Radiosensitizing Effect of PARP Inhibition on Chondrosarcoma and Chondrocyte Cells Is Dependent on Radiation LET.

Chondrosarcoma is a rare malignant tumor that forms in bone and cartilage. The primary treatment involves surgical removal of the tumor with a margin of healthy tissue. Especially if complete surgical removal is not possible, radiation therapy and chemotherapy are used in conjunction with surgery, but with a generally low efficiency.

Carboplatin in metastatic castration-resistant prostate cancer patients with molecular alterations of the DNA damage repair pathway: the PRO-CARBO phase II trial.

Introduction: DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity.

Predicting the impact of rare variants on RNA splicing in CAGI6.

Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant's impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here, we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact.

Case report: Persistent shedding of a live vaccine-derived rubella virus in a young man with severe combined immunodeficiency and cutaneous granuloma.

A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR.

Value of the loss of heterozygosity to BRCA1 variant classification.

At least 10% of the BRCA1/2 tests identify variants of uncertain significance (VUS) while the distinction between pathogenic variants (PV) and benign variants (BV) remains particularly challenging. As a typical tumor suppressor gene, the inactivation of the second wild-type (WT) BRCA1 allele is expected to trigger cancer initiation. Loss of heterozygosity (LOH) of the WT allele is the most frequent mechanism for the BRCA1 biallelic inactivation.

COVID-19 Mortality Among American Indian and Alaska Native Persons - 14 States, January-June 2020.

American Indian/Alaska Native (AI/AN) persons experienced disproportionate mortality during the 2009 influenza A(H1N1) pandemic (1,2). Concerns of a similar trend during the coronavirus disease 2019 (COVID-19) pandemic led to the formation of a workgroup* to assess the prevalence of COVID-19 deaths in the AI/AN population. As of December 2, 2020, CDC has reported 2,689 COVID-19-associated deaths among non-Hispanic AI/AN persons in the United States.

Buprenorphine is a weak dopamine releaser relative to heroin, but its pretreatment attenuates heroin-evoked dopamine release in rats.

Aims: The United States of America is currently in an opioid epidemic. Heroin remains the most lethal opioid option with its death rate increasing by over 500% in the last decade. The rewarding and reinforcing effects of heroin are thought to be mediated by its ability to increase dopamine concentration in the nucleus accumbens shell.

SpliceLauncher: a tool for detection, annotation and relative quantification of alternative junctions from RNAseq data.

Summary: Alternative splicing is an important biological process widely analyzed in molecular diagnostic settings. Indeed, a variant can be pathogenic by splicing alteration and a suspected pathogenic variant (e.g.

An investigation of Salmonella Fluntern illnesses linked to leopard geckos-United States, 2018.

Reptile contact can result in zoonotic non-typhoidal salmonellosis. In April 2018, Oregon Public Health Division contacted CDC about a cluster of four Salmonella serovar Fluntern (SF) illnesses in four states (OR, CA, IA, NY); patients reported contact with geckos, a popular reptile pet. PulseNet, the national molecular subtyping network of food-borne disease surveillance, subsequently identified additional SF clinical isolates.

First estimate of the scale of canonical 5' splice site GT>GC variants capable of generating wild-type transcripts.

It has long been known that canonical 5' splice site (5'SS) GT>GC variants may be compatible with normal splicing. However, to date, the actual scale of canonical 5'SSs capable of generating wild-type transcripts in the case of GT>GC substitutions remains unknown. Herein, combining data derived from a meta-analysis of 45 human disease-causing 5'SS GT>GC variants and a cell culture-based full-length gene splicing assay of 103 5'SS GT>GC substitutions, we estimate that ~15-18% of canonical GT 5'SSs retain their capacity to generate between 1% and 84% normal transcripts when GT is substituted by GC.

Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report.

Background: monoallelic germ-line variants confer a breast cancer risk comparable to the average pathogenic variant. Recommendations for risk reduction strategies in carriers are similar. Elaborating robust criteria to identify variants in without incurring overprediction-is thus of paramount clinical relevance.

Evaluation of Mass Vaccination Clinics in Response to a Serogroup B Meningococcal Disease Outbreak at a Large, Public University-Oregon, 2015.

Purpose: Between January and May 2015, seven people at a large, public university developed invasive serogroup B meningococcal disease. One case was fatal. Attack rates were highest among freshmen and members of sororities, and fraternities (Greek organizations).

Extrapulmonary Nontuberculous Mycobacterial Disease Surveillance - Oregon, 2014-2016.

Nontuberculous mycobacteria (NTM), ubiquitous in soil and water, usually infect immunocompromised persons. However, even healthy persons are susceptible to infection through percutaneous inoculation. Although 77% of NTM diseases manifest as primarily pulmonary illnesses (1), NTM also infect skin, bones, joints, the lymphatic system, and soft tissue.

Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort.

Variant interpretation is the key issue in molecular diagnosis. Spliceogenic variants exemplify this issue as each nucleotide variant can be deleterious via disruption or creation of splice site consensus sequences. Consequently, reliable in silico prediction of variant spliceogenicity would be a major improvement.