Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pharmacokinetics–Time to Alleviation of Symptoms Model to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B

Baloxavir marboxil, the prodrug of baloxavir acid, is an anti‐influenza antiviral. Here, a pharmacokinetics–time to alleviation of symptoms (PK–TTAS) model was developed and used to (I) characterize the PK–TTAS relationship, (II) quantify the impact of covariates, and (III) predict TTAS in different ethnic groups. Data from 1781 otherwise‐healthy (OwH) or high‐risk (HR) patients included in phase II (JapicCTI‐153090) and III studies (NCT02954354 and NCT02949011) were used; patients received either placebo or oral baloxavir marboxil. The natural distribution of TTAS in placebo‐treated patients was modeled, then TTAS data from the baloxavir marboxil arms were added to model the impact of baloxavir acid concentration on TTAS. PK parameters estimated by a population PK model and informed by phase I data (NCT03959332 and KCT0003535) were included to simulate TTAS in Chinese and South Korean patients. Composite symptom score at baseline (TSS0), ethnicity, sex, and patient type (OwH or HR) significantly impacted the natural TTAS distribution. TTAS reduced with increasing baloxavir acid concentrations. Compared with placebo, high and low baloxavir acid exposures (AUC0‐inf 5.13–16.65 and 0.72–5.13 μg.hr/mL, respectively) significantly reduced TTAS; no covariates affected the drug effect on TTAS. Simulated TTAS was similar between OwH or HR Chinese, South Korean, and other Asian patients, with median reductions from placebo between 18.3–18.8 hours and 21.2–22.0 hours in OwH and HR patients, respectively, assuming TSS0 > 10. Ethnicity (Asian vs. non‐Asian) did not significantly impact the drug effect on TTAS; predicted TTAS was similar across different Asian populations. This suggests Chinese and South Korean patients may benefit from similar efficacy as other Asian patients.
Seize the day, …s(e)ize the device: The emerging imaging modality to improve left atrial appendage device sizing

There is still uncertainity about the use of computed tomography‐scan for left atrial appendage occlusion (LAAO) device sizing. The main reason for this disappointing position is likely to relate to the scarcity of robust data, since there is still difference among institutions with regards how to perform measurement of the devices. Dallan et al. report their own experience on the use of a novel computed tomography angiography‐based (CTA) for sizing the Watchman Flex device for LAAO. The authors through the TruPlan software package that a preprocedural CTA sizing protocol can be applied successfully with intracardiac echocardiography guidance and provide excellent procedural outcomes. The applied CTA protocol is safe and can provide high success rates with the WatchmanTM FLX device reducing the number of deployment attempts and reducing the risk of complications.
Developing and validating a university needs instrument to measure the psychosocial needs of university students

Abstract Background University students are four times more likely to experience elevated levels of psychological distress compared to their peers. The psychosocial needs of university students are associated with high psychological distress, stressful life events, and academic performance. Our study focuses on developing a measure to help universities identify these psychosocial needs. Aims The study aimed to develop and validate the factor structure of the University Needs Instrument and identify the relationship between psychosocial needs, psychological distress and academic performance among university students. Sample Undergraduate university students (N = 511) currently studying at university. Method Participants completed demographic questions, the University Needs Instrument and the Kessler‐10 Psychological Distress scale. The University Needs Instrument comprises 30 items within six psychosocial factors (academic support, financial support, support from family, support from friends, practical support and emotional support), each consisting of five items. Results Confirmatory factor analysis showed that all items significantly loaded on the six hypothesized factors. The hypothesized model was supported by the data displaying excellent model fit and psychometric properties. Our analysis determined that the UNI has strong internal consistency. The results also confirmed that university students' high levels of psychological distress and their academic performance may be affected by their psychosocial needs. Conclusions Our findings have provided an initial validation of the UNI to help screen and identify the psychosocial needs of university students. This scale can be used to identify the appropriate psychosocial support that can be offered to students and in turn could help reduce their psychological distress, improve their psychosocial well‐being and increase academic performance.
Neutralizing activity to SARS‐CoV‐2 in 1.2 to 10.0 month convalescent plasma samples of COVID‐19: A transversal surrogate in vitro study performed in Quito‐Ecuador

Coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, was first reported in Wuhan, China, in December 2019. Diagnostic methods for the detection of the virus and seroconversion of neutralizing antibodies (NAbs) in plasma have been developed specifically, but some of them require a BSL3 facility. In this study, we used the SARS‐CoV‐2 Surrogate Virus Neutralization Test Kit to determine the presence or absence of NAbs anti‐receptor binding domain of the viral spike (S) glycoprotein in a BSL2 facility. The sample population was chosen in Quito, Ecuador, with a total of 88 COVID‐19 positive convalescent patients. We determined that 97.7% of the analyzed convalescent sera maintained the presence of NAbs with neutralizing activity, and this activity remained until 10 months after the infection in some cases. In addition, the relationship between the presence of NAbs and immunoglobulin G was significant compared to immunoglobulin M, which tended to be absent over time.
Patterns of Adverse Childhood Experiences and Mental Health: Evidence From College Students in Korea

Adverse childhood experiences (ACEs) are concerning exposures that may have detrimental effects on mental health. Much of the prior evidence on ACEs comes from the U.S and western developed countries. In light of the limited knowledge of ACEs in other social contexts and the interconnection among adversities, this study aims to identify distinct patterns of co-occurring ACEs and examines the associations between those adversities and mental health in South Korea. We used data from a national sample of Korean college students recruited via non-probability quota sampling in 2019 (N = 1037). The dependent variables included three measures of mental health assessed by the Brief Symptom Inventory depression symptoms, anxiety symptoms, and somatization symptoms. The independent variable was the patterns of ACEs identified using 14 indicators of childhood adversity. We conducted a Latent Class Analysis with a distal outcome, using the Bolck, Croons, and Hagenaars method. The analysis found four patterns of ACEs: extreme adversity (8%), family violence (20.3%), economic adversity (10.4%), and low adversity (61.3%). The extreme adversity group exhibited multiple exposures, including interpersonal violence in home environments, economic hardship, and bullying victimization by peers. The results suggest that the extreme adversity and family violence groups showed significantly worse mental health symptoms than the economic adversity and low adversity groups. Also, the extreme adversity group reported significantly higher levels of depression symptoms and somatization symptoms than the family violence group. This study expands the current understanding of ACEs and their harmful effects on mental health in young adulthood specific to Korea while comparing them with other social contexts. Researchers and practitioners should recognize the co-occurrence of child adversities, rather than overestimating sole adversity, to develop effective strategies for promoting mental health.
In vitro and in vivo detection of microbial gene expression in bioactivated scaffolds seeded with cyanobacteria

Dermal replacement materials bioactivated with cyanobacteria have shown promising potential for wound regeneration. To date, extraction of cyanobacteria RNA from seeded scaffolds has not been described. The aim of this study was to develop a method to isolate total RNA from bioactivated scaffolds and to propose a new approach in determining living bacteria based on real‐time PCR. Transgenic Synechococcus sp. PCC 7002 (tSyn7002) were seeded in liquid cultures or scaffolds for dermal regeneration in vitro and in vivo for 7 days. RNA was extracted with a 260/280 ratio of ≥2. The small subunit of the 30S ribosome in prokaryotes (16S) and RNAse P protein (rnpA) were validated as reference transcripts for PCR analysis. Gene expression patterns differed in vitro and in vivo. Expression of 16S was significantly upregulated in scaffolds in vitro, as compared to liquid cultures, whilst rnpA expression was comparable. In vivo, both 16S and rnpA showed reduced expression compared to in vitro (16S: in vivo Ct value 13.21 ± 0.32, in vitro 12.44 ± 0.42; rnpA in vivo Ct value 19.87 ± 0.41, in vitro 17.75 ± 1.41). Overall, the results demonstrate rnpA and 16S expression after 7 days of implantation in vitro and in vivo, proving the presence of living bacteria embedded in scaffolds using qPCR.
Integrin-linked kinase affects the sensitivity of esophageal squamous cell carcinoma cells to chemotherapy with cisplatin via the Wnt/beta-catenin signaling pathway

