Category: Nevin Manimala

Sci Rep. 2023 Jan 27;13(1):1487. doi: 10.1038/s41598-023-27695-0.

ABSTRACT

Most of the studies about mental health and quality of life of emerging adults have been conducted in developed countries and non-students’ population has been neglected, limiting the generalisation of the results to other socioeconomic realities. This paper reports the results of an observational study on differences between the two cohorts (students vs non-students) both on mental health and quality of life measures but also on demographic, lifestyle and mental health variables in emerging adults living in a middle-income country. Associations between variables and interactions in the prediction of both outcomes scores were explored to understand how much other variables may contribute to differences between the two groups. We found poorer mental health and worse health-related quality of life in the students than the non-students, although effect sizes were small. Differences between the groups on some sociodemographic predictor variables were statistically significant, showing fairly strong effects, for social status, sleeping hours and parenting, however, none of the predictor variables showed confounding with group effects on both outcomes. Developing countries are growing and work forces are changing, creating a huge global need to understand these changes and the effects on the mental health and quality of life of this evolving population.Registration: ClinicalTrials.gov (NCT04596345).

PMID:36707675 | DOI:10.1038/s41598-023-27695-0

Sci Rep. 2023 Jan 27;13(1):1553. doi: 10.1038/s41598-023-28549-5.

ABSTRACT

Certain cut-off points for sarcopenia screening and diagnosis are arbitrary and based on European populations, with normative references often obtained from healthy young adults. Although respiratory skeletal muscle strength tests represent low-cost clinical measures commonly performed in clinical practice by health professionals, a gap remains regarding whether respiratory skeletal muscle strength tests are adequate and sensitive measures for sarcopenia screening. This study aimed to verify the value of handgrip and respiratory muscle strength as possible discriminators to identify sarcopenia and to establish cut-off points for sarcopenia screening in community-dwelling, Brazilian women. In a cross-sectional study, 154 community-dwelling, Brazilian women (65-96 years) were assessed for appendicular skeletal muscle mass, handgrip (HGS), and respiratory muscular strength, including maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). The data were analyzed using the ROC curve and the Youden Index determined cut-off points. Statistical significance was set at 5%. 88 participants (57%) were sarcopenic. MEP (OR 0.98 [95%CI 0.97, 1.00], p = 0.023) and HGS (OR 0.82 [95% CI 0.75, 0.90], p < 0.001) were independent factors for sarcopenia in older. The optimal cut-off points for identifying sarcopenia were ≤ 77 cmH₂O for MEP (AUC = 0.72), and ≤ 20 kg for HGS (AUC = 0.80). Simple muscular strength tests, including HGS and MEP, may be considered in the identification of sarcopenia in older, community-dwelling, Brazilian women. Future work is still needed to assess external validation of the proposed cut-offs before the clinical application.

PMID:36707661 | DOI:10.1038/s41598-023-28549-5

NPJ Precis Oncol. 2023 Jan 27;7(1):14. doi: 10.1038/s41698-023-00352-5.

ABSTRACT

Advances in computational algorithms and tools have made the prediction of cancer patient outcomes using computational pathology feasible. However, predicting clinical outcomes from pre-treatment histopathologic images remains a challenging task, limited by the poor understanding of tumor immune micro-environments. In this study, an automatic, accurate, comprehensive, interpretable, and reproducible whole slide image (WSI) feature extraction pipeline known as, IMage-based Pathological REgistration and Segmentation Statistics (IMPRESS), is described. We used both H&E and multiplex IHC (PD-L1, CD8+, and CD163+) images, investigated whether artificial intelligence (AI)-based algorithms using automatic feature extraction methods can predict neoadjuvant chemotherapy (NAC) outcomes in HER2-positive (HER2+) and triple-negative breast cancer (TNBC) patients. Features are derived from tumor immune micro-environment and clinical data and used to train machine learning models to accurately predict the response to NAC in breast cancer patients (HER2+ AUC = 0.8975; TNBC AUC = 0.7674). The results demonstrate that this method outperforms the results trained from features that were manually generated by pathologists. The developed image features and algorithms were further externally validated by independent cohorts, yielding encouraging results, especially for the HER2+ subtype.

