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Adult Acute Myeloid Leukemia with the KMT2A-Mixed Lineage Leukemia T10 Fusion: An Analysis of 10 Cases Showed Common Features and Frequent Mutations in the RAS Signaling Pathway.

Acta Haematol 2021 Sep 22:1-7. Epub 2021 Sep 22.

Department of Hematology, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People's Hospital, Changzhou, China.

Mixed lineage leukemia (MLL) T10 is a relatively rare partner for the KMT2A lysine (K)-specific methyltransferase 2A gene. The common features and coexisting mutations of acute myeloid leukemia (AML) patients with KMT2A-MLLT10 remain unknown. In this study, 10 adult AML patients with KMT2A-MLLT10 fusions were picked up from 496 AML patients by using RT-polymerase chain reaction (PCR) and/or fluorescence in situ hybridization, and then screened for mutations in the 49 genes panel with next-generation sequencing and PCR, followed by direct Sanger sequencing. Read More

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September 2021

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Blood Adv 2021 Sep 22. Epub 2021 Sep 22.

University of Texas Southwestern Medical Center, Dallas, Texas, United States.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes for acute myeloid leukemia (AML) patients. We evaluated 8709 AML patients from the CIBMTR database and, after selection and manual curation of cytogenetics data, 3779 patients in CR1 were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis compared to intermediate-risk patients detected an increased risk of relapse for KMT2A-rearranged and adverse-risk patients (HR 1. Read More

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September 2021

Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.

Sci Rep 2021 Sep 21;11(1):18764. Epub 2021 Sep 21.

Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Cytochrome P450 (CYP) signalling pathway has been shown to play a vital role in the vasoreactivity of wild type mouse ophthalmic artery. In this study, we determined the expression, vascular responses and potential mechanisms of the CYP-derived arachidonic acid metabolites. The expression of murine CYP (Cyp2c44) and soluble epoxide hydrolase (sEH) in the wild type ophthalmic artery was determined with immunofluorescence, which showed predominant expression of Cyp2c44 in the vascular smooth muscle cells (VSMC), while sEH was found mainly in the endothelium of the wild type ophthalmic artery. Read More

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September 2021

Biallelic variants in YRDC cause a developmental disorder with progeroid features.

Hum Genet 2021 Sep 20. Epub 2021 Sep 20.

Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37073, Göttingen, Germany.

The highly conserved YrdC domain-containing protein (YRDC) interacts with the well-described KEOPS complex, regulating specific tRNA modifications to ensure accurate protein synthesis. Previous studies have linked the KEOPS complex to a role in promoting telomere maintenance and controlling genome integrity. Here, we report on a newborn with a severe neonatal progeroid phenotype including generalized loss of subcutaneous fat, microcephaly, growth retardation, wrinkled skin, renal failure, and premature death at the age of 12 days. Read More

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September 2021

Effect of a multidisciplinary Severe Immunotherapy Complications Service on outcomes for patients receiving immune checkpoint inhibitor therapy for cancer.

J Immunother Cancer 2021 Sep;9(9)

Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

Background: In 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study's objectives were to evaluate the intervention's (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs.

Methods: A hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016-October 3, 2017) and after (October 3, 2017-October 24, 2018) SIC Service initiation. Read More

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September 2021

Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury.

Crit Care Med 2021 Sep 16. Epub 2021 Sep 16.

Pathophysiology of Injury-Induced Immunosuppression (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon - bioMérieux), Joint Research Unit HCL-bioMérieux, Immunology Laboratory & Anesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. BIOASTER, Lyon, France. Sanofi Pasteur, Marcy l'Etoile, France. GSK, GSK Medicines Research Centre, Stevenage, United Kingdom. Laboratoire de Biochimie (LBC), ESPCI Paris, PSL Université, CNRS UMR8231, Paris, France.

Objectives: The host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies.

Design: Prospective observational cohort study. Read More

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September 2021

The diversity and community structure of symbiotic cyanobacteria in hornworts inferred from long-read amplicon sequencing.

Am J Bot 2021 Sep 17. Epub 2021 Sep 17.

Boyce Thompson Institute, Ithaca, NY, USA.

