Category: Nevin Manimala

Discov Oncol. 2025 May 2;16(1):656. doi: 10.1007/s12672-025-02450-1.

ABSTRACT

OBJECTIVE: The causative relationship between lung cancer subtypes and lipids is yet unknown. This research aims to elucidate the potential causative link connecting lipid levels to lung cancer subtypes, particularly focusing on non-small cell lung cancer (NSCLC), using the Mendelian randomization (MR) method and meta-analysis.

METHODS: Summary statistics were obtained from genome-wide association study (GWAS) datasets. A comprehensive MR analysis was performed to explore the causal role of lipids in NSCLC subtypes. To ensure the reliability of the results, an external dataset was used for validation, and a meta-analysis was performed for further synthesis.

RESULTS: Two of the 179 lipids examined showed potential causal connection with lung adenocarcinoma (LUAD) and three with lung squamous cell carcinoma (LUSC). Specifically, phosphatidylcholine (PC) (16:0_20:4) and PC (18:0_20:4) might be connected to an elevated risk of LUSC, but PC (18:0_20:2) might be linked to a decreased risk. It was discovered that PC (16:1_20:4) and PC (18:0_20:4) might raise the risk for LUAD.

CONCLUSION: Complex lipid metabolic pathways, especially involving PC, are present in NSCLC, and distinct lipid isomers may influence various molecular subtypes in different ways.

PMID:40314895 | DOI:10.1007/s12672-025-02450-1

Can J Anaesth. 2025 May 2. doi: 10.1007/s12630-025-02949-9. Online ahead of print.

ABSTRACT

PURPOSE: According to an analysis of data from the Canadian Institutes for Health Information (CIHI) National Physician Database, the proportion of female anesthesia physicians is substantially lower than the proportion of female physicians in the total physician population. The goal of this study was to identify trends in female representation in the major subgroups of anesthesia providers, including specialists certified by the Royal College of Physician and Surgeons of Canada (RCPSC), international medical graduates, and family physician anesthetists (FPAs).

METHODS: We examined the sex distribution of the existing physician workforce, including anesthesia providers working in urban and rural Canada, using the CIHI National Physician Database (1996-2018). We also examined the sex distribution of physicians entering the workforce using the Canadian Post-MD Education Registry database and calculated descriptive statistics.

RESULTS: The proportion of female physicians increased steadily over time in all groups; nevertheless, the numbers of female FPAs and rural anesthesia providers continued to lag relative to all Canadian physicians (9.4%, 9.4%, and 26.7%, respectively, in 1996; 18.7%, 21.1%, and 42.1%, respectively, in 2018). Of the graduates from RCPSC training programs in 1996, 28% were female, whereas by 2018, 33.5% of graduates were female.

CONCLUSIONS: Female physicians were underrepresented in all subgroups, but the proportions were lowest among FPAs and rural physicians. Given that greater sex diversity in clinical teams is associated with better outcomes, and in light of ongoing workforce shortages, the barriers that prevent female physicians from entering and/or remaining in the anesthesia workforce need to be understood and ameliorated.

PMID:40314871 | DOI:10.1007/s12630-025-02949-9

Eur Geriatr Med. 2025 May 2. doi: 10.1007/s41999-025-01212-0. Online ahead of print.

ABSTRACT

PURPOSE: To validate the Hospital Frailty Risk Score (HFRS) in Chinese hospital settings, describing how patients are allocated to frailty risk groups and how frailty risk is associated with length of stay (LoS) and hospital costs.

DESIGN: Retrospective observational study.

SETTING: Forty-eight hospitals in Lvliang City, Shanxi Province, China.

SUBJECTS: Patients aged 75 years or older hospitalised between 1 January 2022 and 31 December 2023 (n = 34,731).

METHODS: A logistic regression model examined the association between long length of stay (LoS) and frailty risk. A generalised linear model assessed the association between hospital costs and frailty risk. Subgroup analyses of age group, sex, and hospital tiers were conducted.

RESULTS: 22.2% of patients were categorised as having zero risk, 62.4% as low risk, 15.3% as intermediate risk, and 0.08% as high risk. Compared to the zero risk group: for those with low risk, the probability of long LoS was 1.92 (95% CI 1.79-2.06) times higher and hospital costs were ¥1926 (95% CI 1655-2197) higher; for those with intermediate risk, the probability of long LoS was 2.7 (95% CI 2.49-2.96) times higher and hospital costs were ¥4284 (95% CI 3916-4653) higher; and for those with high risk, the probability of long LoS was 6.7 (95% CI 3.06-14.43) times higher and hospital costs were ¥16,613 (95% CI 12,827-20,399) higher. The explanatory power of the HFRS held across subgroups.

