Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV-1 Impairment via UBE3A and HIV-1 Nef Interactions Utilizing the Ubiquitin Proteasome System

Molecular basis of HIV-1 life cycle regulation has thus far focused on viral gene stage-specificity, despite the quintessence of post-function protein elimination processes in the virus life cycle and consequent pathogenesis. Our studies demonstrated that a key pathogenic HIV-1 viral protein, Nef, interacted with ubiquitin (Ub)-protein ligase E3A (UBE3A/E6AP), suggesting that interaction between Nef and UBE3A is integral to regulation of viral and cellular protein decay and thereby the competing HIV-1 and host cell survivals. In fact, Nef and UBE3A degraded reciprocally, and UBE3A-mediated degradation of Nef was significantly more potent than Nef-triggered degradation of UBE3A. Further, UBE3A degraded not only Nef but also HIV-1 structural proteins, Gag, thus significantly inhibiting HIV-1 replication in Jurkat T cells only in the presence of Nef, indicating that interaction between Nef and UBE3Awas pivotal for UBE3A-mediated degradation of the viral proteins. Mechanistic study showed that Nef and UBE3A were specific and antagonistic to each other in regulating proteasome activity and ubiquitination of cellular proteins in general, wherein specific domains of Nef overlapping with the long terminal repeat (LTR) were essential for the observed actions. Further, Nef itself reduced the level of intracellular Gag by degrading a cardinal transcription regulator, Tat, demonstrating a broad role for Nef in the regulation of the HIV-1 life cycle. Taken together, these data demonstrated that the Nef and UBE3A complex plays a crucial role in coordinating viral protein degradation and hence HIV-1 replication, providing insights as to the nature of pathobiologic and defense strategies of HIV-1 and HIV-infected host cells.
Sleepiness as motivation: a potential mechanism for how sleep deprivation affects behavior

Abstract Study Objectives To determine how sleepiness and sleep deprivation drive the motivation to engage in different behaviors. Methods We studied the sleepiness of 123 participants who had been randomized to sleep deprivation or normal sleep, and their willingness to engage in a range of everyday behaviors. Results Self-reported sleepiness was a strong predictor of the motivation to engage in sleep-preparatory behaviors such as shutting one’s eyes (OR = 2.78, 95% CI: 2.19–3.52 for each step up on the Karolinska Sleepiness Scale) and resting (OR = 3.20, CI: 2.46–4.16). Sleepiness was also related to the desire to be cared for by a loved one (OR = 1.49, CI: 1.22–1.82), and preparedness to utilize monetary and energy resources to get to sleep. Conversely, increased sleepiness was associated with a decreased motivation for social and physical activities (e.g. be with friends OR = 0.71, CI: 0.61–0.82; exercise OR = 0.65, CI: 0.56–0.76). Sleep deprivation had similar effects as sleepiness on these behaviors. Neither sleepiness nor sleep deprivation had strong associations with hunger, thirst, or food preferences. Conclusions Our findings indicate that sleepiness is a dynamic motivational drive that promotes sleep-preparatory behaviors and competes with other drives and desired outcomes. Consequently, sleepiness may be a central mechanism by which impaired alertness, for example, due to insufficient sleep, contributes to poor quality of life and adverse health. We propose that sleepiness helps organize behaviors toward the specific goal of assuring sufficient sleep, in competition with other needs and incentives. A theoretical framework on sleepiness and its behavioral consequences are likely to improve our understanding of several disease mechanisms.
MORPHOMETRIC STUDY OF VENTRICULAR SIZES ON NORMAL COMPUTED TOMOGRAPHY SCANS OF ADULT BLACK ZIMBABWEANS AT A DIAGNOSTIC RADIOLOGY CENTRE IN HARARE-A PILOT STUDY

The aim of the present study was to establish the range of the sizes for the different parts of the cerebral ventricular system. These simple measurements should be applicable to the brain Computed Tomography Scan reading without any need for advanced morphometric software package. Three hundred (150 females and 150 males) normal brain CT scans were obtained from a private Diagnostic Radiology centre in Harare for ventricular dimensions measurements (bifrontal, third ventricular and fourth ventricular dimensions). 18 hydrocephalus patients were also included in the study. A MILLENSYS DICOM Viewer Version 9Â® USA software program was used to measure ventricular dimensions in millimetres. This study found an average (MeanÂ±SE) frontal horn diameter, third ventricle width, fourth ventricle width, fourth ventricle height, Frontal Horn ratio (A/B), and the third ventricle ratio (C/D) for the sample being 31. 8Â±0.2mm, 3. 25Â±0.09mm, 10. 6Â±0.1mm, 10. 5Â±0.1, 0. 313Â±0.002, and 0. 030Â±0.002, respectively. Except for the fourth height which was not significantly affected by age (p=0.515), the present study showed that there was a significant difference between different age groups on all of the above measurements and ratios (p<0.01) Criteria have been developed that are measurable, reproducible and applicable in routine diagnosis of dilated cerebral ventricles in adults. In general, the maximum frontal tips diameter greater than 48% or less than 25% corresponding plane are to be considered highly suspicious of abnormal ventricles. The overall frontal horn ratio of the eighteen hydrocephalus patients varied from 0.36 to 0.52 with an overall mean of 0.42.
Risk factors for the transmission of kala-azar in Fangak, South Sudan