Premise: Nitrogen-fixing endosymbioses with cyanobacteria have evolved independently in five very different plant lineages. Expanding knowledge of these symbioses promises to improve the understanding of symbiosis evolution and broaden the toolkit for agricultural engineering to reduce artificial fertilizer use. Here we focused on hornworts, a bryophyte lineage in which all members host cyanobacteria, and investigated factors shaping the diversity of their cyanobiont communities. Read More

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September 2021

[Establishment of chimeric antigen receptor NK92MI cells recognizing HBsAg].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Sep;37(9):788-793

Department of Infection Diseases, First Affiliated Hospital, Bengbu Medical College, Core Partner of National Clinical Research Center for Infection Diseases, Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu 233030, China. *Corresponding author, E-mail:

Objective To construct a lentiviral expression vector of chimeric antigen receptor (CAR) recognizing hepatitis B surface antigen (HBsAg) and make it expressed in NK92MI cells. Methods The CAR was designed and synthesized with the sequence of single chain variable fragment (scFv). Next it was cloned into a lentivirus expression vector, followed by packaging, concentration and titer determination. Read More

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September 2021

Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19.

PLoS Pathog 2021 09 16;17(9):e1009842. Epub 2021 Sep 16.

Infectious Diseases Unit, I. Department of Medicine, University Medical Center, Hamburg-Eppendorf, Germany.

The aim of this study was to define the breadth and specificity of dominant SARS-CoV-2-specific T cell epitopes using a comprehensive set of 135 overlapping 15-mer peptides covering the SARS-CoV-2 envelope (E), membrane (M) and nucleoprotein (N) in a cohort of 34 individuals with acute (n = 10) and resolved (n = 24) COVID-19. Following short-term virus-specific in vitro cultivation, the single peptide-specific CD4+ T cell response of each patient was screened using enzyme linked immuno spot assay (ELISpot) and confirmed by single-peptide intracellular cytokine staining (ICS) for interferon-γ (IFN-γ) production. 97% (n = 33) of patients elicited one or more N, M or E-specific CD4+ T cell responses and each patient targeted on average 21. Read More

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September 2021

RNA Sequencing for Personalized Treatment of Metastatic Leiomyosarcoma: Case Report.

Front Oncol 2021 30;11:666001. Epub 2021 Aug 30.

The Laboratory of Clinical and Genomic Bioinformatics, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Uterine leiomyosarcoma (UL) is a rare malignant tumor that develops from the uterine smooth muscle tissue. Due to the low frequency and lack of sufficient data from clinical trials there is currently no effective treatment that is routinely accepted for UL. Here we report a case of a 65-years-old female patient with metastatic UL, who progressed on ifosfamide and doxorubicin therapy and developed severe hypertensive crisis after administration of second line pazopanib, which lead to treatment termination. Read More

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Patterns of nodal spread in stage III NSCLC: importance of EBUS-TBNA and F-FDG PET/CT for radiotherapy target volume definition.

Radiat Oncol 2021 Sep 15;16(1):176. Epub 2021 Sep 15.

Department of Radiation Therapy, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany.

Purpose: The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC.

Methods: This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011-06/2018). Inclusion criteria were curative treatment intent, F-FDG PET/CT and EBUS-TBNA prior to start of treatment. Read More

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September 2021

Clinical activity of ripretinib in patients with advanced gastrointestinal stromal tumor harboring heterogenous KIT/PDGFRA mutations in the phase 3 INVICTUS study.

Clin Cancer Res 2021 Sep 9. Epub 2021 Sep 9.

Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven.

Purpose: Most patients with gastrointestinal stromal tumor (GIST) have activating mutations in and are initially responsive to tyrosine kinase inhibitors (TKIs). The acquisition of secondary mutations leads to refractory/relapsed disease. This study reports the results of an analysis from the phase 3 INVICTUS study (NCT03353753) characterizing the genomic heterogeneity of tumors from patients with advanced GIST and evaluating ripretinib efficacy across mutation subgroups. Read More

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September 2021

Elevated Flt3L Predicts Long-Term Survival in Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.

Cancers (Basel) 2021 Sep 4;13(17). Epub 2021 Sep 4.

Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany.

Background: The clinical management of high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facilitating patient stratification and guiding treatment decisions. FMS-like tyrosine kinase 3 ligand (Flt3L) is emerging as a prognostic or predictive surrogate marker of host tumoral immune response and might enable the stratification of patients with otherwise comparable tumor features.

Methods: We evaluated Flt3L gene expression in tumor tissue as well as circulating Flt3L levels as potential biomarkers in a cohort of 54 patients with GEP-NEN. Read More

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September 2021

Exome-based preconception carrier testing for consanguineous couples in China.

Prenat Diagn 2021 Sep 6. Epub 2021 Sep 6.

Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.

Objective: To evaluate the utility of clinical exome sequencing (ES)-based carrier screening in Chinese consanguineous couples.

Methods: Consanguineous couples were screened for autosomal recessive (AR) disorders using the clinical ES of 5000 genes associated with human diseases.

