Pub Date : 2025-12-01Epub Date: 2025-11-02DOI: 10.1016/j.mehy.2025.111810
Sallie S. Schneider , Brian T. Pentecost , Ashley R. Banas , Aliyah Dalier , Vignesh Narayanaswamy , Emma C. Gotschlich , Kathleen F. Arcaro
Chronic inflammation likely contributes to breast cancer risk, but epidemiologic studies are inconclusive. Two types of inflammatory episodes in breast tissue, referred to here as clinical mastitis and subclinical mastitis, have received little to no attention as risk factors for breast cancer. Clinical mastitis represents an acute painful inflammatory state of the breast that in most cases will be quickly treated and resolved. In contrast, subclinical mastitis remains undetected in most cases and may represent chronic inflammation. Based on the concentration of sodium (Na) and cytokines in milk, several publications suggest that subclinical mastitis is relatively common and can persist for extended periods. We propose that subclinical mastitis is a modifiable risk factor for breast cancer. This chronic subclinical inflammatory profile in breast tissue may cause genetic instability and perturb epigenetic mechanisms leading to cancer. We suggest studies to determine the extent that subclinical mastitis is associated with breast cancer risk.
{"title":"Subclinical mastitis during lactation: A modifiable risk factor for breast cancer?","authors":"Sallie S. Schneider , Brian T. Pentecost , Ashley R. Banas , Aliyah Dalier , Vignesh Narayanaswamy , Emma C. Gotschlich , Kathleen F. Arcaro","doi":"10.1016/j.mehy.2025.111810","DOIUrl":"10.1016/j.mehy.2025.111810","url":null,"abstract":"<div><div>Chronic inflammation likely contributes to breast cancer risk, but epidemiologic studies are inconclusive. Two types of inflammatory episodes in breast tissue, referred to here as clinical mastitis and subclinical mastitis, have received little to no attention as risk factors for breast cancer. Clinical mastitis represents an acute painful inflammatory state of the breast that in most cases will be quickly treated and resolved. In contrast, subclinical mastitis remains undetected in most cases and may represent chronic inflammation. Based on the concentration of sodium (Na) and cytokines in milk, several publications suggest that subclinical mastitis is relatively common and can persist for extended periods. We propose that subclinical mastitis is a modifiable risk factor for breast cancer. This chronic subclinical inflammatory profile in breast tissue may cause genetic instability and perturb epigenetic mechanisms leading to cancer. We suggest studies to determine the extent that subclinical mastitis is associated with breast cancer risk.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111810"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-23DOI: 10.1016/j.mehy.2025.111793
Yu-Hsiang Lin , Po-Ting Lin , Kuo-Jen Lin , Tzu-Chi Teng , Yu-Ting Chen , Chen-Pang Hou , Jau-Yuan Chen , Chien-Lun Chen
The age-related decline in testosterone, often termed ’andropause,’ is traditionally viewed as an inevitable consequence of aging. However, emerging evidence suggests this decline is more closely associated with accumulating comorbidities than with age itself. We propose a unifying hypothesis of ’sleep disruption-induced hypogonadism,’ an acquired and potentially reversible condition driven by common age-related pathologies such as benign prostatic hyperplasia (BPH), obstructive sleep apnea (OSA), and chronic pain. These conditions precipitate a vicious cycle where symptoms like nocturia cause chronic sleep fragmentation and circadian dysregulation. This, in turn, suppresses the hypothalamic-pituitary–gonadal (HPG) axis, leading to reduced endogenous testosterone. This hypothesis is supported by extensive correlational data linking sleep disorders to low testosterone and, more compellingly, by interventional studies demonstrating that treatment of underlying sleep disruptors—such as BPH surgery or nocturia medication—can significantly restore testosterone levels. This framework also resolves the paradox of why CPAP therapy often fails to raise testosterone by highlighting the powerful confounding role of obesity. The primary implication of this hypothesis is a proposed paradigm shift in clinical practice: from a focus on hormone replacement to a ’sleep-centric,’ cause-oriented approach. We advocate that the diagnostic workup for low testosterone in aging men should include a primary assessment for and treatment of underlying sleep disorders before considering testosterone replacement therapy, fostering a more integrated, multidisciplinary management strategy.
