Contemporary smartphone interaction involves prolonged static postures and attentional diversion, both of which challenge sensorimotor regulation of balance. Yet, emerging evidence suggests that subtle changes in arm elevation may paradoxically enhance postural stability during smartphone use. We hypothesize that arm elevation constitutes a compensatory neuromechanical adaptation that improves whole-body equilibrium through dynamic segmental reweighting. By elevating the arms, users may shift the center of segmental mass upward, engaging tonic activation of scapular and trunk musculature, which in turn increases mechanical coupling and stabilizing stiffness across the axial chain. This redistribution may reduce uncontrolled trunk oscillations and enhance sensorimotor efficiency of balance control, despite concurrent cognitive loading. Preliminary smartphone-based accelerometry observations indicate lower center-of-mass sway magnitudes under elevated-arm conditions, consistent with this proposed stabilization mechanism. If validated, this hypothesis reframes arm elevation during smartphone use as an active, goal-directed stabilizing strategy—rather than a passive by-product of mechanical load—and highlights ergonomic interventions that leverage segmental mechanics to preserve postural stability during mobile multitasking.
{"title":"Arm elevation as a compensatory neuromechanical strategy during smartphone use: a hypothesis on segmental reweighting for postural stability","authors":"Noppharath Sangkarit, Weerasak Tapanya, Saisunee Konsanit","doi":"10.1016/j.mehy.2026.111900","DOIUrl":"10.1016/j.mehy.2026.111900","url":null,"abstract":"<div><div>Contemporary smartphone interaction involves prolonged static postures and attentional diversion, both of which challenge sensorimotor regulation of balance. Yet, emerging evidence suggests that subtle changes in arm elevation may paradoxically enhance postural stability during smartphone use. We hypothesize that arm elevation constitutes a compensatory neuromechanical adaptation that improves whole-body equilibrium through dynamic segmental reweighting. By elevating the arms, users may shift the center of segmental mass upward, engaging tonic activation of scapular and trunk musculature, which in turn increases mechanical coupling and stabilizing stiffness across the axial chain. This redistribution may reduce uncontrolled trunk oscillations and enhance sensorimotor efficiency of balance control, despite concurrent cognitive loading. Preliminary smartphone-based accelerometry observations indicate lower center-of-mass sway magnitudes under elevated-arm conditions, consistent with this proposed stabilization mechanism. If validated, this hypothesis reframes arm elevation during smartphone use as an active, goal-directed stabilizing strategy—rather than a passive by-product of mechanical load—and highlights ergonomic interventions that leverage segmental mechanics to preserve postural stability during mobile multitasking.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111900"},"PeriodicalIF":0.8,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147506","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 : 2026-01-27DOI: 10.1016/j.mehy.2026.111892
S. Shyam Sundar , Sahith Kumar Shetty , K. Brindha
The long-term success of dental implants depends on adequate alveolar bone volume, often necessitating regenerative interventions such as guided bone regeneration and sinus augmentation. Accurate assessment of bone dimensions is critical for planning these procedures, yet manual methods are prone to operator variability and limited reproducibility. Artificial intelligence (AI) has shown promise in dental imaging, with systems such as Dental-YOLO and automated segmentation models achieving high precision in detecting anatomical landmarks. However, existing AI approaches are constrained by dataset diversity, generalizability, and interpretability. We hypothesize that a hybrid Generative Adversarial Network (GAN)–P-TransUNet framework could overcome these limitations by combining GAN-based synthetic data augmentation with transformer-enhanced segmentation for precise and reproducible alveolar bone measurement. This framework could standardize preoperative bone evaluation, optimize regenerative planning, minimize surgical risk, and provide educational value through synthetic datasets. If validated, it has the potential to transform precision-driven regenerative implantology, improving clinical outcomes and patient safety.
