Category: Nevin Manimala

Bioinformatics. 2022 Feb 10:btac076. doi: 10.1093/bioinformatics/btac076. Online ahead of print.

ABSTRACT

MOTIVATION: The identification of pathways and biological processes from differential gene expression is central for interpretation of data collected by transcriptomics assays. Gene-Set Enrichment Analysis (GSEA) is the most common used algorithm to calculate the significance of the relevancy of an annotated gene set with a differential expression signature. To compute significance, GSEA implements permutation tests which are slow and inaccurate for comparing many differential expression signatures to thousands of annotated gene sets.

RESULTS: Here we present blitzGSEA, an algorithm that is based on the same running sum statistic as GSEA, but instead of performing permutations, blitzGSEA approximates the enrichment score probabilities based on Gamma distributions. blitzGSEA achieves dramatic improvement in performance compared with prior GSEA implementations, while approximating small p-values more accurately.

AVAILABILITY: A python package, together with all source code, and a detailed user guide are available from GitHub at: https://github.com/MaayanLab/blitzgsea.

SUPPLEMENTARY INFORMATION: Supplementary text and figures are available at Bioinformatics online.

PMID:35143610 | DOI:10.1093/bioinformatics/btac076

JAMA. 2022 Feb 10. doi: 10.1001/jama.2022.1645. Online ahead of print.

ABSTRACT

IMPORTANCE: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits.

OBJECTIVE: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion.

DESIGN, SETTING, AND PARTICIPANTS: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3.

INTERVENTIONS: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52).

MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death.

RESULTS: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%).

CONCLUSIONS AND RELEVANCE: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

PMID:35143603 | DOI:10.1001/jama.2022.1645

Am J Occup Ther. 2022 Mar 1;76(2):7602205030. doi: 10.5014/ajot.2022.046912.

ABSTRACT

IMPORTANCE: Asian-Americans are more likely than other ethnic groups to care for older family members and less likely to seek mental health services. The research on caregiver burden among Asian-American intergenerational caregivers is limited.

OBJECTIVE: To investigate how spirituality and mental health help-seeking attitudes correlate with and predict perceived feelings of caregiver burden among Asian-American caregivers. Favorable mental health help-seeking attitudes were predicted to negatively correlate with caregiver burden, and spirituality was predicted to negatively correlate with and negatively predict caregiver burden.

DESIGN: Quantitative survey research.

SETTING: Community mental health.

PARTICIPANTS: One hundred one participants were recruited using the following inclusion criteria: Asian-Americans who currently or previously provided care to an Asian family member at least one generation older than the caregiver for at least 1 mo and in the past 3 yr. Outcomes and Measures: Items from the Burden Scale for Family Caregivers, Spirituality Scale, Expressions of Spirituality Inventory-Revised, Mental Help Seeking Attitudes Scale, and Self-Stigma of Seeking Psychological Help measured caregiver burden, spirituality, and mental health help-seeking attitudes.

RESULTS: A statistically significant negative correlation was found between caregiver burden and spirituality and between caregiver burden and mental health help-seeking attitudes. Spirituality and number of domains of care were statistically significant predictors of caregiver burden.

CONCLUSIONS AND RELEVANCE: Spirituality was found to negatively predict caregiver burden among Asian-American intergenerational caregivers. Mental health help-seeking attitudes were negatively correlated with caregiver burden. Occupational therapy practitioners have the opportunity to integrate spirituality and culturally sensitive mental health promotion into their services to Asian-Americans. What This Article Adds: Evidence that spirituality is a negative predictor of caregiver burden for Asian-American intergenerational caregivers offers a unique opportunity for occupational therapy practitioners to offer alternative methods of mental health promotion with this population. Understanding that spirituality and mental health help-seeking attitudes are culturally mediated allows practitioners to be informed about a dynamic in Asian-American culture.

PMID:35143608 | DOI:10.5014/ajot.2022.046912

PLoS One. 2022 Feb 10;17(2):e0263628. doi: 10.1371/journal.pone.0263628. eCollection 2022.

ABSTRACT

BACKGROUND: Migraines is likely to play a protective role in the risk of breast cancer. Some studies have shown that there is an inverse relationship between migraine and breast cancer, and some studies have not found an association; therefore, results from previous studies have been inconclusive and we conducted a meta-analysis to evaluate association between migraine and breast cancer.

METHODS: PubMed, EMBASE, Scopus and Web of Science were searched to identify studies on the association between migraine and breast cancer from January 1, 2000 through March 12, 2021. The pooled relative risk (RR) and the 95% confidence intervals (CI) was used to measure this relationship by assuming a random effects meta-analytic model.

RESULTS: A total of 10 studies were included. Our study revealed that there was statistically significant inverse relationship between migraine and breast cancer in case-control studies 0.68 [95% CI: 0.56, 0.82], but no significant relationship was found in cohort studies 0.98 [95% CI: 0.91, 1.06]. Also, migraine reduced the risk of ductal carcinoma 0.84 [95% CI: 0.73, 0.96], and lobular carcinoma 0.83 [95% CI: 0.73, 0.96]. With respect to ER_PR status no association between migraine and breast cancer was found. We found no evidence of publication bias.

