Personalized medicine

个性化医学
  • 文章类型: Journal Article
    不育症,影响全世界夫妻的普遍和情感负担的状况,在生殖健康方面引起了越来越多的关注。虽然其病因仍然是多方面的,新兴研究探索了血清同型半胱氨酸水平和营养缺乏在影响低生育中的作用。这篇全面的综述综合了当前的知识,首先介绍了低生育力和调查血清同型半胱氨酸水平的意义。它继续阐明营养缺乏的作用,特别是叶酸和维生素B12,在高半胱氨酸代谢,并检查了现有的研究,将高半胱氨酸与不育联系起来。这篇综述探讨了这种关系背后的潜在机制,解决研究结果的变异性及其影响因素。对临床实践的影响,包括评估血清同型半胱氨酸水平,营养干预,和个性化医疗,正在讨论。此外,该综述强调了正在进行的研究的重要性。它呼吁采取行动,以增进我们对低生育力的理解,并改善应对生殖挑战的个人和夫妇的生活。
    Subfertility, a prevalent and emotionally taxing condition affecting couples worldwide, has garnered increasing attention in reproductive health. While its etiology remains multifaceted, emerging research has explored the role of serum homocysteine levels and nutrient deficiencies in influencing subfertility. This comprehensive review synthesizes current knowledge, beginning with an introduction to subfertility and the significance of investigating serum homocysteine levels. It proceeds to elucidate the role of nutrient deficiencies, particularly folate and vitamin B12, in homocysteine metabolism and examines existing research linking homocysteine to subfertility. The review explores potential mechanisms underlying this relationship, addressing the variability in study findings and their contributing factors. Implications for clinical practice, including assessing serum homocysteine levels, nutritional interventions, and personalized medicine, are discussed. Moreover, the review underscores the importance of ongoing research. It offers a call to action for advancing our understanding of subfertility and improving the lives of individuals and couples navigating reproduction challenges.
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  • 文章类型: Journal Article
    癫痫手术是耐药癫痫患者的首选治疗方法,但高达50%的患者在切除一年后仍有癫痫发作.为了帮助进行术前计划并逐个患者地预测术后结果,我们开发了一个个性化计算模型框架,该框架将流行病传播与患者特异性连通性和癫痫基因图相结合:流行病传播癫痫发作和癫痫手术框架(ESSES).在一项回顾性研究(N=15)中拟合了ESSES参数,以重现侵入性脑电图(iEEG)记录的癫痫发作。ESSES再现了iEEG记录的癫痫发作,并且对于良好的患者(无癫痫发作,SF)比不良(无癫痫发作,NSF)结果。我们在这里通过模拟术前条件的盲目设置(切除策略和手术结果)的假前瞻性研究(N=34)来说明ESSES的临床适用性。通过在回顾性研究中设置模型参数,ESSES也可以应用于没有iEEG数据的患者。ESSES可以通过找到基于患者特定模型的最佳切除策略来预测任何切除后良好结果的机会。我们发现SF比NSF患者小,提示NSF患者的网络组织或术前评估结果存在内在差异。实际的手术计划与基于模型的最佳切除重叠更多,在减少模型癫痫传播方面有更大的影响,SF患者比NSF患者。总的来说,ESSES可以正确预测75%的NSF和80.8%的SF病例。我们的结果表明,个性化的计算模型可以通过建议替代切除并提供有关建议切除后良好结果的可能性的信息来告知手术计划。这是第一次使用完全独立的队列并且不需要iEEG记录来验证这种模型。
    癫痫手术的个性化计算模型捕获了癫痫发作传播和切除手术的一些关键方面。要确定是否可以在患者的术前评估期间整合该信息,以改善手术计划和良好手术结果的机会。在这里,我们通过一项伪前瞻性研究来解决这个问题,该研究在模仿术前条件的伪前瞻性研究中应用了癫痫发作传播和癫痫手术的计算框架-ESSES框架。我们发现在这个伪前瞻性的背景下,ESSES可以正确预测75%的NSF和80.8%的SF病例。这一发现表明,个性化的计算模型有可能通过建议替代切除并提供有关建议切除后良好结果的可能性的信息来告知手术计划。
    Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but up to 50% of patients continue to have seizures one year after the resection. In order to aid presurgical planning and predict postsurgical outcome on a patient-by-patient basis, we developed a framework of individualized computational models that combines epidemic spreading with patient-specific connectivity and epileptogeneity maps: the Epidemic Spreading Seizure and Epilepsy Surgery framework (ESSES). ESSES parameters were fitted in a retrospective study (N = 15) to reproduce invasive electroencephalography (iEEG)-recorded seizures. ESSES