{"title":"Sleep-induced hypogonadism: A unifying hypothesis linking BPH, OSA, and low testosterone","authors":"Yu-Hsiang Lin , Po-Ting Lin , Kuo-Jen Lin , Tzu-Chi Teng , Yu-Ting Chen , Chen-Pang Hou , Jau-Yuan Chen , Chien-Lun Chen","doi":"10.1016/j.mehy.2025.111793","DOIUrl":"10.1016/j.mehy.2025.111793","url":null,"abstract":"<div><div>The age-related decline in testosterone, often termed ’andropause,’ is traditionally viewed as an inevitable consequence of aging. However, emerging evidence suggests this decline is more closely associated with accumulating comorbidities than with age itself. We propose a unifying hypothesis of ’sleep disruption-induced hypogonadism,’ an acquired and potentially reversible condition driven by common age-related pathologies such as benign prostatic hyperplasia (BPH), obstructive sleep apnea (OSA), and chronic pain. These conditions precipitate a vicious cycle where symptoms like nocturia cause chronic sleep fragmentation and circadian dysregulation. This, in turn, suppresses the hypothalamic-pituitary–gonadal (HPG) axis, leading to reduced endogenous testosterone. This hypothesis is supported by extensive correlational data linking sleep disorders to low testosterone and, more compellingly, by interventional studies demonstrating that treatment of underlying sleep disruptors—such as BPH surgery or nocturia medication—can significantly restore testosterone levels. This framework also resolves the paradox of why CPAP therapy often fails to raise testosterone by highlighting the powerful confounding role of obesity. The primary implication of this hypothesis is a proposed paradigm shift in clinical practice: from a focus on hormone replacement to a ’sleep-centric,’ cause-oriented approach. We advocate that the diagnostic workup for low testosterone in aging men should include a primary assessment for and treatment of underlying sleep disorders before considering testosterone replacement therapy, fostering a more integrated, multidisciplinary management strategy.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111793"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145366103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-21DOI: 10.1016/j.mehy.2025.111794
Debabrata Dash, Raj Kumar Koiri
Natural and anthropogenic electromagnetic fields (EMFs) are also beginning to be studied as possible environmental etiologic factors for neurologic disease like cognitive impairment, sleep disorder, and neurodegenerative disease. While there has been experience in experimental studies of EMF impacts on neuronal physiology, extensive spatially resolved epidemiologic studies connecting EMF exposure and neurologic disease are few. The present paper outlines a new hypothesis that satellite EMF “hotspots” are mappable and can be linked to adjacent neurological well-being data to quantify population-level hazard. A fictional multi-step approach is presented whereby high-resolution space-based EMF information is combined with epidemiological data of neurological disease. Geospatial analytical techniques viz., hotspot mapping, spatial regression, and cluster detection are suggested to investigate potential correlation, and pilot validation with hand-held EMF meters and small-scale in vitro or in vivo models would examine biological mechanisms such as oxidative stress, neuroinflammation, and neuronal apoptosis. Confounding variables like socioeconomic, genetic, and environmental exposures would be held constant statistically. If confirmed, locations with elevated EMF field intensity would be predicted to have increased neurological disease, geospatial models potentially identifying dose–response relationships. Such an outcome would allow predictive EMF neuro-health risk maps to be developed for public health monitoring and evidence-based urban planning. In total, this theoretical model combines exposure assessment and neuroepidemiology into one framework and provides a basis for geospatial neurology and preclinical identification of vulnerable populations and guides prevention strategies and provokes future empirical and translational research.
