Nevin Manimala

Elife. 2025 Nov 5;14:RP105734. doi: 10.7554/eLife.105734.

ABSTRACT

Numerous studies advocate for a rhythmic mode of perception. However, the evidence in the context of hearing remains inconsistent. We propose that the divergent conclusions drawn from previous work stem from conceptual and methodological issues. These include ambiguous assumptions regarding the origin of rhythmicity, variations in tasks and attentional demands, and differing analytical approaches for statistical testing. To address these points, we conducted a series of experiments in which human participants performed auditory tasks involving monaural targets presented against binaural white noise backgrounds, while also recording eye movements. These experiments varied in whether stimuli were presented randomly or required motor initialisation, the necessity of memory across trials, and the manipulation of attentional demands. Our findings challenge the notion of universal rhythmicity in hearing, but support the existence of paradigm- and ear-specific fluctuations in sensitivity and biases at multiple frequencies. The rhythmicity for sounds in the left and right ears appears independent among participants, and the rhythmicity in performance is possibly linked to oculomotor activity and attentional requirements. Overall, these results may help to resolve conflicting conclusions drawn in previous work and provide specific avenues for further studies into the rhythmicity of auditory perception.

PMID:41190483 | DOI:10.7554/eLife.105734

J R Soc Interface. 2025 Nov;22(232):20250649. doi: 10.1098/rsif.2025.0649. Epub 2025 Nov 5.

NO ABSTRACT

PMID:41190470 | DOI:10.1098/rsif.2025.0649

Ann Otol Rhinol Laryngol. 2025 Nov 5:34894251388843. doi: 10.1177/00034894251388843. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate extended outcomes up to 6 years following bipolar-cautery inferior turbinate reduction (ITR) in a large pediatric cohort.

METHODS: Retrospective case series of 326 children (mean age 9.0 ± 4.1 years) who underwent 12-W bipolar-cautery ITR between December 2017 and May 2024 at a single-surgeon tertiary practice. Concurrent procedures were performed in 82% of patients; 59 underwent ITR alone. Parent-reported nasal breathing improvement was assessed at regular intervals up to 6 years. Statistical analyses included Cochran’s Q tests and generalized estimating equations (GEE).

RESULTS: In the full cohort, nasal breathing improvement rates were: 95.4% at 3 months, 91.7% at 6 months, 90.2% at 1 year, 88.1% at 2 years, and 78.7% at 3 years. Sample sizes decreased beyond 3 years due to follow-up attrition. Cochran’s Q test showed significant changes over time through 3 years (Q = 60.101, P < .001). The ITR-only subgroup showed more marked decline: 98% improvement at 3 months to 69.0% at 3 years (P = .002), compared to more stable rates with concurrent surgery. GEE analysis confirmed significant time effects (P < .001). Compared to ITR alone, concurrent septoplasty (OR 0.39, P = .002) and sinus surgery (OR 0.34, P = .020) were each associated with significantly lower odds of reporting persistent symptoms (i.e., a greater likelihood of improvement). Complications remained low: minor bleeding (4.6%), major bleeding requiring intervention (1.2%), MRSA infection (0.3%), and synechiae (1.5%).

CONCLUSIONS: Bipolar-cautery ITR provides safe, effective symptom improvement with excellent short-term results (>90% at 1 year). However, efficacy declines over time, particularly in ITR-only patients (78.7% overall at 3 years). Concurrent airway procedures may provide more stable outcomes. These findings emphasize the need for long-term follow-up and appropriate patient selection.

PMID:41190463 | DOI:10.1177/00034894251388843

Liver Int. 2025 Dec;45(12):e70424. doi: 10.1111/liv.70424.

ABSTRACT

BACKGROUND AND AIMS: The effectiveness and safety of medications for alcohol use disorder (MAUD) in treating alcohol-associated cirrhosis have not been fully elucidated. This study aims to explore the clinical benefits and risks of MAUD in patients with alcohol-associated cirrhosis and persistent alcohol use.

METHODS: This retrospective cohort study utilised anonymised electronic health records (EHRs) from the TriNetX platform to evaluate the impact of MAUD on mortality, alcohol abstinence rates, hepatocellular carcinoma, hepatic decompensation and healthcare utilisation in patients with alcohol-associated cirrhosis.

