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Endovascular Therapy for Acute Ischemic Stroke in Patients with Large-Vessel Occlusion due to Atherosclerotic Stenosis.

J Stroke Cerebrovasc Dis 2021 Jul 24;30(10):105960. Epub 2021 Jul 24.

Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan.

Objectives: Endovascular therapy (EVT) is safe and effective for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). However, the influence of the AIS subtype (large-artery atherosclerosis [LAA] or cardioembolism [CE]) on clinical outcome in patients treated with EVT remains unclear. This study aimed to evaluate the differences in clinical results between the two subtypes using data from a multicenter prospective registry (RESCUE-Japan Registry 2). Read More

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Discovery of novel pyrazolopyrimidine derivatives as potent mTOR/HDAC bi-functional inhibitors via pharmacophore-merging strategy.

Bioorg Med Chem Lett 2021 Jul 24:128286. Epub 2021 Jul 24.

College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

The mTOR and HDAC dual suppression is meaningful for counteracting drug resistance resulted from kinase mutation and bypass mechanisms. Herein, we communicate our recent discovery of a novel structural series of mTOR/HDAC bi-functional inhibitors featuring the pyrazolopyrimidine core via pharmacophore-merging strategy. More than half of them exerted potent dual-target inhibitory activities. Read More

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Impact of specific serotonin receptor modulation on behavioral flexibility.

Pharmacol Biochem Behav 2021 Jul 24:173243. Epub 2021 Jul 24.

California State University San Bernardino, Department of Psychology, 5500 University Parkway, San Bernardino, CA 92407, United States of America. Electronic address:

Serotonin (5-HT) is known to play a critical role in regulation of essential neural processes, whereas more recent research highlights serotonin's modulatory effects on cognition and executive functioning. Current examinations have identified specific serotonin receptors for their direct impact on behavioral flexibility. Providing definitive evidence for the impact of specific receptor targets on behavioral flexibility is difficult, due to range of behavioral tests used. Read More

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Surgical Treatment for Intrahepatic, Peri-Hilar, and Distal Cholangiocarcinoma: 20-Single Institutional Year Experience.

Am Surg 2021 Jul 27:31348211034751. Epub 2021 Jul 27.

Department of General Surgery, 156400Mayo Clinic, Jacksonville, FL, USA.

Background: Surgical resection is the curative treatment for all subtypes of cholangiocarcinoma (CCA), including intrahepatic, hilar/peri-hilar, and distal. This study evaluates patients with CCA who underwent surgery and determines factors that impact their survival.

Methods: A retrospective cohort study was performed for patients who underwent surgical resection for CCA at our institution from 1995 to 2016. Read More

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TH1902, a new docetaxel-peptide conjugate for the treatment of sortilin-positive triple-negative breast cancer.

Cancer Sci 2021 Jul 27. Epub 2021 Jul 27.

Laboratoire d'Oncologie Moléculaire, Université du Québec à Montréal, Montréal, Québec, Canada.

Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of cancers which lacks the expression and/or amplification of targetable biomarkers (i.e., ER, PR, and HER2), and is often associated with the worse disease-specific outcomes than other breast cancer subtypes. Read More

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Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers.

Aging (Albany NY) 2021 Jul 27;13(undefined). Epub 2021 Jul 27.

Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson's disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. Read More

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Insomnia symptom subtypes and manifestations of prodromal neurodegeneration: a population-based study in the CLSA.

J Clin Sleep Med 2021 Jul 27. Epub 2021 Jul 27.

Research center of the Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada.

Study Objectives: To identify the association between insomnia symptoms and signs of prodromal neurodegeneration, including an analysis of potential differences between sleep-onset and sleep-maintenance insomnia.

Methods: We included those aged 45-85 years, living in one of 10 Canadian provinces in between 2012-2015 (at the baseline), recruited via three population-based sampling methods. Insomnia symptoms were assessed using questions adapted/modified from the Pittsburgh Sleep Quality Index. Read More

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Human Papilloma Virus Distribution Across the African Diaspora.

JCO Glob Oncol 2021 Jul;7:1206-1208

Division of Gynecologic Oncology, Sylvester Comprehensive Cancer Center, MI.

Purpose: Understanding the distribution of human papilloma virus (HPV) subtypes in limited-resource settings is imperative for cancer prevention strategies in these regions. The objective of our study is to compare the prevalence of cervical HPV genotypes in women across the African diaspora.

