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Erratum to “Interaction between the muscarinic system and the PPAR-γ may mitigate the severity of inflammatory bowel disease”, [Med. Hypotheses 204 (2025) 111787] “毒蕈碱系统和PPAR-γ之间的相互作用可能减轻炎症性肠病的严重程度”的勘误,[Med.假说204 (2025)111787]
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 DOI: 10.1016/j.mehy.2025.111811
Diva de Aguiar Magalhães , Danyela Maria Leal Rocha , Rafael da Silva Prudêncio , Antônio Kleiton de Sousa , Stefany Guimarães Sousa , Ana Clara Coelho da Costa , André dos Santos Carvalho , Vanderlene Oliveira Rodrigues , Pedro Henrique Gomes de Azevedo , Kaique Aguiar Souza , João Janilson da Silva Sousa , André Luiz dos Reis Barbosa
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引用次数: 0
Transcriptomic and microRNA profiling of peripheral blood mononuclear cells: A hypothesis for detecting erythropoietin gene doping in athletes 外周血单核细胞的转录组学和microRNA谱分析:一种检测运动员红细胞生成素基因兴奋剂的假设
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-12-01 DOI: 10.1016/j.mehy.2025.111843
Sushmita Kumari , Jayaseelan Murgaiyan , Ankur Sharma
Gene doping, defined as the misuse of gene transfer technologies to enhance athletic performance, poses a growing challenge to both sporting ethics and athlete safety. Traditional detection strategies, such as PCR-based assays, aim to identify the presence of foreign genetic material but are highly vulnerable to sequence alterations and localized gene expression. Despite regulatory bans by bodies like the World Anti-Doping Agency (WADA), no standardized detection method currently exists that can reliably identify gene doping in practice. This paper proposes the hypothesis that transcriptomic and microRNA (miRNA) profiling of peripheral blood mononuclear cells (PBMCs) can reveal a distinct molecular signature indicative of erythropoietin (EPO) gene doping. This “biological footprint” of gene doping, unlike direct transgene detection, reflects systemic changes in gene expression that persist longer and are more difficult to conceal. It is further hypothesized that these transcriptomic changes can be integrated into the Athlete Biological Passport framework, allowing for personalized longitudinal monitoring of athletes. This approach may overcome key limitations of current methods, offering both a broader detection window and resistance to evasion tactics. However, implementation must address the confounding effects of physiological variability due to training, altitude exposure, and individual genetics. Establishing robust statistical baselines and reference datasets will be critical to distinguishing genuine doping signatures from natural fluctuations. If validated, this strategy could transform anti-doping surveillance by focusing not on the genetic agent itself, but on its systemic biological impact, providing a powerful new tool for preserving fairness and safety in sport.
基因兴奋剂被定义为滥用基因转移技术来提高运动成绩,这对体育道德和运动员安全都构成了越来越大的挑战。传统的检测策略,如基于pcr的检测,旨在识别外源遗传物质的存在,但极易受到序列改变和局部基因表达的影响。尽管世界反兴奋剂机构(WADA)等机构颁布了监管禁令,但目前还没有一种标准化的检测方法可以可靠地识别基因兴奋剂。本文提出了一种假设,即外周血单核细胞(pbmc)的转录组学和microRNA (miRNA)谱分析可以揭示红细胞生成素(EPO)基因掺杂的独特分子特征。与直接的转基因检测不同,基因兴奋剂的这种“生物足迹”反映了基因表达的系统性变化,这种变化持续时间更长,更难以隐藏。进一步假设,这些转录组变化可以整合到运动员生物护照框架中,从而允许对运动员进行个性化的纵向监测。这种方法可以克服当前方法的关键限制,提供更广泛的检测窗口和抵抗逃避策略。然而,实施必须解决由训练、海拔暴露和个体遗传引起的生理变异的混淆效应。建立可靠的统计基线和参考数据集对于区分真正的兴奋剂特征和自然波动至关重要。如果得到验证,这一策略可以改变反兴奋剂监督,不再关注遗传因素本身,而是关注其系统的生物学影响,为维护体育运动的公平和安全提供一个强大的新工具。
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引用次数: 0
Is CXCL13 a key player of antibody-mediated rejection in kidney transplantation? A hypothesis based on its role in modulating the humoral response CXCL13是否在肾移植中抗体介导的排斥反应中起关键作用?一种基于它在调节体液反应中的作用的假说
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-28 DOI: 10.1016/j.mehy.2025.111842
Miguel A. Vázquez-Toledo , Carlos A. Guzmán-Martín , Yaneli Juarez-Vicuña , Iván Zepeda-Quiroz , César Flores-Gama , Fausto Sánchez-Muñoz
Antibody-mediated acute rejection (ABMR) is an immunological response generated by the recipient’s immune system against donor antigens. It is characterized by a robust humoral response, resulting in the formation of high-affinity antibodies and endothelial damage. An important factor in acute rejection is the formation of Tertiary Lymphoid Structures (TLS) that facilitate the interaction between Tfh cells and B cells, leading to the production of high-affinity antibodies.
