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Diagnostic accuracy of a novel artificial intelligence system for adenoma detection in daily practice: a prospective non-randomized comparative study.

Endoscopy 2021 Jul 22. Epub 2021 Jul 22.

Department of Gastroenterology and interventional Endoscopy, Krankenhaus Barmherzige Bruder Regensburg, Regensburg, Germany.

Background And Aims: Adenoma detection rate (ADR) varies significantly between endoscopists with up to 26% adenoma miss rate (AMR). Artificial intelligence (AI) systems may improve endoscopic quality and reduce the rate of interval cancer. We evaluated the efficacy of an AI system in real time colonoscopy and its influence on the AMR and the ADR. Read More

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Intraoral Hirudotherapy for Venous Congestion following Free Flap Head and Neck Reconstruction: Novel Intraoral Technique.

ORL J Otorhinolaryngol Relat Spec 2021 Jul 22:1-4. Epub 2021 Jul 22.

Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.

Intraoral hirudotherapy is traditionally used for venous congestion following head and neck free flap reconstruction. Many institutions and healthcare teams have been reluctant to use intraoral leech therapy due to risks such as migration into the airway, increased infection from intraoral manipulation, and patient discomfort. Several protocols recommend blocking the path to the oropharynx via gauze or leaving a tracheotomy in place to protect the airway. Read More

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Neurotransmitters and Neuropeptides decrease PD-1 in T cells of healthy subjects and patients with hepatocellular carcinoma (HCC), and increase their proliferation and eradication of HCC cells.

Neuropeptides 2021 May 12;89:102159. Epub 2021 May 12.

Institute of Gene Therapy, Hadassah Hebrew University Hospital, Ein Karem, Jerusalem 91120, Israel.

T cells of aged people, and of patients with either cancer or severe infections (including COVID-19), are often exhausted, senescent and dysfunctional, leading to increased susceptibilities, complications and mortality. Neurotransmitters and Neuropeptides bind their receptors in T cells, and induce multiple beneficial T cell functions. Yet, T cells of different people vary in the expression levels of Neurotransmitter and Neuropeptide receptors, and in the magnitude of the corresponding effects. Read More

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Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Shoulder: An Orthoregeneration Network (ON) Foundation Review.

Arthroscopy 2021 Jul 19. Epub 2021 Jul 19.

Midwest Orthopaedics at Rush, Chicago, IL, USA. Electronic address:

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Read More

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Design and evaluation of GLP-1 receptor G-protein biased agonist with prolonged efficacy on diabetes.

Life Sci 2021 Jul 19:119844. Epub 2021 Jul 19.

Peking University Third Hospital, Beijing 100191, PR China. Electronic address:

Aim: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as potent drug development target for treating diabetes and obesity. Here, we designed and evaluated novel long-acting GLP-1R G protein biased agonist with potent clinical application.

Main Methods: GLP-1R G-protein biased sequences were screened via a high-throughput autocrine-based strategy and then fused to Exendin (9-39). Read More

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Development of emodepside as a possible adulticidal treatment for human onchocerciasis-The fruit of a successful industrial-academic collaboration.

PLoS Pathog 2021 Jul 22;17(7):e1009682. Epub 2021 Jul 22.

Department of Biomedical Sciences, Iowa State University, Ames, Iowa, United States of America.

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus. Read More

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Collagen XVII inhibits breast cancer cell proliferation and growth through deactivation of the AKT/mTOR signaling pathway.

PLoS One 2021 22;16(7):e0255179. Epub 2021 Jul 22.

Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand.

Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-proliferative effect of COL17 on breast cancer cell through mTOR deactivation. Read More

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Aiming for a bull's-eye: Targeting antifungals to fungi with dectin-decorated liposomes.

PLoS Pathog 2021 Jul 22;17(7):e1009699. Epub 2021 Jul 22.

Department of Microbiology, University of Georgia, Athens, Georgia, United States of America.

Globally, there are several million individuals with life-threatening invasive fungal diseases such as candidiasis, aspergillosis, cryptococcosis, Pneumocystis pneumonia (PCP), and mucormycosis. The mortality rate for these diseases generally exceeds 40%. Annual medical costs to treat these invasive fungal diseases in the United States exceed several billion dollars. Read More

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Estimating the net value of treating hepatitis C virus using sofosbuvir-velpatasvir in India.

PLoS One 2021 22;16(7):e0252764. Epub 2021 Jul 22.

