Nevin Manimala

BMC Public Health. 2024 May 6;24(1):1241. doi: 10.1186/s12889-024-18724-2.

ABSTRACT

BACKGROUND: The impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database.

METHODS: 224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI.

RESULTS: After a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792-0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696-0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise.

CONCLUSIONS: In this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.

PMID:38711032 | DOI:10.1186/s12889-024-18724-2

BMC Genom Data. 2024 May 6;25(1):42. doi: 10.1186/s12863-024-01196-z.

ABSTRACT

BACKGROUND: Shallots are infected by various viruses like Onion yellow dwarf virus (OYDV), Leek yellow stripe virus (LYSV), Shallot latent virus (SLV) and Shallot virus X (ShVX). In India, they have been found to be persistently infected by ShVX. ShVX also infects onion and garlic in combination with other carlaviruses and potyviruses. ShVX is a member of genus Allexivirus of family Alphaflexiviridae. ShVX has a monopartite genome, which is represented by positive sense single-stranded RNA. Globally, only six complete and 3 nearly complete genome sequences of ShV X are reported to date. This number is insufficient to measure a taxon’s true molecular diversity. Moreover, the complete genome sequence of ShVX from Asia has not been reported as yet. Therefore, this study was undertaken to generate a complete genome sequence of ShVX from India.

RESULTS: Shallot virus X (ShVX) is one of the significant threats to Allium crop production. In this study, we report the first complete genome sequence of the ShVX from India through Next-generation sequencing (NGS). The complete genome of the ShVX (Accession No. OK104171), from this study comprised 8911 nucleotides. In-silico analysis of the sequence revealed variability between this isolate and isolates from other countries. The dissimilarities are spread all over the genome specifically some non-coding intergenic regions. Statistical analysis of individual genes for site-specific selection indicates a positive selection in NABP region. The presence of a recombination event was detected in coat protein region. The sequence similarity percentage and phylogenetic analysis indicate ShVX Indian isolate is a distinctly different isolate. Recombination and site-specific selection may have a function in the evolution of this isolate. This is the first detailed study of the ShVX complete genome sequence from Southeast Asia.

CONCLUSION: This study presents the first report of the entire genome sequence of an Indian isolate of ShVX along with an in-depth exploration of its evolutionary traits. The findings highlight the Indian variant as a naturally occurring recombinant, emphasizing the substantial role of recombination in the evolution of this viral species. This insight into the molecular diversity of strains within a specific geographical region holds immense significance for comprehending and forecasting potential epidemics. Consequently, the insights garnered from this research hold practical value for shaping ShVX management strategies and providing a foundation for forthcoming studies delving into its evolutionary trajectory.

PMID:38711021 | DOI:10.1186/s12863-024-01196-z

BMC Cancer. 2024 May 6;24(1):567. doi: 10.1186/s12885-024-12326-2.

ABSTRACT

BACKGROUND: Pyroptosis is a type of programmed cell death mediated by the gasdermin family. Gasdermin B (GSDMB), as a member of gasdermin family, can promote the occurrence of cell pyroptosis. However, the correlations of the GSDMB expression in colorectal cancer with clinicopathological predictors, immune microenvironment, and prognosis are unclear.

METHODS: Specimens from 267 colorectal cancer cases were analyzed by immunohistochemistry to determine GSDMB expression, CD3⁺, CD4⁺, and CD8⁺ T lymphocytes, CD20⁺ B lymphocytes, CD68⁺ macrophages, and S100A8⁺ immune cells. GSDMB expression in cancer cells was scored in the membrane, cytoplasm, and nucleus respectively. GSDMB⁺ immune cell density was calculated. Univariate and multivariate survival analyses were performed. The association of GSDMB expression with other clinicopathological variables and immune cells were also analyzed. Double immunofluorescence was used to identify the nature of GSDMB⁺ immune cells. Cytotoxicity assays and sensitivity assays were performed to detect the sensitivity of cells to 5-fluorouracil.

RESULTS: Multivariate survival analysis showed that cytoplasmic GSDMB expression was an independent favorable prognostic indicator. Patients with positive cytoplasmic or nuclear GSDMB expression would benefit from 5-fluorouracil based chemotherapy. The assays in vitro showed that high GSDMB expression enhanced the sensitivity of colorectal cancer cells to 5-fluorouracil. Patients with positive membranous or nuclear GSDMB expression had more abundant S100A8⁺ immune cells in the tumor invasive front. Positive nuclear GSDMB expression indicated more CD68⁺ macrophages in the tumor microenvironment. Moreover, GSDMB⁺ immune cell density in the stroma was associated with a higher neutrophil percentage but a lower lymphocyte counts and monocyte percentage in peripheral blood. Furthermore, the results of double immunofluorescence showed that GSDMB co-expressed with CD68 or S100A8 in stroma cells.

