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O-GlcNAcylation inhibits hepatic stellate cell activation.

J Gastroenterol Hepatol 2021 Sep 21. Epub 2021 Sep 21.

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.

Protein O-GlcNAcylation is a critical post-translational modification regulating gene expression and fundamental cell functions. O-GlcNAc transferase (OGT) emerged as a key regulator of liver pathophysiology and disease. In this study, we aimed to evaluate the role of OGT in hepatic stellate cells (HSCs) and its consequent role in liver fibrosis. Read More

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September 2021

Dual-task clinical and functional MRI correlates in Parkinson's disease with postural instability and gait disorders.

Parkinsonism Relat Disord 2021 Sep 15;91:88-95. Epub 2021 Sep 15.

Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address:

Background: Dual-task is a challenge for Parkinson's disease patients with postural instability and gait disorders (PD-PIGD).

Objective: This study investigated clinical, cognitive and functional brain correlates of dual-task deficits in PD-PIGD patients using quantitative gait analysis, neuropsychological evaluations and functional MRI (fMRI).

Methods: Twenty-three PD-PIGD patients performed a clinical assessment of gait/balance abilities. Read More

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September 2021

Activation of locus coeruleus to rostromedial tegmental nucleus (RMTg) noradrenergic pathway blunts binge-like ethanol drinking and induces aversive responses in mice.

Neuropharmacology 2021 Sep 18:108797. Epub 2021 Sep 18.

Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, NC, 27599-3270, USA; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, School of Medicine, NC, 27599-7178, USA. Electronic address:

There is strong evidence that ethanol entails aversive effects that can act as a deterrent to overconsumption. We have found that in doses that support the development of a conditioned taste aversion ethanol increases the activity of tyrosine hydroxylase (TH) positive neurons in the locus coeruleus (LC), a primary source of norepinephrine (NE). Using cre-inducible AAV5-ChR2 viruses in TH-ires-cre mice we found that the LC provides NE projections that innervate the rostromedial tegmental nucleus (RMTg), a brain region that has been implicated in the aversive properties of drugs. Read More

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September 2021

BthTX-II from Bothrops jararacussu venom has variants with different oligomeric assemblies: An example of snake venom phospholipases A versatility.

Int J Biol Macromol 2021 Sep 18. Epub 2021 Sep 18.

Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo 18618-689, Brazil. Electronic address:

Phospholipases A (PLAs) are found in almost every venomous snake family. In snakebites, some PLAs can quickly cause local myonecrosis, which may lead to permanent sequelae if antivenom is administered belatedly. They hydrolyse phospholipids in membranes through a catalytic calcium ions-dependent mechanism. Read More

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September 2021

EFFECTIVENESS OF DIFLUPREDNATE FOR THE TREATMENT OF ANTERIOR SCLERITIS.

Am J Ophthalmol 2021 Sep 18. Epub 2021 Sep 18.

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Purpose: To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis.

Design: Retrospective, interventional case series.

Methods: Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from 1/1/2018 to 1/1/2020 included: demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, best-corrected visual acuity (BCVA), and lens status. Read More

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September 2021

Preclinical Evaluation of Inhalational Spectinamide-1599 Therapy against Tuberculosis.

ACS Infect Dis 2021 Sep 21. Epub 2021 Sep 21.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.

The lengthy treatment time for tuberculosis (TB) is a primary cause for the emergence of multidrug resistant tuberculosis (MDR-TB). One approach to improve TB therapy is to develop an inhalational TB therapy that when administered in combination with oral TB drugs eases and shortens treatment. Spectinamides are new semisynthetic analogues of spectinomycin with excellent activity against (), including MDR and XDR strains. Read More

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September 2021

A critical review of the ecological status of lakes and rivers from Canada's Oil Sands Region.

Integr Environ Assess Manag 2021 Sep 21. Epub 2021 Sep 21.

Environmental Stewardship Division, Alberta Environment and Parks, Calgary, AB, Canada.

We synthesize the information available from the peer-reviewed literature on the ecological status of lakes and rivers in the Oil Sands Region (OSR) of Canada. The majority of the research from the OSR has been done in or near the minable region and has examined the concentrations, flux, or enrichment of contaminants of concern (CoCs). Proximity to oil sands facilities and the beginning of commercial activities tends to be associated with greater estimates of CoCs across studies. Read More

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September 2021

Zebrafish (Danio rerio) Oatp2b1 as a functional ortholog of the human OATP2B1 transporter.

Fish Physiol Biochem 2021 Sep 21. Epub 2021 Sep 21.

Laboratory for Molecular Ecotoxicology, Division for Marine and Environmental Research, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.