ABSTRACT Recent studies have shown that the expression of integrin-linked kinase (ILK) was related to the occurrence, development, and malignant progression of esophageal squamous cell carcinoma (ESCC). However, research on the relationship between ILK and the chemosensitivity of ESCC has to date not been reported. The present study found that ILK was highly expressed in ESCC cell lines, and the overexpression of ILK in ESCC cells reduced the incidence of cell apoptosis and alleviated the cytotoxicity on cells induced by cisplatin (CDDP). Inversely, ILK knockdown increased CDDP-induced apoptosis and had an inhibitive effect on the malignant phenotype of ESCC, including cell proliferation, invasion, and migration. In addition, ILK knockdown in ESCC cells inhibited the expression of beta (β)-catenin and activated the wingless/integrated (Wnt) signaling pathway. Furthermore, cellular MYC (c-MYC) and Cylin D1 were the target genes of the Wnt signaling pathway. Rescue experiments showed that the overexpression of β-catenin reversed a tumor’s inhibition and apoptosis abilities induced by ILK knockdown. In conclusion, ILK potentially reduced the CDDP sensitivity of ESCC cells by influencing the activity of the Wnt/β-catenin signaling pathway. GRAPHICAL ABSTRACT
Incidence of flexion‐type supracondylar fractures at a single Australian level one Paediatric Trauma Centre

Supracondylar fractures are the most common elbow fracture. There have been no studies published analysing flexion‐type fractures in the Australian paediatric population. This paper aims to investigate flexion‐type supracondylar fractures in an Australian paediatric population. Eight hundred and three paediatric supracondylar elbow fractures were retrospectively reviewed at one hospital over a 5 year time period. The focus was on flexion‐type fractures.
Association between lowering restriction levels during the coronavirus outbreak and physical activity among adults: a longitudinal observational study in Brazil.

OBJECTIVE The COVID-19 pandemic has had significant consequences on public health and lifestyle and has negatively affected mental health and the level of physical activity worldwide. This study examined the impact of reopening fitness centers and nonessential services and introducing flexible measures to ensure social distancing on physical activity and mental health. MATERIALS AND METHODS This was a longitudinal study. A self-administered questionnaire, including personal, behavioral, physical activity, perception of health, and mood state disorder information, was answered by 128 Brazilians in June 2020 (during severe restrictive measures) and again in April 2021 (after fitness centers and nonessential services were reopened). RESULTS The restriction level adopted in April 2021 was significantly lower than that in June 2020 (p<0.001). The level of physical activity (p<0.001) and health status perception (p<0.001) decreased from June 2020 to April 2021. The median values for depression and anxiety did not differ across the study period. CONCLUSIONS The level of physical activity was reduced during the COVID-19 pandemic, and anxiety and depression were not improved following less restrictive social distancing measures and the reopening of fitness centers. Thus, the return to a prepandemic level of physical activity and mental health status may not be automatic. The results presented herein suggest that the decrease in physical activity observed in the population may be challenging in the postpandemic period.
First-principles simulation of neutral and charged oxygen vacancies in m-ZrO2: an origin of filamentary type resistive switching

Metal oxide ZrO2 has been widely explored for resistive switching application due to excellent properties like high ON/OFF ratio, superior data retention, and low operating voltage. However, the conduction mechanism at the atomistic level is still under debate. Therefore, we have performed comprehensive insights into the role of neutral and charged oxygen vacancies in conduction filament (CF) formation and rupture, which are demonstrated using the atomistic simulation based on density functional theory (DFT). Formation energy demonstrated that the fourfold coordinated oxygen vacancy is more stable. In addition, the electronic properties of the defect included supercell confirm the improvement in electrical conductivity due to the presence of additional energy states near Fermi energy. The CF formation and rupture using threefold and fourfold oxygen vacancies are demonstrated through cohesive energy, electron localization function, and band structure. Cohesive energy analysis confirms the cohesive nature of neutral oxygen vacancies while the isolated behavior for +2 charged oxygen vacancies in the CF. In addition, nudged elastic band calculation is also performed to analyze the oxygen vacancy diffusion energy under different paths. Moreover, we have computed the diffusion coefficient and drift velocity of oxygen vacancies to understand the CF. This DFT study described detailed insight into filamentary type resistive switching observed in the experimentally fabricated device. Therefore, this fundamental study provides the platform to explore the switching mechanism of other oxide materials used for memristor device application.
Interfacial electronic properties of metal/CsSnBr3 heterojunctions

