Tag: pubmed

Cell Biochem Biophys. 2026 Jul 13. doi: 10.1007/s12013-026-02117-w. Online ahead of print.

ABSTRACT

This research aims to explore the human-like taste response of three bitter molecules (chloroquine, denatonium, and saccharin) on the human bronchi receptor T2R agonist using a statistical physics approach. By fitting the concentration-taste response curves, we estimate three model parameters (R_M, n, C_1/2) to assess the intermolecular interactions with T2R receptor sites. In addition, the transduction coefficient (α) of the three tasting molecules has been determined. This analysis provides valuable insights into the binding energy spectrum (AES) and establishes a common gustatory band for the bitter tastes, with adhesive energies distributed over a relatively wide range (2.5-22.5 kJ mol⁻¹). In addition, molecular docking simulations were conducted, revealing that denatonium exhibits stronger binding affinities (28.87 kJ/mol) with the T₂R₁₀ human taste receptor site compared to chloroquine (26.78 kJ/mol). Conversely, saccharin displayed a binding affinity of approximately 23.85 kJ/mol with the binding pocket of the T₂R₃₁ ion channel receptors. This three molecules undergoes theoretical analysis using the DFT/B3LYP/6-311 G(d, p) basis set to determine its frontier orbital features and stability. The type and strength of interactions were identified using the topological parameters of the “Atoms in Molecules” (AIM) method, NCI analysis was used to study intra- and intermolecular noncovalent interactions within a molecular system, as well as natural bond orbital (NBO) analysis. NBO analyses indicate that all three tasting molecules exhibits significant stability. NCI interaction analyses indicate that Van der Waals forces and steric effects are observed in the three tasting molecules. 3D shaded potential surface revealed a projection of LOL examination and the electron localization function (ELF) indicated that an area of electron depletion is observed in the three tasting molecules.

PMID:42440246 | DOI:10.1007/s12013-026-02117-w

Clin Rheumatol. 2026 Jul 13. doi: 10.1007/s10067-026-08131-w. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to describe the clinical characteristics of patients with progressive pulmonary fibrosis (PPF) in systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and to explore factors associated with PPF.

METHODS: Medical records of patients with SSc who visited Seoul St. Mary’s Hospital between April 2015 and March 2025 were retrospectively reviewed. PPF in SSc-ILD was defined as a relative decline in predicted forced vital capacity (FVC) ≥ 10% within 24 months. Clinical characteristics and outcomes were compared using logistic regression and survival analyses.

RESULTS: Among 319 patients with SSc evaluated with thoracic CT, ILD was identified in 168 (52.7%). Of the 140 patients with SSc-ILD who had serial spirometry, 27 (19.3%) developed PPF. Patients with PPF exhibited digital gangrene (25.9% vs. 8.8%, P = 0.02), pulmonary hypertension (40.7% vs. 20.0%, P = 0.04), and mixed NSIP-UIP (11.1% vs. 1.8%, P = 0.049) more frequently than those without PPF. Treatment with methotrexate (37.0% vs. 15.0%, P = 0.01) and nintedanib (18.5% vs. 1.8%, P = 0.003) was also more prevalent. None of the variables remained statistically significant in the multivariable analysis, and overall survival did not differ between patients with and without PPF.

CONCLUSION: In patients with SSc-associated ILD, PPF was associated with prominent vascular manifestations and mixed NSIP-UIP. These findings underscore the heterogeneity of SSc-ILD and highlight the importance of close and longitudinal pulmonary function monitoring to identify disease progression. Key Points • ILD is common in systemic sclerosis, and a subset of patients with SSc-ILD develop PPF. • Patients with PPF more frequently exhibit vascular manifestations and distinct radiologic features, including mixed NSIP-UIP. • Regular longitudinal monitoring with pulmonary function tests is essential for early detection of disease progression in SSc-ILD.

PMID:42440242 | DOI:10.1007/s10067-026-08131-w

J Endocrinol Invest. 2026 Jul 13. doi: 10.1007/s40618-026-02984-3. Online ahead of print.

