Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding COVID-19 vaccine acceptance in Pakistan: an echo of previous immunizations or prospect of change?

ABSTRACT Background As countries ramp up their COVID-19 vaccination programs, attitudes of the population remain a determining player in the success of these plans. This study analyses the factors associated with intent to vaccinate against COVID-19 in the Pakistani population. Methodology This cross-sectional, anonymous, online survey was carried out in April 2021. Participants’ demographic details, experiences relating to COVID-19 and its vaccination, and their health beliefs were inquired and divided across Health Belief Model constructs. Multivariable regression was used to determine factors associated with a No/Not sure vs Yes response for vaccination intention. Results Of the 655 respondents, 62.0% were willing to get vaccinated. Significant predictors of a less likelihood of resisting vaccination included advanced age (AOR 0.25; 95% CI 0.07–0.88), fear of contracting COVID-19 (AOR 0.47; 95% CI 0.27–0.82), hope of preventing its spread (AOR 0.30; 95% CI 0.19–0.49), and community pressure (AOR 0.22; 95% CI 0.13–0.37). Concerns about vaccine reliability (AOR 2.75; 95% CI 1.67–4.53) and religious inhibitions (AOR 2.45; 95% CI 1.34–4.48) swayed people away from vaccination. Conclusion Despite a reasonably good response of Pakistanis to vaccination, factors negatively influencing their intention need to be timely addressed to control this pandemic.
Administration of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) among high school students in the Peruvian Amazon

Abstract This article reports on results of the administration of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to 500 high school students (aged 16–19) in the Peruvian Amazon. Results indicate 68.6% of the sample reported consumption of alcohol in the past three months. One out of four students reported high risk involvement with at least one substance while 1 out of 3 reported moderate risk. This is one of the few instances in which ASSIST was administered to adolescents and offers possibilities for further reflection on drug use at early ages.
Assessment of Renal Function Status in Steady-State Sickle Cell Anaemic Children Using Urine Human Neutrophil Gelatinase-Associated Lipocalin and Albumin:Creatinine Ratio

Introduction: Sickle cell anaemia is characterized by defective haemoglobin synthesis and is associated with both endocrine and metabolic alterations. The effects of this clinical condition on kidney function are multifactorial and often begin early in childhood. This study aims to assess renal function in children with sickle cell anaemia using urine albumin:creatinine ratio (ACR) and urine human neutrophil gelatinase-associated lipocalin (NGAL). Methods: This case-control study was conducted on 200 children aged 5–15 years in 2 tertiary hospitals in South West Nigeria: 150 were of haemoglobin S genotype and 50 were of haemoglobin A genotype. Serum urea, creatinine, urine albumin, and NGAL were assayed by known standard methods. eGFR, urine ACR, and urine NGAL/creatinine ratio (urine NCR) were calculated. Results: The weight, height, BMI, systolic blood pressure, plasma urea, plasma creatinine, and spot urine creatinine of the HbS genotype children were significantly lower compared to that of the HbA genotype children. The eGFR, spot urine albumin, and urine ACR were significantly higher in the HbS group compared to the HbA group. There was no significant difference in the spot urine NGAL and urine NCR between the 2 groups, though both were higher in the HbS group compared to the HbA group. Conclusions: Kidney injury probably starts early in childhood in sickle cell individuals as indicated by the higher urine ACR detected in them. We infer that urine NGAL and uNCR are not sensitive markers of kidney disease especially in young sickle cell individuals possibly because of the hyperfiltration present at this age.
GRB2 enforces homology-directed repair initiation by MRE11