CONCLUSIONS: Compared to patients aged 75 + elsewhere, those in China had lower frailty risk scores, likely reflecting a younger age structure and recording of fewer diagnosis codes. Even so, the HFRS is a powerful predictor of long length of stay and hospital costs in China.

PMID:40314855 | DOI:10.1007/s41999-025-01212-0

Psychometrika. 2025 Mar 27:1-37. doi: 10.1017/psy.2025.10. Online ahead of print.

ABSTRACT

We present a multidimensional data analysis framework for the analysis of ordinal response variables. Underlying the ordinal variables, we assume a continuous latent variable, leading to cumulative logit models. The framework includes unsupervised methods, when no predictor variables are available, and supervised methods, when predictor variables are available. We distinguish between dominance variables and proximity variables, where dominance variables are analyzed using inner product models, whereas the proximity variables are analyzed using distance models. An expectation-majorization-minimization algorithm is derived for estimation of the parameters of the models. We illustrate our methodology with three empirical data sets highlighting the advantages of the proposed framework. A simulation study is conducted to evaluate the performance of the algorithm.

PMID:40314177 | DOI:10.1017/psy.2025.10

BJPsych Open. 2025 May 2;11(3):e91. doi: 10.1192/bjo.2025.33.

ABSTRACT

BACKGROUND: Functional cognitive disorder is an increasingly recognised subtype of functional neurological disorder for which treatment options are currently limited. We have developed a brief online group acceptance and commitment therapy (ACT)-based intervention.

AIMS: To assess the feasibility of conducting a randomised controlled trial of this intervention versus treatment as usual (TAU).

METHOD: The study was a parallel-group, single-blind randomised controlled trial, with participants recruited from cognitive neurology, neuropsychiatry and memory clinics in London. Participants were randomised into two groups: ACT + TAU or TAU alone. Feasibility was assessed on the basis of recruitment and retention rates, the acceptability of the intervention, and signal of efficacy on the primary outcome measure (Acceptance and Action Questionnaire II (AAQ-II)) score, although the study was not powered to demonstrate this statistically. Outcome measures were collected at baseline and at 2, 4 and 6 months post-intervention, including assessments of quality of life, memory, anxiety, depression and healthcare use.

RESULTS: We randomised 44 participants, with a participation rate of 51.1% (95% CI 40.8-61.5%); 36% of referred participants declined involvement, but retention was high, with 81.8% of ACT participants attending at least four sessions, and 64.3% of ACT participants reported being ‘satisfied’ or ‘very satisfied’ compared with 0% in the TAU group. Psychological flexibility as measured using the AAQ-II showed a trend towards modest improvement in the ACT group at 6 months. Other measures (quality of life, mood, memory satisfaction) also demonstrated small to modest positive trends.

CONCLUSIONS: It has proven feasible to conduct a randomised controlled trial of ACT versus TAU.

PMID:40314156 | DOI:10.1192/bjo.2025.33

J Antimicrob Chemother. 2025 May 2:dkaf125. doi: 10.1093/jac/dkaf125. Online ahead of print.

ABSTRACT

BACKGROUND: People living with HIV (PLHIV) who fail first-line ART have a higher risk of failing subsequent ART. We examined viral suppression (VS) among adolescents and youths (AY) failing PI ART in Tanzania.

METHODS: We conducted a retrospective study nested within a national third-line cohort of PLHIV. We analysed data of 147 AY (aged 10-24 years) with failure of PI-based ART between 2020 and 2022 who were followed for 12 months to assess for VS. Descriptive statistics were summarized by demographics and clinical characteristics, and we used logistic regression to assess factors associated with virological failure (VF) and drug resistance mutations (DRMs).

RESULTS: More than 40% of 147 participants had HIV subtype A, 52% (76/147) harboured major PI DRMs and 35% had NRTI mutations. A PI regimen at ART initiation was associated with a major PI DRM adjusted relative risk (aRR) of 1.66 (95% CI: 1.13-2.44; P = 0.010). Among participants with major PI DRMs, 12.2% had intermediate to high levels of resistance to lopinavir and atazanavir, and 2.1% to darunavir, respectively. V82A was the most frequent PI DRM; NRTI mutations included thymidine analogue mutations and absent K65R. VS occurred in 65% of AY who had PI DRMs compared with 45% of those without DRMs; this difference was not statistically significant.