RESULTS: This study evaluated 200 054 patients with alcohol-associated cirrhosis; after propensity score matching, 17 548 patients (8774 in each group) were analysed comparing those treated with MAUD to those without. At 3 years, patients treated with MAUD exhibited significantly lower mortality (21.6% vs. 29.3%, HR 0.731, 95% CI 0.688-0.776, p < 0.001), reduced hepatocellular carcinoma (2.6% vs. 3.3%, HR 0.794, p = 0.010) and fewer hospitalisations (16.7% vs. 24.8%, HR 0.635, p < 0.001). Subgroup analyses revealed that among 5083 patients treated with naltrexone, 3-year mortality was reduced (19.8% vs. 30.3%, HR 0.645, 95% CI 0.596-0.699, p < 0.001), hepatocellular carcinoma incidence was lower (2.6% vs. 3.3%, HR 0.790, p = 0.047) and hepatic decompensation decreased (18.4% vs. 21.1%, HR 0.843, p = 0.004). Among 4108 patients treated with acamprosate, 3-year mortality was reduced (22.6% vs. 29.0%, HR 0.799, 95% CI 0.733-0.871, p < 0.001) and hospitalisations and emergency department visits were significantly lower, though no reduction in hepatocellular carcinoma was observed.

CONCLUSION: This study demonstrates the significant benefits of MAUD in patients with alcohol-associated cirrhosis, including reduced mortality, lower healthcare utilisation and improved alcohol abstinence rates, supporting its integration into standard care protocols.

PMID:41190460 | DOI:10.1111/liv.70424

J Neuropsychol. 2025 Nov 5. doi: 10.1111/jnp.70020. Online ahead of print.

ABSTRACT

Reassessments with the Rey Auditory Verbal Learning Test (RAVLT) may generate learning effects, compromising the validity of the results. In Brazil, there are still no comparative studies between adapted versions of the test in healthy individuals. This study compared scores obtained on versions A and B of the RAVLT-A, routinely used in the neuropsychological assessment of patients with epilepsy and investigated the effects of age, education and version used. A prospective study with 188 cognitively healthy adults was randomly assigned to two groups (version A or B). Comparative analyses between groups and multivariate linear regression models were conducted to examine the impact of age, education and version on RAVLT-A scores. No significant differences were observed between versions A and B of the RAVLT-A (p > .05). Regression indicated a significant influence of age and, especially, education on performance on the test variables. The version used had no statistically relevant impact on the scores. This is the first Brazilian study to examine two adapted versions of the RAVLT-A in healthy adults. The findings demonstrate comparability between versions A and B, supporting their alternate use in reassessments to reduce practice effects. Age and, especially, education significantly influenced performance, emphasizing the need for normative data stratified by both variables, since those commonly used in Brazil are stratified only by age.

PMID:41190450 | DOI:10.1111/jnp.70020

Cancer Rep (Hoboken). 2025 Nov;8(11):e70396. doi: 10.1002/cnr2.70396.

ABSTRACT

BACKGROUND AND OBJECTIVES: Existing literature on ovarian masses necessitating intervention in children by pediatric surgeons and gynecologists in Low- and Middle-Income Countries is sparse and lacks collaborative standardization in management between the two subspecialties. Therefore, this study seeks to assess the range of ovarian masses presenting to these two specialties and to explore variations in management.

METHODS: A 15-year retrospective review of surgically biopsied or excised ovarian masses between subspecialties at two academic hospitals in Johannesburg.

RESULTS: We identified 288 patients, six with bilateral disease and 294 ovarian masses. The mean age was 13.34 years (SD ±5.12). The most common presentation was abdominal pain in 149/288 (51.74%); 117 patients (40.62%) were from pediatric surgery and 171 (59.38%) from gynecology departments. There were 127/288 (44.09%) non-neoplastic and 161/288 (55.90%) neoplastic lesions, of which 110/161 (68.33%) were benign and 51/161 (31.67%) malignant. The neoplastic lesions consisted of 107/161 (66.45%) germ cells, 28/161 (17.39%) surface epithelial tumors, and 26/161 (16.14%) sex cord-stromal tumors. Ovarian-sparing surgery was done in 56/288 (19.44%) patients, 22/117 (18.80%) in pediatric surgery, and 34/171 (19.88%) in gynecology. Laparoscopy was done in 57/288 (19.79%) patients, 24/117 (20.51%) in pediatric surgery, and 19/171 (19.29%) in gynecology. The survival rate in benign masses was 100%, and 86.28% in malignancies.

