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Genome-wide identification of the peanut HD-Zip gene family and AhHDZ15 positively regulating salt and drought stress in heterologously overexpressed Arabidopsis.

Homeodomain-leucine zipper (HD-Zip) transcription factors play important roles in plant growth, development, and abiotic stress responses. However, bioinformatic analyses and functional studies of HD-Zip family in peanut are scarce. In this study, 128 AhHDZ genes were identified and classified into four subfamilies in the phylogenetic analysis. Transcriptomic data and RT-qPCR analysis indicated the expression levels of AhHDZ4 and AhHDZ15 were significantly elevated in response to 12 h of salt stress, while AhHDZ4/15/60/69/126 all showed a progressive increase over time in response to drought stress. AhHDZ15 protein was localized in the nucleus. Under salt and drought stress, the germination rates of AhHDZ15-overexpressing in Arabidopsis were significantly higher than wild-type (WT), and root lengths were also significantly longer than WT. In addition, the SOD, CAT, chlorophyll content, and Relative Leaf Water Content (RLWC) value of leaves in AhHDZ15-overexpressing lines were significantly higher than WT, while the MDA content was significantly lower than WT. The above results indicate that heterologous overexpression of AhHDZ15 enhanced salt and drought tolerance in Arabidopsis. Furthermore, AhHDZ15 could bind to the L1-box element of the AhVNI2 promoter, thereby activating AhVNI2 transcription and enhancing the expression of downstream salt stress-responsive genes. These findings implies a potential function of AhHDZ15 in peanut that requires further validation.

Arabidopsis

Genomic characterization and pathogenicity of ruminant Listeria monocytogenes isolates in a murine oral infection model.

Listeria monocytogenes is a major foodborne pathogen; its ruminant isolates display zoonotic characteristics, causing similar clinical signs in humans, including abortion and encephalitis. However, data on whole genome sequencing and pathogenicity of ruminant L. monocytogenes isolates remain sparse. This study aimed to analyze the genotypic characteristics of L. monocytogenes isolates from ruminants with listeriosis. Furthermore, we assessed the in vivo pathogenicity of four ruminant L. monocytogenes isolates, characterized via whole-genome sequencing-based genetic clustering, in orogastrically inoculated mice. The isolate LM18 (serotype 1/2b, ST224, SL6178) had the lowest lethal dose compared to the other three isolates including previous hypervirulence type (serotype 4b, ST1, SL1) and caused secondary bacteremia in lungs, with sustained bacterial loads in the spleen and liver. Genomic (listeria pathogenicity island -1 and -3) and virulence gene (actA and llsX) mutation analyses associated with virulence suggested from well-recognized studies could not elucidate the virulence of the isolates. SSI-1, which only exists in the isolate LM18 (serotype 1/2b, ST224, SL6178), may help L. monocytogenes survive in the gastrointestinal environment, thereby affecting its virulence. Further research should investigate the role of SSI-1 in the pathogenicity of L. monocytogenes. Moreover, additional studies utilizing larger datasets of ruminant isolates are required to validate our genotypic characterization and to obtain a comprehensive picture of further genotypic differences crucial for L. monocytogenes pathogenicity.

Animals

Comprehensive analysis suggests CRIF1 is a potential target in breast cancer associated with prognosis and immune infiltration.

BACKGROUND: CRIF1 is a multifunctional factor that regulates cell biological processes such as the cell cycle, cell proliferation, and energy metabolism, and it is a new molecule that contributes to the poor prognosis of many malignancies. However, its involvement in breast cancer development is not fully known. MATERIALS AND METHODS: To investigate the relationship between CRIF1 expression, prognosis, and clinical characteristics using The Cancer Genome Atlas (TCGA-BRCA). The relationship between CRIF1 expression and the immunological microenvironment was investigated using CIBERSORT, ESTIMATE. Breast tissue and CRIF1 expression were validated by IHC. A tiny interfering plasmid was designed to transiently transfect breast cancer cell lines, and proliferation-related functional tests were carried out. The effect of sh CRIF1 on tumor formation was confirmed using a subcutaneous tumor experiment in naked mice. RESULTS: We discovered that CRIF1 was highly elevated in breast cancer tissues and associated with a poor prognosis. CRIF1 stimulates breast cancer cell proliferation, migration, and invasion. Knockdown decreased PI3K/AKT/mTOR signaling, which boosted autophagy activity. Immune infiltration research revealed that patients with high CRIF1 expression had higher CD8+ T cell expression but reduced macrophage M2 expression. CONCLUSION: Upregulation of CRIF1 in breast cancer cells enhances malignant behavior, which may be mediated by PI3K/AKT/mTOR signaling and is linked to cellular autophagy.

