Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis

Abstract The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstituted-1,2,4-oxadiazole derivatives (3a–3i) were tested against H37Rv, MDR and XDR strains of MTB. Of which, compound 3a with para-trifluorophenyl substituted oxadiazole showed excellent activity against the susceptible H37Rv and MDR-MTB strain with a MIC values of 8 and 16 µg/ml, respectively. To understand the mechanism of action of these compounds (3a–3i) and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, in silico ADMET predictions showed satisfactory properties for these compounds, collectively, making them, particularly compound 3a, promising leads worthy of further optimisation.
Self-consciousness and depression in precocious pubertal children

Objective To explore self-consciousness and depression in children with precocious puberty (PP) and analyse its effect on children of both sexes. Methods Sixty children with PP and 60 non-PP children matched for sex and age participated in the study. Children were assessed using the Birleson Depression Self-Rating Scale for Children and the Piers–Harris Children’s Self-Concept Scale. Results There were significant differences in physical appearance and attributes, anxiety, happiness and satisfaction between PP children and non-PP children. PP children had significantly higher depression than non-PP children. In the PP group, girls were significantly more prone to anxiety and unhappiness than boys. Conclusion: There were sex differences in the effect of PP on children’s self-consciousness, and girls were more prone to anxiety and unhappiness. More attention should be paid to improving the physical and mental health of children with PP.
ABO blood group and COVID-19: an updated systematic literature review and meta-analysis.

BACKGROUND Following the first reports in the literature, the association between the ABO blood group and SARS-CoV-2 infection has been investigated by a number of studies, although with varying results. The main object of this systematic review was to assess the relationship between the ABO blood group and the occurrence and severity of COVID-19. MATERIALS AND METHODS A systematic literature search using appropriate MeSH terms was performed through Medline and PubMed. The outcomes considered were the prevalence of the blood group O vs non-O types in SARS-CoV-2 infected and non-infected subjects, and the severity of SARS-CoV-2 infection according to ABO group. The methodological quality of the studies included in the analysis was assessed with the Newcastle-Ottawa Scale, and the overall quality of the available evidence using the GRADE system. Benchmarks used to evaluate the effect size were odd ratios (ORs) for case control studies and risk ratios (RRs) for cohort studies. RESULTS Twenty-one studies were included in the analysis. Overall, individuals with group O had a lower infection rate compared to individuals of non-O group (OR: 0.81; 95% CI: 0.75, 0.86). However, the difference in the effect size was significantly lower in cohort studies compared to case control studies. No evidence was found indicating an effect of the O type on the disease severity in the infected patients. DISCUSSION We have found low/very low evidence that group O individuals are less susceptible to SARS-CoV-2 infection compared to those in the non-O group. No evidence was found indicating an effect of the O type on disease severity in SARS-CoV-2 infection.
The association of nursing home quality ratings and spread of COVID‐19

The coronavirus disease 2019 (COVID‐19) pandemic has severely affected nursing home residents. Given the continued high incidence of COVID‐19, and the likelihood that new variants and other infectious agents may cause future outbreaks, we sought to understand the relationship of nursing home quality ratings and measures of COVID‐19 outbreak severity and persistence.
Decatungstate‐Mediated C(sp3)–H Heteroarylation via Radical‐Polar Crossover in Batch and Flow

Abstract Photocatalytic hydrogen atom transfer is a very powerful strategy for the regioselective C(sp3)–H functionalization of organic molecules. Herein, we report on the unprecedented combination of decatungstate hydrogen atom transfer photocatalysis with the oxidative radical–polar crossover concept to access the direct net‐oxidative C(sp3)–H heteroarylation. The present methodology demonstrates a high functional group tolerance (40 examples) and is scalable when using continuous‐flow reactor technology. The developed protocol is also amenable to the late‐stage functionalization of biologically relevant molecules such as stanozolol, (−)‐ambroxide, podophyllotoxin, and dideoxyribose.
Beyond a traumatic loss: The experiences of mourning alone after parental death during COVID-19 pandemic

Abstract Millions of adolescents around the world lost their loved ones due to the COVID-19 pandemic; at the same time, health protocols in many countries do not allow mourners to practice their familiar rituals around death and dying. This study explored the experience of 15 Iranian adolescents who had lost their parent(s) during the pandemic through a phenomenological approach. Two main themes including distress in a shattered life and crisis in crisis were extracted from the interviews. Findings highlight the importance of immediate and alternative ways of support for adolescents who lost their parents during the pandemic.
Effectiveness of Self-Management on Adherence to Self-Care and on Health Status among Elderly People with Hypertension