CXCL13 is a chemokine known for its ability to recruit B cells. It plays an important role in the formation of these ectopic lymphoid niches, which have been associated with poor prognoses for renal allograft survival. CXCL13 organizes CXCR5+ lymphocytes and sustains an inflammatory milieu through cell recruitment and cytokine induction. In this work, we specifically propose that CXCL13 contributes to ABMR through two key mechanisms: (1) allowing the spatial and functional integration of Tfh and B cells within TLS to enhance affinity maturation and class switching; and (2) perpetuating a self-sustaining circuit of inflammation and alloantigen recognition that drives sustained donor-specific antibody (DSA) production and endothelial damage.
The convergence of these mechanisms, driven by the persistent action of CXCL13 within the allograft, could define a new pathophysiological axis in ABMR. Targeting the CXCL13-CXCR5 signaling pathway could represent a promising immunomodulatory strategy to interrupt local humoral amplification, preserve graft integrity, and improve long-term outcomes in kidney transplant recipients.
抗体介导的急性排斥反应(ABMR)是由受体免疫系统对供体抗原产生的免疫反应。它的特点是强大的体液反应,导致形成高亲和力抗体和内皮损伤。急性排斥反应的一个重要因素是三级淋巴结构(TLS)的形成,它促进Tfh细胞和B细胞之间的相互作用,导致高亲和力抗体的产生。CXCL13是一种趋化因子,以其招募B细胞的能力而闻名。它在这些异位淋巴细胞龛的形成中起重要作用,而异位淋巴细胞龛与同种异体肾移植生存的不良预后有关。CXCL13组织CXCR5+淋巴细胞,通过细胞募集和细胞因子诱导维持炎症环境。在这项工作中,我们特别提出CXCL13通过两个关键机制促进ABMR:(1)允许Tfh和B细胞在TLS内的空间和功能整合,以促进亲和成熟和类切换;(2)维持炎症和异体抗原识别的自我维持回路,驱动持续的供体特异性抗体(DSA)产生和内皮损伤。在同种异体移植物内CXCL13持续作用的驱动下,这些机制的融合可能在ABMR中定义一个新的病理生理轴。靶向CXCL13-CXCR5信号通路可能是一种有前途的免疫调节策略,可以中断局部体液扩增,保持移植物的完整性,并改善肾移植受者的长期预后。
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引用次数: 0
Bayesian hypothesis generation: a probabilistic framework for evaluating novel hypotheses before data collection 贝叶斯假设生成:在数据收集之前评估新假设的概率框架
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-25 DOI: 10.1016/j.mehy.2025.111841
Tan Aik Kah
Scientific progress depends not only on data but also on the ability to generate and evaluate hypotheses under uncertainty. Conventional frameworks—dominated by binary judgments of “proven” versus “implausible”—struggle in early, high-stakes contexts where evidence is sparse. This paper introduces Bayesian hypothesis generation (BHG), a formal probabilistic framework for structured belief-updating. By defining priors, estimating likelihood ratios, and updating posteriors, BHG replaces intuition-driven reasoning with a transparent method that allows probabilities to evolve dynamically as evidence accrues. Retrospective case studies illustrate its utility. In the early phases of the Nipah virus outbreak, suspicions about Helicobacter pylori and gastric cancer, and the bovine spongiform encephalopathy crisis, BHG could have quantified plausibility before definitive proof, providing a principled basis for precautionary action. A prospective example in retinal micro(nano)plastics—now empirically confirmed in human retina— shows how BHG can separate signal from artifact: a model-derived posterior probability of 2.3 %, though modest, was sufficient to justify further investigation. BHG thus offers a systematic approach to hypothesis management, balancing skepticism with openness. It accelerates the pre-validation phase by highlighting which ideas merit attention, resources, or dismissal. To operationalize BHG, I propose integrating it into journal review policies, funding criteria, computational tools, and training curricula. BHG does not replace empirical validation but complements it, providing a disciplined framework for managing uncertainty. By legitimizing structured probability updating, it enhances science’s ability to recognize emerging risks and explore novel ideas with rigor and efficiency.