reproduced the iEEG-recorded seizures, and significantly better so for patients with good (seizure-free, SF) than bad (nonseizure-free, NSF) outcome. We illustrate here the clinical applicability of ESSES with a pseudo-prospective study (N = 34) with a blind setting (to the resection strategy and surgical outcome) that emulated presurgical conditions. By setting the model parameters in the retrospective study, ESSES could be applied also to patients without iEEG data. ESSES could predict the chances of good outcome after any resection by finding patient-specific model-based optimal resection strategies, which we found to be smaller for SF than NSF patients, suggesting an intrinsic difference in the network organization or presurgical evaluation results of NSF patients. The actual surgical plan overlapped more with the model-based optimal resection, and had a larger effect in decreasing modeled seizure propagation, for SF patients than for NSF patients. Overall, ESSES could correctly predict 75% of NSF and 80.8% of SF cases pseudo-prospectively. Our results show that individualised computational models may inform surgical planning by suggesting alternative resections and providing information on the likelihood of a good outcome after a proposed resection. This is the first time that such a model is validated with a fully independent cohort and without the need for iEEG recordings.
    Individualized computational models of epilepsy surgery capture some of the key aspects of seizure propagation and the resective surgery. It is to be established whether this information can be integrated during the presurgical evaluation of the patient to improve surgical planning and the chances of a good surgical outcome. Here we address this question with a pseudo-prospective study that applies a computational framework of seizure propagation and epilepsy surgery—the ESSES framework—in a pseudo-prospective study mimicking the presurgical conditions. We found that within this pseudo-prospective setting, ESSES could correctly predict 75% of NSF and 80.8% of SF cases. This finding suggests the potential of individualised computational models to inform surgical planning by suggesting alternative resections and providing information on the likelihood of a good outcome after a proposed resection.
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  • 文章类型: Journal Article
    背景:很少有研究评估拒绝列出肝移植候选者的频率和原因。
    目的:评估肝移植不合格率及其动机。
    方法:对成年患者进行了一项单中心回顾性研究,该研究需要对肝移植合格性进行正式的多学科评估。使用多变量逻辑回归评估上市的预测因子。
    结果:在我们的中心,314例患者在三年内进行肝移植之前进行了多学科检查。移植评估的最常见原因是失代偿性肝硬化(51.6%)和肝细胞癌(35.7%)。整个队列的非上市率为53.8%,移植率为34.4%。收集了二百零五个不合格的动机。最常见的禁忌症是心理(9.3%),心血管(6.8%),和外科(5.9%)。不适当或过早转诊占76例(37.1%)。在多变量分析中,其他医院的转诊(OR:2.113;95CI:1.259-3.548)是未上市的独立预测因子.
    结论:非上市决定发生在我们队列的一半中,并且基于三分之一的病例中的不适当或过早转诊。从另一家医院转诊被视为非上市的强预测因子。
    BACKGROUND: Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.
    OBJECTIVE: To assess the ineligibility rate for liver transplantation and its motivations.
    METHODS: A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility. The predictors for listing were evaluated using multivariable logistic regression.
