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PubMed2026

Genome-wide identification and functional validation of asparagine synthetase genes (NtASNs) in Nicotiana tabacum.

Asparagine (Asn) is pivotal for plant nitrogen (N) metabolism and plays indispensable roles in plant growth, development, and stress tolerance. However, the systematic characteristics and core functions of asparagine synthetase genes (NtASNs) in tobacco remain unclear. Through a comprehensive genome-wide investigation, nine members of the NtASN gene family were identified. Subsequent CRISPR/Cas9-mediated knockout and overexpression assays of these NtASN genes revealed that NtASN1e, NtASN2a, and NtASN2b are the core genes responsible for Asn biosynthesis in tobacco. Their knockout reduced asparagine synthetase activity and Asn content, delayed seed germination by 2-3 days, and displayed elevated oxidative injury when exposed to salinity conditions. In contrast, overexpression of these genes elevated Asn accumulation. Subcellular localization analysis indicated that NtASN1e was localized to both the cytoplasm and chloroplasts, whereas NtASN2a exhibited dual localization in the cytoplasm and endoplasmic reticulum, and NtASN2b was mainly localized in the cytoplasm. This study systematically clarifies the evolutionary characteristics and core functions of the NtASN gene family and provides candidate genes for optimizing nitrogen metabolism and improving salt-stress adaptation in tobacco. These findings hold important practical significance for molecular breeding and product quality improvement in industrial crops.

Nicotiana↗

PubMed2026

Olive leaf protein hydrolysates yield gastro-resistant peptides with antioxidant and anti-inflammatory potential: peptidomics, in vitro validation and molecular docking analyses.

Olive (Olea europaea L.) leaves are an abundant olive-oil by-product and a promising feedstock for sustainable valorisation. An olive leaf protein isolate (OLPI) from olive-leaf powder (OLP) was enzymatically hydrolysed to yield seven hydrolysates (OLPHs). All showed notable antioxidant activity as whole hydrolysate matrices (EC₅₀ = 0.11-0.28 mg mL-1); likely reflecting the combined contribution of released peptides and co-extracted phenolic compounds; the 15-min Alcalase product (OLPH15A) showed high activity with the shortest processing time. Its INFOGEST digest (dOLPH15A) attenuated LPS-induced inflammation in Caco-2 cells, down-regulating pro-inflammatory and up-regulating anti-inflammatory genes. Peptidomics identified 7037 peptides in OLPH15A and 534 in dOLPH15A, from which twenty gastro-resistant sequences were prioritised for in silico analysis. Multi-tool prediction and docking highlighted four peptides, GAAGGIGQPL, QSAYPGTGPL, GGGAGGGDGGIL and LDAQFPGVN, with favourable predicted affinity for the TLR4/MD2 complex, suggesting that they may contribute to the observed immunomodulatory response. These findings position olive leaves as a viable source of protein hydrolysate-based ingredients with antioxidant and anti-inflammatory potential, advancing the valorisation of olive-oil by-products.

Olea↗

PubMed2026

Phytolacca acinosa Roxb. induces intestinal toxicity through the histamine-MLCK-tight junction axis: Integrated evidence from proteomics, metabolomics, intestinal organoids and epithelial barrier validation.

Phytolacca acinosa Roxb. (PR) is a saponin-rich medicinal plant associated with gastrointestinal toxicity, but the mechanisms underlying PR-induced intestinal barrier injury remain unclear. In this study, raw PR extract was analytically characterized by UPLC-ZenoTOF-MS/MS, confirming triterpenoid saponins as the predominant constituents. C57BL/6 J mice were orally exposed to characterized PR extract (1.20 or 12.0 g/kg for 5 h), and Caco-2 cells and mouse intestinal organoids were used to assess epithelial toxicity and barrier disruption. Histopathology, ELISA, FITC-dextran permeability assays, immunofluorescence, CCK-8, LDH release, western blotting, DIA-based proteomics and untargeted metabolomics were integrated to define toxicological mechanisms. PR induced dose-dependent intestinal inflammation and barrier dysfunction, with the ileum as the most sensitive target. PR increased serum DAO and D-lactate and intestinal TNF-α and IL-1β, disrupted organoid morphology, enhanced epithelial permeability, and reduced ZO-1 expression. Proteomics revealed changes in inflammatory, lipid-metabolic, cytoskeletal and tight-junction pathways, including upregulation of MLCK3 and phospholipase-related proteins and downregulation of ZO-1 and ZO-2. Metabolomics identified histidine metabolism disturbance and histamine accumulation. Integrated multi-omics and pharmacological validation indicated that histamine activated the PLC/IP₃/Ca²⁺/CaM/MLCK cascade, promoting MLC phosphorylation, tight-junction disassembly and epithelial leakiness. MLCK inhibition partially restored ZO-1/ZO-2 expression and attenuated PR-induced epithelial injury. These findings identify the histamine-MLCK-tight junction axis as a key mechanism of PR-induced intestinal toxicity and support hazard identification of saponin-rich PR exposure.

