byl719 and Lung-Neoplasms

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; Lasers, Semiconductor; Lenalidomide; Leptin; Lethal Dose 50; Levonorgestrel; Limit of Detection; Lipid Metabolism; Lipid Metabolism Disorders; Lipogenesis; Lipopolysaccharides; Liquid Biopsy; Liver; Liver Abscess, Pyogenic; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Longevity; Lung Neoplasms; Luteolin; Lymph Nodes; Lymphocyte Activation; Macaca fascicularis; Macrophages; Mad2 Proteins; Magnetic Resonance Imaging; Male; Mammary Glands, Human; Manganese; Manganese Compounds; MAP Kinase Signaling System; Materials Testing; Maternal Health Services; MCF-7 Cells; Medicaid; Medicine, Chinese Traditional; Melanoma; Membrane Proteins; Mental Health; Mercury; Metal Nanoparticles; Metals, Heavy; Metformin; Methionine Adenosyltransferase; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Mice, Nude; Microalgae; Microbial Sensitivity Tests; Microglia; MicroRNAs; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Middle Aged; Mitochondria; Mitochondrial Proteins; Mitral Valve; Mitral Valve Insufficiency; Models, Anatomic; Molecular Structure; Molybdenum; Monocarboxylic Acid Transporters; Moths; MPTP Poisoning; Multigene Family; Multiparametric Magnetic Resonance Imaging; Multiple Myeloma; Muscle, Skeletal; Mutagens; Mutation; Myeloid Cells; Nanocomposites; Nanofibers; Nanomedicine; Nanoparticles; Nanowires; Neoadjuvant Therapy; Neomycin; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Stem Cells; Neostriatum; Neovascularization, Pathologic; Netherlands; Neuromuscular Agents; Neurons; NF-E2-Related Factor 2; NF-kappa B; Nickel; Nitrogen Oxides; Non-alcoholic Fatty Liver Disease; Nucleosides; Nucleotidyltransferases; Nutritional Status; Obesity, Morbid; Ofloxacin; Oils, Volatile; Oligopeptides; Oncogene Protein v-akt; Optical Imaging; Organic Cation Transport Proteins; Organophosphonates; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Osteoblasts; Osteogenesis; Oxidation-Reduction; Oxidative Stress; Oxides; Oxygen Isotopes; Pancreas; Pancreaticoduodenectomy; Pandemics; Particle Size; Particulate Matter; Patient Acceptance of Health Care; Patient Compliance; PC-3 Cells; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Peroxides; Peru; Pest Control, Biological; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Phylogeny; Pilot Projects; Piperidines; Plant Bark; Plant Extracts; Plant Leaves; Plasmids; Platelet Function Tests; Pneumonia, Viral; Podocytes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Polyethylene Terephthalates; Polymers; Polymorphism, Single Nucleotide; Porosity; Portugal; Positron-Emission Tomography; Postoperative Complications; Postural Balance; Potassium Channels, Inwardly Rectifying; Povidone; Powders; Precancerous Conditions; Precision Medicine; Predictive Value of Tests; Pregnancy; Prenatal Care; Prognosis; Promoter Regions, Genetic; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Proteasome Inhibitors; Protective Agents; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein Transport; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-akt; Psychiatric Nursing; PTEN Phosphohydrolase; Pulmonary Embolism; Pyrimethamine; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reactive Oxygen Species; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Receptors, G-Protein-Coupled; Recombinational DNA Repair; Recovery of Function; Regional Blood Flow; Renal Dialysis; Renin; Renin-Angiotensin System; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Distress Syndrome; Retrospective Studies; Rhodamines; Risk Assessment; Risk Factors; RNA, Long Noncoding; RNA, Messenger; Running; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salinity; Salmeterol Xinafoate; Sarcoma; Seasons; Shoulder Injuries; Signal Transduction; Silicon Dioxide; Silver; Sirtuin 1; Sirtuins; Skull Fractures; Social Determinants of Health; Sodium; Sodium Fluoride; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Soil; Soil Pollutants; Spain; Spectrophotometry; Spectroscopy, Fourier Transform Infrared; Staphylococcal Protein A; Staphylococcus aureus; Stem Cells; Stereoisomerism; Stomach Neoplasms; Streptomyces; Strontium; Structure-Activity