Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “C.637 A > G mutation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

2,158 records · Page 18Linked to original sources
PubMed2026

Epitranscriptomic erasers in bivalves: Evolutionary divergence and species-specific transcriptional plasticity of the ALKBH family under acute thermal stress.

The AlkB homolog (ALKBH) family of Fe(II)/α-ketoglutarate-dependent dioxygenases mediates nucleic acid demethylation, thereby governing RNA metabolism and genomic stability. Despite their pivotal roles in epitranscriptomic regulation across vertebrates, the evolutionary dynamics and functional significance of ALKBH proteins in bivalve mollusks remain largely unexplored. Here, we present a comprehensive phylogenomic analysis of 210 ALKBH genes identified across 35 bivalve species. Our analyses reveal a distinct evolutionary trajectory characterized by the lineage-specific loss of ALKBH4 and the restricted distribution of ALKBH5 to the Mytilidae family, contrasting sharply with vertebrate repertoires. Using the noble scallop (Chlamys nobilis) and Pacific oyster (Crassostrea gigas) as model systems, we demonstrate that ALKBH genes exhibit conserved spatiotemporal expression patterns, with pronounced enrichment in gonadal tissues and during metamorphic transitions, implicating these enzymes in gametogenesis and larval development. Furthermore, comparative thermal stress experiments reveal divergent transcriptional plasticity: the subtropical scallop C. nobilis mounts rapid, transient induction of ALKBH1/2/6 under heat shock, whereas the eurythermal oyster C. gigas maintains sustained ALKBH3 expression, potentially underpinning its superior thermal tolerance. Conversely, cold stress elicits bimodal regulation in C. nobilis, with ALKBH1/2 upregulation contrasting with ALKBH6/7/8 suppression. These findings illuminate the functional diversification of bivalve ALKBH genes and their potential utility as molecular biomarkers for assessing developmental competence and thermal resilience in shellfish aquaculture.

Animals↗
PubMed2026

Effects of Esketamine on Postoperative Hospital Anxiety and Depression Scale Scores in Patients Undergoing Laparoscopic Radical Resection for Colorectal Cancer.

OBJECTIVE: To investigate the effects of intravenous esketamine on postoperative Hospital Anxiety and Depression Scale (HADS) scores in patients undergoing laparoscopic radical resection for colorectal cancer. METHODS: In this prospective, randomized, placebo-controlled study, adult patients for elective laparoscopic radical resection were randomly assigned (1:1) to a control group (group C) or an esketamine group (group PE). Group C received conventional general anesthesia and patient-controlled intravenous analgesia (PCIA). In group PE, esketamine 0.5&#x2009;mg/kg was injected during induction of anesthesia, with esketamine 1&#x2009;mg/kg added to PCIA. Primary outcome was HADS score on postoperative day 1. Secondary outcomes included HADS scores on postoperative days 3 and 7, sleep quality scores, postoperative level of consciousness, complication rate, length of hospital stay, 24&#x2009;h inflammatory factors, and satisfaction scores. RESULTS: Group PE showed significantly lower HADS-A and HADS-D scores on postoperative days 1 and 3 , reduced 24&#x2009;h interleukin-6 (IL-6) leveland higher patient satisfaction compared with group C (all p&#x2009;<&#x2009;0.05). CONCLUSIONS: Esketamine given during induction and in PCIA reduced early-stage postoperative HADS scores and improved patient satisfaction in colorectal cancer patients.

Humans↗
PubMed2026

Peripheral inflammation and executive function among community samples across the lifespan: A systematic review and meta-analysis.

