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Nevin Manimala Statistics

Genome-wide temporal landscaping of DNA methylation in pregnant women delivering at term: a GARBH-InI study

Epigenomics. 2023 Jun 21. doi: 10.2217/epi-2023-0145. Online ahead of print.

ABSTRACT

Background: We performed an epigenome-wide longitudinal DNA methylation study on an Indian cohort of pregnant women, GARBH-Ini, at three time points during pregnancy and at delivery. Aim & objective: Our aim was to identify temporal DNA methylation changes in maternal peripheral blood during the period of gestation and assess their impact on biological pathways critical for term delivery. Results: Significantly differentially methylated CpGs were identified by linear mixed model analysis (Bonferroni p < 0.01) and classified into two distinct temporal methylation trends: increasing and decreasing during gestation. Genes with upward methylation trend were enriched for T-cell activity, while those with a downward trend were enriched for solute transport and cell structure organization functions. Conclusion: Consistent trends of DNA methylation in maternal peripheral blood point to the sentinel function of T cells in the maintenance of pregnancy, and the importance of coordinated cellular remodeling to facilitate term delivery.

PMID:37345372 | DOI:10.2217/epi-2023-0145

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Owner-assisted recovery and early discharge after surgical treatment in dogs with brachycephalic obstructive airway syndrome

J Small Anim Pract. 2023 Jun 21. doi: 10.1111/jsap.13647. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aims to describe a perioperative protocol for dogs recovered from anaesthesia with the owners and discharged from the hospital on the same day after surgical management of brachycephalic obstructive airway syndrome and to determine whether implementation of this protocol was associated with reduced incidence of complications compared with standard anaesthesia recovery and 24 hours hospitalisation.

MATERIALS AND METHODS: Medical records of dogs that underwent brachycephalic obstructive airway surgery over two consecutive years (June 2017 to May 2019) were reviewed retrospectively. Signalment, clinical signs, diagnostic findings, surgical procedures and postoperative respiratory complications were recorded. Data were compared using the chi-squared or Fisher’s exact tests.

RESULTS: Sixty-three dogs met the inclusion criteria for the study. Forty-two dogs underwent owner-assisted recovery and 21 dogs standard recovery. No statistical difference was found between groups in age, breed, gender, severity of respiratory or gastrointestinal clinical signs and surgical techniques employed. The incidence of postoperative complications was higher in dogs that received standard recovery (28%) compared to dogs recovered with the owners (2%). None of the dogs recovered with the owners and discharged the same day required veterinary assistance after discharge from the hospital.

CLINICAL SIGNIFICANCE: Corrective surgery for brachycephalic obstructive airway syndrome was associated with lower postoperative respiratory complications when dogs were discharged on the same day after recovery with the owners. Owner-assisted recovery and early discharge are possible and safe and may decrease the incidence of postoperative complications. However, other unmeasured factors may have contributed to the lower complication rate in dogs recovered with the owners during the course of this study.

PMID:37345349 | DOI:10.1111/jsap.13647

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Nevin Manimala Statistics

Early MRI features of new paramagnetic rim lesions in Multiple Sclerosis

Ann Neurol. 2023 Jun 21. doi: 10.1002/ana.26727. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine early MRI features of new multiple sclerosis (MS) lesions that will develop into paramagnetic rim lesions (PRLs), which have been associated with progressive tissue injury in MS.

METHODS: New contrast enhancing lesions (CELs) observed on routine clinical MRI were imaged at 7-tesla (T) within 4 weeks of observation, and 3 and 6 months later. The 6-month MRI was used to classify PRL status (PRL or non-PRL). The relationship between early lesion characteristics and subsequent PRL status was assessed using generalized linear mixed effects models. Random forest classification was performed to classify early predictors of subsequent PRL status.

RESULTS: From 93 CELs in 23 MS patients, 37 lesions developed into a PRL. In lesions that developed into PRLs compared to those that did not, the average lesion T1 on the initial 7T MRI was 1994 ms compared to 1670 ms (p-value < 0.001) and the average volume was 168.7 mL compared to 44 mL (p-value < 0.001) in lesions that did not. These volume differences were also found on 3T scans (p-value < 0.001) and for intensity-normalized T1 -w (p-value = 0.011) and FLAIR (p-value = 0.005). The area under the receiver operating characteristic curve for the random forest classification with leave-one-out cross validation was found to be 0.86 using initial 7T features.