CONCLUSION: Our analysis demonstrated a statistically significantly inverse relationship between migraine and total risk of breast cancer only in case-control studies. In summary, cohort studies do not support an inverse association between migraine and incident breast cancer. While in case-control studies, migraine has an inverse association with ductal carcinoma and lobular carcinoma of breast.

PMID:35143585 | DOI:10.1371/journal.pone.0263628

PLoS One. 2022 Feb 10;17(2):e0263708. doi: 10.1371/journal.pone.0263708. eCollection 2022.

ABSTRACT

BACKGROUND: Pertussis or whooping cough is a vaccine-preventable, highly contagious, respiratory illness caused by Bordetella pertussis or Bordetella parapertussis. Infants and young children have remained most susceptible to pertussis-related morbidity and mortality. The aim of this study was to investigate pertussis infection and analyze the associated factors involved in the occurrence of the cases.

METHODS: Community-based case-control was conducted in Dahena district, Northwest Ethiopia, from March 27-April 30, 2019. All cases ages 1-18 years old were identified by using the clinical standard case definition of pertussis adopted from World Health Organization (WHO). Data was collected using a structured questionnaire via face-to-face interviews. The data collected was cleaned, coded and entered into Epi info version 7.2.1.0 and exported to SPSS version 23 for statistical analysis. Bivariable and multivariable logistic regression analysis were employed to identify predictors. Factors with a p-value of < 0.05 were considered as independent risk factors of pertussis infection in multivariable logistic regression analysis.

RESULT: A total of 122 pertussis cases were enrolled from the Azila cluster of the Dahena district. Of these figures, 64 (52.5%) were females. The overall attack rate (AR) of pertussis cases in the cluster was 8.6/10000 population. The sex-specific AR of females was 8.9/10000 population. The multivariable logistic regression analysis showed that; being unvaccinated 4.17 (AOR, 4.17, 95% CI, 1.914-9.091), contact to cases 2.93 (AOR: 2.93, 95% CI 1.223-6.996), and living in a house with no window 2.6 (AOR: 2.6(95% CI 1.071 to 6.322) were the independent significantly risk factors for pertussis infection.

CONCLUSION: The contributing factor for pertussis infection was associated with case-contact, living in the house without windows and being unvaccinated. Wag Hemra Zone and Dahena district health office should encourage the vaccination activities of the cluster health center and awareness for the community should be practiced to limit disease transmission.

PMID:35143575 | DOI:10.1371/journal.pone.0263708

PLoS One. 2022 Feb 10;17(2):e0263809. doi: 10.1371/journal.pone.0263809. eCollection 2022.

ABSTRACT

BACKGROUND: Maternity waiting home (MWH) is a direct strategy to improve newborn and maternal survival. The utilization of MWH, however, remains very low in Ethiopia. Men involvement in maternal health programs is a key strategy to increase utilization of maternal health services, including MWH. This study defines men involvement in-terms of men’s participation in deciding to admit their spouse to an MWH, accompanying their spouse to an MWH, providing financial support, availing food at an MWH, and taking care of the home or children. Thus, the current study aims to identify factors affecting men’s involvement in MWH utilization.

METHODS: A community-based cross-sectional study was conducted from October 1st to December 30th, 2018. Four hundred three men were involved in the study. Data were analyzed by the statistical package for social science (SPSS) version 23. Independent predictors were identified by a multivariable logistic regression model. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were reported.

RESULTS: Men’s involvement in MWH was 55.6% (50.71, 60.45). Age (AOR = 0.86, 95% CI = 0.82-0.94), knowledge about MWH (AOR = 4.74, 95% CI = 2.65-8.49), decision-making power (AOR = 4.00, 95% CI = 1.38-11.57), and receiving counseling about MWH during spousal antenatal care visits (AOR = 9.15, 95% CI = 3.34-25.03) had statistically significant associations with men’s involvement in MWH utilization.

CONCLUSIONS: Nearly, half of the male partners were involved in MWH utilization. Men’s age, MWH knowledge, decision-making power, and receiving counseling were factors affecting their involvement in MWH utilization. Interventions targeting to improve male involvement in MWH utilization should focus on building men’s knowledge about MWH, increasing male involvement in ANC with an appropriate level of counseling about MWH, and changing patriarchal thinking in society with appropriate behavioral interventions such as community-based health education.

PMID:35143556 | DOI:10.1371/journal.pone.0263809

PLoS One. 2022 Feb 10;17(2):e0263717. doi: 10.1371/journal.pone.0263717. eCollection 2022.

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate the sex-related differences on the risks of perioperative and late outcomes for adult acute aortic dissection (AAD) patients following surgical management.