{"title":"Hybrid GAN–P-TransUNet framework for alveolar bone regeneration in dental implant planning: A hypothesis","authors":"S. Shyam Sundar , Sahith Kumar Shetty , K. Brindha","doi":"10.1016/j.mehy.2026.111892","DOIUrl":"10.1016/j.mehy.2026.111892","url":null,"abstract":"<div><div>The long-term success of dental implants depends on adequate alveolar bone volume, often necessitating regenerative interventions such as guided bone regeneration and sinus augmentation. Accurate assessment of bone dimensions is critical for planning these procedures, yet manual methods are prone to operator variability and limited reproducibility. Artificial intelligence (AI) has shown promise in dental imaging, with systems such as Dental-YOLO and automated segmentation models achieving high precision in detecting anatomical landmarks. However, existing AI approaches are constrained by dataset diversity, generalizability, and interpretability. We hypothesize that a hybrid Generative Adversarial Network (GAN)–P-TransUNet framework could overcome these limitations by combining GAN-based synthetic data augmentation with transformer-enhanced segmentation for precise and reproducible alveolar bone measurement. This framework could standardize preoperative bone evaluation, optimize regenerative planning, minimize surgical risk, and provide educational value through synthetic datasets. If validated, it has the potential to transform precision-driven regenerative implantology, improving clinical outcomes and patient safety.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111892"},"PeriodicalIF":0.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079813","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 : 2026-01-27DOI: 10.1016/j.mehy.2026.111891
Ning Li , Yumin Heng , Tianyang Lv , Xiaoyue Ge , Changkui Liu , Kaijin Hu
Traumatic temporomandibular joint ankylosis (TTMJA), with its high recurrence rate post-surgery, lacks a unifying pathogenesis theory, hindering effective prevention. We propose a novel four-stage cascade hypothesis that highlights early lymphatic dysfunction—rather than hematoma organization—as a key early determinant of pathological repair. High-energy trauma releases free fibrocartilage fragments into the joint space, where they may act as ’osteogenic seeds’. Subsequent mechanical zonation of the joint into micromotion and stable zones then drives spatially distinct osteogenic pathways (endochondral and intramembranous ossification), explaining the histopathological heterogeneity of the ankylotic mass. This process culminates in piezoelectric-guided vascular fusion and osteoclast-suppressed consolidation, forming a complete bony bridge. Empirically testable in established models, this hypothesis delineates clear therapeutic windows: early intervention targeting lymphatic repair and debris clearance (≤7 days), followed by mechanical modulation (7–21 days), and late osteoclast reactivation (>60 days). This framework reframes clinical management by advocating stage-specific interventions within defined therapeutic windows to shift from reactive surgery to mechanism-based prevention.
{"title":"A novel hypothesis on the pathogenesis of traumatic temporomandibular joint ankylosis","authors":"Ning Li , Yumin Heng , Tianyang Lv , Xiaoyue Ge , Changkui Liu , Kaijin Hu","doi":"10.1016/j.mehy.2026.111891","DOIUrl":"10.1016/j.mehy.2026.111891","url":null,"abstract":"<div><div>Traumatic temporomandibular joint ankylosis (TTMJA), with its high recurrence rate post-surgery, lacks a unifying pathogenesis theory, hindering effective prevention. We propose a novel four-stage cascade hypothesis that highlights early lymphatic dysfunction—rather than hematoma organization—as a key early determinant of pathological repair. High-energy trauma releases<!--> <!-->free fibrocartilage fragments into the joint space, where they may act as ’osteogenic seeds’. Subsequent<!--> <!-->mechanical zonation<!--> <!-->of the joint into micromotion and stable zones then drives spatially distinct osteogenic pathways (endochondral and intramembranous ossification), explaining the histopathological heterogeneity of the ankylotic mass. This process culminates in piezoelectric-guided vascular fusion and osteoclast-suppressed consolidation, forming a complete bony bridge. Empirically testable in established models, this hypothesis delineates clear therapeutic windows: early intervention targeting lymphatic repair and debris clearance (≤7 days), followed by mechanical modulation (7–21 days), and late osteoclast reactivation (>60 days). This framework reframes clinical management by advocating stage-specific interventions within defined therapeutic windows to shift from reactive surgery to mechanism-based prevention.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111891"},"PeriodicalIF":0.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079883","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 : 2026-01-27DOI: 10.1016/j.mehy.2026.111893
Ayah Al-Qasrawi
Despite major advances in tumor cell biology, metastatic disease remains the principal cause of nearly 90% of cancer-related deaths. While the literature characterizes the pre-metastatic niche through processes such as angiogenesis and immune suppression, the molecular basis of organ-specific metastasis—the non-random spread of cancer—remains poorly understood. Traditional models focus on vascular or lymphatic dissemination; however, evidence suggests that biochemical communication between primary tumors and distant tissues is crucial for the selective colonization of metastases. This hypothesis proposes a novel molecular mechanism to explain organ-specific metastasis, mediated by tyrosine kinase (TK) signaling. We hypothesize that primary tumors secrete specific tyrosine kinase proteins in exosomes that interact with overexpressed receptors in secondary organs. This targeted signaling creates a molecular “pre-metastatic niche,” facilitating organ-specific metastasis beyond passive vascular models. Uncovering this signaling axis is essential for better understanding cancer pathophysiology and for developing more targeted therapeutic approaches. Clinical successes demonstrate the therapeutic relevance of TK pathways in managing organ-specific metastases. These include the CNS-penetrant EGFR inhibitor osimertinib in non–small cell lung cancer, the dabrafenib–trametinib combination in BRAF V600 mutant melanoma, and the HER2-targeted regimen incorporating tucatinib for metastatic breast cancers.