{"title":"Satellite-derived EMF mapping for predicting neurological health risks: A medical hypothesis","authors":"Debabrata Dash, Raj Kumar Koiri","doi":"10.1016/j.mehy.2025.111794","DOIUrl":"10.1016/j.mehy.2025.111794","url":null,"abstract":"<div><div>Natural and anthropogenic electromagnetic fields (EMFs) are also beginning to be studied as possible environmental etiologic factors for neurologic disease like cognitive impairment, sleep disorder, and neurodegenerative disease. While there has been experience in experimental studies of EMF impacts on neuronal physiology, extensive spatially resolved epidemiologic studies connecting EMF exposure and neurologic disease are few. The present paper outlines a new hypothesis that satellite EMF “hotspots” are mappable and can be linked to adjacent neurological well-being data to quantify population-level hazard. A fictional multi-step approach is presented whereby high-resolution space-based EMF information is combined with epidemiological data of neurological disease. Geospatial analytical techniques viz., hotspot mapping, spatial regression, and cluster detection are suggested to investigate potential correlation, and pilot validation with hand-held EMF meters and small-scale <em>in vitro</em> or <em>in vivo</em> models would examine biological mechanisms such as oxidative stress, neuroinflammation, and neuronal apoptosis. Confounding variables like socioeconomic, genetic, and environmental exposures would be held constant statistically. If confirmed, locations with elevated EMF field intensity would be predicted to have increased neurological disease, geospatial models potentially identifying dose–response relationships. Such an outcome would allow predictive EMF neuro-health risk maps to be developed for public health monitoring and evidence-based urban planning. In total, this theoretical model combines exposure assessment and neuroepidemiology into one framework and provides a basis for geospatial neurology and preclinical identification of vulnerable populations and guides prevention strategies and provokes future empirical and translational research.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111794"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145340514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-26DOI: 10.1016/j.mehy.2025.111797
Yoshito Mukaino , Masahiko Mukaino
While evidence supports the therapeutic effects of acupuncture, particularly for analgesia, the mechanism for its distant effects remains debated. Conventional neurobiological theories, while valid, do not fully account for the rapid, systemic, and meridian-specific responses seen in clinical practice. This paper proposes a ’tension-reset’ hypothesis based on biotensegrity, positing that the interconnected skin-fascia-muscle complex functions as a multilayered tensional network. We hypothesize that acupuncture needling induces a local ’tension reset’ within this complex through mechanisms such as fascial remodeling, altered hyaluronan fluidity, a dermal ’tension switch,’ and neurogenic muscle relaxation. This localized change in mechanical tension is then rapidly propagated throughout the body-wide tensegrity system via mechanotransduction. We propose that these pathways of force transmission are the anatomical correlates of traditional acupuncture meridians. This model is consistent with clinical observations such as reduced tissue stiffness measured by elastography and the clinical efficacy of tension-based diagnostic and treatment approaches. By framing meridians as biomechanical pathways, this tensegrity-based hypothesis offers a testable framework that bridges Eastern medical concepts with Western science, potentially unifying our understanding of acupuncture and other manual therapies while providing a basis for refining clinical techniques.
