Tag: nevin manimala

Endokrynol Pol. 2026 Jul 27. doi: 10.5603/ep.112146. Online ahead of print.

ABSTRACT

INTRODUCTION: Among all RET proto-oncogene variants, Y791F has been the most controversial and widely debated with regard to itspathogenicity and clinical significance.

MATERIAL AND METHODS: Medical records of 104 RET Y791F variant carriers were retrospectively analyzed. The population comprised 30 probands with medullary thyroid carcinoma (MTC), 6 probands with pheochromocytoma, 63 family members, and 5 patients in whomthe RET Y791F variant was found during genetic screening. The characteristics of the 30 RET Y791F carriers with MTC were comparedwith those of the control group of 208 patients with sporadic MTC.

RESULTS: The median age at surgery in the 30 probands with MTC was 58 years (range: 20-79), and in the control group with sporadic MTC it was 55 years (range: 21-80), with no statistically significant difference (p = 0.16). Multifocal MTC was observed in 8 of 30 operatedprobands (26%) and in 29 of 208 patients (13.9%) with sporadic disease (p = 0.07). Prophylactic surgery was performed in 21 familymembers. No MTC was identified in the postoperative material. Among patients under surveillance, none of the RET Y791F carriersshowed any abnormalities on thyroid ultrasound or any increase in calcitonin concentration. None of the followed-up patients (except 6after adrenalectomy) was diagnosed with pheochromocytoma. None of the 104 RET Y791F carriers had hypercalcemia.

CONCLUSIONS: Based on our results, individuals with the RET Y791F variant do not require enhanced clinical surveillance or prophylactic intervention and should be managed according to general population guidelines, unless additional clinical indications arise.

PMID:42504689 | DOI:10.5603/ep.112146

Turk J Gastroenterol. 2026 Jul 21. doi: 10.5152/tjg.2026.26198. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: miR-143-5p functions as a tumor-suppressive microRNA across various cancer types. The current study investigated the expression, prognostic value, and role of miR-143-5p in colorectal cancer (CRC).

MATERIALS AND METHODS: The expression of miR-143-5p was measured by quantitative reverse transcription polymerase chain reaction. Associations between miR-143-5p expression and clinicopathological characteristics of patients with CRC were statistically analyzed. A series of in vitro cell-based assays were performed to investigate the underlying regulatory mechanisms.

RESULTS: miR-143-5p was downregulated in CRC and may serve as a promising independent prognostic biomarker. Reduced miR- 143-5p expression was associated with adverse clinicopathological characteristics and decreased 5-year overall survival. MYCBP was identified as a direct target of miR-143-5p. Overexpression of miR-143-5p suppressed the malignant behaviors of CRC cells, which were partially restored by enforced MYCBP expression.

CONCLUSION: miR-143-5p is downregulated in CRC and may function as a potential independent prognostic biomarker. Moreover, miR- 143-5p may play a tumor-suppressive role in CRC by specifically targeting MYCBP.

PMID:42504669 | DOI:10.5152/tjg.2026.26198

J Neurogastroenterol Motil. 2026 Jul 30;32(3):396-404. doi: 10.5056/jnm25126.

ABSTRACT

BACKGROUND/AIMS: : The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet is a well-researched treatment for diarrhea-predominant irritable bowel syndrome (IBS-D), but its value for constipation-predominant IBS (IBS-C) is uncertain. Clinicians may hesitate to recommend it for IBS-C, fearing it could worsen constipation or offer little relief. This study aims to assess the diet’s effectiveness across all IBS subtypes, specifically investigating its impact on stool patterns in IBS-C and the correlation with symptom relief.

METHODS: : This prospective service evaluation involved 294 IBS patients (84% female, mean age 44.6) attending dietitian-led group sessions on FODMAP restriction (baseline) and reintroduction (follow-up). The primary outcome was “satisfactory relief of gut symptoms” via the global symptom question; secondary outcomes included changes in stool consistency, IBS subtype, and gastrointestinal symptoms.

RESULTS: : At baseline, 23.8% (70/294) had IBS-C and 35.7% IBS-D (105/294). All subtypes except IBS-M showed significant symptom relief at follow-up (P < 0.001), with no statistically significant difference between IBS-C (50.7%, 35/69) and IBS-D (44.8%, 47/105) (P = 0.158). After FODMAP restriction, 50.7% (35/69) IBS-C remained IBS-C, while 44.9% (31/69) shifted to unclassified IBS (IBS-U). Those who shifted (IBS-C to IBS-U) reported greater relief (74.2%, 23/31 vs 45.7% 16/35, P = 0.019) and reduced pain (P = 0.006), unlike those who remained IBS-C (P = 0.180).