Stanford Graduate School of Business, Stanford, California, United States of America.

Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) have been groundbreaking for their high efficacy across disease genotypes and lack of severe side effects. This study uses a cost-of-illness (COI) approach to estimate the net value conferred by this class of drugs using the cost and efficacy of one of these novel drug combinations, sofosbuvir and velpatasvir (SOF/VEL), recently licensed for generic manufacture in India. This study considers COI of lifetime earnings lost by patients and potential secondarily infected individuals due to disability and premature death from HCV infection. Read More

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Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study.

J Clin Oncol 2021 Jul 22:JCO2003555. Epub 2021 Jul 22.

Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348).

Patients And Methods: Patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Read More

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Modular Platform for the Development of Recombinant Hemoglobin Scavenger Biotherapeutics.

Mol Pharm 2021 Jul 22. Epub 2021 Jul 22.

Division of Internal Medicine, Universitätsspital and University of Zurich, Zurich 8091, Switzerland.

Cell-free hemoglobin (Hb) is a driver of disease progression in conditions with intravascular or localized hemolysis. Genetic and acquired anemias or emergency medical conditions such as aneurysmal subarachnoid hemorrhage involve tissue Hb exposure. Haptoglobin (Hp) captures Hb in an irreversible protein complex and prevents its pathophysiological contributions to vascular nitric oxide depletion and tissue oxidation. Read More

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Exploring Older Adults' Experiences of a Home-Based, Technology-Driven Balance Training Exercise Program Designed to Reduce Fall Risk: A Qualitative Research Study Within a Randomized Controlled Trial.

J Geriatr Phys Ther 2021 Jul 14. Epub 2021 Jul 14.

School of Health, Medicine and Applied Science, Appleton Institute, CQUniversity, Melbourne, Victoria Australia. Public Health, Health Faculty, Torrens University Australia, Adelaide, South Australia, Australia. Physical Activity, Lifestyle, Ageing and Wellbeing Faculty Research Group, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, Australia. Exercise Science Laboratory, School of Kinesiology, Faculty of Medicine, Universidad Finis Terrae, Santiago, Chile. School of Population Health, University of New South Wales, Sydney, Australia. Neuroscience Research Australia, Randwick, Australia. Prince of Wales Hospital Clinical School, University of New South Wales, Sydney, Australia. Centre for Excellence in Population Ageing Research, The University of Sydney, Sydney, Australia. Care and Public Health Research Institute, Department of Health Services Research, Maastricht University, the Netherlands. Institute for Musculoskeletal Health, The University of Sydney and Sydney Local Health District, Sydney, Australia. School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia. School of Health, Medicine and Applied Science, Appleton Institute, CQUniversity, Rockhampton North, Australia.

Background And Purpose: With an aging population, falls have become an increasing public health concern. While face-to-face exercise programs have demonstrated efficacy in reducing falls, their effectiveness is hampered by low participation and adherence. Digital technologies are a novel and potentially effective method for delivering tailored fall prevention exercise programs to older adults. Read More

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Synthesis and characterization of vitamin D-functionalized carbon dots for CRISPR/Cas9 delivery.

Nanomedicine (Lond) 2021 Jul 22. Epub 2021 Jul 22.

Cellular & Molecular Research Center, Iran University of Medical Sciences, Tehran, 1449614535, Iran.

To develop a novel nanovector for the delivery of genetic fragments and CRISPR/Cas9 systems in particular. Vitamin D-functionalized carbon dots (D/CDs) fabricated using one-step microwave-aided methods were characterized by different microscopic and spectroscopic techniques. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry were employed to determine the cell viability and transfection efficiency. Read More

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The place of vericiguat in the landscape of treatment for heart failure with reduced ejection fraction.

Heart Fail Rev 2021 Jul 21. Epub 2021 Jul 21.

Institute of Life Sciences, Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, Pisa, Italy.

The significant morbidity and mortality associated with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function. This pathway is disrupted in HF resulting in decreased protection against myocardial injury. Read More

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Laser treatment of pilonidal disease: a systematic review.

Lasers Med Sci 2021 Jul 22. Epub 2021 Jul 22.

Department of Surgery, University Hospital Centre Zagreb, Kispaticeva 12, 10 000, Zagreb, Croatia.