Background Adherence to self-care is the goal of nursing care for elderly people with hypertension to give them optimal functional health status. The purpose of this paper is to determine the effectiveness of self-management on adherence to self-care and management of health status elderly people living with hypertension in Pekanbaru City. Design and methods This study design was quasi-experimental with a pre-post test with a control group. The self-management intervention was provided through four home visits to elderly people living with hypertension with a caregiver. Samples were taken by the consecutive sampling technique, and a total number 134 elderly people were participants. The instruments used were the adherence to self-care questionnaire and the Short Form 12 Health Survey (SF12) for elderly people. Results The results showed that most of the respondents with hypertension were 60-74 years of age (84.3%), were female (67.9%), of Minang ethnicity (48.5%), had completed primary school (44%), were unemployed (81.3) %), had a family history of hypertension (50%), were non-smokers (52.2%), and had never drunk alcohol (95.5%). The effects of self-management were positive on adherence to caring for themselves (p<0.001) and on health status (p<0.001). The most influencing factor on self-care compliance and health status after being controlled by confounding variables was self-management (p<0.001). Conclusions This study recommends that nursing interventions on self-management for elderly people with hypertension in the community and should be integrated into the Community Health Nurses’ (Perkesmas) program in Indonesia.
Primary cardiovascular risk prediction by LDL-cholesterol in Caucasian middle-aged and older adults: a joint analysis of three cohorts.

AIMS Low-density lipoprotein cholesterol (LDL-C) is an established causal driver of atherosclerotic cardiovascular disease (ASCVD), but its performance and age-dependency as a biomarker for incident events and mortality arising from ASCVD is less clear. The aim was to determine the value of LDL-C as a susceptibility/risk biomarker for incident coronary heart disease (CHD), ASCVD, and stroke events and deaths, for the age groups <50 and ≥50 years. METHODS AND RESULTS The performance of LDL-C was evaluated in three cohorts, FINRISK 2002 (n = 7709), HUSK (n = 5431), and ESTHER (n = 4559), by Cox proportional hazards models, C-statistics, and net reclassification index calculations. Additionally, the hazard ratios (HRs) for the three cohorts were pooled by meta-analysis. The most consistent association was observed for CHD [95% confidence interval (CI) for HRs per standard deviation ranging from 0.99 to 1.37], whereas the results were more modest for ASCVD (0.96-1.18) due to lack of association with stroke (0.77-1.24). The association and discriminatory value of LDL-C with all endpoints in FINRISK 2002 and HUSK were attenuated in subjects 50 years and older [HRs (95% CI) obtained from meta-analysis 1.11 (1.04-1.18) for CHD, 1.15 (1.02-1.29) for CHD death, 1.02 (0.98-1.06) for ASCVD, 1.12 (1.02-1.23) for ASCVD death, and 0.97 (0.89-1.05) for stroke]. CONCLUSION In middle-aged and older adults, associations between LDL-C and all the studied cardiovascular endpoints were relatively weak, while LDL-C showed stronger association with rare events of pre-mature CHD or ASCVD death among middle-aged adults. The predictive performance of LDL-C also depends on the studied cardiovascular endpoint.
Dynamics of Proteins and Macromolecular Machines in Escherichia coli

Proteins are major contributors to the composition and the functions in the cell. They often assemble into larger structures, macromolecular machines, to carry out intricate essential functions. ABSTRACT Proteins are major contributors to the composition and the functions in the cell. They often assemble into larger structures, macromolecular machines, to carry out intricate essential functions. Although huge progress in understanding how macromolecular machines function has been made by reconstituting them in vitro, the role of the intracellular environment is still emerging. The development of fluorescence microscopy techniques in the last 2 decades has allowed us to obtain an increased understanding of proteins and macromolecular machines in cells. Here, we describe how proteins move by diffusion, how they search for their targets, and how they are affected by the intracellular environment. We also describe how proteins assemble into macromolecular machines and provide examples of how frequent subunit turnover is used for them to function and to respond to changes in the intracellular conditions. This review emphasizes the constant movement of molecules in cells, the stochastic nature of reactions, and the dynamic nature of macromolecular machines.
Pinocembrin ameliorates arrhythmias in rats with chronic ischaemic heart failure

Abstract Objective Ventricular arrhythmias (VAs) are a common complication of chronic ischaemic heart failure (CIHF). The purpose of this study is to investigate the efficacy of pinocembrin in a rat model of VAs induced by CIHF and further examine the possible mechanism. Methods Rats were subjected to ligation of left anterior descending coronary artery to mimic CIHF and then received pinocembrin treatment daily for 2 months. The vivo electrophysiology were performed to determine the effect of pinocembrin on ventricular electrical activity. The expression of Cav1.2, Kv4.2, and NGF was determined by Western blot. The structural change of ventricle was tested by the Echocardiography, Masson staining, and HE staining. The effect of pinocembrin on sympathetic nerve-related markers was detected by the immunostaining and the ELISA was used to test for biomarkers associated with heart failure. Results Pinocembrin increased the expression of ion channel protein Cav1.2 and Kv4.3, ameliorated the shortening of action potential duration (APD) and reduced the incidence and duration of ventricular fibrillation (VF). Pinocembrin also reduced the expression of nerve growth factor (NGF) and improved the autonomic nerve remodelling. In addition, pinocembrin reduced the area of infarct area and myocardial fibrosis, accompanied by increasing the expression of connexin protein 43 (CX43). Conclusion We demonstrate that pinocembrin reduces cardiac nerve remodelling and protects against Vas induced by CIHF. The findings suggest that pinocembrin can be a promising candidate for the treatment of VAs.
The Experiences of Women from Atoin Meto Tribe who Performed Sifon Ritual in the Context of HIV/AIDS Transmission

