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Nevin Manimala Statistics

Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

Sci Rep. 2021 Sep 28;11(1):19260. doi: 10.1038/s41598-021-98691-5.

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

PMID:34584155 | DOI:10.1038/s41598-021-98691-5

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Nevin Manimala Statistics

Association between early ventricular arrhythmias and mortality in destination vs. bridge patients on continuous flow LVAD support

Sci Rep. 2021 Sep 28;11(1):19196. doi: 10.1038/s41598-021-98109-2.

ABSTRACT

The association between ventricular arrhythmias (VAs) and mortality in patients supported by continuous flow left ventricular assist devices (LVAD) remains controversial. To evaluate the association between pre-implantation, early (≤ 30 day) post-implantation VAs and mortality in bridge to transplant (BTT) and destination therapy (DT) LVAD patients, separately. The risk factors for post LVAD VAs were also investigated. In this observational cohort study, we included 341 patients who received a first time, continuous flow LVAD between January 1st 2010 and July 30th 2018. We used Kaplan-Meier curves and multivariable cox regression analyses to study the association between VAs and mortality in the BTT and DT populations. The mean age of the cohort was 58 ± 14 years, with 82% males, 53% had ischemic cardiomyopathy, and 45% were DT. The mean follow-up was 2.2 ± 2.1 years. In both BTT and DT cohorts, pre LVAD VAs were not associated with mortality after LVAD implantation (log-rank p = 0.95 and p = 0.089, respectively). In the BTT population, early post-LVAD VAs were not statistically associated with increased mortality (log rank p = 0.072). In the DT patients, early post LVAD VAs were associated with a 67% increase in the hazards rate of mortality on LVAD support (HR 1.67 [1.05-2.65], p = 0.029). The final model was adjusted for type of cardiomyopathy, INTERMACS profile, glomerular filtration rate, post LVAD atrial fibrillation, age and cerebrovascular events. Early post-LVAD VA is common after LVAD implantation and is an independent predictor of mortality in the DT LVAD population.

PMID:34584108 | DOI:10.1038/s41598-021-98109-2

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Nevin Manimala Statistics

Postpartum hemorrhage risk is driven by changes in blood composition through pregnancy

Sci Rep. 2021 Sep 28;11(1):19238. doi: 10.1038/s41598-021-98411-z.

ABSTRACT

The extent to which women differ in the course of blood cell counts throughout pregnancy, and the importance of these changes to pregnancy outcomes has not been well defined. Here, we develop a series of statistical analyses of repeated measures data to reveal the degree to which women differ in the course of pregnancy, predict the changes that occur, and determine the importance of these changes for post-partum hemorrhage (PPH) which is one of the leading causes of maternal mortality. We present a prospective cohort of 4082 births recorded at the University Hospital, Lausanne, Switzerland between 2009 and 2014 where full labour records could be obtained, along with complete blood count data taken at hospital admission. We find significant differences, at a [Formula: see text] level, among women in how blood count values change through pregnancy for mean corpuscular hemoglobin, mean corpuscular volume, mean platelet volume, platelet count and red cell distribution width. We find evidence that almost all complete blood count values show trimester-specific associations with PPH. For example, high platelet count (OR 1.20, 95% CI 1.01-1.53), high mean platelet volume (OR 1.58, 95% CI 1.04-2.08), and high erythrocyte levels (OR 1.36, 95% CI 1.01-1.57) in trimester 1 increased PPH, but high values in trimester 3 decreased PPH risk (OR 0.85, 0.79, 0.67 respectively). We show that differences among women in the course of blood cell counts throughout pregnancy have an important role in shaping pregnancy outcome and tracking blood count value changes through pregnancy improves identification of women at increased risk of postpartum hemorrhage. This study provides greater understanding of the complex changes in blood count values that occur through pregnancy and provides indicators to guide the stratification of patients into risk groups.

PMID:34584125 | DOI:10.1038/s41598-021-98411-z

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Nevin Manimala Statistics

Confronting false discoveries in single-cell differential expression

Nat Commun. 2021 Sep 28;12(1):5692. doi: 10.1038/s41467-021-25960-2.