Pilonidal disease (PD) is a common condition, and there is still an ongoing debate on ideal management that should be minimally invasive, safe, and efficient. The use of radially emitting laser in the treatment of chronic PD is a novel minimally invasive technique, and initial studies with a small number of patients showed promising results. This study aimed to assess the efficacy and safety of chronic PD treatment with a laser using a systematic review of the published literature. Read More

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Using a Systematic Approach to Teach Analysis of the Aging Face.

OTO Open 2021 Jul-Sep;5(3):2473974X211020251. Epub 2021 Jul 9.

Department of Otolaryngology-Head and Neck Surgery, University of Kansas, Kansas City, Kansas, USA.

Objective: To assess the efficacy of a novel systematic approach aimed at improving a resident physician's ability to perform analysis of the aging face.

Study Design: Prospective randomized case-control study.

Setting: Accreditation Council for Graduate Medical Education accredited Otolaryngology-Head and Neck Surgery residency program. Read More

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Registered Influenza Viral Vector Based Vaccine for Cattle in Kazakhstan: Age-Wise Safety and Efficacy Studies.

Front Cell Infect Microbiol 2021 1;11:669196. Epub 2021 Jul 1.

International Center for Vaccinology, Kazakh National Agrarian University (KazNAU), Almaty, Kazakhstan.

A novel influenza viral vector based vaccine (Flu-BA) was introduced for use in cattle in Kazakhstan in 2019. In this study, the safety and efficacy of the vaccine was evaluated in male and female cattle at different ages, and during pregnancy as a part of its registration process. Our data demonstrated that the Flu-BA vaccine was safe after prime or booster vaccination in calves (5-7 months old male and female), heifers (15-17 months old) and cows (6-7 years old) and was not abortogenic in pregnant animals. Read More

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Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML.

Oncoimmunology 2021 8;10(1):1945804. Epub 2021 Jul 8.

GEMoaB GmbH, Dresden, Germany.

Chimeric antigen receptor T cells (CAR-T) targeting CD19 have achieved significant success in patients with B cell malignancies. To date, implementation of CAR-T in other indications remains challenging due to the lack of truly tumor-specific antigens as well as control of CAR-T activity in patients. CD123 is highly expressed in acute myeloid leukemia (AML) blasts including leukemia-initiating cells making it an attractive immunotherapeutic target. Read More

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PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer.

Sci Rep 2021 Jul 21;11(1):14841. Epub 2021 Jul 21.

NIBR Biologics Center, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.

High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses. We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC. Read More

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Targeting c-Myc to overcome acquired resistance of EGFR mutant NSCLC cells to the third generation EGFR tyrosine kinase inhibitor, osimertinib.

Cancer Res 2021 Jul 21. Epub 2021 Jul 21.

Hematology and Medical Oncology, Emory University School of Medicine

Osimertinib (AZD9291 or TAGRISSOTM) is a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for treating patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations or the resistant T790M mutation. However, the inevitable emergence of acquired resistance limits its long-term efficacy. A fuller understanding of the mechanism of action of osimertinib and its linkage to acquired resistance will enable the development of more efficacious therapeutic strategies. Read More

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Observation of synergistic antibacterial properties of prodigiosin from jx-1 with metal ions in clinical isolates of .

Prep Biochem Biotechnol 2021 Jul 21:1-7. Epub 2021 Jul 21.

College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing, China.

Methicillin-resistant (MRSA) infections are a major global health problem, and novel and effective antimicrobial drugs are urgently required to combat this life-threatening pathogen. Prodigiosin (PG) is a bacterial secondary metabolite with excellent anticancer and antibacterial properties. However, little is known about the antibacterial function of PG against MRSA. Read More

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Large, Anionic Liposomes Enable Targeted Intraperitoneal Delivery of a TLR 7/8 Agonist To Repolarize Ovarian Tumors' Microenvironment.

Bioconjug Chem 2021 Jul 21. Epub 2021 Jul 21.

Ovarian cancer is the most lethal gynecological malignancy in the United States. Current standard of treatment includes surgical debulking and chemotherapy, such as cisplatin and paclitaxel. However, the patients' response rate for chemotherapy in ovarian cancer is not optimal, and they often develop chemoresistance and suffer from side effects. Read More

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A Dendritic Cells-Targeting Nano-Vaccine by Coupling Polylactic-Co-Glycolic Acid-Encapsulated Allergen with Mannan Induces Regulatory T Cells.

Int Arch Allergy Immunol 2021 Jul 21:1-11. Epub 2021 Jul 21.

Department of Allergy and Rheumatology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.

