23,263 results match your criteria screens


Evaluation of a polysaccharide-based chiral reversed-phase liquid chromatography screen strategy in pharmaceutical analysis.

J Chromatogr A 2021 Mar 22;1645:462085. Epub 2021 Mar 22.

Bristol Myers Squibb Company, Chemical Process Development, 1 Squibb Drive, New Brunswick, NJ 08903, USA. Electronic address:

Chirality control plays a critical role in developing stereoisomeric drugs. Due to the complexity and lack of predictability in chiral separations, column screening remains the gold standard to initiate chiral method development for active pharmaceutical ingredients (APIs) and synthetic intermediates. Chiral reversed-phase (RP) liquid chromatography (LC) has gained favor over other modes due to its versatility and compatibility in analyzing a wide range of chiral compounds in various matrices. Read More

View Article and Full-Text PDF

Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress.

Cancer Cell 2021 Apr;39(4):566-579.e7

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institute of Health, Rockville, MD 20850, USA; Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Small cell neuroendocrine cancers (SCNCs) are recalcitrant cancers arising from diverse primary sites that lack effective treatments. Using chemical genetic screens, we identified inhibition of ataxia telangiectasia and rad3 related (ATR), the primary activator of the replication stress response, and topoisomerase I (TOP1), nuclear enzyme that suppresses genomic instability, as synergistically cytotoxic in small cell lung cancer (SCLC). In a proof-of-concept study, we combined M6620 (berzosertib), first-in-class ATR inhibitor, and TOP1 inhibitor topotecan in patients with relapsed SCNCs. Read More

View Article and Full-Text PDF

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder.

J Clin Invest 2021 Apr 13. Epub 2021 Apr 13.

Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, United States of America.

Opioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify novel potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. Read More

View Article and Full-Text PDF

Guide RNA Design for Genome-Wide CRISPR Screens in Yarrowia lipolytica.

Methods Mol Biol 2021 ;2307:123-137

Chemical and Environmental Engineering, University of California Riverside, Riverside, CA, USA.

Genome-wide functional genomic screens are essential to determining the genetic underpinning of a biological process. Novel and powerful tools for perturbing gene function, with the help of genetic and epigenetic information, have made it possible to systematically investigate the contribution of every gene to evolved and engineered phenotypes. Functional genomics and screening for enhanced phenotypes become ever more important when dealing with nonconventional hosts. Read More

View Article and Full-Text PDF
January 2021

Predictors of Parental Barriers to Reduce Excessive Child Screen Time Among Parents of Under-Five Children in Selangor, Malaysia: Cross-sectional Study.

J Med Internet Res 2021 Apr 13;23(4):e25219. Epub 2021 Apr 13.

Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.

Background: Globally, there is an increasing prevalence of excessive screen time exposure among young children, including in Malaysia. Parents are advised to limit this exposure, but there are barriers for many of them to follow this recommendation. To date, there is a lack of research on the factors that cause these parental barriers. Read More

View Article and Full-Text PDF

Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition.

Nat Genet 2021 Apr 12. Epub 2021 Apr 12.

Human Oncology and Pathogenesis Program, Memorial Sloan KetterAbsolute numbers of live mature hematopoietic cellsing Cancer Center, New York, NY, USA.

Most eukaryotes harbor two distinct pre-mRNA splicing machineries: the major spliceosome, which removes >99% of introns, and the minor spliceosome, which removes rare, evolutionarily conserved introns. Although hypothesized to serve important regulatory functions, physiologic roles of the minor spliceosome are not well understood. For example, the minor spliceosome component ZRSR2 is subject to recurrent, leukemia-associated mutations, yet functional connections among minor introns, hematopoiesis and cancers are unclear. Read More

View Article and Full-Text PDF

Genome-wide screens uncover KDM2B as a modifier of protein binding to heparan sulfate.

Nat Chem Biol 2021 Apr 12. Epub 2021 Apr 12.

Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.

Heparan sulfate (HS) proteoglycans bind extracellular proteins that participate in cell signaling, attachment and endocytosis. These interactions depend on the arrangement of sulfated sugars in the HS chains generated by well-characterized biosynthetic enzymes; however, the regulation of these enzymes is largely unknown. We conducted genome-wide CRISPR-Cas9 screens with a small-molecule ligand that binds to HS. Read More

View Article and Full-Text PDF

CRISPR screens identify a novel combination treatment targeting BCL-X and WNT signaling for KRAS/BRAF-mutated colorectal cancers.

Oncogene 2021 Apr 12. Epub 2021 Apr 12.

Medical Research Center, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul, Korea.

Metastatic or recurrent colorectal cancer (CRC) patients require systemic chemotherapy, but the therapeutic options of targeted agents remain limited. CRC patients with KRAS or BRAF gene mutations exhibit a worse prognosis and are resistant to anti-EGFR treatment. Previous studies have shown that the expression of anti-apoptotic protein BCL-X is increased in CRC patients with KRAS/BRAF mutations, suggesting BCL-X as a therapeutic target for this subgroup. Read More

View Article and Full-Text PDF

Stability and individual variability of social attachment in imprinting.

