Tag: pubmed

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

Aust J Prim Health. 2024 May;30:PY23046. doi: 10.1071/PY23046.

ABSTRACT

Background Antidepressant use has continually increased in recent decades and although they are an effective treatment for moderate-to-severe depression, when there is no longer a clinical benefit, deprescribing should occur. Currently, routine deprescribing is not part of clinical practice and research shows that there has been an increase in antidepressant users seeking informal support online. This small scoping exercise used a mixed-methods online survey to investigate the motives antidepressant users have for joining social media deprescribing support groups, and what elements of the groups are most valuable to them. Methods Thirty members of two antidepressant deprescribing Facebook groups completed an online survey with quantitative and open-text response questions to determine participant characteristics and motivation for group membership. Quantitative data were analysed using descriptive statistics, and open-text responses were analysed thematically through NVivo. Results Two overarching themes were evident: first, clinician expertise , where participants repeatedly reported a perceived lack of skills around deprescribing by their clinician, not being included in shared decision-making about their treatment, and symptoms of withdrawal during deprescribing going unaddressed. Motivated by the lack of clinical support, peer support developed as the second theme. Here, people sought help online where they received education, knowledge sharing and lived experience guidance for tapering. The Facebook groups also provided validation and peer support, which motivated people to continue engaging with the group. Conclusions Antidepressant users who wish to cease their medication are increasingly subscribing to specialised online support groups due to the lack of information and support from clinicians. This study highlights the ongoing need for such support groups. Improved clinician understanding about the complexities of antidepressant deprescribing is needed to enable them to effectively engage in shared decision-making with their patients.

PMID:38709900 | DOI:10.1071/PY23046

JMIR Hum Factors. 2024 May 6;11:e49519. doi: 10.2196/49519.

ABSTRACT

BACKGROUND: Cigarette smoking remains one of the leading causes of preventable death worldwide. A worldwide study by the World Health Organization concluded that more than 8 million people die every year from smoking, tobacco consumption, and secondhand smoke. The most effective tobacco cessation programs require personalized human intervention combined with costly pharmaceutical supplementation, making them unaffordable or inaccessible to most tobacco users. Thus, digital interventions offer a promising alternative to these traditional methods. However, the leading smartphone apps available in the market today have either not been studied in a clinical setting or are unable to match the smoking cessation success rates of their expensive offline counterparts. We would like to understand whether QuitSure, a novel smoking cessation app built by Rapidkart Online Private Limited, is able to bridge this efficacy gap and deliver affordable and effective smoking cessation at scale.

OBJECTIVE: Our objective was to do an initial exploration into the engagement, efficacy, and safety of QuitSure based on the self-reported experiences of its users. Outcomes measured were program completion, the effect of program completion on smoking behavior, including self-reported cessation outcomes, and negative health events from using the app.

METHODS: All QuitSure registered users who created their accounts on the QuitSure app between April 1, 2021, and February 28, 2022, were sent an anonymized web-based survey. The survey results were added to their engagement data on the app to evaluate the feasibility and efficacy of the app as a smoking cessation intervention. The data were analyzed using descriptive statistics (frequencies and percentages) and the χ² test of independence.

RESULTS: In total, 1299 users who had completed the QuitSure program submitted the survey and satisfied the inclusion criteria of the study. Of these, 1286 participants had completed the program more than 30 days before filling out the survey, and 1040 (80.1%, 95% CI 79.1%-82.6%) of them had maintained prolonged abstinence for at least 30 days after program completion. A majority of participants (770/891, 86.4%) who were still maintaining abstinence at the time of submitting the survey did not experience any severe nicotine withdrawal symptoms, while 41.9% (373/891) experienced no mild withdrawal symptoms either. Smoking quantity prior to completing the program significantly affected quit rates (P<.001), with heavy smokers (>20 cigarettes per day) having a lower 30-day prolonged abstinence rate (relative risk=0.91; 95% CI 90.0%-96.2%) compared to lighter smokers. No additional adverse events outside of known nicotine withdrawal symptoms were reported.

CONCLUSIONS: The nature of web-based surveys and cohort selection allows for extensive unknown biases. However, the efficacy rates of survey respondents who completed the program were high and provide a case for further investigation in the form of randomized controlled trials on the QuitSure tobacco cessation program.

PMID:38709553 | DOI:10.2196/49519