Methods: This study was approved by the African Caribbean Consortium (AC3). Read More

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An Illumina MiSeq-Based Amplicon Sequencing Method for the Detection of Mixed Parasite Infections Using the Blastocystis SSU rRNA Gene as an Example.

Methods Mol Biol 2021 ;2369:67-82

United States Department of Agriculture, Agricultural Research Service, Environmental Microbial Food Safety Laboratory, Beltsville, MD, USA.

Parasite mixed infections remain a relatively unexplored field in part due to the difficulties of unraveling complex mixtures of parasite DNA using classical methods of sequencing. Next-generation amplicon sequencing (NGS) is a powerful tool for exploring mixed infections of multiple genetic variants of the same parasite in clinical, environmental (water or soil), or food samples. Here, we provide a method for NGS-based detection of mixed parasite infections which uses the Blastocystis SSU rRNA gene as an example and includes steps for parasite concentration, DNA extraction, sequencing library preparation, and bioinformatic analysis. Read More

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January 2021

Shared gray matter alterations in subtypes of addiction: a voxel-wise meta-analysis.

Psychopharmacology (Berl) 2021 Jul 27. Epub 2021 Jul 27.

Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Numerous studies based on voxel-based morphometry (VBM) have revealed gray matter (GM) alterations in multiple brain regions for addiction. However, findings are poorly replicated, and it remains elusive whether distinct diagnoses of addiction are underpinned by shared abnormalities. Our aim was to conduct a quantitative meta-analysis of structural neuroimaging studies investigating GM abnormalities in two main categories of addiction: substance use disorders (SUD) and behavioral addictions (BA). Read More

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Comparative venous thromboembolic safety of oral and transdermal postmenopausal hormone therapies among women Veterans.

Menopause 2021 Jul 26. Epub 2021 Jul 26.

Division of Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA Department of Epidemiology, University of Washington, Seattle, WA Department of Medicine, University of Washington, Seattle, WA Kaiser Permanente Washington Health Research Institute, Seattle, WA Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, CA Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

Objective: Hormone therapy (HT) is used by menopausal women to treat vasomotor symptoms. Venous thromboembolism (VTE) is an important risk of HT use, and more knowledge on the comparative safety of different estrogenic compounds is useful for women who use HT for these symptoms. The objective was to compare the risk of VTE among users of oral conjugated equine estrogen (CEE), oral estradiol (E2), and transdermal E2, in a cohort of women veterans. Read More

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Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.

Acta Oncol 2021 Jul 27:1-7. Epub 2021 Jul 27.

Section of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway.

Background: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy. Read More

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A Combination of Healthy Lifestyle Behaviors Reduces Risk of Incident Systemic Lupus Erythematosus.

Arthritis Rheumatol 2021 Jul 27. Epub 2021 Jul 27.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: While the association between individual factors related to lifestyle and the risk of SLE has been previously evaluated, it is unclear how the combination of these factors might affect the risk of incident SLE. We prospectively evaluated whether a combination of healthy lifestyle factors is associated with lower risk of incident SLE and its subtypes (dsDNA positive and negative).

Methods: We included 185,962 women with 203 incident SLE cases (96 anti-dsDNA positive,107 anti-dsDNA negative) during 4,649,477 person-years of follow-up from the Nurses' Health Study (NHS) and NHSII cohorts. Read More

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Quantitative mapping of dense microtubule arrays in mammalian neurons.

Elife 2021 Jul 27;10. Epub 2021 Jul 27.

Biology, Utrecht University, Utrecht, Netherlands.

The neuronal microtubule cytoskeleton underlies the polarization and proper functioning of neurons, amongst others by providing tracks for motor proteins that drive intracellular transport. Different subsets of neuronal microtubules, varying in composition, stability and motor preference, are known to exist, but the high density of microtubules has so far precluded mapping their relative abundance and three-dimensional organization. Here we use different super-resolution techniques (STED, Expansion Microscopy) to explore the nanoscale organization of the neuronal microtubule network in rat hippocampal neurons. Read More

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Prediction and characterization of diffuse large B-cell lymphoma cell-of-origin subtypes using targeted sequencing.

Future Oncol 2021 Jul 27. Epub 2021 Jul 27.

Genentech, Inc., South San Francisco, CA 94080, USA.

