Category: Nevin Manimala

J Audiol Otol. 2022 Oct;26(4):169-181. doi: 10.7874/jao.2022.00234. Epub 2022 Oct 10.

ABSTRACT

BACKGROUND AND OBJECTIVES: Trendy technologies, such as artificial intelligence, virtual reality (VR), and augmented reality (AR) are being increasingly used for hearing loss, tinnitus, and vestibular disease. Thus, we conducted this systematic review and meta-analysis to identify the possible benefits of the use of VR and AR technologies in patients with hearing loss, tinnitus, and/or vestibular dysfunction, with the aim of suggesting potential applications of these technologies for both researchers and clinicians.

MATERIALS AND METHODS: Published articles from 1968 to 2022 were gathered from six electronic journal databases. Applying our specified inclusion and/or exclusion criteria, 23 studies were analyzed. As only one article on hearing loss and two articles on tinnitus were found, 20 studies on vestibular dysfunction were only finally included for the meta-analysis. Standardized mean differences (SMDs) were chosen as estimates to compare the studies. A funnel plot and Egger’s regression analysis were used to identify any risk of bias.

RESULTS: High heterogeneity (I2: 83%, τ2: 0.5431, p<0.01) was identified across the studies on vestibular dysfunction. VR-based rehabilitation was significantly effective for individuals with vestibular disease (SMDs: 0.03, 95% confidence interval [CI]: -0.08 to 0.15, p<0.05). A subgroup analysis revealed that only improvement in the subjective questionnaire was meaningful and statistically significant (SMDs: -0.66, 95% CI: -1.10 to -0.22).

CONCLUSIONS: VR-based vestibular rehabilitation showed potential for subjective rating measures like Dizziness Handicap Index. The negative effect of aging on vestibular disease was indirectly confirmed. More clinical trials and an evidence-based approach are needed to confirm the implementation of state-of-the-art technology for hearing loss and tinnitus, representative diseases in neurotology.

PMID:36285466 | DOI:10.7874/jao.2022.00234

Interv Neuroradiol. 2022 Oct 26:15910199221133863. doi: 10.1177/15910199221133863. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Recent endovascular trials have spurred a paradigm shift toward routine use of CT perfusion (CTP) for decision-making in acute ischemic stroke. CTP use in the late window, however, remains under evaluation. Our objective was to assess the accuracy of CTP-predicted core in the late window.

METHODS: In a retrospective review of our prospectively identified stroke registry at a single, comprehensive stroke center, we included patients with anterior large vessel occlusions presenting within the 6-24 h window who underwent baseline CTP evaluation and achieved TICI2b or TICI3 reperfusion on endovascular treatment. We recorded baseline CTP-predicted core volumes at relative cerebral blood flow (CBF) thresholds of <30% <34%, and <38% using RAPID software. Final infarct volumes (FIV) were calculated using follow up MRI and CT, obtained within 72 h after stroke onset.

RESULTS: Of the eligible patients, 134 met our inclusion criteria. Mean FIV was 39.5 (SD 49.6). Median CTP to reperfusion time was 93.5 min. Median absolute differences between CTP-predicted core and FIV were 14.7, 14.9, and 16.0 ml at <30%, <34%, and <38%, respectively. Correlation between CTP-predicted ischemic cores and FIV was moderate and statistically significant at all thresholds: r = 0.43 (p <0.001), r = 0.43 (p <0.001), and r = 0.42 (p <0.001) at the <30%, <34%, and <38% cutoffs, respectively.

CONCLUSION: CTP cores in the 6-24 h period underestimate FIV, especially with larger infarcts. CTP-predicted core volumes in the late window show moderate positive correlation with FIV.

PMID:36285452 | DOI:10.1177/15910199221133863

J R Soc Interface. 2022 Oct;19(195):20220415. doi: 10.1098/rsif.2022.0415. Epub 2022 Oct 26.

ABSTRACT

DNA methylation occurs predominantly on cytosine-phosphate-guanine (CpG) dinucleotides in the mammalian genome, and the methylation landscape is maintained over mitotic cell division. It has been posited that coupling of maintenance methylation activity among neighbouring CpGs is critical to stability over cellular generations; however, the mechanism is unclear. We used mathematical models and stochastic simulation to analyse data from experiments that probe genome-wide methylation of nascent DNA post-replication in cells. We find that DNA methylation maintenance rates on individual CpGs are locally correlated, and the degree of this correlation varies by genomic regional context. By using theory of protein diffusion along DNA, we show that exponential decay of methylation rate correlation with genomic distance is consistent with enzyme processivity. Our results provide quantitative evidence of genome-wide methyltransferase processivity in vivo. We further developed a method to disentangle different mechanistic sources of kinetic correlations. From the experimental data, we estimate that an individual methyltransferase methylates neighbour CpGs processively if they are 36 basepairs apart, on average. But other mechanisms of coupling dominate for longer inter-CpG distances. Our study demonstrates that quantitative insights into enzymatic mechanisms can be obtained from replication-associated, cell-based genome-wide measurements, by combining data-driven statistical analyses with hypothesis-driven mathematical modelling.