Animals↗

PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (χ2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗

PubMed2026

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals↗

PubMed2026

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2× liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans↗

PubMed2026

Cloning of two Hsp70 genes and association analysis between SNP haplotypes and high temperature tolerance trait in red swamp crayfish (Procambarus clarkii).

Aquaculture is suffering the challenge from high temperature climate. Two Hsp70 genes, PcHsp70-1 and PcHsp70-2, as key genes involved in the high temperature tolerance of red swamp crayfish (Procambarus clarkii) were identified and cloned in this study. Their molecular features and expression patterns were characterized, revealing the distinct tissue-specific upregulation expression under high temperature stress (33 °C). Two SNPs, PcHsp70-1 (SNP258) and PcHsp70-2 (SNP555) were examined to associate with high temperature tolerance in three populations (n = 675). The genotypes of PcHsp70-1-SNP258 (GA) and PcHsp70-2-SNP555 (TT) were significantly associated with stronger high temperature tolerance. Notably, individuals carrying the haplotype of Hap I (GG + TT) showed a survival rate exceeding 70% under high temperature stress, whereas, the Hap VIII (AA + CT) showed it at 5.2%. RNA interference of PcHsp70-1 resulted in a significant decrease expression of the gene GSH-Px and its encoding protein (glutathione peroxidase) activity, and damage in intestinal tissue under high temperature stress. The transcriptome result revealed that PcHsp70-1 participates in regulation of the pathways related to cytoskeletal construction, immune response, apoptosis, and antioxidant defense. These findings indicate that PcHsp70 genes are crucial for the cellular stress response under high temperature stress. The developed Kompetitive Allele Specific PCR (KASP) markers provide valuable tools for the marker-assisted selection of high temperature tolerant crayfish varieties, supporting the sustainable development of aquaculture under the challenge of global warming.

Animals↗

PubMed2026

Integrated photoelectrocatalytic reduction and oxidation processes to achieve efficient degradation of fluoxetine in pharmaceutical wastewater.

Fluorinated organic compounds have been frequently detected in aquatic environments, with the widespread use of fluorinated drugs. The existing processes of urban sewage treatment plants are difficult to completely remove these pollutants containing the persistent C-F bonds. In this work, an integrated system of UV-activated sulfite and UV-assisted electrochemical oxidation was innovatively constructed for efficient degradation of fluoxetine. For the UV-activated sulfite unit system, when the sulfite dosage was 0.5 mmol/L and the initial pH was about 10, the defluorination efficiency of 5 mg/L fluoxetine wastewater under nitrogen atmosphere was about 98 %. Subsequently, the UV-assisted electrochemical oxidation unit system was employed to treat the reduced wastewater mentioned above. When the sodium chloride dosage was 25 mmol/L, the initial pH was about 5, and the current density was 30 mA/cm2, the total organic carbon (TOC) removal of the wastewater arrived at 65 %. Active species capture experiments and ESR tests confirmed that hydrated electrons, hydroxyl, and chlorine radicals were the main components for the efficient degradation of fluoxetine. According to the analysis of Fukui function and HPLC-MS, the degradation pathway of pollutants was proposed including defluorination and mineralization. Meanwhile, the toxicity of intermediates was predicted using the ECOSAR program. In addition, the verification test of actual wastewater treatment indicated that the defluorination and TOC removal efficiency of fluorouracil by the integrated system were similar to those for fluoxetine. This work provided a new approach for the efficient degradation of fluorinated organic pollutants in pharmaceutical wastewater.

Fluoxetine↗

PubMed2026

Data-centric, robust, and explainable multimodal deep learning for clinical decision support: A systematic review.

