Tag: nevin manimala

Phys Rev Lett. 2023 Jun 23;130(25):257101. doi: 10.1103/PhysRevLett.130.257101.

ABSTRACT

Irreversibility is commonly quantified by entropy production. An external observer can estimate it through measuring an observable that is antisymmetric under time reversal like a current. We introduce a general framework that allows us to infer a lower bound on entropy production through measuring the time-resolved statistics of events with any symmetry under time reversal, in particular, time-symmetric instantaneous events. We emphasize Markovianity as a property of certain events rather than of the full system and introduce an operationally accessible criterion for this weakened Markov property. Conceptually, the approach is based on snippets as particular sections of trajectories between two Markovian events, for which a generalized detailed balance relation is discussed.

PMID:37418719 | DOI:10.1103/PhysRevLett.130.257101

Phys Rev Lett. 2023 Jun 23;130(25):258201. doi: 10.1103/PhysRevLett.130.258201.

ABSTRACT

The statistics of noise emitted by ultrathin crumpled sheets is measured while they exhibit logarithmic relaxations under load. We find that the logarithmic relaxation advanced via a series of discrete, audible, micromechanical events that are log-Poisson distributed (i.e., the process becomes a Poisson process when time stamps are replaced by their logarithms). The analysis places constraints on the possible mechanisms underlying the glasslike slow relaxation and memory retention in these systems.

PMID:37418710 | DOI:10.1103/PhysRevLett.130.258201

Aesthet Surg J. 2023 Jul 7:sjad214. doi: 10.1093/asj/sjad214. Online ahead of print.

ABSTRACT

BACKGROUND: The volume and position of the buccal fat pad (BFP) were reported to change with age, which manifests as a hollow midface. Previous studies showed that autologous fat grafting for BFP augmentation could effectively ameliorate midfacial hollowing.

OBJECTIVES: We aimed to introduce a modified fat grafting technique for female patients with midfacial hollowing to restore the volume of BFP, and to evaluate the safety and effectiveness thereof.

METHODS: Two cadavers were used for the dissection of the BFP and the demonstration of our surgical procedures. Forty-eight patients were treated for midfacial hollowing with our modified grafting strategy. Through a percutaneous zygomatic incision, we filled the BFP and observed an immediate amelioration in the hollow area. Improvements were evaluated by Ogee line and its Ogee angle, Face-Q questionnaires, and three-party satisfaction ratings. Clinical profiles were reviewed and statistically analysed.

RESULTS: The Ogee angle was 6.6 ± 1.9° pre-operatively and 3.9 ± 1.4° post-operatively (average reduction, 2.7°). Patients’ Ogee lines were smoother post-operatively, with marked improvements in overall appearance, psychological well-being, and social confidence. Patients reported high satisfaction with decision-making and post-operative outcomes and felt 6.61 ± 2.21 years younger. Overall, 88%, 76%, and 83% of the cases were graded as good and excellent in improvement by surgeon, patient, and the third party, respectively.

CONCLUSIONS: For age-dependent midfacial hollowing in female patients, our modified percutaneous grafting technique was safe and efficacious in restoring BFP volume. With this technique, a smoother Ogee line and a natural, younger midfacial contour could be achieved.

PMID:37418635 | DOI:10.1093/asj/sjad214

J Craniofac Surg. 2023 Jul 6. doi: 10.1097/SCS.0000000000009501. Online ahead of print.

ABSTRACT

This study aimed to evaluate the postsurgical effects from 5 years on the palate after surgical repair of the lip at 3 or 9 months of age in children with cleft lip and palate. Eighty-four digitized dental impressions were divided into the following groups: group 1 (G1): lip surgery at 3 months of life; group 2 (G2): lip surgery at 9 months of life; group 3 (G3): without orofacial cleft. Five angular (C’IC, ICM, IC’M’, CMM’, and C’M’M) and 3 linear parameters (C-C’, c-c’, and M-M’) were evaluated. Statistical analysis was applied with α=5%. Intraclass Correlation Coefficient was significantly smaller in G1 than in G3 (P=0.005), while IC’M’ was significantly smaller in G3 than in G1 (P<0.001). C’M’M was significantly smaller in G1 than in G2 and G3 (P<0.001). The distances C-C’ and c-c’ were significantly smaller in G1 than in G2 and G3 (P<0.001). There was a statistically significant difference in both G1 and G2 (P<0.001, in all) in the analysis of palatal symmetry. Linear regression analysis showed that the, 11.2% of outcomes determined by c-c’ distance can be explained by the age of lip repair (P=0.013). In conclusion, lip surgery at 3 months of life showed a tendency toward more restriction in 5-year postsurgery palate development. The age of cheiloplasty is one of the factors that can influence palatal development; however, other factors may be associated and should be studied.