Higher levels of peripheral inflammatory markers are proposed to disrupt cognitive processes; however, the extent to which this relationship applies to executive functions, specifically, has yet to be systematically evaluated. The current meta-analysis synthesizes all available literature measuring the association between peripheral inflammation and executive functions among community individuals across the lifespan. This systematic review searched Web of Science, PubMed, and PsycINFO for published and unpublished studies, in the English language, that assessed the association between markers of peripheral inflammation and self-report and behavioral measures of executive function. In addition to methodological and demographic information, correlation/beta coefficients were extracted from included studies to quantify the association between inflammation and executive functions. This review included 58 studies, 41 of which were included in the random-effects meta-analysis (N&#x202f;=&#x202f;255,539). Among community individuals, higher levels of CRP and IL-6 were associated with poorer executive functioning. These results did not differ when models accounted for potential confounding variables. Meta-regressions revealed that the relationship between inflammatory biomarkers and executive function did not differ as a function of age, adiposity, or percentage of the sample who identified as female. Results of the present review indicate that higher levels of specific inflammatory markers are associated with lower performance on executive function measures; however, we observed significant heterogeneity in the study design and measurement of both inflammation and executive functioning, suggesting important considerations for future research.

Humans↗
PubMed2026

Outcomes of patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications.

OBJECTIVE: This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia. METHODS: 101 patients with baseline hemoglobin <12.0&#x2009;g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3&#x2009;months post-enrollment and maintained ESA/danazol &#x2265;3&#x2009;months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0&#x2009;g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (&#x2265;50% reduction from baseline) and symptom response (&#x2265;6.5-point improvement in FACT-Lym score). RESULTS: Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3&#x2009;months, n&#x2009;=&#x2009;1242). Mean total daily ruxolitinib dose remained >25&#x2009;mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N&#x2009;=&#x2009;2233). Outcomes were similar between the hemoglobin <12.0&#x2009;g/dL analysis population and patients with baseline hemoglobin <10.0&#x2009;g/dL (n&#x2009;=&#x2009;52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease. DISCUSSION: This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia. CONCLUSION: Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Humans↗
PubMed2026

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans↗
PubMed2026

Diagnostic criteria and severity assessment for syndesmosis injury using magnetic resonance imaging: A systematic review.

High ankle sprains involving syndesmosis injury present challenges in both diagnosis and severity assessment. Magnetic resonance imaging is widely regarded as the preferred modality for evaluating syndesmosis injury and related structural damage. This systematic review primarily examined the diagnostic utility of magnetic resonance imaging. Secondarily, it explores grading and prognostics of syndesmosis injuries with magnetic resonance imaging and identified possible imaging parameters predictive of injury severity. A comprehensive search of MEDLINE, Embase, CINAHL Complete, and Scopus was performed through February 12, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Peer-reviewed human studies in English that used magnetic resonance imaging to assess syndesmosis injury were included. Excluded were review articles, case reports, abstract-only studies, and biomechanical or cadaveric investigations. Twenty-seven studies comprising 1931 ankles met inclusion criteria. Magnetic resonance imaging demonstrated high diagnostic accuracy for complete tears of the anterior and posterior inferior tibiofibular ligaments. Ancillary signs such as the ring-of-fire edema pattern, distal tibiofibular joint effusion, and widening of the distal joint space exhibited high specificity with variable sensitivity and may assist in grading injury severity. Magnetic resonance imaging in chronic syndesmosis injury primarily detects fibrotic scarring and post-injury changes. Evidence gaps remain regarding the parameters that best determine injury severity and indicate early surgical intervention in competitive athletes. Consolidating multiple magnetic resonance imaging findings into standardized diagnostic criteria may improve reliability and clinical decision-making.

Humans↗
PubMed2026

Post-weaning social isolation increases reward-seeking behavior in mice.

