Category: Nevin Manimala

J Comput Chem. 2026 Sep 5;47(23):e70488. doi: 10.1002/jcc.70488.

ABSTRACT

The evaluation of non-covalent interactions remains a cornerstone of density functional theory benchmarking, yet the increasing size of reference datasets like the D1200 presents a significant computational bottleneck. This work introduces an optimized “Diet-D1200” protocol, utilizing a genetic algorithm to identify highly representative subsets of interaction energies across an expansive chemical space, including p-block elements such as Boron, Sulfur, Phosphorus, halogens, and noble gases. By employing a WTMAD-4 (Weighted Total Mean Absolute Deviation) scheme-normalized specifically to the D1200 intrinsic energy scale-we demonstrate that subsets as small as 100 to 250 systems can faithfully reproduce the statistical performance of the full dataset. To evaluate the generalization performance of the optimized subsets and mitigate the risk of overfitting to the training manifold, a rigorous external validation protocol was performed. This assessment utilized twenty density functionals approximations, from GGAs and meta-GGAs to range-separated hybrids and double-hybrids. Our results demonstrate that the Diet-D200 protocol effectively preserves the topological features of the error surface, reducing the computational overhead by 83.3% while maintaining an exceptional Pearson correlation ( r > 0.995 ) with the parent D1200.

PMID:42634015 | DOI:10.1002/jcc.70488

Aust Health Rev. 2026 Sep 3;50(3):AH26030. doi: 10.1071/AH26030.

ABSTRACT

OBJECTIVE: This study aimed to compare demographic, clinical, and early engagement characteristics between participants retained and not retained at 9 months in specialist obesity services.

METHODS: This retrospective cohort study analysed 235 records of patients (mean body mass index 49.2 kg/m²) from eight Australian specialist obesity services. Participants were classified as retained (n = 153) and not retained (n = 82) at 9 months. Demographic variables and baseline comorbidities were examined to identify potential predictors of retention. Appointment adherence and weight reduction outcomes during the first 6 months were also analysed according to retention status. Descriptive statistics and appropriate comparative tests were used to test the differences between groups.

RESULTS: Baseline demographic characteristics were similar between participants retained and not retained at 9 months. Type 2 diabetes was more prevalent among participants retained compared with those not retained (55.6% vs 39.0%; P = 0.02). Eating disorders (7.8% vs 22.0%; P = 0.002), gallstones (1.9% vs 8.6%; P = 0.04), and prior stroke (0.6% vs 8.6%; P = 0.003) were more common in participants who were not retained. Retention at 9 months was associated with significantly higher appointment adherence throughout the study period, with the greatest difference in cumulative 9-month adherence (0.88 vs 0.77, P < 0.001). At 6 months, retained participants achieved significantly greater weight reduction (-9.02 kg ± 10.29 kg vs -5.78 kg ± 10.55 kg; P = 0.04).

CONCLUSIONS: In this cohort, 9-month retention was strongly associated with early appointment adherence and greater 6-month weight reduction. Non-retained patients clustered with eating disorders and prior stroke indicate patients requiring additional support. Early adherence and weight reduction appear key to sustained engagement.

PMID:42634005 | DOI:10.1071/AH26030

J Appl Toxicol. 2026 Aug 23. doi: 10.1002/jat.70396. Online ahead of print.

ABSTRACT

Cantharidin (CTD) possesses potent anticancer activity, whereas its prominent hepatotoxicity severely limits its clinical application. Because the detailed molecular mechanisms responsible for CTD-triggered hepatotoxicity have not been fully elucidated, additional investigations are necessary to uncover its toxicological pathways. This study investigated the mechanism of CTD-triggered hepatotoxicity and the protective effects of exogenous glutathione (GSH) supplementation. In vitro results showed that CTD reduced the GSH/glutathione disulfide (GSSG) ratio and the activities of catalase (CAT) and glutathione peroxidase (GPX) in hepatocytes, induced a compensatory upregulation of superoxide dismutase (SOD), and promoted malondialdehyde (MDA) accumulation. Additionally, CTD downregulated glutamate-cysteine ligase modifier subunit (GCLM) expression, decreased mitochondrial membrane potential (MMP), suppressed B-cell lymphoma 2 (Bcl-2) expression, and upregulated Bcl-2-associated X protein (Bax), cysteine-dependent aspartate-directed protease (caspase-9), downstream caspase-3, and cytochrome c (Cyt c) levels, thereby triggering hepatocyte apoptosis, with no significant changes in cellular cysteine (Cys) content and glutamate-cysteine ligase catalytic subunit (GCLC) expression. In vivo experiments verified that CTD markedly decreased hepatic GSH and Cys levels and downregulated GCLC expression, whereas GCLM expression and hepatic Cyt c levels showed only a slight upward trend without statistical significance. Glutathione ethyl ester (GSH-OEt) pretreatment in vitro and GSH intervention in vivo effectively prevented CTD-caused oxidative damage. Collectively, CTD induces divergent expression patterns of glutamate-cysteine ligase (GCL) subunits in vitro and in vivo, disrupts GSH metabolic homeostasis, and provokes oxidative stress and mitochondrial dysfunction, ultimately leading to hepatocellular injury.