CONCLUSIONS: : IBS-C and IBS-D showed similar symptom relief after FODMAP restriction. Notably, 44.9% of IBS-C patients shifted to normal stool consistency (IBS-U), with greater symptom relief and reduced pain. FODMAP restriction does not necessarily exacerbate constipation in IBS-C and remains a viable treatment option in real world clinical practice.

PMID:42504656 | DOI:10.5056/jnm25126

Cancer Med. 2026 Aug;15(8):e72085. doi: 10.1002/cam4.72085.

ABSTRACT

Ibrutinib has demonstrated inhibition of ErbB/HER tyrosine kinases in preclinical models. This Phase I/II study investigated the safety, efficacy, and immunomodulatory effects of ibrutinib in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on ado-trastuzumab emtansine therapy. In Phase I, cohorts of three patients received ibrutinib 560 mg or 420 mg by mouth once daily combined with standard dosing of trastuzumab. Phase II enrolled additional patients to assess the primary endpoint of clinical benefit rate (CBR) at 420 mg ibrutinib plus trastuzumab. Flow cytometry and NanoString analyses were performed on peripheral blood mononuclear cells. Overall, 26 patients were enrolled. Patients received a median of three prior regimens containing a HER2-targeted therapy in any setting. The most common treatment-related adverse events were bruising, rash, fatigue, and thrombocytopenia. Four patients (15%) experienced cardiac adverse events, including decreased left ventricular ejection fraction in two patients. The CBR of ibrutinib plus trastuzumab was 19.2% (95% confidence interval: 6.6-39.4). Flow cytometry of T- and natural killer (NK)-cell and myeloid-cell panels showed that treatment statistically significantly decreased T helper 17 (T_H17) and myeloid-derived suppressor cells (MDSC) with no decrease in T helper 2 (T_H2) cells. Ibrutinib plus trastuzumab was well-tolerated but had limited anti-tumor activity in patients with heavily pretreated, HER2-positive MBC (NCT03379428). Trial Registration: Clinicaltrials.gov, NCT03379428.

PMID:42504645 | DOI:10.1002/cam4.72085

AIDS. 2026 Jul 24. doi: 10.1097/QAD.0000000000004584. Online ahead of print.

ABSTRACT

OBJECTIVES: To gain insight into HIV prevention pathways of individuals following pre-exposure prophylaxis (PrEP) care disengagement at the Center of Sexual Health in Amsterdam (CSHA), the Netherlands, to improve prevention services.

DESIGN: Cross-sectional study.

METHODS: CSHA clients disengaged from PrEP care were asked to complete an online survey (January-April 2025). The survey included open-ended, closed-ended, and multiple-choice questions on PrEP care discontinuation reasons at CSHA, continuing PrEP care elsewhere and sexual behavior. This was complemented by routine CSHA data. Data was analyzed using descriptive statistics, thematic analysis, and multivariable Bayesian logistic regression to identify determinants of non-PrEP-use elsewhere.

RESULTS: Of the 734 people who disengaged from PrEP care, 273 (37.2%) responded to the questionnaire. Changes in sexual behavior to reduce the chance of HIV acquisition was the main reason for discontinuation (n = 117, 62.6% of those with available data). Among respondents who confirmed their PrEP discontinuation at CSHA and were not living with HIV (n = 247), 82 (33.2%) could still benefit from PrEP. Of those, 56 (68.3%) continued PrEP use elsewhere, leaving a PrEP need of 31.7% (n = 26); 11 (13.4%) did not use any HIV prevention strategy. People who were lost-to-follow-up (i.e., stopping without notification) and ≤35 years old had higher odds of non-PrEP-use elsewhere.

CONCLUSIONS: Most PrEP discontinuations reflected periods without an indication for PrEP. Nevertheless, a substantial proportion of individuals who could benefit from PrEP reported not using HIV prevention after disengagement from PrEP care at CSHA. Our results highlight a need to support these individuals for re-engagement in care to reduce chance of acquiring HIV.

PMID:42504601 | DOI:10.1097/QAD.0000000000004584

Int J Stroke. 2026 Jul 27:17474930261475966. doi: 10.1177/17474930261475966. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse non-motor outcomes are common after stroke, yet their true prevalence and prognosis remain uncertain, partly due to substantial methodological heterogeneity across studies. We aim to undertake a comprehensive synthesis of the available evidence on adverse non-motor outcomes after stroke. First, we aim to examine prevalence across study settings (hospital-based versus population-based cohorts) and to evaluate the influence of outcome definitions, measurement instruments (validated versus non-validated), stroke type (ischaemic stroke, intracerebral haemorrhage, or mixed), and duration of follow-up. Second, we aim to identify study-level characteristics associated with adverse outcomes.

