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PubMed2026

[Pathogenicity analysis and prenatal genetic counseling for five Chinese pedigrees harboring a hemizygous c.-32C>G variant of FGF13 gene].

OBJECTIVE: To explore the pathogenicity and prenatal counseling strategies for five Chinese pedigrees harboring a hemizygous c.-32C>G (NM_001139500.2) variant of fibroblast growth factor 13 (FGF13) gene. METHODS: Five Chinese pedigrees found to carry a hemizygous c.-32C>G variant of the FGF13 gene at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2024 and January 2025 were selected as study subjects. The pedigrees had undergone prenatal diagnosis for a family history of genetic disorders, abnormal fetal ultrasound findings, or advanced maternal age. A retrospective analysis was carried out, wherein clinical data for all members of the pedigrees were obtained through the medical records system and outpatient visit system. Peripheral blood samples were collected from all pedigree members, and amniotic fluid samples were obtained from the probands. Following extraction of genomic DNA, prenatal diagnosis was performed using chromosomal microarray analysis (CMA) and trio whole-exome sequencing (trio-WES). Sanger sequencing was used to determine the carrier status for the candidate variant, and Mini-Mental State Examination (MMSE) was used to assess the cognitive function of hemizygous individuals carrying the FGF13 gene c.-32C>G variant. Pathogenicity of candidate variant was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-171). RESULTS: CMA and trio-WES revealed no pathogenic variants in all probands, whilst trio-WES and Sanger sequencing had identified 11 male individuals carrying a hemizygous c.-32C>G variant of the FGF13 gene from the five pedigrees, which included six adult males, a young boy, and four fetuses. One fetus had undergone termination of pregnancy due to hydrocephalus, one was born pre-term at 34+1 weeks of gestation owing to maternal hypertension, and other two were delivered at full term. Follow-up of the survived males revealed no phenotypic manifestations related to language or intellectual impairment. Among these, three adult males underwent the MMSE assessment, all of whom showed normal cognitive function. Search of the gnomAD database suggested the carrier frequency of FGF13 c.-32C>G variant in the East Asian population to be 0.125%, with 11 hemizygous males documented. Three male patients harboring the variant showed severe intellectual disability. Both in vitro and in vivo studies suggested that it could reduce the translation levels of FGF13 protein. Based on the ACMG guidelines, it was classified as variant of uncertain significance (BS4+PS3_Supporting). CONCLUSION: There is insufficient evidence to classify the FGF13 c.-32C>G as a pathogenic variant in clinical practice, and its presence should not be considered an indication for pregnancy termination due to major birth defects.

Adult↗

PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially β-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating β-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group × Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2026

Interventions to Reduce Loneliness in Informal Caregivers of People With Dementia: A Systematic Review.

AIM: To summarize the current evidence on reducing loneliness among informal caregivers of people with dementia, such as family members or friends. DESIGN: A systematic review. METHODS: The methodological quality was evaluated using the revised Cochrane risk-of-bias tool for randomized controlled trials and the revised JBI critical appraisal checklist for quasi-experimental studies. Data were extracted as predefined and synthesized narratively. The Template for Intervention Description and Replication checklist was used to report the intervention characteristics. DATA SOURCES: Six electronic databases (MEDLINE via PubMed, EMBASE, Cochrane Library, PsycINFO, CINAHL Plus, and Web of Science Core Collection) were searched for studies published in peer-reviewed English journals from the inception of each database until 28 January 2024. RESULTS: Eight studies were included in this review, published between 2002 and 2023, with three being randomized controlled trials. All included interventions were psychosocial. Only one study reported significant improvements in loneliness. Five studies utilized remote and online interventions, such as social networking, psychotherapy, and online social support. Interventions varied in their impact on secondary outcomes, including stress, depressive symptoms, anxiety, and caregiver burden. Four studies demonstrated a positive effect on caregiver stress levels. One pilot trial reported a positive impact on depressive symptoms, and another study noted potential improvements in anxiety. One pilot study reported an average improvement in caregiver burden. CONCLUSION: While the evidence is insufficient for conclusive statements, this systematic review suggests potential benefits of interventions to reduce loneliness and improve mental health among these caregivers. It highlights the promise of remote interventions in addressing loneliness among dementia caregivers. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The findings suggest that tailored interventions, especially those delivered remotely, can enhance the support provided to caregivers, potentially improving their mental health and overall well-being. REPORTING METHOD: This systematic review adhered to the PRISMA statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Humans↗

PubMed2026

The Meaning and Significance of Breastfeeding for Biological Mothers of Children with Cleft Lip and/or Palate.