All-inorganic lead-free perovskite CsSnBr3, has been proved good stability and optoelectronic properties in theory and experiment. However, the interfacial electronic properties of metal/CsSnBr3 are still unclear in electronic devices. Herein, we systematically investigate the interfacial properties of metal electrodes (Al, Ag and Au) and CsSnBr3 with different atomic terminals (SnBr2-T and CsBr-T) through the first-principles calculation. SnBr2-T and CsBr-T have various contact types and Schottky barriers due to their different interaction strengths with metals. In particular, the moderate interlayer coupling strength with Al leads to the ultra-low Schottky barrier and tunneling barrier, which makes Al possess the best contact performance among the studied metals. Furthermore, the external electric field can be effective in regulating the Schottky barrier and realizing the Ohmic contact. These findings provide useful guidance for the design of perovskite-based nanoelectronic devices with high performance.
Demonstration of ameliorating effect of vardenafil through its anti-inflammatory and neuroprotective properties in autism spectrum disorder induced by propionic acid on rat model

Abstract Introduction Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology. In this study, we aimed to determine the ameliorating effects of vardenafil in the ASD rat model induced by propionic acid (PPA) in terms of neurobehavioral changes and also support these effects with histopathological changes, brain biochemical analysis and magnetic resonance spectroscopy (MRS) findings. Materials and methods Twenty-one male rats were randomly assigned into three groups. Group 1 (control, 7 rats) did not receive treatment. Rats in groups 2 and 3 were given PPA at the dose of 250 mg/kg/day intraperitoneally for 5 days. After PPA administration, animals in group 2 (PPAS, 7 rats) were given saline and animals in group 3 (PPAV, 7 rats) were given vardenafil. Behavioral tests were performed between the 20th and 24th days of the study. The rats were taken for MRS on the 25th day. At the end of the study, brain levels of interleukin-2 (IL-2), IL-17, tumor necrosis factor-α, nerve growth factor, cGMP and lactate levels were measured. In the cerebellum and the CA1 and CA3 regions of the hippocampus, counts of neurons and Purkinje cells and glial fibrillary acidic protein (associated with gliosis) were evaluated histologically. Results Three chamber sociability and passive avoiding test, histopathological results, lactate levels derived from MRS, and biochemical biomarkers revealed significant differences among the PPAV and PPAS groups. Conclusion We concluded that vardenafil improves memory and social behaviors and prevent loss of neuronal and Purkinje cell through its anti-inflammatory and neuroprotective effect.
Advances in research on the protective mechanisms of traditional Chinese medicine (TCM) in myocardial ischaemia-reperfusion injury

Abstract Context Developing effective drugs to treat myocardial ischaemia-reperfusion (MI/R) injury is imperative. Traditional Chinese medicines (TCMs) have had considerable success in the treatment of cardiovascular diseases. Elucidating the mechanisms by which TCMs improve MI/R injury can supplement the literature on MI/R prevention and treatment. Objective To summarise TCMs and their main protective mechanisms against MI/R injury reported over the past 40 years. Methods Relevant literature published between 1980 and 2020 in Chinese and English was retrieved from the Web of Science, PubMed, SpringerLink, PubMed Central, Scopus, and Chinese National Knowledge Infrastructure (CNKI) databases. Search terms included ‘medicinal plants’, ‘myocardial ischaemia reperfusion injury’, ‘Chinese medicine prescriptions’, ‘mechanisms’, ‘prevention’, ‘treatment’ and ‘protection’. For inclusion in the analysis, medicinal plants had to be searchable in the China Medical Information Platform and Plant Database. Results We found 71 medicinal species (from 40 families) that have been used to prevent MI/R injury, of which Compositae species (8 species) and Leguminosae species (7 species) made up the majority. Most of the effects associated with these plants are described as antioxidant and anti-inflammatory. Furthermore, we summarised 18 kinds of Chinese compound prescriptions, including the compound Danshen tablet and Baoxin pill, which mainly reduce oxidative stress and regulate mitochondrial energy metabolism. Discussion and conclusions We summarised TCMs that protect against MI/R injury and their pharmacological mechanisms. This in-depth explanation of the roles of TCMs in MI/R injury protection provides a theoretical basis for the research and development of TCM-based treatment drugs.
Probiotic Properties and Optimization of Gamma-Aminobutyric Acid Production by Lactiplantibacillus plantarum FBT215