GRB2 controls radiation-induced DNA damage repair—a predictive biomarker for PARPi and radiation therapy outcome. DNA double-strand break (DSB) repair is initiated by MRE11 nuclease for both homology-directed repair (HDR) and alternative end joining (Alt-EJ). Here, we found that GRB2, crucial to timely proliferative RAS/MAPK pathway activation, unexpectedly forms a biophysically validated GRB2-MRE11 (GM) complex for efficient HDR initiation. GRB2-SH2 domain targets the GM complex to phosphorylated H2AX at DSBs. GRB2 K109 ubiquitination by E3 ubiquitin ligase RBBP6 releases MRE11 promoting HDR. RBBP6 depletion results in prolonged GM complex and HDR defects. GRB2 knockout increased MRE11-XRCC1 complex and Alt-EJ. Reconstitution with separation-of-function GRB2 mutant caused HDR deficiency and synthetic lethality with PARP inhibitor. Cell and cancer genome analyses suggest biomarkers of low GRB2 for noncanonical HDR deficiency and high MRE11 and GRB2 expression for worse survival in HDR-proficient patients. These findings establish GRB2’s role in binding, targeting, and releasing MRE11 to promote efficient HDR over Alt-EJ DSB repair, with implications for genome stability and cancer biology.
Qualitative and quantitative research of propyl lactate in brewed alcoholic beverages

ABSTRACT Recently, propyl lactate has been firstly detected in Chinese Baijiu (Chinese liquor) as one of the odor-active components. In this study, the contents of propyl lactate in other different brewed alcoholic beverages were investigated, including wine, soju, sake, vodka, rum, tequila, whisky and beer, and analyzed by solid-phase microextraction and liquid–liquid extraction coupled with gas chromatography-mass spectrometry, determined by internal standard method followed by GC-MS with selective ion monitoring. The analyses indicated that propyl lactate was present in beer and tequila samples, while not detected in other brewed alcoholic beverages. The results showed that among the 40 beer samples from 11 different countries, 36 of them contained propyl lactate at concentrations in the range of 0.23–51.71 µg L−1. In addition, all of six tequila samples contained propyl lactate at concentrations in the range of 0.77–12.14 mg L−1, and the odor activity values (OAVs) of propyl lactate were greater than 1 in all of the tequila samples. These findings indicated that propyl lactate was widely distributed in beer and tequila; it was also an odor-active component of tequila according to OAVs.
The Monod Model Is Insufficient To Explain Biomass Growth in Nitrogen-Limited Yeast Fermentation

Problematic fermentations still occur in the winemaking industrial practice. Problems include low rates of fermentation, which have been linked to insufficient levels of assimilable nitrogen. ABSTRACT The yeast Saccharomyces cerevisiae is an essential microorganism in food biotechnology, particularly in wine- and beermaking. During wine fermentation, yeasts transform sugars present in grape juice into ethanol and carbon dioxide. The process occurs under batch conditions and is, for the most part, an anaerobic process. Previous studies linked nitrogen-limited conditions with problematic fermentations, with negative consequences for the performance of the process and the quality of the final product. It is therefore of the highest interest to anticipate such problems through mathematical models. Here, we propose a model to explain fermentations under nitrogen-limited anaerobic conditions. We separated biomass formation into two phases: growth and carbohydrate accumulation. Growth was modeled using the well-known Monod equation, while carbohydrate accumulation was modeled by an empirical function analogous to a proportional controller activated by the limitation of available nitrogen. We also proposed to formulate the fermentation rate as a function of the total protein content when relevant data are available. The final model was used to successfully explain experiments taken from the literature, performed under normal and nitrogen-limited conditions. Our results revealed that the Monod model is insufficient to explain biomass formation kinetics in nitrogen-limited fermentations of S. cerevisiae. The goodness of fit of the model proposed here is superior to that of previously published models, offering the means to predict and, thus, control fermentations. IMPORTANCE Problematic fermentations still occur in the industrial winemaking practice. Problems include low rates of fermentation, which have been linked to insufficient levels of assimilable nitrogen. Data and relevant models can help anticipate poor fermentation performance. In this work, we propose a model to predict biomass growth and fermentation rates under nitrogen-limited conditions and tested its performance with previously published experimental data. Our results show that the well-known Monod equation does not suffice to explain biomass formation.
ADP Ribosylation Factor 6 Promotes Contraction and Proliferation, Suppresses Apoptosis and Is Specifically Inhibited by NAV2729 in Prostate Stromal Cells