    RESULTS: In our center, 314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period. The most frequent reasons for transplant evaluation were decompensated cirrhosis (51.6%) and hepatocellular carcinoma (35.7%). The non-listing rate was 53.8% and the transplant rate was 34.4% for the whole cohort. Two hundred and five motivations for ineligibility were collected. The most common contraindications were psychological (9.3%), cardiovascular (6.8%), and surgical (5.9%). Inappropriate or premature referral accounted for 76 (37.1%) cases. On multivariable analysis, a referral from another hospital (OR: 2.113; 95%CI: 1.259-3.548) served as an independent predictor of non-listing.
    CONCLUSIONS: A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three. The referral from another hospital was taken as a strong predictor of non-listing.
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  • 文章类型: Case Reports
    此病例报告描述了希望怀孕的36岁压力性尿失禁(SUI)和膀胱过度活动症(OAB)妇女的治疗选择过程。患者有高血压和2型糖尿病的合并症,这需要考虑改善她的生活质量和生殖健康。最近开发的使用离散数学方法的决策支持工具用于选择适合患者个人情况的治疗方法。分析确定阴道铒激光(VEL)治疗(RenovalaseSPDynamisFotonad.o.o,卢布尔雅那,斯洛文尼亚)最适合该患者。VEL治疗可显着改善SUI和OAB,改变降压药可消除夜尿症。该案例表明图论在SUI患者治疗选择中的潜在应用。
    This case report describes the treatment selection process for a 36-year-old woman with stress urinary incontinence (SUI) and an overactive bladder (OAB) who desired pregnancy. The patient had comorbidities of hypertension and type 2 diabetes, which required consideration to improve her quality of life and reproductive health. A recently developed decision support tool using a discrete mathematical approach was used to select a treatment method tailored to the patient\'s individual situation. The analysis determined that vaginal erbium laser (VEL) treatment (Renovalase SP Dynamis Fotona d.o.o, Ljubljana, Slovenia) was the most suitable for this patient. VEL treatment significantly improved both SUI and OAB and changing antihypertensive medication eliminated nocturia. This case suggests the potential application of graph theory in treatment selection for SUI patients.
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  • 文章类型: Journal Article
    基于细胞培养的技术广泛用于各个领域,例如药物评估,毒性评估,疫苗和生物制药的发展,生殖技术,和再生医学。已经证明,包括胶原蛋白在内的细胞外基质(ECM)蛋白的预吸附,层粘连蛋白和纤连蛋白为细胞粘附提供更多的支持。细胞印迹的目的是通过凝胶或聚合物模仿细胞膜的自然形貌,为调节细胞功能创造可靠的环境。最近的研究结果表明,细胞印迹是通过控制培养细胞与表面的粘附相互作用来指导其行为的工具。因此,在这篇综述中,我们旨在比较不同的细胞培养与印迹方法,并讨论不同的细胞印迹在再生医学中的应用,个性化医疗,疾病建模,和细胞疗法。
    Cell culture-based technologies are widely utilized in various domains such as drug evaluation, toxicity assessment, vaccine and biopharmaceutical development, reproductive technology, and regenerative medicine. It has been demonstrated that pre-adsorption of extracellular matrix (ECM) proteins including collagen, laminin and fibronectin provide more degrees of support for cell adhesion. The purpose of cell imprinting is to imitate the natural topography of cell membranes by gels or polymers to create a reliable environment for the regulation of cell function. The results of recent studies show that cell imprinting is a tool to guide the behavior of cultured cells by controlling their adhesive interactions with surfaces. Therefore, in this review we aim to compare different cell cultures with the imprinting method and discuss different cell imprinting applications in regenerative medicine, personalized medicine, disease modeling, and cell therapy.