INTRODUCTION: Given the functional, emotional, and symbolic challenges imposed by cleft lip and/or palate (CL/P) on exclusive breastfeeding (EBF), mothers often experience early breastfeeding cessation with impacts on maternal identity and the mother-infant bond. This study aimed to explore the meanings, feelings, and experiences of mothers of children with CL/P regarding breastfeeding in the face of these adversities. METHODS: This qualitative study applied the Clinical-Qualitative Method as proposed by Turato. Six in-depth semistructured interviews were conducted with biological mothers of children with CL/P, recruited from a specialized craniofacial reference center in Brazil. Data were analyzed using a qualitative content analysis approach, grounded in psychodynamic concepts from the Medical Psychology theoretical framework. RESULTS: Based on the analysis of the collected material, three analytical categories were identified and constructed: (1) "Existential conflict regarding the inability to fulfill the ideal maternal role"; (2) "Duality between the need and the fear of caregiving"; and (3) "The anguish experienced between tangible and intangible support during breastfeeding."Conclusions:Although the inability to EBF in children with CL/P generates emotional distress, motherhood is reimagined through adaptive forms of care and bonding, highlighting gaps in institutional support and the need for more humanized, emotionally sensitive health practices.

Humans↗

PubMed2026

The future of precision oncology and artificial intelligence in Belgium: scenarios and policy responses.

PURPOSE: Precision medicine, also known as personalized medicine, enables the provision of tailored health services to patients. In the prevention, early detection, and treatment of cancers, precision medicine is highly promising, given the increasing use of genomic profiling for diagnosis and adapting therapies in several tumor types. Artificial Intelligence (AI) can support this process by analyzing vast amounts of relevant data. However, high-quality data and financial investments in the health system are essential for the implementation of precision medicine and AI solutions in routine cancer care. DESIGN/METHODOLOGY/APPROACH: Building on the quantitative outcomes of a foresight exercise published in another study, this article collects qualitative data to gain more detailed insights into the future of precision oncology in Belgium and discusses the role of AI in this field. It reports the results of a series of expert workshops, focusing on four hypothetical future scenarios that are centered around technological and economic issues that must be overcome for the widespread use of precision oncology in Belgium. FINDINGS: The study concludes that all four scenarios discussed in the workshops would require supportive policy measures in Belgium, which should go beyond mere technological and economic considerations, such as involving patient associations and the public in policy design or creating multi-disciplinary expert groups for precision medicine. ORIGINALITY/VALUE: To the best of our knowledge, this is the first study to employ foresight methodology to illustrate possible future scenarios, scrutinize feasible approaches for implementing precision oncology in Belgium, and discuss the use of AI in this context.

Belgium↗

PubMed2026

Neighborhood Deprivation and Screening Mammography Utilization: A Retrospective Cross-Sectional Study.