OATP2B1 belongs to a highly conserved organic anion transporting polypeptide (OATP) family of transporters, involved in the cellular uptake of both endogenous and exogenous compounds. The reported substrates of human OATP2B1 include steroid conjugates, bile salts, and thyroid hormones, as well as pharmaceuticals. Human OATP2B1 has orthologous genes in other vertebrate species, including zebrafish (Danio rerio), a widely used model organism in biomedical and environmental research. Read More

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September 2021

Noradrenaline modulates neuronal and perceptual visual detectability via β-adrenergic receptor.

Psychopharmacology (Berl) 2021 Sep 21. Epub 2021 Sep 21.

Laboratory of Brain Information Science in Sports, Center for Education in Liberal Arts and Sciences, Osaka University, Toyonaka, Osaka, Japan.

Rationale: Noradrenaline (NA) is a neuromodulator secreted from noradrenergic neurons in the locus coeruleus to the whole brain depending on the physiological state and behavioral context. It regulates various brain functions including vision via three major adrenergic receptor (AR) subtypes. Previous studies investigating the noradrenergic modulations on vision reported different effects, including improvement and impairment of perceptual visual sensitivity in rodents via β-AR, an AR subtype. Read More

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September 2021

Roles of Psychosocial Factors on the Association Between Online Social Networking Use Intensity and Depressive Symptoms Among Adolescents: Prospective Cohort Study.

J Med Internet Res 2021 Sep 21;23(9):e21316. Epub 2021 Sep 21.

Center for Health Behaviours Research, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.

Background: The potential mechanisms underlying the association between online social networking use intensity and depressive symptoms are unclear and underresearched.

Objective: We aimed to investigate the potential roles of interpersonal psychosocial factors on the association between online social networking use intensity and depressive symptoms among early adolescents.

Methods: A total of 4237 adolescents from a 9-month longitudinal study were included. Read More

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September 2021

Pluripotent-derived Mesenchymal Stem/stromal Cells: an Overview of the Derivation Protocol Efficacies and the Differences Among the Derived Cells.

Stem Cell Rev Rep 2021 Sep 20. Epub 2021 Sep 20.

Carlos Chagas Institute (ICC/FIOCRUZ-PR), Curitiba, Brazil.

Mesenchymal stem/stromal cells (MSCs) are remarkable tools for regenerative medicine. Therapeutic approaches using these cells can promote increased activity and viability in several cell types through diverse mechanisms such as paracrine and immunomodulatory activities, contributing substantially to tissue regeneration and functional recovery. However, biological samples of human MSCs, usually obtained from adult tissues, often exhibit variable behavior during in vitro culture, especially with respect to cell population heterogeneity, replicative senescence, and consequent loss of functionality. Read More

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September 2021

Two adjacent C-terminal mutations enable expression of aryl-alcohol oxidase from Pleurotus eryngii in Pichia pastoris.

Appl Microbiol Biotechnol 2021 Sep 21. Epub 2021 Sep 21.

Institute of Biochemistry, Heinrich-Heine-University Düsseldorf, Universitätsstraße 1, 40225, Düsseldorf, Germany.

Fungal aryl-alcohol oxidases (AAOs) are attractive biocatalysts because they selectively oxidize a broad range of aromatic and aliphatic allylic primary alcohols while yielding hydrogen peroxide as the only by-product. However, their use is hampered by challenging and often unsuccessful heterologous expression. Production of PeAAO1 from Pleurotus eryngii ATCC 90787 in Pichia pastoris failed, while PeAAO2 from P. Read More

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September 2021

Efficacy and mechanism of the anti-CD38 monoclonal antibody Daratumumab against primary effusion lymphoma.

Cancer Immunol Immunother 2021 Sep 20. Epub 2021 Sep 20.

Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.

Primary effusion lymphoma (PEL) is a rare, aggressive B cell non-Hodgkin's lymphoma of the body cavities with malignant effusions. The prognosis is poor, and no optimal treatment has been established. CD38 is a type II transmembrane glycoprotein known to overexpress in multiple myeloma (MM). Read More

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September 2021

Mitochondria-related changes and metabolic dysfunction in low prognosis patients under the POSEIDON classification.

Hum Reprod 2021 Sep 21. Epub 2021 Sep 21.

Reproductive Medical Center, Peking University People's Hospital, Peking University, Beijing, China.

Study Question: What is the relationship between mitochondria of granulosa cells (GCs) and age and ovarian function in the patients under the POSEIDON classification?

Summary Answer: Our results revealed obvious abnormal mitochondrial-related changes in low prognosis IVF population, where age and the function of ovarian reserve exerted a divergent effect on mitochondrial content and function.

