Tag: nevin manimala

J Chem Inf Model. 2026 Jun 11. doi: 10.1021/acs.jcim.6c00831. Online ahead of print.

ABSTRACT

A unified atlas of 11073 noncovalent complexes spanning quantum-chemical benchmark dimers, deep eutectic solvent formulations, and large supramolecular host-guest assemblies is constructed using the Kulkarni Universal Interaction Descriptor (K-UID), a hierarchically structured hexadecimal addressing system derived from the nine-dimensional Kulkarni-NCI Fingerprint. Discretization of the globally normalized KNF feature space yields 1119 distinct topological families, of which 754 contain two or more members with a median within-family coefficient of variation of 6.93% for the Noncovalent Interaction Score (S_NCI), establishing that topological address membership exhibits statistically consistent interaction descriptor behavior across all four source datasets. A controlled row-shuffling ablation confirms that the KNF feature vector encodes genuine, molecule-specific physical information: random permutation of feature vectors across complexes increases mean absolute error by a factor of 2.8 and drives the coefficient of determination to R² = -1.251, establishing that predictive performance derives from the physical correspondence between features and molecular interaction fields rather than from exploitable distributional properties of the descriptor. Principal component analysis of the KNF feature space reveals a striking asymmetry in topological coverage: the 27-complex S30L supramolecular dataset occupies 39.3% of the accessible PC1-PC2 interaction manifold, a per-compound coverage 652 times greater than NENCI-2021 dimers, with 91.3% of S30L topological families having no analog in the reference benchmarks. Nearest-neighbor matching of deep eutectic solvent and supramolecular complexes to reference-dataset physics twins in the scale-invariant intensive feature space yields a Spearman rank correlation of ρ = 0.283 (p = 1.16 × 10^-52, n = 2789), confirming transferable rank information across molecular scales governed by interaction topology without structural similarity constraints. Family occupancy analysis further reveals that 66.9% of reference topological families (401 of 599) have no experimentally realized DES analog in the current atlas, while 499 DES-exclusive families lie outside the reference benchmark space, establishing that current DES design practice explores a confined, nonrepresentative region of the accessible interaction manifold. Together, these findings establish interaction topology as a transferable classification property and provide a concrete, atlas-defined route to identifying underexplored design space in functional noncovalent materials.

PMID:42275604 | DOI:10.1021/acs.jcim.6c00831

Mol Biol Evol. 2026 Jun 11:msag141. doi: 10.1093/molbev/msag141. Online ahead of print.

ABSTRACT

Credible intervals and credible sets, such as highest posterior density (HPD) intervals, form an integral statistical tool in Bayesian phylogenetics, both for phylogenetic analyses and for development. Readily available for continuous parameters such as base frequencies and clock rates, the vast and complex space of tree topologies poses significant challenges for defining analogous credible sets. Traditional frequency-based approaches are inadequate for diffuse posteriors where sampled trees are often unique. To address this, we introduce novel and efficient methods for estimating the credible level of individual tree topologies using tractable tree distributions, specifically Conditional Clade Distribution (CCD). Furthermore, we propose a new concept called α credible CCD, which encapsulates a CCD whose trees collectively make up α probability. We present algorithms to compute these credible CCDs efficiently and to determine credible levels of tree topologies as well as of subtrees. We evaluate the accuracy of these credible set methods leveraging simulated and real datasets. Furthermore, to demonstrate the utility of our methods, we use well-calibrated simulation studies to evaluate the performance of different CCD models. In particular, we show how the credible set methods can be used to conduct rank-uniformity validation and produce Empirical Cumulative Distribution Function (ECDF) plots, supplementing standard coverage analyses for continuous parameters.

PMID:42275602 | DOI:10.1093/molbev/msag141

Arch Endocrinol Metab. 2026 Jun 10;70(4). doi: 10.20945/2359-4292-2026-0057.

ABSTRACT

OBJECTIVE: To investigate the impact of smoking on serum selenium levels, autoimmune activity, and macular microvascular density in patients with clinically inactive thyroid-associated orbitopathy (TAO), using optical coherence tomography angiography (OCTA).

SUBJECTS AND METHODS: This retrospective cross-sectional study included 44 patients with inactive TAO (24 smokers, 20 non-smokers) and 32 ageand sex-matched healthy controls. All participants underwent ophthalmologic evaluation and laboratory testing for thyroid hormones, selenium, and thyroid-stimulating immunoglobulin (TSI). Macular vessel density was measured using spectral-domain OCTA at the superficial capillary plexus, deep capillary plexus, outer retinal layer, and choriocapillaris. Clinical activity score (CAS) was used to assess disease activity. The collected data were analyzed statistically.