PMID:37418613 | DOI:10.1097/SCS.0000000000009501

Mol Oncol. 2023 Jul 7. doi: 10.1002/1878-0261.13487. Online ahead of print.

ABSTRACT

Histone-lysine N-methyltransferase SETD2 (SETD2), the sole histone methyltransferase that catalyzes trimethylation of lysine 36 on histone H3 (H3K36me3), is often mutated in clear cell renal cell carcinoma (ccRCC). SETD2 mutation and/or loss of H3K36me3 is linked to metastasis and poor outcome in ccRCC patients. Epithelial-to-mesenchymal transition (EMT) is a major pathway that drives invasion and metastasis in various cancer types. Here, using novel kidney epithelial cell lines isogenic for SETD2, we discovered that SETD2 inactivation drives EMT and promotes migration, invasion and stemness in a transforming growth factor beta (TGF-β)-independent manner. This newly identified EMT program is triggered in part through secreted factors, including cytokines and growth factors, and through transcriptional reprogramming. RNA-seq and assay for transposase-accessible chromatin sequencing (ATAC-seq) uncovered key transcription factors upregulated upon SETD2 loss, including SOX2, POU2F2 (OCT2) and PRRX1, that could individually drive EMT and stemness phenotypes in SETD2 wild-type cells. Public expression data from SETD2 wild-type/mutant ccRCC support the EMT transcriptional signatures derived from cell line models. In summary, our studies reveal that SETD2 is a key regulator of EMT phenotypes through cell-intrinsic and cell-extrinsic mechanisms that help explain the association between SETD2 loss and ccRCC metastasis.

PMID:37418588 | DOI:10.1002/1878-0261.13487

AIDS. 2023 Jul 7. doi: 10.1097/QAD.0000000000003646. Online ahead of print.

ABSTRACT

OBJECTIVE: Viral failure in people living with HIV (PLWH) may be influenced by multiple socio-behavioral, clinical, and context-specific factors, and supervised learning approaches may identify novel predictors. We compared the performance of two supervised learning algorithms to predict viral failure in four African countries.

DESIGN: Cohort study.

METHODS: The African Cohort Study is an ongoing, longitudinal cohort enrolling PLWH at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. Participants underwent physical examination, medical history-taking, medical record extraction, socio-behavioral interviews, and laboratory testing. In cross-sectional analyses of enrollment data, viral failure was defined as a viral load ≥1000 copies/mL among participants on antiretroviral therapy (ART) for at least six months. We compared the performance of lasso-type regularized regression and random forests by calculating area under the curve (AUC) and used each to identify factors associated with viral failure; 94 explanatory variables were considered.

RESULTS: Between January 2013 and December 2020, 2,941 PLWH were enrolled, 1,602 had been on ART for at least 6 months, and 1,571 participants with complete case data were included. At enrollment, 190 (12.0%) had viral failure. The lasso regression model was slightly superior to the random forest in its ability to identify PLWH with viral failure (AUC: 0.82 vs 0.75). Both models identified CD4 count, ART regimen, age, self-reported ART adherence and duration on ART as important factors associated with viral failure.

CONCLUSION: These findings corroborate existing literature primarily based on hypothesis-testing statistical approaches and help to generate questions for future investigations that may impact viral failure.

PMID:37418549 | DOI:10.1097/QAD.0000000000003646

PLoS Genet. 2023 Jul 7;19(7):e1010539. doi: 10.1371/journal.pgen.1010539. Online ahead of print.

ABSTRACT

Predicting phenotypes from genotypes is a fundamental task in quantitative genetics. With technological advances, it is now possible to measure multiple phenotypes in large samples. Multiple phenotypes can share their genetic component; therefore, modeling these phenotypes jointly may improve prediction accuracy by leveraging effects that are shared across phenotypes. However, effects can be shared across phenotypes in a variety of ways, so computationally efficient statistical methods are needed that can accurately and flexibly capture patterns of effect sharing. Here, we describe new Bayesian multivariate, multiple regression methods that, by using flexible priors, are able to model and adapt to different patterns of effect sharing and specificity across phenotypes. Simulation results show that these new methods are fast and improve prediction accuracy compared with existing methods in a wide range of settings where effects are shared. Further, in settings where effects are not shared, our methods still perform competitively with state-of-the-art methods. In real data analyses of expression data in the Genotype Tissue Expression (GTEx) project, our methods improve prediction performance on average for all tissues, with the greatest gains in tissues where effects are strongly shared, and in the tissues with smaller sample sizes. While we use gene expression prediction to illustrate our methods, the methods are generally applicable to any multi-phenotype applications, including prediction of polygenic scores and breeding values. Thus, our methods have the potential to provide improvements across fields and organisms.