CONCLUSIONS: More than half of AY who had PI DRMs had a higher proportion of early VS (65%) compared with those without DRMs (45%). Optimal viral load monitoring, adherence intensification and routine drug resistance testing are key strategies to improve VS.

PMID:40314140 | DOI:10.1093/jac/dkaf125

Mol Med Rep. 2025 Jul;32(1):185. doi: 10.3892/mmr.2025.13550. Epub 2025 May 2.

ABSTRACT

High Helicobacter pylori infection rates contribute to high gastric cancer (GC) incidence. While H. pylori infection is associated with GC development its mechanisms are still being studied. The aim of the present study was to examine the differences between H. pylori infection‑induced GC and non‑infected tissues, and to investigate the correlation between nucleotide‑binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome expression and immune cell infiltration in GC, thus providing a theoretical basis for clinical prognosis and immunotherapy. High‑throughput RNA‑sequencing expression data from The Cancer Genome Atlas (TCGA) were analyzed. Additionally, TIMER2.0 and Kaplan‑Meier Plotter were used to analyze the differential expression of NLRP3 mRNA in various tumors, the effect of H. pylori infection on gene expression, and the association between NLRP3 and clinical prognosis among patients with GC. Immunohistochemistry (IHC) was used to assess the effects of NLRP3 protein expression on immune cell infiltration in clinical tissues with or without H. pylori infection. R software was used for data visualization and statistical analysis. TCGA data revealed that the expression levels of NLRP3 in GC tissues were increased compared with those in normal tissues (P<0.05), which was further validated in clinical samples. Furthermore, NLRP3 mRNA expression was significantly elevated in clinical GC tissues infected with H. pylori. Notably higher relative levels of NLRP3 mRNA were observed in tumor tissues with a tumor size ≥5 cm, lymph node metastasis, Tumor‑Node‑Metastasis stage III + IV or poor differentiation compared with the respective controls (P<0.05). IHC confirmed a significant increase in NLRP3 expression within H. pylori‑infected GC tissues compared with that in non‑infected tissues. In GC immune infiltration, NLRP3 expression was revealed to be associated with natural killer cell, whereas it was negatively correlated with regulatory T cells and CD8⁺ T cells. These findings indicated that NLRP3 may promote the polarization of tumor‑associated macrophages towards the M2 phenotype. High NLRP3 expression also promoted the infiltration of CD3⁺ and CD206⁺ cells, which significantly affected the survival rate of patients with GC. The immune infiltration of regulatory T lymphocytes was associated with better survival benefits for patients with GC; however, M2 macrophage infiltration was not conducive to the survival of patients with GC. Furthermore, survival analysis showed that high expression of NLRP3 was associated with a poorer 5‑year overall survival, progression‑free survival and post‑progression survival rates. In conclusion, elevated NLRP3 expression, which may be induced by H. pylori infection, could promote immune cell infiltration potentially by regulating cancer cell proliferation and migration, ultimately leading to an unfavorable prognosis and a notable reduction in the 5‑year survival rate.

PMID:40314099 | DOI:10.3892/mmr.2025.13550

Vet Dermatol. 2025 May 2. doi: 10.1111/vde.13346. Online ahead of print.

ABSTRACT

BACKGROUND: Besides pruritus and skin lesions, cats with feline atopic skin syndrome (FASS) may have seborrhoea.

HYPOTHESIS/OBJECTIVES: The aim of this pilot study was to investigate whether an adsorbent mousse containing tapioca starch, adelmidrol and a nonpharmacological antimicrobial complex could decrease FASS-associated seborrhoea in cats.

ANIMALS: Seven client-owned cats with FASS were included based on the presence of seborrhoea and pruritus (>4 cm on the validated feline pruritus Visual Analog Scale [VAScat]), regardless of the concomitant administration of antiallergic drugs, provided that they were used for ≥1 month before study entry and maintained unchanged.