{"title":"A multilayer ‘tension-reset’ hypothesis: Acupuncture’s distant effects via biotensegrity across skin–fascia–muscle layers","authors":"Yoshito Mukaino , Masahiko Mukaino","doi":"10.1016/j.mehy.2025.111797","DOIUrl":"10.1016/j.mehy.2025.111797","url":null,"abstract":"<div><div>While evidence supports the therapeutic effects of acupuncture, particularly for analgesia, the mechanism for its distant effects remains debated. Conventional neurobiological theories, while valid, do not fully account for the rapid, systemic, and meridian-specific responses seen in clinical practice. This paper proposes a<!--> <!-->’tension-reset’<!--> <!-->hypothesis based on biotensegrity, positing that the interconnected skin-fascia-muscle complex functions as a multilayered tensional network. We hypothesize that acupuncture needling induces a local ’tension reset’ within this complex through mechanisms such as fascial remodeling, altered hyaluronan fluidity, a dermal ’tension switch,’ and neurogenic muscle relaxation. This localized change in mechanical tension is then rapidly propagated throughout the body-wide tensegrity system via mechanotransduction. We propose that these pathways of force transmission are the anatomical correlates of traditional acupuncture meridians. This model is consistent with<!--> <!-->clinical observations such as reduced tissue stiffness measured by elastography and the clinical efficacy of tension-based diagnostic and treatment approaches.<!--> <!-->By framing meridians as biomechanical pathways, this tensegrity-based hypothesis offers a testable framework that bridges Eastern medical concepts with Western science, potentially unifying our understanding of acupuncture and other manual therapies while providing a basis for refining clinical techniques.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111797"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-21DOI: 10.1016/j.mehy.2025.111791
Xiaoyu Wang , Wenjun Jiang , Zuncheng Zheng
The pathogenesis of knee osteoarthritis (KOA) remains incompletely elucidated. Traditional perspectives emphasize the roles of articular cartilage degeneration and soft tissue laxity. This article synthesizes recent research to propose an integrated musculoskeletal biomechanical hypothesis: weakness of muscles is the initiating factor in KOA development, leading to diminished dynamic joint stability, this instability triggers abnormal distribution of contact stresses and excessive loading within the joint. Coupled with the unique anatomical features of the tibia and fibula (such as fibular support and the abundance of trabecular bone in the medial tibia) and underlying osteoporosis, this process ultimately results in “uneven bone settlement” of tibial plateau changes. This settlement further exacerbates varus deformity, joint space narrowing, soft tissue imbalance, and pain, establishing a vicious cycle of KOA progression. The clinical efficacy of the currently employed Proximal Fibular Osteotomy (PFO) and the researches related of knee Joint periarticular muscle strength training provides support for this theory. This hypothesis emphasizes the central importance of muscle strengthening to restore joint stability and early intervention in bone metabolism for the prevention and management of KOA.
{"title":"A novel hypothesis on the pathogenesis of knee osteoarthritis: the muscle weakness-joint instability and stress overload – uneven bone settlement cascade","authors":"Xiaoyu Wang , Wenjun Jiang , Zuncheng Zheng","doi":"10.1016/j.mehy.2025.111791","DOIUrl":"10.1016/j.mehy.2025.111791","url":null,"abstract":"<div><div>The pathogenesis of knee osteoarthritis (KOA) remains incompletely elucidated. Traditional perspectives emphasize the roles of articular cartilage degeneration and soft tissue laxity. This article synthesizes recent research to propose an integrated musculoskeletal biomechanical hypothesis: weakness of muscles is the initiating factor in KOA development, leading to diminished dynamic joint stability, this instability triggers abnormal distribution of contact stresses and excessive loading within the joint. Coupled with the unique anatomical features of the tibia and fibula (such as fibular support and the abundance of trabecular bone in the medial tibia) and underlying osteoporosis, this process ultimately results in “uneven bone settlement” of tibial plateau changes. This settlement further exacerbates varus deformity, joint space narrowing, soft tissue imbalance, and pain, establishing a vicious cycle of KOA progression. The clinical efficacy of the currently employed Proximal Fibular Osteotomy (PFO) and the researches related of knee Joint periarticular muscle strength training provides support for this theory. This hypothesis emphasizes the central importance of muscle strengthening to restore joint stability and early intervention in bone metabolism for the prevention and management of KOA.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111791"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-09DOI: 10.1016/j.mehy.2025.111813
Zhe-Ying Jiang , Zi-Qi Zhu , Ying Wang , Wei-Jia Meng , Cui-Ping Li , Lian-Ping He , Xiang-Hu Wang
Lipid metabolism is crucial for cellular function and overall health. Dysregulation of lipid metabolism is associated with a variety of diseases, including obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases. Studies have shown that the gut microbiota can regulate the synthesis and transformation of bile acids, including Lithocholic acid (LCA). participates in the regulation of glucose, lipid, and drug metabolism by interacting with a variety of nuclear receptors, such as farnesoid X receptor, G-protein-coupled bile acid receptor, Vitamin D receptor, and pregnane X receptor. Recently, it has been discovered that regulating bile acid metabolism through LCA may provide a new strategy for managing lipid metabolism dysregulation. Excessive dietary iron has been proven to significantly affect the composition and diversity of the gut microbiota. Therefore, we hypothesize that dietary iron may indirectly affect lipid metabolism by influencing intestinal LCA levels.