The aim of the present study was to determine cell of origin (COO) from a platform using a DNA-based method, COO DNA classifier (COODC). A targeted exome-sequencing platform that applies the mutational profile of a sample was used to classify COO subtype. Two major mutational signatures associated with COO were identified: Catalogue of Somatic Mutations in Cancer (COSMIC) signature 23 enriched in activated B-cell (ABC) and COSMIC signature 3, which suggested increased frequency in germinal center B-cell (GCB). Read More

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Evaluation of putative CSF biomarkers in paediatric spinal muscular atrophy (SMA) patients before and during treatment with nusinersen.

J Cell Mol Med 2021 Jul 27. Epub 2021 Jul 27.

Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Spinal muscular atrophy (SMA) is a genetic neurodegenerative disorder leading to immobilization and premature death. Currently, three alternative therapeutic options are available. Therefore, biomarkers that might reflect or predict the clinical course of the individual patient with treatment are of great potential use. Read More

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The mechanosensory neurons of touch and their mechanisms of activation.

Nat Rev Neurosci 2021 Jul 26. Epub 2021 Jul 26.

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.

Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. Read More

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Incidence, demographics, and survival of patients with primary pituitary tumors: a SEER database study in 2004-2016.

Sci Rep 2021 Jul 26;11(1):15155. Epub 2021 Jul 26.

Department of Neurosurgery, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, People's Republic of China.

Comprehensive investigations on the incidence and prognosis of pituitary tumors are still lacking. The present study aims to summarize the incidence, demographics, and survival outcome of pituitary adenoma on a population-based level. This study includes all pituitary adenomas reported in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 in the United States. Read More

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Quantitative MRI-based radiomics for noninvasively predicting molecular subtypes and survival in glioma patients.

NPJ Precis Oncol 2021 Jul 26;5(1):72. Epub 2021 Jul 26.

Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Gliomas can be classified into five molecular groups based on the status of IDH mutation, 1p/19q codeletion, and TERT promoter mutation, whereas they need to be obtained by biopsy or surgery. Thus, we aimed to use MRI-based radiomics to noninvasively predict the molecular groups and assess their prognostic value. We retrospectively identified 357 patients with gliomas and extracted radiomic features from their preoperative MRI images. Read More

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K1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits.

Sci Rep 2021 Jul 26;11(1):15180. Epub 2021 Jul 26.

Michael Smith Laboratories, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

K1.1 containing potassium channels play crucial roles towards dampening neuronal excitability. Mice lacking K1. Read More

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CDX-1/CDX-2 Expression Is a Favorable Prognostic Factor in Epstein-Barr Virus-Negative, Mismatch Repair-Proficient Advanced Gastric Cancers.

Gut Liver 2021 Jul 28. Epub 2021 Jul 28.

Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: Caudal type homeobox (CDX)-1 and -2 are reportedly involved in the development and progression of gastric cancer (GC). Although there are several reports on the prognostic significance of CDX-2 expression in GC, it remains controversial. In this study, we sought to validate the prognostic value of CDX-1 and -2 expression according to the histologic and molecular subtypes of GC. Read More

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Prevalence of gp160 polymorphisms known to be related to decreased susceptibility to temsavir in different subtypes of HIV-1 in the Los Alamos National Laboratory HIV Sequence Database.

J Antimicrob Chemother 2021 Jul 23. Epub 2021 Jul 23.

ViiV Healthcare, 36 East Industrial Road, Branford, CT 06405, USA.

Background: Fostemsavir, a prodrug of the gp120-directed attachment inhibitor temsavir, is indicated for use in heavily treatment-experienced individuals with MDR HIV-1. Reduced susceptibility to temsavir in the clinic maps to discrete changes at amino acid positions in gp160: S375, M426, M434 and M475.

Objectives: To query the Los Alamos National Laboratory (LANL) HIV Sequence Database for the prevalence of polymorphisms at gp160 positions of interest. Read More

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Endometrial cancer from early to advanced-stage disease: an update for radiologists.

Abdom Radiol (NY) 2021 Jul 23. Epub 2021 Jul 23.

Department of Radiology, Jackson Memorial Hospital, University of Miami, 1611 NW 12th Avenue, West Wing 279, Miami, FL, 33136, USA.

The purpose of this article is to review the current molecular classification of endometrial cancer, the imaging findings in early and advanced disease, and the current management strategies, focusing on the new systemic therapies for advanced EC. In recent years, the management of endometrial cancer has significantly changed. The molecular characterization of endometrial cancer has shed new light into the biologic behavior of this disease, the International Federation of Gynecology and Obstetrics staging system was recently revised, and imaging was formally incorporated in the management of endometrial cancer. Read More

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Genome-wide gene-smoking interaction study identified novel susceptibility loci for non-small cell lung cancer in Chinese populations.