PURPOSE: Multimodal deep learning is increasingly proposed for clinical decision support (CDS) under a "data-centric" framing that prioritizes label quality, missing-modality robustness, distribution shift, calibration, and explainability. Prior reviews have examined multimodal medical AI, CDS, and data-centric methods separately, but none address their intersection. We mapped the modalities, fusion strategies, and data-centric and explainability techniques used in this recent literature, quantified how often each is implemented rather than merely mentioned, assessed deployment-relevant evidence (external validation, clinical-outcome measurement, equity), and formally appraised study-level risk of bias. METHODS: Following the PRISMA 2020 statement (PROSPERO CRD420261427815; registered retrospectively), we screened 150 records and included primary, clinical, multimodal studies that applied machine or deep learning to a decision-support task and reported at least one quantitative result. Two reviewers screened and extracted data with consensus adjudication. Each study was coded against pre-specified operational definitions, separating implemented or empirically evaluated techniques from those only mentioned. Study-level risk of bias was assessed with PROBAST + AI. Synthesis was narrative. RESULTS: Thirty-one studies met inclusion; 30 (97%) were published between 2024 and 2026, with a median of three modalities (range 2-6), most commonly structured EHR (71%) and imaging (39%). Data-centric techniques were frequently reported (74-84% across label-noise, distribution-shift, calibration, missing-modality and class-imbalance handling; equity 61%). However, external validation was reported in only 4/31 studies (13%), a clinical or provider outcome in 3/31 (10%), and no study reported routine deployment. Overall risk of bias was high in 27/31 studies (87%), driven by the analysis domain. CONCLUSION: Within this recent, self-selected slice of the field, technical robustness and explainability techniques are widely reported but rarely validated out-of-distribution or against clinical outcomes, and the underlying evidence is at high risk of bias. Progress requires external multi-site validation, clinical-outcome measurement, formal bias appraisal, and adherence to AI reporting standards (e.g., TRIPOD + AI) before deployment can be justified.

Deep Learning↗

PubMed2026

Multiplexed CRISPR/Cas9 mediated knockdown of BCH gene in potato enhances beta-carotene to combat vitamin A deficiency.

The inadequate amounts of provitamin A carotenoids in crops contribute to the widespread vitamin A deficiency, leading to malnutrition and blindness in humans. Suppression of the β-carotene hydroxylase (BCH) increases β-carotene levels. In the current study, we utilized the multiplexed CRISPR/Cas9 approach by designing three targets against the BCH gene in a local potato cultivar. Transformation efficiency was recorded as 15%, the successful integration of the CRISPR/Cas9-BCH multiplex construct in potatoes was confirmed through PCR. When analysed using TIDE software, Sanger sequencing revealed the highest indel efficacy of 92.1% in plant 7 and 26.6% in plant 1. qRT-PCR (quantitative real-time PCR) analysis indicated a significant 89-fold reduction in BCH transcript levels in genome-edited potato lines compared to control plants. Spectrophotometry demonstrated a notable increase in beta-carotene levels in genome-edited potato plants, ranging from 0.831 µg/mL FW to 4.236 µg/mL FW, compared to the control plant with the lowest beta-carotene concentration (0.344 µg/mL FW). HPLC analysis further confirmed increased beta-carotene levels in genome-edited potato plants, ranging from 0.11 mg/mL FW to 0.36 mg/mL FW, compared to the unmodified control plant with a minimum beta-carotene value of 0.09 mg/mL. Our results revealed that the multiplexed CRISPR-Cas9 approach targeting the BCH gene results in enhanced beta-carotene contents in potato tubers.

Solanum tuberosum↗

PubMed2026

Vitamin B12 Deficiency in Sickle Cell Disease: Method-Driven Estimates and Systematic Diagnostic Misclassification.

OBJECTIVES: To determine whether the reported 0%-70% prevalence of vitamin B12 deficiency in sickle cell disease (SCD) reflects true population variation or diagnostic misclassification. METHODS: We conducted a PRISMA 2020-compliant systematic review of observational studies (January 1, 2000-May 13, 2026; PROSPERO CRD420251087800) assessing B12 status in SCD. PubMed, AJOL, and Google Scholar were searched with citation tracking and dual screening. Diagnostic validity was assessed across biomarker strategy, analytical platform, thresholds, and confounder control using a proposed context-integrated framework to classify methodological robustness and discordance. RESULTS: Fourteen studies were included (57% high-income; 43% LMIC). The evidence base was dominated by limited diagnostic approaches: 71% used immunoassays, over one-third relied on circulating B12 alone, and functional biomarkers were inconsistently applied without systematic confounder adjustment. Prevalence estimates were strongly influenced by diagnostic methods rather than underlying population biology, ranging from 0% to 70% in single-marker studies (mostly 0%-7.1%, with outliers ~50%-70%) and 6.9%-53% in multi-marker studies. Discordance was substantial and greater in LMIC settings than HIC. CONCLUSION: Current diagnostic approaches in SCD appear method-dependent, generating heterogeneous prevalence estimates with uncertain clinical validity. These findings challenge existing estimates and have implications for clinical practice, research design, and diagnostic equity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420251087800.

