Tag: nevin manimala

J Crohns Colitis. 2022 Aug 23:jjac119. doi: 10.1093/ecco-jcc/jjac119. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Over the past decade, the DNA methylome has been increasingly studied in peripheral blood of inflammatory bowel disease (IBD) patients. However, a comprehensive summary and meta-analysis of peripheral blood leukocyte (PBL) DNA methylation studies has thus far not been conducted. Here, we systematically reviewed all available literature up to February 2022 and summarized the observations by means of meta-analysis.

METHODS: We conducted a systematic search and critical appraisal of IBD-associated DNA methylation studies in PBL using the biomarker-based cross-sectional studies (BIOCROSS) tool. Subsequently, we performed meta-analyses on the summary statistics obtained from epigenome-wide association studies (EWAS) that included patients with Crohn’s Disease (CD), ulcerative colitis (UC) and/or healthy controls (HC).

RESULTS: Altogether, we included 15 studies for systematic review. Critical appraisal revealed large methodological and outcome heterogeneity between studies. Summary statistics were obtained from 4 studies based on a cumulative 552 samples (177 CD, 132 UC and 243 HC). Consistent differential methylation was identified for 256 differentially methylated probes (DMPs; Bonferroni-adjusted p-value ≤0.05) when comparing CD with HC and 103 when comparing UC with HC. Comparing IBD (CD + UC) with HC resulted in 224 DMPs. Importantly, several of the previously identified DMPs, such as VMP1/TMEM49/MIR21 and RPS6KA2, were consistently differentially methylated across all studies.

CONCLUSION: Methodological homogenization of IBD epigenetic studies is needed to allow for easier aggregation and independent validation. Nonetheless, we were capable of confirming previous observations. Our results can serve as the basis for future IBD epigenetic biomarker research in PBL.

PMID:35998097 | DOI:10.1093/ecco-jcc/jjac119

J Prosthodont. 2022 Aug 23. doi: 10.1111/jopr.13597. Online ahead of print.

ABSTRACT

PURPOSE: To compare the accuracy of intraoral scanning (IOS) of the edentulous arch with the hybrid protocol of cast digitization (CD), and to investigate the effect of arch type and area on trueness.

MATERIALS AND METHODS: Participants that were edentulous in both arches were recruited. Two impression protocols were used; the IOS as the test protocol with an IOS device (TRIOS 4; 3Shape, Denmark), and the CD as the control, including tracing compound (TRACING STICKS; Kemdent, UK) for border molding, polyvinyl siloxane (Hydrorise Monophase; Zhermack, Italy) for impression, and cast digitization with a laboratory scanner (ceramill® map400, AMANNGIRRBACH, Germany). Scanned files were exported to a 3D inspection software (Geomagic Control X; 3D Systems, NC, USA) for trueness analysis. The CD file (reference file) for each participant was split into 2 areas; the dynamic area represented the mobile tissues at the peripheral border, and the static area represented the rest of the arch. Statistical analyses were performed with 1-sample t-test for the difference between CD and IOS protocols, paired sample t-test for the difference between the static and dynamic areas for each arch, and independent sample t-test for the difference between the maxillary and mandibular arches for each area, with α = .05. Effect size was calculated with Cohen’s d (d), with 0.2 as small, 0.5 as medium, 0.8 as large.

RESULTS: A total of 21 participants were included. The difference between the IOS and CD protocol was significant for all subset comparisons (p< .001, d:2.5-6.2, large effect size). Dynamic areas had lower trueness in comparison with static areas (p< .001, d = 4.57, large effect size for the maxillary arch, p< .001, d = 3.96, large effect size for the mandibular arch). Mandibular arch had lower trueness in comparison with the maxillary arch (p< .001, d = 1.45, large effect size for the static areas, p = .009, d = 0.85, large effect size for the dynamic areas, p< .001, d = 1.71, large effect size for all areas). Color difference map showed marked positive deviation in the buccal dynamic areas of both arches, and non-matching areas with evident over-stretching.

CONCLUSIONS: While the IOS of edentulous arches could be feasible for attached mucosa, providing a functional shape for the peripheral border remains a challenge, with a thinner and more outward border for the IOS in comparison with the CD protocol. The IOS of the mandibular arch is more difficult and has lower trueness in comparison with the maxillary arch. This article is protected by copyright. All rights reserved.

PMID:35997079 | DOI:10.1111/jopr.13597

J Gastroenterol Hepatol. 2022 Aug 23. doi: 10.1111/jgh.15984. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: As more superficial esophageal cancer (EC) patients are being treated with endoscopic resection (ER), it is important to understand the outcomes, including survival data, of patients who develop metachronous EC and head and neck cancer (HNC). We aimed to evaluate the long-term surveillance and survival outcomes of metachronous EC and HNC after esophageal ER.

