The estrogen hormone receptor (ER) mediated gene expression mainly regulate the development and physiology of primary and secondary reproductive system alongside bone-forming, metabolism and behaviour. Over-expressed ER is associated with several pathological conditions and play a key role in breast cancer occurrence, progression and metastasis. Hibiscus sabdariffa L. or roselle is a rich source of naturally occurring polyphenolic compounds including anthocyanins and reportedly have strong estrogenic activity. To validate these findings, we have investigated the estrogen receptor binding affinity and safety of some previously recorded polyphenols using a suite of computational methods. Our investigation showed the estrogen-receptor binding potential of Pelargonidin, Delphinidin, Cyanidin, and Hibiscetin are more efficient than popular breast cancer drugs, Tamoxifen and Raloxifene, with favourable toxicological parameters and low half maximal inhibitory concentration. This is the first report to investigate the phytochemical basis of estrogenic activity of Hibiscus sabdariffa L.

Evaluation of the effectiveness of protected areas is critical for forest conservation policies and priorities. To evaluate their effectiveness, we used 30-m resolution forest cover change data between 1990 and 2010 for ~4,000 protected areas and analyzed the relationships of the effectiveness of protected areas with socio-economic variables. Our results show that protected areas in the Tropics avoided 83,500 ± 21,200 km2 of deforestation during the 2000s. Brazil’s protected areas have the largest amount of avoided deforestation of 50,000 km2. We also show the amount of international aid received by tropical countries compared to the effectiveness of protected areas. International aid had major benefits in Latin America led by Brazil while tropical Asian countries used the resource ineffectively. Our results demonstrate that protected areas have been relatively more efficient in countries where deforestation pressures were increasing, and governance and forest change monitoring capacity are important factors for enhancing the efficacy of international aid.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

The Pythagorean fuzzy set (PFS), which is characterized by a membership and a non-membership degree and the square sum of them is less or equal to one, can act as an effective tool to express decision makers’ fuzziness and uncertainty. Considering that the Heronian mean (HM) is a powerful aggregation operator which can take the interrelationship between any two arguments, we study the HM in Pythagorean fuzzy environment and propose new operators for aggregating interval-valued Pythagorean fuzzy information. First, we investigate the HM and geometric HM (GHM) under interval-valued intuitionistic fuzzy environment and develop a series of aggregation operators for interval-valued intuitionistic fuzzy numbers (IVIFNs) including interval-valued intuitionistic fuzzy Heronian mean (IVIFHM), interval-valued intuitionistic fuzzy geometric Heronian mean (IVIFGHM), interval-valued intuitionistic fuzzy weighted Heronian mean (IVIFWHM) and interval-valued intuitionistic fuzzy weighted geometric Heronian mean (IVIFWGHM). Second, some desirable and important properties of these aggregation operators are discussed. Third, based on these aggregation operators, a novel approach to multi-attribute decision making (MADM) is proposed. Finally, to demonstrate the validity of the approach, a numerical example is provided and discussed. Moreover, we discuss several real-world applications of these operators within policy-making contexts.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

In the present study, the new biological sources in the form of lichen Usnea orientalis Motyka was screened for its antidermatophytic potential. Six species of dermatophytes were chosen on the basis of their prevalence for antidermatophytic assays, and the Clinical Laboratory Standard Institute (CLSI)-recommended broth microdilution procedure was used to detect the efficacy of extract against dermatophytes. Thin layer chromatography of lichen extracts reveals the presence of two secondary metabolites viz. salazinic acid and usnic acid. U. orientalis extract exhibited promising antidermatophytic activity against all tested pathogens. Amongst all tested pathogens, E. floccosum exhibited most susceptibility towards extract, whereas T. mentagrophytes exhibited the least susceptibility. Topical application of U. orientalis extract might be helpful in the cure of dermal infections.