CONCLUSION: The GSDMB staining patterns are linked to its role in cancer progression, the immune microenvironment, systemic inflammatory response, chemotherapeutic efficacy, and prognosis. Colorectal cancer cells with high GSDMB expression are more sensitive to 5-fluorouracil. However, GSDMB expression in immune cells has different effects on cancer progression from that in cancer cells.

PMID:38711020 | DOI:10.1186/s12885-024-12326-2

BMC Genomics. 2024 May 6;25(1):444. doi: 10.1186/s12864-024-10364-5.

ABSTRACT

BACKGROUND: Normalization is a critical step in the analysis of single-cell RNA-sequencing (scRNA-seq) datasets. Its main goal is to make gene counts comparable within and between cells. To do so, normalization methods must account for technical and biological variability. Numerous normalization methods have been developed addressing different sources of dispersion and making specific assumptions about the count data.

MAIN BODY: The selection of a normalization method has a direct impact on downstream analysis, for example differential gene expression and cluster identification. Thus, the objective of this review is to guide the reader in making an informed decision on the most appropriate normalization method to use. To this aim, we first give an overview of the different single cell sequencing platforms and methods commonly used including isolation and library preparation protocols. Next, we discuss the inherent sources of variability of scRNA-seq datasets. We describe the categories of normalization methods and include examples of each. We also delineate imputation and batch-effect correction methods. Furthermore, we describe data-driven metrics commonly used to evaluate the performance of normalization methods. We also discuss common scRNA-seq methods and toolkits used for integrated data analysis.

CONCLUSIONS: According to the correction performed, normalization methods can be broadly classified as within and between-sample algorithms. Moreover, with respect to the mathematical model used, normalization methods can further be classified into: global scaling methods, generalized linear models, mixed methods, and machine learning-based methods. Each of these methods depict pros and cons and make different statistical assumptions. However, there is no better performing normalization method. Instead, metrics such as silhouette width, K-nearest neighbor batch-effect test, or Highly Variable Genes are recommended to assess the performance of normalization methods.

PMID:38711017 | DOI:10.1186/s12864-024-10364-5

Health Aff (Millwood). 2024 May;43(5):707-716. doi: 10.1377/hlthaff.2023.00742.

ABSTRACT

In July 2020, Hong Kong extended statutory paid maternity leave from ten weeks to fourteen weeks to align with International Labour Organization standards. We used the policy enactment as an observational natural experiment to assess the mental health implications of this policy change on probable postnatal depression (Edinburgh Postnatal Depression Scores of 10 or higher) and postpartum emotional well-being. Using an opportunistic observational study design, we recruited 1,414 survey respondents with births before (August 1-December 10, 2020) and after (December 11, 2020-July 18, 2022) policy implementation. Participants had a mean age of thirty-two, were majority primiparous, and were mostly working in skilled occupations. Our results show that the policy was associated with a 22 percent decrease in mothers experiencing postnatal depressive symptoms and a 33 percent decrease in postpartum emotional well-being interference. Even this modest change in policy, an additional four weeks of paid leave, was associated with significant mental health benefits. Policy makers should consider extending paid maternity leave to international norms to improve mental health among working mothers and to support workforce retention.

PMID:38709965 | DOI:10.1377/hlthaff.2023.00742

Health Aff (Millwood). 2024 May;43(5):725-731. doi: 10.1377/hlthaff.2023.01069.

ABSTRACT

Policy responses to the March 31, 2023, expiration of the Medicaid continuous coverage provision need to consider the difference between self-reported Medicaid participation on government surveys and administrative records of Medicaid enrollment. The difference between the two is known as the “Medicaid undercount.” The size of the undercount increased substantially after the continuous coverage provision took effect in March 2020. Using longitudinal data from the Current Population Survey, we examined this change. We found that assuming that all beneficiaries who ever reported enrolling in Medicaid during the COVID-19 pandemic public health emergency remained enrolled through 2022 (as required by the continuous coverage provision) eliminated the worsening of the undercount. We estimated that nearly half of the 5.9 million people who we projected were likely to become uninsured after the provision expired, or “unwound,” already reported that they were uninsured in the 2022 Current Population Survey. This finding suggests that the impact of ending the continuous coverage provision on the estimated uninsurance rate, based on self-reported survey data, may have been smaller than anticipated. It also means that efforts to address Medicaid unwinding should include people who likely remain eligible for Medicaid but believe that they are already uninsured.

PMID:38709963 | DOI:10.1377/hlthaff.2023.01069

Health Aff (Millwood). 2024 May;43(5):632-640. doi: 10.1377/hlthaff.2023.01163.