PMID:36285438 | DOI:10.1098/rsif.2022.0415

Sci Rep. 2022 Oct 25;12(1):17897. doi: 10.1038/s41598-022-22248-3.

ABSTRACT

The subalpine vegetation in the Eastern Carpathians has been under agropastoral influence as a high-mountain open pasture for about five centuries. Today, the subalpine zone released by human intervention is growing as thickets. In this study, we use a numerical model of tree crowns (CHM, Canopy Height Model) based on laser scanning (LiDAR) and a high-resolution digital terrain model (DTM) to delineate the subalpine thicket distribution. Anselin ‘Local Moran’s I’ statistic was used to find hot and cold spots in vegetation cover. We used a logistic generalized linear model (GLM) and Principal Component Analysis (PCA) to set for the historical, climatic and terrain conditions candidates as the predictors of the present-day distribution of vegetation hot spots. We use variance partitioning to assess the interaction of climate and terrain variables. The resulting model suggests key environmental controls that underlie the vegetation pattern. Namely, snow in terrain depressions protects woody vegetation against abrasion and winter drought and increased insolation reduces the site humidity in the summer on S-E exposure hampering re-vegetation. In addition, the increasing distance from the treeline declines the rate of secondary succession. In all, the spatial model predicts the 35% coverage by thickets as a theoretical maximum of available climatic-terrain niches. The results suggest that the growth of the subalpine thicket, in the face of growing global temperature, may be restricted due to the limited number of niches available.

PMID:36284149 | DOI:10.1038/s41598-022-22248-3

Nat Commun. 2022 Oct 25;13(1):6336. doi: 10.1038/s41467-022-34016-y.

ABSTRACT

Genes with moderate to low expression heritability may explain a large proportion of complex trait etiology, but such genes cannot be sufficiently captured in conventional transcriptome-wide association studies (TWASs), partly due to the relatively small available reference datasets for developing expression genetic prediction models to capture the moderate to low genetically regulated components of gene expression. Here, we introduce a method, the Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction model accuracy and the power of TWAS by using a large expression quantitative trait loci (eQTL) summary-level dataset. We apply SUMMIT to the eQTL summary-level data provided by the eQTLGen consortium. Through simulation studies and analyses of genome-wide association study summary statistics for 24 complex traits, we show that SUMMIT improves the accuracy of expression prediction in blood, successfully builds expression prediction models for genes with low expression heritability, and achieves higher statistical power than several benchmark methods. Finally, we conduct a case study of COVID-19 severity with SUMMIT and identify 11 likely causal genes associated with COVID-19 severity.

PMID:36284135 | DOI:10.1038/s41467-022-34016-y

Sci Rep. 2022 Oct 25;12(1):17856. doi: 10.1038/s41598-022-22507-3.

ABSTRACT

Pre-eclampsia (PE) is a hypertensive condition that occurs during pregnancy and complicates up to 4% of pregnancies. PE exhibits several circadian-related characteristics, and the placenta possesses a functioning molecular clock. We examined the associations of 17 core circadian gene transcripts in placenta with PE vs. non-PE (a mixture of pregnant women with term, preterm, small-for-gestational-age, or chorioamnionitis) using two independent gene expression datasets: GSE75010-157 (80 PE vs. 77 non-PE) and GSE75010-173 (77 PE and 96 non-PE). We found a robust difference in circadian gene expression between PE and non-PE across the two datasets, where CRY1 mRNA increases and NR1D2 and PER3 transcripts decrease in PE placenta. Gene set variation analysis revealed an interplay between co-alterations of circadian clock genes and PE with altered hypoxia, cell migration/invasion, autophagy, and membrane trafficking pathways. Using human placental trophoblast HTR-8 cells, we show that CRY1/2 and NR1D1/2 regulate trophoblast migration. A subgroup study including only term samples demonstrated that CLOCK, NR1D2, and PER3 transcripts were simultaneously decreased in PE placenta, a finding supported by CLOCK protein downregulation in an independent cohort of human term PE placenta samples. These findings provide novel insights into the roles of the molecular clock in the pathogenesis of PE.