ABSTRACT

Differential expression analysis in single-cell transcriptomics enables the dissection of cell-type-specific responses to perturbations such as disease, trauma, or experimental manipulations. While many statistical methods are available to identify differentially expressed genes, the principles that distinguish these methods and their performance remain unclear. Here, we show that the relative performance of these methods is contingent on their ability to account for variation between biological replicates. Methods that ignore this inevitable variation are biased and prone to false discoveries. Indeed, the most widely used methods can discover hundreds of differentially expressed genes in the absence of biological differences. To exemplify these principles, we exposed true and false discoveries of differentially expressed genes in the injured mouse spinal cord.

PMID:34584091 | DOI:10.1038/s41467-021-25960-2

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Nevin Manimala Statistics

Behavioral gender differences are reinforced during the COVID-19 crisis

Sci Rep. 2021 Sep 28;11(1):19241. doi: 10.1038/s41598-021-97394-1.

ABSTRACT

Behavioral gender differences have been found for a wide range of human activities including the way people communicate, move, provision themselves, or organize leisure activities. Using mobile phone data from 1.2 million devices in Austria (15% of the population) across the first phase of the COVID-19 crisis, we quantify gender-specific patterns of communication intensity, mobility, and circadian rhythms. We show the resilience of behavioral patterns with respect to the shock imposed by a strict nation-wide lock-down that Austria experienced in the beginning of the crisis with severe implications on public and private life. We find drastic differences in gender-specific responses during the different phases of the pandemic. After the lock-down gender differences in mobility and communication patterns increased massively, while circadian rhythms tended to synchronize. In particular, women had fewer but longer phone calls than men during the lock-down. Mobility declined massively for both genders, however, women tended to restrict their movement stronger than men. Women showed a stronger tendency to avoid shopping centers and more men frequented recreational areas. After the lock-down, males returned back to normal quicker than women; young age-cohorts return much quicker. Differences are driven by the young and adolescent population. An age stratification highlights the role of retirement on behavioral differences. We find that the length of a day of men and women is reduced by 1 h. We interpret and discuss these findings as signals for underlying social, biological and psychological gender differences when coping with crisis and taking risks.

PMID:34584107 | DOI:10.1038/s41598-021-97394-1

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Nevin Manimala Statistics

Hopscotching jellyfish: combining different duty cycle kinematics can lead to enhanced swimming performance

Bioinspir Biomim. 2021 Sep 29. doi: 10.1088/1748-3190/ac2afe. Online ahead of print.

ABSTRACT

Jellyfish (Medusozoa) have been deemed the most energy-efficient animals in the world. Their bell morphology and relatively simple nervous systems make them attractive to robotocists. Although, the science community has devoted much attention to understanding their swimming performance, there is still much to be learned about the jet propulsive locomotive gait displayed by prolate jellyfish. Traditionally, computational scientists have assumed uniform duty cycle kinematics when computationally modeling jellyfish locomotion. In this study we used fluid-structure interaction modeling to determine possible enhancements in performance from shuffling different duty cycles together across multiple Reynolds numbers and contraction frequencies. Increases in speed and reductions in cost of transport were observed as high as 80% and 50%, respectively. Generally, the net effects were greater for cases involving lower contraction frequencies. Overall, robust duty cycle combinations were determined that led to enhanced or impeded performance.

PMID:34584025 | DOI:10.1088/1748-3190/ac2afe

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Nevin Manimala Statistics

Comparison of High-Flow Nasal Cannula and Noninvasive Ventilation in Acute Hypoxemic Respiratory Failure Due to Severe COVID-19 Pneumonia

Respir Care. 2021 Sep 28:respcare.09130. doi: 10.4187/respcare.09130. Online ahead of print.

ABSTRACT

BACKGROUND: Efficacy of high-flow nasal cannula (HFNC) over noninvasive ventilation (NIV) in severe coronavirus disease 2019 (COVID-19) pneumonia is not known. We aimed to assess the incidence of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 treated with either HFNC or NIV.