Humans↗

PubMed2026

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

PubMed2026

Unacknowledged Burdens and Clinical Assets of BIPOC Genetic Counseling Students: Qualitative Evidence to Inform Supervision.

As the genetic counseling profession works to diversify its predominantly white workforce, understanding the experiences of Black, Indigenous, and People of Color (BIPOC) students is central to equity efforts. While BIPOC students bring invaluable cultural and linguistic diversity that improves patient care, they often navigate clinical training environments that lack diversity and psychological safety. This article draws on data from a longitudinal constructivist qualitative study to examine how racial and ethnic concordance (or lack thereof) with patients and clinical supervisors influenced the clinical training, professional development, and well-being of BIPOC genetic counseling students. Semi-structured interviews were conducted with 25 BIPOC genetic counseling students in the United States and Canada. Interviews were recorded using Zoom.us, transcribed using Rev.com, and analyzed in NVivo using reflexive thematic analysis. The analysis led to the construction of three themes: (1)Shared identity with patients is a clinical advantage: Participants leveraged their cultural and linguistic intuition to establish trust and rapport with patients; (2) Identity navigation involves cognitive and emotional labor: Participants shouldered an unacknowledged burden in managing stereotype threat, overcoming feelings of exclusion, and educating supervisors; and (3) Racial/ethnic identity shapes supervisory dynamics: Participants described BIPOC supervisors as providing identity-affirming support, while some white supervisors avoided discussions about identity or committed microaggressions. These results suggest that BIPOC genetic counseling students have clinical assets rooted in biculturalism, yet carry a burden that often goes unacknowledged of managing power imbalances and pressure to assimilate in predominantly white clinical supervision spaces. To promote equitable training, programs should implement supervisor training on culturally responsive identity broaching, establish independent, transparent mechanisms for students to report biases they encounter in clinic, and expand mentorship networks to provide additional support.

Humans↗

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

Novel environmental contaminant 6PPD-quinone promotes malignant phenotypes in colorectal cancer cells and identifies candidate response-associated genes.

6PPD-quinone (6PPDQ), an oxidative transformation product of the widely used tire antioxidant 6PPD, is a ubiquitous environmental contaminant with bioaccumulation potential and widespread human exposure. Recent epidemiological evidence indicates a positive association between urinary 6PPDQ levels and colorectal cancer (CRC) risk; however, its biological effects on CRC-related phenotypes and associated molecular responses remain unclear. We integrated bioinformatics analysis, prognostic modeling, molecular docking and dynamics simulations, and in vitro experiments to investigate cellular and molecular responses to 6PPDQ in CRC models. Predicted 6PPDQ targets were intersected with CRC prognosis-related genes from The Cancer Genome Atlas, followed by functional enrichment and LASSO regression to construct a prognostic risk model, with 1-, 3-, and 5-year AUC values of 0.727, 0.754, and 0.778, respectively. Molecular docking and 100-ns molecular dynamics simulations suggested interactions between 6PPDQ and candidate proteins, including CPT2, SHC2, SRMS, and STK35. Functional assays showed that 6PPDQ exposure altered proliferation, wound-closure capacity, and invasion in Caco-2 and HCT116 cells across the nanomolar concentration range, with non-monotonic and cell-line-dependent responses. In contrast, NCM460 cells showed no increase in EdU incorporation at 10 or 100 nM, whereas reduced proliferation at higher concentrations was accompanied by increased LDH release. 6PPDQ also altered the expression of several prognosis-associated candidate genes. These findings identify cellular phenotypes and candidate molecular responses associated with 6PPDQ exposure under the tested in vitro conditions, but do not establish their causal roles or in vivo relevance. Further mechanistic and in vivo studies are required.

Humans↗

PubMed2026

Specific Instruments for Caregiving Competence Among Family Caregivers of Cancer Patients: A COSMIN Systematic Review of Psychometric Properties.