RATIONALE AND OBJECTIVES: Access to screening mammography reduces breast cancer mortality disparities. The Area Deprivation Index (ADI) is a validated measure of neighborhood socioeconomic disadvantage linked to adverse health outcomes. There is limited data evaluating mammography utilization among patients residing in areas of higher deprivation. This study evaluated the association between ADI and screening mammography utilization within an accountable care organization (ACO) affiliated with a multicenter academic medical center in the Upper Midwest. METHODS: This retrospective cross-sectional study included women aged 40-85 years attributed to the ACO in 2022, based on Wisconsin Collaborative for Healthcare Quality criteria. The primary outcome was receipt of screening mammography within two years. The primary exposure was ADI, analyzed by decile (ordinal) and as low (deciles 1-5) versus high (deciles 6-10) deprivation. The logistic regression models evaluated associations between ADI and screening, unadjusted and adjusted for age, race, ethnicity, and preferred language. RESULTS: Among 7463 participants with geographic data, 74.4% completed screening. Screening rates were 75.7% in low-deprivation areas versus 66.2% in high-deprivation areas. Increasing ADI decile was associated with reduced screening in unadjusted (OR 0.891, 95% CI 0.87-0.91, p<0.001) and adjusted analyses (OR 0.897, 95% CI 0.88-0.92, p<0.001). Black participants (OR 0.444, p<0.001) and individuals preferring non-English languages (OR 0.333, p<0.001) had lower screening odds after adjustment. CONCLUSION: Higher neighborhood deprivation is independently associated with lower screening mammography utilization. Targeted, equity-focused interventions addressing neighborhood, racial, and language-related barriers are needed to reduce screening disparities.

Area deprivation Index↗

PubMed2026

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n = 2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120 Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5 mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans↗

PubMed2026

Systematic review of machine learning approaches for predicting sickle cell crisis and mortality risk at the climate-health nexus.

BACKGROUND: Sickle cell anemia (SCA) is a severe genetic blood disorder characterized by recurrent vaso-occlusive crises and increased mortality, with the greatest burden occurring in low- and middle-income countries. Climatic and environmental conditions, including temperature variability, humidity, rainfall, air pollution, and seasonal changes, have been associated with disease exacerbation. However, the extent to which these factors have been incorporated into predictive models remains unclear. This study systematically reviews the application of machine learning (ML) models for predicting SCA crises and mortality in relation to climate and environmental factors. METHODOLOGY: The PRISMA guidelines were used, and 34 peer-reviewed studies published between 2005 and 2026 were analyzed to identify the climate variables, ML approaches employed, and predictive performance. The reviewed studies applied a range of ML techniques, including artificial neural networks, random forests, support vector machines, decision trees, logistic regression, and deep learning models. Temperature, humidity, rainfall, wind speed, air quality indicators, and seasonal patterns were the most frequently examined environmental variables. RESULTS: The findings indicate that most existing models rely predominantly on clinical and demographic data, with limited integration of climate information and inadequate representation of high-burden regions, especially Sub-Saharan Africa. Studies incorporating environmental variables reported improved predictive performance and highlighted the potential of climate-informed early warning systems for SCA management. CONCLUSION: The review recommends development of interdisciplinary, climate-aware ML frameworks, expansion of longitudinal environmental datasets, and increased research in underrepresented regions to support climate-resilient and patient-centered SCA care.

Humans↗

PubMed2026

Developmental roles of LSD1/KDM1A-like (LDL) proteins in plants.

LYSINE-SPECIFIC DEMETHYLASE 1-like (LDL) proteins are conserved FAD-dependent amine oxidases that serve as pivotal regulators in plants. While animal systems typically rely on a single LSD1/KDM1A enzyme, the Arabidopsis thaliana genome encodes an expanded family of LDL homologues (FLD, LDL1, LDL2, and LDL3), resulting in substantial subfunctionalization and specialized recruitment mechanisms. This review explores the diverse developmental roles of plant LDLs, ranging from flowering time and circadian clock regulation to heterochromatin maintenance and epigenetic regulation. We discuss the redundant roles of FLD, LDL1, and LDL2 in repressing the floral repressor FLC and their nonredundant specialized function within the CCA1/LHY-TOC1 circadian feedback loop. A central focus of our review is the emerging mechanism of transcription-coupled demethylation, in which LDLs associate with the phosphorylated C-terminal domain of RNA polymerase II to modify chromatin cotranscriptionally within gene bodies. By integrating findings from Arabidopsis thaliana and crops such as tomato and soybean, we illustrate how the diversified LDL-mediated regulatory toolkit facilitates precise, gene-specific regulation. Ultimately, the LDL family represents a cornerstone of the sophisticated epigenetic strategies that regulate plant phenotypic plasticity in response to developmental and environmental cues.

