3,880 results match your criteria selective panel

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease.

Alzheimers Dement (Amst) 2021 2;13(1):e12184. Epub 2021 May 2.

Institute of Psychiatry, Psychology, and Neuroscience Department of Forensic and Neurodevelopmental Sciences King's College London London UK.

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.

Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. Read More

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ACR Appropriateness Criteria® Head Trauma: 2021 Update.

J Am Coll Radiol 2021 May;18(5S):S13-S36

Specialty Chair, Atlanta VA Health Care System and Emory University, Atlanta, Georgia.

Head trauma (ie, head injury) is a significant public health concern and is a leading cause of morbidity and mortality in children and young adults. Neuroimaging plays an important role in the management of head and brain injury, which can be separated into acute (0-7 days), subacute (<3 months), then chronic (>3 months) phases. Over 75% of acute head trauma is classified as mild, of which over 75% have a normal Glasgow Coma Scale score of 15, therefore clinical practice guidelines universally recommend selective CT scanning in this patient population, which is often based on clinical decision rules. Read More

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Founder effects facilitate the use of a genotyping-based approach to molecular diagnosis in Swedish patients with familial hypercholesterolaemia.

J Intern Med 2021 May 6. Epub 2021 May 6.

From the, Cardiometabolic Unit, Clinical Department of Endocrinology, Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden.

Aim: To investigate whether genotyping could be used as a cost-effective screening step, preceding next-generation sequencing (NGS), in molecular diagnosis of familial hypercholesterolaemia (FH) in Swedish patients.

Methods And Results: Three hundred patients of Swedish origin with clinical suspicion of heterozygous FH were analysed using a specific array genotyping panel embedding 112 FH-causing mutations in the LDLR, APOB and PCSK9 genes. The mutations had been selected from previous reports on FH patients in Scandinavia and Finland. Read More

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ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma.

Nature 2021 May 5. Epub 2021 May 5.

Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAF-mutant melanoma, they are ineffective in non-BRAF mutant cells. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAF- and NRAS-mutant melanomas. Read More

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Selective multiplexed enrichment for the detection and quantitation of low-fraction DNA variants via low-depth sequencing.

Nat Biomed Eng 2021 May 3. Epub 2021 May 3.

Department of Bioengineering, Rice University, Houston, TX, USA.

DNA sequence variants with allele fractions below 1% are difficult to detect and quantify by sequencing owing to intrinsic errors in sequencing-by-synthesis methods. Although molecular-identifier barcodes can detect mutations with a variant-allele frequency (VAF) as low as 0.1% using next-generation sequencing (NGS), sequencing depths of over 25,000× are required, thus hampering the detection of mutations at high sensitivity in patient samples and in most samples used in research. Read More

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Performance of 2-Hydroxy-1-Naphthaldehyde-2-Amino Thiazole as a Highly Selective Turn-on Fluorescent Chemosensor for Al(III) Ions Detection and Biological Applications.

J Fluoresc 2021 May 3. Epub 2021 May 3.

Electrochemical materials and devices laboratory, Department of Chemistry, Bharathiar University, Coimbatore, 641046, India.

The thiazole based Schiff base 2-hydroxy-1-naphthaldehyde-2-amino thiazole (receptor1) was synthesized through a single step process and characterized by spectroscopic and analytical techniques. The cation detecting ability of the receptor1 was explored by fluorescent spectroscopic methods. The receptor1 has recognized Al ions by a turn-on process over a panel of other potentially competing metal ions. Read More

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Preclinical Evaluation of Carfilzomib for Infant -Rearranged Acute Lymphoblastic Leukemia.

Front Oncol 2021 15;11:631594. Epub 2021 Apr 15.

Division of Children's Leukaemia and Cancer Research, Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.

Background: Infants with -rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. Read More

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The Expression of Anti-Müllerian Hormone Type II Receptor (AMHRII) in Non-Gynecological Solid Tumors Offers Potential for Broad Therapeutic Intervention in Cancer.

Biology (Basel) 2021 Apr 7;10(4). Epub 2021 Apr 7.

GamaMabs Pharma, Centre Pierre Potier, F-31100 Toulouse, France.

The anti-Müllerian hormone (AMH) belongs to the TGF-β family and plays a key role during fetal sexual development. Various reports have described the expression of AMH type II receptor (AMHRII) in human gynecological cancers including ovarian tumors. According to qRT-PCR results confirmed by specific In-Situ Hybridization (ISH) experiments, AMHRII mRNA is expressed in an extremely restricted number of normal tissues. Read More

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Identification of therapeutic targets of the hijacked super-enhancer complex in EVI1-rearranged leukemia.