The presumed ADP ribosylation factor (ARF) 6 inhibitor NAV2729 inhibits human prostate smooth muscle contraction and proliferation of stromal cells, which are driving factors of voiding symptoms in benign prostatic hyperplasia (BPH). However, its specificity and a confirmed role of ARF6 for smooth muscle contraction are still pending. Here, we generated monoclonal ARF6 knockouts in human prostate stromal cells (WPMY-1), and characterized phenotypes of contractility, growth-related functions, and susceptibility to NAV2729 in knockout and control clones. ARF6 knockout was verified by Western blot. Knockout clones showed impaired contraction and actin organization, reduced proliferation and viability, and increased apoptosis and cell death. In ARF6-expressing control clones, NAV2729 (5 µM) strongly inhibited contraction (67% inhibition across all three control clones), actin organization (72%), proliferation (97%), and viability (up to 82%), and increased apoptosis (5-fold) and cell death (6-fold). In ARF6 knockouts, effects of NAV2729 (5 µM) were widely reduced, including lacking or minor effects on contractions (0% inhibition across all three knockout clones), actin (18%) and proliferation (13%), and lacking increases of apoptosis and cell death. Viability was reduced by NAV2729 with an IC50 of 3.3 µM across all three ARF6 control clones, but of 4.5–8.2 µM in ARF6 knockouts. In conclusion, ARF6 promotes prostate smooth muscle contraction and proliferation of stromal cells. Both are inhibited by NAV2729, which showed high specificity for ARF6 up to 5 µM and represents an attractive compound in the context of BPH. Considering the relevance of smooth muscle-based diseases, shared roles of ARF6 in other smooth muscle types merit further investigation. SIGNIFICANCE STATEMENT By knockout of ARF6 in prostate stromal cells, this study demonstrates the involvement of ARF6 in promotion of prostate smooth muscle contraction and stromal growth, and defines concentration ranges for their ARF6-specific inhibition by NAV2729. Besides the context of benign prostatic hyperplasia and lower urinary tract symptoms, analog ARF6 functions in contraction and growth appear possible in other smooth muscle-rich organs, which merits further attention considering the high clinical relevance of smooth muscle-based diseases.
“If I Don’t Allow Him to Have Sex With Me, Our Relationship Will Be Broken”: Rape, Sexual Coercion, and Sexual Compliance Within Marriage in Rural Cambodia

Rape, sexual coercion, and sexual compliance within marriage are major components of gender-based violence globally. This article examines a range of non-consensual sexual experiences within heterosexual marriage in Aoral and Thpong districts in Kampong Speu, Cambodia. Interviews were conducted with 11 married women and thematically analyzed from a critical realist and feminist perspective. Four categories of non-consensual sex were identified and analyzed (rape/forced sex, sexual coercion, sexual compliance, and internalized pressure). These are discussed in detail, alongside the need for educational efforts that disrupt traditional gender norms that create a context conducive to women’s non-consensual sex in Cambodia.
Letter to the Editor: Proton Pump Inhibitors and Biliary Tract Cancer Risk: Causality or Reverse Causality?

We read with enormous interest the study by Kamal et al.1 For the past two decades, dispute on the carcinogenic effects of PPI has remained. In this retrospective study using nationwide registries, long-term use of PPIs was identified to be associated with increased risks of gallbladder, intrahepatic and extrahepatic bile duct cancers. This study is the first large-scale population-based study assessing biliary tract cancer risks under PPI use, using high-quality data and well-designed methods. Despite the strengths of this study, several issues need further discussion.
Flavan-based phytoconstituents inhibit Mpro, a SARS-COV-2 molecular target, in silico