Social isolation is a growing public health concern. Although isolation at any age is harmful, previous studies have shown that isolation during adolescence, correlating with critical periods of brain development, can impair cognitive function and increase the risk for psychiatric illness later in life. In this study, we utilized a mouse model of social isolation (SI) during adolescence (postnatal day 21-35) and compared performance of isolated and group-housed mice on a touchscreen-based continuous performance test (rCPT) and fixed ratio/progressive ratio (FR/PR) tasks in adulthood. SI improved performance in the rCPT and the improvement in performance was consistent across time bins within the 45-minute testing session. There were no effects of SI on reaction times or reward retrieval latencies. A possible confound for performance in the rCPT would be SI-induced changes in reward-seeking or motivation for the strawberry milk reward. We next compared the SI mice to their group-housed littermate controls on both PR and FR schedules of reinforcement and found that SI mice had higher breakpoints on a PR4 schedule and earned significantly more reinforcers on an FR1 schedule of reinforcement compared to their group-housed littermates, suggesting that high performance in the CPT may be due to increased motivation for food rewards. These data indicate that SI during adolescence has significant effects on reward-seeking behavior in adult mice and may provide a useful behavioral model for studying the link between SI and risk for neuropsychiatric disorders.

Animals↗
PubMed2026

Sensor-based measures of knee brace adherence have low agreement with self-report methods: A multi-measure study among knee osteoarthritis patients.

OBJECTIVE: To explore agreement between self-report and objectively measured adherence to brace wearing by patients with knee osteoarthritis. METHOD: A single-arm observational analysis nested within the PROP OA randomised controlled trial (ISRCTN28555470). Of 237 adults with symptomatic knee osteoarthritis randomised to brace treatment, 60 were included in this sub-study investigating three different methods of assessing knee brace wear time over 26 weeks: 1. Self-report questionnaires (SRQ) at 12 weeks and 26 weeks; 2. Short message service (SMS) questions (days worn in past week, typical hours per day when worn) administered from week 1 to week 24; 3. A skin temperature sensor embedded in the brace, sampling every 10&#x202f;min for 26 weeks. The presence and reason for the sensor were concealed from participants. The estimated proportion of participants meeting "minimum brace use", defined a priori as &#x2265;1&#x202f;h on &#x2265;2 days in past week, was described for each measurement method, overall and by brace type (unloader, neutral). For temperature sensor measurements, time spent above 24&#xb0;C and time spent above 25&#xb0;C were used. Agreement between the measures was summarised by percentage agreement and kappa (&#x138;). RESULTS: The estimated proportions of participants meeting "minimum brace use" at 12 weeks were 83% (SRQ), 83% (SMS), 60% and 58% (temperature sensor, 24&#xb0;C and 25&#xb0;C thresholds, respectively). At 26 weeks, the corresponding estimates reduced to 72%, 71% (SMS at 24 weeks), 43% and 37%. Sensor data suggested the sharpest decline in brace use occurred within the first 12 weeks. Agreement between self-report measures was higher than between self-report measures and sensor (SRQ vs SMS at 12 weeks: 92% agreement, &#x138;=0.67 (95%CI: 0.34, 1.00); SRQ vs Sensor at 12 weeks: 74%, 0.35 (0.10, 0.60); SMS vs Sens at 12 weeks: 76%, 0.36 (0.05, 0.66). Agreement between all measurement methods reduced at 26 weeks. CONCLUSIONS: This novel use of a temperature sensor to monitor brace adherence in knee osteoarthritis indicates that self-report adherence substantially overestimates knee brace wearing time, with implications for clinical trials and practice.

Humans↗
PubMed2026

Effects of intradialytic nutrition on dialysis adequacy and fatigue in hemodialysis patients: a randomized crossover study.

OBJECTIVE: To assess intradialytic nutrition's effects on dialysis adequacy and fatigue in maintenance hemodialysis patients. METHODS: A randomized, two-period, two-sequence, self-controlled crossover trial was conducted in two outpatient hemodialysis centers in T&#xfc;rkiye. Thirty-six patients were randomized; 32 completed both periods. The participants received standardized intradialytic nutrition in one period and no food intake during the control period. Dialysis adequacy was evaluated using the urea reduction ratio and single-pool Kt/V. Intradialytic blood pressure was recorded during dialysis sessions, and fatigue severity was measured using the Piper Fatigue Scale at the end of each period. RESULTS: No significant differences were observed in dialysis adequacy or fatigue scores between the two periods. Intradialytic nutrition was associated with greater reductions in systolic and diastolic blood pressure, particularly during the second hour of dialysis. No clinically relevant adverse events occurred. CONCLUSION: Intradialytic nutrition did not compromise dialysis adequacy or worsen fatigue severity but was associated with increased intradialytic blood pressure reductions. Individualized clinical decisions and careful hemodynamic monitoring are warranted when implementing intradialytic nutritional interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07687498.