METHODS: This study included 627 patients who underwent ER of superficial esophageal squamous cell carcinoma from 2008 to 2016 and were generally followed by annual or biannual esophagogastroduodenoscopy up to 2019 at Osaka International Cancer Institute. Data on metachronous cancer development and causes of death were collected from an integrated database of hospital-based cancer registry and Vital Statistics of Japan.

RESULTS: During a median (range) follow-up period of 67.4 (3.8-142.7) months, 230 patients (36.7%) developed 500 metachronous ECs and 126 patients (20.1%) developed 239 metachronous HNCs, post-ER of index EC. The 3-year, 5-year, and 7-year cumulative incidences were 25.8%, 36.0%, and 43.6% for metachronous EC and 10.9%, 16.0%, and 26.9% for metachronous HNC, respectively. No patients died of metachronous EC, and only seven patients (1.1%) died of metachronous HNC. The 3-year, 5-year, and 7-year disease-specific survival rates were 99.8%, 99.6%, and 98.6%, respectively.

CONCLUSIONS: The incidences of metachronous EC and HNC increase with time over 5 years after esophageal ER; therefore, surveillance endoscopy should be continued over 5 years. Endoscopic surveillance is useful for survivors after esophageal ER given the high incidence and extremely low mortality of metachronous EC and HNC.

PMID:35997074 | DOI:10.1111/jgh.15984

Elife. 2022 Aug 23;11:e74314. doi: 10.7554/eLife.74314.

ABSTRACT

Quantitative descriptions of animal behavior are essential to study the neural substrates of cognitive and emotional processes. Analyses of naturalistic behaviors are often performed by hand or with expensive, inflexible commercial software. Recently, machine learning methods for markerless pose estimation enabled automated tracking of freely moving animals, including in labs with limited coding expertise. However, classifying specific behaviors based on pose data requires additional computational analyses and remains a significant challenge for many groups. We developed BehaviorDEPOT (DEcoding behavior based on POsitional Tracking), a simple, flexible software program that can detect behavior from video timeseries and can analyze the results of experimental assays. BehaviorDEPOT calculates kinematic and postural statistics from keypoint tracking data and creates heuristics that reliably detect behaviors. It requires no programming experience and is applicable to a wide range of behaviors and experimental designs. We provide several hard-coded heuristics. Our freezing detection heuristic achieves above 90% accuracy in videos of mice and rats, including those wearing tethered head-mounts. BehaviorDEPOT also helps researchers develop their own heuristics and incorporate them into the software’s graphical interface. Behavioral data is stored framewise for easy alignment with neural data. We demonstrate the immediate utility and flexibility of BehaviorDEPOT using popular assays including fear conditioning, decision-making in a T-maze, open field, elevated plus maze, and novel object exploration.

PMID:35997072 | DOI:10.7554/eLife.74314

Clin Neuropsychol. 2022 Aug 23:1-14. doi: 10.1080/13854046.2022.2112296. Online ahead of print.

ABSTRACT

Objective: In early stages of disease, the differential diagnosis between Parkinson’s Disease (PD) and atypical parkinsonism, such as Progressive Supranuclear Palsy (PSP), could be challenging. Growing attention has recently been dedicated to investigating neuropsychological markers of degenerative parkinsonism. The Rey-Osterrieth Complex Figure Test (ROCFT) copy score was hypothesized able to differentiate PSP from PD. However, ROCFT is a drawing test requiring multiple cognitive abilities and it is still unknown which of them assumes an important role in PSP performance. Using a qualitative scoring system, we investigated which cognitive abilities underpin the PSP performance at the ROCFT copy trial. Moreover, we evaluated usefulness of the BQSS scores in discriminating PSP from PD. Methods: Thirty PSP-Richardson’s Syndrome (PSP-RS) patients, 30 PD patients, and 30 healthy control (HC) comparable for age, education, and gender were enrolled. All subjects underwent a neuropsychological evaluation; ROCFT copy were evaluated with the 36-Point Score and with the Boston Qualitative Scoring System (BQSS). Results: PSP-RS patients performed worse in ROCFT 36-Point Score and in several BQSS scores compared to other groups. Most suitable scores discriminating PSP-RS from PD were “Perseveration” and “Vertical Expansion” of BQSS. A logistic regression model considering “Perseveration” and “Vertical Expansion” showed a diagnostic accuracy of 83,3% for PSP-RS condition. Conclusion: our findings showed that “Perseveration” and “Vertical Expansion” BQSS scores were useful in discriminating PSP-RS from PD. “Perseveration” and “Vertical Expansion” BQSS scores might be included in the cognitive evaluation along with quantitative scores when PSP diagnosis is considered.

PMID:35997036 | DOI:10.1080/13854046.2022.2112296

Cardiol Young. 2022 Aug 23:1-7. doi: 10.1017/S1047951122002694. Online ahead of print.