Results: We recruited 14 couples who elected to have sequencing. Read More

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September 2021

Clinical Profile of Neonates Admitted with Sepsis to Neonatal Intensive Care Unit of Jimma Medical Center, A Tertiary Hospital in Ethiopia.

Ethiop J Health Sci 2021 May;31(3):485-494

Department of Internal Medicine, Jimma University.

Background: Globally, over 3 million newborn die each year, one million of these attributed to infections. The objective of this study was to determine the etiologies and clinical characteristics of sepsis in neonates admitted to intensive care unit of a tertiary hospital in Ethiopia.

Methods: A longitudinal hospital based cohort study was conducted from April 1 to October 31, 2018 at the neonatal intensive care unit of Jimma Medical Center, southwest Ethiopia. Read More

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Using the 'stranger test' to assess social competency in adult female Long Evans rats reared with a Fischer 344 partner.

Behav Processes 2021 Aug 31;192:104492. Epub 2021 Aug 31.

University of Lethbridge, 4401 Univerisity Drive W, Lethbridge, Alberta, T1K 3M4, Canada.

Rats reared with limited access to a play partner during the juvenile period develop into adults with impairments in various cognitive, emotional, and social skills. The present study assesses the consequences of play deprivation on adult social skills in female Long Evans (LE) rats that were reared with a low-playing Fischer 344 rat over the juvenile period. As adults, their social skills were assessed using the stranger paradigm, by pairing the deprived LE rats with a novel LE partner in a neutral arena. Read More

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Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.

Nat Genet 2021 Sep 2;53(9):1300-1310. Epub 2021 Sep 2.

Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Read More

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September 2021

Gradual development of ammonia-induced syntrophic acetate-oxidizing activities under mesophilic and thermophilic conditions quantitatively tracked using multiple isotopic approaches.

Water Res 2021 Aug 21;204:117586. Epub 2021 Aug 21.

Université Paris-Saclay, INRAE, PRocédés biOtechnologiques au Service de l'Environnement, Antony 92761, France. Electronic address:

Insights into microbiota adaptation to increased ammonia stress, and identification of indicator microorganisms can help to optimize the operation of anaerobic digesters. To identify microbial indicators and investigate their metabolic contribution to acetoclastic methanogenesis (AM), syntrophic acetate oxidation (SAO) or hydrogenotrophic methanogenesis (HM), 40 anaerobic batch reactors fed with acetate of 110 mmol/L were set up at NH-N concentrations of 0.14 g/L, 5. Read More

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Silicon-photomultiplier-based PET/CT reduces the minimum detectable activity of iodine-124.

Sci Rep 2021 Sep 1;11(1):17477. Epub 2021 Sep 1.

Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.

The radioiodine isotope pair I/I is used in a theranostic approach for patient-specific treatment of differentiated thyroid cancer. Lesion detectability is notably higher for I PET (positron emission tomography) than for I gamma camera imaging but can be limited for small and low uptake lesions. The recently introduced silicon-photomultiplier-based (SiPM-based) PET/CT (computed tomography) systems outperform previous-generation systems in detector sensitivity, coincidence time resolution, and spatial resolution. Read More

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September 2021

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From the SPRINT Randomized Clinical Trial.

JAMA Cardiol 2021 Sep 1. Epub 2021 Sep 1.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas.

Importance: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

Objective: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering. Read More

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September 2021

MERS-CoV in sheep, goats, and cattle, United Arab Emirates, 2019: Virological and serological investigations reveal an accidental spillover from dromedaries.

Transbound Emerg Dis 2021 Aug 30. Epub 2021 Aug 30.

Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine, Vienna, Austria.

The recent COVID-19 pandemic has demonstrated again the global threat posed by emerging zoonotic coronaviruses. During the past two decades alone, humans have experienced the emergence of several coronaviruses, such as SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019. To date, MERS-CoV has been detected in 27 countries, with a case fatality ratio of approximately 34. Read More

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Pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools - a cluster randomised trial.

EClinicalMedicine 2021 Sep 25;39:101082. Epub 2021 Aug 25.

Department I of Internal Medicine, Division of Infectious Diseases, University Hospital Cologne, University of Cologne, Cologne, Germany.

Background: The extent to which children and adolescents contribute to SARS-CoV-2 transmission remains not fully understood. Novel high-capacity testing methods may provide real-time epidemiological data in educational settings helping to establish a rational approach to prevent and minimize SARS-CoV-2 transmission. We investigated whether pooling of samples for SARS-CoV-2 detection by RT-qPCR is a sensitive and feasible high-capacity diagnostic strategy for surveillance of SARS-CoV-2 infections in schools. Read More

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September 2021

Multifocal high-grade glioma radiotherapy safety and efficacy.

