Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Four Point of Care (POC) Antigen Assays for the Detection of the SARS-CoV-2 Variant Omicron

In the manuscript, we report an evaluation of the capability of 4 point of care (POC) antigen assays, the BD Veritor, Abbott BinaxNow, Orasure InteliSwab and Quidel QuickVue to detect the Omicron variant of SARS-CoV-2, and we compared their analytical sensitivity for Omicron versus Delta. In this analysis we found that all four assays detected Omicron and Delta at 104 and 105 TCID50/mL, respectively. ABSTRACT Ensuring SARS-CoV-2 diagnostics that can reliably detect emerging variants has been an ongoing challenge. Due to the rapid spread of the Omicron variant, point-of-care (POC) antigen tests have become more widely used. This study aimed at (i) comparing the analytical sensitivity (LOD) of 4 POC antigen assays, BD Veritor, Abbott BinaxNow, Orasure InteliSwab and Quidel QuickVue, for the Omicron versus the Delta variant and (ii) verifying the reproducible detection of Omicron by the 4 antigen assays. The LOD for all four assays were evaluated using Omicron and Delta virus stocks quantified for infectivity and genome copies. The four assays detected all replicates of Omicron and Delta dilutions at 104 and 105 TCID50/mL, respectively. We quantified both viral stocks using droplet digital PCR (ddPCR), which revealed that the Omicron stock had equivalent copies of the N gene to Delta at a one log lower infectious virus. The Abbott BinaxNow and Orasure InteliSwab had the highest analytical sensitivity for Omicron while the Orasure InteliSwab and the Quidel QuickVue had the highest analytical sensitivity for Delta. When 14 SARS-CoV-2 real-time PCR positive nasal/nasopharyngeal swab samples (12 Omicron and 2 Delta, mean Ct = 19.1), were tested by the four assays, only the QuickVue detected all samples. Antigen test positivity correlated with recovery of infectious virus on cell culture in 9 out of 13 tested specimens from symptomatic, asymptomatic, unvaccinated, and vaccinated individuals. Although our study confirms the reduced analytical sensitivity of antigen testing compared to molecular methods, the Omicron variant was detectable by the four evaluated rapid antigen tests. IMPORTANCE In the manuscript, we report an evaluation of the capability of 4 point of care (POC) antigen assays, the BD Veritor, Abbott BinaxNow, Orasure InteliSwab and Quidel QuickVue to detect the Omicron variant of SARS-CoV-2, and we compared their analytical sensitivity for Omicron versus Delta. In this analysis we found that all four assays detected Omicron and Delta at 104 and 105 TCID50/mL, respectively. We further quantified the viral stocks used by droplet digital (ddPCR) and found that the Omicron stock had equivalent copies of the N gene to Delta at a one log lower infectious virus titer and that an increased RNA to infectious virus ratio may be contributing to discrepancies in limit of detection in Omicron compared to Delta. We evaluated 14 SARS-CoV-2 real-time PCR positive nasal/nasopharyngeal swab samples (12 Omicron and 2 Delta), with an average cycle threshold value of 19.1, and only the QuickVue showed 100% agreement.
Predicting Ulcerative Colitis Relapse in Clinical Remission With Fecal Immunochemical Occult Blood Test or Prostaglandin E-Major Urinary Metabolite

INTRODUCTION: The fecal immunochemical occult blood test (FIT) and prostaglandin E-major urinary metabolite (PGE-MUM) have been reported to predict the relapse of ulcerative colitis (UC) during remission. In this study, we directly compared FIT and PGE-MUM in predicting relapse and examined the effect of disease duration on these biomarkers. METHODS: Measurements of 2 biomarkers and endoscopic examination were performed in 73 patients with UC in remission. The patients were followed up for 12 months, and clinical relapse was evaluated. In addition, we divided the patients into long-term disease duration and short-term disease duration groups for analysis. RESULTS: Twenty-one patients (28.8%) relapsed within 12 months. FIT and PGE-MUM levels were significantly higher in the relapsed group than in the remission group. Cutoff values of FIT and PGE-MUM for predicting relapse using receiver operating characteristic analysis were 65.0 ng/mL (area under the curve [AUC]: 0.723) and 25.2 μg/g·Cr (AUC: 0.701), respectively. Patients with FIT ≥ 65.0 ng/mL and PGE-MUM ≥ 25.2 μg/g·Cr had a higher risk of clinical relapse. In the short-term disease duration group, the AUCs of FIT were larger than those of PGE-MUM using receiver operating characteristic analysis, in most instances. By contrast, the AUCs of PGE-MUM were larger than those of FIT in most cases in the long-term disease groups. DISCUSSION: FIT and PEG-MUM were highly accurate in predicting clinical relapse in UC patients with short and long disease durations in remission, respectively.
Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity

Background: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect of attenuated IGF1 signaling on cardiac aging remains controversial. Methods: We performed a lifelong study to assess cardiac health and lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced IGF1 receptor (IGF1R) signaling. Male mice with human IGF1R overexpression or dominant negative phosphoinositide 3-kinase mutation were examined at different life stages by echocardiography, invasive hemodynamics, and treadmill coupled to indirect calorimetry. In vitro assays included cardiac histology, mitochondrial respiration, ATP synthesis, autophagic flux, and targeted metabolome profiling, and immunoblots of key IGF1R downstream targets in mouse and human explanted failing and nonfailing hearts, as well. Results: Young mice with increased IGF1R signaling exhibited superior cardiac function that progressively declined with aging in an accelerated fashion compared with wild-type animals, resulting in heart failure and a reduced lifespan. In contrast, mice with low cardiac IGF1R signaling exhibited inferior cardiac function early in life, but superior cardiac performance during aging, and increased maximum lifespan, as well. Mechanistically, the late-life detrimental effects of IGF1R activation correlated with suppressed autophagic flux and impaired oxidative phosphorylation in the heart. Low IGF1R activity consistently improved myocardial bioenergetics and function of the aging heart in an autophagy-dependent manner. In humans, failing hearts, but not those with compensated hypertrophy, displayed exaggerated IGF1R expression and signaling activity. Conclusions: Our findings indicate that the relationship between IGF1R signaling and cardiac health is not linear, but rather biphasic. Hence, pharmacological inhibitors of the IGF1 pathway, albeit unsuitable for young individuals, might be worth considering in older adults.
Anticoagulant therapy for splanchnic vein thrombosis: an individual patient data meta-analysis

Abstract Robust evidence on the optimal management of splanchnic vein thrombosis (SVT) is lacking. We conducted an individual-patient meta-analysis to evaluate the effectiveness and safety of anticoagulation for SVT. Medline, Embase, and clincaltrials.gov were searched up to June 2021 for prospective cohorts or randomized clinical trials including patients with SVT. Data from individual datasets were merged, and any discrepancy with published data was resolved by contacting study authors. Three studies of a total of 1635 patients were included. Eighty-five percent of patients received anticoagulation for a median duration of 316 days (range, 1-730 days). Overall, incidence rates for recurrent venous thromboembolism (VTE), major bleeding, and mortality were 5.3 per 100 patient-years (p-y; 95% confidence interval [CI], 5.1-5.5), 4.4 per 100 p-y (95% CI, 4.2-4.6), and 13.0 per 100 p-y (95% CI, 12.4-13.6), respectively. The incidence rates of all outcomes were lower during anticoagulation and higher after treatment discontinuation or when anticoagulation was not administered. In multivariable analysis, anticoagulant treatment appeared to be associated with a lower risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.27-0.64), major bleeding (HR, 0.47; 95% CI, 0.30-0.74), and mortality (HR, 0.23; 95% CI, 0.17-0.31). Results were consistent in patients with cirrhosis, solid cancers, myeloproliferative neoplasms, unprovoked SVT, and SVT associated with transient or persistent nonmalignant risk factors. In patients with SVT, the risk of recurrent VTE and major bleeding is substantial. Anticoagulant treatment is associated with reduced risk of both outcomes.
Maternal stress and social support during Hurricane Florence

Abstract In theoretical research on disaster vulnerability, access to resources is critical for optimal outcomes. Studying the impact of a hurricane on maternal stress can expand theories of disaster vulnerability. This is a cross-sectional mixed-methods prospective study of maternal stress during Hurricane Florence in the United States. Results from chi-squares compared the proportion of respondents who reported having support for a financial emergency were significant, specifically that higher income respondents indicated the ability to rely on someone in case of an emergency. A regression analysis indicated that social support was significant and negatively related to stress as a dependent variable, while evacuation status and pregnancy status were not significant predictors of stress. Five themes emerged from the overall qualitative data: concerns about infant feeding, evacuation logistics, general stress, family roles, and ‘other’ issues.
The modest impact of the COVID-19 pandemic on training expectations at internship programs offering specialization in neuropsychology