OBJECTIVE: To evaluate and summarize the psychometric properties of specific instruments for caregiving competence among family caregivers of cancer patients. METHODS: Systematically searched eight databases for studies published up to November 2025. The methodological quality and psychometric properties of the instruments were evaluated using COSMIN 2.0. Evidence grades were rated using the modified GRADE system (four grades: "High," "Moderate," "Low," and "Very Low"), and recommendations were formulated (Category A: recommended, Category B: potential with further validation, and Category C: not recommended). RESULTS: Seven studies were included, comprising three specific instruments: the Care Competency Scale for Family Caregivers in Home Palliative Care (CCSHPC) (n = 1), the Caregiver Caregiving Self-Efficacy Scale-Oral Cancer (CSES-OC) (n = 1), and the Caring Ability of Family Caregivers of Patients with Cancer Scale (CAFCPCS) (n = 5). Both the CCSHPC and CAFCPCS received Category B recommendations, demonstrating "adequate" content validity with evidence grades rated "very low" and "low," respectively. The CAFCPCS also shows good structural validity ("moderate") and internal consistency ("low") in some cultural contexts. The CSES-OC is a Category C recommendation, with high-quality evidence indicating "inadequate" criterion validity. CONCLUSION: Few specific instruments exist, and most did not strictly follow COSMIN guidelines. The CAFCPCS is provisionally recommended based on relative evidence superiority rather than complete psychometric validation. Further cross-cultural and localized instrument development is warranted. IMPLICATIONS FOR NURSING PRACTICE: Use well-validated specific instruments to identify strengths and weaknesses in the caregiving competencies of family caregivers of cancer patients, enabling them to deliver high-quality home-based cancer care.

Female↗

PubMed2026

Diagnostic performance of machine learning models for malignant and non-malignant pleural effusion: Systematic review and meta-analysis.

BACKGROUND: Accurately distinguishing malignant pleural effusion (MPE) from non-malignant pleural effusion is clinically important, but the generalisability and methodological quality of machine-learning (ML) models remain uncertain. METHODS: We searched eight databases to 23 April 2026. Diagnostic performance was pooled using random-effects and Reitsma bivariate models, and study quality was assessed using PROBAST+AI. RESULTS: Forty-two studies were included; 17 contributed to the AUC meta-analysis and 14 to the bivariate analysis. The pooled AUC was 0.90 (95 % CI 0.85-0.94; 95 % prediction interval 0.62-0.98), with sensitivity of 0.80 (95 % CI 0.77-0.83) and specificity of 0.87 (95 % CI 0.79-0.92). Only nine studies reported external, temporal or independent validation. Externally validated studies had a lower pooled AUC than studies without external validation (0.83 vs 0.92), with lower specificity observed in the two externally validated studies contributing sensitivity and specificity data. All 42 development assessments had high overall quality concerns, and all 42 model evaluations were judged at high risk of bias. CONCLUSIONS: ML models showed good apparent accuracy for distinguishing MPE from non-MPE, but the evidence was limited by substantial heterogeneity, high risk of bias and scarce external validation. The pooled estimates reflect the average performance of different selected models rather than the expected accuracy of a single clinical test. ML models should be regarded as adjuncts to existing diagnostic pathways until they are confirmed by rigorous multicentre prospective external validation and clinical-impact studies.

Humans↗

PubMed2026

Identifying stakeholder behaviors for competency-based pharmacy education: A stage 1 behavior change wheel analysis.

INTRODUCTION/OBJECTIVES: Competency-Based Pharmacy Education (CBPE) is a strategic priority for preparing graduates to meet evolving healthcare needs. However, efforts to implement CBPE can stall due to behavioral challenges among faculty, administrators, preceptors, and learners. This study aimed to apply Stage 1 of the Behavior Change Wheel (BCW) to identify stakeholder-specific behaviors and associated determinants needed to implement the five core components of CBPE. METHODS: A multi-method approach grounded in the BCW, the Capability, Opportunity, Motivation - Behavior (COM-B) model, and the Theoretical Domains Framework (TDF) was used. Data were gathered through (1) targeted literature review; (2) structured focus groups with competency-based education experts and pharmacy education stakeholders; and (3) an iterative consensus process. Behaviors were mapped to the five CBPE components: (1) defined competencies, (2) developmental progression, (3) tailored instruction, (4) authentic experiential learning, and (5) programmatic assessment, and then mapped to COM-B and TDF constructs. RESULTS: Over fifty stakeholder-specific behaviors were identified and specified across the CBPE framework. This revealed shared barriers such as limited instructional design knowledge (psychological capability), insufficient assessment of infrastructure (physical opportunity), and misaligned professional identity (reflective motivation). Key TDF domains included knowledge, environmental context, beliefs about capabilities, and professional roles. The behavioral problem statements, specifications, and determinants were identified to support future intervention planning. CONCLUSION: This Stage 1 analysis provides a behaviorally grounded foundation for CBPE implementation by identifying stakeholder behaviors and conditions that enable change. These findings will inform the development of readiness-to-change assessments and targeted interventions (BCW Stages 2 and 3), supporting scalable and sustainable CBPE transformation in pharmacy education.

Education, Pharmacy↗