Tag: pubmed

PLoS Genet. 2022 Jun 16;18(6):e1010251. doi: 10.1371/journal.pgen.1010251. Online ahead of print.

ABSTRACT

More than a decade of genome-wide association studies (GWASs) have identified genetic risk variants that are significantly associated with complex traits. Emerging evidence suggests that the function of trait-associated variants likely acts in a tissue- or cell-type-specific fashion. Yet, it remains challenging to prioritize trait-relevant tissues or cell types to elucidate disease etiology. Here, we present EPIC (cEll tyPe enrIChment), a statistical framework that relates large-scale GWAS summary statistics to cell-type-specific gene expression measurements from single-cell RNA sequencing (scRNA-seq). We derive powerful gene-level test statistics for common and rare variants, separately and jointly, and adopt generalized least squares to prioritize trait-relevant cell types while accounting for the correlation structures both within and between genes. Using enrichment of loci associated with four lipid traits in the liver and enrichment of loci associated with three neurological disorders in the brain as ground truths, we show that EPIC outperforms existing methods. We apply our framework to multiple scRNA-seq datasets from different platforms and identify cell types underlying type 2 diabetes and schizophrenia. The enrichment is replicated using independent GWAS and scRNA-seq datasets and further validated using PubMed search and existing bulk case-control testing results.

PMID:35709291 | DOI:10.1371/journal.pgen.1010251

PLoS One. 2022 Jun 16;17(6):e0270150. doi: 10.1371/journal.pone.0270150. eCollection 2022.

ABSTRACT

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

PMID:35709239 | DOI:10.1371/journal.pone.0270150

PLoS One. 2022 Jun 16;17(6):e0269893. doi: 10.1371/journal.pone.0269893. eCollection 2022.

ABSTRACT

This Korean population-based study aimed to describe the patterns of hypothyroidism after adjuvant radiation therapy (RT) in patients with breast cancer. The Korean Health Insurance Review and Assessment Service database was searched for patients with invasive breast carcinomas. We calculated the cumulative incidence and incidence rates per 1,000 person-years of subsequent hypothyroidism and compared them using the log-rank test and the Cox proportional hazards model. Between 2007 and 2018, 117,135 women diagnosed with breast cancer with a median follow-up time of 4.6 years were identified. The 8-year incidence of hypothyroidism was 9.3% in patients treated with radiation and 8.6% in those treated without radiation (p = 0.002). The incidence rates per 1,000 person-years in the corresponding treatment groups were 6.2 and 5.7 cases, respectively. The hazard ratio (HR) in patients receiving RT was 1.081 (95% confidence interval [CI], 1.013-1.134; p = 0.002). After mastectomy, RT showed a trend toward a higher risk of hypothyroidism (HR = 1.248; 95% CI, 0.977-1.595; p = 0.076). Our study provides one of the largest population-based data analyses regarding the risk of hypothyroidism among Korean patients with breast cancer. The adjusted risk for patients treated with RT exceeded that for patients with breast cancer treated without RT. The effect was evident immediately after treatment and lasted up to approximately 9 years.

PMID:35709221 | DOI:10.1371/journal.pone.0269893

PLoS One. 2022 Jun 16;17(6):e0270019. doi: 10.1371/journal.pone.0270019. eCollection 2022.

ABSTRACT

OBJECTIVES: The objective of this research aimed to investigate the correlation involving serum albumin with diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).

METHODS: From 2011 to 2020, the National Health and Nutrition Examination Survey (NHANES) surveyed 45462 participants. We used the relevant data to conduct descriptive statistics, linear regression, and Logistic regression analysis.

RESULTS: After adjusting for age, sex, and race, as well as all other variables, serum albumin was significantly negatively related to DR (P<0.001). Furthermore, after controlling for confounding factors, the third quartile (Q3) and the fourth quartile (Q4) had quite a negative significant relationship with the incidence of DR (P<0.01). The second quartile had a significant positive correlation with DR, whereas the observed negative correlations were not statistically meaningful (P>0.05).

CONCLUSION: Albumin levels in the serum have a quantitatively significant negative correlation with DR. Serum albumin levels in the blood can be used as a reference point for protracted follow-up of people with T2DM.

PMID:35709212 | DOI:10.1371/journal.pone.0270019

PLoS One. 2022 Jun 16;17(6):e0267144. doi: 10.1371/journal.pone.0267144. eCollection 2022.

ABSTRACT

BACKGROUND: Since the COVID-19 pandemic, the demand for online courses has increased enormously. Therefore, finding new methods to improve medical education is imperative.

OBJECTIVE: The aim of this study was to compare the self-reports of the individual student-centered virtual teaching techniques (seminar versus fishbowl) in a group of medical students.

METHODS: During the second semester of 2020, students in the clinical phase of the study (n = 144) participated in the optional subject of Sports Medicine. The students were divided into 2 groups. One group (n = 72) received the knowledge transfer in the form of a virtual seminar, the other group (n = 72) in the form of a virtual fishbowl.