Leukemia 2021 Apr 28. Epub 2021 Apr 28.

Molecular Leukemogenesis, German Cancer Research Center, Heidelberg, Germany.

Deregulation of the EVI1 proto-oncogene by the GATA2 distal hematopoietic enhancer (G2DHE) is a key event in high-risk acute myeloid leukemia carrying 3q21q26 aberrations (3q-AML). Upon chromosomal rearrangement, G2DHE acquires characteristics of a super-enhancer and causes overexpression of EVI1 at 3q26.2. Read More

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Comparison of ultrasound with biomarkers to identify large-for-gestational age in women screened for gestational diabetes mellitus.

J Matern Fetal Neonatal Med 2021 Apr 28:1-6. Epub 2021 Apr 28.

UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, Dublin, Ireland.

Objective: Large-for-gestational-age (LGA) is associated with both fetal and maternal complications. One of the few modifiable risk factors for LGA is Gestational Diabetes Mellitus (GDM); for this reason, fetal growth is usually monitored by ultrasound in the third trimester. This prospective study compared a panel of ten established biomarkers measured at the time of selective screening for GDM at 26-28 weeks gestation with the ultrasound prediction of LGA. Read More

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Development of NIR-II Photoacoustic Probes Tailored for Deep-Tissue Sensing of Nitric Oxide.

J Am Chem Soc 2021 May 27;143(18):7196-7202. Epub 2021 Apr 27.

Department of Chemistry and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Photoacoustic (PA) imaging has emerged as a reliable technique for diverse biomedical applications ranging from disease screening to analyte sensing. Most contemporary PA imaging agents employ NIR-I light (650-900 nm) to generate an ultrasound signal; however, there is significant interference from endogenous biomolecules such as hemoglobin that are PA active in this window. Transitioning to longer excitation wavelengths (i. Read More

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Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition.

SLAS Discov 2021 Apr 24:24725552211008853. Epub 2021 Apr 24.

National Cancer Institute (NCI) RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.

Oncogenic forms of KRAS proteins are known to be drivers of pancreatic, colorectal, and lung cancers. The goal of this study is to identify chemical leads that inhibit oncogenic KRAS signaling. We first developed an isogenic panel of mouse embryonic fibroblast (MEF) cell lines that carry wild-type RAS, oncogenic KRAS, and oncogenic BRAF. Read More

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Morpho-agronomic, biochemical and molecular analysis of genetic diversity in the Mesoamerican common bean panel.

PLoS One 2021 22;16(4):e0249858. Epub 2021 Apr 22.

Agronomy Department, Universidade Estadual de Londrina (UEL), Londrina, Paraná, Brazil.

The common bean (Phaseolus vulgaris L.) is of great importance to the food and nutritional security of many populations, and exploitation of the crop's genetic diversity is essential for the success of breeding programs. Thus, the aim of the present study was to evaluate the genetic diversity of 215 common bean accessions, which included cultivars, obsolete cultivars, improved lines, and landraces using morpho-agronomic and biochemical traits, and amplified fragment length polymorphism markers (AFLP). Read More

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Selective modulation of a pan-essential protein as a therapeutic strategy in cancer.

Cancer Discov 2021 Apr 21. Epub 2021 Apr 21.

Department of Pediatric Oncology, Dana-Farber Cancer Institute

Cancer dependency maps, which use CRISPR/Cas9 depletion screens to profile the landscape of genetic dependencies in hundreds of cancer cell lines, have identified context-specific dependencies that could be therapeutically exploited. An ideal therapy is both lethal and precise, but these depletion screens cannot readily distinguish between gene effects that are cytostatic or cytotoxic. Here, we employ a diverse panel of functional genomic screening assays to identify NXT1 as a selective and rapidly lethal in vivo-relevant genetic dependency in MYCN-amplified neuroblastoma. Read More

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Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

Langenbecks Arch Surg 2021 May 21;406(3):571-585. Epub 2021 Apr 21.

Ratajczak & Partner, Freiburg, Germany.

Background And Aims: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK).

Methods: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF).

Results: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. Read More

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The Bisindole Alkaloids Angustilongines M and A from Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization.

J Nat Prod 2021 Apr 19. Epub 2021 Apr 19.

Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.

A new linearly fused macroline-sarpagine bisindole, angustilongine M (), was isolated from the methanolic extract of . The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (). Compounds and showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. Read More

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Management of neurogenic bladder dysfunction in children update and recommendations on medical treatment.