ABSTRACT

BACKGROUND: Testicular adrenal rest tumors (TARTs) are benign, hormonally responsive testicular lesions in male patients with congenital adrenal hyperplasia (CAH). TARTs represent a leading contributor to gonadal dysfunction and infertility in this population. This study aimed to investigate the clinical and genetic characteristics of TARTs and to identify clinical indicators that may facilitate their early detection.

METHODS: A retrospective cohort study included 38 male patients with biochemically and molecularly confirmed CAH who were followed at our pediatric endocrinology clinic between January 2019 and January 2025. Demographic characteristics, underlying enzymatic defects, CYP21A2 and CYP11B1 genotype, clinical phenotype, hormonal profiles-including adrenocorticotropic hormone (ACTH) and 17-hydroxyprogesterone (17-OHP) concentrations-pubertal status, skeletal maturation as assessed by bone age, and scrotal ultrasonographic findings were systematically retrieved from medical records and analyzed.

RESULTS: TARTs were identified in 14 of 38 patients, corresponding to a prevalence of 36.8%. Of the affected individuals, 12 (85.7%) harbored 21-hydroxylase deficiency and 2 (14.3%) had 11β-hydroxylase deficiency. No statistically significant differences were observed in ACTH or 17-OHP levels between patients with and without TART (p = 0.75 and p = 0.36, respectively). TARTs were significantly more prevalent among patients with the salt-wasting phenotype relative to other clinical forms (p = 0.002) and among pubertal compared with prepubertal patients (p = 0.016). Skeletal maturation, as reflected by bone age advancement, was significantly more pronounced in the TART-positive group (p = 0.012). Multivariable logistic regression analysis identified bone age advancement (OR = 1.76; 95% CI: 1.10-2.83; p = 0.019) and pubertal status (OR = 12.5; 95% CI: 1.7-91.6; p = 0.013) as factors independently associated with the presence of TART.

CONCLUSIONS: Bone age advancement was independently associated with the presence of TART and may represent a clinically useful marker associated with TART in male patients with CAH. These findings suggest that bone age assessment may complement isolated hormonal measurements and may help identify patients who could benefit from closer ultrasonographic surveillance. Early detection and timely therapeutic intervention remain important for preserving gonadal function and future fertility.

PMID:42440236 | DOI:10.1007/s40618-026-02984-3

Radiol Med. 2026 Jul 13. doi: 10.1007/s11547-026-02260-7. Online ahead of print.

ABSTRACT

PURPOSE: Clinical application of late iodine enhancement (LIE) for myocardial scar identification is limited by low contrast-to-noise ratio (CNR). Photon-counting detector-CT (PCD-CT) can improve image quality providing spectral information and low image noise. The aim of the study was to assess the impact of spectral analysis and reconstruction parameters on LIE image quality using PCD-CT.

MATERIAL AND METHODS: This single-center retrospective study included 74 patients undergoing PCD-CT between May 2024 and July 2025 for myocardial scar evaluation. Images from patients with visible LIE were reconstructed using four parameter combinations (Qr40 and Qr36 kernels; 0.4-mm and 2-mm slice thickness) and analyzed at monoenergetic levels (40-120 keV, 10 keV increment) using a dedicated workstation. CNR and signal-to-noise ratio (SNR) were calculated for each reconstruction.

RESULTS: Among 74 patients, 41 (55%) had myocardial scar (M:F 32:9; 62 years [IQR,56-71]) and 24/41 (59%) had an implantable cardioverter defibrillator (ICD). Scars were predominantly transmural (21/41, 51%). A 40-keV VMI achieved the highest CNR and SNR, regardless of reconstruction parameters (p < 0.05), with median CNR of 5.36 [IQR, 4.07-6.88] using 2-mm slice thickness and Qr36 kernel. Scar pattern, ICD, and BMI did not significantly affect either CNR or SNR (p > 0.05). In the exploratory subgroup of 16 patients undergoing LGE-MRI, CNR is not statistically different between LIE-CT at 40 keV with 2-mm slice thickness from LGE-MRI (5.36 [IQR,4.07-6.88] vs. 8.04 [IQR,6.67-9.89]; p = 0.178).