METHODS: This was a single-center randomized controlled trial performed in the COVID-19 ICU of a tertiary care teaching hospital in New Delhi, India. One hundred and nine subjects with severe COVID-19 pneumonia presenting with acute hypoxemic respiratory failure were recruited and allocated to either HFNC (n = 55) or NIV (n = 54) arm. Primary outcome was intubation by 48 h. Secondary outcomes were improvement in oxygenation by 48 h, intubation rate at day 7, and in-hospital mortality.

RESULTS: Baseline characteristics and PaO2 /FIO2 ratio were similar in both the groups. Intubation rate at 48 h was similar between the groups (33% NIV vs 20% HFNC, relative risk 0.6, 95% CI 0.31-1.15, P = .12). Intubation rate at day 7 was lower in the HFNC (27.27%) compared to the NIV group (46.29%) (relative risk 0.59, 95% CI 0.35-0.99, P = .045), and this difference remained significant after adjustment for the incidence of chronic kidney disease and the arterial pH (adjusted OR 0.40, 95% CI 0.17-0.93, P = .03). Hospital mortality was similar between HFNC (29.1%) and NIV (46.2%) group (relative risk 0.6, 95% CI 0.38-1.04, P = .06).

CONCLUSIONS: We were not able to demonstrate a statistically significant improvement of oxygenation parameters nor of the intubation rate at 48 h between NIV and HFNC. These findings should be further tested in a larger randomized controlled trial.The study was registered at the Clinical Trials Registry of India (www.ctri.nic.in; reference number: CTRI/2020/07/026835) on July 27, 2020.

PMID:34584010 | DOI:10.4187/respcare.09130

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Nevin Manimala Statistics

T2-weighted short-tau-inversion-recovery imaging reflects disease activity of cardiac sarcoidosis

Open Heart. 2021 Sep;8(2):e001728. doi: 10.1136/openhrt-2021-001728.

ABSTRACT

OBJECTIVE: We investigated the diagnostic performance of semi-quantitative hyperintensity on T2-weighted short-tau-inversion-recovery black-blood (T2W-STIR-BB) images in identifying active cardiac sarcoidosis (CS) in patients, and compared it with that of 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET).

METHODS: This retrospective study included 40 steroid-naive patients (age 63.1±12.9 years, 20 men) diagnosed with CS who underwent both cardiac MRI and FDG-PET imaging. Active CS cases were defined as satisfying at least one of the following criteria for conventional indices: exacerbation of ventricular arrhythmia, newly identified advanced atrioventricular block, greater than 5% decrease in left ventricular ejection fraction on echocardiography, positive finding on gallium-scintigraphy or elevated levels of sarcoidosis-related serum biomarkers. T2W-STIR-BB images were semi-quantitatively analysed using a myocardium-to-spleen ratio (MSR). The diagnostic performance of T2W-STIR-BB and FDG-PET imaging for detecting active CS was investigated.

RESULTS: Thirty-three patients satisfied at least one criterion and were considered as having active CS. Thirty patients (75%) tested positive with T2W-STIR-BB imaging, and 25 patients (63%) tested positive with FDG-PET. The sensitivity, specificity, accuracy, and positive and negative predictive values for identifying active CS by semi-quantitative MSR on T2W-STIR-BB images were 79%, 43%, 73%, 87% and 30%, respectively. These results were statistically comparable to those of FDG-PET (70%, 71%, 70%, 92% and 33%, respectively).

CONCLUSIONS: When using conventional diagnostic indices for active CS as the gold standard, T2W-STIR-BB imaging demonstrated comparable diagnostic performance to that of FDG-PET. The semi-quantitative analysis of high signal intensity on T2W-STIR-BB images using MSR was useful for detection of active CS.

PMID:34583984 | DOI:10.1136/openhrt-2021-001728

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Nevin Manimala Statistics

Investigation of the interplay between circulating lipids and IGF-I and relevance to breast cancer risk: an observational and Mendelian randomization study

Cancer Epidemiol Biomarkers Prev. 2021 Sep 28:cebp.0315.2021. doi: 10.1158/1055-9965.EPI-21-0315. Online ahead of print.