Abstract Objective: Given the decreased clinical training opportunities during the COVID-19 pandemic, this study aimed to provide insights into how training directors and supervising neuropsychologists from internships offering neuropsychology training adjusted expectations of competitive applicants. Method: Respondents (n = 50) from internships offering at least an “exposure” in neuropsychology completed questions about how training expectations of competitive applicants have changed because of the COVID-19 pandemic. Results: Most respondents reported decreased expectations for clinical hours and research productivity and increased expectations for telehealth experience and involvement in working with culturally diverse populations. Additionally, more than half of respondents from programs at university-affiliated and Veteran Affairs medical centers indicated reduced expectations for average number of integrated reports. Furthermore, compared to respondents at Veteran Affairs medical centers, respondents at university-affiliated medical centers stated decreased expectations for average number of paper presentations. Conclusions: The COVID-19 pandemic has motivated subtle changes in expectations of competitive neuropsychology-oriented internship applicants, specific to clinical experience, research productivity, and prioritization of certain application materials. Qualitative responses suggest that many respondents endeavored to improve applicant screening rather than lower expectations for applicants. As a result, consistent with previous recommendations, the importance of fit between trainee and training program should continue to be emphasized by prospective applicants. These findings have important implications for trainees for the next several years, as graduate students at all stages of training ultimately progress to the internship application stage.
The impact of medical therapy on left ventricular strain: Current state and future perspectives

The speckle tracking strain is becoming a frequently used marker of subclinical left ventricular systolic dysfunction. Despite the wide range of data concerning left ventricular strain variability in the general population and its changes in various pathologic conditions, the information about the impact of medical therapy on left ventricle strain is limited. This article provides an analysis of published studies of left ventricle strain changes in response to different agents and combinations of medical therapies used for hypertension and congestive heart failure.
Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling.

BACKGROUND Efficient recovery of circulating tumor DNA (ctDNA) depends on the quantity and quality of circulating cell-free DNA (ccfDNA). Here, we evaluated whether various ccfDNA extraction methods routinely applied in Dutch laboratories affect ccfDNA yield, ccfDNA integrity, and mutant ctDNA detection, using identical lung cancer patient-derived plasma samples. METHODS Aliquots of 4 high-volume diagnostic leukapheresis plasma samples and one artificial reference plasma sample with predetermined tumor-derived mutations were distributed among 14 Dutch laboratories. Extractions of ccfDNA were performed according to local routine standard operating procedures and were analyzed at a central reference laboratory for mutant detection and assessment of ccfDNA quantity and integrity. RESULTS Mutant molecule levels in extracted ccfDNA samples varied considerably between laboratories, but there was no indication of consistent above or below average performance. Compared to silica membrane-based methods, samples extracted with magnetic beads-based kits revealed an overall lower total ccfDNA yield (-29%; P < 0.0001) and recovered fewer mutant molecules (-41%; P < 0.01). The variant allelic frequency and sample integrity were similar. In samples with a higher-than-average total ccfDNA yield, an augmented recovery of mutant molecules was observed. CONCLUSIONS In the Netherlands, we encountered diversity in preanalytical workflows with potential consequences on mutant ctDNA detection in clinical practice. Silica membrane-based methodologies resulted in the highest total ccfDNA yield and are therefore preferred to detect low copy numbers of relevant mutations. Harmonization of the extraction workflow for accurate quantification and sensitive detection is required to prevent introduction of technical divergence in the preanalytical phase and reduce interlaboratory discrepancies.
PD‐L1 expression and FGFR‐mutations among Danish patients diagnosed with metastatic urothelial carcinoma: A retrospective and descriptive study

Checkpoint inhibitors have changed the treatment landscape of advanced urothelial carcinoma (mUC), and recently, a fibroblast‐growth‐factor‐receptor (FGFR) inhibitor has been introduced. This study aimed at estimating programmed death‐ligand 1 (PD‐L1) expression in primary tumors (PTs) and the PD‐L1 expression concordance between PTs and paired metastases in 100 patients with UC managed in the real‐world setting. Further, the aim was to investigate FGFR1–3 aberrations and the correlation between FGFR1–3 aberrations and PD‐L1 expression. PD‐L1 immunohistochemistry was performed on 100 formalin‐fixed paraffin‐embedded archival primary UC samples and 55 matched metastases using the 22C3 PD‐L1 assay. PD‐L1 expression was determined by the combined positive score, considered positive at ≥10. Targeted next‐generation sequencing on the S5+/Prime System with the Oncomine Comprehensive Assay version 3 was used to detect FGFR1‐3 aberrations in PTs. We found that 29 of 100 PTs had positive PD‐L1 expression. The PD‐L1 concordance rate was 71%. FGFR1‐3 aberrations were observed in 18% of PTs, most frequently FGFR3 amplifications or mutations. We found no association between FGFR1‐3 aberrations and PT PD‐L1 expression (p = 0.379). Our data emphasize the need for further studies in predictive biomarkers.
Placenta accreta spectrum—A single‐center retrospective observational cohort study of multidisciplinary management over time