科学进步不仅取决于数据,而且取决于在不确定性下产生和评估假设的能力。传统的框架——由“已证实”和“不可信”的二元判断主导——在证据稀少的早期高风险环境中挣扎。介绍了一种用于结构化信念更新的概率框架——贝叶斯假设生成(BHG)。通过定义先验、估计似然比和更新后验,BHG用一种透明的方法取代了直觉驱动的推理,这种方法允许概率随着证据的积累而动态演变。回顾性案例研究说明了它的实用性。在尼帕病毒暴发的早期阶段、对幽门螺杆菌和胃癌的怀疑以及牛海绵状脑病危机中,BHG可以在确定证据之前对合理性进行量化,为预防行动提供原则基础。在视网膜微(纳米)塑料中有一个前瞻性的例子——现在在人类视网膜中得到了经验证实——显示了BHG是如何将信号从伪影中分离出来的:模型推导的后验概率为2.3%,尽管不大,但足以证明进一步的研究是合理的。因此,BHG提供了一种系统的假设管理方法,平衡了怀疑与开放。它通过突出哪些想法值得关注、资源或驳回来加速预验证阶段。为了实施BHG,我建议将其整合到期刊评审政策、资助标准、计算工具和培训课程中。BHG不会取代经验验证,而是对其进行补充,为管理不确定性提供了一个有纪律的框架。通过使结构化的概率更新合法化,它增强了科学识别新出现的风险和严谨高效地探索新思想的能力。
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引用次数: 0
Reducing hyper mirroring in misophonia: A proposal for cortico-cortical paired associative stimulation (ccPAS) as a potential intervention for treatment 减少恐音症的过度镜像:皮质-皮质配对联想刺激(ccPAS)作为治疗的潜在干预措施的建议
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-24 DOI: 10.1016/j.mehy.2025.111840
Pradeep Dheerendra , Sukhbinder Kumar , Phillip E. Gander , Joel I. Berger , Lars F. Muckli
Misophonia, a condition characterized by intense emotional and physiological reactions to specific human-generated sounds, was recently proposed as a disorder of hyper mirroring, in which there is an over-representation of the actions of others. A recent study used rTMS to indirectly reduce the hyperactivity in the anterior insula of people with misophonia, leading to a modest reduction in misophonic distress. But further research is needed to optimize TMS for greater efficacy. Recent TMS studies using a paired associative approach have shown that it could be used to reduce automatic mirroring in healthy controls. We propose the use of ccPAS for reducing the aberrant “hyper” connectivity of the motor cortex, suggested to be associated with mirroring, found in misophonia which is directly accessible to TMS. We hope this theoretically driven neuromodulation approach can take advantage of recent advances in brain stimulation and address the need for developing an effective evidence-based treatment for misophonia.