Circadian clock↗

PubMed2026

Community pharmacists' perspectives on resupplying and prescribing contraceptives: a descriptive qualitative study in Australia.

OBJECTIVES: Australia has commenced implementing contraceptive resupply and prescribing by community pharmacists to improve equity in method access. This study aimed to investigate pharmacist's acceptability of hormonal contraceptive resupply and prescribing. METHODS: Participants were recruited via convenience sampling and had provided contraceptive counseling consistent with the ALLIANCE intervention (i.e. structured, patient-centered, effectiveness-based care) to women seeking the emergency contraceptive pill or presenting prescriptions for medical abortion medicines. This qualitative descriptive study was embedded within the ALLIANCE trial, whose process evaluation included semi-structured interviews with pharmacist participants. The interview guide, containing questions on pharmacists' views of the resupply and prescribing service, was reviewed by the ALLIANCE Trial Chief Investigators and piloted in June 2024 with the SPHERE Pharmacy Advisory Circle. Thirteen questions were developed using the Theoretical Framework of Acceptability (TFA). Two researchers conducted line-by-line coding using an iteratively refined codebook, with codes mapped to TFA constructs to examine operationalization in pharmacists' delivery of hormonal contraception. KEY FINDINGS: Although pharmacists (n = 24) perceived that the service could be cost- and time-saving to patients, they raised concerns of unintentionally removing general practitioner (GP)-led monitoring of patients and overstepping GPs' roles. While pharmacists felt confident in their expertise and generally supported the service, they expressed hesitation about initiating contraceptive prescriptions, for which they felt further training and access to comprehensive medical records were required. Additional barriers included increased workload pressures, lack of reimbursement, and inadequate staffing. CONCLUSIONS: Overall, providing a resupply service appears to be acceptable to community pharmacists because it relies on the GP's initial assessment but prescribing less so. However, evaluation is needed post-implementation to explore sustainability, feasibility, and long-term impact on patient outcomes.

contraception↗

PubMed2026

Microbial signal profiles and organism-level concordance between plasma metagenomic sequencing and blood culture in suspected bloodstream infection.

Plasma metagenomic next-generation sequencing (mNGS) and blood culture detect different components of the microbial signal and frequently produce discordant organism reports. We characterized microbial signal class, report-derived burden, organism-level concordance, and independent clinical attribution in a retrospective, single-center, episode-level cohort. Among 329 episodes with evaluable plasma mNGS reports, 315 had blood culture performed; 232 were mNGS positive/culture negative and 53 were positive by both methods. In the 232 discordant episodes, the recorded routine-care diagnosis classified 124 as bloodstream infection (BSI) and 108 as non-BSI. Nonviral signals were present in 78.2% and 42.6%, respectively (P < 0.001), and median maximum report-derived sequence counts were 98.5 and 11.5 (P < 0.001). Two laboratory physicians then independently reviewed source records using structured criteria while masked to the recorded BSI label and mNGS organism and sequence-count information. Initial agreement for the five-category BSI assessment was 97.6% (Cohen's kappa, 0.960). Within the mNGS-positive/culture-negative subgroup, adjudicated BSI likelihood showed a modest ordinal association with report burden (Spearman rho = 0.190; P = 0.004), while mNGS organisms were considered supported in 1 episode, plausible in 158, unlikely or contaminant in 72, and unresolved in 1. Among 53 dual-positive episodes, 33 (62.3%) shared at least one species, but only 5 (9.4%) had complete species-set concordance. Plasma mNGS and blood culture therefore frequently generated non-equivalent organism sets. Signal class and report burden contributed graded contextual evidence, but organism-level attribution required clinical review and orthogonal microbiology rather than binary positivity alone.

Humans↗

PubMed2026

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 × 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (β=0.087; P=.003), injunctive norms (β=0.078; P=.009), perceived susceptibility (β=0.051; P=.03), perceived benefits (β=0.253; P<.001), and trust (β=0.33; P<.001), and negatively associated with perceived severity (β=-0.047; P=.049) and privacy concerns (β=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans↗

PubMed2026

Long-Term Survey to Assess Recurrence and Complications of Surgically Treated Pleomorphic Adenoma.

