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Nevin Manimala Statistics

Proteomic study on the lymphocytes from pregnant Wistar rat females treated with immunosuppressive regimen

Clin Transl Sci. 2022 Nov 10. doi: 10.1111/cts.13432. Online ahead of print.

ABSTRACT

Kidney transplantation remains the therapeutic option for patients with end-stage kidney disease. Current immunosuppressive regimens are efficient in combating acute kidney rejection. However, insights into chronic kidney allograft injury remains limited. Simultaneously, pregnancy is more common after kidney transplantation than during dialysis treatment. Due to ethical issues, comprehensive studies on the impact of immunosuppressive regimens on pregnancy are challenging. The study aimed to investigate the proteomic status of lymphocytes obtained from pregnant female rats under immunosuppressive treatment. The experiment involved a group of 10 female, pregnant Wistar rats, five of which were treated with tacrolimus, mofetil mycophenolate, and glucocorticosteroids; five were used as control. The lymphocytes were obtained and analyzed with mass spectrometry. Measurements were processed by a database search in the ProteinPilot software with a cutoff of 1% false discovery rate. The outcomes were verified statistically by a t-test (p value < 0.05) regarding proteins up- and downregulation. A total of 2082 proteins were identified in all experiments. Eight hundred five proteins were quantified in an absolute manner in a data-independent acquisition-total protein approach analysis. Ninety-five proteins were recognized as present at different concentrations in analyzed groups and were annotated to intracellular pathways. The proteins involved in nonsense-mediated decay and L13a-mediated translational silencing of ceruloplasmin expression were recognized as downregulated. The set of proteins clinically identified as acute phase proteins was upregulated. Despite the blockade of adaptive cellular immunity, the lymphocytes in the analyzed group reveal sustained proinflammatory status with decreased ability to regulate translation. This potentially affects pregnancy and immunity.

PMID:36366854 | DOI:10.1111/cts.13432

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Nevin Manimala Statistics

Risk of non-ovarian cancer in a nationwide-based study of nearly 5,000 women with borderline ovarian tumors in Denmark

Int J Cancer. 2022 Nov 10. doi: 10.1002/ijc.34354. Online ahead of print.

ABSTRACT

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of non-ovarian cancers in women with serous or mucinous BOTs compared to the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5,000 women with BOTs (2,506 serous and 2,493 mucinous) in Denmark, 1978-2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific non-ovarian cancers. Compared to general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR=1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR=3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR=3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR=1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR=1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR=2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several non-ovarian cancers, likely due to some shared risk factors or genetic characteristics. This article is protected by copyright. All rights reserved.

PMID:36366853 | DOI:10.1002/ijc.34354

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Nevin Manimala Statistics

Observational, Multicenter Study on the Efficacy, Tolerability, and Safety of Nintedanib in Patients with Idiopathic Pulmonary Fibrosis Older than 80 Years

Respiration. 2022 Nov 10:1-9. doi: 10.1159/000527308. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) primarily affects old patients. Old age is a predictor of mortality. Nintedanib, the only antifibrotic drug approved in Italy for patients aged >80 years, can slow the progression of IPF by reducing the rate of decline in forced vital capacity (FVC) and the risk of exacerbations.

OBJECTIVES: The primary aim of the study was to compare the decline of FVC after 12 months of nintedanib in patients aged >80 years versus younger patients. Differences related to other functional data, safety, tolerability, hospitalizations, exacerbations, and mortality were evaluated.

METHODS: An observational, retrospective, multicenter study was carried out in Italy.

RESULTS: 159 (122 [76.7%] males) patients were recruited: 106 (66.7%) aged ≤80 years and 53 (33.3%) aged >80 years. FVC decline after 12 months of therapy was not significantly different (-45 mL [-170; 75] vs. -20 mL [-138; 110] mL; p: 0.51). No differences were found for other functional data. Diarrhea was the most frequent adverse event (AE). Rate and type of any AEs, permanent/temporary dose reduction, or drug discontinuation were not significantly different between patients aged ≤80 vs. >80 years. Furthermore, acute exacerbations, hospitalization, and mortality were not significantly different.

CONCLUSIONS: Nintedanib is effective and safe in patients with IPF aged >80 years, and no significant differences were found when clinical outcomes were compared with those of younger patients. Thus, older age should not be a barrier for the early prescription of antifibrotic treatment in IPF patients.

PMID:36366821 | DOI:10.1159/000527308

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Nevin Manimala Statistics

A methodological comparison of discriminant function analysis and binary logistic regression for estimating sex in forensic research and case-work

Med Sci Law. 2022 Nov 10:258024221136687. doi: 10.1177/00258024221136687. Online ahead of print.