恐音症是一种对特定的人类声音产生强烈的情绪和生理反应的症状,最近被认为是一种过度镜像的疾病,在这种疾病中,对他人的行为有过度的再现。最近的一项研究使用rTMS间接减少恐音症患者前脑岛的过度活动,导致恐音症痛苦的适度减少。但需要进一步的研究来优化经颅磁刺激以获得更大的疗效。最近使用配对联想方法的经颅磁刺激研究表明,它可用于减少健康对照中的自动镜像。我们建议使用ccPAS来减少运动皮层的异常“超”连通性,这被认为与镜像有关,在恐音症中发现,这可以直接通过TMS获得。我们希望这种理论驱动的神经调节方法可以利用脑刺激的最新进展,并解决开发一种有效的基于证据的恐音症治疗方法的需要。
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引用次数: 0
Late intraocular lens dislocation arises from two independent biomechanical pathways: Structural failure and interface fatigue 晚期人工晶状体脱位由两种独立的生物力学途径引起:结构破坏和界面疲劳
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-24 DOI: 10.1016/j.mehy.2025.111839
Akira Hirata
Late in-the-bag intraocular lens (IOL) dislocation occurs in 0.1–3 % of patients undergoing cataract surgery, with this prevalence increasing to 15 % in high-risk populations. The current theory attributes all cases to the progressive weakening of zonular fibers, culminating in a single failure mechanism; however, this universal paradigm cannot explain the variety of clinical presentations. This paper proposes that late IOL dislocation results from the failure of a dynamic mechanical system through two independent biomechanical pathways: (1) the structural failure pathway, progressive stiffness reduction through material failure in exfoliation syndrome and dead bag syndrome, and (2) the interface fatigue pathway, repeated cyclic loading causing zonular lamella delamination in post-vitrectomy cases without zonular fiber degradation. Histopathological analysis revealed pathway-specific patterns: all exfoliation syndrome cases (9/9, 100 %) showed zonular fiber rupture, whereas evaluable non-exfoliation cases showed zonular lamella detachment (14/14, 100 % of evaluable cases; 87.5 % of the total 16 non-exfoliation cases); the remaining 2 cases showed dead bag syndrome, where interface assessment was not possible. Temporal patterns were also correlated with exfoliation syndrome cases typically occurring 7–12 years after cataract surgery versus 2–10 years after vitrectomy. When both factors coexist, the risk increases additively, indicating pathway independence. This framework supports pathway-specific interventions, such as capsular tension rings for structural failure and biocompatible vitreous substitutes for dynamic instability, which shift risk stratification from universal protocols to personalized monitoring strategies based on the underlying failure mechanisms.
在接受白内障手术的患者中,有0.1% - 3%的患者会发生囊内人工晶状体(IOL)脱位,在高危人群中,这一比例增加到15%。目前的理论将所有情况归因于带状纤维的逐渐弱化,最终形成单一的破坏机制;然而,这种普遍的范式并不能解释临床表现的多样性。本文提出,晚期IOL脱位是动态力学系统通过两个独立的生物力学途径失效的结果:(1)结构破坏途径,脱落综合征和死袋综合征中材料破坏导致的渐进式刚度降低;(2)界面疲劳途径,反复循环载荷导致玻璃体切除术后无带状纤维降解的带状板层脱层。组织病理学分析显示通路特异性模式:所有脱落综合征病例(9/ 9,100 %)表现为带状纤维断裂,而可评估的非脱落病例表现为带状板层脱离(14/ 14,100 %的可评估病例,占16例非脱落病例的87.5%);其余2例为死袋综合征,无法进行界面评估。时间模式也与脱落综合征病例相关,通常发生在白内障手术后7-12年,而不是玻璃体切除术后2-10年。当这两种因素同时存在时,风险叠加增加,表明路径独立性。该框架支持通路特异性干预,如用于结构破坏的荚膜张力环和用于动态不稳定的生物相容性玻璃体替代品,这将风险分层从通用协议转变为基于潜在破坏机制的个性化监测策略。
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引用次数: 0
Controlled intracranial pressure elevation via cerebrospinal fluid infusion: a novel hemostatic hypothesis for hematoma expansion in traumatic brain contusion 通过脑脊液输注控制颅内压升高:创伤性脑挫伤血肿扩张的一种新的止血假说
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-22 DOI: 10.1016/j.mehy.2025.111837
Tianzun Li, Ji Xia, Yunpeng Dong, Jun Chen, Mingliang Ren
