Miracle-dz/UniFAR-FTUs huggingface dataset:
Symptom severity and well-being of patients with mental illness during the COVID-19 pandemic: a two-wave survey

Abstract Purpose of the article To examine changes in symptom severity and well-being during the coronavirus disease 2019 (COVID-19) pandemic among individuals with pre-existing mental illness. Materials and methods In February 2021, we conducted a follow-up questionnaire-based survey among adults with mental illness, who responded to a similar survey on mental health in June 2020. The participants completed the 18-item Brief Symptom Inventory (BSI-18), the five-item World Health Organization Well-Being Index (WHO-5), and 14 questions evaluating worsening or improvement in mental health using the pre-pandemic period as reference. The survey data were merged with sociodemographic and clinical data from the medical records of all invitees to the first survey, enabling analysis of attrition and weighting of the results. Results A total of 613 of 992 (62%) invitees participated in the follow-up wave of the survey. The weighted mean WHO-5 and BSI-18 scores were 38 and 27, respectively, and did not differ statistically significantly from the first wave. Multivariate logistic regression showed that having a vocational education (skilled worker/craftsman) was positively associated with reporting deterioration in psychological well-being (OR: 2.95, 95%CI: 1.14–7.81), while being unemployed was negatively associated with reporting deterioration in psychological well-being (OR: 0.20, 95%CI: 0.07–0.56) from the first to the second survey wave. The most common reason for self-reported deterioration in mental health was loneliness (70%). Conclusions Approximately one year into the COVID-19 pandemic, the level of symptoms remained high, whereas the level of psychological well-being remained low among patients with mental illness.
Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non–Muscle-Invasive Bladder Cancer

Abstract Purpose: Identification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non–muscle-invasive bladder cancer (NMIBC), the most common form of urothelial carcinoma, is understudied. Experimental Design: Germline analysis was conducted on paired tumor/normal sequencing results from two distinct cohorts of patients initially diagnosed with NMIBC. Associations between clinicopathologic features and clinical outcomes with the presence of P/LP germline variants in ≥76 hereditary cancer predisposition genes were analyzed. Results: A similar frequency of P/LP germline variants were seen in our two NMIBC cohorts [12% (12/99) vs. 8.7% (10/115), P = 0.4]. In the combined analysis, P/LP germline variants were found only in patients with high-grade NMIBC (22/163), but none of the 46 patients with low-grade NMIBC (13.5% vs. 0%, P = 0.005). Fifteen (9.2%) patients with high-grade NMIBC had P/LP variants in DNA damage response genes, most within the nucleotide excision repair (ERCC2/3) and homologous recombination repair (BRCA1, NBN, RAD50) pathways. Contrary to prior reports in patients with NMIBC not receiving Bacillus Calmette-Guerin (BCG), P/LP germline variants were not associated with worse recurrence-free or progression-free survival in patients treated with BCG or with risk of developing upper tract urothelial carcinoma. Conclusions: Our results support offering germline counseling and testing for all patients with high-grade bladder cancer, regardless of initial tumor stage. Therapeutic strategies that target impaired DNA repair may benefit patients with high-grade NMIBC.
Comparison of bacterial communities on the surface of concrete breakwater structures and ambient bacterioplankton

Breakwater structures made of concrete are used widely around the world, and the bacteria living on these surfaces can cause the concrete to deteriorate. In this study, we collected bacterial biofilms from concrete breakwater structures located along the coast of an island, a mainland coast, and a freshwater riverbank as well as planktonic water samples from each site, and we analysed their bacterial community structures using Illumina sequencing. At the phylum level, Proteobacteria and Actinobacteria dominated planktonic samples, whereas Cyanobacteria, Proteobacteria and Bacteroidetes dominated the biofilm samples. High Cyanobacteria abundance was found in all biofilm samples. Bacterial communities significantly varied between planktonic and biofilm samples and between biofilm samples from seawater and freshwater. Only a small number of bacterial operational taxonomic units were shared by planktonic and biofilm samples from each sampling site. The permanganate index in ambient water had a more significant impact on biofilm bacterial communities than on planktonic samples. Additionally, ammonia nitrogen and total nitrogen contents were positively correlated and salinity was negatively correlated with bacterial beta diversity in biofilm samples.
Optimization and evaluation of a two-stage chromogenic assay procedure for measurement of emicizumab plasma levels

