9. Biomechanisms that may underly the observed therapeutic bone-associated effects of inductive coupling (IC) in vivo stimulation. The electromagnetic fields (EMF) delivered by IC pass the cyto,"[95, 693, 1102, 877]",figure_caption,0.92,"[""figure_title label: Figure 9. Biomechanisms that may underly the observed therap""]",figure_caption,0.92,display_zone,legend_like,figure_number,True,True
19,5,text,"Factor of Activated T Cells 1 (NFATc1), promoting its nuclear translocation and a subsequent increase in the transcription of genes related to the Wnt/ $ \beta $-catenin pathway. $ ^{[192]} $ Followin","[96, 916, 589, 1435]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
19,6,text,"increased sAC, serum cAMP, p-PKA and p-CREB.[102,121]
This sequence of events promotes osteoblastogenic effects, for
example by allowing the accumulation of β-catenin[201] and thus
cross-talking with ","[604, 914, 1099, 1137]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
19,7,text,"In contrast, IC stimulation can also regulate osteoclast differentiation and activity, by increasing the OPG/RANKL ratio. The increase in OPG expression, together with a decrease in RANKL expression, ","[604, 1139, 1099, 1433]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
19,5,text,"Factor of Activated T Cells 1 (NFATc1), promoting its nuclear translocation and a subsequent increase in the transcription of genes related to the Wnt/ $ \beta $-catenin pathway. $ ^{[192]} $ Followin","[96, 916, 589, 1435]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
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19,7,text,"In contrast, IC stimulation can also regulate osteoclast differentiation and activity, by increasing the OPG/RANKL ratio. The increase in OPG expression, together with a decrease in RANKL expression, ","[604, 1139, 1099, 1433]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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20,0,header,"ADVANCED
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20,3,text,"of bone resorption, and thus a decrease in serum CTX. $ ^{[87,88,102,112,120,121,126,180]} $ Netrin 4 may also play a role in the PEMF-induced decrease of osteoclastogenesis, $ ^{[202]} $ since PEMF i","[90, 138, 582, 359]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
20,4,text,"In vitro experiments suggest two other parallel and interacting mechanisms of action by which IC may lead to decreased osteoclast and increased osteoblast activities. PEMF was observed to induce, at a","[89, 360, 582, 1025]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
20,5,text,"In summary, there are various possible cellular events by which IC stimuli modulate osteogenic and osteoclastic activities to increase bone formation and decrease bone resorption, underscoring IC ther","[89, 1024, 582, 1293]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
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20,7,text,"This review analyzed 117 studies (73 in animal models, and 44 in human patients) using magnetic stimulation delivered by IC devices for musculoskeletal therapy purposes. Overall, from the studies here","[90, 1371, 582, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,unknown_like,none,True,True
20,8,text,"www.small-science-journal.com
the studies here analyzed, IC stimulation is an attractive option
for the clinical management of bone and cartilage disorders. IC is
a non-invasive therapy, with the MF b","[597, 140, 1093, 1305]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
20,9,text,"Hopefully, the transversal knowledge presented herein will serve as a valuable guide as we navigate the path toward optimizing clinical evidence and personalized IC-based treatment strategies. A deepe","[598, 1306, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,,body_like,none,True,True
20,3,text,"of bone resorption, and thus a decrease in serum CTX. $ ^{[87,88,102,112,120,121,126,180]} $ Netrin 4 may also play a role in the PEMF-induced decrease of osteoclastogenesis, $ ^{[202]} $ since PEMF i","[90, 138, 582, 359]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
20,4,text,"In vitro experiments suggest two other parallel and interacting mechanisms of action by which IC may lead to decreased osteoclast and increased osteoblast activities. PEMF was observed to induce, at a","[89, 360, 582, 1025]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
20,5,text,"In summary, there are various possible cellular events by which IC stimuli modulate osteogenic and osteoclastic activities to increase bone formation and decrease bone resorption, underscoring IC ther","[89, 1024, 582, 1293]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
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20,7,text,"This review analyzed 117 studies (73 in animal models, and 44 in human patients) using magnetic stimulation delivered by IC devices for musculoskeletal therapy purposes. Overall, from the studies here","[90, 1371, 582, 1439]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,unknown_like,none,True,True
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20,9,text,"Hopefully, the transversal knowledge presented herein will serve as a valuable guide as we navigate the path toward optimizing clinical evidence and personalized IC-based treatment strategies. A deepe","[598, 1306, 1093, 1440]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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21,0,header,"ADVANCED
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21,3,text,"devices, will be vital for pushing forward the clinical implementation and achieve the full therapeutic potential of IC stimulation for musculoskeletal disorders, toward more effective and tailored pa","[97, 138, 587, 228]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,4,paragraph_title,Supporting Information,"[98, 266, 329, 292]",backmatter_heading,0.5,"[""backmatter boundary candidate: Supporting Information""]",backmatter_boundary_candidate,0.5,,heading_like,none,True,True
21,5,text,Supporting Information is available from the Wiley Online Library or from the author.,"[97, 302, 586, 341]",backmatter_body,0.6,"[""default body_paragraph for text label"", ""promoted in tail spread from body_paragraph""]",body_paragraph,0.6,body_zone,body_like,none,True,True
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21,5,text,Supporting Information is available from the Wiley Online Library or from the author.,"[97, 302, 586, 341]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,6,paragraph_title,Acknowledgements,"[98, 381, 288, 406]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements""]",sub_subsection_heading,0.6,body_zone,heading_like,short_fragment,True,True
21,7,text,"J.G.S.F. and B.M.de.S. contributed equally to this work. The authors acknowledge the support of Fundação para a Ciência e Tecnologia (Portugal), Centro 2020, the COMPETE program, QREN, and the Europea","[96, 417, 588, 666]",backmatter_body,0.6,"[""default body_paragraph for text label"", ""promoted in tail spread from body_paragraph""]",body_paragraph,0.6,,unknown_like,none,True,True
21,8,paragraph_title,Conflict of Interest,"[98, 704, 284, 729]",subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Conflict of Interest""]",subsection_heading,0.6,frontmatter_side_zone,support_like,none,True,True