Hematoma expansion (HE) following traumatic brain contusion has been recognized as a predictor of neurological deterioration and poor outcomes, but there is currently no effective hemostatic strategy to halt its progression. We propose a novel hypothesis: controlled infusion of artificial cerebrospinal fluid (aCSF) into the cerebrospinal fluid (CSF) space via an external ventricular drain (EVD) or lumbar drain to deliberately elevate intracranial pressure (ICP) within a defined therapeutic window. For instance, ICP could be increased to 25–30 mmHg over 30 minutes and then maintained at 20–25 mmHg for several hours. We expect that this sustained, global elevation will exert a tamponade effect on low-pressure microvascular bleeding within contused brain tissue, thereby promoting hemostasis. The rationale draws on the principle of compressive hemostasis, the demonstrated physiological tolerance to monitored ICP elevation when cerebral perfusion pressure is preserved, and the feasibility of adapting existing neurocritical care infrastructure. If validated, this minimally invasive, physiology-guided approach could address a critical therapeutic gap in early TBI management by limiting hematoma growth, which may reduce mortality, reoperation rates, and long-term disability.
外伤性脑挫伤后血肿扩张(HE)被认为是神经功能恶化和预后不良的预测指标,但目前没有有效的止血策略来阻止其进展。我们提出了一个新的假设:在一个确定的治疗窗口内,通过脑室外引流管(EVD)或腰椎引流管将人工脑脊液(aCSF)控制输注到脑脊液(CSF)空间,以故意提高颅内压(ICP)。例如,ICP可以在30分钟内增加到25-30 mmHg,然后在几个小时内保持在20-25 mmHg。我们期望这种持续的、全面的升高将对挫伤脑组织内的低压微血管出血起到填塞作用,从而促进止血。其基本原理是基于压缩止血的原理,在脑灌注压保持的情况下监测ICP升高的生理耐受性,以及适应现有神经危重症护理基础设施的可行性。如果得到验证,这种微创、生理引导的方法可以通过限制血肿生长来解决早期TBI治疗的关键治疗空白,这可能会降低死亡率、再手术率和长期残疾。
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引用次数: 0
A hypothesis on the suitability of the aquatic crustacean, Daphnia pulex as an animal model for investigating Parkinson’s disease mechanisms 水生甲壳类动物水蚤作为研究帕金森病机制的动物模型的适用性假设
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-22 DOI: 10.1016/j.mehy.2025.111838
OP Neethumol, Sarthak Khurana, Vignesh Olakkal, Mullasseril Rinkuraj, Prabha Joseph Mariam, Usha Rajamma, Goutam Chandra, Kochupurackal P. Mohanakumar
One of the most consistent neurodegenerative disorders, Parkinson’s disease (PD), is a chronic, progressive, debilitating condition with no cure existing. Movement is majorly affected in the disease, which is caused by the depletion of the neurotransmitter dopamine, resulting from degeneration of the midbrain nigrostriatal dopaminergic neurons in the brain. Several laboratory mammals, such as primates and laboratory-bred rodents, are employed for modelling the disease for investigations of PD pathophysiology and drug screening for PD. In the absence of higher mental functions in the laboratory rodents, primates are employed for the final meaningful research output, especially in terms of PD motor and non-motor behavioural syndromes. Serious ethical concerns in using primates and laboratory-bred higher vertebrates, including marmosets, canines, and rodents in research, warrant the use of lower organisms, such as fish, worms, and flies, to investigate cellular-level signalling and molecular behavioural pharmacology of PD. These animals could be manipulated to exhibit a common PD phenotype, the movement disabilities that are constituent with the loss of brain dopamine. In the present hypothesis, a crustacean zooplankton Daphnia pulex, with its characteristic quantifiable movement patterns, warrants it as a preferable animal for modelling the human disease. Easy culture conditions, requirements of inexpensive laboratory settings, existence of parthenogenetic reproduction, a well-formed neural communication system consisting of cholinergic and aminergic transmissions make these crustaceans ideal for employing in PD research. The prospects of using Daphnia pulex for investigating the pathophysiology of PD, is proposed here. We hypothesize that exposure of D. pulex to neurotoxins causing PD syndromes in humans will induce measurable alterations in movement and associated neurochemical signalling that parallel key features of human PD.