Humans

Status of dementia care among healthcare practitioners in Nigerian tertiary hospitals: a cross-sectional study.

BACKGROUND/OBJECTIVES: Dementia is an escalating public health concern globally. This study evaluated the knowledge, attitudes, practices, and perceived barriers to dementia care among healthcare practitioners in Nigerian tertiary hospitals, aiming to identify practitioner-related sociodemographic predictors and systemic barriers affecting dementia care delivery. METHODS: We collected data from May 2024 to May 2025 for this cross-sectional study in 12 purposively selected tertiary hospitals across Nigeria's six geopolitical zones. Participants included physicians, nurses, pharmacists, and other professionals involved in geriatric psychiatric care. Using multistage and convenience sampling, 394 respondents were recruited (response rate: 99.5%). Data were collected via a validated Dementia Care Practice Questionnaire (Cronbach's α = 0.84) and analyzed with SPSS v22. Descriptive statistics, Chi-square tests, and odds ratios (ORs) identified associations (significance: p ≤ 0.05). RESULTS: Of 394 respondents, 51.5% were aged ≥40 years, and 54.8% were female. While 62.9% demonstrated adequate knowledge, negative perceptions (51.3%) and attitudes (56.9%) were common. Despite this, 71.3% reported engagement in dementia care, and 75.6% demonstrated appropriate professional help-seeking behaviour when confronted with dementia care challenges. Practitioner-reported barriers included limited training opportunities, geographical barriers affecting patient access to dementia services, and inadequate staffing. Predictors of desirable care practices among healthcare practitioners included age ≥40 years, female gender, Christian affiliation, and ≥5 years of professional experience. CONCLUSION: Although many healthcare practitioners are involved in dementia care, gaps in perceptions, attitudes, and structural support persist. Interventions should focus on targeted training, system strengthening, and policy reform to improve dementia care outcomes.

Barriers to care

Depression and amyloid-β across CSF, PET, and plasma biomarkers: a systematic review and meta-analysis.

Alzheimer's disease is increasingly defined by biomarker evidence of amyloid-β and tau pathology, sharpening questions about whether late-life depression contributes to, or instead reflects, this pathology. We conducted a systematic review and meta-analysis of studies published between 2000 and 2025 that compared amyloid-β biomarkers in adults with and without depression, with depression defined by validated clinical diagnoses or symptom rating scales. Twenty-four studies were included, spanning three biomarker sources: cerebrospinal fluid, positron emission tomography imaging, and plasma. Across all sources, the pooled difference in amyloid-β burden between depressed and non-depressed individuals was small and clustered near zero, indicating only a weak, statistically non-significant tendency toward higher amyloid in depression. When the three sources were examined separately, each yielded a similar near-null result, although between-study heterogeneity was considerable for cerebrospinal fluid and plasma and moderate for imaging. Importantly, a prespecified subgroup analysis showed that imaging results diverged by quantification method: studies using the simpler standardized uptake value ratio clustered around zero, whereas the smaller group of studies using kinetic distribution volume ratio modelling showed a significant positive association, suggesting that methodological choices critically influence the observed relationship. Taken together, these findings indicate that depression is not consistently accompanied by greater amyloid-β burden across widely used biomarker platforms. The distribution volume ratio signal nonetheless raises the possibility of subtle associations that cruder methods may obscure, and suggests that depression may shape Alzheimer's disease trajectories more by modifying the clinical impact of amyloid than by altering its amount.