21,9,text,The authors declare no conflict of interest.,"[98, 741, 390, 761]",frontmatter_noise,0.6,"[""default body_paragraph for text label"", ""frontmatter_side_zone excluded from body flow""]",frontmatter_noise,0.6,frontmatter_side_zone,support_like,none,False,False
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21,11,text,"animal models, clinical studies, combined magnetic fields (CMF), inductive coupling, musculoskeletal disorders, pre-clinical studies, pulsed electromagnetic fields (PEMF)","[97, 850, 586, 910]",backmatter_body,0.6,"[""default body_paragraph for text label"", ""promoted in tail spread from body_paragraph""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,12,text,"Received: November 21, 2023","[381, 922, 586, 941]",backmatter_body,0.6,"[""default body_paragraph for text label"", ""promoted in tail spread from body_paragraph""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,13,text,"Revised: February 5, 2024","[408, 943, 587, 961]",backmatter_body,0.6,"[""default body_paragraph for text label"", ""promoted in tail spread from body_paragraph""]",body_paragraph,0.6,body_zone,body_like,none,True,True
21,14,text,"Published online: February 26, 2024","[341, 962, 586, 982]",backmatter_body,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,body_zone,support_like,none,True,True
21,7,text,"J.G.S.F. and B.M.de.S. contributed equally to this work. The authors acknowledge the support of Fundação para a Ciência e Tecnologia (Portugal), Centro 2020, the COMPETE program, QREN, and the Europea","[96, 417, 588, 666]",reference_item,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,reference_zone,unknown_like,none,True,True
21,8,paragraph_title,Conflict of Interest,"[98, 704, 284, 729]",unknown_structural,0.6,"[""unnumbered paragraph_title, inferred level subsection_heading: Conflict of Interest""]",subsection_heading,0.6,tail_nonref_hold_zone,support_like,none,False,True
21,9,text,The authors declare no conflict of interest.,"[98, 741, 390, 761]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,,support_like,none,False,False
21,10,paragraph_title,Keywords,"[99, 814, 195, 839]",sub_subsection_heading,0.6,"[""unnumbered paragraph_title, inferred level sub_subsection_heading: Keywords""]",sub_subsection_heading,0.6,tail_nonref_hold_zone,heading_like,short_fragment,True,True
21,11,text,"animal models, clinical studies, combined magnetic fields (CMF), inductive coupling, musculoskeletal disorders, pre-clinical studies, pulsed electromagnetic fields (PEMF)","[97, 850, 586, 910]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
21,12,text,"Received: November 21, 2023","[381, 922, 586, 941]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
21,13,text,"Revised: February 5, 2024","[408, 943, 587, 961]",body_paragraph,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,body_like,none,True,True
21,14,text,"Published online: February 26, 2024","[341, 962, 586, 982]",frontmatter_noise,0.88,"[""default body_paragraph for text label"", ""late role resolution: editorial phrase cross-validates non-body classification"", ""zone=body_zone"", ""style_family=support_like""]",body_paragraph,0.6,,support_like,none,False,False
21,15,reference_content,"[1] T. Vos, S. S. Lim, C. Abbafati, K. M. Abbas, M. Abbasi, M. Abbasifard, M. Abbasi-Kangevari, H. Abbastabar, F. Abd-Allah, A. Abdelalim, M. Abdollahi, I. Abdollahpour, H. Abolhassani, V. Aboyans, E.","[105, 1027, 586, 1191]",reference_item,0.85,"[""reference content label: [1] T. Vos, S. S. Lim, C. Abbafati, K. M. Abbas, M. Abbasi, ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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@ -474,7 +433,7 @@ www.advancedsciencenews.com","[99, 32, 317, 106]",noise,0.9,"[""header label""]"
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23,61,reference_content,"[151] H. Shi, J. Xiong, Y. Chen, J. Wang, X. Qiu, Y. Wang, Y. Qiu, BMC Musculoskelet. Disord. 2013, 14, 35.","[609, 1377, 1097, 1414]",reference_item,0.85,"[""reference content label: [151] H. Shi, J. Xiong, Y. Chen, J. Wang, X. Qiu, Y. Wang, Y""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
23,62,reference_content,"[152] B. D. Adams, G. K. Frykman, J. Taleisnik, J. Hand Surg. 1992, 17, 910.","[610, 1418, 1096, 1438]",reference_item,0.85,"[""reference content label: [152] B. D. Adams, G. K. Frykman, J. Taleisnik, J. Hand Surg""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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24,59,reference_content,"[210] R. Bernardo, A. Rodrigues, M. P. Soares dos Santos, P. Carneiro, A. Lopes, J. Sequeira Amaral, V. Sequeira Amaral, R. Morais, Med. Eng. Phys. 2019, 73, 77.","[604, 1290, 1089, 1349]",reference_item,0.85,"[""reference content label: [210] R. Bernardo, A. Rodrigues, M. P. Soares dos Santos, P.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
24,60,reference_content,"[211] T. S. S. Carvalho, P. M. C. Torres, J. H. Belo, J. Mano, S. M. Olhero, Adv. NanoBiomed Res. 2023, 3, 2300035.","[604, 1351, 1090, 1389]",reference_item,0.85,"[""reference content label: [211] T. S. S. Carvalho, P. M. C. Torres, J. H. Belo, J. Man""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True
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45 3 10 7 figure_title Musculoskeletal conditions assessed in animal models Animal models receiving IC stimulation [382, 514, 849, 539] [622, 151, 921, 174] figure_caption figure_caption_candidate 0.85 ["figure_title label: Musculoskeletal conditions assessed in animal models"] ["figure_title label: Animal models receiving IC stimulation"] figure_caption 0.85 body_zone legend_like none True False True False
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51 3 16 13 figure_title Figure 1. General trends of IC stimulation on pre-clinical studies with animal models of musculoskeletal disorders. A) IC stimulation methods applied; B) Type of animal models used; C) Musculoskeletal E [97, 1255, 1098, 1418] [621, 908, 639, 930] figure_caption figure_inner_text 0.92 0.9 ["figure_title label: Figure 1. General trends of IC stimulation on pre-clinical s"] ["panel label / figure inner text: E"] figure_caption figure_inner_text 0.92 0.9 display_zone support_like legend_like figure_number panel_label True True
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54 3 19 16 footer figure_title © 2024 The Authors. Small Science published by Wiley-VCH GmbH Figure 1. General trends of IC stimulation on pre-clinical studies with animal models of musculoskeletal disorders. A) IC stimulation methods applied; B) Type of animal models used; C) Musculoskeletal [687, 1479, 1096, 1499] [97, 1255, 1098, 1418] noise figure_caption 0.9 0.92 ["footer label"] ["figure_title label: Figure 1. General trends of IC stimulation on pre-clinical s"] noise figure_caption 0.9 0.92 body_zone display_zone body_like legend_like none figure_number False True False True
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59 4 3 0 text header mineral density (BMD), soft tissue healing, spine fusion, and osteoarthritis, as well as in healthy subjects. Bone defects $ ^{[59-81]} $ were the most assessed condition (in 27.4% of the studies; Fig ADVANCED SCIENCE NEWS www.advancedsciencenews.com [89, 137, 582, 298] [92, 31, 312, 107] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