帕金森病(PD)是最常见的神经退行性疾病之一,是一种慢性、进行性、使人衰弱的疾病,目前尚无治愈方法。这种疾病主要影响运动,它是由大脑中脑黑质纹状体多巴胺能神经元退化导致的神经递质多巴胺耗竭引起的。几种实验室哺乳动物,如灵长类动物和实验室饲养的啮齿动物,被用于PD病理生理学研究和PD药物筛选的疾病建模。在实验室啮齿类动物缺乏高级心理功能的情况下,灵长类动物被用于最终有意义的研究成果,特别是在PD运动和非运动行为综合征方面。在研究中使用灵长类动物和实验室培育的高等脊椎动物(包括狨猴、犬科动物和啮齿动物)存在严重的伦理问题,因此需要使用低等生物(如鱼、蠕虫和苍蝇)来研究PD的细胞水平信号传导和分子行为药理学。这些动物可以通过操纵来表现出一种常见的PD表型,即与大脑多巴胺缺失有关的运动障碍。在目前的假设中,一种甲壳类浮游动物水蚤,以其特有的可量化的运动模式,保证了它作为模拟人类疾病的首选动物。简单的培养条件,低廉的实验室环境要求,孤雌生殖的存在,由胆碱能和胺能传递组成的良好的神经通信系统使这些甲壳类动物成为PD研究的理想选择。本文对水蚤在帕金森病病理生理学研究中的应用前景进行了展望。我们假设,暴露于导致人类PD综合征的神经毒素中,会导致可测量的运动和相关神经化学信号的改变,这些改变与人类PD的关键特征相似。
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引用次数: 0
Tomatoes and Parkinson’s disease – an old hypothesis revisited 西红柿和帕金森氏症——一个古老的假说被重新审视
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-21 DOI: 10.1016/j.mehy.2025.111836
Jolien S. Bogers , Kimberly C. Paul , E. Ray Dorsey , Bastiaan R. Bloem
In 1989, Jacob I. Sage proposed that tomatoes might contribute to the aetiology of Parkinson’s disease (PD). At the time, his hypothesis mainly served as a provocative “tongue-in-cheek” illustration of the complex challenges that come with identifying the true cause for a globally occurring disease that emerged as a largely new condition in the early 19th century. We here discuss why this hypothesis may have been less far-fetched than originally thought, using some circumstantial and observational evidence to underpin this idea. Specifically, growing evidence suggests that pesticide exposure is a relevant risk factor for PD and some seemingly neurotoxic pesticides are used to grow tomatoes. The number of pesticides used agriculturally, including on tomatoes, has increased in the past decades. Also, the prevalence of Parkinson’s disease seems to grow fastest in countries with the highest growth in tomato production. We fully acknowledge the speculative nature of our hypothesis, and that the provided circumstantial evidence by no means proves that tomatoes, and specifically pesticide application on tomato crops, are an actual cause of Parkinson’s disease. We do hope to raise further awareness for the notion that the global increase in the use of pesticides, compounded by a potential for cumulative neurotoxic effects due to exposure to mixtures of environmental chemicals, could exacerbate the global rise in PD, highlighting the need for improved risk assessments and preventative measures.