To evaluate whether the results of a previous study that showed a decrease in blood loss and transfusions with a multidisciplinary approach, including a fixed team when delivering women diagnosed with placenta accreta spectrum at Sahlgrenska University Hospital, remained low throughout time, and to investigate hospital stay and maternal and neonatal complications during a time period with varying team structure compared with previous periods.
Facing Uncertainty: Interpretation of Ambiguous Emotional Faces in Childhood Social Anxiety Disorder

ABSTRACT Objective The current study examined whether children with a social anxiety disorder (SAD) demonstrate divergent facial emotion processing and a disorder-specific negative interpretation bias in the processing of facial emotional expressions. This study aimed to overcome previous study limitations by including both a nonsocially anxious control group and a healthy control group to examine whether childhood SAD is characterized by a general emotion labeling deficit, and/or by a negative interpretation bias, indicated by systematic misclassifications, or a lower threshold for recognizing threatening emotions. Method Participants were 132 children aged 7–12 years (M age = 9.15; 45.5% female). Children with SAD (n = 42) were compared to children with other, nonsocial, anxiety disorders (n = 40) and healthy control children (n = 50) on a novel facial emotion recognition task. Children judged ambiguous happy/neutral, angry/neutral and fear/neutral faces that were morphed at different intensities (10%, 30%, 50%, 70%). Results Children with SAD did not differ from other groups in their accuracy of identifying emotions. They did not show systematic misclassifications or a heightened sensitivity to negative, threatening faces either. Rather, children with nonsocial anxiety disorders showed a generally heightened sensitivity to emotional faces. Conclusions The current study does not provide evidence for a general deficit in labeling of emotional faces in childhood SAD. Childhood SAD was not characterized by an interpretation bias in processing emotional faces. Children with nonsocial anxiety disorders may benefit from assistance in accurately interpreting the degree of emotionality in interpersonal situations.
Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration

Abstract Background Isavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats. Objectives To determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose. Animals Eight healthy, adult research cats. Methods Four cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed. Results Both PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%. Conclusions and Clinical Importance Isavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.
An increase in force after stretch of diaphragm fibers and myofibrils is accompanied by an increase in sarcomere length non-uniformities and Ca2+ sensitivity.

When muscle fibers from limb muscles are stretched while activated, the force increases to a steady-state level that is higher than that produced during isometric contractions at a corresponding sarcomere length, a phenomenon known as residual force enhancement (RFE). The mechanisms responsible for the RFE are an increased stiffness of titin molecules which may lead to an increased Ca2+ sensitivity of the contractile apparatus,and the development of sarcomere length non-uniformities. RFE is not observed in cardiac muscles, which makes this phenomenon specific to certain preparations. The aim of this study was to investigate if the RFE is present in the diaphragm, and its potential association with an increased Ca2+ sensitivity and the development of sarcomere length non-uniformities. We used two preparations: single intact fibers and myofibrils isolated from the diaphragm from mice. We investigated RFE in a variety of lengths across the force-length relationship. RFE was observed in both preparations at all lengths investigated, and was larger with increasing magnitudes of stretch. RFE was accompanied by an increased Ca2+ sensitivity as shown by a change in the force-pCa2+-curve, and increased sarcomere length non-uniformities. Therefore, RFE is a phenomenon commonly observed in skeletal muscles, with mechanisms that are similar across preparations.
Children for integrity: The influence of moral stories on pre-schoolers’ integrity values

This study aimed to analyze the effect of an integrity intervention program in preschool focusing on the use of moral integrity stories that resemble the Jordanian cultural identity on children’s moral integrity values. A total of 200 preschoolers’ (4- to 5-year-olds) participated in the study, 95 female and 105 male participants from three private preschools in Amman were recruited. The sample was randomly selected and divided into experimental and control groups. Two-way ANOVA analysis was used to analyze the data. The results revealed main effect (p < 0.0001) of the intervention for each dimension of the scale, empathy, honesty, respect, and courage, and the overall scale of integrity was in favor of the experimental group, with no main effect of the intervention by gender on any scale dimension. This study concluded that use of moral stories to integrate core moral values in pre-schoolers’ from the beginning aid in developing honesty, empathy, courageous and respectful intentions in coming generation to improve prosocial attitude leading to overall benefit to Jordanian society.