Miracle-dz/UniFAR-FTUs huggingface dataset:
An open, prospective cohort study of VV116 in Chinese participants infected with SARS-CoV-2 omicron variants

ABSTRACT Omicron variant of SARS-CoV-2 has become the predominant variant worldwide. VV116 is an oral drug with robust anti-SARS-CoV-2 efficacy in preclinical studies. We conducted an open, prospective cohort study to evaluate its safety and effectiveness in Chinese participants infected with the omicron variant from March 8th, 2022 to March 24th, 2022. 136 hospitalized nonsevere patients confirmed with COVID-19 were enrolled including 60 patients who received VV116 (300 mg, BID×5 days) in the treatment group and 76 patients who didn’t receive VV116 in the control group besides standard treatment. Viral load shedding time and adverse events were collected during the follow-up. There was no significant difference in baseline characteristics between the VV116 group and the control group, except for a higher symptom prevalence in the control group (P = 0.021). The median time from the first positive test to the first VV116 administration was 5 (range: 2-10) days. Participants who received VV116 within 5 days since the first positive test had a shorter viral shedding time than the control group (8.56 vs 11.13 days), and cox regression analysis showed adjusted HR of 2.37 [95%CI 1.50-3.75], P < 0.001. In symptomatic subgroup, VV116 group had a shorter viral shedding time than the control group (P = 0.016). A total of 9 adverse events with no serious adverse events were reported in the VV116 group, all of them were resolved without intervention. VV116 is a safe, effective oral antiviral drug, which shows a better performance within the early onset of omicron infection.
Cognitive workload evaluation of landmarks and routes using virtual reality

Investigating whether landmarks and routes affect navigational efficiency and learning transfer in traffic is essential. In this study, a virtual reality-based driving system was employed to determine the effects of landmarks and routes on human neurocognitive behavior. The participants made four (4) journeys to predetermined destinations. They were provided with different landmarks and routes to aid in reaching their respective destinations. We considered two (2) groups and conducted two (2) sessions per group in this study. Each group had sufficient and insufficient landmarks. We hypothesized that using insufficient landmarks would elicit an increase in psychophysiological activation, such as increased heart rate, eye gaze, and pupil size, which would cause participants to make more errors. Moreover, easy and difficult routes elicited different cognitive workloads. Thus, a high cognitive load would negatively affect the participants when trying to apply the knowledge acquired at the beginning of the exercise. In addition, the navigational efficiency of routes with sufficient landmarks was remarkably higher than that of routes with insufficient landmarks. We evaluated the effects of landmarks and routes by assessing the recorded information of the drivers’ pupil size, heart rate, and driving performance data. An analytical strategy, several machine learning algorithms, and data fusion methods have been employed to measure the neurocognitive load of each participant for user classification. The results showed that insufficient landmarks and difficult routes increased pupil size and heart rate, which caused the participants to make more errors. The results also indicated that easy routes with sufficient landmarks were deemed more efficient for navigation, where users’ cognitive loads were much lower than those with insufficient landmarks and difficult routes. The high cognitive workload hindered the participants when trying to apply the knowledge acquired at the beginning of the exercise. Meanwhile, the data fusion method achieved higher accuracy than the other classification methods. The results of this study will help improve the use of landmarks and design of driving routes, as well as paving the way to analyze traffic safety using the drivers’ cognition and performance data.
Student Thinking in the Professional Development of College Biology Instructors: An Analysis through the Lens of Sociocultural Theory

An important facet of inclusive, student-centered science teaching is for college instructors to reveal and respond to student thinking. Professional development (PD) provides formal settings for instructors to develop skills attending and responding to student ideas in their teaching. Using the lens of sociocultural theory, the purpose of this study was to explore the learning experiences of college instructors in long-term faculty learning communities (FLCs) that focused on student thinking. This study employed a qualitative design using semistructured interviews, analyzed through qualitative thematic analysis. We investigated the ways that social interactions focused on artifacts of student learning facilitated college instructors’ internalization of knowledge about teaching and learning. We found that participants valued the social space of the FLC for the camaraderie and diverse perspectives it facilitated and that participants internalized the discussions from their FLCs in the form of new insights into student thinking and plans for improving teaching. Our data support the idea that PD for college science teaching that includes social space focused on artifacts of student learning will lead to instructor learning. Further, our data point to the fruitfulness of new research to expand our knowledge of the implications of sociocultural theory for college science PD.
A novel approach to type 3 diabetes mechanism: The interplay between noncoding RNAs and insulin signaling pathway in Alzheimer's disease