This article reports a case controlled study of kala-azar done in Fangak County in 2007. Fifty-six percent of the cases were under 5 years old. Most patients came for treatment two months or more after the onset of symptoms. Outdoor night-time activities and the use of “smoking” (non-insecticide treated) bed nets were associated with kala-azar infection whereas the use of bed nets during the rainy season decreased the risk of infection. It is recommended that there should be a greater distribution of treated bed nets and more kala-azar treatment centres in the county. Note: This article reports the results of a study into some risk factors for the transmission of kala-azar in Fangak in 2007. There was another recent outbreak in this area on 2010 (1, 2). Recommendations were again made to distribute more treated bed nets and to open more kala-azar treatment centres. The official Ministry of Health guideline for the treatment of kala-azar is at the end of this article.
Challenges And Factors Associated With Poor Glycemic Control Among Type 2 Diabetes Mellitus Patients At Nekemte Referral Hospital, Western Ethiopia

Background Diabetes is increasing at an alarming rate throughout the world, and ~80% of diabetics live in developing countries. Similar to the rest of sub-Saharan African countries, Ethiopia is experiencing a significant burden of diabetes, with increased prevalence, complications, and mortality, as well as life threatening disabilities. Reasons for poor glycemic control among type 2 diabetes patients are complex and multivariable. Hence, this study aimed to identify challenges and factors associated with poor glycemic control among type 2 diabetes patients. Method A hospital-based cross-sectional study was conducted among type 2 diabetic patients attending the diabetic clinic of Nekemte Referral Hospital (NRH) from February 1 to April 30, 2018. Fasting blood glucose levels of the last three clinic visits were obtained and the mean fasting blood glucose measurement was used to determine the level of glycemic control. Analysis included both descriptive and inferential statistics with SPSS version 20.0. Predictor variable P<0.05 was considered statistically significant. Results Out of the total 228 included type 2 diabetes mellitus (DM) patients, 51.8% were males. The mean age of patients was 43±12.4 years and 154 (67.5%) were found to not be following their general dietary program correctly. Nearly one third, 73 (32%), of patients never attended diabetic education and 52 (22.8%) of the patients had greater than 10 years’ duration on treatment. The majority, 148 (64.9%), of patients had poor blood glucose control. Age 40–60 years (AOR=2.01, 95% CI=0.04–0.06, P=0.044), being illiterate (AOR=3.12, 95% CI=1.52–8.50, P=0.001), having informal education only (AOR=2.28, 95% CI=2.14–32.60, P=0.024), longer duration of diabetes treatment (>10 years) (AOR=3.94, 95% CI=1.51–27.83, P=0.012), inadequate physical exercise (AOR=3.19, 95% CI=1.05–19.84, P=0.019), and smoking (AOR=4.51, 95% CI=0.00–0.50, P=0.022) were independent predictors of poor glycemic control on multivariable logistic regression analysis. Conclusion Nearly two-thirds of patients had poorly controlled diabetes. Age, exercise, level of education, duration of the treatment, and smoking were significantly associated with poor glycemic control. Health facilities should provide continuous education, and barriers of glycemic control should be explored with further research.
Firm Acquisitions by Family Firms: A Mixed Gamble Approach

This study elucidates the mixed gamble confronting family firms when considering a related firm acquisition. The socioemotional and financial wealth trade-off associated with related firm acquisitions as well as their long-term horizon turns family firms more likely to undertake a related acquisition than nonfamily firms, especially when they are performing above their aspiration level. Postmerger performance pattern confirms that family firms are able to create long-term value through these acquisitions, and by doing so, they surpass nonfamily firms. These findings stand in contrast to commonly used behavioral agency predictions but can be reconciled with theory through a mixed gamble lens.
Prevalence and Associated Factors of Hyperechoic Pancreas on Sonography