{"title":"Molecular signaling between primary tumor and secondary tumor through tyrosine kinase","authors":"Ayah Al-Qasrawi","doi":"10.1016/j.mehy.2026.111893","DOIUrl":"10.1016/j.mehy.2026.111893","url":null,"abstract":"<div><div>Despite major advances in tumor cell biology, metastatic disease remains the principal cause of nearly 90% of cancer-related deaths. While the literature characterizes the pre-metastatic niche through processes such as angiogenesis and immune suppression, the molecular basis of organ-specific metastasis—the non-random spread of cancer—remains poorly understood. Traditional models focus on vascular or lymphatic dissemination; however, evidence suggests that biochemical communication between primary tumors and distant tissues is crucial for the selective colonization of metastases. This hypothesis proposes a novel molecular mechanism to explain organ-specific metastasis, mediated by tyrosine kinase (TK) signaling. We hypothesize that primary tumors secrete specific tyrosine kinase proteins in exosomes that interact with overexpressed receptors in secondary organs. This targeted signaling creates a molecular “pre-metastatic niche,” facilitating organ-specific metastasis beyond passive vascular models. Uncovering this signaling axis is essential for better understanding cancer pathophysiology and for developing more targeted therapeutic approaches. Clinical successes demonstrate the therapeutic relevance of TK pathways in managing organ-specific metastases. These include the CNS-penetrant EGFR inhibitor osimertinib in non–small cell lung cancer, the dabrafenib–trametinib combination in BRAF V600 mutant melanoma, and the HER2-targeted regimen incorporating tucatinib for metastatic breast cancers.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111893"},"PeriodicalIF":0.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079816","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 : 2026-01-27DOI: 10.1016/j.mehy.2026.111890
Fèlix Faming Wang
{"title":"Comment on: Refinements to the hypothesis of climate-driven decline in human core body temperature","authors":"Fèlix Faming Wang","doi":"10.1016/j.mehy.2026.111890","DOIUrl":"10.1016/j.mehy.2026.111890","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111890"},"PeriodicalIF":0.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079815","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 : 2026-01-25DOI: 10.1016/j.mehy.2026.111889
Mohammed Abrahim , Brittany Abrahim
Rosacea is a common, chronic inflammatory skin condition primarily affecting the human face. Clinical manifestations range from mild erythema to disfiguring phymatous changes, such as rhinophyma. Despite extensive research, its primary etiology remains unclear. Current evidence suggests that the disease may begin with an initial vascular insult, which then triggers an inflammatory cascade modulated by genetic, environmental, and microbial factors. However, the mechanisms underlying this initial vascular dysfunction have yet to be elucidated.
We propose the “Cheeky Ape Hypothesis,” which offers a novel evolutionary and anatomical potential contributor to the pathophysiology of rosacea. This hypothesis posits that impaired venous return within the facial vein and its tributaries—resulting from bilateral venous compression within the buccal fat pad, a uniquely human anatomical feature—could play a contributory role in initiating of the disease. As deep buccal fat is specific to humans, this anatomical specialization may represent an evolutionary trade-off, which could partly help explain the distinctive prevalence of rosacea in humans. The hypothesis suggests that the interplay between facial venous flow and adipose tissue distribution underpins the pathogenesis of rosacea. Rigorous experimental and clinical studies will be required to investigate and validate the proposed mechanism.