RESULTS: Smokers with TAO exhibited significantly higher CAS (p = 0.016) and TSI levels (p = 0.027), and lower serum selenium concentrations (p = 0.042) compared to non-smokers. Central superficial and deep capillary plexus densities were significantly reduced in smokers versus healthy controls (p = 0.029 and p = 0.017, respectively). No significant differences were observed between smokers and non-smokers within the TAO group, or in the outer retinal layer and choriocapillaris layers among all groups.

CONCLUSION: Smoking status was associated with lower selenium levels, higher TSI levels, and increased CAS. Furthermore, retinal microvascular attenuation detected by OCTA, even in the absence of clinical activity in TAO, may serve as a significant indicator of persistent vascular deterioration.

PMID:42275591 | DOI:10.20945/2359-4292-2026-0057

Psychol Health Med. 2026 Jun 11:1-16. doi: 10.1080/13548506.2026.2686302. Online ahead of print.

ABSTRACT

This study aimed to investigate the level of self-regulatory fatigue and its associated factors among young and middle-aged adults with type 2 diabetes mellitus (T2DM), examining the mediating role of psychological resilience in the relationship between perceived social support and self-regulatory fatigue. A cross-sectional study was conducted from August to December 2025 in Shandong Province, China. A total of 261 patients aged 18-59 years with T2DM were recruited via convenience sampling from a tertiary hospital. Participants completed a series of structured questionnaires, including the Self-Regulatory Fatigue Scale, the Connor-Davidson Resilience Scale, and the Scale of Perceived Social Support. The data were analyzed using descriptive statistics, Pearson’s correlation, multiple linear regression, and mediation analysis with the SPSS PROCESS macro. The mean score for self-regulatory fatigue was 42.22 ± 5.72, which was higher than the general population norm. Multivariate linear regression analysis identified longer diabetes duration (β = 0.106, p = 0.01), greater number of complications (β = 0.102, p = 0.008), lower psychological resilience (β = -0.142, p = 0.013), lower perceived social support (β = -0.508, p < 0.001) and lower self-management behaviors (β = -0.144, p < 0.001) as significant independent predictors of higher self-regulatory fatigue. Mediation analysis revealed that psychological resilience partially mediated the relationship between social support and self-regulatory fatigue accounting for 22.4% of the total effect. The present study identifies elevated levels of self-regulatory fatigue in young and middle-aged patients with T2DM, particularly in the cognitive dimension. The study emphasizes the significance of social support and psychological resilience as modifiable protective factors, with resilience mediating the effect of support to a certain extent. These findings support the integration of psychosocial strategies into diabetes care with a view to alleviating self-regulatory burden.

PMID:42275582 | DOI:10.1080/13548506.2026.2686302

JMIR Res Protoc. 2026 Jun 11;15:e90704. doi: 10.2196/90704.

ABSTRACT

BACKGROUND: Specifically in primary musculoskeletal care settings, the employment of advanced physiotherapy practice (APP) roles seems to be safe, as well as clinically and financially effective. In tertiary care settings, the implementation of APP roles is still in its infancy. A structured identification of relevant APP roles and a definition of practice areas, needed skills, and core competencies is widely pending.

OBJECTIVE: This study aims to identify and prioritize the most relevant areas of tertiary care for the implementation of APP roles within the German health care system. Additionally, it is aimed to achieve expert consensus on practice areas, needed skills, and core competencies relevant to execute identified roles.

METHODS: A total of 100 national experts will be invited to participate in a 3-round Delphi survey. Participants will purposively be sampled among physiotherapists with extensive clinical and/or academic experiences in German tertiary care. Data will be pseudonymized and collected via online questionnaires. In Delphi round 1, close-ended questions on relevant APP roles and open-ended input on practice areas, skills, and core competencies will be queried. Open-ended questions will be structured according to key domains of the National Health Service multiprofessional framework for advanced clinical practice. In round 2, participants will rate close-ended items on practice areas, skills, and core competencies that emerged from open-ended questions of round 1. Each item will be rated on a 7-point Likert scale ranging from “not relevant at all” to “extremely relevant.” Consensus will be set on ≥70% agreement per item (including “5=fairly relevant,” “6=very relevant,” and “7=extremely relevant”). Items with agreements of ≤30% will be excluded. Items of 31% to 69% agreement will be reevaluated in round 3. Descriptive statistics (median, IQR, and absolute and relative frequencies) will be used to visualize response patterns, and McNemar and Wilcoxon signed-rank tests will be applied to explore changes between rounds.