PMID:36707660 | DOI:10.1038/s41698-023-00352-5

Pharm Stat. 2023 Jan 27. doi: 10.1002/pst.2290. Online ahead of print.

ABSTRACT

Here we present as case study how re-randomization tests were performed in two randomized, controlled clinical trials as sensitivity analyses, as recommended by the United States Food and Drug Administration in the context of adaptive randomization. This was done to confirm primary conclusions on immunological noninferiority of an investigational new fully liquid presentation of a quadrivalent cross-reacting material conjugate meningococcal vaccine (MenACWY-CRM), over its licensed lyophilized/liquid presentation. In two phase 2b studies (Study #1: NCT03652610; Study #2: NCT03433482), noninferiority of the fully liquid presentation of MenACWY-CRM to the licensed presentation was assessed and demonstrated for immune responses against meningococcal serogroup A (MenA), the only vaccine component modified from lyophilized to liquid in the new presentation. The original vaccine assignment algorithm, with a minimization procedure accounting for center or center within age strata, was used to re-randomize participants belonging to the fully liquid and licensed vaccine groups while keeping antibody responses, covariates and entry order as observed. Test statistics under re-randomization were generated according to the ANCOVA model used in the primary analysis. To confirm immunological noninferiority following re-randomization, the corresponding p-values had to be <0.025. For both studies and all primary objective evaluations, the re-randomization p-values were well below 0.025 (0.0004 for Study #1; 0.0001 for the two co-primary endpoints in Study #2). Re-randomization tests performed to comply with a regulatory request confirmed the primary conclusions of immunological noninferiority for the MenA of the fully liquid compared to the licensed vaccine presentation.

PMID:36707656 | DOI:10.1002/pst.2290

Nat Hum Behav. 2023 Jan;7(1):15-26. doi: 10.1038/s41562-022-01497-2. Epub 2023 Jan 26.

ABSTRACT

Flexibility in the design, analysis and interpretation of scientific studies creates a multiplicity of possible research outcomes. Scientists are granted considerable latitude to selectively use and report the hypotheses, variables and analyses that create the most positive, coherent and attractive story while suppressing those that are negative or inconvenient. This creates a risk of bias that can lead to scientists fooling themselves and fooling others. Preregistration involves declaring a research plan (for example, hypotheses, design and statistical analyses) in a public registry before the research outcomes are known. Preregistration (1) reduces the risk of bias by encouraging outcome-independent decision-making and (2) increases transparency, enabling others to assess the risk of bias and calibrate their confidence in research outcomes. In this Perspective, we briefly review the historical evolution of preregistration in medicine, psychology and other domains, clarify its pragmatic functions, discuss relevant meta-research, and provide recommendations for scientists and journal editors.

PMID:36707644 | DOI:10.1038/s41562-022-01497-2

Eur J Hum Genet. 2023 Jan 27. doi: 10.1038/s41431-022-01257-w. Online ahead of print.

ABSTRACT

Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07-2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08-1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs.

PMID:36707629 | DOI:10.1038/s41431-022-01257-w

Sci Rep. 2023 Jan 27;13(1):1548. doi: 10.1038/s41598-023-28809-4.

NO ABSTRACT

PMID:36707616 | DOI:10.1038/s41598-023-28809-4

NPJ Parkinsons Dis. 2023 Jan 27;9(1):11. doi: 10.1038/s41531-023-00462-8.