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  • 文章类型: Journal Article
    背景:急诊科拥挤继续威胁患者的安全并导致患者预后不良。先前设计用于预测住院的模型存在偏见。成功估计患者入院概率的预测模型将有助于减少或预防急诊科“登机”和医院“出口障碍”,并通过提前入院和避免旷日持久的床位采购流程来减少急诊科的拥挤。
    目的:通过利用现有的临床描述符,开发一种模型来预测即将从急诊科住院的成年患者在患者就诊早期(即,患者生物标志物)在分诊时常规收集并记录在医院的电子病历中。生物标志物有利于建模,因为它们在分诊时的早期和常规收集;瞬时可用性;标准化定义,测量,和解释;以及他们摆脱患者病史的限制(即,他们不会受到不准确的病史患者报告的影响,不可用的报告,或延迟报告检索)。
    方法:这项回顾性队列研究评估了急诊科成年患者1年的连续数据事件,并开发了一种算法来预测哪些患者需要即将入院。评估了八个预测变量在患者急诊科就诊结果中的作用。采用Logistic回归对研究数据进行建模。
    结果:8预测模型包括以下生物标志物:年龄,收缩压,舒张压,心率,呼吸频率,温度,性别,和敏锐度水平。该模型使用这些生物标志物来识别需要住院的急诊科患者。我们的模型表现很好,观察到的和预测的录取之间有很好的一致性,这表明了一个很好的拟合和校准良好的模型,显示出很好的能力来区分谁会入院和不会入院。
    结论:这个基于主要数据的预测模型确定了急诊科患者入院风险增加。这些可操作的信息可用于改善患者护理和医院运营,特别是通过预测分诊后哪些患者可能入院,从而减少急诊科的拥挤,从而提供所需的信息,以在护理连续体中更早地启动复杂的入院和床位分配过程。
    BACKGROUND: Emergency department crowding continues to threaten patient safety and cause poor patient outcomes. Prior models designed to predict hospital admission have had biases. Predictive models that successfully estimate the probability of patient hospital admission would be useful in reducing or preventing emergency department \"boarding\" and hospital \"exit block\" and would reduce emergency department crowding by initiating earlier hospital admission and avoiding protracted bed procurement processes.
    OBJECTIVE: To develop a model to predict imminent adult patient hospital admission from the emergency department early in the patient visit by utilizing existing clinical descriptors (ie, patient biomarkers) that are routinely collected at triage and captured in the hospital\'s electronic medical records. Biomarkers are advantageous for modeling due to their early and routine collection at triage; instantaneous availability; standardized definition, measurement, and interpretation; and their freedom from the confines of patient histories (ie, they are not affected by inaccurate patient reports on medical history, unavailable reports, or delayed report retrieval).
    METHODS: This retrospective cohort study evaluated 1 year of consecutive data events among adult patients admitted to the emergency department and developed an algorithm that predicted which patients would require imminent hospital admission. Eight predictor variables were evaluated for their roles in the outcome of the patient emergency department visit. Logistic regression was used to model the study data.
    RESULTS: The 8-predictor model included the following biomarkers: age, systolic blood pressure, diastolic blood pressure, heart rate, respiration rate, temperature, gender, and acuity level. The model used these biomarkers to identify emergency department patients who required hospital admission. Our model performed well, with good agreement between observed and predicted admissions, indicating a well-fitting and well-calibrated model that showed good ability to discriminate between patients who would and would not be admitted.
    CONCLUSIONS: This prediction model based on primary data identified emergency department patients with an increased risk of hospital admission. This actionable information can be used to improve patient care and hospital operations, especially by reducing emergency department crowding by looking ahead to predict which patients are likely to be admitted following triage, thereby providing needed information to initiate the complex admission and bed assignment processes much earlier in the care continuum.