Today, growing evidence indicates that patients with type 2 diabetes (T2D) are at a higher risk of developing Alzheimer's disease (AD). Indeed, AD as one of the main causes of dementia in people aged more than 65 years can be aggravated by insulin resistance (IR) and other metabolic risk factors related to T2D which are also linked to the function of the brain. Remarkably, a new term called “type 3 diabetes” has been suggested for those people who are diagnosed with AD while also showing the symptoms of IR and T2D. In this regard, the role of genetic and epigenetic changes associated with AD has been confirmed by many studies. On the other hand, it should be noted that the insulin signaling pathway is highly regulated by various mechanisms, including epigenetic factors. Among these, the role of noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs has been comprehensively studied with respect to the pathology of AD and the most well‐known underlying mechanisms. Nevertheless, the number of studies exploring the association between ncRNAs and the downstream targets of the insulin signaling pathway in the development of AD has notably increased in recent years. With this in view, the present study aimed to review the interplay between different ncRNAs and the insulin signaling pathway targets in the pathogenesis of AD to find a new approach in the field of combining biomarkers or therapeutic targets for this disease.
DNA-PKcs-dependent phosphorylation of RECQL4 promotes NHEJ by stabilizing the NHEJ machinery at DNA double-strand breaks

Abstract Non-homologous end joining (NHEJ) is the major pathway that mediates the repair of DNA double-strand breaks (DSBs) generated by ionizing radiation (IR). Previously, the DNA helicase RECQL4 was implicated in promoting NHEJ, but its role in the pathway remains unresolved. In this study, we report that RECQL4 stabilizes the NHEJ machinery at DSBs to promote repair. Specifically, we find that RECQL4 interacts with the NHEJ core factor DNA-PKcs and the interaction is increased following IR. RECQL4 promotes DNA end bridging mediated by DNA-PKcs and Ku70/80 in vitro and the accumulation/retention of NHEJ factors at DSBs in vivo. Moreover, interaction between DNA-PKcs and the other core NHEJ proteins following IR treatment is attenuated in the absence of RECQL4. These data indicate that RECQL4 promotes the stabilization of the NHEJ factors at DSBs to support formation of the NHEJ long-range synaptic complex. In addition, we observed that the kinase activity of DNA-PKcs is required for accumulation of RECQL4 to DSBs and that DNA-PKcs phosphorylates RECQL4 at six serine/threonine residues. Blocking phosphorylation at these sites reduced the recruitment of RECQL4 to DSBs, attenuated the interaction between RECQL4 and NHEJ factors, destabilized interactions between the NHEJ machinery, and resulted in decreased NHEJ. Collectively, these data illustrate reciprocal regulation between RECQL4 and DNA-PKcs in NHEJ.
Arginase-1 Is Required for Macrophage-Mediated Renal Tubule Regeneration

Significance Statement Proinflammatory macrophages that infiltrate the kidney after ischemia-reperfusion injury later transition to a proreparative state characterized by expression of multiple proteins including arginase-1 (Arg1). By comparing the kidney repair response after ischemia-reperfusion injury in mice that lack macrophage Arg1 expression with littermate controls, we show that macrophage Arg1 plays a critical role in renal recovery in part by promoting renal epithelial cell proliferative repair. Thus, therapeutic interventions that enhance Arg1 expression may improve renal recovery after kidney injury. Background After kidney injury, macrophages transition from initial proinflammatory activation to a proreparative phenotype characterized by expression of arginase-1 (Arg1), mannose receptor 1 (Mrc1), and macrophage scavenger receptor 1 (Msr1). The mechanism by which these alternatively activated macrophages promote repair is unknown. Methods We characterized the macrophage and renal responses after ischemia-reperfusion injury with contralateral nephrectomy in LysM-Cre;Arg1fl/fl mice and littermate controls and used in vitro coculture of macrophages and tubular cells to determine how macrophage-expressed arginase-1 promotes kidney repair. Results After ischemia-reperfusion injury with contralateral nephrectomy, Arg1-expressing macrophages were almost exclusively located in the outer stripe of the medulla adjacent to injured S3 tubule segments containing luminal debris or casts. Macrophage Arg1 expression was reduced by more than 90% in injured LysM-Cre;Arg1fl/fl mice, resulting in decreased mouse survival, decreased renal tubular cell proliferation and decreased renal repair compared with littermate controls. In vitro studies demonstrate that tubular cells exposed apically to dead cell debris secrete high levels of GM-CSF and induce reparative macrophage activation, with those macrophages in turn secreting Arg1-dependent factor(s) that directly stimulate tubular cell proliferation. Conclusions GM-CSF–induced, proreparative macrophages express arginase-1, which is required for the S3 tubular cell proliferative response that promotes renal repair after ischemia-reperfusion injury.
Conductive Ink with Circular Life Cycle for Printed Electronics