ABSTRACT

There is growing evidence that patients with type 2 diabetes mellitus (DM) have an increased risk of developing Parkinson’s disease (PD) and share similar dysregulated pathways. We aimed to determine whether the risk of PD increases as diabetes progresses among patients with type 2 DM. Using a nationally representative database from the Korean National Health Insurance System, 2,362,072 individuals (≥40 years of age) with type 2 DM who underwent regular health checkups during 2009-2012 were followed up until the end of 2018. The diabetes severity score parameters included the number of oral hypoglycemic agents, diabetes duration, insulin use, or presence of chronic kidney disease, diabetic retinopathy, or cardiovascular disease. Each of these characteristics was scored as one unit of diabetes severity and their sum was defined as a diabetes severity score from 0-6. We identified 17,046 incident PD cases during the follow-up. Each component of the diabetes severity score showed a similar intensity for the risk of PD. Compared with subjects with no parameters, HR values (95% confidence intervals) of PD were 1.09 (1.04-1.15) in subjects with one diabetes severity score parameter, 1.28 (1.22-1.35) in subjects with two parameters, 1.55 (1.46-1.65) in subjects with three parameters, 1.96 (1.82-2.11) in subjects with four parameters, 2.08 (1.83-2.36) in subjects with five parameters, and 2.78 (2.05-3.79) in subjects with six parameters. Diabetes severity was associated with an increased risk of developing PD. Severe diabetes may be a risk factor for the development of PD.

PMID:36707543 | DOI:10.1038/s41531-023-00462-8

Commun Med (Lond). 2023 Jan 27;3(1):11. doi: 10.1038/s43856-023-00244-6.

ABSTRACT

BACKGROUND: The oxytocin receptor gene (OXTR) is regulated, in part, by DNA methylation. This mechanism has implications for uterine contractility during labor and for prevention or treatment of postpartum hemorrhage, an important contributor to global maternal morbidity and mortality.

METHODS: We measured and compared the level of OXTR DNA methylation between matched blood and uterine myometrium to evaluate blood as an indicator of uterine methylation status using targeted pyrosequencing and sites from the Illumina EPIC Array. Next, we tested for OXTR DNA methylation differences in blood between individuals who experienced a postpartum hemorrhage arising from uterine atony and matched controls following vaginal birth. Bivariate statistical tests, generalized linear modeling and Poisson regression were used in the analyses.

RESULTS: Here we show a significant positive correlation between blood and uterine DNA methylation levels at several OXTR loci. Females with higher OXTR DNA methylation in blood had required significantly more exogenous oxytocin during parturition. With higher DNA methylation, those who had oxytocin administered during labor had significantly greater relative risk for postpartum hemorrhage (IRR 2.95, 95% CI 1.53-5.71).

CONCLUSIONS: We provide evidence that epigenetic variability in OXTR is associated with the amount of oxytocin administered during parturition and moderates subsequent postpartum hemorrhage. Methylation can be measured using a peripheral tissue, suggesting potential use in identifying individuals susceptible to postpartum hemorrhage. Future studies are needed to quantify myometrial gene expression in connection with OXTR methylation.

PMID:36707542 | DOI:10.1038/s43856-023-00244-6

Sci Rep. 2023 Jan 27;13(1):1498. doi: 10.1038/s41598-023-28794-8.

ABSTRACT

Bambara groundnut has significant role to play in terms of food security, even though researchers in agriculture have paid very little attention to the crop in the past. This study aimed to investigate the high-yielding accessions in three environments. A total of 34 phenological, vegetative and yield traits were measured and analyzed statistically with R software. There were significant differences in all the traits except for plant height, initial plant stand, panicle length per stem, and petiole length. Across the three environments, TVSU-455 gave the highest values for the total number of pods (42.67), final plant stands (7.67), fresh seed weights (45.83), number of seeds per plant (46.62), hundred seed weight with a value (124.56), dry seed weight (27.14), fresh pod weight (92.65), harvest index of 0.57, yield per plot (45.83) and unshelled yield per plot (550.26). TVSU-455 was the only accession in cluster I of the dendrogram based on its superiority over other accessions. The clustering analysis produced a dendrogram categorizing the 15 accessions into 4 groups based on the vegetative, phenological, and yield traits. There were significant differences among the correlations of the 34 traits. The first two principle components explained 56.16% of the total variation with each dimension accounting for 39.85% and 16. 31% variation, respectively. TVSU-455 can be recommended for stability analysis.

PMID:36707537 | DOI:10.1038/s41598-023-28794-8