{"title":"The cheeky ape hypothesis: Is rosacea the evolutionary price of human buccal fat?","authors":"Mohammed Abrahim , Brittany Abrahim","doi":"10.1016/j.mehy.2026.111889","DOIUrl":"10.1016/j.mehy.2026.111889","url":null,"abstract":"<div><div>Rosacea is a common, chronic inflammatory skin condition primarily affecting the human face. Clinical manifestations range from mild erythema to disfiguring phymatous changes, such as rhinophyma. Despite extensive research, its primary etiology remains unclear. Current evidence suggests that the disease may begin with an initial vascular insult, which then triggers an inflammatory cascade modulated by genetic, environmental, and microbial factors. However, the mechanisms underlying this initial vascular dysfunction have yet to be elucidated.</div><div>We propose the “Cheeky Ape Hypothesis,” which offers a novel evolutionary and anatomical potential contributor to the pathophysiology of rosacea. This hypothesis posits that impaired venous return within the facial vein and its tributaries—resulting from bilateral venous compression within the buccal fat pad, a uniquely human anatomical feature—could play a contributory role in initiating of the disease. As deep buccal fat is specific to humans, this anatomical specialization may represent an evolutionary trade-off, which could partly help explain the distinctive prevalence of rosacea in humans. The hypothesis suggests that the interplay between facial venous flow and adipose tissue distribution underpins the pathogenesis of rosacea. Rigorous experimental and clinical studies will be required to investigate and validate the proposed mechanism.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111889"},"PeriodicalIF":0.8,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079814","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 : 2026-01-20DOI: 10.1016/j.mehy.2026.111888
Mahdieh Emadi
The dynamic interaction between organisms and their environment has been a cornerstone of biological research, yet the mechanisms underlying this relationship remain incompletely understood. Recent advances in fields such as enactivism and ecological psychology have emphasized the active role organisms play in shaping their environments, suggesting that perception and action are deeply intertwined. However, existing theories often limit their focus to cognitive or passive reactive processes. This manuscript introduces Endogenous Mirroring Phenomena (EMP) as a novel theoretical framework, positing that biological systems possess intrinsic mechanisms that actively mirror environmental stimuli across the molecular, cellular, and systemic levels. Unlike biophotonic emissions or mirror neuron activity, which primarily address localized or specific reactive processes, EMP proposes a comprehensive, organized reflection of environmental cues that influences physiological regulation, adaptation, and evolution. This concept not only broadens our understanding of biological complexity but also offers new avenues for research on cellular communication, signaling, and evolutionary biology. By establishing EMP as a unifying principle, this work challenges traditional views and sets the stage for future interdisciplinary exploration.
{"title":"Endogenous Mirroring Phenomena (EMP): a paradigm shift in biological sciences","authors":"Mahdieh Emadi","doi":"10.1016/j.mehy.2026.111888","DOIUrl":"10.1016/j.mehy.2026.111888","url":null,"abstract":"<div><div>The dynamic interaction between organisms and their environment has been a cornerstone of biological research, yet the mechanisms underlying this relationship remain incompletely understood. Recent advances in fields such as enactivism and ecological psychology have emphasized the active role organisms play in shaping their environments, suggesting that perception and action are deeply intertwined. However, existing theories often limit their focus to cognitive or passive reactive processes. This manuscript introduces Endogenous Mirroring Phenomena (EMP) as a novel theoretical framework, positing that biological systems possess intrinsic mechanisms that actively mirror environmental stimuli across the molecular, cellular, and systemic levels. Unlike biophotonic emissions or mirror neuron activity, which primarily address localized or specific reactive processes, EMP proposes a comprehensive, organized reflection of environmental cues that influences physiological regulation, adaptation, and evolution. This concept not only broadens our understanding of biological complexity but also offers new avenues for research on cellular communication, signaling, and evolutionary biology. By establishing EMP as a unifying principle, this work challenges traditional views and sets the stage for future interdisciplinary exploration.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111888"},"PeriodicalIF":0.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079817","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 : 2026-01-19DOI: 10.1016/j.mehy.2026.111887
Masato Hiki
Cancer initiation and progression have traditionally been interpreted primarily through the accumulation of genetic mutations and the dysregulation of intracellular signaling pathways. At the same time, increasing evidence indicates that the tumor microenvironment—particularly hypoxia and pathological angiogenesis—plays a critical role in tumor cell survival, clonal selection, and therapeutic resistance. However, how genetic alterations and hypoxia-driven metabolic adaptation are functionally integrated during stepwise tumor progression remains incompletely understood.
In this manuscript, we propose a dual hypothesis framework in which hypoxia-induced mitochondrial silencing and hypoxic niches maintained by pathological angiogenesis cooperatively shape cancer progression in hypoxia-prone solid tumors. Mitochondrial silencing is defined here as a functional mitochondrial state in which oxidative metabolism is suppressed and the executional capacity of mitochondria-dependent apoptosis is attenuated, despite the structural persistence of mitochondria. We further propose that this state functions as a third regulatory layer of apoptosis control, distinct from classical pro- and anti-apoptotic signaling pathways.