Electronic waste carries energetic costs and an environmental burden rivaling that of plastic waste due to the rarity and toxicity of the heavy‐metal components. Recyclable conductive composites are introduced for printed circuits formulated with polycaprolactone (PCL), conductive fillers, and enzyme/protectant nanoclusters. Circuits can be printed with flexibility (breaking strain ≈80%) and conductivity (≈2.1 × 104 S m−1). These composites are degraded at the end of life by immersion in warm water with programmable latency. Approximately 94% of the functional fillers can be recycled and reused with similar device performance. The printed circuits remain functional and degradable after shelf storage for at least 7 months at room temperature and one month of continuous operation under electrical voltage. The present studies provide composite design toward recyclable and easily disposable printed electronics for applications such as wearable electronics, biosensors, and soft robotics.
Perspective-taking is associated with increased discriminability of affective states in the ventromedial prefrontal cortex

Abstract Recent work using multivariate-pattern analysis (MVPA) on functional magnetic resonance imaging (fMRI) data has found that distinct affective states produce correspondingly distinct patterns of neural activity in the cerebral cortex. However, it is unclear whether individual differences in the distinctiveness of neural patterns evoked by affective stimuli underlie empathic abilities such as perspective-taking (PT). Accordingly, we examined whether we could predict PT tendency from the classification of blood-oxygen-level-dependent (BOLD) fMRI activation patterns while participants (n = 57) imagined themselves in affectively charged scenarios. We used an MVPA searchlight analysis to map where in the brain activity patterns permitted the classification of four affective states: happiness, sadness, fear and disgust. Classification accuracy was significantly above chance levels in most of the prefrontal cortex and in the posterior medial cortices. Furthermore, participants’ self-reported PT was positively associated with classification accuracy in the ventromedial prefrontal cortex and insula. This finding has implications for understanding affective processing in the prefrontal cortex and for interpreting the cognitive significance of classifiable affective brain states. Our multivariate approach suggests that PT ability may rely on the grain of internally simulated affective representations rather than simply the global strength.
Oral Swab Specimens Tested With Xpert MTB/RIF Ultra Assay for Diagnosis of Pulmonary Tuberculosis in Children: A Diagnostic Accuracy Study

Abstract Background Microbiologic diagnosis of childhood tuberculosis may be difficult. Oral swab specimens are a potential noninvasive alternative to sputum specimens for diagnosis. Methods This was a prospective diagnostic accuracy study of oral swab specimens (buccal and tongue) for pulmonary tuberculosis diagnosis in children (aged ≤ 15 years) in 2 South African hospital sites. Children with cough of any duration as well as a positive tuberculin skin test result, tuberculosis contact, loss of weight, or chest radiograph suggestive of pulmonary tuberculosis were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Xpert MTB/RIF Ultra) assay and liquid culture. Oral swab specimens were obtained before sputum specimens, frozen, and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed tuberculosis, unconfirmed tuberculosis (receipt of tuberculosis treatment), or unlikely tuberculosis according to National Institutes of Health consensus definitions based on sputum microbiologic results. Results Among 291 participants (median age [interquartile range], 32 [14–73] months), 57 (20%) had human immunodeficiency virus (HIV), and 87 (30%) were malnourished; 90 (31%) had confirmed pulmonary tuberculosis (rifampicin resistant in 6 [7%] ), 157 (54%), unconfirmed pulmonary tuberculosis, and 44 (15%), unlikely tuberculosis. A single oral swab specimen was obtained from 126 (43%) of the participants (tongue in 96 and buccal in 30) and 2 swab specimens from 165 (57%) (tongue in 110 and buccal in 55). Sensitivity was low (22% [95% confidence interval, 15%–32%]) for all swab specimens combined (with confirmed pulmonary tuberculosis as reference), but specificity was high (100% [91%–100%]). The highest sensitivity was 33% (95% confidence interval, 15%–58%) among participants with HIV. The overall yield was 6.9% with 1 oral swab specimen and 7.2% with 2. Conclusions Use of the Xpert MTB/RIF Ultra assay with oral swab specimens provides poor yield for microbiologic pulmonary tuberculosis confirmation in children.
Strengthening Primary Healthcare through accelerated advancement of the global pharmacy workforce: a cross-sectional survey of 88 countries