ABSTRACT

BACKGROUND: Despite high survival after bidirectional cavopulmonary anastomosis, a considerable number of patients suffer significant post-operative morbidities related to prolonged length of stay.

METHODS: A single-center retrospective cohort study of all consecutive patients undergoing a first-time bidirectional cavopulmonary anastomosis from 2006 to 2019.

RESULTS: Prolonged length of stay was defined as hospital stay greater than the 75th percentile for our cohort. Of 195 patients who met inclusion criteria, the median post-operative length of stay was 8 days (interquartile range, 4-15 days). Prolonged length of stay was defined as greater than 15 days. In multivariate analysis, greater than mild systemic atrioventricular valve regurgitation (odds ratio 3.7, 95% CI 1.05-13.068, p = 0.04), longer length of stay after the initial palliative procedure (odds ratio 1.028, 95% CI 1.004-1.05, p = 0.02), and pre-operative higher superior vena cava oxygen saturation (odds ratio 0.922, 95% CI 0.85-0.99, p = 0.04) maintained statistical significance as independent risk and protective factors for prolonged length of stay. A one-level increase in the severity of pre-operative systemic atrioventricular valve regurgitation was associated with a multiplicative change in the odds ratio of prolonged length of stay of 5.45 (p = 0.005) independent of the severity of systemic ventricular dysfunction.

CONCLUSION: Pre-operative characteristics with greater than mild systemic atrioventricular valve regurgitation, longer length of stay after the initial palliative procedure, and lower superior vena cava oxygen saturation were associated with prolonged length of stay after a first-time bidirectional cavopulmonary anastomosis.

PMID:35997027 | DOI:10.1017/S1047951122002694

Circulation. 2022 Aug 23:101161CIRCULATIONAHA122059435. doi: 10.1161/CIRCULATIONAHA.122.059435. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension (PH) characterized by obliterative pulmonary vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis of PAH is not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, in particular, with connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related to immune reactions, was investigated in relation to the pathogenesis of PH.

METHODS: We first examined the expression levels of ZC3H12A (encoding Regnase-1) in peripheral blood mononuclear cells from patients with PH classified under various types of PH, searching for an association between the ZC3H12A expression and clinical features. We then generated mice lacking Regnase-1 in myeloid cells, including alveolar macrophages, and examined right ventricular systolic pressures and histological changes in the lung. We further performed a comprehensive analysis of the transcriptome of alveolar macrophages and pulmonary arteries to identify genes regulated by Regnase-1 in alveolar macrophages.

RESULTS: ZC3H12A expression in peripheral blood mononuclear cells was inversely correlated with the prognosis and severity of disease in patients with PH, in particular, in connective tissue disease-PAH. The critical role of Regnase-1 in controlling PAH was also reinforced by the analysis of mice lacking Regnase-1 in alveolar macrophages. These mice spontaneously developed severe PAH, characterized by the elevated right ventricular systolic pressures and irreversible pulmonary vascular remodeling, which recapitulated the pathology of patients with PAH. Transcriptomic analysis of alveolar macrophages and pulmonary arteries of these PAH mice revealed that Il6, Il1b, and Pdgfa/b are potential targets of Regnase-1 in alveolar macrophages in the regulation of PAH. The inhibition of IL-6 (interleukin-6) by an anti-IL-6 receptor antibody or platelet-derived growth factor by imatinib but not IL-1β (interleukin-1β) by anakinra, ameliorated the pathogenesis of PAH.

CONCLUSIONS: Regnase-1 maintains lung innate immune homeostasis through the control of IL-6 and platelet-derived growth factor in alveolar macrophages, thereby suppressing the development of PAH in mice. Furthermore, the decreased expression of Regnase-1 in various types of PH implies its involvement in PH pathogenesis and may serve as a disease biomarker, and a therapeutic target for PH as well.

PMID:35997026 | DOI:10.1161/CIRCULATIONAHA.122.059435

Stroke. 2022 Aug 23:101161STROKEAHA122039086. doi: 10.1161/STROKEAHA.122.039086. Online ahead of print.

ABSTRACT

BACKGROUND: Although chronic kidney disease (CKD) is associated with worse stroke outcomes, data regarding the influence of CKD on intravenous thrombolysis outcomes are scarce. We sought to assess the efficacy and safety of intravenous thrombolysis for acute ischemic stroke with unknown onset time in patients with CKD.

METHODS: Patients with an acute stroke of unknown onset time from the EOS trials (Evaluation of Unknown Onset Stroke Thrombolysis) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing intravenous thrombolysis with placebo/standard treatment. CKD was defined as baseline estimated glomerular filtration rate of <60 ml/min/1.73m² Mixed-effect logistic-regression analysis was performed to evaluate treatment effects. A favorable outcome was defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality.