As a second component of the hypothesis, we suggest that structurally and functionally abnormal tumor neovasculature generates spatially heterogeneous microenvironments characterized by limited red blood cell–mediated oxygen delivery but relatively preserved diffusion of glucose. Such hypoxic, glucose-accessible niches are predicted to preferentially select for and maintain cell populations adapted to mitochondrial silencing and glycolysis-dominant metabolism, thereby supporting clonal persistence, heterogeneity, and progression.
Although this work does not present experimental data, it provides a testable conceptual framework that repositions mitochondrial functional state as a central integrator of genetic alterations and microenvironmental constraints, and offers new perspectives on apoptosis resistance and metabolic adaptation in hypoxic solid tumors.
{"title":"Hypoxia-induced mitochondrial silencing as a proposed third axis of apoptosis control in solid tumors: a dual hypothesis linking initiation–promotion transition to hypoxic niche maintenance","authors":"Masato Hiki","doi":"10.1016/j.mehy.2026.111887","DOIUrl":"10.1016/j.mehy.2026.111887","url":null,"abstract":"<div><div>Cancer initiation and progression have traditionally been interpreted primarily through the accumulation of genetic mutations and the dysregulation of intracellular signaling pathways. At the same time, increasing evidence indicates that the tumor microenvironment—particularly hypoxia and pathological angiogenesis—plays a critical role in tumor cell survival, clonal selection, and therapeutic resistance. However, how genetic alterations and hypoxia-driven metabolic adaptation are functionally integrated during stepwise tumor progression remains incompletely understood.</div><div>In this manuscript, we propose a dual hypothesis framework in which hypoxia-induced mitochondrial silencing and hypoxic niches maintained by pathological angiogenesis cooperatively shape cancer progression in hypoxia-prone solid tumors. Mitochondrial silencing is defined here as a functional mitochondrial state in which oxidative metabolism is suppressed and the executional capacity of mitochondria-dependent apoptosis is attenuated, despite the structural persistence of mitochondria. We further propose that this state functions as a third regulatory layer of apoptosis control, distinct from classical pro- and anti-apoptotic signaling pathways.</div><div>As a second component of the hypothesis, we suggest that structurally and functionally abnormal tumor neovasculature generates spatially heterogeneous microenvironments characterized by limited red blood cell–mediated oxygen delivery but relatively preserved diffusion of glucose. Such hypoxic, glucose-accessible niches are predicted to preferentially select for and maintain cell populations adapted to mitochondrial silencing and glycolysis-dominant metabolism, thereby supporting clonal persistence, heterogeneity, and progression.</div><div>Although this work does not present experimental data, it provides a testable conceptual framework that repositions mitochondrial functional state as a central integrator of genetic alterations and microenvironmental constraints, and offers new perspectives on apoptosis resistance and metabolic adaptation in hypoxic solid tumors.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111887"},"PeriodicalIF":0.8,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036237","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 : 2026-01-17DOI: 10.1016/j.mehy.2026.111885
Nazia Hassan , Ayan K. Das , Asgar Ali
Recurrent Vulvovaginal Candidiasis (RVVC) is characterised as four or more symptomatic episodes of vulvovaginal candidiasis in a year, with partial resolution between episodes and microbiologic confirmation in at least two episodes. The prominent symptoms include vaginal-itching, discharge, erythema, oedema, and burning sensation. Biofilm development and antifungal resistance perpetuate RVVC symptoms by seeding Candida colonisation, infection relapse, and persistence. The microbial landscape of RVVC is predominantly C. albicans (90%) and emerging non-albicans Candida (NAC) species, including C. tropicalis, C. parapsilosis, C. krusei, and C. dubliniensis. The rare isolates, C. auris and S. cerevisiae, also contribute to ecological complexity in multi-species biofilms by enhancing resilience and interfering with quorum sensing. This hypothesis proposes that RVVC persistence is sustained not only by species-specific biofilm traits and virulence gene expression (ALS3, HWP1, EFG1, TUP1, BEM2), but also by interspecies interactions within multispecies vaginal biofilms that augment antifungal resistance and persistence. We propose that profiling clinical isolates could help reveal correlations between antifungal susceptibility, biofilm architecture, and gene-level regulation. The hypothesis highlights the translational importance of multispecies, multidrug-resistant, and rare Candida biofilms as key modulators of resistance and virulence traits. The proposed framework includes culture-based identification, antifungal susceptibility testing, in vitro biofilm assays, confocal microscopy, and qPCR analysis. These approaches will define biofilm-associated resistance patterns and establish quantitative molecular biomarkers to guide novel formulation designs, in vivo validation, and species-specific antifungal stewardship.