METHODS: We searched PubMed, MEDLINE, EMBASE, Scopus, Web of Science, and PsycINFO via Ovid (1st January 1999 – 30th November 2025) for prospective cohorts reporting 11 non-motor outcomes: anxiety, depression, apathy, fatigue, sleep disturbance, social participation, pain, bladder, bowel, and sexual dysfunction. Pooled prevalence according to study setting (hospital versus population) was estimated using random-effects models; outcome definitions and measures were synthesised using descriptive statistics, and meta-regression analysis was used to identify associated factors. The quality of all included studies was assessed with the Newcastle-Ottawa Scale.

RESULTS: A total of 357 prospective cohort studies, (247 541 participants; mean age 64 years; 247 male-predominant studies) were included, with a follow-up between 30 days to 10 years after stroke with median follow-up 6 months [IQR 3-12]. Half of the studies were hospital based 181/352 (51%). Of the included studies, 195 (55%) included participants with ischaemic stroke, 148 (42%) included participants with ischaemic stroke or intracerebral haemorrhage, while only 10 (3%) included participants with intracerebral haemorrhage. Across all analysis heterogeneity ranged I2 41%-99%. We found no significant differences in the prevalence of adverse non-motor outcomes between hospital versus population settings, except, bowel dysfunction was more frequently reported in population-based studies (61%, 95% Cl 54%-67% vs 47%, 95% Cl 37%-58%, p=0.005). Non-validated outcome measures were used in 156/352 studies (44.3%). Studies using non-validated outcome measures showed higher pooled prevalence of anxiety (34%, 95% Cl 29%-40%, vs 25%, 95% Cl 20%-33%, p<0.001), apathy (32%, 95% Cl 27%-36, vs 22%, 95% 13%-41%, p=0.005), sleep disturbance (62%, 95% Cl 54%-73%, vs 51%, 95% Cl 44%-58%, p<0.001), and bowel dysfunction (56%, 95% Cl 43%-69% vs. 49%, 95% Cl 38%-60%, p=0.027). Majority of studies 207/352 (59%), were conducted within 30 days to 6 months after stroke, whereas only 41/352 (12%) examined non-motor outcomes beyond 2 years post-stroke. Older age (>60 years), stroke due to ICH, and use of non-validated outcome measures were significantly associated with a higher prevalence of adverse non-motor outcomes across multiple domains.

CONCLUSIONS: Non-motor outcomes are highly prevalent after stroke in hospital and population settings. However, we found methodological limitations across included studies, including limited evidence on non-motor outcomes after ICH, poor characterisation of stroke type, frequent use of non-validated outcome measures, and few studies assessing outcomes beyond two years after stroke. Our findings indicate an urgent need for long-term, methodologically rigorous studies of non-motor outcomes after stroke to enable consistent assessment, inform life after stroke pathways, and improve clinical care.

PMID:42504592 | DOI:10.1177/17474930261475966

J Biol Rhythms. 2026 Jul 27:7487304261469609. doi: 10.1177/07487304261469609. Online ahead of print.

ABSTRACT

Circadian rhythms have been shown to regulate sleep-wake timing across the lifespan, yet many questions remain about early childhood circadian physiology. Understanding dim-light melatonin onset (DLMO) and offset (DLMOff), established markers of circadian phase, is essential for characterizing circadian rhythms in early childhood. We examined the distribution of salivary DLMO and DLMOff and their relationship with actigraphic sleep timing across 20 healthy preschoolers (M = 4.31 ± 0.34 years, 45% female). After maintaining a consistent sleep schedule for 7 days, children completed an in-home circadian assessment. Children were awoken 1.5 h before habitual wake time, and saliva samples were collected in 20- to 30-min intervals throughout the morning to determine DLMOff, then in the evening until 50 min past habitual bedtime to assess DLMO. A 4-pg/ml threshold was used to calculate each phase marker. DLMO ranged from 17:22 to 20:40 (M = 18:55 ± 0:54) and was positively associated with bedtime, sleep onset, and midsleep. In contrast, morning melatonin levels were highly variable, allowing DLMOff calculation in only 8 participants. Within this small subsample, later DLMOff was associated with later chronotype (r = 0.81), sleep offset (r = 0.84), and midsleep (r = 0.80). Across the full sample, interpolated melatonin levels at habitual wake remained ≥ 4 pg/ml for 45% of children, a pattern broadly consistent with findings in adults, in which a majority of participants exhibit DLMOff after habitual wake time. These findings indicate that although evening melatonin profiles were consistently well-defined, permitting reliable calculations of DLMO across all participants, morning melatonin patterns were often irregular in young children. When able to be calculated, DLMOff showed strong associations with sleep timing, suggesting it could be a reliable marker of circadian phase. However, high variability and fluctuating morning melatonin patterns make DLMOff difficult to determine in many preschool-aged children.