60 4 4 1 text header in pre-clinical studies to deliver PEMF is schematically presented in Figure 1D. Additionally, Figure 1E portrays a photograph of an actual IC stimulation device used in a pre-clinical study here revi small science [599, 137, 1092, 226] [1008, 13, 1091, 81] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone body_like unknown_like none short_fragment True False True False
61 4 5 2 text header The tested pulse frequencies ranged from 1 Hz $ ^{[73]} $–400 Hz, $ ^{[66]} $ with the most tested frequency being 15 Hz (in 36.5% of the tested frequencies, Figure 2A). Unless stated otherwise, all www.small-science-journal.com [600, 224, 1093, 297] [877, 86, 1091, 107] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
62 4 6 3 chart text mineral density (BMD), soft tissue healing, spine fusion, and osteoarthritis, as well as in healthy subjects. Bone defects $ ^{[59-81]} $ were the most assessed condition (in 27.4% of the studies; Fig [192, 337, 582, 844] [89, 137, 582, 298] media_asset body_paragraph 0.85 0.6 ["media label: chart"] ["default body_paragraph for text label"] media_asset body_paragraph 0.85 0.6 body_zone body_like empty none True True
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64 4 8 5 chart text The tested pulse frequencies ranged from 1 Hz $ ^{[73]} $–400 Hz, $ ^{[66]} $ with the most tested frequency being 15 Hz (in 36.5% of the tested frequencies, Figure 2A). Unless stated otherwise, all [193, 857, 572, 1223] [600, 224, 1093, 297] media_asset body_paragraph 0.85 0.6 ["media label: chart"] ["default body_paragraph for text label"] media_asset body_paragraph 0.85 0.6 body_zone body_like empty none True True
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69 4 13 10 footer figure_title © 2024 The Authors. Small Science published by Wiley-VCH GmbH Figure 2. IC stimuli parameters applied in animal pre-clinical studies. Graphical analysis of the different IC stimulation parameters used in the 73 animal studies reviewed, plotting the number of stu [680, 1479, 1091, 1499] [91, 1237, 1092, 1440] noise figure_caption 0.9 0.92 ["footer label"] ["figure_title label: Figure 2. IC stimuli parameters applied in animal pre-clinic"] noise figure_caption 0.9 0.92 body_zone display_zone body_like legend_like none figure_number False True False True
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78 5 7 4 text PEMF have been applied to determine whether bone tissues from healthy rats responded well to electromagnetic stimuli. These studies were focused on major macroscopical and micro-architectural effects Regarding the biological outcomes, these may differ due to anatomical and physiological differences between the animal models. For comparative purposes, the biological outcomes were analyzed by groups [94, 926, 589, 1441] [96, 406, 588, 564] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
79 5 8 5 text paragraph_title Increased expression levels of femur p-PKA and p-CREB, soluble adenyl cyclase (sAC), and serum cAMP were also observed, indi- cating osteogenic effects through the sAC/cAMP/PKA/CREB signaling pathway. 2.2. Effects of IC Stimulation on Small-Sized Animals [605, 137, 1097, 230] [97, 593, 505, 616] body_paragraph subsection_heading 0.6 0.85 ["default body_paragraph for text label"] ["paragraph_title label with numbering: 2.2. Effects of IC Stimulation on Small-Sized Animals"] body_paragraph subsection_heading 0.6 0.85 body_zone body_like none heading_numbered True True
80 5 9 6 paragraph_title text 2.2.1. Managing Bone Defects in Small-Sized Animals Through IC Stimulation Rats (Rattus norvegicus) were the most used animal models to test IC stimulation in vivo (Figure 1). Rats are anatomic and physiologically well-studied, have fast growth and reproductive rates and req [607, 258, 1006, 308] [96, 637, 588, 927] subsection_heading body_paragraph 0.85 0.6 ["paragraph_title label with numbering: 2.2.1. Managing Bone Defects in Small-Sized Animals Through "] ["default body_paragraph for text label"] subsection_heading body_paragraph 0.85 0.6 body_zone body_like heading_numbered none True True
81 5 10 7 text PEMF of rather different parameters were applied to heal rat bone defects (fractures and osteotomies) and consolidate bone fusions, with promising effects such as faster osseous bridging, assessed by PEMF have been applied to determine whether bone tissues from healthy rats responded well to electromagnetic stimuli. These studies were focused on major macroscopical and micro-architectural effects [604, 327, 1099, 883] [94, 926, 589, 1441] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
5 11 text Studies using PEMF of higher pulse frequencies, from 20 to 400 Hz, have mostly reported positive impacts on bone healing (Figure 2). For example, PEMF of 50 Hz and 1.5 mT, applied to rat tibial fractu [605, 884, 1098, 1327] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
5 12 text An FDA-approved PEMF device, Physio-Stim, delivering pulses at the most commonly used frequency (15 Hz pulse), of triangular or sawtooth bursts at 3.85 kHz, and 2.0 mT with a daily exposure of 3 h day [604, 1326, 1098, 1440] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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83 5 15 9 footer paragraph_title © 2024 The Authors. Small Science published by Wiley-VCH GmbH 2.2.1. Managing Bone Defects in Small-Sized Animals Through IC Stimulation [687, 1479, 1096, 1498] [607, 258, 1006, 308] noise sub_subsection_heading 0.9 0.85 ["footer label"] ["paragraph_title label with numbering: 2.2.1. Managing Bone Defects in Small-Sized Animals Through "] noise sub_subsection_heading 0.9 0.85 body_zone body_like none heading_numbered False True False True
84 5 16 10 aside_text text 26884046, 2024, 5. Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smse.20290303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrary PEMF of rather different parameters were applied to heal rat bone defects (fractures and osteotomies) and consolidate bone fusions, with promising effects such as faster osseous bridging, assessed by [1153, 29, 1171, 1541] [604, 327, 1099, 883] noise body_paragraph 0.95 0.6 ["margin-band narrow/tall geometry; treated as noise"] ["default body_paragraph for text label"] noise body_paragraph 0.95 0.6 body_zone body_like none False True False True
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100 7 6 1 9 header text small science For disuse osteoporosis models, PEMF of 10 Hz and 3.82 mT, for 40 min day $ ^{-1} $ over 12 weeks, improved bone microarchitecture (increased Tb.Area and Tb.N; reduced Tb.S) and increased serum OC by [1014, 14, 1098, 80] [598, 955, 1093, 1440] noise body_paragraph 0.9 0.6 ["header label"] ["default body_paragraph for text label"] noise body_paragraph 0.9 0.6 body_zone unknown_like body_like short_fragment none False True False True
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102 7 6 3 11 text footer animals), and acted on bone remodeling pathways: +42.1% serum TGF-β1 and −21.7% serum IL-6.[111] PEMF of higher frequency (50 Hz) and lower MF strength (0.6 mT), applied for 1.5 h day−1 over 4 weeks, 2300303 (6 of 25) [95, 139, 588, 582] [400, 1476, 541, 1499] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like reference_like none reference_numeric_dot True False True False