Background and Aims: In the liver, diffuse hyperechoic regions usually represent fat deposits. Hyperechoic or bright regions in the pancreas, however, are not well studied. We investigated the clinical implications of hyperechoic pancreas to understand the prevalence and associated factors of this finding.Materials and Methods: A total of 353 sonograms of the pancreas of subjects who underwent a comprehensive health examination in a medical center were reviewed and included in the current analysis. Metabolic syndrome criteria from the National Cholesterol Education Program Adult Treatment Panel III (ATP III in the Asia-Pacific Region) were applied. Hyperechoic pancreas was defined as a homogeneous echogenicity of the pancreatic body that was slightly lower than or equal to the echogenicity of retroperitoneal fat.Results: Sonographically hyperechoic pancreas was significantly associated with male gender (odds ratio OR, 2.22; 95% confidence interval CI, 1.34-3.68), waist circumference (male ≥ 90 cm, female ≥ 80 cm; OR, 2.82; 95% CI, 1.53-5.20), and total cholesterol (≥ 200 mg/dL; OR, 1.87; 95% CI, 1.15-3.03). Hyperechoic pancreas was correlated with fatty liver. The incidence of metabolic syndrome was higher in the hyperechoic pancreas group.Conclusions: The prevalence of sonographically hyperechoic regions in the pancreas was associated with greater waist circumference and other types of hyperlipidemia. Sonographically hyperechoic pancreas showed a strong correlation with fatty liver and metabolic syndrome. Therefore, sonographically hyperechoic pancreas may indicate the presence of ”fatty pancreas”.
Robust Stability of Trait-Like Vulnerability or Resilience to Common Types of Sleep Deprivation in a Large Sample of Adults.

STUDY OBJECTIVES Sleep loss produces large individual differences in neurobehavioral responses, with marked vulnerability or resilience among individuals. Such differences are stable with repeated exposures to acute total sleep deprivation (TSD) or chronic sleep restriction (SR) within short (weeks) and long (years) intervals. Whether trait-like responses are observed to commonly experienced types of sleep loss and across various demographically defined groups remains unknown. METHODS 83 adults completed 2 baseline nights (10h-12h time-in-bed, TIB) followed by 5 4h TIB SR nights or 36h TSD. Subjects then received 4 12h TIB recovery nights followed by 5 SR nights or 36h TSD, in counterbalanced order to the first sleep loss sequence. Neurobehavioral tests were completed every 2h during wakefulness. RESULTS Subjects who displayed neurobehavioral vulnerability to TSD displayed vulnerability to SR, evidenced by substantial to near perfect intraclass correlation coefficients (ICCs; 78%-91% across measures). Sex, race, age, body mass index (BMI), season and sleep loss order did not impact ICCs significantly. Individuals exhibited significant consistency of responses within, but not between, performance and subjective domains. CONCLUSIONS Using the largest, most diverse sample to date, we demonstrate for the first time the remarkable stability of phenotypic neurobehavioral responses to commonly experienced sleep loss types, across demographic variables and different performance and subjective measures. Since sex, race, age, BMI, and season did not affect ICCs, these variables are not useful for determining stability of responses to sleep loss, underscoring the criticality of biological predictors. Our findings inform mathematical models and are relevant for the general population and military and health professions.
The Use of Tablet-Based Multiple-Pass 24-Hour Dietary Recall Application (MP24Diet) to Collect Dietary Intake of Children under Two Years Old in the Prospective Cohort Study in Indonesia

Dietary intake data are crucial for developing or evaluating nutrition interventions to improve the nutritional status of populations. The collection of accurate and reliable dietary data in developing countries, however, remains challenging. The emergence of new technologies, which facilitate electronic data capture, might address some of these challenges. This paper aims to describe an application developed to collect a multiple-pass 24-h dietary recall, using electronic data capture, and compare the results to those estimated using a paper-based method. In this study, a tablet-based application was developed, in the CommCare platform, to evaluate the effectiveness, for improving dietary adequacy, of a package of behavior change interventions to reduce stunting and anemia among 6–23-month-old children in East Java, Indonesia (Baduta project). Dietary intakes of energy and nutrients were estimated using electronic data capture in the cohort study of the Baduta project (n = 680). We compared these results with those estimated using paper-based data capture in the project’s end-line cross-sectional study (n = 2740). We found a higher percentage of children classified as acceptable energy reporters (reported energy intake within the 95% CI of Total Energy Expenditure) with the electronic data capture compared with paper-based data capture (i.e., 60.8%, 72.4% and 80.7% for 6–8-, 9–11- and 12–23-month-old children, respectively, vs. 40.9%, 56.9%, and 54.3%, respectively). The estimated mean energy and nutrient intakes were not significantly different between these dietary data capture methods. These results suggest dietary data collection, using a tablet-based application, is feasible and can improve the quality of dietary data collected in developing countries.
A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