Humans

Multimodal intervention benefits: Responder analysis of J-MINT PRIME Kanagawa trial.

INTRODUCTION: The J-MINT PRIME Kanagawa trial was an 18-month multimodal intervention (incorporating exercise, nutrition, and metabolic management) for dementia prevention. Because the primary analysis showed no significant benefits, we performed an exploratory responder analysis to identify responsive subpopulations. METHODS: We analyzed the Full Analysis Set comprising 188 participants. Classification and regression tree (CART) analysis, applied to the intervention arm, identified baseline predictors of cognitive improvement. These rules were then applied to the entire cohort to evaluate treatment effects on the Mini-Mental State Examination (MMSE) using fully adjusted mixed-effects models for repeated measures (MMRM). RESULTS: CART identified a "Target Group" (N = 108) characterized by baseline profiles such as an MMSE score < 28 or specific metabolic ranges (e.g., LDL-C < 135 mg/dL). Within this target group, the intervention significantly preserved MMSE trajectories compared with the control group (group &#xd7; time interaction, P = 0.022). In contrast, the Non-Target Group (N = 80), consisting of high-functioning individuals (MMSE &#x2265; 28), exhibited no significant group &#xd7; time interaction. DISCUSSION: Multimodal interventions may effectively preserve global cognition in older adults with sub-threshold cognitive decline. Careful targeting of appropriate populations, while considering potential longitudinal measurement artifacts (e.g., practice effects), is essential. These findings provide a hypothesis-generating framework that warrants external validation in future prevention trials.

Humans

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n&#x202f;=&#x202f;45) and those with hEDS (n&#x202f;=&#x202f;45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

Humans

Factors influencing the enhancement&#xa0;of the new iron triangle&#xa0;in healthcare organisations.

PURPOSE: A new paradigm, "healthcare's new iron triangle," has been developed to emphasise the technological perspective of healthcare delivery, focusing on automation, value and empathy. The study aims to build a conceptual model and to identify factors for the enhancement of the new iron triangle in healthcare organisations. DESIGN/METHODOLOGY/APPROACH: The healthcare organisation is the primary focus point of the current study. To determine the factors, a survey of the literature and healthcare experts' opinions was conducted. The&#xa0;healthcare professionals validated the identified factors. Data for this study were gathered using a closed-ended questionnaire and scheduled interviews. The study employed "Total Interpretive Structural Modeling methodology and Matriced' Impacts Croise&#xb4;s Multiplication Appliqu&#xe9;&#xb4; a UN Classement/Cross-Impact Matrix Multiplication Applied to a Classification (MICMAC) analysis" to address the "why" and "how" the factors interact and prioritise the identified factors. FINDINGS: The study found that organisational structure (F8), artificial intelligence (F1), innovation (F2) and human resources (F5) are the driving or key factors of the study. RESEARCH LIMITATIONS/IMPLICATIONS: The study primarily focused on identifying factors for the enhancement of a new iron triangle in healthcare organisations. The scope could eventually be expanded to explore more areas. PRACTICAL IMPLICATIONS: Academics and other stakeholders will have a better understanding of the key drivers for the enhancement of the new iron triangle in healthcare organisations. ORIGINALITY/VALUE: In this study, total interpretive structural modeling and cross-impact MICMAC analysis are proposed as an innovative approach to address the new iron triangle in healthcare organisations.

Humans

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units

Oxygen-controlled gamma-irradiation and annealing enable terminal processing of collagen-based biomaterials.