PMID:36284122 | DOI:10.1038/s41598-022-22507-3

Sci Rep. 2022 Oct 25;12(1):17854. doi: 10.1038/s41598-022-20412-3.

ABSTRACT

Hepatic encephalopathy (HE) is a deterioration of brain function in patients suffering from chronic liver disease, cirrhosis as a result of elevated blood ammonia and the production of pseudo-neurotransmitters. Herein, we investigated the chemical composition of hexane extract from Origanum vulgare (O. vulgare) leaves as well as its possible protective effects against thioacetamide (TAA)-induced HE in rats. GC-MS analysis of the extract revealed tentative identification of twenty-five compounds (82.93%), predominated by cholesten-3-one (27.30%), followed by γ-tocopherol (13.52%), α-tocopherol (5.01%), β-amyrin (5.24%) and α-amyrin (4.89%). Albino rats were distributed into seven groups (n = 7). G₁ served as negative control; G₂ and G₃ served as controls treated with O. vulgare (100 and 200 mg/kg/p.o b.w, respectively); G₄ served as TAA-positive control group (100 mg/kg/day/i.p., three alternative days per week for six weeks); G5, G6, and G7 served as TAA -induced HE rat model that received O. vulgare 100, O. vulgare 200, and silymarin (100 mg/kg of SILY, as standard drug), respectively. TAA showed depressive and anxiety-like behaviors in forced swimming test (FST) and reduction of cognitive score in elevated plus-maze test (EPMT) as well as impairment of locomotor and exploratory activities in open-field test (OFT). TAA caused a significant decline in body weight gain; however, the relative liver weight and brain water content were statistically increased. TAA-intoxicated rats showed significant increase of serum biomarker enzymes, proinflammatory cytokines, blood ammonia levels, brain serotonin, acetyl cholinesterase and cellular lipid peroxidation with significant decrease of brain dopamine, norepinephrine, antioxidant status. The hepatoprotective/neuro-protective activities of O. vulgare was found to be comparable with that of SILY in HE rats model. Where, treatment of TAA-intoxicated rats with O. vulgare attenuated anxiety, depressive-related behaviors, and reduced the biochemical changes in HE-induced by TAA. Therefore, O. vulgare could be an excellent hepato-/neuroprotective against hepatic injury and HE via improving the oxidative/inflammatory status through its antioxidant and neuro-modulatory properties and its effect is equal to that of SILY.

PMID:36284120 | DOI:10.1038/s41598-022-20412-3

Dermatol Ther (Heidelb). 2022 Oct 25. doi: 10.1007/s13555-022-00831-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Chlormethine (CL) gel is a skin-directed therapy approved for treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in the USA. MF-CTCL has a chronic clinical course, requiring long-term maintenance therapy with one or more therapies. This analysis describes real-world patterns of maintenance therapy and use of concomitant therapy with CL gel among patients with stage IA/IB MF-CTCL.

METHODS: In a US-based registry, MF-CTCL patients treated with CL gel were enrolled between 3/2015 and 10/2018 across 46 centers and followed for up to 2 years. Patient demographics, clinical characteristics, CL gel treatment patterns, concomitant treatments, clinical response, and adverse events (AEs) were collected from medical records. Descriptive statistics are reported.

RESULTS: Of the 206 patients with stage IA/IB MF-CTCL, 58.7% were male, and average age was 60.7 years with 4.6 years since diagnosis. Topical steroids, phototherapy, and topical retinoids were used concomitantly with CL gel in 62.6%, 26.2%, and 6.3% of patients, respectively. Most concomitant therapies (up to 85%) were started before CL gel initiation and, in about half of the cases (up to 57%), were used concurrently for ≥ 12 months. Overall, 158 (76.7%) patients experienced partial response (PR) and 144 continued with maintenance therapy. After achieving PR, most patients (74.3%) kept the same maintenance therapy schedule, most commonly once daily. Of patients who had any skin-related AE (31.6%) or skin-related AEs associated with CL gel (28.2%), nearly half experienced CL gel treatment interruption and ~40% had a dosing reduction. The observed real-world treatment patterns were concordant with National Comprehensive Cancer Network (NCCN) guidelines.