INTERPRETATION: New MS lesions that evolve into PRLs can be identified early in lesion evolution. These findings suggest that biological mechanisms underlying PRL development begin early, which has important implications for clinical trials targeting PRLs development and subsequent therapeutics. This article is protected by copyright. All rights reserved.

PMID:37345334 | DOI:10.1002/ana.26727

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Macular and Peripapillary Vascular Densities in Non-Glaucomatous Eyes of Patients with Unilateral Glaucoma

Turk J Ophthalmol. 2023 Jun 21;53(3):154-160. doi: 10.4274/tjo.galenos.2022.68302.

ABSTRACT

OBJECTIVES: Our purpose was to investigate vascular alterations in the non-glaucomatous eyes of patients with unilateral primary open angle glaucoma using optical coherence tomography angiography and to evaluate the role of vascular damage in glaucoma pathogenesis.

MATERIALS AND METHODS: This cross-sectional study included 60 eyes of 30 patients with unilateral glaucoma (63.4±8.8 years) and 30 eyes of 30 healthy subjects (65.6±9.1 years). Three groups were formed: group A, affected eyes of unilateral glaucoma patients; Group B, non-glaucomatous eyes of unilateral glaucoma patients; and group C, healthy controls.

RESULTS: When group A was compared with groups B and C, significant differences were detected in rim area, cup volume, mean cup/disc ratio, and retinal nerve fiber layer thickness parameters (p<0.001 for all). No significant difference was detected between groups B and C (p>0.05 for all). In peripapillary and macular vessel density (VD) comparisons, all parameters except intradisc VD were found to be lower in group A (p<0.0167 for all). No statistically significant difference was detected between groups B and C (p>0.05 for all).

CONCLUSION: The VD values in eyes with glaucoma were found to be lower than in the other two groups. However, no difference was observed between the non-glaucomatous eyes of glaucoma patients and those of healthy individuals. Thus, the results did not support our hypothesis that VD alterations would be observed in the fellow eyes of patients with unilateral glaucoma if the vascular pathway were responsible in the pathogenesis of glaucoma.

PMID:37345299 | DOI:10.4274/tjo.galenos.2022.68302

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Quantification of early nonpharmaceutical interventions aimed at slowing transmission of Coronavirus Disease 2019 in the Navajo Nation and surrounding states (Arizona, Colorado, New Mexico, and Utah)

PLOS Glob Public Health. 2023 Jun 21;3(6):e0001490. doi: 10.1371/journal.pgph.0001490. eCollection 2023.

ABSTRACT

During an early period of the Coronavirus Disease 2019 (COVID-19) pandemic, the Navajo Nation, much like New York City, experienced a relatively high rate of disease transmission. Yet, between January and October 2020, it experienced only a single period of growth in new COVID-19 cases, which ended when cases peaked in May 2020. The daily number of new cases slowly decayed in the summer of 2020 until late September 2020. In contrast, the surrounding states of Arizona, Colorado, New Mexico, and Utah all experienced at least two periods of growth in the same time frame, with second surges beginning in late May to early June. Here, we investigated these differences in disease transmission dynamics with the objective of quantifying the contributions of non-pharmaceutical interventions (NPIs) (e.g., behaviors that limit disease transmission). We considered a compartmental model accounting for distinct periods of NPIs to analyze the epidemic in each of the five regions. We used Bayesian inference to estimate region-specific model parameters from regional surveillance data (daily reports of new COVID-19 cases) and to quantify uncertainty in parameter estimates and model predictions. Our results suggest that NPIs in the Navajo Nation were sustained over the period of interest, whereas in the surrounding states, NPIs were relaxed, which allowed for subsequent surges in cases. Our region-specific model parameterizations allow us to quantify the impacts of NPIs on disease incidence in the regions of interest.