Emicizumab mimics the hemostatic activity of activated factor VIII (FVIIIa) within the tenase complex. Despite functional similarities between FVIIIa and emicizumab, conventional laboratory methods designed for monitoring of FVIII activity are inappropriate for the measurement of emicizumab. At present, a modified one stage (FVIII) assay (mOSA) is mainly used for emicizumab monitoring. Two-stage chromogenic FVIII assays based on human factors can be used, although limited performance due to lack of corresponding optimization might be observed. Furthermore, the presence of FVIII or anticoagulants in the patient sample may falsify assay results. To address these issues, we optimized and evaluated a two-stage chromogenic assay (emi-tenase) for measurement of emicizumab in plasma samples. Heat inactivation of samples was established to abolish the influence of endogenous or substituted FVIII. The lower limit of quantification (LLoQ) was found to be 2 μg/ml in a manual assay format and 9.5 μg/ml on an automated coagulation analyzer. Intra- and inter-assay coefficients of variation (CV) did not exceed 20%. Analysis of 17 patient plasma samples with severe haemophilia A under emicizumab treatment showed good correlation of results between the emi-tenase assay and the mOSA (Cohens Kappa coefficient = 0.9). Taken together, the emi-tenase assay allows specific measurement of emicizumab plasma levels over a broad concentration range (10 μg/ml to 100 μg/ml). The assay can be applied on an automated coagulation analyzer, demonstrating its applicability within a routine laboratory setting.
Enrichment of circulating trophoblasts from maternal blood using filtration-based Metacell® technology

In a cell-based non-invasive prenatal test (cbNIPT), intact circulating trophoblasts (CTs) are isolated from maternal blood for subsequent genetic analysis. Enrichment of these CTs from maternal blood is the most challenging step in the cbNIPT workflow. This study aims to assess the suitability of the filtration-based Metacell® technology to enrich CTs from maternal blood at week 10 to 13 of gestation. The Metacell® technology is a novel size-based enrichment technology that combines blood filtration through 8 μm pores with an in vitro culture method. Three protocols were evaluated. First, 8 mL or 16 mL of maternal blood was filtered and subsequently cultured in vitro on the separation membrane for 3 days in RPMI 1640. In addition, 16 mL of maternal blood was filtered, and immediately processed without further culturing. Y-chromosome-specific qPCR or STR analysis was performed to evaluate the enrichment of CTs. A total of 44 samples from pregnant women, out of which 26 were carrying a male fetus, were processed. Although five enriched male fetus samples show detectable male DNA quantities, it cannot be excluded that the obtained positive signal is caused by cell-free fetal DNA sticking to the Metacell® separation membrane. In conclusion, the Metacell® technology, tested as described, is not suitable for consistent enrichment of CTs.
Efficacy of outcome prediction of the respiratory ECMO survival prediction score and the predicting death for severe ARDS on VV-ECMO score for patients with acute respiratory distress syndrome on extracorporeal membrane oxygenation