{"title":"Species-specific biofilm traits and virulence gene expression in recurrent vulvovaginal candidiasis: a translational hypothesis","authors":"Nazia Hassan , Ayan K. Das , Asgar Ali","doi":"10.1016/j.mehy.2026.111885","DOIUrl":"10.1016/j.mehy.2026.111885","url":null,"abstract":"<div><div>Recurrent Vulvovaginal Candidiasis (RVVC) is characterised as four or more symptomatic episodes of vulvovaginal candidiasis in a year, with partial resolution between episodes and microbiologic confirmation in at least two episodes. The prominent symptoms include vaginal-itching, discharge, erythema, oedema, and burning sensation. Biofilm development and antifungal resistance perpetuate RVVC symptoms by seeding <em>Candida</em> colonisation, infection relapse, and persistence. The microbial landscape of RVVC is predominantly <em>C. albicans</em> (90%) and emerging non-albicans <em>Candida</em> (NAC) species, including <em>C. tropicalis</em>, <em>C. parapsilosis</em>, <em>C. krusei</em>, and <em>C. dubliniensis</em>. The rare isolates, <em>C. auris</em> and <em>S. cerevisiae,</em> also contribute to ecological complexity in multi-species biofilms by enhancing resilience and interfering with quorum sensing. This hypothesis proposes that RVVC persistence is sustained not only by species-specific biofilm traits and virulence gene expression (ALS3, HWP1, EFG1, TUP1, BEM2), but also by interspecies interactions within multispecies vaginal biofilms that augment antifungal resistance and persistence. We propose that profiling clinical isolates could help reveal correlations between antifungal susceptibility, biofilm architecture, and gene-level regulation. The hypothesis highlights the translational importance of multispecies, multidrug-resistant, and rare Candida biofilms as key modulators of resistance and virulence traits. The proposed framework includes culture-based identification, antifungal susceptibility testing, in vitro biofilm assays, confocal microscopy, and qPCR analysis. These approaches will define biofilm-associated resistance patterns and establish quantitative molecular biomarkers to guide novel formulation designs, in vivo validation, and species-specific antifungal stewardship.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111885"},"PeriodicalIF":0.8,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036238","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 : 2026-01-17DOI: 10.1016/j.mehy.2026.111877
Bogdan-Alexandru Hagiu
The SARS-CoV-2 virus persists for up to 80 days in the brainstem of golden hamsters and this fact is correlated with dopaminergic dysfunctions and changes in the expression of some genes, including the suppression of DRD2. Since moderate-intensity physical exercise stimulates the expression of DRD2, it was hypothesized that this type of physical training can be used for the prophylaxis of neurological disorders in Long COVID. Testing the hypothesis can be performed on the same experimental animals and the results can be evidenced by histological and immunohistochemical analyses, transcriptomics, and behavioral tests. In this way, cases of Parkinson’s disease following SARS-C0V-2 infection could also be prevented, if this causal link is confirmed.
{"title":"Moderate-intensity exercise as a preventive strategy against dopaminergic dysfunction in Long COVID: A mechanistic hypothesis","authors":"Bogdan-Alexandru Hagiu","doi":"10.1016/j.mehy.2026.111877","DOIUrl":"10.1016/j.mehy.2026.111877","url":null,"abstract":"<div><div>The SARS-CoV-2 virus persists for up to 80 days in the brainstem of golden hamsters and this fact is correlated with dopaminergic dysfunctions and changes in the expression of some genes, including the suppression of DRD2. Since moderate-intensity physical exercise stimulates the expression of DRD2, it was hypothesized that this type of physical training can be used for the prophylaxis of neurological disorders in Long COVID. Testing the hypothesis can be performed on the same experimental animals and the results can be evidenced by histological and immunohistochemical analyses, transcriptomics, and behavioral tests. In this way, cases of Parkinson’s disease following SARS-C0V-2 infection could also be prevented, if this causal link is confirmed.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"208 ","pages":"Article 111877"},"PeriodicalIF":0.8,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035920","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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