From 0e04bcd5f7ff2af27857e8c09d9aaff6622b2318 Mon Sep 17 00:00:00 2001 From: LLLin000 <809867916@qq.com> Date: Mon, 29 Jun 2026 12:32:03 +0800 Subject: [PATCH] fix: post-P1 bio detection fixes MIME-Version: 1.0 Content-Type: text/plain; charset=UTF-8 Content-Transfer-Encoding: 8bit - Raise word limit 80→200 (real bio text is 90-100 words) - Add structured_insert_candidate to Pass C role list (fixes Barbara bio miss) - Fix page-agnostic block_id filter in ocr_figures.py (lines 4479, 4529) - Was filtering by bare block_id, colliding same id across pages - Changed to (page, block_id) tuples - Add bio passes (Pass B+C) to ocr_rebuild.py pipeline --- paperforge/worker/ocr_bio.py | 6 +- paperforge/worker/ocr_figures.py | 22 +- paperforge/worker/ocr_rebuild.py | 16 ++ .../ocr_real_papers/4AG67PBH/block_trace.csv | 213 +++++++----------- 4 files changed, 123 insertions(+), 134 deletions(-) diff --git a/paperforge/worker/ocr_bio.py b/paperforge/worker/ocr_bio.py index 85d76487..047b925e 100644 --- a/paperforge/worker/ocr_bio.py +++ b/paperforge/worker/ocr_bio.py @@ -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 "") diff --git a/paperforge/worker/ocr_figures.py b/paperforge/worker/ocr_figures.py index 2d36f5c1..f9aae4bd 100644 --- a/paperforge/worker/ocr_figures.py +++ b/paperforge/worker/ocr_figures.py @@ -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( diff --git a/paperforge/worker/ocr_rebuild.py b/paperforge/worker/ocr_rebuild.py index ba5c7c97..cf339378 100644 --- a/paperforge/worker/ocr_rebuild.py +++ b/paperforge/worker/ocr_rebuild.py @@ -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 diff --git a/tests/fixtures/ocr_real_papers/4AG67PBH/block_trace.csv b/tests/fixtures/ocr_real_papers/4AG67PBH/block_trace.csv index 8fa41ece..f1976b99 100644 --- a/tests/fixtures/ocr_real_papers/4AG67PBH/block_trace.csv +++ b/tests/fixtures/ocr_real_papers/4AG67PBH/block_trace.csv @@ -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 9,16,footer,2300303 (9 of 25),"[406, 1476, 547, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False @@ -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""]" 10,9,image,,"[125, 941, 486, 1183]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,True,True 10,10,image,,"[556, 944, 832, 1180]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,True,True 10,11,image,,"[837, 954, 1079, 1181]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,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,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 10,13,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 10,14,number,2300303 (10 of 25),"[396, 1476, 545, 1499]",noise,0.9,"[""page number label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False 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""]" 13,13,figure_title,E,"[277, 854, 295, 875]",figure_inner_text,0.9,"[""panel label / figure inner text: E""]",figure_inner_text,0.9,display_zone,legend_like,panel_label,True,True 13,14,image,,"[319, 863, 491, 1048]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,unknown_like,empty,True,True 13,15,image,,"[506, 733, 717, 1046]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,body_zone,body_like,empty,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,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 +13,18,text,,"[604, 1263, 1098, 1422]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,body_zone,body_like,empty,False,True 13,19,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 13,20,footer,2300303 (13 of 25),"[402, 1476, 551, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False 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 14,16,footer,2300303 (14 of 25),"[396, 1476, 545, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False @@ -315,10 +291,8 @@ www.advancedsciencenews.com","[98, 31, 318, 106]",noise,0.9,"[""header label""]" 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 15,11,footer,2300303 (15 of 25),"[403, 1476, 551, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False @@ -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 16,11,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 16,12,footer,2300303 (16 of 25),"[395, 1476, 546, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,reference_like,reference_numeric_dot,False,False @@ -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 17,1,header,small science,"[1014, 14, 1098, 80]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False 17,2,header,www.small-science-journal.com,"[884, 86, 1097, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False -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 +17,15,paragraph_title,4. The Potential Biomechanism Behind IC Therapeutic Effects,"[606, 1212, 1018, 1266]",reference_item,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,True,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,tail_nonref_hold_zone,body_like,none,True,True 17,17,footer,"Small Sci. 2024, 4, 2300303","[99, 1479, 267, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -17,18,footer,2300303 (17 of 25),"[402, 1476, 552, 1499]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +17,18,footer,2300303 (17 of 25),"[402, 1476, 552, 1499]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 17,19,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[686, 1479, 1097, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False 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 @@ -376,14 +344,11 @@ www.advancedsciencenews.com","[92, 32, 312, 105]",noise,0.9,"[""header label""]" 18,1,header,small science,"[1008, 13, 1092, 80]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False 18,2,header,www.small-science-journal.com,"[878, 86, 1091, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False 