CONCLUSION: This study highlights the diverse spectrum of ovarian masses managed by pediatric surgeons and gynecologists. A laparoscopic approach combined with ovarian preservation, which was comparable between specialties, should be the preferred method for managing benign lesions whenever feasible. These findings underscore the need for standardized, collaborative guidelines between pediatric surgeons and gynecologists to ensure consistent and optimal management of ovarian masses in children.

PMID:41190447 | DOI:10.1002/cnr2.70396

Circ Genom Precis Med. 2025 Nov 5:e005233. doi: 10.1161/CIRCGEN.125.005233. Online ahead of print.

ABSTRACT

BACKGROUND: Atherosclerosis is a pathophysiological process common to a range of cardiovascular diseases. We reasoned that considering clinical presentations of atherosclerosis across the coronary, peripheral, and cerebrovasculature as a single entity would enhance statistical power to identify rare genetic variation driving pathological processes across multiple vascular beds.

METHODS: We performed an exome-wide association study of atherosclerotic cardiovascular disease in 434 438 UK Biobank participants of European ancestry.

RESULTS: We identified rare, predicted damaging variants in HTRA1, SGTB (small glutamine-rich tetratricopeptide repeat co-chaperone beta), and RBM12 to be associated with risk of atherosclerotic cardiovascular disease, independent of known risk factors. Both SGTB and HTRA1 were downregulated in the aorta of patients with coronary artery disease compared with controls. Loss-of-function variants in the RNA-binding protein RBM12 increased the risk of coronary, cerebrovascular, and peripheral vascular diseases to a similar extent. SGTB increased the risk of atherosclerotic cardiovascular disease in the coronary and peripheral circulations but not the cerebrovasculature. While loss-of-function variants in HTRA1 are known to cause monogenic stroke syndromes, we found that damaging missense variants in HTRA1 are associated with increased risk of disease in both the cerebrovascular and coronary circulation. Surprisingly, the increased risk of coronary artery disease was driven predominantly by a single missense variant (p.R227W; minor allele frequency, 0.009). In vitro, the R227W mutant HTRA1 efficiently proteolyzed the disordered substrate casein but not aggregated α-synuclein. In contrast, a stroke risk-raising variant (D320N) could not efficiently process any of the tested substrates.

CONCLUSIONS: We identified novel genetic variants predisposing to atherosclerotic cardiovascular diseases that act independently of established cardiovascular risk factors. The observed phenotypic and functional heterogeneities between HTRA1 variants suggest that distinct biochemical mechanisms drive HTRA1-related vascular disease in the brain and heart.

PMID:41190437 | DOI:10.1161/CIRCGEN.125.005233

J Oral Rehabil. 2025 Nov 5. doi: 10.1111/joor.70093. Online ahead of print.

ABSTRACT

BACKGROUND: The recently developed BruxScreen consists of two parts: BruxScreen-Q (self-report questionnaire) and BruxScreen-C (clinical assessment).

OBJECTIVES: To test the intra- and inter-rater reliability, construct validity, acceptability and feasibility of the BruxScreen-Q and BruxScreen-C and assess their concordance among Dutch dental students.

METHODS: 88 out of 109 potentially eligible dental master students completed a set of questionnaires two times (Q1; Q2) and participated in two clinical workshops (CE1; CE2), using the BruxScreen-Q and BruxScreen-C, respectively. Intra-rater reliability of the BruxScreen-Q and concordance between the BruxScreen-Q and BruxScreen-C were assessed using Cohen’s (weighted) Kappa. Intra- and inter-rater reliability of the BruxScreen-C were analysed using intraclass correlation coefficients calculated from generalised linear mixed-effects models. Construct validity of the BruxScreen-Q was tested using Spearman’s Rank Correlation or Mann-Whitney U test based on hypothesis testing. Acceptability and feasibility of the BruxScreen were assessed using descriptive statistics.