Radiat Oncol 2021 Aug 28;16(1):165. Epub 2021 Aug 28.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Background: Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making. Read More

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Anterior nasal versus nasal mid-turbinate sampling for a SARS-CoV-2 antigen-detecting rapid test: does localisation or professional collection matter?

Infect Dis (Lond) 2021 Aug 27:1-6. Epub 2021 Aug 27.

Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Tropical Medicine and International Health, Berlin, Germany.

Introduction: Most SARS-CoV-2 antigen-detecting rapid diagnostic tests require nasopharyngeal sampling, which is frequently perceived as uncomfortable and requires healthcare professionals, thus limiting scale-up. Nasal sampling could enable self-sampling and increase acceptability. The term nasal sampling is often not used uniformly and sampling protocols differ. Read More

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Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells.

Int J Mol Sci 2021 Aug 10;22(16). Epub 2021 Aug 10.

Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy.

Despite the recurring outbreak of resistance mechanisms and adverse reactions, doxorubicin (Doxo) still remains the standard-of-care for several cancers, including osteosarcoma (OS). As an appealing source of phytochemical compounds, naturally occurring molecules have extensively been reported to overcome Doxo limitations in preclinical models. Unlike other dietary polyphenols, only few studies recognize chlorogenic acid (CGA) as a potential partner in combination therapy, while, conversely, its anticancer evidence is steadily growing, ultimately in OS. Read More

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Analysis of Human Gut Microbiota Composition Associated to the Presence of Commensal and Pathogen Microorganisms in Côte d'Ivoire.

Microorganisms 2021 Aug 18;9(8). Epub 2021 Aug 18.

Centre Don Orione Pour Handicapés Physiques, Bonoua BP 21, Côte d'Ivoire.

Background: The human gut microbiota is a microbial ecosystem contributing to the maintenance of host health with functions related to immune and metabolic aspects. Relations between microbiota and enteric pathogens in sub-Saharan Africa are scarcely investigated. The present study explored gut microbiota composition associated to the presence of common enteric pathogens and commensal microorganisms, e. Read More

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Dual Contraceptive Use and Factor Associated with People Living with HIV/AIDS: A Systematic Review and Meta-Analysis.

Infect Dis Obstet Gynecol 2021 16;2021:5440722. Epub 2021 Aug 16.

Department of Nursing, College of Medicine and Health Science, Wolkite University, Wolkite, Ethiopia.

Introduction: A dual contraceptive method is the usage of any modern contraceptive method with male or female condoms which could lower sexually transmitted diseases and unwanted pregnancy. Ethiopian standard utilization of dual contraceptive is low. The hassle is more severe for HIV/AIDS-infected people. Read More

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Mortality risk among 5-year survivors of childhood cancer in Germany-Results from the CVSS study (Cardiac and Vascular late Sequelae in long-term Survivors of childhood cancer study).

Int J Cancer 2021 Aug 25. Epub 2021 Aug 25.

Division of Childhood Cancer Epidemiology, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Read More

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Epstein - Barr virus epidemiology in HIV infected transsexuals.

J Pak Med Assoc 2021 Aug;71(8):1984-1988

Department of Sport Sciences, Gomal University, Dera Ismail Khan, KP, Pakistan.

Objective: To molecularly characterise the relationship between Epstein-Barr virus (EBV) genotypes and Pashtun ethnicity.

Methods: The cross-sectional study was conducted from November 2018 to December 2019 after approval from the Gomal University, Dera Ismail Khan, Pakistan, and comprised blood samples from transgender sex workers who were seropositive for human immunodeficiency virus-1 and seronegative for human immunodeficiency virus residing in two cities of Khyber Pakhtunkhwa province and Islamabad, the federal capital. Formalin-fixed paraffin-embedded (FFPE). Read More

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Comparison of four commercial, automated antigen tests to detect SARS-CoV-2 variants of concern.

Med Microbiol Immunol 2021 Aug 20. Epub 2021 Aug 20.

Max Von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, LMU München, Munich, Germany.

A versatile portfolio of diagnostic tests is essential for the containment of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Besides nucleic acid-based test systems and point-of-care (POCT) antigen (Ag) tests, quantitative, laboratory-based nucleocapsid Ag tests for SARS-CoV-2 have recently been launched. Here, we evaluated four commercial Ag tests on automated platforms and one POCT to detect SARS-CoV-2. Read More

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