RESULTS: Data collection took place between January and May 2026. For the first Delphi round, 98 experts were invited, of which 37 fully completed round 1. In round 2, these 37 experts were invited, of which 34 fully completed Delphi round 2. Following these response rates, we were confident to receive the targeted study sample of 20 experts after data collection of Delphi round 3 was completed. Data collection for the third and final round was completed in May 2026 and included 32 final respondents.

CONCLUSIONS: Findings will support evidence-based APP role development and contribute to optimizing tertiary care areas relevant to physiotherapy care in Germany.

PMID:42275572 | DOI:10.2196/90704

J Occup Environ Hyg. 2026 Jun 11:1-13. doi: 10.1080/15459624.2026.2668076. Online ahead of print.

ABSTRACT

Noise in the clinical dental setting has been shown to exceed safe levels, and the risk to dental professionals, including occupational noise-induced hearing loss, is well-established. This pilot study investigated dentists’ perceptions and experiences of the use of custom-made earplugs as a means of attending to the risk in the clinical dental setting. Dentists were recruited using convenience and purposive sampling and provided with custom-made attenuated earplugs, which were worn for a period of 12 weeks of usual clinical dental practice. Questionnaires were completed periodically. Data were analyzed statistically and thematically. There was a total of eight participants. Participants recognized the risk of hearing loss and supported the promotion and inclusion of hearing protection as a part of personal protective equipment. Participants noted an improved focus due to a reduction in noise perception. Disadvantages included discomfort and communication challenges. This pilot study assessed the process for, and feasibility of, conducting a larger-scale study and will contribute to the reliability and validity of such, which is recommended.

PMID:42275558 | DOI:10.1080/15459624.2026.2668076

Curr Med Res Opin. 2026 Jun 11:1-11. doi: 10.1080/03007995.2026.2683436. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment-resistant depression (TRD) imposes a substantial economic burden on South Korea, yet limited cost data exist for the TRD stage. This study estimated the 28-day societal costs of TRD across distinct health states.

METHODS: A mixed micro-macro-costing approach was used to estimate direct medical, non-medical, and indirect costs from a societal perspective across four health states (major depressive episodes [MDE], treatment response, remission, and recovery). Healthcare resource utilization was assessed through expert consultation with eight board-certified psychiatrists. The unit costs were derived from national fee schedules, published literature, and national statistics. Indirect costs included productivity losses due to absenteeism, presenteeism, and suicide-related mortality.

RESULTS: Over a 28-day cycle, the per-patient direct medical cost in the MDE state ($803.2) was 15.2 times higher than that in the recovery state ($52.8). From a societal perspective, the 28-day economic burden during the MDE state ($2,388.4) was 25.7 times greater than that of the recovery state ($93.1). In the MDE state, indirect costs constituted the largest component of this 28-day societal burden ($1,074.6; 45% of total costs), followed by direct medical costs ($803.2; 34%).

CONCLUSIONS: TRD imposes a substantial economic burden on South Korea, with costs peaking during acute episodes. These findings underscore the critical importance of clinical interventions that reduce episode duration and accelerate recovery to minimize healthcare utilization and societal costs.

PMID:42275136 | DOI:10.1080/03007995.2026.2683436

Curr Med Res Opin. 2026 Jun 11:1-10. doi: 10.1080/03007995.2026.2682588. Online ahead of print.

ABSTRACT

OBJECTIVE: to investigate whether drug resistance is differentially reported for integrase strand-transfer inhibitors (INSTIs) in a global pharmacovigilance database.

METHODS: A disproportionality analysis was conducted to assess resistance to the five available INSTIs using VigiBase, the WHO global database of individual case safety reports (ICSRs). ICSRs were identified through Medical Dictionary for Regulatory Activities – MedDRA preferred terms (PTs) drug resistance, drug resistance mutation, genotype drug resistance test/test positive, multiple-drug resistance and pathogen resistance between October 2007 and September 2024. Descriptive analyses were employed to characterize individual cases according to sociodemographic and reporting-related variables. Disproportionality signals for at least one resistance-related MedDRA PTs compared with all other drugs in the database were expressed as reporting odds ratios (ROR) and information component (IC), with 95% confidence intervals (CI).

RESULTS: 35,406,826 deduplicated ICSRs were identified; 22,825 comprised reports of drug resistance and 1,084 involved exposure to INSTIs. Cases of HIV resistance were predominantly males. Most reports were regarded as serious and originated from Europe and the Americas. Disproportionality signals for drug resistance were observed for all first-generation (ROR= 52.5; CI 95% = 47.6-57.9; IC = 5.56; 95% CI = 5.4-5.7 – raltegravir) and second-generation INSTIs (ROR = 55.9; CI 95% = 50.8-61.5; IC = 5.65; 95% CI = 5.5-5.8 – dolutegravir).