{"title":"Excess iron in food could indirectly affect lipid metabolism by affecting intestinal lithocholic acid levels: A scientific hypothesis","authors":"Zhe-Ying Jiang , Zi-Qi Zhu , Ying Wang , Wei-Jia Meng , Cui-Ping Li , Lian-Ping He , Xiang-Hu Wang","doi":"10.1016/j.mehy.2025.111813","DOIUrl":"10.1016/j.mehy.2025.111813","url":null,"abstract":"<div><div>Lipid metabolism is crucial for cellular function and overall health. Dysregulation of lipid metabolism is associated with a variety of diseases, including obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases. Studies have shown that the gut microbiota can regulate the synthesis and transformation of bile acids, including Lithocholic acid (LCA). participates in the regulation of glucose, lipid, and drug metabolism by interacting with a variety of nuclear receptors, such as farnesoid X receptor, G-protein-coupled bile acid receptor, Vitamin D receptor, and pregnane X receptor. Recently, it has been discovered that regulating bile acid metabolism through LCA may provide a new strategy for managing lipid metabolism dysregulation. Excessive dietary iron has been proven to significantly affect the composition and diversity of the gut microbiota. Therefore, we hypothesize that dietary iron may indirectly affect lipid metabolism by influencing intestinal LCA levels.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111813"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-17DOI: 10.1016/j.mehy.2025.111822
Kevin Ricardo Espinosa Yépez
The development of novel antiviral drugs is urgently needed due to the high mortality caused by viral infections. Emerging viral strains and highly transmissible pathogens further increase this threat. Recently, the COVID-19 pandemic has resulted in millions of deaths worldwide, and it is highly probable that it will not be the last pandemic to emerge. Therefore, there is a pressing need for new therapeutic options that offer improved efficacy and safety. These options would enable physicians and patients to select the most appropriate treatment for each clinical situation.
In this context, the present article aims to encourage discussion and research on the development of innovative antiviral therapeutics by proposing a hypothesis for a novel potential antiviral drug. Specifically, this manuscript explores the concept of using messenger RNA, encapsulated in lipid nanoparticles, to encode 2′,5′-oligoadenylate synthetase 3 and latent ribonuclease.
The manuscript also discusses the potential advantages, limitations, and translational considerations of this approach in comparison with existing antiviral therapies.
{"title":"Could mRNA delivery of OAS3 and RNase L provide a novel broad-spectrum antiviral therapy?","authors":"Kevin Ricardo Espinosa Yépez","doi":"10.1016/j.mehy.2025.111822","DOIUrl":"10.1016/j.mehy.2025.111822","url":null,"abstract":"<div><div>The development of novel antiviral drugs is urgently needed due to the high mortality caused by viral infections. Emerging viral strains and highly transmissible pathogens further increase this threat. Recently, the COVID-19 pandemic has resulted in millions of deaths worldwide, and it is highly probable that it will not be the last pandemic to emerge. Therefore, there is a pressing need for new therapeutic options that offer improved efficacy and safety. These options would enable physicians and patients to select the most appropriate treatment for each clinical situation.</div><div>In this context, the present article aims to encourage discussion and research on the development of innovative antiviral therapeutics by proposing a hypothesis for a novel potential antiviral drug. Specifically, this manuscript explores the concept of using messenger RNA, encapsulated in lipid nanoparticles, to encode 2′,5′-oligoadenylate synthetase 3 and latent ribonuclease.</div><div>The manuscript also discusses the potential advantages, limitations, and translational considerations of this approach in comparison with existing antiviral therapies.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111822"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-25DOI: 10.1016/j.mehy.2025.111795
Michał C. Czarnogórski , Layla Settaf-Cherif, Tomasz Drewa, Jan Adamowicz
Despite the unprecedented progress in urological treatment of both benign and malignant bladder conditions, considerable proportion of patients still develop end-stage bladder failure that will eventually require cystectomy. The majority of cystectomies is performed due to bladder cancer. Radical cystectomy with urinary diversion utilizing bowel segments is at present a gold standard, yet it is associated with considerable metabolic complications. With the advent of urinary bladder transplantation research, the new hope emerged for well-informed individuals who would like to preserve natural way of voiding. The vascularized composite bladder allograft transplantation was proven technically and clinically feasible, although for now the indications include only benign bladder conditions, due to the considerable recurrence rate of bladder cancer. We propose hypothetical therapeutic option for non-muscle invasive bladder cancer patients, namely urinary bladder autotransplantation, with blader mucosa decellularization, and subsequent cell seeding with recipients own urothelial progenitor cells. Theoretically, the patient would not require immunosuppressive agents, and would retain natural way of voiding, thus avoiding repeated transurethral bladder tumor resections, BCG instillations, and maintaining high quality of life.