PMID:42633976 | DOI:10.1002/jat.70396

Magn Reson Med Sci. 2026;25(4). doi: 10.2463/mrms.mp.2026-0023.

ABSTRACT

PURPOSE: Pseudo-continuous arterial spin labeling (pCASL) MRI is a widely used, noninvasive, contrast-agent-free technique for measuring cerebral blood flow (CBF) and assessing vascular dysfunction across diverse clinical settings and murine disease models. In practice, arterial-transit artifacts that generate hyperintense signal in CBF maps warrant careful consideration. While these effects are well characterized in humans, they are less well understood in mice owing to the marked interspecies physiological differences.

METHODS: To address this knowledge gap, we systematically characterized pCASL hyperintense signal as a function of post-labeling delay (PLD) and crusher-gradient strength in mice. Numerical simulations were also performed to validate the experimental findings.

RESULTS: We found that hyperintense signals in mice extend to arteries, major veins, and ventricular structures. Such a pattern was different from human pCASL images, where hyperintense signals are predominantly present in arteries. Statistical analyses supported a PLD of 500 milliseconds as a pragmatic balance between detection sensitivity and suppression of vascular contamination. Additional experiments and numerical simulations showed that, within the tested range, stronger crusher gradients provided little extra vascular suppression-primarily because large vessel calibers relative to small voxels limit intravoxel phase dispersion.

CONCLUSION: These findings refine the interpretation of murine pCASL signals and facilitate more accurate perfusion imaging in preclinical pathophysiological studies.

PMID:42633933 | DOI:10.2463/mrms.mp.2026-0023

Int Wound J. 2026 Aug;23(8):e71018. doi: 10.1111/iwj.71018.

ABSTRACT

Pilonidal sinus disease (PSD) is a common acquired condition of the sacrococcygeal region; despite numerous described surgical techniques, long-term outcomes remain highly variable. We compared long-term recurrence and postoperative infection among nine surgical techniques in a large single-centre cohort. We retrospectively analysed 2222 patients with primary PSD who underwent surgery between January 2006 and December 2020 at a single tertiary referral centre in Turkey and had a minimum follow-up of 5 years. Patients presenting with recurrent disease were excluded. Nine surgical techniques were evaluated. Recurrence was analysed as a time-to-event outcome using Kaplan-Meier estimates and multivariable Cox proportional hazards regression. The 5-year cumulative recurrence was 7.9% (175/2222) and postoperative infection 6.9% (154/2222); overall recurrence was 10.2% (226/2222). Recurrence and infection differed statistically significantly among surgical techniques (both p < 0.001). The lowest recurrence rates were observed with the Karydakis flap (1.5%), Bascom cleft lift (2.3%) and Dufourmentel flap (2.4%). Most recurrences occurred within the first 2 years, with a median time to recurrence of 20 months (IQR 12-36). Compared with lay-open treatment, the Karydakis flap (HR 0.19, 95% CI 0.12-0.30), Bascom cleft lift (HR 0.25, 95% CI 0.14-0.43), Limberg flap (HR 0.32, 95% CI 0.19-0.53) and Dufourmentel flap (HR 0.26, 95% CI 0.12-0.57) were independently associated with lower risk of recurrence, whereas a higher body mass index (HR 1.05 per 1 kg/m², 95% CI 1.01-1.09) and current smoking (HR 1.98, 95% CI 1.54-2.55) were independently associated with an increased recurrence risk. Off-midline flap techniques were associated with superior long-term outcomes, with lower recurrence and infection than midline or secondary-healing approaches. Taken together, the findings of this study support the use of the Karydakis flap and Bascom cleft lift as first-line surgical options for PSD management.