PMID:37342996 | DOI:10.1371/journal.pgph.0001490

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Characterization of cerebrospinal fluid (CSF) microbiota at the time of initial surgical intervention for children with hydrocephalus

PLoS One. 2023 Jun 21;18(6):e0280682. doi: 10.1371/journal.pone.0280682. eCollection 2023.

ABSTRACT

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention.

STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in STGG or standard clinical) were further analyzed using whole-genome amplification sequencing (WGAS).

RESULTS: 11/66 (17%) samples stored in STGG and 1/36 (3%) that underwent standard clinical microbiological culture demonstrated bacterial growth. Of the organisms present, 8 were common skin flora and 4 were potential pathogens; only 1 was also qPCR positive. WGAS findings and STGG culture findings were concordant for only 1 sample, identifying Staphylococcus epidermidis. No significant difference in time to second surgical intervention was observed between the STGG culture-positive and negative groups.

CONCLUSION(S): Using high sensitivity methods, we detected the presence of bacteria in a subset of CSF samples at the time of first surgery. Therefore, the true presence of bacteria in CSF of children with hydrocephalus cannot be ruled out, though our findings may suggest these bacteria are contaminants or false positives of the detection methods. Regardless of origin, the detection of microbiota in the CSF of these children may not have any clinical significance.

PMID:37342995 | DOI:10.1371/journal.pone.0280682

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The role of author identities in peer review

PLoS One. 2023 Jun 21;18(6):e0286206. doi: 10.1371/journal.pone.0286206. eCollection 2023.

ABSTRACT

There is widespread debate on whether to anonymize author identities in peer review. The key argument for anonymization is to mitigate bias, whereas arguments against anonymization posit various uses of author identities in the review process. The Innovations in Theoretical Computer Science (ITCS) 2023 conference adopted a middle ground by initially anonymizing the author identities from reviewers, revealing them after the reviewer had submitted their initial reviews, and allowing the reviewer to change their review subsequently. We present an analysis of the reviews pertaining to the identification and use of author identities. Our key findings are: (I) A majority of reviewers self-report not knowing and being unable to guess the authors’ identities for the papers they were reviewing. (II) After the initial submission of reviews, 7.1% of reviews changed their overall merit score and 3.8% changed their self-reported reviewer expertise. (III) There is a very weak and statistically insignificant correlation of the rank of authors’ affiliations with the change in overall merit; there is a weak but statistically significant correlation with respect to change in reviewer expertise. We also conducted an anonymous survey to obtain opinions from reviewers and authors. The main findings from the 200 survey responses are: (i) A vast majority of participants favor anonymizing author identities in some form. (ii) The “middle-ground” initiative of ITCS 2023 was appreciated. (iii) Detecting conflicts of interest is a challenge that needs to be addressed if author identities are anonymized. Overall, these findings support anonymization of author identities in some form (e.g., as was done in ITCS 2023), as long as there is a robust and efficient way to check conflicts of interest.

PMID:37342992 | DOI:10.1371/journal.pone.0286206

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Prognostic factors of COVID-19: an umbrella review endorsed by the International Society for Pharmacoepidemiology

Clin Pharmacol Ther. 2023 Jun 21. doi: 10.1002/cpt.2977. Online ahead of print.

ABSTRACT

During the COVID-19 pandemic, the urgency for updated evidence to inform public health and clinical care placed systematic literature reviews (SLR) at the cornerstone of research. We aimed to summarize evidence on prognostic factors for COVID-19 outcomes through published SLRs and to critically assess quality elements in the findings’ interpretation. An umbrella review was conducted via electronic databases from January 2020 to April 2022. All SLRs (and meta-analyses) in English were considered. Data screening and extraction were conducted by two independent reviewers. AMSTAR 2 tool was used to assess SLR quality. The study was registered with PROSPERO (CRD4202232576). Out of 4,564 publications, 171 SLRs were included of which 3 were umbrella reviews. Our primary analysis included 35 SLRs published in 2022 which incorporated studies since the beginning of the pandemic. Consistent findings showed that, for adults, older age, obesity, heart disease, diabetes, and cancer were more strongly predictive of risk of hospitalization, intensive care unit admission, and mortality due to COVID-19. Male sex was associated with higher risk of short-term adverse outcomes, but female sex was associated with higher risk of long COVID. For children, socioeconomic determinants that may unravel COVID-19 disparities were rarely reported. This review highlights key prognostic factors of COVID-19, which can help clinicians and health officers identify high-risk groups for optimal care. Findings can also help optimize confounding adjustment and patient phenotyping in comparative effectiveness research. A living SLR approach may facilitate dissemination of new findings. This paper is endorsed by the International Society for Pharmacoepidemiology.