ABSTRACT

BACKGROUND: Circulating lipids and insulin-like growth factor 1(IGF-I) have been reliably associated with breast cancer(BCa). Observational studies suggest an interplay between lipids and IGF-I, however, whether these relationships are causal and if pathways from these phenotypes to BCa overlap is unclear.

METHODS: Mendelian Randomisation(MR) was conducted to estimate the relationship between lipids or IGF-I and BCa risk using genetic summary statistics for lipids(low-density lipoprotein cholesterol, LDL-C;high-density lipoprotein cholesterol,HDL-C; triglycerides,TGs), IGF-I and BCa from GLGC/UKBB(N=239,119), CHARGE/UKBB(N=252,547) and BCAC(N=247,173), respectively. Cross-sectional observational and MR analyses were conducted to assess the bi-directional relationship between lipids and IGF-I in SHIP(N=3,812) and UKBB(N=422,389), and using genetic summary statistics from GLGC(N=188,577) and CHARGE/UKBB(N=469,872).

RESULTS: In multivariable MR(MVMR) analyses, the OR for BCa per 1-SD increase in HDL-C or TG was 1.08(95%CI:1.04,1.13) and 0.94(95%CI:0.89,0.98), respectively. The OR for BCa per 1-SD increase in IGF-I was 1.09(95%CI:1.04,1.15). MR analyses suggested a bi-directional TG-IGF-I relationship (TG-IGF-I beta per 1-SD:-0.13;95%CI:-0.23,-0.04;and IGF-I-TG beta per 1-SD:-0.11;95%CI:-0.18,-0.05). There was little evidence for a causal relationship between HDL-C and LDL-C with IGF-I. In MVMR analyses, associations of TG or IGF-I with BCa were robust to adjustment for IGF-I or TG, respectively.

CONCLUSIONS: Our findings suggest a causal role of HDL-C, TG and IGF-I in BCa. Observational and MR analyses support an interplay between IGF-I and TG, however, MVMR estimates suggest that TG and IGF-I may act independently to influence BCa.

IMPACT: Our findings should be considered in the development of prevention strategies for BCa, where interventions are known to modify circulating lipids and IGF-I.

PMID:34583967 | DOI:10.1158/1055-9965.EPI-21-0315

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Nevin Manimala Statistics

Excess deaths reveal unequal impact of COVID-19 in Ecuador

BMJ Glob Health. 2021 Sep;6(9):e006446. doi: 10.1136/bmjgh-2021-006446.

ABSTRACT

Latin America has struggled to control the transmission of COVID-19. Comparison of excess death (ED) rates during the pandemic reveals that Ecuador is among the highest impacted countries. In this analysis, we update our previous findings with the most complete all-cause mortality records available for 2020, disaggregated by sex, age, ethnicity and geography. Our study shows that in 2020, Ecuador had a 64% ED rate (95% CI 63% to 65%) or 64% more deaths than expected. Men had a higher ED rate, 75% (95% CI 73% to 76%), than women’s 51% (95% CI 49% to 52%), and this pattern of higher EDs for men than women held for most age groups. The only exception was the 20-29 age group, where women had 19% more deaths, compared to 10% more deaths for men, but that difference is not statistically significant. The analysis provides striking evidence of the lack of COVID-19 diagnostic testing in Ecuador: the confirmed COVID-19 deaths in 2020 accounted for only 21% of total EDs. Our significant finding is that indigenous populations, who typically account for about 5% of the deaths, show almost four times the ED rate of the majority mestizo group. Indigenous women in each age group have higher ED rates than the general population and, in ages between 20 and 49 years, they have higher ED rates than indigenous men. Indigenous women in the age group 20-29 years had an ED rate of 141%, which is commensurate to the ED rate of indigenous women older than 40 years.

PMID:34583975 | DOI:10.1136/bmjgh-2021-006446