PMID:42633928 | DOI:10.1111/iwj.71018

J Epidemiol. 2026 Aug 22. doi: 10.2188/jea.JE20260213. Online ahead of print.

ABSTRACT

BACKGROUND: Few studies have specifically examined the relationship between social media use and uptake of COVID-19 booster. This study examined the association between social media use and COVID-19 booster vaccination uptake in Japan during the pandemic.

METHODS: A series of cross-sectional surveys was conducted using rapid online questionnaires among residents of Iwate Prefecture, Japan, from October 1 to 3, 2021, and from December 11 to 17, 2023 (n = 4,026). Vaccination status was assessed using a single question: “What is your vaccination status?”. Respondents were categorized into two groups: individuals with incomplete booster uptake (those who had received one or two doses; n = 226) and booster acceptors (those who had received at least three doses; n = 3,800). Social media use was defined as self-reported use of Twitter, Facebook, Instagram, YouTube, or other social networking services. Logistic regression analyses were conducted to examine the association between social media use and receipt of a COVID-19 booster vaccination.

RESULTS: Social media use was significantly associated with higher odds of incomplete booster uptake of COVID-19 vaccination. This association remained statistically significant after adjustment for relevant covariates (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.21-2.39). Individuals with a history of COVID-19 infection prior to the initiation of booster vaccinations were less likely to receive a booster dose in an exploratory analysis (OR 3.06, 95% CI 1.28-7.32).

CONCLUSION: Differential associations between media use and COVID-19 booster uptake may provide important insights for designing effective communication strategies to improve vaccine acceptance in future pandemics.

PMID:42633927 | DOI:10.2188/jea.JE20260213

J Epidemiol. 2026 Aug 22. doi: 10.2188/jea.JE20260096. Online ahead of print.

ABSTRACT

BACKGROUND: The Area Deprivation Index (ADI) is widely used to monitor health inequalities and often used as a proxy for individual socioeconomic status (SES). However, the extent to which it reflects individual SES remains unclear. This study aimed to establish evidence linking neighborhood-level ADI with individual SES indicators in Japan and examine whether similar patterns of association are observed across independent population-based cohorts.

METHODS: We analyzed baseline data from two population-based cohorts: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) (baseline survey, 2011-2016; ages 40-74 years; N=100,024) and the Yokohama Health Study (YHS) (baseline survey, 2023; ages 30-69 years; N=8,860). ADI was ranked into quartiles (Q1: lowest, Q4: highest deprivation) based on the distribution across all postcodes in Japan and linked to each participant by residential area. Logistic regression models estimated associations between ADI quartile and low income (<1.53 million JPY) or limited education (≤9 or ≤12 years) by gender.

RESULTS: Higher ADI showed increasing trends of association with low income and ≤9 years of education in both cohorts and across genders, with p for trend <0.001 for all. In contrast, associations with ≤12 years of education were less consistent across cohorts and subgroups, with no significant trend observed among women in JPHC-NEXT (p for trend = 0.74).

CONCLUSIONS: While the ADI consistently reflected income-related disadvantage across cohorts, its association with educational attainment varied across contexts. This should be carefully considered when using or interpreting ADI-based measures of health inequality in Japan.

PMID:42633923 | DOI:10.2188/jea.JE20260096

Biol Pharm Bull. 2026;49(8):1276-1284. doi: 10.1248/bpb.b26-00209.

ABSTRACT

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in immunocompromised patients. While ganciclovir (GCV) is commonly used for its management, pharmacokinetic (PK) targets for optimal efficacy and minimal toxicity remain controversial. This study aimed to explore the association of PK parameters with the efficacy and safety of GCV in the treatment of CMV infection. We conducted a prospective study of adult patients who received intravenous GCV for CMV infection. Treatment efficacy was defined as a ≥50% reduction in CMV antigen-positive cells using a pp65 antigenemia test. The highest or lowest hematological, hepatic, and renal laboratory values were used to assess safety. Individual PK parameters (area under the concentration-time curve [AUC]_24h, trough [C_min], and peak [C_max]) plasma concentration were estimated using multiple GCV plasma concentrations from each patient. Associations between PK parameters and efficacy/safety were assessed. Of 23 patients, 20 (87.0%) exhibited an effective response. Median estimated AUC_24h, C_min, and C_max values were 45.5 mg·h/L, 0.5 mg/L, and 6.8 mg/L, respectively. AUC_24h and C_min were not significantly associated with the efficacy of GCV (odds ratio [OR] 1.05, 95% confidence interval [CI] 0.96-1.16, p = 0.301; OR 0.92, 95% CI 0.11-7.86, p = 0.942). C_max showed a relatively large but nonsignificant OR (OR 2.45, 95% CI 0.84-7.09, p = 0.099). No clinically relevant associations between PK parameters and safety were observed. Baseline laboratory values were associated with safety. In conclusion, no statistically significant associations were identified between GCV PK parameters and the treatment efficacy/safety of CMV infection in adult patients.