What Is Known Already: Mitochondria have an important role in the cross-talk between GCs and oocytes. However, factors affecting mitochondria of GCs and related mechanisms are still poorly understood. Read More

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September 2021

Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice.

bioRxiv 2021 Sep 17. Epub 2021 Sep 17.

The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective SARS-CoV-2 vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. Additionally, the emergence of SARS-CoV-2 variants of concern with their potential to escape therapeutic monoclonal antibodies emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Read More

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September 2021

Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents.

Oncogene 2021 Sep 20. Epub 2021 Sep 20.

Department of Urology, Osaka Medical and Pharmaceutical University, Osaka, 569-8686, Japan.

There has been accumulating evidence for the clinical benefit of chemoradiation therapy (CRT), whereas mechanisms in CRT-recurrent clones derived from the primary tumor are still elusive. Herein, we identified an aberrant BUB1B/BUBR1 expression in CRT-recurrent clones in bladder cancer (BC) by comprehensive proteomic analysis. CRT-recurrent BC cells exhibited a cell-cycle-independent upregulation of BUB1B/BUBR1 expression rendering an enhanced DNA repair activity in response to DNA double-strand breaks (DSBs). Read More

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September 2021

Dancing Against falls iN Community-dwElling older adults (DANCE): a study protocol of a stratified, block-randomised trial.

Inj Prev 2021 Sep 20. Epub 2021 Sep 20.

Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

Background: Unintentional falls among older adults are of primary importance due to their impact on quality of life. Falling accounts for 95% of hip fractures, leading to an approximately six times increased risk of death within the first 3 months. Furthermore, physical and cognitive parameters are risk factors for falls. Read More

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September 2021

Physical activity and the progression of coronary artery calcification.

Heart 2021 Sep 20. Epub 2021 Sep 20.

Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Background: The association of physical activity with the development and progression of coronary artery calcium (CAC) scores has not been studied. This study aimed to evaluate the prospective association between physical activity and CAC scores in apparently healthy adults.

Methods: Prospective cohort study of men and women free of overt cardiovascular disease who underwent comprehensive health screening examinations between 1 March 2011 and 31 December 2017. Read More

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September 2021

Functional characterization of ovine dorsal root ganglion neurons reveal peripheral sensitization after osteochondral defect.

eNeuro 2021 Sep 17. Epub 2021 Sep 17.

Department of Pharmacology, University of Cambridge, UK

Knee joint trauma can cause an osteochondral defect (OD), a risk factor for osteoarthritis and cause of debilitating pain in patients. Rodent OD models are less translatable due to their smaller joint size and open growth plate. This study proposes sheep as a translationally relevant model to understand the neuronal basis of OD pain. Read More

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September 2021

Cancer detection via primary care urgent referral and association with practice characteristics: a retrospective cross-sectional study in England from 2009/2010 to 2018/2019.

Br J Gen Pract 2021 Jun 25. Epub 2021 Jun 25.

School of Cancer and Pharmaceutical Sciences, King's College London, London.

Background: There is substantial variation in the use of urgent suspected cancer referral (2-week wait [2WW]) between practices.

Aim: To examine the change in use of 2WW referrals in England over 10 years (2009/2010 to 2018/2019) and the practice and population factors associated with cancer detection.

Design And Setting: Retrospective cross-sectional study of English general practices and their 2WW referral and Cancer Waiting Times database detection data (all cancers other than non-melanoma skin cancers) from 2009/2010 to 2018/2019. Read More

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Microbial river-to-sea continuum: gradients in benthic and planktonic diversity, osmoregulation and nutrient cycling.

Microbiome 2021 Sep 20;9(1):190. Epub 2021 Sep 20.

School of Biological Sciences, University of Auckland, Auckland, 1010, New Zealand.

Background: Coastal aquatic ecosystems include chemically distinct, but highly interconnected environments. Across a freshwater-to-marine transect, aquatic communities are exposed to large variations in salinity and nutrient availability as tidal cycles create periodic fluctuations in local conditions. These factors are predicted to strongly influence the resident microbial community structure and functioning, and alter the structure of aquatic food webs and biogeochemical cycles. Read More

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September 2021

Multisensory integration in cortical regions responding to locomotion-related visual and somatomotor signals.

Neuroimage 2021 Sep 17:118581. Epub 2021 Sep 17.

Department of Cognitive and Motor Rehabilitation and Neuroimaging, Santa Lucia Foundation (IRCCS Fondazione Santa Lucia), Rome, Italy; Department of Movement, Human and Health Sciences, University of Rome ''Foro Italico'', Rome, Italy.