1989年,Jacob I. Sage提出西红柿可能与帕金森病(PD)的病因有关。当时,他的假设主要是作为一种挑衅性的“半开玩笑”的说明,说明了在19世纪初出现的一种基本上是新的疾病,在确定一种全球流行疾病的真正原因时所面临的复杂挑战。我们在这里讨论为什么这个假设可能没有最初认为的那么牵强,使用一些间接和观察证据来支持这一观点。具体来说,越来越多的证据表明,农药暴露是帕金森病的一个相关风险因素,一些看似神经毒性的农药被用于种植西红柿。在过去的几十年里,农业上使用的杀虫剂,包括番茄上的杀虫剂,都有所增加。此外,帕金森氏症的患病率似乎在番茄产量增长最快的国家增长最快。我们完全承认我们假设的推测性,并且所提供的间接证据绝不能证明西红柿,特别是在西红柿作物上施用农药是帕金森病的实际原因。我们确实希望进一步提高人们的认识,即全球农药使用的增加,加上暴露于环境化学品混合物可能产生累积的神经毒性效应,可能加剧全球PD的上升,突出了改进风险评估和预防措施的必要性。
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引用次数: 0
A hypothesis of Cybernetic Medicine: Redefining health and disease through control theory 控制论医学的假设:通过控制理论重新定义健康和疾病
IF 0.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-11-19 DOI: 10.1016/j.mehy.2025.111823
Shiwei Wang, Xiaoyu Li
Reductionist medicine struggles with the systemic, multifactorial nature of complex chronic diseases, necessitating a new theoretical framework, as evidenced by the limited translatability of single-target therapies and persistent residual mortality in conditions such as heart failure. We hypothesize a new theoretical framework: the human body is an integrated MIMO biological control system, with inputs comprising regulable hormones, neural signals, and pharmaceuticals, and outputs consisting of measurable vital signs and metabolite levels. In this paradigm, disease is fundamentally redefined-not as a static component failure, but as a quantifiable reduction in systemic resilience-formally represented by a pathological shift in the system’s dynamic characteristics indicating instability. This framework provides a theoretical foundation for Cybernetic Medicine through two interlinked pillars: (1) system-identification-based diagnostics, and (2) control-theoretic therapeutic design. First, it establishes a new diagnostic paradigm based on system identification, enabling the derivation of personalized, predictive “Digital Twin” models from routine physiological data including wearable biosensors, Brain-computer interface data, continuous vitals, and imaging-derived biomarkers. These models allow for dynamic phenotyping of an individual’s functional state and preclinical risk assessment. Second, it pioneers the development of control-theoretic intervention strategies aimed not at downstream symptom management, but at actively remodeling the system’s dynamics to restore robust stability, within explicitly defined safety and ethical constraints. By reframing pathophysiology through rigorous control-engineering formalism, this hypothesis delineates a pathway toward proactive, model-informed, and precision-stabilizing medicine.
简化主义医学与复杂慢性疾病的系统性、多因素性质作斗争,需要一个新的理论框架,单靶点治疗的有限可翻译性和心力衰竭等疾病的持续残留死亡率证明了这一点。我们假设了一个新的理论框架:人体是一个集成的MIMO生物控制系统,输入包括可调节的激素、神经信号和药物,输出包括可测量的生命体征和代谢物水平。在这一范式中,疾病从根本上被重新定义——不是静态的部件失效,而是系统恢复力的可量化减少——正式表现为系统动态特征的病理转变,表明不稳定。这个框架通过两个相互关联的支柱为控制论医学提供了理论基础:(1)基于系统识别的诊断,(2)控制理论的治疗设计。首先,它建立了一种基于系统识别的新诊断范式,能够从常规生理数据(包括可穿戴生物传感器、脑机接口数据、连续生命体征和成像衍生的生物标志物)中推导出个性化、预测性的“数字孪生”模型。这些模型允许个体功能状态的动态表型和临床前风险评估。其次,它开创了控制理论干预策略的发展,其目的不是针对下游症状管理,而是在明确定义的安全和伦理约束下,积极重塑系统的动态,以恢复强大的稳定性。通过严格的控制工程形式主义重构病理生理学,这一假说描绘了一条通向主动、模型知情和精确稳定医学的途径。
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Medical hypotheses
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