Int Braz J Urol 2021 Feb 28;47. Epub 2021 Feb 28.

Service of Urology, Italian Hospital, Buenos Aires, Argentina.

Introduction: Defective closure of the neural tube affects different systems and generates sequelae, such as neurogenic bladder (NB). Myelomeningocele (MMC) represents the most frequent and most severe cause of NB in children. Damage of the renal parenchyma in children with NB acquired in postnatal stages is preventable given adequate evaluation, follow-up and proactive management. Read More

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February 2021

Small Molecule Targeting of Oxysterol-Binding Protein (OSBP)-Related Protein 4 and OSBP Inhibits Ovarian Cancer Cell Proliferation in Monolayer and Spheroid Cell Models.

ACS Pharmacol Transl Sci 2021 Apr 4;4(2):744-756. Epub 2021 Feb 4.

Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United States.

The development of precision drugs for the selective treatment of ovarian cancer will require targeting proliferative factors selectively expressed in ovarian tumors or targeting unique physiological microenvironments specific for ovarian tumors. Here, we report that oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is a potential druggable precision target in ovarian cancer cells. ORP4 has limited expression in normal tissues and was recently recognized to be a cancer-specific driver of cellular proliferation, including in patient-isolated leukemias. Read More

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Comparative Activity and Off-Target Effects in Cells of the CHK1 Inhibitors MK-8776, SRA737, and LY2606368.

ACS Pharmacol Transl Sci 2021 Apr 12;4(2):730-743. Epub 2021 Feb 12.

Department of Molecular and Systems Biology and Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, United States.

DNA damage activates the checkpoint protein CHK1 to arrest cell cycle progression, providing time for repair and recovery. Consequently, inhibitors of CHK1 (CHK1i) enhance damage-induced cell death. Additionally, CHK1i elicits single agent cytotoxicity in some cell lines. Read More

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Evidence of a hormonal reshuffle in the cecal metabolome fingerprint of a strain of rats resistant to decompression sickness.

Sci Rep 2021 Apr 15;11(1):8317. Epub 2021 Apr 15.

Univ Brest, ORPHY, IBSAM, 29200, Brest, France.

On one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the fecal metabolome from rat caecum. On the other side, there is high inter-individual variability in terms of occurrence of DCS. One could wonder whether the fecal metabolome could be linked to the DCS-susceptibility. Read More

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Rational engraftment of quaternary-interactive acidic loops for anti-HIV-1 antibody improvement.

J Virol 2021 Apr 7. Epub 2021 Apr 7.

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA

Broadly neutralizing antibodies (bNAbs) are the focus of increasing interest for human immunodeficiency virus type-1 (HIV-1) prevention and treatment. Although several bNAbs are already under clinical evaluation, the development of antibodies with even greater potency and breadth remains a priority. Recently, we reported a novel strategy for improving bNAbs against the CD4-binding site (CD4bs) of gp120 by engraftment of the elongated framework region 3 (FR3) from VRC03, which confers the ability to establish quaternary interactions with a second gp120 protomer. Read More

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Labelling Selective Sweeps Used in Durum Wheat Breeding from a Diverse and Structured Panel of Landraces and Cultivars.

Biology (Basel) 2021 Mar 24;10(4). Epub 2021 Mar 24.

Sustainable Field Crops Programme, Institute for Food and Agricultural Research and Technology (IRTA), 25198 Lleida, Spain.

A panel of 387 durum wheat genotypes including Mediterranean landraces and modern cultivars was characterized with 46,161 diversity arrays technology (DArTseq) markers. Analysis of population structure uncovered the existence of five subpopulations (SP) related to the pattern of migration of durum wheat from the domestication area to the west of the Mediterranean basin (SPs 1, 2, and 3) and further improved germplasm (SPs 4 and 5). The total genetic diversity () was 0. Read More

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Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor.

Sci Transl Med 2021 Mar;13(587)

INSERM U1186, Gustave-Roussy Cancer Center, Université Paris-Saclay, 94805 Villejuif, France.

The development and survival of cancer cells require adaptive mechanisms to stress. Such adaptations can confer intrinsic vulnerabilities, enabling the selective targeting of cancer cells. Through a pooled in vivo short hairpin RNA (shRNA) screen, we identified the adenosine triphosphatase associated with diverse cellular activities (AAA-ATPase) valosin-containing protein (VCP) as a top stress-related vulnerability in acute myeloid leukemia (AML). Read More

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Enzyme-Agnostic Lysosomal Screen Identifies New Legumain-Cleavable ADC Linkers.