Abstract A well-validated in-silico approach can provide promising drug candidates for the treatment of the ongoing CoVID19 pandemic. In this study, we have screened 32 phytochemical constituents (PCCs) with Mpro binding site (PDB:6W63) based on which we identified three possible candidates that are likely to be effective against CoVID19—viz., licoleafol (binding energy: −8.1 kcal/mol), epicatechin gallate (–8.5 kcal/mol) and silibinin (–8.4 kcal/mol) that result in higher binding affinity than the known inhibitor, X77 (–7.7 kcal/mol). Molecular dynamics (MD) simulations of PCCs-Mpro complex confirmed molecular docking results with high structural and dynamical stability. The selected compounds were found to exhibit low mean squared displacements (licoleafol: 2.25 ± 0.43 Å, epicatechin gallate: 1.93 ± 0.35 Å, and silibinin: 1.39 ± 0.19 Å) and overall low fluctuations of the binding complexes (root mean squared fluctuations below 2 Å). Visualization of the MD trajectories and structural analyses revealed that they remain confined to the initial binding region, with mean fluctuations lower than 3 Å. To access the collective motion of the atoms, we performed principal component analysis demonstrating that the first 10 principal components are the major contributors (approximate contribution of 80%) and are responsible for the overall PCCs motion. Considering that the three selected PCCs share the same flavan backbone and exhibit antiviral activity against hepatitis C, we opine that licoleafol, epi-catechin gallate, and silibinin can be promising anti-CoVID19 drug candidates. Communicated by Ramaswamy H. Sarma
Comprehensive Clinicopathologic Analysis for Mismatch Repair Protein Expression in Unselected Endometrial Carcinoma Patients With an Emphasis on the Role of MLH1 Deficiency

Screening for mismatch repair (MMR) deficiency in unselected patients with endometrial carcinoma (EC) and the clinicopathologic descriptions of ECs with MMR deficiency have been well demonstrated in Western populations, but studies on Asian populations are relatively scarce. In this study, we described the clinicopathologic features of ECs according to MMR status in unselected Taiwanese patients. We also conducted subgroup analysis of MMR-deficient (dMMR) cases according to the presence or absence of MLH1. Patients diagnosed with ECs between January 2017 and February 2020 at our institution were included. Immunohistochemistry analysis of MLH1, PMS2, MSH2, and MSH6 proteins on endometrial primary tumors and clinicopathologic variables were assessed retrospectively. A total of 231 EC patients were enrolled, of whom 50 (21.6%) had dMMR tumors. Of these 50 cases, 39 had tumors that lacked MLH1 expression and 11 were positive for MLH1. The overall dMMR group was significantly related to older age, parity, and high histologic grade compared with the MMR-proficient (pMMR) group. ECs with MLH1 deficiency were obviously associated with several poor pathologic features, including high histologic grade, lymph node metastasis, and lymphovascular space invasion. Moreover, we first reported that parity and the late age at menopause are strongly correlated with MLH1-related dMMR EC group compared with pMMR group. In conclusion, triaging EC patients into pMMR, MLH1-related dMMR and non–MLH1-related dMMR groups by immunohistochemistry analysis may help clinicians to predict disease behavior and guide further management. The strong association between parity and MLH1-related dMMR ECs warrants further investigation on the underlying mechanism.
Blue light-irradiated human keloid fibroblasts: an in vitro study

Blue LED light irradiation is currently under investigation because of its effect in wound healing improvement. In this context, several mechanisms of action are likely to occur at the same time, consistently with the presence of different light absorbers within the skin. In our previous studies we observed the wound healing in superficial abrasions in an in vivo murine model. The results evidenced that both inflammatory infiltrate and myofibroblasts activity increase after irradiation. In this study we focused on evaluating the consequences of light absorption in fibroblasts from human cells culture: they play a key role in wound healing, both in physiological conditions and in pathological ones, such as keloid scarring. In particular we used keloids fibroblasts as a new target in order to investigate a possible metabolic or cellular mechanism correlation. Human keloid tissues were excised during standard surgery and immediately underwent primary cell culture extraction. Fibroblasts were allowed to grow in the appropriate conditions and then exposed to blue light. A metabolic colorimetric test (WST-8) was then performed. The tests evidenced an effect in mitochondrial activity, which could be modulated by the duration of the treatment. Electrophysiology pointed out a different behavior of irradiated fibroblasts. In conclusion, the Blue LED light affects the metabolic activity of fibroblasts and thus the cellular proliferation rate. No specific effect was found on keloid fibroblasts, thus indicating a very basic intracellular component, such as cytochromes, being the target of the treatment.
Nonlinear dynamics of fully developed swirling jets