18,3,image,,"[189, 137, 994, 1132]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,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,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 +18,6,text,,"[599, 1326, 1093, 1440]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,,body_like,empty,False,True 18,7,footer,"Small Sci. 2024, 4, 2300303","[94, 1479, 260, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -18,8,footer,2300303 (18 of 25),"[396, 1476, 545, 1499]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +18,8,footer,2300303 (18 of 25),"[396, 1476, 545, 1499]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 18,9,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[680, 1479, 1091, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False 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 @@ -393,14 +358,11 @@ www.advancedsciencenews.com","[98, 32, 317, 105]",noise,0.9,"[""header label""]" 19,2,header,www.small-science-journal.com,"[884, 87, 1097, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False 19,3,image,,"[147, 141, 1052, 672]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True 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 +19,6,text,,"[604, 914, 1099, 1137]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,,body_like,empty,False,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_zone,body_like,none,True,True 19,8,footer,"Small Sci. 2024, 4, 2300303","[99, 1479, 267, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -19,9,footer,2300303 (19 of 25),"[402, 1476, 552, 1499]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +19,9,footer,2300303 (19 of 25),"[402, 1476, 552, 1499]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 19,10,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[687, 1479, 1097, 1499]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False 19,11,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, 1542]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False 20,0,header,"ADVANCED @@ -408,18 +370,15 @@ SCIENCE NEWS www.advancedsciencenews.com","[92, 32, 311, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False 20,1,header,small science,"[1008, 14, 1092, 81]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False 20,2,header,www.small-science-journal.com,"[878, 86, 1091, 107]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False -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 -20,6,paragraph_title,5. General Conclusions and Future Perspectives,"[90, 1328, 561, 1355]",section_heading,0.85,"[""paragraph_title label with numbering: 5. General Conclusions and Future Perspectives""]",section_heading,0.85,,heading_like,heading_numbered,True,True -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 +20,6,paragraph_title,5. General Conclusions and Future Perspectives,"[90, 1328, 561, 1355]",section_heading,0.85,"[""paragraph_title label with numbering: 5. General Conclusions and Future Perspectives""]",section_heading,0.85,body_zone,heading_like,heading_numbered,True,True +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 +20,8,text,,"[597, 140, 1093, 1305]",unknown_structural,0.3,"[""short text, uncertain role""]",unknown_structural,0.3,,body_like,empty,False,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_zone,body_like,none,True,True 20,10,footer,"Small Sci. 2024, 4, 2300303","[93, 1479, 261, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -20,11,footer,2300303 (20 of 25),"[396, 1476, 545, 1499]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +20,11,footer,2300303 (20 of 25),"[396, 1476, 545, 1499]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 20,12,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[680, 1479, 1091, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False 20,13,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, 29, 1171, 1541]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False 21,0,header,"ADVANCED @@ -428,17 +387,17 @@ www.advancedsciencenews.com","[99, 32, 317, 106]",noise,0.9,"[""header label""]" 21,1,header,small science,"[1015, 14, 1098, 80]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False 21,2,header,www.small-science-journal.com,"[884, 87, 1097, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False 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 +21,4,paragraph_title,Supporting Information,"[98, 266, 329, 292]",backmatter_boundary_candidate,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]",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 -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,body_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]",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 21,16,reference_content,"[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","[108, 1193, 586, 1353]",reference_item,0.85,"[""reference content label: [2] H. Wang, K. M. Abbas, M. Abbasifard, M. Abbasi-Kangevari""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True 21,17,reference_content,"[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. ","[107, 1356, 587, 1438]",reference_item,0.85,"[""reference content label: [3] T. Vos, A. D. Flaxman, M. Naghavi, R. Lozano, C. Michaud""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True @@ -474,7 +433,7 @@ www.advancedsciencenews.com","[99, 32, 317, 106]",noise,0.9,"[""header label""]" 21,47,reference_content,"[32] J. C. Gan, P. A. Glazer, Eur. Spine J. 2006, 15, 1301.","[609, 1355, 994, 1375]",reference_item,0.85,"[""reference content label: [32] J. C. Gan, P. A. Glazer, Eur. Spine J. 2006, 15, 1301.""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True 21,48,reference_content,"[33] C. T. Rubin, S. Judex, Y.