103 7 6 4 12 text footer In cases of drug-induced osteoporosis, PEMF of 7.3 Hz and 0.8 mT for 1 h day $ ^{-1} $ over 4 weeks reverted heparin-induced bone loss, increasing new bone area by 4-fold and reducing serum CTX ( $ -2 © 2024 The Authors. Small Science published by Wiley-VCH GmbH [95, 583, 588, 805] [679, 1479, 1091, 1499] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
7 5 text Finally, in senile osteoporosis models, PEMF of 8 Hz and 3.82 mT (applied for 40 min day $ ^{-1} $) partially reverted aging-related bone deterioration, after 12 weeks of stimulation. Improved BMD, bo [95, 805, 588, 1052] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
7 6 paragraph_title 2.2.4. IC Stimulation to Improve Implant Osseointegration in Small-Sized Animals [97, 1080, 548, 1127] subsection_heading 0.85 ["paragraph_title label with numbering: 2.2.4. IC Stimulation to Improve Implant Osseointegration in"] subsection_heading 0.85 body_zone body_like heading_numbered True True
7 7 text IC stimulation was also tested on rat implants’ osseointegration. A study applying PEMF with the most common parameters (15 Hz, 1.0 mT), has compared the effectiveness of 1 vs 3 h day $ ^{-1} $ exposu [95, 1148, 587, 1440] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
104 7 6 8 13 text aside_text increased peri-implant and osteotomy ossification were observed in the group stimulated for 0.5 h twice-a-day with PEMF of 50 Hz and high MF strength (72 mT), demonstrating that this IC ther- apy can a 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.20290303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrary [604, 138, 1098, 497] [1153, 28, 1171, 1540] body_paragraph noise 0.6 0.95 ["default body_paragraph for text label"] ["margin-band narrow/tall geometry; treated as noise"] body_paragraph noise 0.6 0.95 body_zone body_like none True False True False
105 7 9 0 paragraph_title header 2.2.5. Handling Osteoarthritis in Small-Sized Animals with IC Stimulation ADVANCED SCIENCE NEWS www.advancedsciencenews.com [606, 525, 1064, 572] [98, 32, 316, 106] subsection_heading noise 0.85 0.9 ["paragraph_title label with numbering: 2.2.5. Handling Osteoarthritis in Small-Sized Animals with I"] ["header label"] subsection_heading noise 0.85 0.9 body_zone body_like heading_numbered none True False True False
106 7 10 1 text header In two studies of a rat model mimicking temporomandibular joint osteoarthritis, PEMF of 2 mT and 15 Hz pulses (bursts of 5 kHz), applied for 2 h day $ ^{-1} $ over 3 or 6 weeks, partially reversed mic small science [604, 593, 1099, 1218] [1014, 14, 1098, 80] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone body_like unknown_like none short_fragment True False True False
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115 8 7 3 10 text two pulse frequencies: 3/ and 75 Hz. Both frequencies lowered Fibrillation Index (FI) and SBT, with the 75 Hz being more beneficial to cartilage (+20.6% thickness; −18.5% cartilage FI). Nevertheless, In two studies of a rat model mimicking temporomandibular joint osteoarthritis, PEMF of 2 mT and 15 Hz pulses (bursts of 5 kHz), applied for 2 h day $ ^{-1} $ over 3 or 6 weeks, partially reversed mic [90, 137, 582, 252] [604, 593, 1099, 1218] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
116 8 7 4 11 paragraph_title text 2.3. Effects of IC Stimulation on Intermediate-Sized Animals Other animals used as osteoarthritis models are guinea pigs (Cavia porcellus) of the Dunkin-Hartley breed, that spontaneously develop degenerative joint diseases around 3 months old. $ ^{[104]} $ Impr [90, 285, 552, 307] [605, 1216, 1099, 1441] subsection_heading body_paragraph 0.85 0.6 ["paragraph_title label with numbering: 2.3. Effects of IC Stimulation on Intermediate-Sized Animals"] ["default body_paragraph for text label"] subsection_heading body_paragraph 0.85 0.6 body_zone body_like heading_numbered none True True
117 8 7 5 12 text footer Rabbits (Oryctolagus cuniculus) are the second usual choice to study IC stimulation on bone remodeling and implants' osseointegration (Figure 1). Comparatively to smaller models, rabbits undergo more Small Sci. 2024, 4, 2300303 [90, 329, 582, 557] [99, 1479, 267, 1498] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
118 8 7 6 13 paragraph_title footer 2.3.1. Managing Bone Defects in Intermediate-Sized Animals Using IC Stimulation 2300303 (7 of 25) [91, 589, 539, 635] [406, 1476, 547, 1499] subsection_heading noise 0.85 0.9 ["paragraph_title label with numbering: 2.3.1. Managing Bone Defects in Intermediate-Sized Animals U"] ["footer label"] subsection_heading noise 0.85 0.9 body_zone body_like reference_like heading_numbered reference_numeric_dot True False True False
119 8 7 7 14 text footer Various studies investigated the IC stimulation impact on callus and bone formation in rabbits' bone defects (fractures/osteotomies).[67,68,71,72,76,79] Daily distracted tibial osteotomies, exposed to © 2024 The Authors. Small Science published by Wiley-VCH GmbH [90, 658, 583, 1438] [686, 1479, 1097, 1499] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
120 8 7 8 15 paragraph_title aside_text 2.3.2. IC Stimulation Effects on Implant Osseointegration in Intermediate-Sized Animals 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [601, 140, 1044, 187] [1153, 22, 1171, 1535] subsection_heading noise 0.85 0.95 ["paragraph_title label with numbering: 2.3.2. IC Stimulation Effects on Implant Osseointegration in"] ["margin-band narrow/tall geometry; treated as noise"] subsection_heading noise 0.85 0.95 body_zone body_like heading_numbered none True False True False
121 8 9 0 text header Bone replacement of rabbits' hindlimbs was commonly used to test IC-induced implant osseointegration. Matsumoto et al.[82] applied 100 Hz PEMF to improve osseointegration of dental implants in rabbits ADVANCED SCIENCE NEWS www.advancedsciencenews.com [598, 208, 1093, 589] [92, 32, 312, 106] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
8 10 text Another study using PEMF of similar MF strengths but at 1/10 of the pulse frequency and with increased exposure (10 Hz, 0.2–0.4 mT, 24 h day $ ^{-1} $) for up to 4 weeks, also improved osseointegratio [599, 588, 1093, 1350] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
8 11 text In a study comparing tibial implants, PEMF of 1.5 Hz (quasi-square pulses), 0.18 mT, applied 8 h day $ ^{-1} $ for 6 weeks, accelerated bone formation and maturation (thicker trabeculae; most signific [599, 1349, 1093, 1440] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
8 12 footer Small Sci. 2024, 4, 2300303 [93, 1479, 261, 1498] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
122 8 13 1 footer header 2300303 (8 of 25) small science [401, 1476, 541, 1499] [1008, 13, 1092, 80] noise 0.9 ["footer label"] ["header label"] noise 0.9 body_zone reference_like unknown_like reference_numeric_dot short_fragment False False
123 8 14 2 footer header © 2024 The Authors. Small Science published by Wiley-VCH GmbH www.small-science-journal.com [680, 1479, 1091, 1498] [878, 86, 1091, 106] noise 0.9 ["footer label"] ["header label"] noise 0.9 body_zone body_like none False False