CONCLUSION: PCD-CT LIE demonstrated the highest CNR at 40-keV VMI with 2-mm slice thickness, regardless of scar pattern, BMI, or ICD presence.

PMID:42440227 | DOI:10.1007/s11547-026-02260-7

Bull Math Biol. 2026 Jul 13;88(8):135. doi: 10.1007/s11538-026-01702-7.

ABSTRACT

This paper provides a rigorous mathematical resolution of the open global stability problem for a “shock-and-kill” model of HIV-1/SIV infection in brain reservoirs recently formulated by Roda et al. (2021). The model explicitly incorporates the effects of latency-reversing agents and enhanced immune clearance of reactivated cells. We derive an explicit formula for the basic reproduction number $R_0$ , which serves as the sole threshold parameter governing viral eradication versus persistence and integrates infection pathways from both productive and latent compartments. By combining the next-generation matrix approach with an extended graph-theoretic Lyapunov method for multigraphs with parallel arcs, we rigorously establish that the disease-free equilibrium is globally asymptotically stable when $R_0\le 1$ , whereas a unique productive equilibrium exists and is globally asymptotically stable when $R_0>1$ . To resolve the sign-indefinite quadratic perturbations induced by structurally distinct parallel transmission arcs-a fundamental bottleneck of classical graph-theoretic Lyapunov schemes-we develop a refined composite Lyapunov framework equipped with hierarchically calibrated parameters. Systematic asymptotic scaling and multi-parameter tuning eliminate indefinite cyclic quadratic interactions, securing strict negative definiteness of the Lyapunov derivative and overcoming key limitations of conventional graph-based methods. These global stability results provide a definitive mathematical answer to whether therapeutic interventions guarantee viral eradication or lead to persistent brain-reservoir infection. Furthermore, they furnish a rigorous theoretical foundation for the “shock-and-kill” strategy and establish mathematically precise conditions to guide the design of safe, effective interventions for eliminating HIV-1/SIV from CNS reservoirs.

PMID:42440225 | DOI:10.1007/s11538-026-01702-7

Eur J Clin Microbiol Infect Dis. 2026 Jul 13. doi: 10.1007/s10096-026-05593-3. Online ahead of print.

ABSTRACT

BACKGROUND: Cellulitis is a common cause of hospital admission, yet the clinical relevance and predictors of bacteremia remain incompletely characterized. Identifying patients at risk of bloodstream infection may help optimize diagnostic strategies and clinical management.

METHODS: We conducted a retrospective observational study at a tertiary-care hospital including all consecutive patients hospitalized with cellulitis between January 2019 and December 2024. Patients without blood cultures were excluded. Clinical severity was stratified using the CREST classification. Microbiological data, antibiotic therapy, hospital outcomes, and follow-up at 1 and 3 months were analyzed.

RESULTS: Among 311 episodes included, bacteremia was confirmed in 46 cases (14.8%). Patients with bacteremia showed significantly higher clinical severity at admission, with CREST grades III-IV present in 56.5% compared with 36.6% in non-bacteremia patients (p < 0.001). Sepsis occurred in 65.2% of bacteremia cases versus 24.5% of non-bacteremia cases (p < 0.001). Bacteremia was associated with longer hospital stay (18 ± 18.3 vs 13 ± 9.7 days; p = 0.003) and more frequent antibiotic modifications during admission (p = 0.023). Streptococcal species and Staphylococcus aureus showed a higher propensity for bloodstream invasion. In-hospital mortality was higher among bacteremia patients (13.0% vs 7.9%), although the difference was not statistically significant. Three-month mortality reached 14.3% in the bacteremia group compared with 9.9% in non-bacteremia patients.

