The SARS-CoV-2 differential genomic adaptation in response to varying UVindex reveals potential genomic resources for better COVID-19 diagnosis and prevention.

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from five different UVindex regions (25 countries) was subjected to in-depth downstream genome-wide analysis. The recurrent variants that best respond to UV-solar radiations were extracted and extensively annotated to determine their possible effects and impacts on gene functions. This study revealed 515 recurrent single nucleotide variants (rcntSNVs) as SARS-CoV-2 genomic responses to UV-solar radiation, of which 380 were found to be distinct. For all discovered rcntSNVs, 596 functional effects (rcntEffs) were detected, containing 290 missense, 194 synonymous, 81 regulatory, and 31 in the intergenic region. The highest counts of missense rcntSNVs in spike (27) and nucleocapsid (26) genes explain the SARS-CoV-2 genomic adjustment to escape immunity and prevent UV-induced DNA damage, respectively. Among all, the most commonly observed rcntEffs were four missenses (RdRp-Pro327Leu, N-Arg203Lys, N-Gly204Arg, and Spike-Asp614Gly) and one synonymous (ORF1ab-Phe924Phe) functional effects. The highest number of rcntSNVs found distinct and were uniquely attributed to the specific UVindex regions, proposing solar-UV radiation as one of the driving forces for SARS-CoV-2 differential genomic adaptation. The phylogenetic relationship indicated the high UVindex region populating SARS-CoV-2 as the recent progenitor of all included samples. Altogether, these results provide baseline genomic data that may need to be included for preparing UVindex region-specific future diagnostic and vaccine formulations.

Computational vaccinology guided design of multi-epitopes subunit vaccine designing against Hantaan virus and its validation through immune simulations.

The Hantaan virus belongs to Bunyaviridae family, an emerging virus that is responsible for hemorrhagic fevers. The virus is distributed worldwide and as of now there is no successful antiviral drug or vaccine developed to protect against the viral infections. Immunization or vaccination is an alternative approach for the protection against viral infections. A cost effective and thermodynamically stable vaccine should be developed to prevent a future possible pandemic. In this study a vaccine candidate was designed against the Hantaan virus, multiple immunoinformatics and reverse vaccinology tools were utilized for the prediction of both B and T cell epitopes for Nuceloprotein, RNA dependent RNA polymerase L and Envelope protein of the Hantaan virus. The individual epitopes were modeled for docking with respective HLAs and a multi-epitopes subunit vaccine candidate was constructued by joining together carefully evaluated B and T cell epitopes with suitable linkers. The vaccine model was evaluated for several physiochameical parameters i.e. Molecular weight, instability index and aliphatic index among the others, followed by 3D modeling of the vaccine for docking with TLR-4. Based on previous studies, Human beta-defensin was liked at the N-terminus of the vaccine sequence as an adjuvant to enhance immunogenicity. The docked complexes of vaccine-TLR-4 were then evaluated for residual interactions. Moreover, to validate final vaccine construct, immune simulations was carried out by C-IMMSIM server. A natural immune reponse was predicted by the immune simulation analysis. In-silico cloning was carried out using E. coli as host resulting in 0.93 CAI value, which suggests that the vaccine construct will attain maximal expression in E. coli host. The vaccine designed in this study needs experimental verification to confirm the immunogenicity and efficacy of the vaccine and ultimately used against Hantaan virus associated infections.

Retraction: Team-based Learning and the Analytical Skills of Medical Students as a Consequence of Increased Problem Difficulty.

[This retracts the article DOI: 10.7759/cureus.4639.].

Team-based Learning and the Analytical Skills of Medical Students as a Consequence of Increased Problem Difficulty.

Problem-based learning is a learner-centered teaching method, which uses real-world scenarios to promote student learning of concepts and principles. The aim of our study is to analyze the consequence of increased problem difficulty on team-based learning and the analytical skills of medical students. In our prospective descriptive study, two problem-based learning scenarios prepared on the topic of hypercortisolism were given to 197 students in two successive sessions. At the end of two sessions, the perceptions of students about team-based learning were documented using a five-point Likert scale on a standardized questionnaire for both scenarios (simple and complex) simultaneously. A written test consisting of multiple-choice questions (MCQs) and short essay questions (SEQs) was given at the end of a complex scenario to test the problem-solving skills and retention of knowledge. No statistically significant difference (p> 0.05) was noted in team-based learning between the simple and complex problem-based learning scenario. MCQs and SEQs of C-2 (interpretation) level were attempted well than C-1 (recall) level and C3 (problem-solving) level. In conclusion, the understanding of the problem by the medical students was improved; however, there was no significant improvement in the problem-solving skills and knowledge retention of the students.

Pancytopenia in a Patient with Stevens-Johnson Syndrome: A Case Report with Literature Review.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions triggered due to a medication that involves the necrosis and desquamation of the skin and mucous membranes. Only one out of 1,000,000 people are affected by the condition. The exact pathophysiology of the disease is still unknown. However, many complications of the disease can occur; pancytopenia and pleural effusion are an even rarer find. Here we present a case of a 17-year-old male who presented with fever and rash for 15 days associated with bleeding per rectum, hemoptysis, and conjunctival hemorrhages. Laboratory investigations showed severe pancytopenia, deranged liver function tests (LFTs), and hypocellular bone marrow. The patient started showing improvement after 10 days post-admission with supportive care and multiple transfusions.

Cholangiocarcinoma in a Resected Biliary Cyst: Importance of Follow-up.

Biliary cysts are rare cystic dilatations of the biliary tree. Biliary cysts are positively associated with several significant complications, amongst them, cholangiocarcinoma befalls the most dreadful one. The elevated incidence is 20-30% in the unresected cyst and 0.7% in resected cysts. Magnetic resonance imaging (MRI) scan, magnetic resonance cholangiopancreatography (MRCP) or a contrast-enhanced computed tomography (CECT) is applied for the initial diagnostic study but the ultimate diagnosis ordinarily requires the tissue biopsy. Currently, the sole curative option involves the complete surgical resection of the lesion, with standard chemotherapy and active radiation applied as an alternative for the unresectable tumors. Despite the curative surgery the percentage of eternal recurrence of the tumor indefinitely persists, and effective post-surgical surveillance is reasonably demanded. We report a case of 29-year-old female with local recurrence of cholangiocarcinoma in a previously resected biliary cyst type I. The curative resection of the choledochal cyst only minimizes the considerable risk of the possible development of future cholangiocarcinoma but it does not completely prevent it. The appropriate follow-up for potential patients who have been typically treated for a biliary cyst is unclear. The lethal course of cholangiocarcinoma is believed due to its slow asymptomatic growing phase. Therefore, to adequately screen for malignancy, periodic imaging along with annual liver tests represents a reasonable approach to prevent the possible development of this appalling complication.