124 8 15 3 aside_text text 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar two pulse frequencies: 3/ and 75 Hz. Both frequencies lowered Fibrillation Index (FI) and SBT, with the 75 Hz being more beneficial to cartilage (+20.6% thickness; −18.5% cartilage FI). Nevertheless, [1153, 29, 1171, 1534] [90, 137, 582, 252] noise body_paragraph 0.95 0.6 ["margin-band narrow/tall geometry; treated as noise"] ["default body_paragraph for text label"] noise body_paragraph 0.95 0.6 body_zone body_like none False True False True
132 9 8 7 11 paragraph_title text 2.4. Effects of IC Stimulation on Medium-Sized Animals In a study comparing tibial implants, PEMF of 1.5 Hz (quasi-square pulses), 0.18 mT, applied 8 h day $ ^{-1} $ for 6 weeks, accelerated bone formation and maturation (thicker trabeculae; most signific [96, 1327, 527, 1350] [599, 1349, 1093, 1440] subsection_heading body_paragraph 0.85 0.6 ["paragraph_title label with numbering: 2.4. Effects of IC Stimulation on Medium-Sized Animals"] ["default body_paragraph for text label"] subsection_heading body_paragraph 0.85 0.6 body_zone body_like heading_numbered none True True
133 9 8 8 12 text footer Dogs (Canis lupus familiaris) were not widely used to assess IC stimulation (Figure 1) but can offer some advantages when studying the bone response to injury and treatments. Their skeleton is similar Small Sci. 2024, 4, 2300303 [96, 1371, 588, 1440] [93, 1479, 261, 1498] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
134 9 8 9 13 text footer Their skeleton is similar to humans in bone weight, density, organic and inorganic composition, water fraction, secondary osteons, epiphyseal fusion after maturity, intracortical remodel- ing activity 2300303 (8 of 25) [604, 138, 1098, 362] [401, 1476, 541, 1499] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like reference_like none reference_numeric_dot True False True False
135 9 8 10 14 paragraph_title footer 2.4.1. Managing Bone Defects in Medium-Sized Animals Through IC Stimulation © 2024 The Authors. Small Science published by Wiley-VCH GmbH [607, 388, 1091, 435] [680, 1479, 1091, 1498] subsection_heading noise 0.85 0.9 ["paragraph_title label with numbering: 2.4.1. Managing Bone Defects in Medium-Sized Animals Through"] ["footer label"] subsection_heading noise 0.85 0.9 body_zone body_like heading_numbered none True False True False
136 9 8 11 15 text aside_text The earliest evidence of PEMF effects on bone dates back to 1974 with a study on bone defects, when dog fibular osteotomies were stimulated for 24 h day $ ^{-1} $ with PEMF of 1 or 65 Hz over 4 weeks. 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [604, 456, 1098, 678] [1153, 29, 1171, 1534] body_paragraph noise 0.6 0.95 ["default body_paragraph for text label"] ["margin-band narrow/tall geometry; treated as noise"] body_paragraph noise 0.6 0.95 body_zone body_like none True False True False
137 9 12 0 text header Other findings in dogs also support the use of PEMF to repair bone defects and improve the success rate of bone (spine) fusion. $ ^{[62,131]} $ Exposure of osteotomized tibiae for 1 h day $ ^{-1} $ to ADVANCED SCIENCE NEWS www.advancedsciencenews.com [604, 678, 1098, 1011] [98, 32, 318, 106] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
138 9 13 1 paragraph_title header 2.4.2. IC Stimulation of Medium-Sized Animals with Osteoporosis and Cartilage Defects small science [606, 1037, 1092, 1085] [1014, 13, 1098, 80] subsection_heading noise 0.85 0.9 ["paragraph_title label with numbering: 2.4.2. IC Stimulation of Medium-Sized Animals with Osteoporo"] ["header label"] subsection_heading noise 0.85 0.9 body_zone body_like unknown_like heading_numbered short_fragment True False True False
9 14 text In OVX osteoporosis dog models, PEMF of 1.5 Hz for 1 h day $ ^{-1} $ during 12 weeks reduced bone loss from 23.1% to 9.5%, but had no effect on bone remodeling within the bone cortex. $ ^{[132]} $ For [604, 1104, 1099, 1439] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
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139 9 17 2 footer header © 2024 The Authors. Small Science published by Wiley-VCH GmbH www.small-science-journal.com [686, 1479, 1097, 1499] [884, 86, 1097, 107] noise 0.9 ["footer label"] ["header label"] noise 0.9 body_zone body_like none False False
140 9 18 3 aside_text text 26884046, 2024, 5. Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar hydroxyapatite (HA) but not around tricalcium phosphate (TCP) implants.[91] Moreover, HA tibial implants stimulated with PEMF of higher pulse frequency and MF strength (50 Hz, 8 mT), for 0.5 h twice-a [1153, 22, 1172, 1542] [95, 138, 588, 493] noise body_paragraph 0.95 0.6 ["margin-band narrow/tall geometry; treated as noise"] ["default body_paragraph for text label"] noise body_paragraph 0.95 0.6 body_zone body_like none False True False True
141 10 9 0 4 header text ADVANCED SCIENCE NEWS www.advancedsciencenews.com Implant osseointegration was also evaluated in low BMD conditions, namely in type-1 diabetes mellitus (T1DM) rabbit models and in glucocorticoids-treated rabbits.[87,88] Both studies used the same por [92, 31, 311, 106] [96, 494, 588, 1027] noise body_paragraph 0.9 0.6 ["header label"] ["default body_paragraph for text label"] noise body_paragraph 0.9 0.6 body_zone body_like none False True False True
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151 10 9 10 14 image text In OVX osteoporosis dog models, PEMF of 1.5 Hz for 1 h day $ ^{-1} $ during 12 weeks reduced bone loss from 23.1% to 9.5%, but had no effect on bone remodeling within the bone cortex. $ ^{[132]} $ For [556, 944, 832, 1180] [604, 1104, 1099, 1439] media_asset body_paragraph 0.85 0.6 ["media label: image"] ["default body_paragraph for text label"] media_asset body_paragraph 0.85 0.6 body_zone body_like empty none True True
152 10 9 11 15 image footer Small Sci. 2024, 4, 2300303 [837, 954, 1079, 1181] [98, 1479, 267, 1498] media_asset noise 0.85 0.9 ["media label: image"] ["footer label"] media_asset noise 0.85 0.9 body_zone body_like empty none True False True False
153 10 9 12 16 figure_title footer Figure 3. Examples of biological outcomes commonly assessed in IC stimulation studies using animal models. A) Improved trabecular bone microarchitecture and cortical bone thickness of femurs of rats s 2300303 (9 of 25) [88, 1197, 1095, 1439] [406, 1476, 547, 1499] figure_caption noise 0.92 0.9 ["figure_title label: Figure 3. Examples of biological outcomes commonly assessed "] ["footer label"] figure_caption noise 0.92 0.9 display_zone support_like reference_like figure_number reference_numeric_dot True False True False
154 10 9 13 17 footer Small Sci. 2024, 4, 2300303 © 2024 The Authors. Small Science published by Wiley-VCH GmbH [94, 1479, 261, 1498] [686, 1479, 1097, 1499] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
155 10 9 14 18 number aside_text 2300303 (10 of 25) 26884046, 2024, 5. Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [396, 1476, 545, 1499] [1153, 22, 1172, 1542] noise 0.9 0.95 ["page number label"] ["margin-band narrow/tall geometry; treated as noise"] noise 0.9 0.95 body_zone reference_like body_like reference_numeric_dot none False False