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  • 文章类型: Journal Article
    脓毒症相关急性肾损伤(SA-AKI)是危重患者的严重并发症,导致更高的死亡率,发病率,和成本。SA-AKI的复杂病理生理学需要警惕的临床监测和适当的,迅速干预。虽然传统的统计分析已经确定了SA-AKI的严重危险因素,不同研究的结果不一致.这引起了人们对利用人工智能(AI)和机器学习(ML)更好地预测SA-AKI的兴趣。ML可以通过分析大量数据集来发现人类无法识别的复杂模式。监督学习模型如XGBoost和RNN-LSTM已被证明在预测SA-AKI发病和随后的死亡率方面非常准确。经常超过传统的风险评分。同时,无监督学习揭示了不同SA-AKI患者中临床相关的亚表型,实现更多量身定制的护理。此外,它有可能通过基于患者结局的持续改进来优化脓毒症治疗以预防SA-AKI.然而,利用AI/ML带来了关于数据隐私的道德和实践挑战,算法偏差,和法规遵从性。AI/ML允许早期风险检测,个性化管理,最佳治疗策略,和SA-AKI管理的协作学习。未来的方向包括实时患者监测,模拟数据生成,和及时干预的预测算法。然而,向临床实践的平稳过渡需要持续的模型增强和严格的监管监督。在这篇文章中,我们概述了用于解决SA-AKI的常规方法,并探讨了AI和ML如何应用于诊断和管理SA-AKI,突出了他们彻底改变SA-AKI护理的潜力。
    Sepsis-associated acute kidney injury (SA-AKI) is a serious complication in critically ill patients, resulting in higher mortality, morbidity, and cost. The intricate pathophysiology of SA-AKI requires vigilant clinical monitoring and appropriate, prompt intervention. While traditional statistical analyses have identified severe risk factors for SA-AKI, the results have been inconsistent across studies. This has led to growing interest in leveraging artificial intelligence (AI) and machine learning (ML) to predict SA-AKI better. ML can uncover complex patterns beyond human discernment by analyzing vast datasets. Supervised learning models like XGBoost and RNN-LSTM have proven remarkably accurate at predicting SA-AKI onset and subsequent mortality, often surpassing traditional risk scores. Meanwhile, unsupervised learning reveals clinically relevant sub-phenotypes among diverse SA-AKI patients, enabling more tailored care. In addition, it potentially optimizes sepsis treatment to prevent SA-AKI through continual refinement based on patient outcomes. However, utilizing AI/ML presents ethical and practical challenges regarding data privacy, algorithmic biases, and regulatory compliance. AI/ML allows early risk detection, personalized management, optimal treatment strategies, and collaborative learning for SA-AKI management. Future directions include real-time patient monitoring, simulated data generation, and predictive algorithms for timely interventions. However, a smooth transition to clinical practice demands continuous model enhancements and rigorous regulatory oversight. In this article, we outlined the conventional methods used to address SA-AKI and explore how AI and ML can be applied to diagnose and manage SA-AKI, highlighting their potential to revolutionize SA-AKI care.
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  • 文章类型: Journal Article
    对已发表的科学文献进行评论,以了解在制药领域使用3D生物硝化的益处和潜在观点。这项工作是根据系统评价和荟萃分析(PRISMA)报告荟萃分析和系统评价的首选报告项目进行的。科学数据库PubMed,Scopus,谷歌学者,和ScienceDirect被用来使用以下关键字搜索和提取数据:3D生物打印,药物研发,个性化医疗,制药公司,临床试验,药物测试。综述了生物打印在药剂学中应用的几个方面的数据点。生物打印的主要应用是新药分子的开发以及个性化药物的制备,但最大的好处是药物筛选和测试。3D打印领域的增长促进了制药应用,能够为个体患者开发个性化的药物筛选和药物递送系统。生物打印提供了根据患者个人需求按需打印药物的机会,制作形状,结构,和剂量适合每个病人的身体状况,即,打印特定药物以控制释放速率;打印多孔片剂以减少吞咽困难;制作经皮微针贴片以减轻患者疼痛;等等。另一方面,生物打印可以精确控制细胞和生物材料的分布以构建类器官,或者器官芯片,用于在模仿特定疾病特征的打印器官上测试药物,而不是动物测试和临床试验。生物打印的发展有可能提供定制的药物筛选平台和药物输送系统,满足一系列个性化需求。以及药物开发和患者治疗不同阶段的前景。生物打印在药物的临床前和临床测试中的作用在缩短在市场上推出医药产品的时间方面也具有重要意义。