Background Sifon is a sexual intercourse ritual after male circumcision from the Atoin Meto tribe that contributed to HIV/AIDS transmission. Ritual Sifon may put at risk for HIV infection and also the sexual transmisson diseases. Doing ritual Sifon as a culture, without using protection during intercourse becomes one way to get HIV infection from infected men. Few study explore this phenomenon among women who becomes Sifon women. Therefore, the aim of this study is to explore the experience of Sifon women in the context of HIV/AIDS transmission. Design and Methods The data was collected from March 2020 to July 2020. This study used a phenomenological approach with a purposive sampling technique. Inclusion criteria: the women from Atoin Meto tribe aged above eighteen years old who have been Sifon women for at least six months. The participants were recruited through traditional healers in Nekbaun village of Kupang District and Timor Tengah Selatan District. The data was analysed by Collaizi method. Results Thirteen women were interviewed and we found four themes: lack of knowledge about HIV/AIDS transmission, unaware became Sifon women, women experienced of STDs, using traditional medicine to treat STDs (Timor medicine). Conclusions The interpretation of Sifonwomen's experiences that performed Sifon rituals indicated that Sifon is a risk factor for transmitting HIV/AIDS. Preventive and promotional educational programs with cultural approach are needed to reduce the risk of HIV/AIDS transmission.
Ghrelin receptor signalling is not required for glucocorticoid-induced obesity in female mice.

Chronic exposure to high circulating glucocorticoid or ghrelin concentrations increases food intake, weight gain and adiposity, suggesting that ghrelin could contribute to the metabolic effects of chronic glucocorticoids. In male mice, however, blocking ghrelin receptor (GHSR) signalling increased the weight gain and adiposity induced by chronic corticosterone (CORT), rather than attenuating them. In the current study, we investigated the role of GHSR signalling in the metabolic effects of chronic exposure to high circulating CORT in female mice. To do this, female WT and GHSR KO mice were treated with either CORT in a 1% ethanol (EtOH) solution or 1% EtOH alone in their drinking water for 32 days (N=5-8/group). Body weight, food, and water intake as well as vaginal cyclicity were assessed daily. As expected, CORT treatment induced significant increases in body weight, food intake, adiposity and also impaired glucose tolerance. In contrast to results observed in male mice, WT and GHSR KO female mice did not differ on any of these parameters. Neither plasma levels of ghrelin, LEAP-2, the endogenous GHSR antagonist produced by the liver, nor their ratio were altered by chronic glucocorticoid exposure. In addition, CORT treatment disrupted vaginal cyclicity, produced a reduction in sucrose consumption and increased locomotor activity regardless of genotype. Chronic CORT also decreased exploration in WT but not GHSR KO mice. Collectively, these data suggest that most metabolic, endocrine, reproductive and behavioral effects of chronic CORT exposure are independent of GHSR signalling in female mice.
Revisiting brain rewiring and plasticity in children born without corpus callosum

Abstract The corpus callosum is the largest white matter pathway connecting homologous structures of the two cerebral hemispheres. Remarkably, children and adults with developmental absence of the corpus callosum (callosal dysgenesis, CD) show typical interhemispheric integration, which is classically impaired in adult split‐brain patients, for whom the corpus callosum is surgically severed. Tovar‐Moll and colleagues (2014) proposed alternative neural pathways involved in the preservation of interhemispheric transfer. In a sample of six adults with CD, they revealed two homotopic bundles crossing the midline via the anterior and posterior commissures and connecting parietal cortices, and the microstructural properties of these aberrant bundles were associated with functional connectivity of these regions. The aberrant bundles were specific to CD and not visualised in healthy brains. We extended this study in a developmental cohort of 20 children with CD and 29 typically developing controls (TDC). The two anomalous white‐matter bundles were visualised using tractography. Associations between structural properties of these bundles and their regional functional connectivity were explored. The proposed atypical bundles were observed in 30% of our CD cohort crossing via the anterior commissure, and in 30% crossing via the posterior commissure (also observed in 6.9% of TDC). However, the structural property measures of these bundles were not associated with parietal functional connectivity, bringing into question their role and implication for interhemispheric functional connectivity in CD. It is possible that very early disruption of embryological callosal development enhances neuroplasticity and facilitates the formation of these proposed alternative neural pathways, but further evidence is needed.
Maternal Characteristics Mediating the Impact of Household Poverty on the Nutritional Status of Children Under 5 Years of Age in Bangladesh

Objectives: We explored the maternal characteristics that mediate the effect of household poverty on childhood undernutrition. Methods: We used the population-based Bangladesh Demographic Health Survey data from 2014 for demographic characteristics, child and maternal factors. Results: Of the 7173 under-5 children, 3456 (48.2%) had undernutrition. The prevalence of undernutrition was less common in wealthy households (poorest vs richest: adjusted prevalence ratio [aPR] = 1.37), mothers having history of antenatal care (ANC) visits (no visit vs ≥ 4 visits: aPR = 1.22), maternal higher education (no education vs higher education: aPR = 1.54), and mothers with good nutritional status (underweight vs healthy: aPR = 1.13). The risk of undernutrition (37.1%) was attributed to household wealth, mediated 55% by maternal factors; of which 20% by maternal education, 21% by ANC visits, and 14% by maternal nutritional status. Conclusions: Our study findings outlined higher maternal education, ≥ 4 ANC visits and good maternal nutritional status in mediating the impact of household wealth on childhood nutrition.
Structural and biochemical properties of L‐asparaginase

l‐Asparaginase (a hydrolase converting l‐asparagine to l‐aspartic acid) was the first enzyme to be used in clinical practice as an anticancer agent after its approval in 1978 as a component of a treatment protocol for childhood acute lymphoblastic leukemia. Structural and biochemical properties of l‐asparaginases have been extensively investigated during the last half‐century, providing an accurate structural description of the enzyme isolated from a variety of sources, as well as clarifying the mechanism of its activity. This review provides a critical assessment of the current state of knowledge of primarily structural, but also selected biochemical properties of ‘bacterial‐type’ l‐asparaginases from different organisms. The most extensively studied members of this enzyme family are l‐asparaginases highly homologous to one of the two enzymes from Escherichia coli (usually referred to as EcAI and EcAII). Members of this enzyme family, although often called bacterial‐type l‐asparaginases, have been also identified in such divergent organisms as archaea or eukarya. Over 100 structural models of l‐asparaginases have been deposited in the Protein Data Bank during the last 30 years. One of the prime achievements of structure‐centered approaches was the elucidation of the details of the mechanism of enzymatic action of this unique hydrolase that utilizes a side chain of threonine as the primary nucleophile. The molecular basis of other important properties of these enzymes, such as their substrate specificity, is still being evaluated. Results of structural and mechanistic studies of l‐asparaginases are being utilized in efforts to improve the clinical properties of this important anticancer drug.
Hyaluronic Acid Increases Anti-Inflammatory Efficacy of Rectal 5-Amino Salicylic Acid Administration in a Murine Colitis Model

5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.
Outcomes after breast-conserving surgery or mastectomy in patients with triple-negative breast cancer: meta-analysis.

BACKGROUND In patients with triple-negative breast cancer (TNBC), oncological and survival outcomes based on locoregional treatment are poorly understood. In particular, the safety of breast-conserving surgery (BCS) for TNBC has been questioned. METHODS A meta-analysis was performed to evaluate locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) rates in patients with TNBC who had breast-conserving surgery versus mastectomy. Estimates were pooled in random-effects analysis. The effect of study-level co-variables was assessed by univariable metaregression. RESULTS Fourteen studies, including 19 819 patients operated for TNBC met the inclusion criteria; 9828 patients (49.6 per cent) underwent BCS and 9991 (50.4 per cent) had a mastectomy. Patients with smaller tumours were more likely to be selected for BCS (pooled odds ratio (OR) for T1 tumours 1.95, 95 per cent c.i. 1.64 to 2.32; P < 0.001). The pooled OR for LRR was 0.64 (0.48 to 0.85; P = 0.002), indicating a statistically significantly lower odds of LRR among women who had BCS relative to mastectomy. The pooled OR for DM was 0.70 (0.53 to 0.94; P = 0.02), indicating a lower odds of DM among women who had BCS; however, this difference diminished with increasing study-level age and follow-up time. A pooled hazard ratio of 0.78 (0.69 to 0.89; P < 0.001) showed a significantly lower hazard for all-cause mortality among women undergoing BCS versus mastectomy. CONCLUSION These results should be interpreted cautiously owing to likely differences in selection for BCS or mastectomy in the included studies. Patients with TNBC selected for BCS do not, however, have a worse prognosis than those treated with mastectomy, and breast conservation can be offered when feasible clinically.