CONCLUSION: The study results suggest that continuing CL gel maintenance therapy and combining treatments with CL gel are common practice in the real-world setting, with most maintained on a stable dosing schedule. Careful management of AEs may help patients maintain long-term optimal dosing with less treatment interruptions and dosing reductions.

PMID:36284059 | DOI:10.1007/s13555-022-00831-w

Int J Behav Med. 2022 Oct 25. doi: 10.1007/s12529-022-10131-4. Online ahead of print.

ABSTRACT

BACKGROUND: People with advanced cancer experience psychological distress due to physical symptoms, functional decline, and a limited prognosis. Difficult thoughts, feelings, and emotions may exacerbate distress and lead to avoidance of these experiences which is sometimes referred to as experiential avoidance (EA). Advanced cancer patients may be more likely to engage in EA especially when no obvious solutions to their problems exist. This study aims to examine the terms used to describe EA, the processes that might indicate EA, associations between EA and psychological distress, and to understand why individuals might engage in EA.

METHODS: A mixed-methods review. Literature search of Medline, Embase, Psych INFO, and CINAHL 1980-October 2019.

INCLUSION: adults ≥ 18 years; advanced cancer not amenable to cure.

EXCLUSION: no measures of EA or psychological distress. Risk of bias and study quality assessed. Evidence of statistical techniques collected. Themes coded, grouped, and developed based on meaning.

RESULTS: Nineteen studies identified, 13 quantitative studies and 6 qualitative. The quantitative of which 6 compared early-stage cancers with advanced cancers and examined subscales of EA alongside mood, quality of life, and psychological distress. EA covers a range or terms of which ‘avoidant coping’ is the commonest. EA is manifest as cognitive, behavioural, and emotional avoidance. A thematic synthesis suggests the function of EA is to protect people from distress, and from confronting or expressing difficult emotions by avoiding communication about cancer, controlling negative information, and maintaining normality and hope and optimism.

CONCLUSIONS: EA may be beneficial in the short term to alleviate distress, but in the longer term, it can impair function and limit engagement in life. Greater clinical awareness of the complexity of EA behaviours is needed. Clinicians and researchers should define EA precisely and be aware of the function it may serve in the short and longer term. Future research studies may consider using specific measures of EA as a primary outcome, to assess the impact of psychological interventions such as ACT.

PMID:36284042 | DOI:10.1007/s12529-022-10131-4

Cancer Causes Control. 2022 Oct 25. doi: 10.1007/s10552-022-01646-y. Online ahead of print.

ABSTRACT

PURPOSE: Clinical trials advance the standard of care for patients. Patients enrolled in trials should represent the population who would benefit from the intervention in clinical practice. The aim of this study was to assess whether clinical trials enrolling patients with gynecologic cancers report racial and ethnic participant composition and to examine the level of diversity in clinical trials.

METHODS: Using ClinicalTrials.gov, we identified clinical trials enrolling patients with ovarian, uterine/endometrial, cervical, vaginal, and vulvar cancers from 1988 to 2019. Race and ethnicity data were extracted from participant demographics. Descriptive statistics on race, ethnicity, cancer type, location, study status, and sponsor type were calculated. Among trials which reported race and/or ethnicity, sub-analyses were performed on composition of race and ethnicity by funding source, location, and completed study status.

RESULTS: A total of 1,882 trials met inclusion criteria; only 179 trials (9.5%) reported race information. Of these, the racial distribution of enrollees was 66.9% White, 8.6% Asian, 8.5% Black/African American, 0.4% Indian/Alaskan Native, 0.1% Native Hawaiian/Pacific Islander, 1.0% more than one race, and 14.5% unknown. Only 100 (5.3%) trials reported ethnicity. Except for trials enrolling patients with cervical cancer which enrolled 65.2% White and 62.1% Non-Hispanic/Latino/a patients, enrollees in trials for other gynecologic cancers were over 80% White and 88% Non-Hispanic/Latino/a. Industry funded trials enrolled higher proportions of White (68.4%) participants than non-industry funded trials (57.5%). Domestic trials report race (11.5%) and ethnicity (7.6%) at higher rates than international trials (6.9% and 2.3%, respectively). Reporting of race (1.7% vs. 13.9%) and ethnicity (1.7% vs. 11.1%) has increased over time for patients enrolled in 2000 vs. 2018.

CONCLUSION: Less than 10% of trials enrolling patients with gynecologic malignancies report racial/ethnic participant composition on ClinicalTrials.gov. Accurate reporting of participant race/ethnicity is imperative to ensuring minority representation in clinical trials.

PMID:36284031 | DOI:10.1007/s10552-022-01646-y