ABSTRACT

The purpose of this study is to assess the accuracy of two multivariate statistical approaches for estimating sex from human external ear anthropometry, namely, discriminant function analysis (DFA) and binary logistic regression (BLR). A cross-sectional sample of 497 participants (233 males and 264 females) aged 18-35 years (24.42 ± 5.17) was obtained from Himachal Pradesh state of North India. Both the ears of the participants (994) were examined for anthropometric measurements. A total of 12 anthropometric measurements were taken independently on the left and right ear of each individual with the help of a pair of sliding calipers using a standard method. The sex of the population groups was discriminated against using binary logistic regression and discriminant function analysis. The predictive percentage of sex estimation computed from both the models were substantially the same, that is, 76.3% from DFA and 76.2% from BLR, with nearly comparable (∼0.02) sensitivity, specificity, positive predictive value, and negative predictive values, whereas the values of correct predicted percentage were 0.1% higher in DFA than BLR. Moreover, the other comparison metrics, such as classification error, B-index, and Matthews correlation coefficient indicated that both models performed equally well. The study highlighted that if the assumptions of the statistical methods are met, both methods are equally capable of discriminating the population depending on sex. The study recommends that the discriminant function analysis and binary logistic regression may be used synonymously in forensic research and case-work pertaining to the estimation of sex and various other forensic situations.

PMID:36366800 | DOI:10.1177/00258024221136687

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Nevin Manimala Statistics

Dirichlet process mixture models for regression discontinuity designs

Stat Methods Med Res. 2022 Nov 10:9622802221129044. doi: 10.1177/09622802221129044. Online ahead of print.

ABSTRACT

The regression discontinuity design is a quasi-experimental design that estimates the causal effect of a treatment when its assignment is defined by a threshold for a continuous variable. The regression discontinuity design assumes that subjects with measurements within a bandwidth around the threshold belong to a common population, so that the threshold can be seen as a randomising device assigning treatment to those falling just above the threshold and withholding it from those who fall below. Bandwidth selection represents a compelling decision for the regression discontinuity design analysis as results may be highly sensitive to its choice. A few methods to select the optimal bandwidth, mainly from the econometric literature, have been proposed. However, their use in practice is limited. We propose a methodology that, tackling the problem from an applied point of view, considers units’ exchangeability, that is, their similarity with respect to measured covariates, as the main criteria to select subjects for the analysis, irrespectively of their distance from the threshold. We cluster the sample using a Dirichlet process mixture model to identify balanced and homogeneous clusters. Our proposal exploits the posterior similarity matrix, which contains the pairwise probabilities that two observations are allocated to the same cluster in the Markov chain Monte Carlo sample. Thus we include in the regression discontinuity design analysis only those clusters for which we have stronger evidence of exchangeability. We illustrate the validity of our methodology with both a simulated experiment and a motivating example on the effect of statins on cholesterol levels.

PMID:36366738 | DOI:10.1177/09622802221129044

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Nevin Manimala Statistics

Genetic Diversity and Possible Origins of the Hepatitis B Virus in Siberian Natives

Viruses. 2022 Nov 7;14(11):2465. doi: 10.3390/v14112465.

ABSTRACT

A total of 381 hepatitis B virus (HBV) DNA sequences collected from nine groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strains from Central Asian republics and Mongolia. Different HBV subgenotypes predominated in various native Siberian populations. Subgenotype D1 was dominant in Altaian Kazakhs (100%), Tuvans (100%), and Teleuts (100%) of southern Siberia as well as in Dolgans and Nganasans (69%), who inhabit the polar Taimyr Peninsula. D2 was the most prevalent subgenotype in the combined group of Nenets, Komi, and Khants of the northern Yamalo-Nenets Autonomous Region (71%) and in Yakuts (36%) from northeastern Siberia. D3 was the main subgenotype in South Altaians (76%) and Buryats (40%) of southeastern Siberia, and in Chukchi (51%) of the Russian Far East. Subgenotype C2 was found in Taimyr (19%) and Chukchi (27%), while subgenotype A2 was common in Yakuts (33%). In contrast, D2 was dominant (56%) in urban populations of the former western USSR, and D1 (62%) in Central Asian republics and Mongolia. Statistical analysis demonstrated that the studied groups are epidemiologically isolated from each other and might have contracted HBV from different sources during the settlement of Siberia.

PMID:36366563 | DOI:10.3390/v14112465

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Nevin Manimala Statistics

A Modified PINN Approach for Identifiable Compartmental Models in Epidemiology with Application to COVID-19

Viruses. 2022 Nov 7;14(11):2464. doi: 10.3390/v14112464.