ABSTRACT

In March 2021, California implemented a vaccine equity policy that prioritized COVID-19 vaccine allocation to communities identified as least advantaged by an area-based socioeconomic measure, the Healthy Places Index. We conducted quasi-experimental and counterfactual analyses to estimate the effect of this policy on COVID-19 vaccination, case, hospitalization, and death rates. Among prioritized communities, vaccination rates increased 28.4 percent after policy implementation. Furthermore, an estimated 160,892 COVID-19 cases, 10,248 hospitalizations, and 679 deaths in the least-advantaged communities were averted by the policy. Despite these improvements, the share of COVID-19 cases, hospitalizations, and deaths in prioritized communities remained elevated. These estimates were robust in sensitivity analyses that tested exchangeability between prioritized communities and those not prioritized by the policy; model specifications; and potential temporal confounders, including prior infections. Correcting for disparities by strategically allocating limited resources to the least-advantaged or most-affected communities can reduce the impacts of COVID-19 and other diseases but might not eliminate health disparities.

PMID:38709962 | DOI:10.1377/hlthaff.2023.01163

Health Aff (Millwood). 2024 May;43(5):682-690. doi: 10.1377/hlthaff.2023.01098.

ABSTRACT

Women who are pregnant or recently gave birth are significantly more likely to be killed by an intimate partner than nonpregnant, nonpostpartum women of reproductive age, implicating the risk of fatal violence conferred by pregnancy itself. The rapidly increasing passage of state legislation has restricted or banned access to abortion care across the US. We used the most recent and only source of population-based data to examine the association between state laws that restrict access to abortion and trends in intimate partner violence-related homicide among women and girls ages 10-44 during the period 2014-20. Using robust difference-in-differences ecologic modeling, we found that enforcement of each additional Targeted Regulation of Abortion Providers (TRAP) law was associated with a 3.4 percent increase in the rate of intimate partner violence-related homicide in this population. We estimated that 24.3 intimate partner violence-related homicides of women and girls ages 10-44 were associated with TRAP laws implemented in the states and years included in this analysis. Assessment of policies that restrict access to abortion should consider their potential harm to reproductive-age women through the risk for violent death.

PMID:38709960 | DOI:10.1377/hlthaff.2023.01098

Proc Natl Acad Sci U S A. 2024 May 14;121(20):e2306287121. doi: 10.1073/pnas.2306287121. Epub 2024 May 6.

ABSTRACT

This study examines the impact of residential mobility on electoral participation among the poor by matching data from Moving to Opportunity, a US-based multicity housing-mobility experiment, with nationwide individual voter data. Nearly all participants in the experiment were Black and Hispanic families who originally lived in high-poverty public housing developments. Notably, the study finds that receiving a housing voucher to move to a low-poverty neighborhood decreased adult participants’ voter participation for nearly two decades-a negative impact equal to or outpacing that of the most effective get-out-the-vote campaigns in absolute magnitude. This finding has important implications for understanding residential mobility as a long-run depressant of voter turnout among extremely low-income adults.

PMID:38709927 | DOI:10.1073/pnas.2306287121

Proc Natl Acad Sci U S A. 2024 May 14;121(20):e2318855121. doi: 10.1073/pnas.2318855121. Epub 2024 May 6.

ABSTRACT

TipA, a MerR family transcription factor from Streptomyces lividans, promotes antibiotic resistance by sequestering broad-spectrum thiopeptide-based antibiotics, thus counteracting their inhibitory effect on ribosomes. TipAS, a minimal binding motif which is expressed as an isoform of TipA, harbors a partially disordered N-terminal subdomain that folds upon binding multiple antibiotics. The extent and nature of the underlying molecular heterogeneity in TipAS that shapes its promiscuous folding-function landscape is an open question and is critical for understanding antibiotic-sequestration mechanisms. Here, combining equilibrium and time-resolved experiments, statistical modeling, and simulations, we show that the TipAS native ensemble exhibits a pre-equilibrium between binding-incompetent and binding-competent substates, with the fully folded state appearing only as an excited state under physiological conditions. The binding-competent state characterized by a partially structured N-terminal subdomain loses structure progressively in the physiological range of temperatures, swells on temperature increase, and displays slow conformational exchange across multiple conformations. Binding to the bactericidal antibiotic thiostrepton follows a combination of induced-fit and conformational-selection-like mechanisms, via partial binding and concomitant stabilization of the binding-competent substate. These ensemble features are evolutionarily conserved across orthologs from select bacteria that infect humans, underscoring the functional role of partial disorder in the native ensemble of antibiotic-sequestering proteins belonging to the MerR family.

PMID:38709926 | DOI:10.1073/pnas.2318855121