CONCLUSION: Bacteremia complicating cellulitis is uncommon but associated with greater clinical severity, longer hospitalization, and increased therapeutic complexity. Severity stratification tools such as CREST may assist in identifying patients at increased risk of bacteremia; however, given their limited discriminatory performance, they should not be used in isolation to guide blood culture collection or other clinical decisions.

PMID:42440220 | DOI:10.1007/s10096-026-05593-3

Discov Ment Health. 2026 Jul 13. doi: 10.1007/s44192-026-00536-y. Online ahead of print.

ABSTRACT

BACKGROUND: Mental health disorders including depression, anxiety, and substance use disorders affect an estimated 150 million people across Africa, yet services remain grossly under-resourced and largely inaccessible. In many settings, including Nigeria, limited awareness, stigmatizing attitudes, and suboptimal mental health practices further compound the burden. This study assessed knowledge, attitudes, and practices (KAP) toward mental health among adults in northwest Nigeria.

METHODS: We conducted a community-based cross-sectional study in Jigawa State, northwest Nigeria, guided by the classical Knowledge-Attitude-Practice (KAP) framework. A total of 398 adults were recruited using a multistage sampling technique. Data were collected through a combination of online surveys and interviewer-administered questionnaires. Statistical analyses were performed using IBM SPSS version 22.0, with significance set at p ≤ 0.05.

RESULTS: Participants had a mean age of 34.5 ± 8.2 years (range: 18-65), with 83.9% aged 25-45 years. Although 70.9% demonstrated adequate mental health knowledge, attitudes and practices were considerably poorer. Less than half expressed willingness to interact comfortably with individuals living with mental illness (43.2%), believed they could lead productive lives (44.2%), or had ever sought professional help for mental or emotional concerns (43.7%). Only 34.7% rejected the notion that individuals with mental illness are inherently dangerous, and just 20.4% would permit their children to interact with someone experiencing mental illness. Overall, 48.5% exhibited positive attitudes, and 46.7% reported satisfactory practices. Female sex independently predicted both knowledge and attitudes. Females were twice as likely as males to have adequate knowledge (aOR = 2.0; 95% CI: 1.1-3.6) and nearly twice as likely to demonstrate positive attitudes (aOR = 1.9; 95% CI: 1.1-3.5). Prior hospitalization and known family history of mental illness were significantly associated with more favorable attitudes. Residence in the southwest senatorial zone independently predicted satisfactory practices (aOR = 0.4; 95% CI: 0.2-0.9), while absence of prior mental illness was associated with lower odds of appropriate practices (aOR = 0.4; 95% CI: 0.2-0.9). Knowledge scores demonstrated moderate positive correlations with both attitudes (r = 0.4, p < 0.001) and practices (r = 0.4, p < 0.001).

CONCLUSION: Despite relatively adequate levels of knowledge, attitudes and practices toward mental health remain suboptimal among adults in northwest Nigeria. Consistent with the classical KAP framework, knowledge was positively associated with both attitudes and practices. Strengthening community-level mental health literacy, reducing stigma, and expanding accessible services are urgently needed to translate knowledge gains into improved behavioral outcomes.

PMID:42440215 | DOI:10.1007/s44192-026-00536-y

Drugs Real World Outcomes. 2026 Jul 13. doi: 10.1007/s40801-026-00568-4. Online ahead of print.

ABSTRACT

BACKGROUND: Rare cases of myocarditis and pericarditis following mRNA coronavirus disease-19 (COVID-19) vaccination have been reported, primarily among males under 30 years of age. Although the underlying mechanisms remain unclear, cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and obesity have been hypothesized as potential contributors. Using the Vaccine Adverse Event Reporting System (VAERS), this study investigated whether these comorbidities were disproportionately reported among young adult males with myocarditis or pericarditis following mRNA COVID-19 vaccination compared with vaccinated and general populations. Additionally, this study represents a novel application of disproportionality principles in spontaneous reporting databases to explore, beyond signal detection, the factors that might be associated with the occurrence of an adverse event.

