Innumerable pathogens including RNA viruses have catastrophic pandemic propensity, in turn, SARS-CoV-2 infection is highly contagious. Emergence of SARS-CoV-2 variants with high mutation rate additionally codifies infectious ability of virus and arisen clinical imputations to human health. Although, our knowledge of mechanism of virus infection and its impact on host system has been substantially demystified, uncertainties about the emergence of virus are still not fully understood. To date, there are no potentially curative drugs are identified against the viral infection. Even though, drugs are repurposed in the initial period of infection, many are significantly negative in clinical trials. Moreover, the infection is dependent on organ status, co-morbid conditions, variant of virus and geographic region. This review article aims to comprehensively describe the SARS-CoV-2 infection and the impacts in the host cellular system. This review also briefly provides an overview of genome, proteome and metabolome associated risk to infection and the advancement of therapeutics in SARS-CoV-2 infection management.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) coexisting with chorea is very rare.
METHODS: We present the case of a 48-year-old man with ALS and chorea; the diagnostic certainty was high based on clinical examination results. Combining the data from literature, we analyzed the characteristics of patients with ALS and chorea. We found that ALS coexisting with chorea is very rare, but is often hereditary with a genetic mutation. Most patients with ALS and chorea are caused by abnormal amplification of a CAG sequence in the HTT gene, and these patients have a mild course of disease. The FUS, VCP, and SETX genes also have low mutation frequencies in patients with ALS and chorea.
CONCLUSIONS: The abnormal amplification of a CAG sequence in the HTT gene in ALS with chorea has an obvious familial genetic tendency, and most patients have a mild disease course.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.

UNASSIGNED: The molecular basis of prostate cancer is highly heterogeneous. Our study aimed to perform the mutation analysis of KRAS, BRAF, PIK3CA, and immunohistochemical (IHC) evaluation of EGFR, HER2, p16, and PTEN to demonstrate new areas for targeted therapies.
UNASSIGNED: A total of 24 prostatectomy samples diagnosed with adenocarcinoma were analyzed by microarray hybridization. Also, these samples were IHC stained for EGFR, HER2, P16, and PTEN. The cases were divided into two groups based on low and high Gleason scores. All findings were compared with the clinicopathological parameters of the patients.
UNASSIGNED: While KRAS mutation was in 3/24 (12.5%) of our cases, BRAF and PIK3CA mutations were not detected. There was no significant difference between the groups in terms of KRAS mutation frequency. HER2 was immunohistochemically negative in all samples. There was no correlation between EGFR, P16 immunopositivity, and clinicopathological features.
UNASSIGNED: KRAS mutation frequency is similar to those in Asian populations. BRAF and PIK3CA mutation frequencies have been reported in the literature in the range of 0-15% and 0-10.4%, respectively, consistent with our study findings. HER2 immunoexpression is a controversial issue in the literature. EGFR and p16 expressions may not correlate with the stage.

The burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins.
Searches were conducted in Embase and Medline and supplemented with recent conference proceedings. Included studies were not limited by intervention, geography, or publication year.
Seventy-eight unique studies were included; 53 reporting mutation frequency, 13 prognostic impact, 36 clinical outcomes, and one humanistic burden. No economic burden data were identified. The frequency of Exon 20ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of all EGFR mutations. Data on the prognostic impact of Exon 20ins were heterogeneous but highlighted poorer outcomes in patients with Exon 20ins mutation compared with patients with other EGFR mutations and EGFR wildtype across a wide range of therapies and treatment lines. Comparative evidence on the clinical efficacy and safety of currently available therapies were limited, as were sample sizes of studies reporting on real-world effectiveness. Nine single-arm trials and 27 observational studies reported clinical outcomes for patients with Exon 20ins. Trends towards better survival and response were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were less favorable. Limited safety data were reported. One conference abstract described the symptom burden for Exon 20ins patients with fatigue and pain being most common.
Findings of the systematic review show a high unmet need for safe and efficacious treatments for patients with Exon 20ins as well and need for further evidence generation to better understand the patient-level and economic impact for these patients.

Mutations in the GJB2 gene are a main cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be ∼16% in Iran, but would vary among different ethnic groups. Here, we have taken together and reviewed results from our two previous publications and data from searching other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in central Iran. In all, 332 unrelated families were included and analyzed for the prevalence and type of the GJB2 gene mutations. In total, the frequency of GJB2 mutations was found to be 16% in the central provinces, which is significantly higher than those identified in southern populations of Iran. Also, c.35delG was the most frequent mutation in the related population. The present study suggests that mutations in the GJB2 gene, especially c.35delG, are important causes of HL in central Iran and can be used as a basis of genetic counseling and clinical guidelines in this region.