During real-world locomotion, in order to be able to move along a path or avoid an obstacle, continuous changes in self-motion direction (i.e. heading) are needed. Read More

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September 2021

Compounded Cerium Nitrate-Silver Sulfadiazine Cream is Safe and Effective for the Treatment of Burn Wounds: A Burn Center's Four-Year Experience.

J Burn Care Res 2021 Sep 20. Epub 2021 Sep 20.

Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC, USA.

Wound infections and sepsis are significant causes of morbidity after burn injury and can be alleviated by early excision and grafting. In situations that preclude early surgery, topical agents allow for a safer delay. Cerium nitrate compounded with silver sulfadiazine (Ce-SSD) is a burn cream that provides broad antibacterial activity, forms a temporary barrier, and promotes re-epithelialization. Read More

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September 2021

Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia.

Blood 2021 Sep 20. Epub 2021 Sep 20.

Fred Hutchinson, United States.

Uproleselan (GMI-1271) is a novel E-selectin antagonist that disrupts cell survival pathways, enhances chemotherapy response, improves survival in mouse xenograft and syngeneic models, and decreases chemotherapy toxicity in vivo. A phase 1/2 study (NCT02306291) evaluated the safety, tolerability, and anti-leukemic activity of uproleselan (5-20 mg/kg) with MEC (mitoxantrone, etoposide, cytarabine) among patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Among the first 19 patients, no dose-limiting toxicities were observed. Read More

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September 2021

Deficiency of leads to accelerated aging and neuroprotection in MPTP-induced Parkinson's disease mice.

Aging (Albany NY) 2021 Sep 20;13(undefined). Epub 2021 Sep 20.

Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.

Studies reveal a linkage of miR-29s in aging and Parkinson's disease (PD). Here we show that the serum levels of miR-29s in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice exhibited dynamic changes. The role of in aging and PD was studied utilizing gene knockout mice ( KO). Read More

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September 2021

Bile salts promote ToxR regulon activation during growth under virulence inducing conditions.

Infect Immun 2021 Sep 20:IAI0044121. Epub 2021 Sep 20.

University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA.

Cholera is an epidemic disease caused by the Gram-negative bacterium . is found in aquatic ecosystems and infects people through the consumption of contaminated food or water. Following ingestion, responds to host cues to activate the expression of critical virulence genes that are under control of a hierarchical regulatory system called the ToxR regulon. Read More

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September 2021

Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population.

Circulation 2021 Sep 20;144(12):916-929. Epub 2021 Sep 20.

Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden.

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.

Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). Read More

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September 2021

Potential Long-Term Health Problems Associated with Ultra-Endurance Running: A Narrative Review.

Sports Med 2021 Sep 20. Epub 2021 Sep 20.

Centro de Investigación y Diagnóstico en Salud y Deporte (CIDISAD), Escuela Ciencias del Movimiento Humano y Calidad de Vida (CIEMHCAVI), Universidad Nacional, Heredia, Costa Rica.

It is well established that physical activity reduces all-cause mortality and can prolong life. Ultra-endurance running (UER) is an extreme sport that is becoming increasingly popular, and comprises running races above marathon distance, exceeding 6 h, and/or running fixed distances on multiple days. Serious acute adverse events are rare, but there is mounting evidence that UER may lead to long-term health problems. Read More

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September 2021

Effect of Nitinol on Metabolic and Coagulation Activity of Endothelial Cells Culture.

Bull Exp Biol Med 2021 Sep 20. Epub 2021 Sep 20.

Ryazan State Medical University, Ministry of Health of the Russian Federation, Ryazan, Russia.

We studied the effect of nitinol, the most prevalent material for endovascular stents, on metabolic and coagulation activity of a primary culture of human umbilical vein endothelial cells (HUVEC). Metabolic activity was evaluated using MTS-test and by the level of stable NO metabolites in the conditioned medium, coagulation activity was assessed by activity of von Willebrand factor (vWF) and levels of plasminogen activator inhibitor-1 (PAI-1) and soluble endothelial protein C receptors (sEPCR). Exposure to nitinol reduced metabolic activity of the cell culture by 11. Read More

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September 2021

Resistance training in heart failure patients: a systematic review and meta-analysis.

Heart Fail Rev 2021 Sep 20. Epub 2021 Sep 20.

School of Science and Technology, University of New England, Armidale, NSW, 2351, Australia.

Aerobic training (AT) has been the primary mode of exercise training in cardiac rehabilitation. Historically, the reason for the prescription of AT was that it was speculated that although RT may be beneficial for some clinical outcomes, it may have an adverse effect on ventricular structure and function. However, RT has now made its way into current cardiac rehabilitation guidelines, including those directed towards patients with HF, albeit differences exist across institutions and guidelines. Read More

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September 2021