Humans↗
PubMed2026

Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Psychedelic agents induce a window of heightened neuroplasticity that extends beyond acute intoxication, during which neural circuits are more amenable to change. This period may facilitate changes in cognition relevant to the treatment of psychiatric disorders. This systematic review synthesised clinical and preclinical evidence of subacute and long-term (&#x2265;1&#x202f;day) effects of classic and non-classic psychedelics on cognition. MEDLINE, EMBASE, APA PsycInfo and Web of Science were searched to identify human and animal studies investigating psychedelics and cognition (executive function, attention, decision-making). Sixty-seven (47 clinical, 20 preclinical) articles met inclusion criteria. Psilocybin demonstrated the most consistent evidence of subacute and longer-term cognitive improvement, particularly in cognitive flexibility and attention. Ketamine showed enhancement across cognitive domains, although findings were heterogeneous. LSD and DMT showed no consistent subacute changes, while MDMA was associated with transient cognitive impairments that resolved within days. Risk of bias assessments revealed selective outcome reporting, poor reporting of missing data and inadequate methodological detail, limiting the confidence of findings. Current evidence provides preliminary support for subacute changes in cognition following administration of select psychedelic agents. Cognitive improvements were more frequently seen in psychiatric populations than healthy subjects, which may reflect a remediation of existing cognitive deficit rather than enhancement above normal functioning. Adequately powered, controlled studies with standardised reporting of cognitive outcomes are required to determine the magnitude, durability and clinical relevance of psychedelic-associated cognitive change.

Hallucinogens↗
PubMed2026

Genetic Screening of Colombian Patients With Early-Onset Parkinson Disease.

BACKGROUND AND OBJECTIVES: Early-onset Parkinson disease (EOPD), defined as symptom onset before 50 years of age, accounts for approximately 10% of patients and is suggested to have a greater genetic component than typical late-onset forms of the disease. Recessive variants in PRKN, PINK1, and DJ-1, are the most common genetic cause of EOPD, however, most studies are in patients of white ancestry. This study aims to analyze genetic variants in PRKN, PINK1, and DJ-1 in Colombian patients to help address the gap in EOPD genetic research of South American populations. METHODS: We analyzed 43 unrelated patients with EOPD using Sanger sequencing for the PRKN, PINK1, and DJ-1 genes and employed multiplex ligation-dependent probe amplification to detect copy number variants. Additionally, long-read whole-genome sequencing was conducted on 3 unresolved patients with age at onset before 30 years of age (long-read sequencing [LRS] patient A-C). RESULTS: We identified known pathogenic single-nucleotide variants and copy number variants in the PRKN gene accounting for 2 patients' disease (4.6% of patients). We observed 2 pathogenic variants in PRKN (c.155delA; p.N52Mfs*29 and c.1083+1G>A) in patient 1, who reported an age at onset of 16 years. We further detected a homozygous duplication of PRKN exons 5-6 in an additional patient, age at onset of 18 years. DISCUSSION: Our study helps characterize genetic contributors to EOPD in Colombian patients, demonstrating genetic forms (PRKN, PINK1, and DJ-1) are rare. Our results highlight a need to include diverse populations in research to improve genetic understanding of disease.

Journal Article↗
PubMed2026

Genome-wide SNP data support species boundaries in sympatric Polylepis Ruiz & Pav. (Rosaceae) species from Bolivia and Ecuador.