Carcinogenesis 2021 Jul 23. Epub 2021 Jul 23.

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.

Gene-smoking interactions play important roles in the development of non-small cell lung cancer (NSCLC). To identify single nucleotide polymorphisms (SNPs) that modify the association of smoking behavior with NSCLC risk, we conducted a genome-wide gene-smoking interaction study in Chinese populations. The genome-wide interaction analysis between SNPs and smoking status (ever- versus never-smokers) was carried out using genome-wide association studies (GWAS) of NSCLC, which included 13,327 cases and 13,328 controls. Read More

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The Association of Post-Traumatic Stress Disorder with longitudinal change in Glomerular Filtration Rate in World Trade Center responders.

Psychosom Med 2021 Jul 7. Epub 2021 Jul 7.

Department of Medicine, Division of Nephrology, Stony Brook University Stony Brook WTC Wellness Program Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai Department of Medicine, University of California, San Francisco Department of Family and Community Medicine, Saint Louis University Department of Family, Population, and Preventative Medicine, Program in Public Health, Stony Brook University Department of Applied Mathematics and Statistics, Stony Brook University Department of Medicine, Division of Infectious Diseases, Stony Brook University.

Objective: High levels of psychological distress increase the risk of a wide range of medical diseases. We investigated the association between posttraumatic stress disorder (PTSD) and kidney disease in this study.

Methods: World Trade Center (WTC) responders were included if they had ≥2 measures of estimated glomerular filtration rate (eGFR). Read More

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MicroRNA-192-5p inhibits migration of triple negative breast cancer cells and directly regulates Rho GTPase Activating Protein 19.

Genes Chromosomes Cancer 2021 Jul 23. Epub 2021 Jul 23.

Department of Human Genetics, Hannover Medical School, Hannover, Germany.

Among the different breast cancer subtypes, triple-negative breast cancer (TNBC) is associated with a poor prognosis, low survival rates and high expression of histone deacetylases. Treatment with histone deacetylase inhibitor trichostatin A (TSA) leads to an increased expression of potential tumor-suppressive miRNAs. Characterization of these miRNAs can help to find new molecular targets for treatment of TNBC. Read More

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Ligands and DNA in the allosteric control of retinoid receptors function.

Essays Biochem 2021 Jul 23. Epub 2021 Jul 23.

Centre de Biologie Structurale (CBS), Inserm, CNRS, Univ Montpellier, Montpellier, France.

Retinoids are a family of compounds that include both vitamin A (all-trans retinol) and its naturally occurring metabolites such as retinoic acids (e.g. all-trans retinoic acid) as well as synthetic analogs. Read More

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Cholangiocarcinoma.

Pathologica 2021 Jun;113(3):158-169

Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy.

Liver cancer represents the third leading cause of cancer-related death worldwide. Cholangiocarcinoma (CCA) is the second most common type of liver cancer after hepatocellular carcinoma, accounting for 10-15% of all primary liver malignancies. Both the incidence and mortality of CCA have been steadily increasing during the last decade. Read More

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The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer.

Sci Rep 2021 Jul 22;11(1):14951. Epub 2021 Jul 22.

Laboratory Medicine Program, University Health Network, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada.

Combination chemotherapy, either modified FOLFIRINOX (mFFX) or gemcitabine-nabpaclitaxel, are used in the treatment of most patients with advanced pancreatic ductal adenocarcinoma (PDAC), yet robust biomarkers of outcome are currently lacking to guide regimen selection. Here, we tested GATA6 immunohistochemistry (IHC) as a putative biomarker in advanced PDAC. GATA6 is a transcription factor in normal pancreas development. Read More

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Phylogenetic analysis of the 5' untranslated region of HCV from cirrhotic patients in Khyber Pakhtunkhwa, Pakistan.

Sci Rep 2021 Jul 22;11(1):15023. Epub 2021 Jul 22.

Department of Microbiology and Biotechnology, Abasyn University Peshawar, Khyber Pakhtunkhwa, Pakistan.

Hepatitis C virus (HCV), a small, single-stranded RNA virus with a 9.6 kb genome, is one of the most common causes of liver diseases. Sequencing of the 5' untranslated region (UTR) is usually used for HCV genotyping, but it is less important in numerous subtypes due to its scarce sequence variations. Read More

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