ABSTRACT

Many approaches using compartmental models have been used to study the COVID-19 pandemic, with machine learning methods applied to these models having particularly notable success. We consider the Susceptible-Infected-Confirmed-Recovered-Deceased (SICRD) compartmental model, with the goal of estimating the unknown infected compartment I, and several unknown parameters. We apply a variation of a “Physics Informed Neural Network” (PINN), which uses knowledge of the system to aid learning. First, we ensure estimation is possible by verifying the model’s identifiability. Then, we propose a wavelet transform to process data for the network training. Finally, our central result is a novel modification of the PINN’s loss function to reduce the number of simultaneously considered unknowns. We find that our modified network is capable of stable, efficient, and accurate estimation, while the unmodified network consistently yields incorrect values. The modified network is also shown to be efficient enough to be applied to a model with time-varying parameters. We present an application of our model results for ranking states by their estimated relative testing efficiency. Our findings suggest the effectiveness of our modified PINN network, especially in the case of multiple unknown variables.

PMID:36366562 | DOI:10.3390/v14112464

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Nevin Manimala Statistics

Correction to: Making sense of diabetes medication decisions: a mixed methods cluster randomized trial using a conversation aid intervention

Endocrine. 2022 Nov 10. doi: 10.1007/s12020-022-03240-3. Online ahead of print.

NO ABSTRACT

PMID:36357824 | DOI:10.1007/s12020-022-03240-3

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Nevin Manimala Statistics

Association between the history of abortion and gestational diabetes mellitus: A meta-analysis

Endocrine. 2022 Nov 10. doi: 10.1007/s12020-022-03246-x. Online ahead of print.

ABSTRACT

PURPOSE: Gestational diabetes mellitus (GDM) is a common metabolic disease in pregnant women. The purpose of this study was to determine whether a history of abortion increases the risk of GDM by meta-analysis.

METHODS: A comprehensive literature search was conducted in nine databases of studies on the association between abortion history and GDM up to April 12, 2022. Fixed- or random-effects models were used to estimate the pooled odds ratio (OR) and 95% CI. The I square value (I2) was used to assess heterogeneity. Possible sources of heterogeneity were explored by conducting subgroup analysis and meta-regression. A sensitivity analysis was also performed for this meta-analysis. Publication bias was assessed by funnel plots and Egger’s tests.

RESULTS: Thirty-one studies enrolling 311,900 subjects were included in this meta-analysis. The risk of GDM was higher in women who experienced abortion than in those who did not (OR = 1.41 95% CI: 1.28-1.55, I2 = 66.8%). The risk of GDM increased with an increasing number of abortions (1 time: OR = 1.67, 95% CI = 1.26-2.22; 2 times: OR = 2.10, 95% CI = 1.26-3.49; ≥3 times: OR = 2.49, 95% CI = 1.24-5.01). Both spontaneous abortion (OR = 1.52, 95% CI = 1.30-1.78) and induced abortion (OR = 1.07, 95% CI = 1.03-1.11) were associated with an increased risk of GDM.

CONCLUSIONS: A history of abortion was associated with an increased risk of GDM in pregnant women, which may be a risk factor for predicting GDM.

PMID:36357823 | DOI:10.1007/s12020-022-03246-x

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Nevin Manimala Statistics

Post-randomization Differences in Condomless Vaginal Sex Among Women Randomized to Intramuscular Depot Medroxyprogesterone Acetate Injections, a Copper Intrauterine Device or a Levonorgestrel Implant in the ECHO Trial

AIDS Behav. 2022 Nov 11. doi: 10.1007/s10461-022-03834-y. Online ahead of print.

ABSTRACT

The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial found no substantial difference in HIV acquisition risk between women randomised to injectable intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. We evaluated post-randomization sexual behavior using an objective marker of condomless vaginal sex in a subset of participants. We conducted a sub-study among 458 ECHO participants at three sites (Cape Town, Johannesburg, Kisumu) to evaluate the frequency of condomless vaginal sex, measured by prostate specific antigen (PSA) detection in vaginal swabs, collected at the month 6 and final visit and the concordance of self-reported condomless vaginal sex with PSA detection, by randomized arm. We compared PSA detection frequency and concordance of PSA and self-reported condomless vaginal sex, by randomized group using Cochran-Mantel-Haenszel tests and adjusted generalized logistic growth curve models. PSA was detected less frequently in the DMPA-IM (16%), compared to the Cu-IUD (21%) and LNG implant (24%) groups, although results were not statistically significant in the unadjusted model when accounting for pre-specified multiple-testing criteria. There were significant differences in PSA detection between the DMPA-IM and LNG-implant groups (odds ratio 0.61 (95% CI 0.40, 0.94) in the adjusted model. There was moderate discordance between self-reported condomless vaginal sex and detection of PSA that was similar across randomized groups. These data suggest that women randomized to Cu-IUD and LNG implant may have had condomless sex more frequently than women randomized to DMPA-IM. The discordance between detectable PSA and self-reported sexual behaviour has important implications for design of future HIV prevention studies.

PMID:36357806 | DOI:10.1007/s10461-022-03834-y