Species delimitation in the South American genus Polylepis is notoriously challenging due to high morphological similarity and phenotypic plasticity, likely driven by hybridization and gene flow. Previous phylogenetic studies suggested that genetic structure aligns more strongly with geography than with taxonomy, questioning existing species concepts and hampering conservation efforts. We used double-digest RAD sequencing (ddRADseq) to generate genome-wide SNP data for 11 Polylepis species sampled across multiple localities in Bolivia and Ecuador. Population genetic analyses, phylogenetic inference, and network approaches were combined to assess whether genetic structure aligns more closely with taxonomy or geography. Morphologically defined species formed largely cohesive genetic lineages across regions, with species identity explaining substantially more genetic variation than locality. While localized admixture and reticulation were detected among closely related taxa, widespread species showed strong genetic cohesion and clear separation from congeners. Our results indicate that the sampled Polylepis species from Bolivia and Ecuador maintain distinct genetic identities despite localized signals consistent with gene flow. This genome-wide support for current taxonomy highlights Polylepis as a valuable model for studying speciation under gene flow and indicates that multiple geographic sampling will be essential in reconstructing a robust phylogeny of the genus, with important implications for conservation planning in Andean montane forests.

Bolivia↗
PubMed2026

Risk Factors and Predictive Model for Postoperative High Myopia in Children Undergoing Congenital Cataract Surgery With Intraocular Lens Implantation.

PURPOSE: To identify risk factors associated with the development of high myopia following congenital cataract surgery and to establish a robust predictive model. DESIGN: Retrospective clinical cohort study. SUBJECTS: This retrospective study included 106 pediatric patients who underwent congenital cataract surgery with primary IOL implantation (mean follow-up 8.19 years). The model was externally validated in an independent cohort of 72 patients with a mean follow-up of 7.83 years. METHODS: Preoperative and postoperative ocular biometric parameters were collected. Risk factors for postoperative high myopia were analyzed using Cox proportional hazards regression, which served as the basis for model construction. The predictive performance of the model was rigorously evaluated for discrimination and calibration. Discriminative ability was quantified using Harrell's C-index and the area under the receiver operating characteristic curve (AUC). Model calibration was assessed via calibration plots by comparing predicted probabilities with actual observed outcomes. Internal validation was performed using a bootstrapping method (500 iterations) to ensure model stability and adjust for potential overfitting. RESULTS: An initial postoperative refraction of <+0.75D, and a higher IOL Power to Axial length Ratio (IOL/AL ratio) were identified as significant risk factors for the development of postoperative high myopia. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. The predictive model demonstrated robust performance, achieving a C-index of 0.711 (internal validation C-index: 0.713). The area under the receiver operating characteristic curve (AUC) values for predicting high myopia at 5 and 10 years were 0.858 and 0.745, respectively. Furthermore, calibration curves demonstrated excellent agreement between the predicted and observed outcomes throughout the follow-up period. In external validation, the model achieved a C-index of 0.825, 5-year AUC of 0.833, and 10-year AUC of 0.713. CONCLUSIONS: Our analysis established that initial postoperative refraction <+0.75D, and an elevated IOL/AL ratio are key determinants of high myopia risk following surgery. Shorter preoperative axial length was associated with a greater magnitude of postoperative myopic shift. This predictive framework provides clinicians with a practical tool to optimize preoperative IOL selection and identify high-risk infants who require vigilant myopia prevention and balanced amblyopia management.

Humans↗
PubMed2026

Culture of infectious human norovirus isolated from live contaminated oysters.

