Identification of 22 novel mutations in patients with Glanzmann's thrombasthenia

Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect that characterized by reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists. GT is characterized by normal platelet count, prolonged bleeding time, and abnormal clot retraction. The defect is caused by mutations in the genes encoding GPIIb or GPIIIa that result in qualitative or quantitative abnormalities of the platelet membrane GPIIb/IIIa. GT occurs in high frequency in certain ethnic populations with an increased incidence of consanguinity, such as Indians, Iranians, Iraqi Jews, Palastinian and Jordanian Arabs and French gypsies. Forty-five unrelated patients of GT were enrolled in the study to identify the causative molecular defects and also to correlate the genotype with the phenotype. Molecular modeling was performed for the novel missense mutations. The current study identifies 22 novel mutations in these patients. Missense mutations were identified as the defects responsible for most of the GT patients (59%). Even though missense was common, the study concludes that the genetic defect is heterogeneous in nature and difficult to design a DNA marker for carrier detection in GT

Tropical Cyclone Intensity and Track Prediction in the Bay of Bengal Using LSTM-CSO Method

Tropical cyclones (TC) are extreme weather conditions caused by severe circular storms that originate in warm oceans. They are strong destructive forces that cause disastrous effects on human life and property and lead to economic damage. Therefore, it is necessary to forecast the TC intensity to avoid the issues. This study proposes a TC intensity forecast using Long-Short Term Memory (LSTM) with Cat Swarm Optimization (CSO). The LSTM method was optimized using the Cat Swarm Optimization technique to improve accuracy and reduce prediction errors. In this study, the prediction was carried out using the latitude, longitude, pressure, and wind speed of tropical cyclones from 2003 to 2019 in the Bay of Bengal. The performance of the proposed system was evaluated using the performance metrics, such as accuracy, Root Mean Square Error (RMSE), Average Absolute Position Error, Mean Absolute Error (MAE), and Area Under Receiver Operating Characteristic Curve (AUROC). The performance of the proposed system is compared with the results of other traditional methods, and the results show that the LSTM-CSO method outperforms other methods in TC intensity and track prediction

Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion

Hepatitis C virus (HCV) represents a challenging global health threat to similar to 200 million infected individuals. Clinical data suggest that only similar to 10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.Funding Agencies|High Impact Research (HIR), University of Malaya [625/1/HIR/139]; University Malaya Fellowship Scheme [FG019-17AFR]; Swedish Research Council [AI52731]; Swedish Physicians Against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine (SvenskaLakaresallskapet)</p

Synergistic Effect of Surfactant on Disperser Energy and Liquefaction Potential of Macroalgae (<i>Ulva intestinalis</i>) for Biofuel Production

The objective of this study was to evaluate the effect of surfactant on disperser homogenization pretreatment for macroalgae (Ulva intestinalis) to enhance biogas production. The macroalgae are subjected to surfactant coupled disperser pretreatment, which enhanced the liquefaction and improved the biomethane production. The outcome of this study revealed that 10,000 rpm at 20 min with a specific energy input of 1748.352 kJ/ kg total solids (TS) are the optimum conditions for surfactant disperser pretreatment (SDP), which resulted in the liquefaction rate of 20.08% with soluble organics release of 1215 mg/L and showed a better result than disperser pretreatment (DP) with a liquefaction rate of 14%. Biomethane production through the SDP method was found to be 0.2 g chemical oxygen demand (COD)/g COD, which was higher than DP (0.11 g COD/g COD). SDP was identified to be a synergetic pretreatment method with an energy ratio and net profit of about 0.91 and 104.04 United States dollars (USD)/ton, respectively

Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and Omicron BA.1.1.529 but not with Omicron BA.1.1 and BA.2 variants

The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (&amp;lt;5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics.Funding Agencies|Xiamen University Malaysia Research Funding (XMUMRF) [XMUMRF/2018-C2/ILAB/0001, XMUMRF/2020-C5/ITCM/0003, XMUMRF/2018-C1/IENG/0005]; Swedish Research Council; Swedish, Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Swedish Society of Medicine [AI52731]; Department of Science and Technology-Science and Engineering Research Board, Government of India [CRG/2019/006096]; CALF; Linkoeping University Hospital Research Fund</p

Table_1_Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and Omicron BA.1.1.529 but not with Omicron BA.1.1 and BA.2 variants.pdf

The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (<5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics.</p

Table_2_Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and Omicron BA.1.1.529 but not with Omicron BA.1.1 and BA.2 variants.pdf

The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (<5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics.</p