RESULTS: Virtual seminar and virtual fishbowl students gave insights into these teaching techniques. Most of the students from the virtual fishbowl group believed that the virtual fishbowl format allowed them to be more actively involved in learning. The mean quiz scores were statistically higher for students in the virtual fishbowl group than students in the virtual seminar group (p < 0. 001).

CONCLUSION: This study concluded that virtual seminars and virtual fishbowl formats could be served as structured learning and teaching formats. At the same time, the virtual fishbowl format can promote an active exchange of knowledge from students’ perspectives.

PMID:35709198 | DOI:10.1371/journal.pone.0267144

PLoS One. 2022 Jun 16;17(6):e0269369. doi: 10.1371/journal.pone.0269369. eCollection 2022.

ABSTRACT

Recently there have been tremendous efforts to develop statistical procedures which allow to determine subgroups of patients for which certain treatments are effective. This article focuses on the selection of prognostic and predictive genetic biomarkers based on a relatively large number of candidate Single Nucleotide Polymorphisms (SNPs). We consider models which include prognostic markers as main effects and predictive markers as interaction effects with treatment. We compare different high-dimensional selection approaches including adaptive lasso, a Bayesian adaptive version of the Sorted L-One Penalized Estimator (SLOBE) and a modified version of the Bayesian Information Criterion (mBIC2). These are compared with classical multiple testing procedures for individual markers. Having identified predictive markers we consider several different approaches how to specify subgroups susceptible to treatment. Our main conclusion is that selection based on mBIC2 and SLOBE has similar predictive performance as the adaptive lasso while including substantially fewer biomarkers.

PMID:35709188 | DOI:10.1371/journal.pone.0269369

PLoS One. 2022 Jun 16;17(6):e0269339. doi: 10.1371/journal.pone.0269339. eCollection 2022.

ABSTRACT

Use of face coverings has been shown to reduce transmission of SARS-CoV-2. Despite encouragements from the CDC and other public health entities, resistance to usage of masks remains, forcing government entities to create mandates to compel use. The state of Oklahoma did not create a state-wide mask mandate, but numerous municipalities within the state did. This study compares case rates in communities with mandates to those without mandates, at the same time and in the same state (thus keeping other mitigation approaches similar). Diagnosed cases of COVID-19 were extracted from the Oklahoma State Department of Health reportable disease database. Daily case rates were established based upon listed city of residence. The daily case rate difference between each locality with a mask mandate were compared to rates for the portions of the state without a mandate. All differences were then set to a d0 point of reference (date of mandate implementation). Piecewise linear regression analysis of the difference in SARS-CoV-2 infection rates between mandated and non-mandated populations before and after adoption of mask mandates was then done. Prior to adopting mask mandates, those municipalities that eventually adopted mandates had higher transmission rates than the rest of the state, with the mean case rate difference per 100,000 people increasing by 0.32 cases per day (slope of difference = 0.32; 95% CI 0.13 to 0.51). For the post-mandate time period, the differences are decreasing (slope of -0.24; 95% CI -0.32 to -0.15). The pre- and post- mandate slopes differed significantly (p<0.001). The change in slope direction (-0.59; 95% CI -0.80 to -0.37) shows a move toward reconvergence in new case diagnoses between the two populations. Compared to rates in communities without mask mandates, transmission rates of SARS-CoV-2 slowed notably in those communities that adopted a mask mandate. This study suggests that government mandates may play a role in reducing transmission of SARS-CoV-2, and other infectious respiratory conditions.

PMID:35709189 | DOI:10.1371/journal.pone.0269339

PLoS One. 2022 Jun 16;17(6):e0269995. doi: 10.1371/journal.pone.0269995. eCollection 2022.

ABSTRACT

OBJECTIVE: To assess association between Hashimoto thyroiditis (HT) and clinical outcomes of papillary thyroid carcinoma (PTC).

METHODS: Databases including Pubmed, Embase, Cochrane Library, and Web of Science were searched. Weighed mean differences (WMDs) and odds ratios (ORs) were used to evaluate association between HT and clinical outcomes of PTC, and the effect size was represented by 95% confidence intervals (CIs). Heterogeneity test was performed for each indicator. If the heterogeneity statistic I2≥50%, random-effects model analysis was carried out, otherwise, fixed-effect model analysis was performed. Sensitivity analysis was performed for all outcomes, and publication bias was tested by Begg’s test.