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157 10 16 1 aside_text header 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar small science [1154, 30, 1171, 1536] [1009, 13, 1092, 80] noise 0.95 0.9 ["margin-band narrow/tall geometry; treated as noise"] ["header label"] noise 0.95 0.9 body_zone body_like unknown_like none short_fragment False False
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168 11 10 10 12 text figure_title The clinical application of IC stimulation to treat multiple complications has been under development since the middle of the $ 20^{th} $ century. This therapeutic is gaining increasing popularity in Figure 3. Examples of biological outcomes commonly assessed in IC stimulation studies using animal models. A) Improved trabecular bone microarchitecture and cortical bone thickness of femurs of rats s [605, 639, 1098, 928] [88, 1197, 1095, 1439] body_paragraph figure_caption 0.6 0.92 ["default body_paragraph for text label"] ["figure_title label: Figure 3. Examples of biological outcomes commonly assessed "] body_paragraph figure_caption 0.6 0.92 body_zone display_zone body_like legend_like none figure_number True True
169 11 10 11 13 text footer IC clinical studies mainly used devices delivering PEMF (in 88.6% of the studies) (Figure 5A). FDA-approved stimulators are the most used devices to test the efficacy of IC musculoskeletal therapy in Small Sci. 2024, 4, 2300303 [604, 928, 1098, 1305] [94, 1479, 261, 1498] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone body_like none True False True False
170 11 10 12 14 text number Regarding the IC stimuli parameters applied in clinical studies (Figure 6A–D), there is first to highlight that the clinical studies reported less frequently the stimuli parameters applied than the pr 2300303 (10 of 25) [604, 1305, 1098, 1440] [396, 1476, 545, 1499] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["page number label"] body_paragraph noise 0.6 0.9 body_zone body_like reference_like none reference_numeric_dot True False True False
171 11 10 13 15 footer Small Sci. 2024, 4, 2300303 © 2024 The Authors. Small Science published by Wiley-VCH GmbH [99, 1479, 267, 1498] [681, 1479, 1090, 1498] noise 0.9 ["footer label"] noise 0.9 body_zone body_like none False False
172 11 10 14 16 footer aside_text 2300303 (11 of 25) 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [402, 1476, 551, 1499] [1154, 30, 1171, 1536] noise 0.9 0.95 ["footer label"] ["margin-band narrow/tall geometry; treated as noise"] noise 0.9 0.95 body_zone reference_like body_like reference_numeric_dot none False False
173 11 15 0 footer header © 2024 The Authors. Small Science published by Wiley-VCH GmbH ADVANCED SCIENCE NEWS www.advancedsciencenews.com [687, 1479, 1097, 1498] [98, 32, 317, 106] noise 0.9 ["footer label"] ["header label"] noise 0.9 body_zone body_like none False False
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176 12 11 4 3 figure_title text B Radiological outcomes in animal models properties, including bone bending stiffness, callus/bone elastic modulus, torque and load bearing, have also improved upon IC stimulation. At a molecular/biochemical level, IC stimulation activated o [537, 143, 903, 164] [96, 139, 588, 315] figure_caption body_paragraph 0.85 0.6 ["figure_title label: B Radiological outcomes in animal models"] ["default body_paragraph for text label"] figure_caption body_paragraph 0.85 0.6 body_zone legend_like body_like none True True
177 12 11 5 4 chart text A general overview of IC stimulation efficacy in animal studies is presented in Figure 2, which presents improvements versus no improvements according to stimuli frequency, MF strength or exposure tim [515, 164, 1020, 497] [96, 316, 588, 756] media_asset body_paragraph 0.85 0.6 ["media label: chart"] ["default body_paragraph for text label"] media_asset body_paragraph 0.85 0.6 body_zone body_like empty none True True
178 12 11 6 5 figure_title text C Overall, whenever biological outcomes were assessed, IC stimulation induced improvements in more than 75% of the assays, regardless of the assessed outcome (Figure 4A). Nevertheless, radiological and [257, 513, 276, 532] [96, 758, 588, 1439] figure_inner_text body_paragraph 0.9 0.6 ["panel label / figure inner text: C"] ["default body_paragraph for text label"] figure_inner_text body_paragraph 0.9 0.6 display_zone body_zone legend_like body_like panel_label none True True
179 12 11 7 6 figure_title text Histological/Biochemical outcomes in animal models [346, 514, 732, 533] [605, 139, 1098, 293] figure_caption_candidate unknown_structural 0.85 0.3 ["figure_title label: Histological/Biochemical outcomes in animal models"] ["short text, uncertain role"] figure_caption unknown_structural 0.85 0.3 body_zone legend_like body_like none empty False False True
180 12 11 8 7 chart text In general, the studies applying IC stimulation to animal models revealed promising success rates, although radiological and biomechanical outcomes should be more thoroughly assessed. The available da [258, 542, 875, 887] [605, 294, 1098, 518] media_asset body_paragraph 0.85 0.6 ["media label: chart"] ["default body_paragraph for text label"] media_asset body_paragraph 0.85 0.6 body_zone body_like empty none True True
181 12 11 9 8 figure_title paragraph_title D Biomechanical outcomes in animal models 3. Clinical Studies of IC Therapies [262, 902, 664, 924] [607, 557, 942, 583] figure_caption section_heading 0.85 ["figure_title label: D Biomechanical outcomes in animal models"] ["paragraph_title label with numbering: 3. Clinical Studies of IC Therapies"] figure_caption section_heading 0.85 body_zone legend_like reference_like none reference_numeric_dot True True
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217 14 13 9 11 figure_title image Figure 6. IC stimuli parameters applied in clinical studies. Types of IC stimulation parameters used on patients with musculoskeletal disorders, number of studies in which they were used, and their re [89, 879, 1095, 1042] [319, 731, 491, 854] figure_caption media_asset 0.92 0.85 ["figure_title label: Figure 6. IC stimuli parameters applied in clinical studies."] ["media label: image"] figure_caption media_asset 0.92 0.85 display_zone body_zone legend_like unknown_like figure_number empty True True
254 16 15 13 6 footer figure_title © 2024 The Authors. Small Science published by Wiley-VCH GmbH Figure 7. Analysis of the efficacy of the IC in vivo stimulation parameters (magnetic field and frequency) on human patients, based on the reported bone-associated outcomes. A) Overview of the IC effi [679, 1479, 1091, 1499] [97, 1118, 1099, 1261] noise figure_caption 0.9 0.92 ["footer label"] ["figure_title label: Figure 7. Analysis of the efficacy of the IC in vivo stimula"] noise figure_caption 0.9 0.92 body_zone display_zone body_like legend_like none figure_number False True False True
255 16 15 14 7 aside_text text 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar 1007 ununited fractures. Similar success rates were obtained when comparing PEMF against surgery with bone grafts, to treat ununited tibial fractures. Aaron et al. $ ^{[162]} $ (2004) concluded that b [1153, 22, 1171, 1542] [96, 1301, 588, 1437] noise body_paragraph 0.95 0.78 ["margin-band narrow/tall geometry; treated as noise"] ["default body_paragraph for text label", "late role resolution: non-body family 'reference_like' overrides body_paragraph", "style_family_authority=reference_marker", "context_source=block"] noise body_paragraph 0.95 0.6 body_zone body_like reference_like none reference_numeric_dot False True False True