OBJECTIVE(S): To (1) report on the long-term recurrence rate of surgically managed pleomorphic adenoma (PA) and (2) assess long-term surgical outcomes after parotidectomyMethods:Cross-sectional survey of all patients with a pathologic diagnosis of PA who underwent surgical management in a tertiary care center from 01/1997 to 12/2023 and had access to an electronic patient portal. Surveys were delivered via electronic patient portal or phone call with 6 questions to assess recurrence and long-term surgical outcomes. Time to first recurrence and recurrence free survival were analyzed using a Kaplan-Meier curve. RESULTS: Seven hundred-forty-five patients met inclusion criteria and received the survey, with a 56% response rate (n = 420). The clinical median follow-up length was 51 days, which extended to a median length of 6.2 years following the survey. The median change in follow-up length was 5.37 years (P < .001). The recurrence rate was 1% at 5 years, with a median time to first recurrence of 7.54 years. 13% and 9% of responders reported facial asymmetry and incisional cosmetic concerns, respectively. 33% of patients reported experiencing Frey syndrome, which increased from 5.2% of survey responders with documented Frey syndrome at their original post-operative assessment. CONCLUSION: Long-term assessment of PA outcomes confirms low recurrence rates, suggesting regular surveillance of recurrence is likely unnecessary. Complaints of Frey syndrome increased in frequency with longer term follow-up, which should be considered during patient counseling. LEVEL OF EVIDENCE: 3.

Humans↗

PubMed2026

Functional characterization of the MdFLZ2 gene in drought and salt stress tolerance in apple.

Drought and salt stress are significant environmental limitations that severely constrain plant growth and productivity, therefore, enhancing stress tolerance is a key goal in crop improvement. The plant-specific FCS-like zinc finger (FLZ) proteins have been identified as important regulators of stress adaptation. In this study, we conducted a genome-wide characterization of the FLZ gene family in apple and functionally characterized MdFLZ2. qRT-PCR analysis revealed that MdFLZ2 was differentially expressed across various tissues and transcriptionally induced by both drought and salt stress. Subcellular localization assays demonstrated that the MdFLZ2 protein is localized to both the nucleus and the cytoplasm. The overexpression of MdFLZ2 in apple calli, Arabidopsis and tomato conferred increased resistance to drought and salt stress. In addition, yeast two-hybrid (Y2H) assays confirmed that MdFLZ2 interacted with MdSnRK1.1, and similar interactions were also detected between other MdFLZ family members and MdSnRK1.1. Collectively, our findings suggest MdFLZ2 as a positive regulator of drought and salt tolerance and highlight its potential to serve as a genetic resource for abiotic stress improvement.

Malus↗

PubMed2026

Symptom Burden After Dialysis Initiation and Its Association With Hospitalization.

RATIONALE & OBJECTIVE: Symptom burden is distressing for patients living with kidney failure, but there is limited information about the combination of symptoms and individual symptoms that most strongly predict health care use in this group. We classified and summarized patients' symptom burden levels and changes over time and estimated associations with hospitalizations among patients receiving incident hemodialysis. STUDY DESIGN: Longitudinal, observational. SETTING & PARTICIPANTS: Individuals initiating dialysis in the United States. EXPOSURE: Kidney Disease Quality of Life-36 (KDQOL-36) measure. OUTCOME: First hospitalization after dialysis initiation. ANALYTICAL APPROACH: Latent transition analysis was used to identify symptom burden classes using the KDQOL-36. Cox regression models were used to assess whether individual KDQOL-36 symptoms and symptom burden groups were associated with hospitalization risk after dialysis initiation, independent of demographics and comorbid conditions. RESULTS: 1,818 participants were Black (29%), were aged >65 years (59%), were women (42%), had diabetes (49%), and had hypertension (74%). Latent transition analysis identified the following 3 symptom burden groups: (1) low (low severity of all symptoms and kidney disease impacts), (2) moderate (high physical health impact and overall burden of kidney disease), and (3) high (high levels of all symptoms and kidney disease impact). After adjusting for patient characteristics, all KDQOL-36 scales except the Effects of Kidney Disease scale were associated with a higher hazard of hospitalization. Using the symptom burden groups, a high symptom burden was associated with a 20% increase in the hazard of hospitalization. A 1-category worsening in pain interference and in fatigue was associated with a 12% and an 8% increased hazard of hospitalization, respectively. LIMITATIONS: Findings may not generalize outside the United States. CONCLUSIONS: Pain interference and fatigue, as well as an overall symptom burden, are useful prognostic indicators in patients receiving in-center hemodialysis. Symptom burden should remain a treatment target in hemodialysis.