Gamma irradiation is a widely adopted method for terminal sterilization of medical devices; however, its application to collagen-based extracellular matrix (ECM) materials remains limited due to radiation-induced degradation of structural integrity and mechanical performance. Here, we present an engineered terminal-processing strategy that combines oxygen controlled gamma irradiation (25-30&#xa0;kGy) with post-irradiation dry-heat annealing to preserve ECM functionality while achieving effective sterilization. By modulating oxygen availability during irradiation, this approach alters radical reaction pathways, suppresses oxygen-mediated oxidative degradation, and generates a metastable radical-containing intermediate, which is subsequently converted into a structurally stabilized collagen network through thermal annealing. As a result, the treated matrices preserved ECM integrity and recovered clinically relevant mechanical properties. Furthermore, the process achieved cumulative viral reductions exceeding 6 log10 across a representative panel including enveloped and non-enveloped DNA and RNA viruses, demonstrating compatibility with sterility assurance and viral safety requirements for biologically derived medical devices. Notably, preliminary observations indicate that mechanical integrity can be partially preserved even at elevated irradiation doses up to 50&#xa0;kGy, suggesting potential applicability to sterilization validation frameworks requiring higher assurance levels. Overall, this work establishes a mechanistically grounded terminal-processing paradigm that enables control of radical fate, decouples sterilization efficacy from material degradation, and integrates sterilization, viral safety, and functional preservation into a unified and scalable framework for collagen-based biomaterials. This concept repositions gamma-irradiation from a purely degradative process to a controllable tool for tuning collagen structure and performance.

Gamma Rays

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

Contrasting redox-related physiological responses associated with HaGATA23 and HaGATA36 during Orobanche cumana parasitism in sunflower (Helianthus annuus L.).

Helianthus annuus is an economically important Asteraceae species used for seed oil production and ornamental purposes, but its production is seriously affected by the root-parasitic plant Orobanche cumana. GATA transcription factors are zinc-finger DNA-binding regulators involved in plant development and stress adaptation. However, the molecular characteristics of GATA transcription factors in Helianthus annuus and their contribution to Helianthus annuus -Orobanche cumana interaction remain poorly understood. Here, 36 HaGATA members were retrieved from the Helianthus annuus genome and classified into four phylogenetic clades. Chromosomal placement, collinearity, gene structure, motif composition, and promoter elements varied among the 36 HaGATA members, indicating evolutionary conservation coupled with functional diversification. Expression analysis and RT-qPCR analyses revealed differential expression patterns among HaGATA genes under O. cumana stress, with HaGATA23 markedly downregulated and HaGATA36 strongly upregulated. Overexpression of HaGATA23 was associated with increased malondialdehyde (MDA) accumulation and unfavorable changes in antioxidant enzyme activities, whereas its silencing showed the opposite physiological tendency. In contrast, overexpression of HaGATA36 reduced malondialdehyde accumulation, increased peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activities, while its silencing showed the reverse tendency. These results indicate that HaGATA23 and HaGATA36 are candidate genes associated with contrasting redox-related physiological responses during O. cumana stress. This work provides evidence that GATA transcription factors are associated with redox-related physiological responses in sunflower under O. cumana treatment and identifies HaGATA23 and HaGATA36 as functionally divergent candidate genes for further validation.

Helianthus

Functional Reading Activities to Motivate and Empower: Maintenance of Reading Outcomes for Young Adults With Intellectual and Developmental Disabilities Following a Randomized Controlled Trial.

PURPOSE: This study examined whether the effects of Functional Reading Activities to Motivate and Empower (FRAME), a functional, strategy-based reading comprehension intervention for young adults with intellectual and developmental disabilities (IDDs), were maintained 6 months following the completion of the intervention and explored participants' perceptions of the intervention's feasibility, relevance, and perceived impact. METHOD: Participants were 44 young adults with IDDs (ages 18-26 years) who participated in a previously reported randomized controlled trial (FRAME participants: n = 23; controls: n = 21). Trial outcomes were assessed via telepractice at pretest, posttest, and 6-month follow-up. Six-month maintenance analyses focused on outcomes that demonstrated significant posttest group differences: use of (a) reading comprehension strategies (proximal) and (b) reading comprehension questions (distal). Participant perceptions (social validity) were collected post-intervention from FRAME participants using a structured interview protocol with closed- and open-ended items. RESULTS: At the 6-month follow-up, FRAME participants demonstrated sustained but reduced improvements in strategy use relative to controls (p = .040). Between-groups differences were not maintained for reading comprehension questions (p = .091). Participants reported high acceptability and perceived relevance of FRAME, with qualitative themes reflecting perceived improvements in comprehension, self-improvement, and increased independence. CONCLUSION: Findings suggest that FRAME supports sustainable gains in reading comprehension strategy use and is perceived as meaningful and feasible for young adults with IDDs, although additional supports may be needed to promote sustained improvements in distal comprehension outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33307218.