{"title":"Decellularization of urinary bladder autograft in the treatment of bladder cancer","authors":"Michał C. Czarnogórski , Layla Settaf-Cherif, Tomasz Drewa, Jan Adamowicz","doi":"10.1016/j.mehy.2025.111795","DOIUrl":"10.1016/j.mehy.2025.111795","url":null,"abstract":"<div><div>Despite the unprecedented progress in urological treatment of both benign and malignant bladder conditions, considerable proportion of patients still develop end-stage bladder failure that will eventually require cystectomy. The majority of cystectomies is performed due to bladder cancer. Radical cystectomy with urinary diversion utilizing bowel segments is at present a gold standard, yet it is associated with considerable metabolic complications. With the advent of urinary bladder transplantation research, the new hope emerged for well-informed individuals who would like to preserve natural way of voiding. The vascularized composite bladder allograft transplantation was proven technically and clinically feasible, although for now the indications include only benign bladder conditions, due to the considerable recurrence rate of bladder cancer. We propose hypothetical therapeutic option for non-muscle invasive bladder cancer patients, namely urinary bladder autotransplantation, with blader mucosa decellularization, and subsequent cell seeding with recipients own urothelial progenitor cells. Theoretically, the patient would not require immunosuppressive agents, and would retain natural way of voiding, thus avoiding repeated transurethral bladder tumor resections, BCG instillations, and maintaining high quality of life.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111795"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-23DOI: 10.1016/j.mehy.2025.111792
Sun Mo Nam , Nohil Park , Chul-Kee Park , Munyoung Chang , Sungroh Yoon
Brain tumor surgery on eloquent areas faces critical challenges in predicting postoperative deficits and recovery trajectories in current practice. We hypothesize that Large Language Models (LLMs) could potentially serve as individualized virtual simulation models for surgical outcome prediction and treatment optimization for language-eloquent areas. Our hypothesis encompasses four key propositions: (1) LLM architectures may exhibit structural–functional similarities to human language networks, (2) layer-wise ablation could potentially model lesion-induced language damage, (3) fine-tuning protocols might approximate neuroplasticity mechanisms, and (4) these computational models could generate patient-specific prediction tools. We conducted proof-of-concept neuron masking experiments using Qwen2.5 models on CommonsenseQA benchmarks, revealing layer-specific vulnerability patterns showing similarities to neurofunctional anatomical organization. Early layers showed catastrophic dysfunction with diverse language damage patterns. Middle layers demonstrated semantic processing deficits resembling ventral stream damage, while late layers showed executive dysfunction and failure of social context awareness. Final layers exhibited variable patterns including anomic patterns and semantic control deficits. Vision-language model validation using Philadelphia Naming Test confirmed anomic-like patterns with word-finding difficulties in final layers. Fine-tuning experiments simulated rehabilitation outcomes, showing differential recovery potential across layer groups with threshold effects. These proof-of-concept findings suggest LLM-based brain simulation could have a role in neurosurgical planning by providing personalized deficit prediction, recovery modeling, and enabling more precise surgical decision-making for brain tumor patients.