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257 17 15 1 9 header text small science Examples of setups with positive osteogenic effects include the EBI Bone Healing System Model 420 (15 Hz pulses, 4.5 kHz bursts, 8–10 h day $ ^{-1} $) to treat scaphoid non-unions, which [1014, 14, 1098, 80] [605, 1368, 1098, 1436] noise body_paragraph 0.9 0.6 ["header label"] ["default body_paragraph for text label"] noise body_paragraph 0.9 0.6 body_zone unknown_like body_like short_fragment none False True False True
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259 17 15 3 11 text footer prosthesis, BMD levels at 0 and 90 post-operative days, were measured on different zones following stimulation with PEMF of 75 Hz, 2.0 mT (6 h day $ ^{-1} $). Although no significant differences were 2300303 (15 of 25) [96, 139, 588, 361] [403, 1476, 551, 1499] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 unknown_like reference_like none reference_numeric_dot True False True False
17 4 paragraph_title 3.2.4. Handling Osteoarthritis in Humans Through IC Stimulation [97, 387, 585, 411] subsection_heading 0.85 ["paragraph_title label with numbering: 3.2.4. Handling Osteoarthritis in Humans Through IC Stimulat"] subsection_heading 0.85 unknown_like heading_numbered True True
17 5 text Only two studies tested the efficacy of PEMF on (knee) osteoarthritis. One study used the FDA-approved MAGCELL ARTHRO device to deliver PEMF of 8 Hz, 105 mT for 5 min twice-a-day, for 15 days, and ati [96, 431, 588, 742] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 unknown_like none True True
17 6 paragraph_title 3.2.5. Addressing Soft Tissue Disorders in Humans with IC Stimulation [97, 767, 528, 815] subsection_heading 0.85 ["paragraph_title label with numbering: 3.2.5. Addressing Soft Tissue Disorders in Humans with IC St"] subsection_heading 0.85 unknown_like heading_numbered True True
260 17 15 7 12 text footer In the only study on IC clinical application for soft tissues reported in the literature, PEMF stimuli of very high frequency (1 kHz pulses, with 27 MHz bursts) could improve soft tissue healing, pain © 2024 The Authors. Small Science published by Wiley-VCH GmbH [96, 835, 588, 950] [687, 1479, 1096, 1498] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["footer label"] body_paragraph noise 0.6 0.9 body_zone unknown_like body_like none True False True False
261 17 15 8 13 paragraph_title aside_text 3.3. Findings from IC Clinical Studies 26884046, 2024, 5. Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [97, 973, 387, 997] [1154, 28, 1171, 1540] subsection_heading noise 0.85 0.95 ["paragraph_title label with numbering: 3.3. Findings from IC Clinical Studies"] ["margin-band narrow/tall geometry; treated as noise"] subsection_heading noise 0.85 0.95 body_zone unknown_like body_like heading_numbered none True False True False
262 17 16 9 0 text header The relative efficacy of the IC clinical studies, according to the applied stimuli parameters, is presented in Figure 6 (global overview for each parameter) and Figure 7, which associates pairs of fre ADVANCED SCIENCE NEWS www.advancedsciencenews.com [95, 1018, 587, 1129] [92, 32, 311, 106] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 body_zone unknown_like body_like none True False True False
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278 18 17 4 1 figure_title header Figure 8. Examples of biological outcomes assessed in IC stimulation studies in humans. A) Anteroposterior and lateral radiographs of a distal tibial nonunion: i) 10 months after fracture; ii) after P small science [90, 1149, 1093, 1293] [1014, 14, 1098, 80] figure_caption noise 0.92 0.9 ["figure_title label: Figure 8. Examples of biological outcomes assessed in IC sti"] ["header label"] figure_caption noise 0.92 0.9 display_zone support_like unknown_like figure_number short_fragment True False True False
279 18 17 5 2 text header storages, increasing the cytosolic Ca²⁺ concentration. This potentially occurs through the activation of ryanodine-dependent Ca²⁺ channels (RyR) or inositol 1,4,5-triphosphate receptors (IP₃R) of the www.small-science-journal.com [90, 1326, 581, 1439] [884, 86, 1097, 106] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 unknown_like none True False True False
280 18 17 6 3 text coupled with the activation of voltage-sensitive enzymes, the reorganization of the cytoskeleton, and the activation of Ca2þ-dependent enzymes, including calmodulin (CaM).[190] In osteoblasts, calcine prosthesis, BMD levels at 0 and 90 post-operative days, were measured on different zones following stimulation with PEMF of 75 Hz, 2.0 mT (6 h day $ ^{-1} $). Although no significant differences were [599, 1326, 1093, 1440] [96, 139, 588, 361] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like unknown_like none True True
281 18 17 7 4 footer paragraph_title Small Sci. 2024, 4, 2300303 3.2.4. Handling Osteoarthritis in Humans Through IC Stimulation [94, 1479, 260, 1498] [97, 387, 585, 411] noise sub_subsection_heading 0.9 0.85 ["footer label"] ["paragraph_title label with numbering: 3.2.4. Handling Osteoarthritis in Humans Through IC Stimulat"] noise sub_subsection_heading 0.9 0.85 body_zone unknown_like none heading_numbered False True False True
282 18 17 8 5 footer text 2300303 (18 of 25) Only two studies tested the efficacy of PEMF on (knee) osteoarthritis. One study used the FDA-approved MAGCELL ARTHRO device to deliver PEMF of 8 Hz, 105 mT for 5 min twice-a-day, for 15 days, and ati [396, 1476, 545, 1499] [96, 431, 588, 742] noise body_paragraph 0.9 0.6 ["footer label"] ["default body_paragraph for text label"] noise body_paragraph 0.9 0.6 reference_zone body_zone reference_like unknown_like reference_numeric_dot none False True False True
291 19 17 6 14 text increased sAC, serum cAMP, p-PKA and p-CREB.[102,121] This sequence of events promotes osteoblastogenic effects, for example by allowing the accumulation of β-catenin[201] and thus cross-talking with Overall, this study indicates that it would be desirable to develop more attractive devices for daily use, with the ability to provide personalized stimuli, and highlights the need to comprehensively [604, 914, 1099, 1137] [605, 1065, 1099, 1178] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
292 19 17 7 15 text paragraph_title In contrast, IC stimulation can also regulate osteoclast differentiation and activity, by increasing the OPG/RANKL ratio. The increase in OPG expression, together with a decrease in RANKL expression, 4. The Potential Biomechanism Behind IC Therapeutic Effects [604, 1139, 1099, 1433] [606, 1212, 1018, 1266] body_paragraph reference_item 0.6 0.85 ["default body_paragraph for text label"] ["paragraph_title label with numbering: 4. The Potential Biomechanism Behind IC Therapeutic Effects"] body_paragraph section_heading 0.6 0.85 reference_zone body_like reference_like none reference_numeric_dot True True