    To create a review of the published scientific literature on the benefits and potential perspectives of the use of 3D bio-nitrification in the field of pharmaceutics. This work was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting meta-analyses and systematic reviews. The scientific databases PubMed, Scopus, Google Scholar, and ScienceDirect were used to search and extract data using the following keywords: 3D bioprinting, drug research and development, personalized medicine, pharmaceutical companies, clinical trials, drug testing. The data points to several aspects of the application of bioprinting in pharmaceutics were reviewed. The main applications of bioprinting are in the development of new drug molecules as well as in the preparation of personalized drugs, but the greatest benefits are in terms of drug screening and testing. Growth in the field of 3D printing has facilitated pharmaceutical applications, enabling the development of personalized drug screening and drug delivery systems for individual patients. Bioprinting presents the opportunity to print drugs on demand according to the individual needs of the patient, making the shape, structure, and dosage suitable for each of the patient\'s physical conditions, i.e., print specific drugs for controlled release rates; print porous tablets to reduce swallowing difficulties; make transdermal microneedle patches to reduce patient pain; and so on. On the other hand, bioprinting can precisely control the distribution of cells and biomaterials to build organoids, or an Organ-on-a-Chip, for the testing of drugs on printed organs mimicking specified disease characteristics instead of animal testing and clinical trials. The development of bioprinting has the potential to offer customized drug screening platforms and drug delivery systems meeting a range of individualized needs, as well as prospects at different stages of drug development and patient therapy. The role of bioprinting in preclinical and clinical testing of drugs is also of significant importance in terms of shortening the time to launch a medicinal product on the market.
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  • 文章类型: Journal Article
    一些传染因子有可能在细胞微环境中引起特定的修饰,这可能有利于致癌过程。目前,有特定的病毒和细菌,如人乳头瘤病毒(HPV)和幽门螺杆菌,已被确定为肿瘤形成的危险因素。沙眼衣原体(CT)感染是全球最常见的细菌性性传播感染之一。最近的欧洲数据证实了整个欧洲的持续上涨。男女感染通常无症状,需要一个筛查计划来早期发现。尽管如此,不是所有的欧洲国家都有。沙眼衣原体可引起慢性和持续性感染,导致炎症,并且有合理的生物学机制将生殖器感染与肿瘤发生联系起来。在这里,我们旨在了解引起子宫内膜的CT生殖器感染的流行病学和生物学合理性,卵巢,还有宫颈肿瘤.此外,我们涵盖了一些可用于研究这种潜在关联的最佳体外技术。此外,我们捍卫个性化医疗策略的观点,通过发现一些生物标志物来治疗这些患者。这篇综述支持了在这一领域发展进一步基础研究的必要性,为了研究和确定衣原体生殖器感染在肿瘤发生中的作用。
    Some infectious agents have the potential to cause specific modifications in the cellular microenvironment that could be propitious to the carcinogenesis process. Currently, there are specific viruses and bacteria, such as human papillomavirus (HPV) and Helicobacter pylori, that are well established as risk factors for neoplasia. Chlamydia trachomatis (CT) infections are one of the most common bacterial sexually transmitted infections worldwide, and recent European data confirmed a continuous rise across Europe. The infection is often asymptomatic in both sexes, requiring a screening program for early detection. Notwithstanding, not all countries in Europe have it. Chlamydia trachomatis can cause chronic and persistent infections, resulting in inflammation, and there are plausible biological mechanisms that link the genital infection with tumorigenesis. Herein, we aimed to understand the epidemiological and biological plausibility of CT genital infections causing endometrial, ovarian, and cervical tumors. Also, we covered some of the best suitable in vitro techniques that could be used to study this potential association. In addition, we defend the point of view of a personalized medicine strategy to treat those patients through the discovery of some biomarkers that could allow it. This review supports the need for the development of further fundamental studies in this area, in order to investigate and establish the role of chlamydial genital infections in oncogenesis.
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