Human noroviruses are a major cause of foodborne outbreaks worldwide. Filter-feeding shellfish, such as oysters, can bioaccumulate these viruses in their digestive tissue when grown in sewage-impacted coastal areas and are often implicated in norovirus foodborne outbreaks. Despite the high sensitivity of current molecular assays, these methods for norovirus detection in shellfish fail to distinguish between infectious and non-infectious particles. Assessing norovirus infectivity in shellfish remains a challenge due to the lack of suitable isolation methods that maintain capsid integrity. In this study, a protocol for isolating infectious norovirus from oyster tissues, based on chloroform-butanol elution and polyethylene glycol concentration (CB-PEG), was optimized for the recovery of human norovirus GI and GII. While CB-PEG method recovered various norovirus GI and GII genotypes, it was less efficient at the genomic level than a protocol based on proteinase K elution (adapted from ISO 15216) and showed genotype-dependent viral recovery rates. By optimizing the flocculation step, we improved the method's compatibility with human intestinal enteroid (HIE) cultures. Using this approach, we successfully quantified infectious norovirus GII.3 titers recovered from artificially-contaminated live oysters. Interestingly, infectious virus was better isolated following a freezing step of the digestive tissues, with titers ranging from 13 to 40 TCID50/mL for positive samples. In conclusion, this study established an optimized methodological approach for the relative quantification of infectious norovirus GII.3 in shellfish, paving the way for future research on viral persistence and inactivation strategies in this foodstuff.

Norovirus↗
PubMed2026

Sex- and age-specific associations of VEGFA polymorphisms with multiple sclerosis susceptibility.

AIM: To evaluate six VEGFA polymorphisms (rs1570360, rs699947, rs3025033, rs2146323, rs1413711 and rs833061) and serum VEGFA concentrations in 270 Lithuanian patients with multiple sclerosis (MS) and 270 matched healthy controls. METHODS: Genotyping was performed using real-time PCR, and serum VEGFA levels were measured by enzyme-linked immunosorbent assay. Statistical analyses were conducted using IBM SPSS version 31.0. RESULTS: Nominal differences in VEGFA genotype and allele distributions were observed in sex- and age-stratified analyses. Among females, the rs1413711 C allele was more frequent (p&#x2009;=&#x2009;0.005), whereas the rs833061 C allele was less frequent (p&#x2009;=&#x2009;0.006), in MS patients than controls. In participants aged >38 years, the rs1413711 C allele was also more frequent in MS cases (57.5% vs. 46.0%, p&#x2009;=&#x2009;0.008). Logistic regression identified nominal associations, particularly for rs1413711, rs699947 and rs833061, but none remained significant after correction for multiple testing. Serum VEGFA levels were higher in MS patients than controls (p&#x2009;=&#x2009;0.004). Nominal genotype-related differences in serum VEGFA levels and haplotype associations with reduced MS odds were also observed, but did not remain significant after multiple-testing correction. No consistent associations were found between VEGFA variants and clinical parameters. CONCLUSION: VEGFA genetic variation and elevated serum VEGFA may be associated with MS, but the genetic findings require confirmation in larger independent cohorts.

Humans↗
PubMed2026

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 &#xb1; 9 years, 41% were women, mean eGFR was 48.2 &#xb1; 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗
PubMed2026

Feeding the disease: The impact of nutritional supplementation on Nosema (Vairimorpha) infection in honey bees (Apis mellifera).

Honey bees (Apis mellifera) experience variable colony losses across regions and years, with infectious diseases representing a key component of colony health challenges. Among the most prevalent pathogens are the microsporidian parasites Nosema apis and Nosema ceranae, whose impacts on host survival and transmission vary widely depending on context. While nutritional supplementation is commonly used to support honey bee health, its effects on Nosema infection outcomes remain unclear. Here, we experimentally tested whether dietary enrichment alters survival and infection intensity following exposure to a mixed Nosema inoculum. Newly emerged worker bees were challenged with Nosema spores and maintained on either a basic sucrose diet or the same diet supplemented with a commercial pollen substitute. Dietary enrichment significantly increased both mortality risk and infection intensity in Nosema-infected bees, while having no detectable effect on survival in uninfected controls. These results indicate that supplementation can, counter intuitively, exacerbate nosemosis by promoting parasite replication rather than enhancing host resistance. Our findings highlight the importance of distinguishing nutritional effects on host tolerance versus resistance, and caution that interventions intended to improve bee nutrition may inadvertently increase pathogen production and transmission potential under certain conditions.

Animals↗
PubMed2026

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p&#x202f;<&#x202f;0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans↗