Background Extracorporeal Membrane Oxygenation (ECMO) therapy for respiratory failure is an increasingly popular modality of support. Patient selection is an important aspect of outcome success. This review assesses the efficacy of the popular prognostic tools Respiratory ECMO Survival Prediction Score (RESP) and Predicting Death for Severe ARDS on VV-ECMO score (PRESERVE) for ECMO patient selection. Methods A literature search was performed. Six publications were found to match the specified selection criteria. These publications were assessed and compared using the area under the receiver operating characteristic (AUROC) curve statistical method to ascertain the discriminatory ability of the models to predict treatment outcome. Results Six articles were included in this review from 306 screened, of which all were retrospective cohort studies. Data was generated over a period of 3–9 years from 13 referring hospitals. Studies consisted of 467 male and 221 female (30 unknown) participants in total with a high heterogeneity. The PRESERVE prognostic model was found to have a higher AUROC score than the RESP model, however both models were found to be sub-optimal in their discriminatory ability. A high chance of bias was seen across all included studies. Conclusion It was the findings of this review, indicated by analysis using the AUROC measures, that the prognostic model PRESERVE performed better than RESP for predicting post ECMO therapy outcomes, for patients presenting with Acute Respiratory Distress Syndrome within their respective validated time frames, i.e., RESP at Intensive care unit (ICU) discharge and PRESERVE at 6 months post ICU discharge. However, It was recognized that comparator groups were small thereby introducing bias into the study. Further prospective, randomized studies would be necessary to effectively assess the utility of these predictive survival scores.
Role of Mutations in Differential Recognition of Viral RNA Molecules by Peptides

The conserved noncoding RNA elements in viral genomes interact with proteins to regulate various events during viral replication. We report studies on the recognition mechanisms of two helical peptides, namely, a native (Rev) peptide and a lab-evolved (RSG1.2) peptide, by a highly conserved viral RNA element from the human immunodeficiency virus 1 genome. Specifically, we investigated the physical interactions between the viral RNA molecule and helical peptides by computing free energy changes on mutating key amino acid residues involved in recognition of an internal loop in the viral RNA molecule.
Boosting confidence without boosting performance: item strength creates the illusion of source accuracy

ABSTRACT People often express high confidence for misremembered sources. Starns and Ksander ([2016]. Item strength influences source confidence and alters source memory zROC slopes. Journal of Experimental Psychology: Learning, Memory, and Cognition, 42(3), 351-365; hereafter SK16) found that this happens more often when a person is highly confident in memory for the item itself, and that simply increasing item memory can increase high-confidence source errors. Under the decision heuristic account, this pattern emerges because strong item memories contaminate source judgments by promoting high confidence responses even when source evidence is relatively weak. Consequently, strengthening item memory is predicted to increase confidence for both correct and incorrect source responses; however, SK16 could not assess this key prediction because their item-strength manipulation also impaired source memory. We report two experiments with new item-strengthening manipulations designed to minimise source memory impairments. Results replicated the evidence for the decision heuristic account reported by SK16 and provided additional support by showing a boost in source confidence for both correct and error responses when item memory was strengthened without accompanying source impairments .
A type IV Autotaxin inhibitor ameliorates acute liver injury and nonalcoholic steatohepatitis

The lysophosphatidic acid (LPA) signaling axis is an important but rather underexplored pathway in liver disease. LPA is predominantly produced by Autotaxin (ATX) that has gained significant attention with an impressive number of ATX inhibitors (type I‐IV) reported. Here, we evaluated the therapeutic potential of a (yet unexplored) type IV inhibitor, Cpd17, in liver injury. We first confirmed the involvement of the ATX‐LPA signaling axis in human and murine diseased livers. Then, we evaluated the effects of Cpd17, in comparison with the classic type I inhibitor PF8380, in vitro, where Cpd17 showed higher efficacy. Thereafter, we characterized the mechanism‐of‐action of both inhibitors and found that Cpd17 was more potent in inhibiting RhoA‐mediated cytoskeletal remodeling, and phosphorylation of MAPK/ERK and AKT/PKB. Finally, the therapeutic potential of Cpd17 was investigated in CCl4‐induced acute liver injury and diet‐induced nonalcoholic steatohepatitis, demonstrating an excellent potential of Cpd17 in reducing liver injury in both disease models in vivo. We conclude that ATX inhibition, by type IV inhibitor in particular, has an excellent potential for clinical application in liver diseases.
Quality of life and health status in older adults (≥65 years) up to five years following colorectal cancer treatment: Findings from the ColoREctal Wellbeing (CREW) cohort study