{"title":"An LLM as a virtual simulation model for language-eloquent area surgery in human","authors":"Sun Mo Nam , Nohil Park , Chul-Kee Park , Munyoung Chang , Sungroh Yoon","doi":"10.1016/j.mehy.2025.111792","DOIUrl":"10.1016/j.mehy.2025.111792","url":null,"abstract":"<div><div>Brain tumor surgery on eloquent areas faces critical challenges in predicting postoperative deficits and recovery trajectories in current practice. We hypothesize that Large Language Models (LLMs) could potentially serve as individualized virtual simulation models for surgical outcome prediction and treatment optimization for language-eloquent areas. Our hypothesis encompasses four key propositions: (1) LLM architectures may exhibit structural–functional similarities to human language networks, (2) layer-wise ablation could potentially model lesion-induced language damage, (3) fine-tuning protocols might approximate neuroplasticity mechanisms, and (4) these computational models could generate patient-specific prediction tools. We conducted proof-of-concept neuron masking experiments using Qwen2.5 models on CommonsenseQA benchmarks, revealing layer-specific vulnerability patterns showing similarities to neurofunctional anatomical organization. Early layers showed catastrophic dysfunction with diverse language damage patterns. Middle layers demonstrated semantic processing deficits resembling ventral stream damage, while late layers showed executive dysfunction and failure of social context awareness. Final layers exhibited variable patterns including anomic patterns and semantic control deficits. Vision-language model validation using Philadelphia Naming Test confirmed anomic-like patterns with word-finding difficulties in final layers. Fine-tuning experiments simulated rehabilitation outcomes, showing differential recovery potential across layer groups with threshold effects. These proof-of-concept findings suggest LLM-based brain simulation could have a role in neurosurgical planning by providing personalized deficit prediction, recovery modeling, and enabling more precise surgical decision-making for brain tumor patients.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"205 ","pages":"Article 111792"},"PeriodicalIF":0.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-27DOI: 10.1016/j.mehy.2025.111775
Andrew James Swift
Facial asymmetry is a common but underexplored phenomenon. While often attributed to skeletal or developmental variation, this paper presents a novel theoretical mechanism that may account for progressive neuromuscular asymmetry in individuals who habitually sleep on one side. We propose that repeated facial muscle activation during REM sleep, combined with unilateral compression from habitual side-sleeping, may cause long-term asymmetrical hypertrophy of facial muscles. Drawing from anatomical, physiological, and observational insights, this hypothesis is grounded in known features of REM sleep including eye movement, facial expression, and partial motor activation. The paper explores possible implications for emotional expressivity and psychosocial identity, supported by an anonymised case. Future research avenues are proposed for validating this hypothesis, with relevance to sleep medicine, affective neuroscience, and facial physiology.
{"title":"Facial asymmetry from one-sided sleep? A hypothesis linking REM activity and muscle hypertrophy","authors":"Andrew James Swift","doi":"10.1016/j.mehy.2025.111775","DOIUrl":"10.1016/j.mehy.2025.111775","url":null,"abstract":"<div><div>Facial asymmetry is a common but underexplored phenomenon. While often attributed to skeletal or developmental variation, this paper presents a novel theoretical mechanism that may account for progressive neuromuscular asymmetry in individuals who habitually sleep on one side. We propose that repeated facial muscle activation during REM sleep, combined with unilateral compression from habitual side-sleeping, may cause long-term asymmetrical hypertrophy of facial muscles. Drawing from anatomical, physiological, and observational insights, this hypothesis is grounded in known features of REM sleep including eye movement, facial expression, and partial motor activation. The paper explores possible implications for emotional expressivity and psychosocial identity, supported by an anonymised case. Future research avenues are proposed for validating this hypothesis, with relevance to sleep medicine, affective neuroscience, and facial physiology.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"204 ","pages":"Article 111775"},"PeriodicalIF":0.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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