METHODS AND RESULTS: By using Taiwan National Health Insurance Research Database, totally 1,410 female and 3,432 male patients were identified to first-ever receive type A AAD open surgery or type B AAD stenting treatment from 2004 to 2013. We assessed the sex-related difference on outcomes, including in-hospital mortality, all-cause mortality, aortic death, redo aortic surgery, ischemic stroke, and depression during the follow-up period. The analysis was done separately for type A and type B surgeries.

RESULTS: On average, female patients diagnosed with AAD were older than males. There was no significant sex difference of in-hospital mortality or all-cause mortality for both type A open and type B stent surgeries. The risk of redo aortic surgery was significantly greater in males than females (7.8% vs. 4%; unadjusted subdistribution hazard ratio [SHR] 0.51, 95% CI 0.38-0.69) for type A open surgery, but not for type B stent surgery. Noticeably, the risk of newly-diagnosed depression was significantly greater in females than males (8% vs. 5.1%; unadjusted SHR 1.6, 95% CI 1.24-2.06) for type A open surgery, but not for type B stent surgery.

CONCLUSIONS: No significant sex-related difference was found for the in-hospital mortality or accumulative all-cause mortality. However, there were more redo aortic surgeries for males and more postoperative depression for females in type A AAD population.

PMID:35143568 | DOI:10.1371/journal.pone.0263717

PLoS One. 2022 Feb 10;17(2):e0263367. doi: 10.1371/journal.pone.0263367. eCollection 2022.

ABSTRACT

This work presents a tool for forecasting the spread of the new coronavirus in Mexico City, which is based on a mathematical model with a metapopulation structure that uses Bayesian statistics and is inspired by a data-driven approach. The daily mobility of people in Mexico City is mathematically represented by an origin-destination matrix using the open mobility data from Google and the Transportation Mexican Survey. This matrix is incorporated in a compartmental model. We calibrate the model against borough-level incidence data collected between 27 February 2020 and 27 October 2020, while using Bayesian inference to estimate critical epidemiological characteristics associated with the coronavirus spread. Given that working with metapopulation models leads to rather high computational time consumption, and parameter estimation of these models may lead to high memory RAM consumption, we do a clustering analysis that is based on mobility trends to work on these clusters of borough separately instead of taken all of the boroughs together at once. This clustering analysis can be implemented in smaller or larger scales in different parts of the world. In addition, this clustering analysis is divided into the phases that the government of Mexico City has set up to restrict individual movement in the city. We also calculate the reproductive number in Mexico City using the next generation operator method and the inferred model parameters obtaining that this threshold is in the interval (1.2713, 1.3054). Our analysis of mobility trends can be helpful when making public health decisions.

PMID:35143548 | DOI:10.1371/journal.pone.0263367

PLoS One. 2022 Feb 10;17(2):e0263174. doi: 10.1371/journal.pone.0263174. eCollection 2022.

ABSTRACT

The factor structure of neuropsychological functioning among a large sample (N = 831) of American youth (ages 12-21 at baseline) was investigated in order to identify an optimal model. Candidate models were selected based on their potential to provide service to the study of adolescent development and the effects of heavy episodic alcohol consumption. Data on neuropsychological functioning were obtained from the NCANDA study. This is a longitudinal community study of the effects of alcohol exposure on neurodevelopment. Three conceptually motivated and one empirically motivated factor analysis model of neuropsychological domains were compared based on penalized-likelihood selection criteria and model fit statistics. Two conceptually-motivated models were found to have adequate fit and pattern invariance to function as a measurement model for the Penn Computerized Neurocognitive Battery (Penn CNB) anchored neuropsychological battery in NCANDA. Corroboration of previous factor analysis models was obtained, in addition to the identification of an alternative factor model that has higher discriminant capacity for neuropsychological domains hypothesized to be most sensitive to alcohol exposure in human adolescents. The findings support the use of a factor model developed originally for the Penn CNB and a model developed specifically for the NCANDA project. The NCANDA 8-Factor Model has conceptual and empirical advantages that were identified in the current and prior studies. These advantages are particularly valuable when applied in alcohol research settings.

PMID:35143554 | DOI:10.1371/journal.pone.0263174

PLoS One. 2022 Feb 10;17(2):e0263402. doi: 10.1371/journal.pone.0263402. eCollection 2022.

ABSTRACT

Biologics targeting PD-1, PD-L1, and CTLA-4 immune checkpoint proteins have been used in a variety of tumor types including small and non-small cell lung cancers, melanoma, and renal cell carcinoma. Their anti-tumor activity is achieved through amplifying components of the patient’s own immune system to target immune response evading cancer cells. However, this unique mechanism of action causes a range of immune related adverse events, irAEs, that affect multiple physiological systems in the body. These irAEs, depending on severity, often cause suspension or discontinuation of therapy and, in rare cases, may lead to fatal outcomes. In this study we focused on pembrolizumab, a PD-1 inhibitor currently approved for multiple types of cancer. We analyzed over ten thousand adverse event reports from Keynote clinical trials of pembrolizumab for various cancer indications with or without co-occurring infections, and observed a statistically significant 80% increase in the risk of developing an irAE in subjects with infections.

PMID:35143542 | DOI:10.1371/journal.pone.0263402