RESULTS: Intra-rater reliability for BruxScreen-Q was fair to substantial. Intra- and inter-rater reliability for BruxScreen-C varied from poor to excellent. BruxScreen-Q showed moderate construct validity, based on the acceptable consistency between the actual and hypothesised effect size of the questionnaire items. BruxScreen-Q (Q2) and BruxScreen-C (CE2) were found both acceptable and feasible by a majority of the students. There was no agreement between subject-based bruxism according to the BruxScreen-Q and clinically based bruxism according to the BruxScreen-C.

CONCLUSION: The BruxScreen demonstrates acceptable reliability, construct validity, acceptability and feasibility in assessing both subject-based bruxism and clinically based bruxism. However, there is a discrepancy between self-reported bruxism and the clinicians’ diagnosis.

PMID:41190434 | DOI:10.1111/joor.70093

Microbiologyopen. 2025 Dec;14(6):e70113. doi: 10.1002/mbo3.70113.

ABSTRACT

The beneficial effects of probiotics on the immune system are well established; however, the precise mechanisms underlying their action remain incompletely understood. To date, the impact of probiotics in home mechanically ventilated (HMV) patients has not been investigated. This study evaluated the effects of oral supplementation with Lacticaseibacillus rhamnosus GG ATCC 53103 (LGG) on nasal microbiota composition and selected immune parameters in HMV patients. Thirty-one individuals, following a 3-month probiotic-free washout period, received LGG at a dose of 8 × 10⁹ CFU/day for 6 months. Nasal swabs and blood samples were collected at baseline, and after 3 and 6 months, to assess nasal microflora, Th1/Th2 balance, and levels of IL-2, IL-4, IL-5, IL-10, TNF-α, and IFN-γ. A statistically significant increase in IL-2 was observed at both 3 and 6 months (p = 0.0307; p = 0.0001, respectively), along with a transient rise in IFN-γ at 3 months (p = 0.0253) and IL-4 at 6 months (p = 0.0297). The IFN-γ/IL-10 ratio also increased at 3 months (p = 0.0394). No significant changes were detected in the remaining cytokines or nasal bacterial flora. Notably, none of the participants required antibiotic therapy during the intervention period-contrasting with prior seasons, when at least one course was typically necessary. Given the critical role of IL-2 and IFN-γ in anti-infective immunity, their elevation may indicate enhanced resistance to infection, while increased IL-4 may reflect modulation of inflammation. These findings suggest that LGG supplementation, due to its safety, affordability, and immunomodulatory potential, may be a valuable adjunctive strategy to reduce infection risk and improve outcomes in HMV patients.

PMID:41190418 | DOI:10.1002/mbo3.70113

Clin Nephrol. 2025 Nov 5. doi: 10.5414/CN111790. Online ahead of print.

ABSTRACT

BACKGROUND: Roxadustat is used for treating chronic kidney disease (CKD) patients, particularly those on hemodialysis with comorbid cancer. Some studies suggest a link between roxadustat and cancer progression, but the mechanisms remain unclear, highlighting the need for further investigation into potential causal links.

MATERIALS AND METHODS: We employed a two-sample Mendelian randomization (MR) analysis to explore associations between genetic variations in Roxadustat targets and 14 cancer types. Single-nucleotide polymorphisms (SNPs) in the Egl-9 family hypoxia inducible factor 1 (EGLN1) and Egl-9 family hypoxia inducible factor 2 EGLN2 genes, related to hemoglobin levels, were chosen as instrumental variables. Analyses used inverse variance-weighted (IVW)-MR and summary data-based MR (SMR) approaches, assessing horizontal pleiotropy with Mendelian randomization Egger (MR-Egger) and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and using the heterogeneity in dependent instrumental variables (HEIDI) test for SMR.

RESULTS: Summary statistics were derived from three UK studies involving 172,925 individuals. IVW-MR revealed a positive association between EGLN1 variants and breast cancer (OR = 1.644) and lung adenocarcinoma (OR = 2.117), while negative associations were found for malignant non-melanoma skin cancer and kidney cancer. SMR confirmed the links to breast cancer and a decrease in skin cancer risk. EGLN2 expression was positively associated with prostate and lung cancers and negatively with estrogen receptor (ER)- breast and brain cancers.

CONCLUSION: Our findings support a potential causal relationship between the inhibition of EGLN1 and EGLN2 and the development of specific cancer types.

PMID:41190396 | DOI:10.5414/CN111790