Several ongoing international prostate cancer (PC) clinical trials are exploring therapies that target the DNA damage response (DDR) pathway. This systematic review summarizes the prevalence of DDR mutation carriers in the unselected (general) PC and familial PC populations. A total of 11 electronic databases, 10 conference proceedings, and grey literature sources were searched from their inception to December 2017. Studies reporting the prevalence of somatic and/or germline DDR mutations were summarized. Metastatic PC (mPC), castration‑resistant PC (CRPC) and metastatic CRPC (mCRPC) subgroups were included. A total of 11,648 records were retrieved, and 80 studies (103 records) across all PC populations were included; 59 records were of unselected PC and 13 records of familial PC. Most data were available for DDR panels (n=12 studies), ataxia telangiectasia mutated (ATM; n=13), breast cancer susceptibility gene (BRCA)1 (n=14) and BRCA2 (n=20). ATM, BRCA2 and partner and localizer of BRCA2 (PALB2) had the highest mutation rates (≥4%). Median prevalence rates for DDR germline mutations were 18.6% in PC (range, 17.2‑19%; three studies, n=1,712), 11.6% in mPC (range, 11.4‑11.8%; two studies, n=1,261) and 8.3% in mCRPC (range, 7.5‑9.1%; two studies, n=738). Median prevalence rates for DDR somatic mutations were 10.7% in PC (range, 4.9‑22%; three studies, n=680), 13.2% in mPC (range, 10‑16.4%; two studies, n=105) and not reported (NR) in mCRPC. The prevalence of DDR germline and/or somatic mutations was 27% in PC (one study, n=221), 22.67% in mCRPC (one study, n=150) and NR in mPC. In familial PC, median mutation prevalence was 12.1% (range, 7.3‑16.9%) for germline DDR (two studies, n=315) and 3.7% (range, 1.3‑7.9%) for BRCA2 (six studies, n=945). In total, 88% of studies were at a high risk of bias. The prevalence of DDR gene mutations in PC varied widely within somatic subgroups depending on study size, genetic screening techniques, DDR mutation definition and PC diagnosis; somatic and/or germline DDR mutation prevalence was in the range of 23‑27% in PC. These findings support DDR mutation testing for all patients with PC (including those with mCRPC). With the advent of the latest clinical practice PC guidelines highlighting the importance of DDR mutation screening, and ongoing mCRPC clinical trials evaluating DDR mutation‑targeted drugs, future larger epidemiological studies are warranted to further quantify the international burden of DDR mutations in PC.

OBJECTIVE: To investigate the status of familial hypercholesterolemia (FH) research and the characteristics of patients with FH in China.
METHODS: Published papers in Chinese or English language from PubMed, SinoMed and CNKI databases from 1971 to March 2018 were searched using \'Familial hypercholesterolemia\', \'Chinese\' and \'Han\' as keywords. A systematic review of studies on familial hypercholesterolemia was then conducted.
RESULTS: A total of 391 articles were found, in which 22% were in English and 78% were in Chinese; approximately 43% are case reports and 34% are genetic reports according to the study type; 52% discussed the status of the disease and 11% investigated the subclinical status according to the study content. Furthermore, 96% of the articles were published by tertiary hospitals and 46% were conducted by cardiologists. The first expert consensus was issued in February 2018. Of the 163 case reports published before 2018, 48.7% used the Chinese FH clinical diagnostic criteria and 34.4% did not clearly indicate the diagnostic criteria. The incidence rates of low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) mutations were 82% and 9%, and proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations were rare in Chinese patients with FH. However, the data on lipid-lowering treatment rates, compliance rates and cardiovascular events in FH remain insufficient.
CONCLUSIONS: Large-scale epidemiological investigation of FH has not been demonstrated, the recognition of FH remains rudimentary, and the guidelines are incomplete in China. The diagnosis and management of Chinese FH needs to be improved.

BACKGROUND: Our goal was to investigate the prevalence of the epidermal growth factor receptor (EGFR) mutation in Middle East and African countries and to compare its prevalence with that shown in other populations.
METHODS: We used PubMed and the Cochrane Library databases to conduct a literature search using the terms \"[EGFR] AND [mutation] AND [Non Small Cell Lung Cancer] AND [Middle East OR Africa].\" We assessed studies published in English and French from 2004 until 2016.
RESULTS: Ten relevant studies were included in this systematic review. Overall, 1215 patients with non-small cell lung cancer (NSCLC) were included in this analysis. The overall ratio of male to female patients was 2.15. Of total patients included, 41.1% had never smoked and 85.8% had been diagnosed with adenocarcinoma. In 8 of the 10 studies, polymerase chain reaction (PCR) analyses were conducted to identify EGFR mutations. In total, 257 patients had an EGFR mutation, corresponding to a prevalence of 21.2%. The most frequent abnormality detected in all of the studies was in exon 19. In addition, all studies concluded the presence of a correlation between EGFR mutation status and female sex, non-smoking status, and adenocarcinoma subtype.
CONCLUSIONS: The EGFR mutation frequency in Middle East and African patients is higher than that shown in white populations but still lower than the frequency reported in Asian populations.

BACKGROUND: Atopic disorders have been reported in CHARGE syndrome, but the prevalence and underlying mechanisms are not known.
METHODS: We performed a retrospective study of atopic disorders in 23 individuals with CHARGE syndrome, and reviewed other published reports of atopic disorders in CHARGE syndrome. We assayed for enrichment of atopic disorders in CHARGE syndrome based on gender and presence of a CHD7 pathogenic variant.
RESULTS: In our cohort, 65% (15/23) of individuals with CHARGE syndrome were found to have a pathogenic CHD7 variant. Overall, 65% (15/23) of individuals with CHARGE had atopic disorders. Among the 23 individuals with CHARGE, 22% (5/23) had food allergy, 26% (6/23) exhibited drug allergy, 22% (5/23) had contact allergy, 9% (2/23) had allergic rhinitis, and 22% (5/23) had asthma. In our cohort, the proportion of males to females with CHARGE and atopic disorders was 11:4 (P < 0.01), and there was no significant difference between atopic disorders in individuals with CHD7 pathogenic variants and those without CHD7 pathogenic variants (P > 0.05).
CONCLUSIONS: In our cohort of 23 individuals with CHARGE syndrome, 15 (65%) exhibited atopic disorders, with a slight male predominance.