Background: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen.

Objectives: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. Read More

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Efficacy of a Novel Medical Adhesive for Sealing Lung Parenchyma: An in vitro Study in Rabbit Lungs.

Eur Surg Res 2021 Jul 21:1-7. Epub 2021 Jul 21.

Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Aachen, Germany.

Introduction: During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evaluate whether the novel medical adhesive VIVO (Adhesys Medical GmbH Aachen, Germany) is a reliable alternative sealing technique to routine surgical procedures. Read More

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Melatonin improves learning and memory of mice with chronic social isolation stress via an interaction between microglia polarization and BDNF/TrkB/CREB signaling pathway.

Eur J Pharmacol 2021 Jul 18;908:174358. Epub 2021 Jul 18.

Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Chronic social isolation stress (SIS) could impair learning and memory-related behaviors. Herein, we investigated the efficacy of Melatonin in treatment of memory despair and also its possible underlying mechanism of action in an animal model of SIS. For this purpose, mice were allocated to two opposing conditions, including social condition (SC) and isolated condition (IC), for five weeks. Read More

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Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer.

Cell Rep 2021 Jul;36(3):109394

Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany; Nuvisan Innovation Campus Berlin GmbH, 13353 Berlin, Germany.

Novel treatment options for metastatic colorectal cancer (CRC) are urgently needed to improve patient outcome. Here, we screen a library of non-characterized small molecules against a heterogeneous collection of patient-derived CRC spheroids. By prioritizing compounds with inhibitory activity in a subset of-but not all-spheroid cultures, NCT02 is identified as a candidate with minimal risk of non-specific toxicity. Read More

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Development of a novel formulation method to prepare liposomal Epacadostat.

Eur J Pharm Sci 2021 Jul 18;165:105954. Epub 2021 Jul 18.

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: One of the important metabolic pathways in cancer progression is tryptophan catabolism by the indoleamin-2,3-dioxygenase (IDO) enzyme, which suppresses the immune system and induces tolerance. Inhibition of IDO1 is an important therapeutic goal for immunotherapy in many cancers such as metastatic melanoma. Epacadostat (EPA) is a very strong inhibitor of IDO1, and its clinical studies are being performed in a higher clinical phase than other inhibitors. Read More

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Comparison of procedural efficacy, balloon nadir temperature and incidence of phrenic nerve palsy between two cryoballoon technologies for pulmonary vein isolation: a systematic review and meta-analysis.

J Cardiovasc Electrophysiol 2021 Jul 21. Epub 2021 Jul 21.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Introduction: In May 2020 a novel cryoballoon system (POLARx, Boston Scientific) became available for catheter ablation of atrial fibrillation (AF). The design of the cryoballoon is comparable to the Arctic Front Advance Pro (AFA-Pro, Medtronic), but it is more compliant during freezing. We compared the procedural efficacy, biophysical parameters and risk of phrenic nerve palsy (PNP) between the two cryoballoons. Read More

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Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe.

Epilepsia 2021 Jul 21. Epub 2021 Jul 21.

Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Objective: Impaired memory is a common comorbidity of refractory temporal lobe epilepsy (TLE) and often perceived by patients as more problematic than the seizures themselves. The objective of this study is to understand what the relationship of these behavioral impairments is to the underlying pathophysiology, as there are currently no treatments for these deficits, and it remains unknown what circuits are affected.

Methods: We recorded single neurons in the medial temporal lobes (MTLs) of 62 patients (37 with refractory TLE) who performed a visual recognition memory task to characterize the relationship between behavior, tuning, and anatomical location of memory selective and visually selective neurons. Read More

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Assessment of antiviral coatings for high-touch surfaces using human coronaviruses HCoV-229E and SARS-CoV-2.

Appl Environ Microbiol 2021 Jul 21:AEM0109821. Epub 2021 Jul 21.

Société des Produits Nestlé, Nestlé Research, Institute of Food Safety and Analytical Science, 1000, Lausanne 26, Switzerland.

A novel and robust approach to evaluate the antiviral activity of coatings was developed, assessing three commercially available leave-on surface coating products for efficacy against human coronaviruses HCoV-229E and SARS-CoV-2. The assessment is based on three criteria that reflect real-life settings, namely (i) immediate antiviral effect, (ii) effect after repeated cleaning of the coated surface, and (iii) antiviral activity in the presence of organic material. The results showed that only a copper compound-based coating successfully met all three criteria. Read More

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