PMID:42504584 | DOI:10.1177/07487304261469609

Zhonghua Liu Xing Bing Xue Za Zhi. 2026 Jul 27;47:1-8. doi: 10.3760/cma.j.cn112338-20260330-00208. Online ahead of print.

ABSTRACT

Acute respiratory infections (ARIs) are characterized by high morbidity, strong transmissibility, and non-specific clinical manifestations, posing substantial challenges to conventional single-source surveillance systems for early warning. This review systematically summarizes recent advances in ARIs identification and spatiotemporal cluster analysis based on multi-source medical data, focusing on three core technical domains. In terms of medical text information extraction, methodologies have progressively evolved from keyword matching to deep semantic understanding powered by large language models; regarding multimodal medical data fusion, the review covers data-level, feature-level, and decision-level fusion strategies; and in spatiotemporal cluster analysis, both traditional statistical methods and artificial intelligence-based models are discussed. Current research faces key challenges including inconsistent data standards, ambiguous boundaries in data ethics and application scope, incomplete spatial information, and insufficient model interpretability. Future efforts should prioritize advancing medical data standardization and interoperability, and developing hybrid modeling frameworks that balance computational efficiency with interpretability, thereby enabling the transition of ARIs surveillance from passive identification to proactive and precision-oriented early warning.

PMID:42504575 | DOI:10.3760/cma.j.cn112338-20260330-00208

Int J Stroke. 2026 Jul 27:17474930261475853. doi: 10.1177/17474930261475853. Online ahead of print.

ABSTRACT

Most stroke trials conventionally use outcome measures that reflect a single point of concern, such as functional outcomes or neurological improvement. Such a focus has a limited capacity to reflect the holistic nature of clinical reality, where multiple facets of health are of importance.Other clinical areas are increasingly embracing alternative approaches that better reflect the multifaceted nature of health outcomes, driven by the development of Win Statistics methodology. These methods compare the outcomes for all possible pairs of patients from the treatment versus control group and summarise the treatment effect as a combination of proportions of such comparisons where the person from the treatment group has a better/worse outcome when compared to the person in the control group. In this context, “better outcome” is defined holistically, based on information collected across multiple health facets (e.g. mortality, symptom reduction and quality of life).Such approaches are highly applicable to stroke research. They are a direct extension of “Tournament Methods” that are already used to analyse modified Rankin Scale data, and several stroke trials have already adopted this new approach to better reflect the multifaceted nature of stroke. Despite this, there is little guidance available to stroke researchers who wish to make use of the approach. This article provides a review of how to effectively use Tournament Methods to reflect the multifaceted nature of stoke.We review how Tournament Methods may be used to estimate treatment effects that simultaneously consider multiple clinical outcomes.We describe methods that have been used within stroke to combine multiple clinical outcomes for Tournament Methods analysis, provide an overview of the effect size measure estimates commonly used to summarise treatment effects, and discuss both available statistical methods and software for the analysis, visualisation and reporting of Win Statistics. We provide practical recommendations for conducting and reporting statistical analyses under the Tournament Methods approach using published stroke trials as illustrative examples. We further present newly developed point-and-click software that provides easy access to statistical codes for conducting Tournament Methods analyses and facilitates the use of our recommendations.

PMID:42504538 | DOI:10.1177/17474930261475853

Biom J. 2026 Aug;68(4):e70152. doi: 10.1002/bimj.70152.

ABSTRACT

Confirmatory multi-lab preclinical trials are a powerful experimental strategy to enable decisions to transition from preclinical to clinical settings. With their complexity, such study designs pose several challenges in statistical planning, analysis, and reporting of experiments. To address these, we convened an expert group of biostatisticians and biomedical scientists currently involved in such trials to summarize in a tutorial the most common challenges and offer general guidance. Furthermore, we incorporated statistical advice from existing clinical trials’ guidelines and adapted it into recommendations for preclinical trials. We describe strategies on key topics such as calculating sample sizes, handling differences between centers, and selecting relevant covariates. Additionally, we give guidance on statistical methods to account for lab effects and proper reporting of analyses. We embed this in a general discussion on remaining open questions to advance the analysis of preclinical confirmatory studies. The provided general, non-case-specific guidance serves as a conversation starter between biomedical scientists and statisticians to develop robust statistical analysis strategies for confirmatory multi-lab preclinical trials.

PMID:42504463 | DOI:10.1002/bimj.70152