RESULTS: Totally 47,237 patients in 65 articles were enrolled in this study, of which 12909 patients with HT and 34328 patients without HT. Our result indicated that PTC patients with HT tended to have lower risks of lymph node metastasis (OR: 0.787, 95%CI: 0.686-0.903, P = 0.001), distant metastasis (OR: 0.435, 95%CI: 0.279-0.676, P<0.001), extrathyroidal extension (OR: 0.745, 95%CI: 0.657-0.845, P<0.001), recurrence (OR: 0.627, 95%CI: 0.483-0.813, P<0.001), vascular invasion (OR: 0.718, 95%CI: 0.572-0.901, P = 0.004), and a better 20-year survival rate (OR: 1.396, 95%CI: 1.109-1.758, P = 0.005) while had higher risks of multifocality (OR: 1.245, 95%CI: 1.132-1.368, P<0.001), perineural infiltration (OR: 1.922, 95%CI: 1.195-3.093, P = 0.007), and bilaterality (OR: 1.394, 95%CI: 1.118-1.739, P = 0.003).

CONCLUSIONS: PTC patients with HT may have favorable clinicopathologic characteristics, compared to PTCs without HT. More prospective studies are needed to further elucidate this relationship.

PMID:35709179 | DOI:10.1371/journal.pone.0269995

PLoS One. 2022 Jun 16;17(6):e0269911. doi: 10.1371/journal.pone.0269911. eCollection 2022.

ABSTRACT

BACKGROUND: Dementia is a big medical and socioeconomic problem on aging society, and cardiac diseases have already shown a significant contribution to developing dementia. However, the risk of dementia related to hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has never been evaluated.

METHODS: In a large-scale longitudinal cohort using National Health Insurance database, 4,645 subjects with HCM aged ≥50 years between 2010 and 2016 were collected and matched with 13,935 controls, based on propensity scores (1:3). We investigated the incidence and risk of dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) between groups.

RESULTS: During follow-up (median 3.9 years after 1-year lag), incident dementia occurred in 739 subjects (4.0%): 78.2% for AD and 13.0% for VaD. The incidence of dementia, AD, and VaD were 23.0, 18.0, and 2.9/1,000 person-years, respectively, and was generally more prevalent in HCM. HCM group had a 50% increased risk of dementia, particularly AD, whereas there was no difference in the risk of VaD. The impact of HCM on AD (HR 1.52, 95% CI 1.26-1.84, p<0.001) was comparable with that of diabetes mellitus and smoking. Increased risk of AD in relation to HCM was consistent in various subgroups including younger healthier population.

CONCLUSIONS: This is the first to demonstrate the increased risk of dementia, mainly AD rather than VaD, in subjects with HCM. Early surveillance and active prevention for cognitive impairment could help for a better quality of life in an era that HCM is considered a chronic manageable disease with low mortality.

PMID:35709174 | DOI:10.1371/journal.pone.0269911

PLoS One. 2022 Jun 16;17(6):e0269921. doi: 10.1371/journal.pone.0269921. eCollection 2022.

ABSTRACT

INTRODUCTION: Consumer escalation systems allow patients and families to escalate concerns about acute clinical deterioration. Hospital staff can impact upon the success of this process. As part of evaluation processes within a Local Health Network, where a consumer escalation system was introduced in accordance with National requirements, we sought to explore clinicians’ understanding and perceptions of consumer escalation.

METHODS: Voluntary and anonymous staff surveys pre, and post, system introduction. Quantitative data was analysed using descriptive statistics, chi-square independence, and non-parametric independent samples median tests. Qualitative data was evaluated using content analysis and cross-referenced with quantitative responses.

RESULTS: Respondent’s (pre: 215; post: 89) area of work varied significantly between survey periods. Most agreed that patients/families have a sound knowledge of a patient’s typical health status (pre: 192/215 (89.3%); post 82/88 (93.2%)) and that patients/families should be encouraged to escalate concerns of deterioration to ward staff (pre: 209/212 (98.6%); post: 85/89 (95.5%)). Respondent perceptions of patient/family ability to recognise clinical deterioration varied. Staff agreement towards local response expectations decreased as the degree of clinical requirement increased. Staff concerns of increased workloads (pre: 90/214 (42.1%); post 12/72 (16.7%), p<0.001) and conflict generation (pre: 71/213 (33.3%); post: 7/71 (9.9%), p = 0.001) decreased significantly following system introduction. However, clinician perceptions of positive system effects also decreased (patient-staff rapport pre: 163/213 (76.5%); post: 38/72 (52.8%), p = 0.001; patient centred care pre: 188/214 (87.9%); post: 53/72 (73.6%), p = 0.012; patient safety pre: 173/214 (80.8%); post: 49/72 (68.1%), p = 0.077). Only 53% of respondents (pre: 112/213 (52.6%); post: 48/88 (54.5%)) perceived that patient/family have sufficient confidence to escalate concerns.

CONCLUSION: Consumer escalation systems require staff support. Staff perceptions may indicate, and act as, barriers to the operation of consumer escalation processes. Further exploration in identifying and managing staff barriers is crucial to the success of consumer escalation.

PMID:35709173 | DOI:10.1371/journal.pone.0269921