-X. Qin, J. Rubin, in Osteoporosis, 4th ed. (Eds: R. Marcus, D. Feldman, D. W. Dempster, M. Luckey, J. A. Cauley), Academic Press, San Diego 2013, pp. 517–535.","[610, 1378, 1097, 1437]",reference_item,0.85,"[""reference content label: [33] C. T. Rubin, S. Judex, Y.-X. Qin, J. Rubin, in Osteopor""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True 21,49,footer,"Small Sci. 2024, 4, 2300303","[99, 1480, 266, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -21,50,footer,2300303 (21 of 25),"[402, 1477, 551, 1498]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +21,50,footer,2300303 (21 of 25),"[402, 1477, 551, 1498]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 21,51,footer,© 2024 The Authors. Small Science published by Wiley-VCH GmbH,"[687, 1480, 1096, 1498]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False 21,52,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","[1155, 32, 1171, 1536]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False 22,0,header,"ADVANCED @@ -542,7 +501,7 @@ www.advancedsciencenews.com","[93, 32, 311, 105]",noise,0.9,"[""header label""]" 22,60,reference_content,"[91] T. Shimizu, J. E. Zerwekh, T. Videman, K. Gill, V. Mooney, R. E. Holmes, H. K. Hagler, J. Orthop. Res. 1988, 6, 248.","[604, 1356, 1089, 1395]",reference_item,0.85,"[""reference content label: [91] T. Shimizu, J. E. Zerwekh, T. Videman, K. Gill, V. Moon""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True 22,61,reference_content,"[92] J. A. Spadaro, S. A. Albanese, S. E. Chase, J. Orthop. Res. 1990, 8, 685.","[603, 1398, 1090, 1435]",reference_item,0.85,"[""reference content label: [92] J. A. Spadaro, S. A. Albanese, S. E. Chase, J. Orthop. ""]",reference_item,0.85,reference_zone,reference_like,reference_numeric_bracket,True,True 22,62,footer,"Small Sci. 2024, 4, 2300303","[94, 1480, 260, 1497]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -22,63,footer,2300303 (22 of 25),"[396, 1477, 545, 1498]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +22,63,footer,2300303 (22 of 25),"[396, 1477, 545, 1498]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 22,64,footer,© 2024 The Authors. 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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 23,63,footer,"Small Sci. 2024, 4, 2300303","[100, 1480, 266, 1497]",noise,0.9,"[""footer label""]",noise,0.9,,unknown_like,none,False,False -23,64,footer,2300303 (23 of 25),"[403, 1477, 551, 1498]",noise,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,False,False +23,64,footer,2300303 (23 of 25),"[403, 1477, 551, 1498]",reference_item,0.9,"[""footer label""]",noise,0.9,reference_zone,reference_like,reference_numeric_dot,True,True 23,65,footer,© 2024 The Authors. 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See the Terms and Conditions (https://onlinelibrar","[1155, 34, 1171, 1537]",noise,0.95,"[""margin-band narrow/tall geometry; treated as noise""]",noise,0.95,,unknown_like,none,False,False 25,0,header,"ADVANCED @@ -687,14 +646,14 @@ www.advancedsciencenews.com","[98, 32, 318, 106]",noise,0.9,"[""header label""]" 25,1,header,small science,"[1014, 14, 1098, 81]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,short_fragment,False,False 25,2,header,www.small-science-journal.com,"[884, 86, 1097, 106]",noise,0.9,"[""header label""]",noise,0.9,,unknown_like,none,False,False 25,3,image,,"[112, 150, 261, 343]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True -25,4,figure_title,"José G. S. Figueiredo is a Ph.D. student of Rehabilitation Sciences at Institute of Biomedicine (iBiMED), Department of Medical Sciences of the University of Aveiro, since 2022 and a research fellow a","[270, 144, 1067, 301]",figure_caption,0.85,"[""figure_title label: Jos\u00e9 G. S. Figueiredo is a Ph.D. student of Rehabilitation S""]",figure_caption,0.85,,legend_like,none,True,True +25,4,figure_title,"José G. S. Figueiredo is a Ph.D. student of Rehabilitation Sciences at Institute of Biomedicine (iBiMED), Department of Medical Sciences of the University of Aveiro, since 2022 and a research fellow a","[270, 144, 1067, 301]",reference_item,0.85,"[""figure_title label: Jos\u00e9 G. S. Figueiredo is a Ph.D. student of Rehabilitation S""]",figure_caption,0.85,reference_zone,legend_like,none,True,True 25,5,image,,"[117, 357, 262, 549]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True -25,6,text,"Bárbara M. de Sousa holds a BSc in Biomedical Sciences and a MSc in Biochemistry and is currently a Ph.D. student in Biomedicine (University of Aveiro, Portugal). Bárbara's research interests revolve ","[271, 354, 1077, 489]",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 +25,6,text,"Bárbara M. de Sousa holds a BSc in Biomedical Sciences and a MSc in Biochemistry and is currently a Ph.D. student in Biomedicine (University of Aveiro, Portugal). Bárbara's research interests revolve ","[271, 354, 1077, 489]",structured_insert_candidate,0.6,"[""default body_paragraph for text label""]",body_paragraph,0.6,tail_nonref_hold_zone,unknown_like,none,False,False 25,7,image,,"[116, 564, 264, 762]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True 25,8,text,"Marco P. Soares dos Santos is assistant professor at the Department of Mechanical Engineering of the University of Aveiro, Portugal, since 2020. He graduated in Electrical and Computers Engineering fr","[270, 561, 1076, 720]",reference_item,0.82,"[""default body_paragraph for text label"", ""late role resolution: reference_like family + reference zone"", ""style_family_authority=reference_marker"", ""context_source=block""]",body_paragraph,0.6,reference_zone,reference_like,citation_line,True,True 25,9,image,,"[117, 771, 262, 967]",media_asset,0.85,"[""media label: image""]",media_asset,0.85,,unknown_like,empty,True,True 25,10,text,"Sandra I. 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