Sci Rep 2021 Apr 12;11(1):7914. Epub 2021 Apr 12.

Center for Mind and Brain Sciences, University of Trento, Trento, Italy.

Filial imprinting has become a model for understanding memory, learning and social behaviour in neonate animals. This mechanism allows the youngs of precocial bird species to learn the characteristics of conspicuous visual stimuli and display affiliative response to them. Although longer exposures to an object produce stronger preferences for it afterwards, this relation is not linear. Read More

View Article and Full-Text PDF

The Analytical Performance of Six Urine Drug Screens on Cobas 6000 and ARCHITECT i2000 Compared to LC-MS/MS Gold Standard.

Clin Biochem 2021 Apr 9. Epub 2021 Apr 9.

Department of Pathology, Dalhousie University, Halifax, NS, Canada; Department of Pathology and Laboratory Medicine, Nova Scotia Health Authority (NSHA), Halifax, NS, Canada.

Background: Immunoassays provide a rapid tool for the screening of drugs-of-abuse (DOA). However, results are presumptive and confirmatory testing is warranted. To reduce associated cost and delay, laboratories should employ assays with high positive and negative predictive values (PPVs and NPVs). Read More

View Article and Full-Text PDF

Structure-based phylogeny identifies Avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice.

J Clin Invest 2021 Apr 12. Epub 2021 Apr 12.

Department of Ophthalmology, Stanford University, Palo Alto, United States of America.

Drugs targeting host proteins can act prophylactically to reduce viral burden early in disease and limit morbidity, even with antivirals and vaccination. Transmembrane serine protease 2 (TMPRSS2) is a human protease required for SARS-CoV-2 viral entry and may represent such a target. We hypothesized that drugs selected from proteins related by their tertiary structure, rather than their primary structure, were likely to interact with TMPRSS2. Read More

View Article and Full-Text PDF

Functional Movement Screen Detected Asymmetry & Normative Values Among College-Aged Students.

Int J Sports Phys Ther 2021 Apr 1;16(2):450-458. Epub 2021 Apr 1.

Texas A&M Central Texas.

Background: The Functional Movement Screen (FMS™) is a popular test used by sports medicine professionals to identify dysfunctional movement patterns by analyzing mobility and stability during prescribed movements. Although the FMS™ has been a popular topic of research in recent years, normative data and asymmetries in college-aged students have not been established through research.

Purpose: The objective was to determine normative FMS™ scores, report frequency counts for FMS™ asymmetries, and determine if the number of sports seasons and number of different sports an individual participated in during high school varied between university students that showed FMS™ identified asymmetries. Read More

View Article and Full-Text PDF

Varenicline for the Treatment of Cocaine Dependence.

J Addict Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (KGL, JP, MM, MT, PF, KMK); Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (KS).

Objectives: Varenicline is a partial agonist at the α2β4 and α6β2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6β2 receptors are implicated in the neural reward circuitry activated by cocaine use. A preliminary clinical trial suggested that varenicline treatment reduced cocaine use. Read More

View Article and Full-Text PDF

A simple technique to mitigate microplastic pollution and its mobility (via ballast water) in the global ocean.

Environ Pollut 2021 Apr 1;283:117070. Epub 2021 Apr 1.

Department of Biotechnology, Parvatibai Chowgule College of Arts and Science, Margao, Goa, 403601, India.

Ballast water transport is considered as one of the major vectors for dispersal of microplastics around the global oceans. In this commentary, a simple, inexpensive solution has been proposed to reduce microplastic pollution and its mobility via ballast water. A screening chamber (with stainless steel three layered mesh) is proposed to be attached to the existing Ballast Water Treatment Systems (BWTSs) in cargo ships to filter back-flushed sea water from BWTSs. Read More

View Article and Full-Text PDF

Examining brief and ultra-brief anxiety and depression screening methods in a real-world epilepsy clinic sample.

Epilepsy Behav 2021 Apr 8;118:107943. Epub 2021 Apr 8.

Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA. Electronic address:

Objective: Recent epilepsy quality measure recommendations for depression and anxiety screening endorse ultra-brief screeners, the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2). Thus, it is important to assess how symptom detection may be affected using ultra-brief screeners compared with slightly longer, well-validated instruments: Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) and Generalized Anxiety Disorder-7 (GAD-7). The objective was to compare symptom detection by brief versus ultra-brief depression and anxiety screeners in a large real-world epilepsy clinic sample. Read More

View Article and Full-Text PDF

Pyrrole-2 carboxamides - A novel class of insect ryanodine receptor activators.

Pestic Biochem Physiol 2021 May 21;174:104798. Epub 2021 Feb 21.

FMC, Agricultural Solutions Discovery Biology, Stine Research Center, 1090 Elkton Road, Newark, DE 19711, USA.

The ryanodine receptor (RyR) is an intracellular calcium channel critical to the regulation of insect muscle contraction and the target site of diamide insecticides such as chlorantraniliprole, cyantraniliprole and flubendiamide. To-date, diamides are the only known class of synthetic molecules with high potency against insect RyRs. Target-based screening of an informer library led to discovery of a novel class of RyR activators, pyrrole-2-carboxamides. Read More

View Article and Full-Text PDF