CONCLUSIONS: HIV drug resistance to all INSTIs as well significant disproportionate safety signals were identified. These findings should be interpreted with caution given the inherent limitations of spontaneous reporting. Resistance monitoring in clinical settings is relevant.

PMID:42275135 | DOI:10.1080/03007995.2026.2682588

Integr Comp Biol. 2026 Jun 11:icag083. doi: 10.1093/icb/icag083. Online ahead of print.

ABSTRACT

Long-lived marine mammals such as bowhead whales (Balaena mysticetus) provide rare opportunities to examine physiological responses to past environmental and anthropogenic pressures. Using baleen plates from six adult females, we constructed up to 18 years of longitudinal profiles per individual for eight analytes: corticosterone, cortisol, dehydroepiandrosterone and its sulfated form (DHEA(S)), progesterone, testosterone, triiodothyronine (T3), and stable isotope ratios of carbon (δ13C) and nitrogen (δ15N). These records spanned three distinct periods (regimes): the 1850s-1870s, marked by commercial whaling and a warm Pacific Decadal Oscillation (PDO) phase; the 1940s-1960s, a cold PDO phase with Arctic stability and multiple La Niña events; and the 1970s-1980s, which included a major PDO regime shift and strong El Niño events. We identified 1-8 putative pregnancies per individual based on progesterone profiles, with variation in gestation length (13-21 months), interpregnancy interval (8 months to >4 years), and apparent pregnancy loss or calf loss. Pregnancy was associated with elevated corticosterone, DHEA(S), and testosterone. Certain hormones varied significantly with regime: DHEA(S) and testosterone were higher in the 1850s-1870s relative to at least one later regime, whereas T3 was significantly lower in the 1970s-1980s compared to earlier periods. δ¹³C was a significant negative predictor of T3, suggesting a potential link between foraging habitat and metabolic output. These findings highlight baleen as a retrospective biomonitoring tool and reveal potential reproductive plasticity and physiological responses of female bowheads to environmental change.

PMID:42275131 | DOI:10.1093/icb/icag083

Nephrol Dial Transplant. 2026 Jun 11:gfag130. doi: 10.1093/ndt/gfag130. Online ahead of print.

ABSTRACT

BACKGROUND AND HYPOTHESIS: Iohexol and 99mTc-DTPA are commonly used exogenous filtration markers for determining measured glomerular filtration rate (mGFR). Traditional intravenous sampling is time-consuming and often inconvenient in clinical practice, whereas dried blood spot (DBS) sampling is a promising alternative. This study used population pharmacokinetic modeling (popPK) and traditional performance statistics to investigate whether intravenous and DBS sampling can be used interchangeably for measuring GFR in older medical patients with low appetite.

METHODS: Older patients aged ≥65 years with poor appetite, defined as a Simplified Nutritional Appetite Questionnaire (SNAQ) score ≤14, received intravenous administration of iohexol and 99mTc-DTPA, followed by sampling over 4-8 hours intravenously (for both tracers) and by DBS (for iohexol). Gentamicin 5 mg/kg was used as a model drug and administered intravenously to all patients, followed by plasma sampling over 22 hours. Employing a previously developed gentamicin popPK model, model fit improvement for each mGFR method was evaluated by reduction in objective function value (OFV) and inter-individual variability (IIV) when including mGFR as a covariate on clearance. Performance of each method relative to intravenous iohexol sampling was also evaluated by bias (median difference) and P15 (percentage of values within 15%).

RESULTS: 51 older patients (51% male, aged 67-96) were included. All three mGFR methods improved model fit when implemented as covariates on gentamicin clearance in popPK models (-ΔOFV = 115.6-137.6). The improvements were greater when mGFR was expressed in mL/min, rather than mL/min/1.73 m2. Compared to intravenous sampling of iohexol, DBS sampling of iohexol performed better (bias [95% CI] = 2 [0-3] mL/min, P15 = 98% [94.1%-100%]) than intravenous sampling of 99mTc-DTPA (bias = 4 [3-5] mL/min, P15 = 78.4% [66.7%-88.2%]).

CONCLUSIONS: Compared to intravenous sampling of iohexol or 99mTc-DTPA, DBS sampling of iohexol yielded similar improvements to model fit when incorporated as a covariate on gentamicin clearance in a popPK model.

PMID:42275113 | DOI:10.1093/ndt/gfag130