Objective Colorectal cancer (CRC) is common in older adults, with more than 70% of diagnoses in people aged ≥65 years. Despite this, there is a knowledge gap regarding longer-term outcomes in this population. Here, we identify those older people most at risk of poor quality of life (QoL) and health status in the five years following CRC treatment. Materials and methods CREW is a UK longitudinal cohort study investigating factors associated with health and wellbeing recovery following curative-intent CRC surgery. Participants completed self-report questionnaires pre-surgery, then at least annually up to five years. Longitudinal analyses explored the prevalence and pre-surgery risk factors of poor QoL (QLACS-GSS) and health status (EQ-5D: presence/absence of problems in five domains) in older (≥65 years) participants over five years. Results 501 participants aged ≥65years completed questionnaires pre-surgery; 45% completed questionnaires five years later. Oldest-old participants (≥80 years) reported poorer QoL (18% higher QLACS-GSS) and 2–4 times higher odds of having problems with mobility or usual activities, compared with the youngest-old (65–69 years) over follow-up. Baseline higher self-efficacy was significantly associated with better QoL (10–30% lower QLACS-GSS scores compared to those with low self-efficacy) and lower odds of problems in all EQ-5D domains. Adequate social support was significantly associated with better QoL (8% lower QLACS-GSS) and lower odds of problems with usual activities (OR = 0.62) and anxiety/depression (OR = 0.56). Conclusion There are important differences in QoL and health status outcomes for the oldest-old during CRC recovery. CREW reveals pre-surgery risk factors that are amenable to intervention including self-efficacy and social support.
Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19

Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID‐19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID‐19 pneumonia only accounts for a part of COVID‐19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well‐known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients.
The Added Value of Baseline Health-Related Quality of Life in Predicting Survival in High-Risk Prostate Cancer Patients Following Radical Prostatectomy

Purpose: Several studies have shown baseline health-related quality of life to be a valuable prognostic indicator of survival outcomes for various cancer entities in the metastatic setting. To date, there is no evidence regarding the prognostic value of baseline health-related quality of life for patients undergoing radical prostatectomy due to localized prostate cancer. Materials and Methods: A total of 1,029 patients with high-risk prostate cancer according to National Comprehensive Cancer Network® risk stratification and prospectively assessed baseline health-related quality of life prior to radical prostatectomy were identified. Patients were stratified by global health status domain of the QLQ-C30 questionnaire. Oncologic endpoints were biochemical recurrence-free survival and metastasis-free survival. Multivariable Cox regression models were performed to assess prognostic significance of baseline global health status on survival outcomes. Harrell’s discrimination C-index was applied to calculate the predictive accuracy of the model and previously described risk stratification models. Decision curve analysis was applied to test the clinical net benefit associated with adding global health status to our multivariable model (P < .05). Results: Median follow-up was 43 months. In multivariable analysis, global health status was confirmed as an independent predictor for increased biochemical recurrence-free survival (HR .97, 95% CI .96-.99; P = .001) and metastasis-free survival (HR .96, 95% CI .93-.99; P = .013), indicating a relative risk reduction of 2.9% for biochemical recurrence-free survival and 3.7% for metastasis-free survival per 1-point increase of baseline global health status. Adding baseline health-related quality of life to our model and to the Cancer of the Prostate Risk Assessment and National Comprehensive Cancer Network score improved discrimination in predicting biochemical recurrence-free survival and metastasis-free survival of the respective models. Decision curve analysis revealed a net benefit over all threshold probabilities. Conclusions: Our findings highlight baseline health-related quality of life to be a valuable and robust prognostic factor for patients with localized high-risk prostate cancer prior to radical prostatectomy. Baseline health-related quality of life increased prognostic accuracy of biochemical recurrence-free survival and metastasis-free survival.
Muscle Strength, Agility, and Body Composition in Children With Intestinal Failure on Parenteral Nutrition