Gamma-aminobutyric acid (GABA) improves various physiological illnesses, including diabetes, hypertension, depression, memory lapse, and insomnia in humans. Therefore, interest in the commercial production of GABA is steadily increasing. Lactic acid bacteria (LAB) have widely been reported as a GABA producer and are safe for human consumption. In this study, GABA-producing LAB were preliminarily identified and quantified via GABase assay. The acid and bile tolerance of the L. plantarum FBT215 strain were evaluated. The one-factor-at-a-time (OFAT) strategy was applied to determine the optimal conditions for GABA production using HPLC. Response surface methodology (RSM) with Box-Behnken design was used to predict the optimum GABA production. The strain FBT215 was shown to be acid and bile tolerant. The optimization of GABA production via the OFAT strategy resulted in an average GABA concentration of 1688.65 ± 14.29 μg/ml, while it was 1812.16 ± 23.16 μg/ml when RSM was applied. In conclusion, this study provides the optimum culture conditions for GABA production by the strain FBT215 and indicates that L. plantarum FBT215 is potentially promising for commercial functional probiotics with health claims.
Prevalence, severity, and characteristics of medical device related pressure injuries in adult intensive care patients: A prospective observational study

This study was intended to determine the characteristics of Medical Related Pressure Injury (MDRPI) in adult intensive care patients. MDRIs are recognized as significant and complex health problems among hospitalized patients. Underestimated true scale of the problem is evident because the systematic clinical evaluation of MDRPI occurrence is not part of routine skin assessment among intensive care patients. A prospective approach was used to obtain data of MDRPIs with two weeks follow up to monitor the prevention and treatment strategies. Participants were 329 adult patients from three large referral and teaching centres in Jordan. Data were collected using a screening form that included demographic and clinical characteristics, and a list of medical devices. The primary outcome for this study was MDRPI and defined as a pressure injury (PI) found on the skin or mucous membrane with a medical device in use at the location of the injury (EPUAP, 2019). The patients with MDRPI were followed up for 2 weeks for prevention and treatment strategies. Prevalence of MDRPI was 5.01% (15/299) with 41 injuries, 27/41 (65.8%) were skin injuries and 14/41(34.2%) were mucosal. Most mucous membrane MDRPIs were at mouth/lips and caused by ET tube and meatal orifice caused by foley catheter. Skin MDRPIs were at the nose and caused by NG tube and hands by peripheral intravenous line and arms caused by blood pressure cuff. Inadequate prevention was provided on daily care as only 177 prevention and treatment interventions were provided over 2 weeks for 15 patients. As a growing problem among Jordanian adults in intensive care, MDRPI required the need for effective prevention. About one‐thirds of MDRPIs were mucosal, a finding not previously reported, indicating the need to include mucous membrane assessment with skin assessment when a medical device such as NG and ET tubes or foley catheters are in use. Prevention and treatment interventions provided to patients with MDRPIs were not systematic and based on routine care with no clear guidelines. A consensus has yet to be reached suggesting the need to establish effective prevention strategies for medical device‐related pressure injuries. Future research is recommended to follow up MDRPI prevention and treatment strategies among patients in ICU. We suggest to continue studying the prevalence of MDRPIs and monitoring the location, prevention and treatment of both skin and mucosal MDRPIs.