RESULTS: Baseline data on renal function were available for 688 of 843 patients. Of these, CKD was present in 146 (21%), including 69 of 351 patients receiving alteplase and 77 of 337 patients receiving placebo/standard treatment. Overall, treatment with alteplase was associated with higher odds of favorable outcome, and CKD did not modify the treatment effect (P_interaction=0.834). A favorable outcome was observed in 31 of 69 (46%) patients with CKD in the alteplase group and in 28 of 77 (36%) patients with CKD in the control group (adjusted odds ratio, 1.19 [95% CI, 0.55-2.58]). Among patients with CKD, symptomatic intracranial hemorrhage occurred in 2 patients (3%) in the alteplase group but in none of the controls (P=0.133). At 90 days, death was reported in 3 patients (4%) in the alteplase group compared with 2 patients (3%) in the controls (P=0.539).

CONCLUSIONS: The present analysis indicates that the benefit of alteplase does not differ between stroke patients with unknown onset time with and without CKD, although the statistical power was lacking to confirm the efficacy in subgroups. This study only applies to mild-to-moderate or predialysis CKD.

PMID:35997023 | DOI:10.1161/STROKEAHA.122.039086

Hypertension. 2022 Aug 23:101161HYPERTENSIONAHA12219183. doi: 10.1161/HYPERTENSIONAHA.122.19183. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension maintains rapid cell proliferation and vascular remodeling through metabolic reprogramming. Recent studies suggested that circRNAs play important role in pulmonary vascular remodeling and pulmonary arterial smooth muscle cells proliferation. However, the relationship between circRNA, cell proliferation, and metabolic reprogramming in pulmonary arterial hypertension has not been investigated.

METHODS: RNA-seq and qRT-PCR reveal the differential expression profile of circRNA in pulmonary arteries of pulmonary arterial hypertension rat models. Transfection was used to examine the effects of circSMOC1 on pulmonary artery smooth muscle cells, and the roles of circSMOC1 in vivo were investigated by adenoassociated virus. Mass spectrometry, RNA pull-down, RNA immunoprecipitation, and dual-luciferase reporter assay were performed to investigate the signaling pathway of circSMOC1 regulating the metabolic reprogramming.

RESULTS: CircSMOC1 was significantly downregulated in pulmonary arteries of pulmonary arterial hypertension rats. CircSMOC1 knockdown promoted proliferation and migration and enhanced aerobic glycolysis of pulmonary artery smooth muscle cells. CircSMOC1 overexpression in vivo alleviates pulmonary vascular remodeling, right ventricular pressure, and right heart hypertrophy. In the nucleus, circSMOC1 directly binds to PTBP1 (polypyrimidine tract-binding protein), competitively inhibits the specific splicing of PKM (pyruvate kinase M) premRNA, resulting in the upregulation of PKM2 (pyruvate kinase M2), the key enzyme of aerobic glycolysis, to enhance glycolysis. In the cytoplasm, circSMOC1 acted as a miR-329-3p sponge, and its reduction in pulmonary arterial hypertension suppressed PDHB (pyruvate dehydrogenase E1 subunit beta) expression, leading to the impairment of mitochondrial oxidative phosphorylation.

CONCLUSIONS: circSMOC1 is crucially involved in the metabolic reprogramming of pulmonary artery smooth muscle cells through PTBP1 and miR-329-3p to regulate pulmonary vascular remodeling in pulmonary arterial hypertension.

PMID:35997022 | DOI:10.1161/HYPERTENSIONAHA.122.19183

Chem Commun (Camb). 2022 Aug 23. doi: 10.1039/d2cc03598g. Online ahead of print.

ABSTRACT

Advancements in computer science and software engineering have greatly facilitated mass spectrometry (MS)-based untargeted metabolomics. Nowadays, gigabytes of metabolomics data are routinely generated from MS platforms, containing condensed structural and quantitative information from thousands of metabolites. Manual data processing is almost impossible due to the large data size. Therefore, in the “omics” era, we are faced with new challenges, the big data challenges of how to accurately and efficiently process the raw data, extract the biological information, and visualize the results from the gigantic amount of collected data. Although important, proposing solutions to address these big data challenges requires broad interdisciplinary knowledge, which can be challenging for many metabolomics practitioners. Our laboratory in the Department of Chemistry at the University of British Columbia is committed to combining analytical chemistry, computer science, and statistics to develop bioinformatics tools that address these big data challenges. In this Feature Article, we elaborate on the major big data challenges in metabolomics, including data acquisition, feature extraction, quantitative measurements, statistical analysis, and metabolite annotation. We also introduce our recently developed bioinformatics solutions for these challenges. Notably, all of the bioinformatics tools and source codes are freely available on GitHub (https://www.github.com/HuanLab), along with revised and regularly updated content.

PMID:35997016 | DOI:10.1039/d2cc03598g