METHODS: An observed-versus-expected analysis was conducted using reports of myocarditis or pericarditis following mRNA COVID-19 vaccination among males aged 18-30 recorded in VAERS between 2021 and 2022. The prevalence of hypertension, diabetes, dyslipidemia, and obesity among reported cases was compared with prevalence estimates derived from epidemiological studies of vaccinated populations and national population statistics. In addition, disproportionality analyses were performed using comparator groups consisting of reports associated with other vaccines and other adverse events following immunization (AEFIs) within VAERS.

RESULTS: A total of 859 eligible reports of myocarditis/pericarditis following mRNA COVID-19 vaccination were identified among males aged 18-30. The prevalence of hypertension, diabetes, dyslipidemia, and obesity was 0.35%, 0.58%, 0.81%, and 1.75%, respectively and was significantly lower than those reported in vaccinated and prepandemic general populations. In disproportionality analyses, myocarditis/pericarditis reports following mRNA vaccination showed higher prevalence of dyslipidemia and obesity, but lower prevalence of hypertension, compared with selected VAERS comparator groups. However, absolute comorbidity prevalence remained low across all groups.

CONCLUSIONS: No evidence of a modifying role for hypertension, diabetes, dyslipidemia, or obesity was observed for the increased reporting of myocarditis/pericarditis among young adult males following mRNA COVID-19 vaccination. Despite the limitations inherent to spontaneous reporting systems, this study highlights a novel application of disproportionality-based approaches within VAERS to explore potential risk modifiers of vaccine-related adverse events in a hypothesis-generating manner.

PMID:42440199 | DOI:10.1007/s40801-026-00568-4

Biometrics. 2026 Jul 1;82(3):ujag126. doi: 10.1093/biomtc/ujag126.

ABSTRACT

Emerging technologies enable continuous monitoring of temporal exposures to disease risk factors, leading to complex exposure processes characterized by subject-specific numbers and durations of exposure episodes. A key scientific question is how the number and duration of such episodes influence disease risk. Existing methods typically rely on scalar summaries or time-indexed representations and are not naturally suited to model duration-dependent risk accumulation at the episode level. We introduce the FLexible Accumulation ModEl (FLAME), a semiparametric model for risk accumulation at the level of individual exposure episodes, with duration as the primary driver of risk. FLAME is motivated by and applied to quantifying the association between the duration of intraoperative hypotension and acute kidney injury (AKI) following cardiac surgery. The estimated risk accumulation function reveals that, although 60 one-minute hypotensive episodes are associated with an AKI probability of 0.24, a single sustained 60-minute episode increases that probability to 0.33, representing a 38% increase despite identical total duration. These findings provide actionable insights for intraoperative hemodynamic management and demonstrate the importance of accounting for episodic exposure patterns. While motivated by cardiac surgery, FLAME is broadly applicable to other settings involving high-resolution temporal exposures. An R package, flameRisk, is provided to facilitate the application of the method in practice.

PMID:42439082 | DOI:10.1093/biomtc/ujag126

Biometrics. 2026 Jul 1;82(3):ujag125. doi: 10.1093/biomtc/ujag125.

ABSTRACT

Dynamic systems involving a population of subjects often feature significant variability among the individual trajectories. Mixed-effects ordinary differential equations (ODEs) provide a natural modeling framework for such systems, where subjects share the same functional form for the ODEs but have subject-specific parameters. However, inference for nonlinear mixed-effects ODE models remains challenging, particularly in settings where the system is only partially observed or the trajectories are highly sensitive to the model parameters. In pharmacokinetic modeling, for example, the observed data also tend to be sparse and noisy. To address these challenges, we propose an extension of manifold-constrained Gaussian processes for inference of general mixed-effects ODE models within a Bayesian statistical framework. We evaluate our method on simulated examples, demonstrating its ability to provide fast and accurate inference for parameters and trajectories using nested optimization. To illustrate the practical efficacy of the proposed method, we provide a real data analysis of a pharmacokinetic model used for an HIV combination therapy study.

PMID:42439081 | DOI:10.1093/biomtc/ujag125