Bioconjug Chem 2021 04 31;32(4):842-858. Epub 2021 Mar 31.

School of Pharmacy and Pharmaceutical Sciences, Binghamton University, P.O. Box 6000, Binghamton, New York 13902, United States.

Over the past two decades, antibody drug conjugates (ADCs) and small molecule drug conjugates (SMDCs) have widely employed valine-citruline and related cathepsin-cleavable linkers due to their stability in plasma and their rapid cleavage by lysosomal cathepsins. However, a number of recent studies have illustrated that these linkers are subject to cleavage by exogenous enzymes such as Ces1C and neutrophil elastase, thus resulting in off-target release of drug. As such, there is a need to diversify the portfolio of ADC linkers in order to overcome nonspecific drug release. Read More

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Development and Validation of High-Content Analysis for Screening HDAC6-Selective Inhibitors.

SLAS Discov 2021 Mar 30:24725552211002463. Epub 2021 Mar 30.

Discovery Project Unit, HitGen, Chengdu, Sichuan, China.

Throughout recent decades, histone deacetylase (HDAC) inhibitors have shown encouraging potential in cancer treatment, and several pan-HDAC inhibitors have been approved for treating malignant cancers. Numerous adverse effects of pan-HDAC inhibitors have been reported, however, during preclinical and clinical evaluations. To avoid undesirable responses, an increasing number of investigations are focusing on the development of isotype-selective HDAC inhibitors. Read More

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SAF-248, a novel PI3Kδ-selective inhibitor, potently suppresses the growth of diffuse large B-cell lymphoma.

Acta Pharmacol Sin 2021 Mar 29. Epub 2021 Mar 29.

Division of Anti-tumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

PI3Kδ is expressed predominately in leukocytes and overexpressed in B-cell-related malignances. PI3Kδ has been validated as a promising target for cancer therapy, and specific PI3Kδ inhibitors were approved for clinical practice. However, the substantial toxicity and relatively low efficacy as a monotherapy in diffuse large B-cell lymphoma (DLBCL) limit their clinical use. Read More

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Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis.

PLoS Med 2021 Mar 29;18(3):e1003506. Epub 2021 Mar 29.

Multiple Births Foundation, London, United Kingdom.

Background: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.

Methods And Findings: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. Read More

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Photoprotection according to skin phototype and dermatoses: practical recommendations from an expert panel.

J Eur Acad Dermatol Venereol 2021 Mar 25. Epub 2021 Mar 25.

IUF Leibniz Research Institute for Environmental Medicine, Dusseldorf, Germany.

Increasing evidence on the impact of the different wavelengths of sunlight on the skin demonstrates the need for tailored recommendations of sunscreen according to skin phototype and dermatoses, which is now possible due to advances in the filters and formulations of sunscreens. A selective literature search was performed by an international expert panel, focusing on the type of sunscreen to recommend for photoaging, skin cancers, photodermatoses, pigmentary disorders and skin inflammatory disorders. Protection against ultraviolet (UV)B is especially important for light skin as there is a high risk of sunburn, DNA damage and skin cancers. Read More

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Detection of differentially culturable tubercle bacteria in sputum using mycobacterial culture filtrates.

Sci Rep 2021 Mar 22;11(1):6493. Epub 2021 Mar 22.

Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and the National Health Laboratory Service, P. O. Box 1038, Johannesburg, 2000, South Africa.

Rapid detection of tuberculosis (TB) infection is paramount to curb further transmission. The gold standard for this remains mycobacterial culture, however emerging evidence confirms the presence of differentially culturable tubercle bacteria (DCTB) in clinical specimens. These bacteria do not grow under standard culture conditions and require the presence of culture filtrate (CF), from axenic cultures of Mycobacterium tuberculosis (Mtb), to emerge. Read More

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Detection of breeding signatures in wheat using a linkage disequilibrium-corrected mapping approach.

Sci Rep 2021 Mar 9;11(1):5527. Epub 2021 Mar 9.

Institute of Crop Science and Resource Conservation (INRES), Plant Breeding, University of Bonn, Bonn, Germany.

Marker assisted breeding, facilitated by reference genome assemblies, can help to produce cultivars adapted to changing environmental conditions. However, anomalous linkage disequilibrium (LD), where single markers show high LD with markers on other chromosomes but low LD with adjacent markers, is a serious impediment for genetic studies. We used a LD-correction approach to overcome these drawbacks, correcting the physical position of markers derived from 15 and 135 K arrays in a diversity panel of bread wheat representing 50 years of breeding history. Read More

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