Objective Advancing the pharmacy workforce contributes to strengthening primary healthcare and accelerating progress towards universal health coverage. This study aimed to identify key enablers to support policy development for national pharmacy workforce advancement. Design A cross-sectional country-level questionnaire was distributed from July 2018 to March 2019. Setting National-level or country-level pharmacy workforce development policy. Participants Professional leadership associations and national agencies of the International Pharmaceutical Federation (FIP). The FIP global database included 129 countries. Measures The questionnaire was designed to collate data on the scope of advanced and specialist practice in respondent countries. Multiple correspondence analysis and subsequent cluster analysis were conducted to explore the associations and patterns of country-level attributes of systems in place for the pharmacy workforce advancement in order to develop a general transnational model for country-level advanced practice development. Results Eighty-eight countries (68.2% response rate) responded to the questionnaire. Factors that enhance and contribute to advanced practice policy development include the country’s socioeconomic factors and the availability of national practice advancement concepts. The essential advancement concepts include the availability of framework and professional recognition systems, programmes assisting advanced practice development and workforce advancement and recognition opportunities. Cluster analysis identified three clusters of country respondents. First cluster included low-income and middle-income with poor pharmacy advancement implementation, second cluster included a higher socioeconomic status with weaker pharmacy workforce advancement implementation and third cluster included upper middle-income to high-income countries and high rates of pharmacy advancement implementation. Conclusion The key factors identified in this study can be used to support a transnational approach to pharmacy workforce advancement. The three clusters identified highlighted that workforce advancement was not an exclusive trait of higher-income countries. Lessons from countries that have already adopted concepts of advancement in pharmacy practice could be adopted to other countries to accelerate the progress of advanced practice globally.
Comparison of conventional and liquid-based Pap smear methods in the diagnosis of precancerous cervical lesions

Abstract Cervical cancer is one of the five most common cancers among women. The present study aimed to compare conventional and liquid-based Pap smear methods in 2018 in Kerman, Iran. This was a cross-sectional study. Pap smear samples (conventional Pap smear (CN) and liquid-based cytology (LBC)) were collected from five health centres in Kerman. Samples were classified into two groups of liquid and CNs, and each group was classified into normal, abnormal (including, atypical squamous cells of undetermined significance (ASCUS+), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H+), low-grade squamous intraepithelial lesion (LSIL+), high-grade squamous intraepithelial lesion (HSIL+) and cancer+) and unsatisfactory. Descriptive data analysis and chi-square/Fisher's exact test were performed in SPSS 20 (SPSS Inc., Chicago, IL). Totally, 31,513 women were screened by two CN and LBC. The mean age of subjects was 39.73 ± 9.58 years. The unsatisfactory smears (1.4% versus 0.02%; p=.001) and ASCUS+ (45.1% versus 39.4%; p=.007) were more reported by conventional tests, while LSIL+ (33.1% versus 38.9%; p=.005) was reported by the LBC test. Among women who were younger than 40 years, the CIN2+ that was found by LBC was significantly more than the CN method (37.4% versus 31.7, p=.04) and among older women (older than 40 years) the CIN1+ was significantly more as well (18% versus 13.6%, p=.05). The present study showed that, although LBC had many advantages, CN is still useful. Further studies are to be suggested as a clinical trial in another population with a large number of participants to compare the diagnosing methods of cervical cancers. Impact Statement What is already known on this subject? The conventional Pap smear (CN) and liquid-based cytology (LBC) methods are the most common methods for screening cervical cancers. Previously, in some studies, LBC was reported as a better method and in some studies, traditional method was preferred. Conflicting results were found in previous articles. What do the results of this study add? LBC compared to CN could find truer abnormal cases. The superiority of the LBC method is seen in cases such as reducing unsatisfactory cases, etc. LBC compared to CN could find more CIN+. Also, LBC could find more CIN1+ among women older than 40 years and more CIN+ ≥2 among younger women. What are the implications of these findings for clinical practice and/or further research? Although LBC has many advantages and it is easier, CN is still useful and both methods are suitable for cervical abnormality and cancer detection. CN cannot be declared an outdated method.
Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry

Abstract Background Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. Objective To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. Methods Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. Results Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). Conclusion The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.
Covid-19, Fiscal Policies, and Small-and-Medium-Sized Firm Survival: Evidence From the Cross-Country Matching Analysis

Objective The present study examines the effect of fiscal policies on firm survival for small-and-medium-sized enterprises in the cross-country level firm-level data. Research Design A propensity score matching analysis is utilised for the post-COVID-19 period firms by using the World Bank Enterprise Follow-up Surveys for the pandemic period. Small-and-medium-sized enterprises are essential to the economy; firm failures can increase in a pandemic. Results The obtained findings show that the effect of fiscal policies has an essential effect on small-and-medium-sized enterprises survival in the COVID-19 pandemic period by using a cross-country heterogenous firm-level sample. Conclusions In this context, the present study shed new light on the link between COVID-19-related fiscal policies and small-and-medium-sized firm survival in developing countries.