MATERIALS AND METHODS: Cats were evaluated weekly by owners and every other week by veterinary surgeons for 2 (optionally 4) weeks using a four-item skin seborrhoeic index (SSI). The VAScat and the scoring feline allergic dermatitis (SCORFAD) index also were used to assess pruritus and skin lesion severity, respectively. The Wilcoxon signed-rank test was used for pre- versus post-treatment comparisons.

RESULTS: At the end of Week 2, the mean score value for SSI was significantly decreased (p = 0.016). At the same time point, the mean severity of pruritus and the mean SCORFAD index value had also decreased (p = 0.016). Moreover, 86% of the investigators were ‘satisfied’ or ‘very satisfied’ with the tested mousse. Four cats continued the study up to Week 4 and showed a further, albeit nonsignificant, decrease in all evaluated scores.

CONCLUSIONS AND CLINICAL RELEVANCE: These preliminary findings have promising implications for clinical practice in cats with FASS-associated seborrhoea and are worth further investigation.

PMID:40314094 | DOI:10.1111/vde.13346

Equine Vet J. 2025 May 2. doi: 10.1111/evj.14513. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical signs of pituitary pars intermedia dysfunction (PPID) are frequently mistaken for ‘normal’ ageing and may not be optimally assessed. Objective quality of life (QoL) assessment could improve clinical decision-making.

OBJECTIVES: To develop an owner-reported health-related quality-of-life (HRQoL) assessment tool for equines with PPID. To assess factors associated with HRQoL scores.

STUDY DESIGN: Quantitative, cross-sectional study.

METHODS: HRQoL tool development followed a standard psychometric process of item (any aspect of PPID and its management that could impact QoL) identification (following interviews with veterinarians, owners and clinical record reviews), selection (online owner questionnaire) and refinement (statistical analyses; chi-squared and Cronbach’s alpha). General Linear Models were used to identify factors associated with HRQoL scores.

RESULTS: Forty-two items associated with PPID were identified. Thirty-seven items were selected for the online questionnaire. In total, 612 complete responses (n = 343 PPID and n = 269 non-PPID horses) were obtained. Through stepwise statistical item refinement, 24 items remained in the final HRQoL tool (overall Cronbach’s α = 0.835). HRQoL scores ranged from 0 (best) to 1 (worst) QoL. Median (interquartile range) HRQoL scores were 0.33 (0.22-0.44) and 0.20 (0.14-0.27) for PPID and non-PPID horses respectively. HRQoL scores for all horses were worse if they had PPID (p < 0.001) or other chronic medical conditions and were older (p < 0.015). For PPID horses specifically, HRQoL scores were also worse if they had other chronic medical conditions (p = 0.02), but HRQoL scores were not associated with current PPID treatment (treated vs. untreated horses with a PPID diagnosis), bodyweight, age, breed, sex or years since diagnosis.

MAIN LIMITATIONS: Limited numbers of untreated PPID horses.

CONCLUSION: The HRQoL tool is valid and reliable for use in horses with PPID and can be applied in further research. PPID horses with another chronic disease had worse HRQoL scores, which should be considered in other studies evaluating disease impact.

PMID:40314080 | DOI:10.1111/evj.14513

Angew Chem Int Ed Engl. 2025 May 2:e202505548. doi: 10.1002/anie.202505548. Online ahead of print.

ABSTRACT

We investigate two unusual phenomena in self-assembly of anisotropic molecules from isotropic (Iso) melt: a heat-capacity (Cp) maximum, and spontaneous formation of the recently discovered chiral liquid (Iso*). Based on experiments on new non-chiral monomers, dimers and polymers, we construct a statistical theory that shows why many complex mesostructures form in two stages: continuous equilibrium growth of nano-clusters in melt through strong interactions, causing the Cp-maximum, followed by establishment of positional long-range order (LRO) through a weak first-order transition. We also show why many achiral compounds additionally form an intermediate chiral Iso* liquid through what we find is a second-order transition. We propose that the first process is equivalent to “supramolecular polymerization” in solutions, where the lack of inter-cluster interaction rules out LRO. Furthermore, we argue that separation into a broad and a sharp transition is universal in condensed matter where strong interactions by themselves cannot lead to LRO, either because the clusters are 1D or due to strong frustration. Clusters must first grow to critical size when, at Tc, the combined weak interactions reach ~kBTc, prompting LRO formation. A situation similar to that in soft self-assembly is seen in spin ordering in magnetic crystals, but only near 0 K.

PMID:40314063 | DOI:10.1002/anie.202505548