PMID:37342987 | DOI:10.1002/cpt.2977

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Machine learning based canine posture estimation using inertial data

PLoS One. 2023 Jun 21;18(6):e0286311. doi: 10.1371/journal.pone.0286311. eCollection 2023.

ABSTRACT

The aim of this study was to design a new canine posture estimation system specifically for working dogs. The system was composed of Inertial Measurement Units (IMUs) that are commercially available, and a supervised learning algorithm which was developed for different behaviours. Three IMUs, each containing a 3-axis accelerometer, gyroscope, and magnetometer, were attached to the dogs’ chest, back, and neck. To build and test the model, data were collected during a video-recorded behaviour test where the trainee assistance dogs performed static postures (standing, sitting, lying down) and dynamic activities (walking, body shake). Advanced feature extraction techniques were employed for the first time in this field, including statistical, temporal, and spectral methods. The most important features for posture prediction were chosen using Select K Best with ANOVA F-value. The individual contributions of each IMU, sensor, and feature type were analysed using Select K Best scores and Random Forest feature importance. Results showed that the back and chest IMUs were more important than the neck IMU, and the accelerometers were more important than the gyroscopes. The addition of IMUs to the chest and back of dog harnesses is recommended to improve performance. Additionally, statistical and temporal feature domains were more important than spectral feature domains. Three novel cascade arrangements of Random Forest and Isolation Forest were fitted to the dataset. The best classifier achieved an f1-macro of 0.83 and an f1-weighted of 0.90 for the prediction of the five postures, demonstrating a better performance than previous studies. These results were attributed to the data collection methodology (number of subjects and observations, multiple IMUs, use of common working dog breeds) and novel machine learning techniques (advanced feature extraction, feature selection and modelling arrangements) employed. The dataset and code used are publicly available on Mendeley Data and GitHub, respectively.

PMID:37342986 | DOI:10.1371/journal.pone.0286311

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The COVID-19 Crisis and the Incidence of Alcohol-Related Deaths in Poland

Med Sci Monit. 2023 Jun 21;29:e940904. doi: 10.12659/MSM.940904.

ABSTRACT

BACKGROUND Identifying risk and protective factors for excessive alcohol consumption can inform targeted health policies, reducing the impact of potential mental health crises. This study examined the validity and reliability of COVID-19-related death data and explored the correlations among age, sex, residential status, alcohol abuse, and healthcare access. MATERIAL AND METHODS This analysis of Polish residents’ mortality relies on individual data from the register of deaths maintained by Statistics Poland. This study examined deviations in the number of deaths between 2020 and 2021 by analyzing specific causes of death. RESULTS Alcohol abusers had increased COVID-19 risk factors compared to the general population. F10 values were 22% higher than expected in 2020, aligning with predictions for 2021. Higher mortality rates were observed in the first year of the pandemic. In 2020, women and rural residents were more affected (31% and 25% higher than expected, respectively), while men and urban residents were less affected (21% and 20% higher than expected, respectively). In 2021, the trend reversed, with men 2% higher than predicted and women 4% lower. Urban area residents had a 77% lower than expected value, while rural area residents were similar (8% higher). Overall mortality exceeded expectations in both 2020 (13% higher) and 2021 (23% higher). In 2021, alcohol-related non-mental health problems increased by more than 40% in standardized death rates (SDRs). CONCLUSIONS Alcohol-related deaths reflect the hidden effects of the pandemic. Measuring the pandemic’s impact on global excess mortality is hindered by inconsistencies in COVID-19 death reporting.

PMID:37342984 | DOI:10.12659/MSM.940904