PMID:42633913 | DOI:10.1248/bpb.b26-00209

Int Wound J. 2026 Aug;23(8):e71011. doi: 10.1111/iwj.71011.

ABSTRACT

Pressure ulcers/injuries at the posterior heel commonly develop in patients with limited mobility or sensation, where movements such as sliding in bed generate shear forces that elevate the deep soft tissue stresses. Prophylactic multilayer dressings are recommended to reduce this injury risk, yet many current products incorporate high-friction silicone adhesives for attaching the dressing to the skin, which may increase shear transfer to the skin and subdermally while a patient is moving or being moved. This study evaluated a multilayer dressing featuring an Aquacel Hydrofiber Technology skin-contact layer that exhibits moisture-responsive friction reduction. Finite element models of a posterior heel resting on a support surface were developed to simulate compressive and shear loading during patient sliding-in-bed, comparing no dressing, dry (new) and moist (used) dressing conditions. Moisture exposure reduced the skin-dressing coefficient of friction from 1.55 to 0.22, leading to substantial reduction in soft tissue strain and stress exposures, such that high-magnitude strain and stress concentrations (> 75th-percentile) were effectively absent within the modelled loading domain under the simulated conditions. Moisture-induced friction reduction facilitated controlled micro-sliding at the skin interface, attenuating shear transfer into skin and subcutaneous tissues. These findings demonstrate that moisture-responsive interfacial friction adaptation is an important mechanism of action contributing to the biomechanical protective efficacy of prophylactic dressings.

PMID:42633909 | DOI:10.1111/iwj.71011

J Subst Use Addict Treat. 2026 Aug 23:210096. doi: 10.1016/j.josat.2026.210096. Online ahead of print.

ABSTRACT

BACKGROUND: Gender differences in substance use disorders (SUDs) are well documented globally; however, evidence from psychiatric inpatient populations in sub-Saharan Africa remains limited. In Nigeria, sociocultural norms, stigma, and structural barriers may differentially influence treatment access, clinical presentation, and outcomes among men and women with SUD. This study examined gender differences in substance use patterns, psychiatric comorbidity, treatment outcomes, and relapse among psychiatric inpatients in Nigeria.

METHODS: This retrospective study reviewed the medical records of adults admitted with a primary diagnosis of SUD to a tertiary psychiatric hospital in southeastern Nigeria between 2018 and 2024. Analyses compared male and female patients based on sex as recorded in the clinical records. Data on substance use patterns, psychiatric comorbidity, treatment outcomes, and relapse within six months after discharge were extracted and analyzed using bivariate statistics and multivariable binary logistic regression.

RESULTS: A total of 286 patients were included, the majority of whom were male. Men were more likely to present with cannabis use, polysubstance use, and longer durations of substance use, whereas women more commonly presented with opioid use and shorter durations of use. Psychiatric comorbidity was common in both groups, although psychotic disorders predominated among men and anxiety disorders among women. Female patients had longer hospital stays and were more likely to achieve planned discharge following clinical improvement, whereas male patients had higher rates of discharge against medical advice and relapse within six months. Male sex remained independently associated with relapse after adjustment for age, duration of substance use, psychiatric comorbidity, and polysubstance use.

CONCLUSIONS: Important gender differences were observed in the clinical presentation, treatment outcomes, and relapse of psychiatric inpatients with SUD in Nigeria. These findings support the implementation of gender-responsive addiction services that improve treatment access for women while strengthening relapse prevention, discharge planning, and continuity of care for men.

PMID:42633882 | DOI:10.1016/j.josat.2026.210096