Hemodialysis↗

PubMed2026

A systematic review and meta-analysis of radiation-induced oral complications in head and neck cancer: Prevalence and clinical outcomes.

BACKGROUND: Radiation-induced oral complications, notably xerostomia and oral mucositis (OM), are common and debilitating in patients with head and neck cancer (HNC), adversely affecting swallowing, nutritional intake, and overall quality of life (QoL). OBJECTIVES: This review aimed to quantify the prevalence of radiation-induced xerostomia and OM and synthesize their impact on dysphagia and nutritional status among HNC patients undergoing radiotherapy (RT). METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Comprehensive searches were performed in MEDLINE, Scopus, SciFinder, Embase, and PubMed for studies published between January 2019 and December 2025. Data from 51 studies were extracted and synthesized. RESULTS: The pooled prevalence was 85% (95% CI: 81.6-87.9%) for xerostomia and 88.3% (95% CI: 73.9-95.3%) for any-grade OM. Severe OM (Grade 3-4) had a prevalence of 39.5% (95% CI: 23.1-58.8%). These complications were strongly interrelated and significantly associated with dysphagia (69.8%; 95% CI: 53.1-83.7%), malnutrition (66.6%; 95% CI: 37.3-95.9%), and poor QoL (pooled mean QoL score: 64.13/100). Studies employing advanced radiation techniques (e.g., IMRT) demonstrated a lower prevalence of xerostomia (OR = 0.58, 95% CI: 0.42-0.80) compared to conventional RT. CONCLUSION: Radiation-induced oral complications (xerostomia & OM) remain prevalent and clinically significant burden in HNC patients, contributing to a cascade of functional impairments and diminished QoL. These findings highlight the need for preventive strategies, symptom management interventions, and the broader adoption of advanced RT techniques. Longitudinal research is warranted to further evaluate long-term outcomes and guide patient-centered care models.

Humans↗

PubMed2026

Systematic identification pepper CaE2F transcription factor reveals the role of CaDPb in drought stress response.

The EARLY 2 FACTOR (E2F) transcription factor (TF) family plays a pivotal role in regulating plant development and adaptations to environmental stresses. However, the physiological function of E2Fs in pepper (Capsicum annuum L.) are not well elucidated. In this work, we conduct a comprehensive genome-wide annotation of the E2F family within the Zunla-1 pepper genome and further explore the biological roles of CaDPb in response to drought stress. Through systematic bioinformatics analysis, we identify a total of nine CaE2F genes within the Zunla-1 genome, categorizing them into three distinct subgroups. Additionally, we discover multiple cis-regulatory elements in the CaE2F promoter regions associated with responses to plant hormones and drought stress. Public RNA-seq datasets reveal distinct expression profiles of CaE2F genes across various pepper tissues and their responses to environmental stimuli and plant hormones. Subsequently, the CaDPb gene is further functionally verified in drought response. Our findings indicate that TRV2:CaDPb silenced pepper plants are more sensitivity to drought. Furthermore, we show that CaDPb participates in the regulation of reactive oxygen species (ROS) production, the expression of drought-responsive genes, and the modulation of stomatal aperture. Taken together, our findings provide a comprehensive characterization of E2F genes in pepper and offer insights into the biological function of CaDPb in pepper drought stress response.

Capsicum↗