Objectives: With increasing number of children with intestinal failure (IF) on long-term parenteral nutrition (PN), this study assesses the impact of IF on muscle strength, speed, and agility and body composition (BC), identifying clinical factors that may predict impairment. Methods: Cross-sectional study in children 5–18 years with IF on PN. Assessments included Bruininks-Oseretsky Test of Motor Proficiency-2 strength and agility subtest (BOT-2), and grip strength. BC data from dual-energy x-ray absorptiometry (DXA) measurements and clinical variables were collected by chart abstraction. Data were compared to age and sex matched controls and population norms. Results: Twenty-one children with IF (14 males), median age 8.33 (IQR: 6.96–11.04) years and 33 controls (20 males), 8.25 (6.67–10.79) years were included. Strength and agility (P < 0.001) and grip strength (P = 0.001) differed between groups. Nine of 21 (43%) of children with IF scored >1 standard deviation (SD) below mean on BOT-2 and 13 of 21 (62%) had grip strength >1 SD below mean. DXA measurements showed 10 of 18 (56%) of children had lower fat-free mass (FFM)% and higher fat mass (FM)% than reference norms. Decreased FFM% was associated with lower BOT-2 scores (r = 0.479; P = 0.044) and grip strength scores >1 SD below mean (P = 0.047). Additional clinical factors significantly impacting strength and agility included prematurity, height, hospitalizations, sepsis, and small bowel length. Conclusions: Children with IF are at risk of decreased muscle strength and agility, along with altered BC. Ongoing medical, nutritional, and rehabilitation intervention is vital to optimize outcomes.
Delivery of a Group Hypnosis Protocol for Managing Chronic Pain in Outpatient Integrative Medicine

ABSTRACT Although strong evidence exists for using individual hypnosis to treat pain, evidence regarding group applications is limited. This project evaluated changes in multiple outcome measures in persons with chronic pain treated with 8 weeks of group hypnosis. Eighty-five adults with diverse chronic pain etiologies completed an 8-session, structured group hypnosis treatment. Pain intensity, pain interference, and global health were evaluated at baseline, posttreatment, and 3- and 6-months posttreatment. Linear mixed effects models assessed changes in outcomes over time. In a model testing, all three outcome measures simultaneously, participants improved substantially from pre- to posttreatment and maintained improvement across follow-up. Analyses of individual outcomes showed significant pre- to posttreatment reductions in pain intensity and interference, which were maintained for pain intensity and continued to improve for pain interference across follow-up. The findings provide compelling preliminary evidence that a group format is an effective delivery system for teaching individual skills in using hypnosis for chronic pain management. Larger randomized controlled trials are warranted to demonstrate equivalence of outcomes between treatment modes.
Integrating flipped drain and power gating techniques for efficient FinFET logic circuits

Power dissipation is a main attention for designing complementary metal oxide semiconductor Very Large Scale Integration (VLSI) circuits in deep sub‐micron technology. Constant field device scaling leads to high transistor density, reduction in power supply, lower threshold voltage, and reduction in oxide thickness. This gives rise to short channel effects and increases the leakage currents causing power dissipation. In this paper, based on literature survey, new flipped drain gating (FDG) technique is proposed for mitigation of leakage currents; further FDG technique is integrated with power gating technique which makes power dissipation lower than FDG. Proposed techniques are integrated with FinFET technology and applied on Logic Gates and bench mark circuits on HSPICE simulator. Simulation is carried out at 27°C temperature by using 20 to 7‐nm Berkley Predictive Technology Module. Simulation results at 10‐MHz frequency shows maximum saving in leakage power using FDG technique at input vector 01 as 80.35% compared with conventional drain gating for EXOR logic. Similarly, FDG technique saves maximum dynamic power of 25.98% when compared with conventional drain gating for AND logic.