Herein, we report the synthesis and cytotoxic effects of novel chlorinated plastoquinone analogs (ABQ1–17) against different leukemic cells. Compounds ABQ3, ABQ11, and ABQ12 demonstrated a pronounced antiproliferative effect against chronic myelogenous leukemia (CML) K562 cell line with IC50 values of 0.82 ± 0.07, 0.28 ± 0.03, and 0.98 ± 0.22 μM, respectively. Among them, ABQ11 showed approximately three times higher selectivity than imatinib on CML. ABQ11‐treated CML cells induced significant apoptosis at low concentration. Inhibitory effect of ABQ11 against eight different tyrosine kinases, including ABL1, was investigated. ABQ11 inhibited ABL1 with IC50 value of 13.12 ± 1.71 μM, indicating that the moderate inhibition of ABL1 kinase is just an in‐part mechanism of its outstanding cellular activity. Molecular docking of ABQ11 into ABL1 kinase ATP‐binding pocket revealed the formation of some key interactions. Furthermore, DNA cleavage assay showed that ABQ11 strongly disintegrated DNA at 1 μM concentration in the presence of iron (II) complex system, assuming that the major mechanism for the anticancer effects of ABQ11 is DNA cleavage. In silico ADMET prediction revealed that ABQ11 is a drug‐like small molecule with a favorable safety profile. Taken together, ABQ11 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from imatinib.
Serum IgA Fc effector functions in infectious disease and cancer

Immunoglobulin (Ig) A is the most abundant antibody isotype present at mucosal surfaces and the second most abundant in human serum. In addition to preventing pathogen entry at mucosal surfaces, IgA can control and eradicate bacterial and viral infections through a variety of antibody‐mediated innate effector cell mechanisms. The role of mucosal IgA in infection (e.g. neutralization) and in inflammatory homeostasis (e.g. allergy and autoimmunity) has been extensively investigated; by contrast, serum IgA is comparatively understudied. IgA binding to fragment crystallizable alpha receptor plays a dual role in the activation and inhibition of innate effector cell functions. Mounting evidence suggests that serum IgA induces potent effector functions against various bacterial and some viral infections including Neisseria meningitidis and rotavirus. Furthermore, in the era of immunotherapy, serum IgA provides an interesting alternative to classical IgG monoclonal antibodies to treat cancer and infectious pathogens. Here we discuss the role of serum IgA in infectious diseases with reference to bacterial and viral infections and the potential for IgA as a monoclonal antibody therapy.
Development and Validation of a Prognostic Nomogram to Guide Decision-Making for High-Grade Digestive Neuroendocrine Neoplasms.

BACKGROUND The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy. SUBJECTS, MATERIALS, AND METHODS We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one. RESULTS The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001). CONCLUSION The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials. IMPLICATIONS FOR PRACTICE The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.
A qualitative exploration of mentally tough behaviour in Australian football

ABSTRACT The primary aim of this research was to generate insight into observable mentally tough behaviours, or MTb, across different contexts (e.g., training and competition) in an Australian football (AF) environment. A second aim of this research was to explore the utility of MTb as a distinct concept, and identify common behavioural qualities associated with MTb that separate it from other similar constructs. In total, 10 experienced full-time football operations staff were interviewed using a semi-structured interview guide, with inductive thematic analysis employed to analyse the data. Five main themes relating to MTb were identified: adaptive development, consistent training conduct, composed performance actions, responsible and accountable, and team supportive. Overall, the findings of the research provided preliminary support for the proposition that there exists a collection of MTb that are displayed more frequently by athletes considered to possess high levels of mental toughness compared to athletes who are perceived to have low levels of this psychological capacity. We propose a collection of necessary and sufficient behavioural qualities and a working definition of MTb to further our understanding of potential strategies to develop MT.
Cost-effectiveness of a multi-stage school-based asthma case detection program in an urban school system

Asthma is a common chronic condition of childhood that results in frequent exacerbations associated with school absences, emergency department visits, and hospitalizations. School-based case detection to identify children with undiagnosed or poorly controlled asthma may reduce asthma morbidity; however, it is uncertain whether the resources consumed by case detection are justified by the expected improvements in health outcomes. Cost-effectiveness analysis using a decision tree with multiple Markov models to simulate asthma-related costs and outcomes in primarily urban, low-income, AfricanAmerican, elementary-age school children is performed. Modeled health states include symptom free, symptomatic, and exacerbation recovery days, as well as emergency department visits and hospitalizations. The time horizon is one year divided into 365 cycles. Two questionnaire only and two multi-stage interventions incorporating spirometry only or spirometry and exercise testing are evaluated. The analysis is performed from the societal perspective and is reported in 2006 dollars per quality adjusted life year (QALY) gained. The multi-stage with spirometry and exercise testing (MSwET) intervention is the most cost-effective intervention, with an incremental cost-effectiveness ratio (ICER) of $107,200 per QALY. Probabilistic sampling demonstrates that 90% of the observed ICERs fall between $47,400 and $155,500 per QALY. Ninety-five percent of the