Analysis of mutations in CDC27, CTBP2, HYDIN and KMT5A genes in carotid paragangliomas

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from paraganglionic tissue of the carotid body localizing at the bifurcation of carotid artery. These tumors are slowly growing, but occasionally they become aggressive and metastatic. Surgical treatment remains high-risk and extremely challenging; radiation and chemotherapy are poorly effective. The study of molecular pathogenesis of CPGLs will allow developing novel therapeutic approaches and revealing biomarkers. Previously, we performed the exome sequencing of 52 CPGLs and estimated mutational load (ML). Paired histologically normal tissues or blood were unavailable, so potentially germline mutations were excluded from the analysis with strong filtering conditions using 1000 Genomes Project and ExAC databases. In this work, ten genes (ZNF717, CDC27, FRG2C, FAM104B, CTBP2, HLA-DRB1, HYDIN, KMT5A, MUC3A, and PRSS3) characterized by the highest level of mutational load were analyzed. Using several prediction algorithms (SIFT, PolyPhen-2, MutationTaster, and LRT), potentially pathogenic mutations were identified in four genes (CDC27, CTBP2, HYDIN, and KMT5A). Many of these mutations occurred in the majority of cases, and their mutation type was checked using exome sequencing data of blood prepared with the same exome enrichment kit that was used for preparation of exome libraries from CPGLs. The majority of the mutations were germline that can apparently be associated with annotation errors in 1000 Genomes Pro ject and ExAC. However, part of the mutations identified in CDC27, CTBP2, HYDIN, and KMT5A remain potentially pathogenic, and there is a large body of data on the involvement of these genes in the formation and progression of other tumors. This allows considering CDC27, CTBP2, HYDIN, and KMT5A genes as potentially associated with CPGL pathogenesis and requires taking them into account in further investigations. Thus, there is a necessity to improve the methods for identification of cancer-asso ciated genes as well as pathogenic mutations

Clinical features of post-COVID-19 period. Results of the international register “Dynamic analysis of comorbidities in SARS-CoV-2 survivors (AKTIV SARS-CoV-2)”. Data from 6-month follow-up

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods.The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period

Oligothiophene-S,S-dioxides: A new class of thiophene-based materials

We report here that bissilylated oligothiophenes may be selectively oxidized at the thienyl sulfurs by m-chloroperbenzoic acid (m-CPBA) to afford stable S,S-dioxides having alternate aromatic and nonaromatic moieties. These compounds are characterized by enhanced electron delocalization, smaller optical gap, and greater electron affinity than the “fully aromatic” precursors

From easily oxidized to easily reduced thiophene-based materials

We report here a new strategy towards functionalization of oligothiophenes that consists of the chemical transformation of thienyl sulfurs into the corresponding S,S-dioxides. We show that this kind of functionalization, which implies the dearomatization of the thiophene rings, leads to very stable oligomers with increased electron delocalization and has also a dramatic effect on their electron affinity as deduced from their electrochemical reduction potential. It is worth mentioning that the synthesis and the characterization of unsubstituted thiophene S,S-dioxide has been reported only very recently and that only S,S-dioxides derived from polysubstituted thiophene are stable at room temperature. So far, no electrochemical data on this kind of compound have yet been published

Oligothiophene S,S-dioxides: Towards n-type semiconductor oligothiophenes?

A new class of thiophene based materials - oligothiophene S,S-dioxides, characterized by a much greater electron affinity than the precursor oligothiophenes - is described. © 1998 Elsevier Science B.V

International register “Dynamics analysis of comorbidities in SARS-CoV-2 survivors” (AKTIV SARS-CoV-2): analysis of 1,000 patients

COVID-19 is a severe infection with high mortality. The concept of the disease has been shaped to a greater extent on the basis of large registers from the USA, Spain, Italy, and China. However, there is no information on the disease characteristics in Caucasian patients.Therefore, we created an international register with the estimated capacity of 5,000 patients — Dynamics Analysis of Comorbidities in SARS-CoV-2 Survivors (AKTIV SARS-CoV-2), which brought together professionals from the Russian Federation, Republic of Armenia, Republic of Kazakhstan, and Kyrgyz Republic. The article presents the first analysis of the register involving 1,003 patients. It was shown that the most significant difference of the Caucasian population was the higher effect of multimorbidity on the mortality risk vs other registers. More pronounced effect on mortality of such diseases as diabetes, obesity, hypertension, chronic kidney disease, and age over 60 years was also revealed

International register “Dynamics analysis of comorbidities in SARS-CoV-2 survivors” (AKTIV) and the register “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2)

The organizer of the registers “Dynamics analysis of comorbidities in SARSCoV-2 survivors” (AKTIV) and “Analysis of hospitalizations of comorbid patients infected during the second wave of SARS-CoV-2 outbreak” (AKTIV 2) is the Eurasian Association of Therapists (EAT). Currently, there are no clinical registries in the Eurasian region designed to collect and analyze information on long-term outcomes of COVID-19 survivors with comorbid conditions. The aim of the register is to assess the impact of a novel coronavirus infection on long-term course of chronic non-communicable diseases 3, 6, 12 months after recovery, as well as to obtain information on the effect of comorbidity on the severity of COVID-19. Analysis of hospitalized patients of a possible second wave is planned for register “AKTIV 2”. To achieve this goal, the register will include men and women over 18 years of age diagnosed with COVID-19 who are treated in a hospital or in outpatient basis. The register includes 25 centers in 5 federal districts of the Russian Federation, centers in the Republic of Armenia, the Republic of Kazakhstan, the Republic of Kyrgyzstan, the Republic of Belarus, the Republic of Moldova, and the Republic of Uzbekistan. The estimated capacity of the register is 5400 patients

International register “Dynamics analysis of comorbidities in SARS-CoV-2 survivors” (AKTIV SARS-CoV-2): analysis of predictors of short-term adverse outcomes in COVID-19

The international AKTIV register presents a detailed description of out- and inpatients with COVID-19 in the Eurasian region. It was found that hospitalized patients had more comorbidities. In addition, these patients were older and there were more men than among outpatients. Among the traditional risk factors, obesity and hypertension had a significant negative effect on prognosis, which was more significant for patients 60 years of age and older. Among comorbidities, CVDs had the maximum negative effect on prognosis, and this effect was more significant for patients 60 years of age and older. Among other comorbidities, type 2 and 1 diabetes, chronic kidney disease, chronic obstructive pulmonary disease, cancer and anemia had a negative impact on the prognosis. This effect was also more significant (with the exception of type 1 diabetes) for patients 60 years and older. The death risk in patients with COVID-19 depended on the severity and type of multimorbidity. Clusters of diseases typical for deceased patients were identified and their impact on prognosis was determined. The most unfavorable was a cluster of 4 diseases, including hypertension, coronary artery disease, heart failure, and diabetes mellitus. The data obtained should be taken into account when planning measures for prevention (vaccination priority groups), treatment and rehabilitation of COVID-19 survivors