Globally, football as a sport has recorded the highest rate of injury morbidity compared with other sports due to the high degree of contact between the players. Coaches play an important role in reducing injuries among the players. The objective of this study was to explore the pattern of football-related sports injuries among junior high school footballers in Dhaka, Bangladesh. A descriptive cross-sectional study was conducted between January 2019 to March 2019 in 20 junior high schools in Dhaka Metropolitan city. We observed 368 boys in the age range of 10 to 18 years old. A pre-structured questionnaire was provided to six trained junior physiotherapists to conduct the face-to-face interview with the boys in the school setting. Most students were from middle-income families. The injury prevalence of defenders was the most (157, 42.7%) followed by mid-fielders (132, 35.94%), forwards (63, 17.1%), and goalkeepers (16, 4.3%). Tackling was the main cause of injury in 21.1% of cases followed by foul play in 19.1% of the cases. In July, there were more injuries (69.0%) and associated muscle strain. Injured footballers did not visit sports physiotherapists as much as they did other health profession and the association was significant. When considering scientific knowledge, students were aware of fitness, flexibility & endurance (25.5%), sports massage (24.5%), the relation of body structure with sports Injury (21.2%), warm-up and/or cool down (19.6%). Based on the study, it was seen that students had no scientific knowledge of sports. As sports is a key activity for school-going children, comprehensive sports injury preventive knowledge is needed for students and sports teachers and coaches. Access to sports physiotherapists is also needed to prevent and manage sports injury at the field level and for rehabilitation.

Thalassemia is a common monogenic autosomal disorder prevalent in India. HbE beta thalassemia is a compound heterozygous state of two different beta globin mutations (HBB), predominant in the Eastern India. In HbE-beta thalassemia (β⁺/β°) patients, one HBB mutation does not produce any functional protein (β°); another mutation produces a structural altered haemoglobin, variant E (β⁺). It has been observed that in HbE-beta thalassemia patients with same type of HBB mutations, there exist diverse phenotypic presentation ranging from very severe, with regular transfusion-dependence to clinically non severe requiring very less transfusion or no transfusion. To explore this phenotypic mystery, we performed trio based expanded whole exome sequencing (WES) of two extreme phenotypes of HbE beta thalassemia subjects with similar HBB genotype and their parents. For WES library preparation, Agilent Sure select V6+UTR kit was used and sequencing was done through the Illumina HiSeq 2500 platform. This study aimed to search for de novo or inherited variants associated with the clinical severity. Six significant inherited variants were found in the genes, ATOH8, TTLL4, P2RX7, PRSS54, SLC9C2 and VRK2 in severe subject, however only one significant inherited variant in MTRR gene was found in non-severe subject. Bioinformatic analysis also confirms that each variant significantly changes in respective protein structure. The identified genes were either associated with iron absorption, oxidative stress, hematopoietic stem cell differentiation, structural organization of RBC cytoskeleton or regulating anemia. No significant de novo variant were identified associated with clinical severity. The finding of this study indicates that the combined effect of mutation load in major pathways may responsible for severe phenotype.

Introduction: Left atrial hypertension is one of the pathophysiologies of heart failure with preserved ejection fraction. We hypothesized that left atrial pressure response (LAPR) to incremental pacing is higher in patients with atrial fibrillation (AF) and can predict left ventricular diastolic dysfunction. Methods: Patients requiring left atrial access as a part of a therapeutic procedure for AF (n=204, AF group) or supraventricular tachycardia (n=34, control group) were analyzed (male n=183, 54±12 years old). LAPR was measured during incremental pacing. Results: Baseline left atrial pressure and LAPR at all pacing rates were not different between the AF and control groups. They were higher in patients with a high E/e’ (≥ 8) than in those with a low E/e’ (< 8). LAPR at a pacing interval of 400ms and E/e' were positively correlated (r=0.373, p<0.001). Body mass index and a high E/e' were independent predictors of pacing-induced left atrial hypertension. Conclusions: The LAPR to incremental pacing was constant regardless of AF. The non-invasive echocardiographic marker E/e' reflected pacing-induced left atrial hypertension.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - >70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - > 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those > 2.0 and < 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.