PMID:37418505 | DOI:10.1371/journal.pgen.1010539

PLoS One. 2023 Jul 7;18(7):e0288335. doi: 10.1371/journal.pone.0288335. eCollection 2023.

ABSTRACT

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world’s population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the “Medicines for Malaria Venture” organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds’ ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 μM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 μM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 μM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.

PMID:37418497 | DOI:10.1371/journal.pone.0288335

PLoS Genet. 2023 Jul 7;19(7):e1010807. doi: 10.1371/journal.pgen.1010807. Online ahead of print.

ABSTRACT

Germline mutation is the mechanism by which genetic variation in a population is created. Inferences derived from mutation rate models are fundamental to many population genetics inference methods. Previous models have demonstrated that nucleotides flanking polymorphic sites-the local sequence context-explain variation in the probability that a site is polymorphic. However, limitations to these models exist as the size of the local sequence context window expands. These include a lack of robustness to data sparsity at typical sample sizes, lack of regularization to generate parsimonious models and lack of quantified uncertainty in estimated rates to facilitate comparison between models. To address these limitations, we developed Baymer, a regularized Bayesian hierarchical tree model that captures the heterogeneous effect of sequence contexts on polymorphism probabilities. Baymer implements an adaptive Metropolis-within-Gibbs Markov Chain Monte Carlo sampling scheme to estimate the posterior distributions of sequence-context based probabilities that a site is polymorphic. We show that Baymer accurately infers polymorphism probabilities and well-calibrated posterior distributions, robustly handles data sparsity, appropriately regularizes to return parsimonious models, and scales computationally at least up to 9-mer context windows. We demonstrate application of Baymer in three ways-first, identifying differences in polymorphism probabilities between continental populations in the 1000 Genomes Phase 3 dataset, second, in a sparse data setting to examine the use of polymorphism models as a proxy for de novo mutation probabilities as a function of variant age, sequence context window size, and demographic history, and third, comparing model concordance between different great ape species. We find a shared context-dependent mutation rate architecture underlying our models, enabling a transfer-learning inspired strategy for modeling germline mutations. In summary, Baymer is an accurate polymorphism probability estimation algorithm that automatically adapts to data sparsity at different sequence context levels, thereby making efficient use of the available data.

PMID:37418489 | DOI:10.1371/journal.pgen.1010807

PLoS One. 2023 Jul 7;18(7):e0288227. doi: 10.1371/journal.pone.0288227. eCollection 2023.

ABSTRACT

This study investigated the relationship between psychological skills and fitness levels among elite taekwondo athletes. A total of ten Iranian male elite taekwondo athletes (mean age of 20.6±2 years, BMI 18.78±0.62 kg/m2, and fat percentage of 8.87±1.46%) participated in the study. The Sports Emotional Intelligence Questionnaire, Sports Success Scale, Sport Mental Toughness Questionnaire, and Mindfulness Inventory for Sport were used to assess psychological factors. The Wingate test was used to determine anaerobic power, and the Bruce test to determine aerobic fitness. Descriptive statistics and Spearman rank correlation coefficients were utilised to examine any relationships between subscales. Statistically significant correlations were recorded between the evaluation of feelings (EI scale) and VO2peak (ml/kg/min) (r = -0.70, p = 0.0235) and between social skills (EI scale) and relative peak power (W/kg) (r = 0.84, p = 0.0026). Also, between optimism (EI scale) and VO2peak (ml/kg/min) (r = -0.70, p = 0.0252) and between optimism (EI scale) and HR-MAX (r = -0.75, p = 0.0123); and, finally, between control (mental toughness scale) and relative peak power (W/kg) (r = 0.67, p = 0.0360). These findings demonstrate relationships between psychological factors and the advantages of good anaerobic and aerobic capabilities. Finally, the study also demonstrated that elite taekwondo athletes have high mental performance abilities that are interrelated with anaerobic and aerobic performance.

PMID:37418479 | DOI:10.1371/journal.pone.0288227