Humans

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

BACKGROUND: Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length, its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear. METHODS: Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression. RESULTS: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing / metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohort (pooled HR=1.29, p=0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression. CONCLUSION: These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.

RNA-binding proteins

The effect of hip abductor or external rotator strength on dynamic knee valgus in healthy subjects-a systematic review with partial meta-analysis.

BACKGROUND: Weak hip abductors and external rotators (ER) have long been suggested to cause increased dynamic knee valgus. Patients are often prescribed strengthening of these muscles with the expectation that it will reduce their risk of pain and injury. The validity of this claim remains unclear. METHOD: We conducted a systematic review and partial meta-analysis assessing the association between hip strength and knee valgus in healthy subjects. An online search was conducted in May 2026. Databases included Medline, EMBASE, CINAHL and Google Scholar. INCLUSION CRITERIA: English language, asymptomatic subjects, dynamometric hip strength, single or multi-camera kinematic analysis, and statistical tests of difference or correlations between hip abductor or ER strength and dynamic valgus. Data were extracted concerning study design, subject characteristics, relevant outcome measures and statistics. RESULTS: 22 papers qualified for inclusion. Hip abductor correlations: 12 papers found no significant correlation, 2 supported the hypothesis and 2 found evidence contrary. Hip ER correlations: 8 papers found no significant correlation, 2 supported the hypothesis and 2 were contrary. Group differences for hip abduction strength: 3 papers found no difference, 2 found significant differences in support of the hypothesis, 1 found significant difference to contrary. Group differences for ER strength: 1 paper found no significant difference. None of the partial meta-analyses achieved statistical significance. CONCLUSION: Weakness in hip abductors or external rotators may not result in increased dynamic knee valgus in healthy subjects. While continued research may further illuminate our understanding, we discuss alternative explanations.

Humans

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female

Pelvic lymph node dissection in prostate cancer: current evidence, controversies, and future directions.

BACKGROUND: Pelvic lymph node dissection (PLND) remains controversial in the management of prostate cancer. Although it provides the most accurate pathological staging, its therapeutic value beyond staging has long been debated due to conflicting evidence and concerns regarding procedure-related morbidity. OBJECTIVE: To critically evaluate the contemporary role of PLND, particularly extended pelvic lymph node dissection (ePLND), in prostate cancer management in the context of modern imaging, risk stratification tools, and evolving oncologic endpoints. EVIDENCE ACQUISITION: A narrative review of recent literature was conducted, focusing on high-level evidence including randomized trials, observational studies, and contemporary guideline recommendations addressing the indications, extent, oncologic outcomes, and complications of PLND. EVIDENCE SYNTHESIS: Recent randomized and observational studies suggest that ePLND improves nodal staging accuracy and may be associated with modest improvements in metastasis-free survival (MFS) in selected patients with intermediate- and high-risk prostate cancer, although the absolute benefit remains limited and causality is not definitively established. Advances in molecular imaging, particularly prostate-specific membrane antigen (PSMA) PET/CT, together with multiparametric MRI, validated nomograms, and emerging genomic classifiers, now allow more precise identification of patients most likely to benefit from ePLND. The integration of these tools supports a more individualized surgical strategy, including image-guided and sentinel lymph node approaches designed to maximize staging accuracy while minimizing unnecessary dissection. CONCLUSIONS: In the contemporary PSMA imaging era, ePLND continues to play an important role in nodal staging and may contribute to improved oncologic outcomes in carefully selected patients.

Humans

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy