A data-driven global flood forecasting system for medium to large rivers.

Losses from catastrophic floods are driving intense efforts to increase preparedness and improve response to disastrous flood events by providing early warnings. Yet accurate flood forecasting remains a challenge due to uncertainty in modeling, calibrating, and validating a useful early warning system. This paper presents the Requisitely Simple (ReqSim) flood forecasting system that includes key variables and processes of basin hydrology and atmospheric forcing in a data-driven modeling framework. The simplicity of the modeling structure and data requirements of the system allows for customization and implementation in any medium to large rain-fed river basin globally, provided there are water level or discharge measurements at the forecast locations. The proposed system's efficacy is demonstrated in this paper through providing useful forecasts for various river basins around the world. This include 3-10-day forecasts for the Ganges and Brahmaputra rivers in South Asia, 2-3-day forecast for the Amur and Yangtze rivers in East Asia, 5-10-day forecasts for the Niger, Congo and Zambezi rivers in West and Central Africa, 6-8-day forecasts for the Danube River in Europe, 2-5-day forecasts for the Parana River in South America, and 2-7-day forecasts for the Mississippi, Missouri, Ohio, and Arkansas rivers in the USA. The study also quantifies the effect of basin size, topography, hydrometeorology, and river flow controls on forecast accuracy and lead times. Results indicate that ReqSim's forecasts perform better in river systems with moderate slopes, high flow persistence, and less flow controls. The simple structure, minimal data requirements, ease of operation, and useful operational accuracy make ReqSim an attractive option for effective real-time flood forecasting in medium and large river basins worldwide.

Evaluation of environmental impacts of cotton polo shirt production in Bangladesh using life cycle assessment.

The textile industry is widely considered as one of the most pollutant-releasing sectors globally. As the world is moving toward sustainability, it is essential to thoroughly assess how a textile product affects the environment. The aim of this study is to investigate the environmental impact of textile manufacturing in Bangladesh using life cycle assessment (LCA) method. A cradle-to-gate LCA was conducted to produce 1000 units of cotton polo shirts following ISO 14040 standards. LCA was also conducted for each final product at every manufacturing stage of cotton polo shirt, including the production of 1000 kg of cotton fibers, 1000 kg of yarn, 1000 kg of grey fabrics, 1000 kg of dyed-finished fabrics, and finally, assembling of 1000 pieces of polo shirts. Inventory analysis revealed that for producing 1000 pieces of polo shirts, 0.12 hector of land, 363.89 kg of cotton fiber, 324.84 kg of yarn, 320.45 kg of knitted fabric, and 299.5 kg of dyed-finished fabrics were required. The study also found that 1550.9 kWh of electricity, 15.47 L of diesel, and 72.54 m3 of natural gas were needed to produce 1000 pieces of polo shirts. The potential environmental impacts were categorized into 12 different types based on the CML 2001 method and calculated using openLCA 2.0 software. The outcomes of LCA revealed considerable environmental impacts in different categories during manufacturing of cotton polo shirts in Bangladesh. For example, the global warming potential (GWP) associated with the manufacturing of 1000 pieces of polo shirts was 1345.97 kg CO2-eq. Among several production stages of polo shirts, the highest contributor of GWP was dyeing section (38.36 %), followed by cotton fiber production (29.32 %) and yarn manufacturing (18.92 %). The obtained data also revealed that for cultivating cotton fibers, manufacturing of yarn and grey fabrics, and finally dyeing-finishing of same quantity fabric (1000 kg), the GWP were 1084.41 kg CO2-eq, 783.67 kg CO2-eq, 145.88 kg CO2-eq, 1723.88 kg CO2-eq, 314.94 kg CO2-eq, respectively. The outcome of the impact assessment will be crucial for decision-making when it comes to taking remedial actions to lessen negative environmental consequences for the sustainable development of textile industry in Bangladesh.

Association of low serum 25-Hydroxy vitamin D [25(OH) d] with hepatic encephalopathy in patients with decompensated liver cirrhosis.

BACKGROUND AND STUDY AIMS: The mechanism of hepatic encephalopathy is complex and has not been conclusively established. Recent studies support lower serum 25-Hydroxy Vitamin D [25(OH) D] levels in patients with hepatic encephalopathy. This study aimed to evaluate the association between serum 25(OH) D and hepatic encephalopathy in patients with decompensated cirrhosis of liver. PATIENTS AND METHODS: A total of 70 cirrhosis patients (35 cases of hepatic encephalopathy and 35 patients without encephalopathy as control, mean age 53.07 ± 12.99 years, 67 % male) were recruited for this study. Assessment of the severity of cirrhosis was done by using a model for end-stage liver disease(MELD) and Child Turcotte Pugh (CTP) scores, and assessment of the severity of hepatic encephalopathy was done according to West Haven criteria. Serum 25 (OH) D level was measured by Chemiluminescent Microparticle Immuno Assay(CMIA). RESULTS: The mean serum 25(OH) D level among hepatic encephalopathy patients was significantly lower in comparison to the control group without encephalopathy (18.76 ± 8.84 nmol/L vs 31.19 ± 13.9 nmol/L, P<0.0001). 91.4 % of hepatic encephalopathy patients had moderate to severe 25(OH)D deficiency as compared to 51.4 % in the control group. There was a significant correlation observed between the severity of the 25 (OH) D deficiency and the severity of liver disease (r =  - 0.35, P = 0.002). No statistically significant difference in serum 25(OH) D levels was found among patients with different hepatic encephalopathy grades (P = 0.416). CONCLUSION: A significant association was found between a low serum 25(OH) D leveland hepatic encephalopathy. It requires further large-scale multicenter studies to establish it as a risk factor and predictor of hepatic encephalopathy.

CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC.

BACKGROUND: The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considerable advancements in treatment, the success in diagnosing HNSCC at an early stage still needs to be improved. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Sonic Hedgehog (Shh) are overexpressed in various cancers, including HNSCC, and have recently been proposed as possible therapeutic targets for HNSCC. Circulating Tumor Cell (CTC) is a novel concept used for the early detection of cancers, and studies have suggested that a higher CTC count is associated with the aggressiveness of HNSCC and poor survival rates. Therefore, we aimed to establish molecular markers for the early diagnosis of HNSCC considering Shh/Nrf2 overexpression in the background. In addition, the relation between Shh/Nrf2 and CTCs is still unexplored in HNSCC patients. METHODS: In the present study, we selected a cohort of 151 HNSCC patients and categorized them as CTC positive or negative based on the presence or absence of CTCs in their peripheral blood. Data on demographic and clinicopathological features with the survival of the patients were analyzed to select the patient cohort to study Shh/Nrf2 expression. Shh and Nrf2 expression was measured by qRT-PCR. RESULTS: Considering significant demographic [smoking, betel leaf (p-value < 0.0001)] and clinicopathological risk factors [RBC count (p < 0.05), Platelet count (p < 0.05), Neutrophil count (p < 0.005), MCV (p < 0.0001), NLR (p < 0.05), MLR (p < 0.05)], patients who tested positive for CTC also exhibited significant overexpression of Shh/Nrf2 in both blood and tissue compared to CTC-negative patients. A strong association exists between CTCs and tumor grade. Following chemotherapy (a combination of Cisplatin, 5FU, and Paclitaxel), the frequency of CTCs was significantly decreased in patients with HNSCC who had tested positive for CTCs. The Kaplan-Meier plot illustrated that a higher number of CTCs is associated with poorer overall survival (OS) in patients with HNSCC. CONCLUSIONS: Detecting CTCs, and higher expression of Shh and Nrf2 in HNSCC patients' blood, can be a promising tool for diagnosing and prognosticating HNSCC.

Unraveling the impact of ORF3a Q57H mutation on SARS-CoV-2: insights from molecular dynamics.

ORF3a is a conserved accessory protein of SARS-CoV-2, linked to viral infection and pathogenesis, with acquired mutations at various locations. Previous studies have shown that the occurrence of the Q57H mutation is higher in comparison to other positions in ORF3a. This mutation is known to induce conformational changes, yet the extent of structural alteration and its role in the viral adaptation process remain unknown. Here we performed molecular dynamics (MD) simulations of wt-ORF3a, Q57H, and Q57A mutants to analyze structural changes caused by mutations compared to the native protein. The MD analysis revealed that Q57H and Q57A mutants show significant structural changes in the dimer conformation than the wt-ORF3a. This dimer conformer narrows down the ion channel cavity, which reduces Na + or K + permeability leading to decrease the antigenic response that can help the virus to escape the host immune system. Non-bonding interaction analysis shows the Q57H mutant has more interacting residues, resulting in more stability within dimer conformation than the wt-ORF3a and Q57A. Moreover, both mutant dimers (Q57H and Q57A) form a novel salt-bridge interaction at the same position between A:Asp142 and B:Lys61, whereas such an interaction is absent in the wt-ORF3a dimer. We have also noticed that the TM3 domain's flexibility in Q57H is increased because of strong inter-domain interactions of TM1 and TM2 within the dimer conformation. These unusual interactions and flexibility of Q57H mutant can have significant impacts on the SARS-CoV-2 adaptations, virulence, transmission, and immune system evasion. Our findings are consistent with the previous experimental data and provided details information on the structural perturbation in ORF3a caused by mutations, which can help better understand the structural change at the molecular level as well as the reason for the high virulence properties of this variant.Communicated by Ramaswamy H. Sarma.

Structural and functional effects of the L84S mutant in the SARS-COV-2 ORF8 dimer based on microsecond molecular dynamics study.

The L84S mutation has been observed frequently in the ORF8 protein of SARS-CoV-2, which is an accessory protein involved in various important functions such as virus propagation, pathogenesis, and evading the immune response. However, the specific effects of this mutation on the dimeric structure of ORF8 and its impacts on interactions with host components and immune responses are not well understood. In this study, we performed one microsecond molecular dynamics (MD) simulation and analyzed the dimeric behavior of the L84S and L84A mutants in comparison to the native protein. The MD simulations revealed that both mutations caused changes in the conformation of the ORF8 dimer, influenced protein folding mechanisms, and affected the overall structural stability. In particular, the 73YIDI76 motif has found to be significantly affected by the L84S mutation, leading to structural flexibility in the region connecting the C-terminal ß4 and ß5 strands. This flexibility might be responsible for virus immune modulation.  The free energy landscape (FEL) and principle component analysis (PCA) have also supported our investigation. Overall, the L84S and L84A mutations affect the ORF8 dimeric interfaces by reducing the frequency of protein-protein interacting residues (Arg52, Lys53, Arg98, Ile104, Arg115, Val117, Asp119, Phe120, and Ile121) in the ORF8 dimer.  Our findings provide detail insights for further research in designing structure-based therapeutics against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Reduced IFN-γ levels along with changes in hematologic and immunologic parameters are key to COVID-19 severity in Bangladeshi patients.

The manifestation of coronavirus disease 2019 (COVID-19) severity and mortality has been associated with dysregulation of the immune response, often influenced by racial disparities and conferred by changes in hematologic and immunologic parameters. These biological and hematologic parameters as well as cytokine profiles were investigated in a cohort of 61 COVID-19-positive patients (categorized into mild, moderate, and severe groups) from Bangladesh using standard analytical methods. The data reported that the interleukin (IL)-4 and IL-6 levels were significantly increased, whereas the levels of interferon (IFN)-γ were significantly reduced in patients with severe COVID-19 (p < 0.05) compared with those in patients with mild and/or moderate COVID-19. The extent of erythrocyte sedimentation rate (ESR); neutrophil count; and levels of ferritin, C-reactive protein (CRP), and D-dimer (p < 0.05) were found to be significantly increased, whereas the white blood cell (WBC), lymphocyte, eosinophil, and platelet counts (p < 0.05) were observed to be significantly reduced in patients with severe COVID-19 compared with those in the patients in other 2 groups. Our study exhibited a significantly higher IL-6-to-lymphocyte ratio in patients with severe COVID-19 than in those with mild and moderate COVID-19. The calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and ferritin-to-ESR ratio were significantly increased in patients with severe COVID-19. The increase in the IL-4 and IL-6 levels along with CRP and D-dimer levels may envisage a hyperinflammatory environment and immune dysregulation, which contribute to prolonged viral persistence, leading to severe disease. However, the reduced level of IFN-γ can be attributed to a less fatality toll in Bangladesh compared with that in the rest of the world.

Genetic alterations of Keap1 confers chemotherapeutic resistance through functional activation of Nrf2 and Notch pathway in head and neck squamous cell carcinoma.

Keap1 mutations regulate Nrf2 activity and lead to chemoresistance in cancers. Yet the underlying molecular mechanisms of chemoresistance are poorly explored. By focusing and genotyping head and neck squamous cell carcinoma (HNSCC) that had available pathologic and clinical data, we provide evidence that Keap1 displays frequent alterations (17%) in HNSCC. Functional loss of Keap1 results in significant activation of Nrf2 and promotes cancer cell growth, proliferation, and elevated cancer stem cell (CSCs) self-renewal efficiency and resistance to oxidative stress. Furthermore, decreased Keap1 activity in these cells increased nuclear accumulation of Nrf2 and activation of the Notch pathway, causing enhanced transcriptional alterations of antioxidants, xenobiotic metabolism enzymes, and resistance to chemotherapeutic treatment. Limiting the Nrf2 activity by either Keap1 complementation or by Nrf2 silencing increased the sensitivity to chemotherapy in Keap1-mutated cells and repressed the CSC self-renewal activity. Our findings suggest that Keap1 mutations define a distinct disease phenotype and the Keap1-Nrf2 pathway is one of the leading molecular mechanisms for clinical chemotherapeutic resistance. Targeting this pathway may provide a potential and attractive personalized treatment strategy for overcoming chemotherapeutic resistance conferred by Keap1 mutations.

Detection of SARS-CoV-2 RNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) on Self-Collected Nasal Swab Compared With Professionally Collected Nasopharyngeal Swab.

BACKGROUND: Self-collection of nasal swabs for the detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) would considerably increase the testing capability and decrease the risk of transmission among healthcare workers (HCW) and the use of personal protective equipment (PPE). OBJECTIVES: This study aimed to evaluate the performance of self-collected nasal swabs compared with professionally collected nasopharyngeal (NP) swabs for detection of SARS-CoV-2 RNA by RT-PCR. MATERIALS AND METHODS: We performed a cross-sectional study where the suspected cases of coronavirus disease 2019 (COVID-19) were instructed about the self-collection of nasal swabs from their mid-turbinate. The results were compared to a nasopharyngeal swab collected by a trained healthcare worker in the same patient at the same sitting. RESULTS: We enrolled 100 participants, of which, 69 (69%) were male and 31 (31%) were female. The median age of the study participant was 36 years. Of the participants, 58 (58%) were symptomatic, and the commonest clinical presentation was cough, which was present in 42 (42%) participants. Out of 100 samples, 31 (31%) professionally collected nasopharyngeal swabs and 28 (28%) self-collected nasal swabs were positive for SARS-CoV-2 by RT-PCR. Out of 31 professionally collected positive samples, three samples were negative in self-collection. Out of 28 self-collected positive samples, no sample was negative in the professional collection. The sensitivity and specificity of self-collected nasal swabs compared to professionally collected nasopharyngeal swabs were 90.32% and 100.00%, respectively. The sensitivity of self-collected nasal was 100% when the cycle threshold (Ct) value of the professionally collected NP swab was less than 30. CONCLUSION: Our study showed that self-collected nasal swabs' sensitivities were similar to professionally collected NP swabs with a high viral load (low Ct value). Hence, this method could be used when the patient is symptomatic and come to the health providers in the early stage of COVID-19 illness.

Sero-prevalence and risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in a rural district of Bangladesh: A cohort study.

Background: Bangladesh reported its first COVID-19 case on March 8, 2020. Despite lockdowns and promoting behavioural interventions, as of December 31, 2021, Bangladesh reported 1.5 million confirmed cases and 27 904 COVID-19-related deaths. To understand the course of the pandemic and identify risk factors for SARs-Cov-2 infection, we conducted a cohort study from November 2020 to December 2021 in rural Bangladesh. Methods: After obtaining informed consent and collecting baseline data on COVID-19 knowledge, comorbidities, socioeconomic status, and lifestyle, we collected data on COVID-like illness and care-seeking weekly for 54 weeks for women (n = 2683) and their children (n = 2433). Between March and July 2021, we tested all participants for SARS-CoV-2 antibodies using ROCHE's Elecsys® test kit. We calculated seropositivity rates and 95% confidence intervals (95% CI) separately for women and children. In addition, we calculated unadjusted and adjusted relative risk (RR) and 95% CI of seropositivity for different age and risk groups using log-binomial regression models. Results: Overall, about one-third of women (35.8%, 95% CI = 33.7-37.9) and one-fifth of children (21.3%, 95% CI = 19.2-23.6) were seropositive for SARS-CoV-2 antibodies. The seroprevalence rate doubled for women and tripled for children between March 2021 and July 2021. Compared to women and children with the highest household wealth (HHW) tertile, both women and children from poorer households had a lower risk of infection (RR, 95% CI for lowest HHW tertile women (0.83 (0.71-0.97)) and children (0.75 (0.57-0.98)). Most infections were asymptomatic or mild. In addition, the risk of infection among women was higher if she reported chewing tobacco (RR = 1.19,95% CI = 1.03-1.38) and if her husband had an occupation requiring him to work indoors (RR = 1.16, 95% CI = 1.02-1.32). The risk of infection was higher among children if paternal education was >5 years (RR = 1.37, 95% CI = 1.10-1.71) than in children with a paternal education of ≤5 years. Conclusions: We provided prospectively collected population-based data, which could contribute to designing feasible strategies against COVID-19 tailored to high-risk groups. The most feasible strategy may be promoting preventive care practices; however, collecting data on reported practices is inadequate. More in-depth understanding of the factors related to adoption and adherence to the practices is essential.

Patient factors associated with the offering of telehealth appointments from primary care physicians among Medicare Beneficiaries: Results from a national survey.

INTRODUCTION: This study assessed patient factors associated with self-reported telehealth offerings from their primary care physicians (PCPs) among Medicare beneficiaries during the COVID-19 pandemic, and compared potential telehealth accessibility of telehealth appointments from PCP by US census region before and during the COVID-19 pandemic. METHODS: Data were from the Medicare Current Beneficiary Survey (MCBS) 2021 Winter COVID-19 Supplement. We conducted a multivariable logistic regression to examine patient-level factors associated with telehealth offerings. RESULTS: Overall, 78% Medicare beneficiaries reported that they had access to telehealth appointments from their PCPs during the COVID-19 pandemic. Majority beneficiary respondents reported to have Internet access (82.1%) and own at least one type of computer device (81.5%). Respondents with Internet access (Adjusted Odds Ratio (AOR) = 1.66, 95% Confidence Interval (CI): 1.38, 2.00; p < 0.0001) and owning a device (AOR = 1.43, 95 %CI: 1.19, 1.72; p < 0.0001) were more likely to report PCP telehealth offerings controlling for patient characteristic variables in the model. Respondents who were female (AOR = 1.16, 95 %CI: 1.02, 1.31; p = 0.020), age group of 65-74 years (AOR = 1.29, 95 %CI: 1.07, 1.56; p = 0.008), income ≥$25,000 (AOR = 1.36, 95 %CI: 1.18 1.56; p < 0.0001), metropolitan residence (AOR = 1.96, 95 %CI: 1.72, 2.24; p < 0.0001), and with a history of weakened immune system (AOR = 1.46, 95 %CI: 1.18, 1.80; p < 0.0001) or diabetes (AOR = 1.20, 95 %CI: 1.06, 1.37; p = 0.005) were more likely to report PCP telehealth offerings compared to their counterparts. Non-Hispanic Black (AOR = 0.70, 95 %CI: 0.58, 0.85; p < 0.0001) (compared to Non-Hispanic-White) and beneficiaries living in the South (compared to those living in the Northwest, Midwest, and West) were less likely to report PCP telehealth offerings. DISCUSSION: Key findings suggested health disparities existed in telehealth offerings from PCPs in terms of Internet access, device owning, age, race/ethnicity, income, residential locations, and census regions. Policy makers should consider these health disparities and provide targeted incentives and/or interventions when expanding and encouraging utilization of telehealth among Medicare beneficiaries.

Heavy metal pollution through hand loom-dyeing effluents and its effect on the community health.

Kumarkhali upazila in Kushtia district of western Bangladesh has become especially vulnerable to dye-effluent pollution over the last two decades. Twenty dyeing effluent samples were obtained at random from various dyeing units and used to determine the heavy metal concentration. The effluent pH, electrical conductivity and total dissolved solids ranged from 3.69 to 13.68, 627 to 7160 mS cm-1 and 4140 to 19800 mg L-1, respectively. In dyeing effluents, the average concentrations of Zn, Cu, Pb, Mn, Fe and Cr ions were 5.50, 82.75, 6.80, 14.27, 66.03 and 65.28 µg mL-1, respectively, while the amount of Cd was barely detectable. Total annual discharges of Cu, Zn, Pb, Mn, Fe and Cr were found to be 21.52, 1.43, 1.77, 3.71, 17.12 and 16.98 kg year-1, respectively, which were high enough to pollute the local environment. According to the survey report, only a minority were aware of public safety measures and proper disposal procedures, though many respondents were conscious of the dangers associated with dyes and chemical substances. Most interviewees (58.33%) used synthetic dyes and other dangerous chemicals throughout the dyeing process, despite the fact that 43.33% did not use hand gloves. A remarkable 80% of respondents were improperly disposing of unused dyes and chemicals. Overall, there was a lack of awareness, right attitude and appropriate behavioural patterns about using dyeing chemicals. To prevent the negative effects of dyeing effluents on the community in the research area, environmental conservation rules should be appropriately implemented.

Evaluation of Antioxidant, Cytotoxic, Anti-Inflammatory, Antiarthritic, Thrombolytic, and Anthelmintic Activity of Methanol Extract of Lepidagathis hyalina Nees Root.

Lepidagathis hyalina Nees is an ethnomedicinally potential Asian herb, locally used to treat cardiovascular diseases and coughs. The study was intended to evaluate qualitative and quantitative investigation to ensure numerous pharmacological properties of methanol extracts of L. hyalina Ness root (MELHR). MELHR manifested strong radical scavenging activity in the reducing power and DPPH (1, 1-diphenyl-2-picrylhydrazyl) assays, and phenol and flavonoid in the quantitative assays. In the study of the thrombolytic assay, MELHR showed moderate explicit percentage of clot lysis (29.39 ± 1.40%) with moderate (135.35 µg/mL) toxic properties. The in vitro anti-inflammatory activity was evaluated by the inhibition of hypotonicity-induced RBC hemolysis, whereas the plant extract exhibited a significant (pp ˂ 0.005) dose-dependent inhibition and the highest inhibition was found 55.01 ± 3.22% at 1000 µg/mL concentration. Moreover, the MELHR also showed significant (p < 0.005) dose-dependent potentiality on protein denaturation which is considered as antiarthritic activity, and the peak inhibition was found significant (71.97 ± 2.71%) at 1000 µg/mL concentration. MELHR also exhibited the dose-dependent and statistically significant anthelmintic potential on aquarium worm (Tubifex tubifex). So, the present investigation suggests that L. hyalina could be the best choice for the management of cardiovascular, inflammation, arthritis, and anthelmintic diseases. Further investigation should be necessary to determine behind the mechanism of bioactivity and therapeutic potential of this plant.

Structure and dynamics of membrane protein in SARS-CoV-2.

SARS-CoV-2 membrane (M) protein performs a variety of critical functions in virus infection cycle. However, the expression and purification of membrane protein structure is difficult despite tremendous progress. In this study, the 3 D structure is modeled followed by intensive validation and molecular dynamics simulation. The lack of suitable homologous templates (>30% sequence identities) leads us to construct the membrane protein models using template-free modeling (de novo or ab initio) approach with Robetta and trRosetta servers. Comparing with other model structures, it is evident that trRosetta (TM-score: 0.64; TM region RMSD: 2 Å) can provide the best model than Robetta (TM-score: 0.61; TM region RMSD: 3.3 Å) and I-TASSER (TM-score: 0.45; TM region RMSD: 6.5 Å). 100 ns molecular dynamics simulations are performed on the model structures by incorporating membrane environment. Moreover, secondary structure elements and principal component analysis (PCA) have also been performed on MD simulation data. Finally, trRosetta model is utilized for interpretation and visualization of interacting residues during protein-protein interactions. The common interacting residues including Phe103, Arg107, Met109, Trp110, Arg131, and Glu135 in the C-terminal domain of M protein are identified in membrane-spike and membrane-nucleocapsid protein complexes. The active site residues are also predicted for potential drug and peptide binding. Overall, this study might be helpful to design drugs and peptides against the modeled membrane protein of SARS-CoV-2 to accelerate further investigation. Communicated by Ramaswamy H. Sarma.

Repurposing fusion inhibitor peptide against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out of 17 peptides, Fp13 and Fp14 showed better binding affinity toward HR1 compared to a control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore the time-dependent interactions of the fusion peptide with HR1, molecular dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural and energy parameters of Fp13-HR1 and Fp14-HR1 complexes demonstrated lower fluctuations compared to the control EK1-HR1 complex. Furthermore, principal component analysis and free energy landscape study revealed that these two peptides (Fp13 and Fp14) strongly bind to the HR1 with higher affinity than that of control EK1. Tyr917, Asn919, Gln926, lys933, and Gln949 residues in HR1 protein were found to be crucial residues for peptide interaction. Notably, Fp13, Fp14 showed reasonably better binding free energy and hydrogen bond contribution than that of EK1. Taken together, Fp13 and Fp14 peptides may be highly specific for HR1 which can potentially prevent the formation of the fusion core and could be further developed as therapeutics for treatment or prophylaxis of SARS-CoV-2 infection.

Disproportionate COVID-19 vaccine acceptance rate among healthcare professionals on the eve of nationwide vaccine distribution in Bangladesh.

BACKGROUND: Acceptance of the COVID-19 vaccine by the target groups would play a crucial role in stemming the pandemic. Healthcare professionals (HCPs) are the priority group for vaccination due to them having the highest risk of exposure to infection. This survey aimed to assess their acceptance of COVID-19 vaccines in Bangladesh. RESEARCH DESIGN AND METHODS: A cross-sectional survey using an online questionnaire was conducted between January 3 to 25, 2021, among HCPs (n = 834) in Bangladesh. RESULTS: Less than 50% of HCPs would receive the vaccine against COVID-19 if available and 54% were willing to take the vaccine at some stage in the future. Female participants (OR:1.64;95%CI:1.172-2.297), respondents between 18-34 years old (OR:2.42; 95% CI:1.314-4.463), HCPs in the public sector (OR:2.09; 95% CI:1.521-2.878), and those who did not receive a flu vaccine in the previous year (OR:3.1; 95% CI:1.552-6.001) were more likely to delay vaccination. CONCLUSIONS: The study revealed that, if available, less than half of the HCPs would accept a COVID-19 vaccine in Bangladesh. To ensure the broader success of the vaccination drive, tailored strategies and vaccine promotion campaigns targeting HCPs and the general population are needed.

Diagnostic Accuracy of Detecting Diabetic Retinopathy by Using Digital Fundus Photographs in the Peripheral Health Facilities of Bangladesh: Validation Study.

BACKGROUND: Diabetic retinopathy can cause blindness even in the absence of symptoms. Although routine eye screening remains the mainstay of diabetic retinopathy treatment and it can prevent 95% of blindness, this screening is not available in many low- and middle-income countries even though these countries contribute to 75% of the global diabetic retinopathy burden. OBJECTIVE: The aim of this study was to assess the diagnostic accuracy of diabetic retinopathy screening done by non-ophthalmologists using 2 different digital fundus cameras and to assess the risk factors for the occurrence of diabetic retinopathy. METHODS: This validation study was conducted in 6 peripheral health facilities in Bangladesh from July 2017 to June 2018. A double-blinded diagnostic approach was used to test the accuracy of the diabetic retinopathy screening done by non-ophthalmologists against the gold standard diagnosis by ophthalmology-trained eye consultants. Retinal images were taken by using either a desk-based camera or a hand-held camera following pupil dilatation. Test accuracy was assessed using measures of sensitivity, specificity, and positive and negative predictive values. Overall agreement with the gold standard test was reported using the Cohen kappa statistic (κ) and area under the receiver operating curve (AUROC). Risk factors for diabetic retinopathy occurrence were assessed using binary logistic regression. RESULTS: In 1455 patients with diabetes, the overall sensitivity to detect any form of diabetic retinopathy by non-ophthalmologists was 86.6% (483/558, 95% CI 83.5%-89.3%) and the specificity was 78.6% (705/897, 95% CI 75.8%-81.2%). The accuracy of the correct classification was excellent with a desk-based camera (AUROC 0.901, 95% CI 0.88-0.92) and fair with a hand-held camera (AUROC 0.710, 95% CI 0.67-0.74). Out of the 3 non-ophthalmologist categories, registered nurses and paramedics had strong agreement with kappa values of 0.70 and 0.85 in the diabetic retinopathy assessment, respectively, whereas the nonclinical trained staff had weak agreement (κ=0.35). The odds of having retinopathy increased with the duration of diabetes measured in 5-year intervals (P<.001); the odds of having retinopathy in patients with diabetes for 5-10 years (odds ratio [OR] 1.81, 95% CI 1.37-2.41) and more than 10 years (OR 3.88, 95% CI 2.91-5.15) were greater than that in patients with diabetes for less than 5 years. Obesity was found to have a negative association (P=.04) with diabetic retinopathy. CONCLUSIONS: Digital fundus photography is an effective screening tool with acceptable diagnostic accuracy. Our findings suggest that diabetic retinopathy screening can be accurately performed by health care personnel other than eye consultants. People with more than 5 years of diabetes should receive priority in any community-level retinopathy screening program. In a country like Bangladesh where no diabetic retinopathy screening services exist, the use of hand-held cameras can be considered as a cost-effective option for potential system-wide implementation.

Chemotherapeutic resistance of head and neck squamous cell carcinoma is mediated by EpCAM induction driven by IL-6/p62 associated Nrf2-antioxidant pathway activation.

Overexpression of epithelial cell adhesion molecule (EpCAM) has been associated with chemotherapeutic resistance, leads to aggressive tumor behavior, and results in an adverse clinical outcome. The molecular mechanism by which EpCAM enrichment is linked to therapeutic resistance via Nrf2, a key regulator of antioxidant genes is unknown. We have investigated the link between EpCAM and the Nrf2 pathway in light of therapeutic resistance using head and neck squamous cell carcinoma (HNSCC) patient tumor samples and cell lines. We report that EpCAM was highly expressed in Nrf2-positive and HPV-negative HNSCC cells. In addition, cisplatin-resistant tumor cells consisted of a higher proportion of EpCAMhigh cells compared to the cisplatin sensitive counterpart. EpCAMhigh populations exhibited resistance to cisplatin, a higher efficiency in colony formation, sphere growth and invasion capacity, and demonstrated reduced reactive oxygen species (ROS) activity. Furthermore, Nrf2 expression was significantly higher in EpCAMhigh populations. Mechanistically, expression of Nrf2 and its target genes were most prominently observed in EpCAMhigh populations. Silencing of EpCAM expression resulted in the attenuation of expressions of Nrf2 and SOD1 concomitant with a reduction of Sox2 expression. On the other hand, silencing of Nrf2 expression rendered EpCAMhigh populations sensitive to cisplatin treatment accompanied by the inhibition of colony formation, sphere formation, and invasion efficiency and increased ROS activity. The molecular mechanistic link between EpCAM expression and activation of Nrf2 was found to be a concerted interaction of interleukin-6 (IL-6) and p62. Silencing of p62 expression in EpCAMhigh populations resulted in the attenuation of Nrf2 pathway activation suggesting that Nrf2 pathway activation promoted resistance to cisplatin in EpCAMhigh populations. We propose that therapeutic targeting the Nrf2-EpCAM axis might be an excellent approach to modulate stress resistance and thereby survival of HNSCC patients enriched in EpCAMhigh populations.

Environmentally-friendly thermal and acoustic insulation materials from recycled textiles.

Continuing increase in energy consumption and environmental pollution are some of the main challenges of the 21st century. One of the approaches to overcome these challenges is to increase the use of recycled materials and environmentally-friendly approaches to manufacturing. Thermal and acoustic insulation in buildings and transport vehicles from recycled textiles can play an important role in energy savings and reduction of environmental pollution. Textiles contribute a significant amount to the waste stream since most of these valuable fiber products are discarded after use. These discarded but valuable textiles can be recycled to produce several products including thermal and acoustic insulation materials. In this paper, a comprehensive review of the current state of textile waste generation and its environmental effects, and present progress of using industrial and post-consumer recycled textiles in insulation materials is provided. Mechanism of acoustic and thermal insulation materials of textile fibers are also reviewed. Existing research of some textile waste used as building insulation materials, method of conversion of textile waste into building insulation materials, comparative analysis of different insulation materials and life cycle assessment of textile fibers are assessed.