Abstract This paper characterises the steady and time-periodic behaviour of swirling jets using numerical bifurcation analysis. Its objective is to elucidate the dynamics of fully developed, unconfined, laminar swirling jets under variations in the Reynolds number $\textit {Re}$ and swirl ratio $S$. Within the $(0,0)\leq (\textit {Re},S)\leq (300,3)$ range, the steady, axisymmetric flow exhibits several distinct patterns ranging from a quasi-columnar jet along the central axis at low $S$ to a radial jet attached to the containing wall at high $S$ with various forms of vortex breakdown in between. A cusp bifurcation appears in the steady solution manifold which triggers bistable behaviour due to a competition between inner and outer low pressure regions associated with vortex breakdown and entrainment of the ambient fluid, respectively. Instability of the steady flow is linked to eigenmodes which are singly ($|m|=1$) or doubly ($|m|=2$) azimuthally periodic, although additional instabilities with other azimuthal wavenumbers occur at $(\textit {Re},S)$-values beyond the leading neutral curves. The various branches of limit cycle solutions stemming from these neutral curves are associated with both super- and sub-critical Hopf bifurcations. The resulting unsteady flow fields exhibit a wide array of rotating, three-dimensional flow structures, and comparisons between the time-averaged and steady flow patterns highlight the role of these unsteady nonlinear interactions on the overall behaviour of swirling jets. Similarities and differences between this laterally unconfined jet and broader classes of swirling flows, including confined swirling jets and unconfined vortex models, are also discussed.
Predicting respiratory failure for COVID-19 patients in Japan: a simple clinical score for evaluating the need for hospitalisation

Abstract Predicting the need for hospitalisation of patients with coronavirus disease 2019 (COVID-19) is important for preventing healthcare disruptions. This observational study aimed to use the COVID-19 Registry Japan (COVIREGI-JP) to develop a simple scoring system to predict respiratory failure due to COVID-19 using only underlying diseases and symptoms. A total of 6873 patients with COVID-19 admitted to Japanese medical institutions between 1 June 2020 and 2 December 2020 were included and divided into derivation and validation cohorts according to the date of admission. We used multivariable logistic regression analysis to create a simple risk score model, with respiratory failure as the outcome for young (18–39 years), middle-aged (40–64 years) and older (≥65 years) groups, using sex, age, body mass index, medical history and symptoms. The models selected for each age group were quite different. Areas under the receiver operating characteristic curves for the simple risk score model were 0.87, 0.79 and 0.80 for young, middle-aged and elderly derivation cohorts, and 0.81, 0.80 and 0.67 in the validation cohorts. Calibration of the model was good. The simple scoring system may be useful in the appropriate allocation of medical resources during the COVID-19 pandemic.
Can clinical pharmacists utilize telehealth to double the safety and efficacy of oral anticoagulation while reducing health care costs and improving patient satisfaction in patients with atrial fibrillation?

Published reports from the United States and New Zealand have described excellent control of the international normalized ratio (INR) and improved patient satisfaction in warfarin‐treated patients whose therapy was managed by clinically trained pharmacists using point of care (POC, or “fingerstick”) blood testing and online technology. This report examines the projected impact of such management on clinical outcomes and health care costs by using previously published information which quantified the relationships between anticoagulation control and rates of thromboembolism, major hemorrhage, and death.
Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli

Microvilli are conserved actin-based surface protrusions that have been repurposed throughout evolution to fulfill diverse cell functions. In the case of transporting epithelia, microvilli are supported by a core of actin filaments bundled in parallel by villin, fimbrin, and espin. Remarkably, microvilli biogenesis persists in mice lacking all three of these factors, suggesting the existence of unknown bundlers. We identified Mitotic Spindle Positioning (MISP) as an actin binding factor that localizes specifically to the rootlet end of the microvillus. MISP promotes rootlet elongation in cells, and purified MISP exhibits potent filament bundling activity in vitro. MISP-bundled filaments also recruit fimbrin, which further elongates and stabilizes bundles. MISP confinement to the rootlet is enforced by ezrin, which prevents decoration of the membrane-wrapped distal end of the core bundle. These discoveries reveal how epithelial cells optimize apical membrane surface area and offer insight on the remarkable robustness of microvilli biogenesis.