293 19 17 8 16 footer text Small Sci. 2024, 4, 2300303 At the turn of the 21 $ ^{st} $ century, various groups started attempting to infer the biomechanisms underlying the IC effects on the musculoskeletal system, with this line of research accelerating i [99, 1479, 267, 1498] [604, 1282, 1099, 1439] noise body_paragraph 0.9 0.6 ["footer label"] ["default body_paragraph for text label"] noise body_paragraph 0.9 0.6 tail_nonref_hold_zone unknown_like body_like none False True False True
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298 20 18 3 0 text header of bone resorption, and thus a decrease in serum CTX. $ ^{[87,88,102,112,120,121,126,180]} $ Netrin 4 may also play a role in the PEMF-induced decrease of osteoclastogenesis, $ ^{[202]} $ since PEMF i ADVANCED SCIENCE NEWS www.advancedsciencenews.com [90, 138, 582, 359] [92, 32, 312, 105] body_paragraph noise 0.6 0.9 ["default body_paragraph for text label"] ["header label"] body_paragraph noise 0.6 0.9 unknown_like none True False True False
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308 20 18 13 10 aside_text 26884046, 2024, 5. Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smse.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smse.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [1154, 29, 1171, 1541] [1154, 30, 1171, 1542] noise 0.95 ["margin-band narrow/tall geometry; treated as noise"] noise 0.95 unknown_like none False False
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21 3 text devices, will be vital for pushing forward the clinical implementation and achieve the full therapeutic potential of IC stimulation for musculoskeletal disorders, toward more effective and tailored pa [97, 138, 587, 228] body_paragraph 0.6 ["default body_paragraph for text label"] body_paragraph 0.6 body_zone body_like none True True
21 4 paragraph_title Supporting Information [98, 266, 329, 292] backmatter_heading 0.5 ["backmatter boundary candidate: Supporting Information"] backmatter_boundary_candidate 0.5 heading_like none True True
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312 21 19 6 3 paragraph_title image Acknowledgements [98, 381, 288, 406] [147, 141, 1052, 672] sub_subsection_heading media_asset 0.6 0.85 ["unnumbered paragraph_title, inferred level sub_subsection_heading: Acknowledgements"] ["media label: image"] sub_subsection_heading media_asset 0.6 0.85 body_zone heading_like unknown_like short_fragment empty True True
313 21 19 7 4 text figure_title J.G.S.F. and B.M.de.S. contributed equally to this work. The authors acknowledge the support of Fundação para a Ciência e Tecnologia (Portugal), Centro 2020, the COMPETE program, QREN, and the Europea Figure 9. Biomechanisms that may underly the observed therapeutic bone-associated effects of inductive coupling (IC) in vivo stimulation. The electromagnetic fields (EMF) delivered by IC pass the cyto [96, 417, 588, 666] [95, 693, 1102, 877] backmatter_body figure_caption 0.6 0.92 ["default body_paragraph for text label", "promoted in tail spread from body_paragraph"] ["figure_title label: Figure 9. Biomechanisms that may underly the observed therap"] body_paragraph figure_caption 0.6 0.92 display_zone unknown_like legend_like none figure_number True True
314 21 19 8 5 paragraph_title text Conflict of Interest Factor of Activated T Cells 1 (NFATc1), promoting its nuclear translocation and a subsequent increase in the transcription of genes related to the Wnt/ $ \beta $-catenin pathway. $ ^{[192]} $ Followin [98, 704, 284, 729] [96, 916, 589, 1435] subsection_heading body_paragraph 0.6 ["unnumbered paragraph_title, inferred level subsection_heading: Conflict of Interest"] ["default body_paragraph for text label"] subsection_heading body_paragraph 0.6 frontmatter_side_zone body_zone support_like unknown_like none True True
315 21 19 9 6 text The authors declare no conflict of interest. [98, 741, 390, 761] [604, 914, 1099, 1137] frontmatter_noise unknown_structural 0.6 0.3 ["default body_paragraph for text label", "frontmatter_side_zone excluded from body flow"] ["short text, uncertain role"] frontmatter_noise unknown_structural 0.6 0.3 frontmatter_side_zone support_like body_like none empty False False True
320 21 19 14 11 text aside_text Published online: February 26, 2024 26884046, 2024, 5, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/smsc.202300303 by CochraneChina, Wiley Online Library on [19/07/2025]. See the Terms and Conditions (https://onlinelibrar [341, 962, 586, 982] [1153, 29, 1171, 1542] backmatter_body noise 0.88 0.95 ["default body_paragraph for text label", "late role resolution: editorial phrase cross-validates non-body classification", "zone=body_zone", "style_family=support_like"] ["margin-band narrow/tall geometry; treated as noise"] body_paragraph noise 0.6 0.95 body_zone support_like unknown_like none True False True False
321 21 20 15 0 reference_content header [1] T. Vos, S. S. Lim, C. Abbafati, K. M. Abbas, M. Abbasi, M. Abbasifard, M. Abbasi-Kangevari, H. Abbastabar, F. Abd-Allah, A. Abdelalim, M. Abdollahi, I. Abdollahpour, H. Abolhassani, V. Aboyans, E. ADVANCED SCIENCE NEWS www.advancedsciencenews.com [105, 1027, 586, 1191] [92, 32, 311, 106] reference_item noise 0.85 0.9 ["reference content label: [1] T. Vos, S. S. Lim, C. Abbafati, K. M. Abbas, M. Abbasi, "] ["header label"] reference_item noise 0.85 0.9 reference_zone reference_like unknown_like reference_numeric_bracket none True False True False
322 21 20 16 1 reference_content header [2] H. Wang, K. M. Abbas, M. Abbasifard, M. Abbasi-Kangevari, H. Abbastabar, F. Abd-Allah, A. Abdelalim, H. Abolhassani, L. G. Abreu, M. R. M. Abrigo, A. I. Abushouk, M. Adabi, T. Adair, O. M. Adebayo small science [108, 1193, 586, 1353] [1008, 14, 1092, 81] reference_item noise 0.85 0.9 ["reference content label: [2] H. Wang, K. M. Abbas, M. Abbasifard, M. Abbasi-Kangevari"] ["header label"] reference_item noise 0.85 0.9 reference_zone reference_like unknown_like reference_numeric_bracket short_fragment True False True False
323 21 20 17 2 reference_content header [3] T. Vos, A. D. Flaxman, M. Naghavi, R. Lozano, C. Michaud, M. Ezzati, K. Shibuya, J. A. Salomon, S. Abdalla, V. Aboyans, J. Abraham, I. Ackerman, R. Aggarwal, S. Y. Ahn, M. K. Ali, M. Alvarado, H. www.small-science-journal.com [107, 1356, 587, 1438] [878, 86, 1091, 107] reference_item noise 0.85 0.9 ["reference content label: [3] T. Vos, A. D. Flaxman, M. Naghavi, R. Lozano, C. Michaud"] ["header label"] reference_item noise 0.85 0.9 reference_zone reference_like unknown_like reference_numeric_bracket none True False True False
324 21 20 18 3 reference_content text L. M. Baddour, A. N. Bahalim, S. Barker-Collo, L. H. Barrero, D. H. Bartels, M.-G. Basáñez, A. Baxter, M. L. Bell, E. J. Benjamin, D. Bennett, et al., Lancet 2012, 380, 2163. of bone resorption, and thus a decrease in serum CTX. $ ^{[87,88,102,112,120,121,126,180]} $ Netrin 4 may also play a role in the PEMF-induced decrease of osteoclastogenesis, $ ^{[202]} $ since PEMF i [638, 140, 1096, 201] [90, 138, 582, 359] reference_item body_paragraph 0.85 0.6 ["reference content label: L. M. Baddour, A. N. Bahalim, S. Barker-Collo, L. H. Barrero"] ["default body_paragraph for text label"] reference_item body_paragraph 0.85 0.6 reference_zone body_zone unknown_like none True True
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