Relationship; Students, Nursing; Substance-Related Disorders; Succinic Acid; Sulfur; Surface Properties; Survival Rate; Survivin; Symporters; T-Lymphocytes; Temozolomide; Tensile Strength; Thiazoles; Thiobacillus; Thiohydantoins; Thiourea; Thrombectomy; Time Factors; Titanium; Tobacco Mosaic Virus; Tobacco Use Disorder; Toll-Like Receptor 4; Toluene; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Toxicity Tests, Acute; Toxicity Tests, Subacute; Transcriptional Activation; Treatment Outcome; Troponin I; Tumor Cells, Cultured; Tumor Escape; Tumor Hypoxia; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Tyrosine; Ubiquitin-Protein Ligases; Ubiquitination; Ultrasonic Waves; United Kingdom; United States; United States Department of Veterans Affairs; Up-Regulation; Urea; Uric Acid; Urinary Bladder Neoplasms; Urinary Bladder, Neurogenic; Urine; Urodynamics; User-Computer Interface; Vemurafenib; Verbenaceae; Veterans; Veterans Health; Viral Load; Virtual Reality; Vitiligo; Water Pollutants, Chemical; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Xylenes; Young Adult; Zinc; Zinc Oxide; Zinc Sulfate; Zoonoses

The present study aimed to assess the prevalence of symptoms of anxiety and depression among health professionals in the three most affected regions in Cameroon.. The study was a descriptive cross-sectional type. Participants were health care professionals working in the three chosen regions of Cameroon. The non_probability convinient sample technique and that of the snowball were valued via a web questionnaire. The non-exhaustive sample size was 292. The diagnosis of anxiety and depression was made by the HAD (Hospital Anxiety and Depression scale).. Les auteurs rapportent que le secteur médical est classé à un plus grand risque de contracter le COVID-19 et de le propager potentiellement à d’autres. Le nombre sans cesse croissant de cas confirmés et suspects, la pression dans les soins, l’épuisement des équipements de protection individuelle et le manque de médicaments spécifiques peuvent contribuer à un vécu anxio-dépressif significatif. La présente étude s’est donnée pour ambition d’évaluer la prévalence des symptômes de l’anxiété et de la dépression chez les professionnels de santé dans les trois Régions les plus concernées au Cameroun.. Le choix des trois Régions du Cameroun se justifie non seulement par le fait qu’elles totalisent 95,8 % des cas de coronavirus au pays depuis le début de la pandémie, mais aussi parce qu’elles disposent de plus de la moitié des personnels de santé (56 %). Il s’agit d’une étude transversale, descriptive et analytique. Les participants sont des professionnels de la santé en service dans les Régions du Centre, Littoral et de l’Ouest du Cameroun. La méthode d’échantillonnage non probabiliste de convenance couplée à celle de boule de neige via un web questionnaire a été adoptée. La collecte des données a duré du 5 au 19 avril 2020, intervalle de temps après lequel on n’avait plus eu de répondants. À la fin de cette période, la taille de l’échantillon non exhaustive était de 292 professionnels. Le diagnostic de l’état anxio-dépressive était posé via l’échelle de HAD (Hospital Anxiety and Depression scale). Dans le HAD, chaque réponse cotée évalue de manière semi-quantitative l’intensité du symptôme au cours de la semaine écoulée. Un score total est obtenu ainsi que des scores aux deux sous-échelles : le score maximal est de 42 pour l’échelle globale et de 21 pour chacune des sous-échelles. Le coefficient alpha de Cronbach est de 0,70 pour la dépression et de 0,74 pour l’anxiété. Certains auteurs après plusieurs travaux ont proposé qu’une note inférieure ou égale à 7 indique une absence d’anxiété ou de dépression ; celle comprise entre 8 et 10 suggère une anxiété ou une dépression faible à bénigne ; entre 11 et 14, pour une anxiété ou une dépression modérée ; enfin, une note comprise entre 15 et 21 est révélatrice d’une anxiété sévère. Le logiciel Excel 2013 et Epi Info version 7.2.2.6 ont été utilisés pour les traitements statistiques. Les liens entre les variables ont été considérées significatifs pour une valeur de. L’amélioration des conditions de travail et notamment la fourniture d’équipement de protection, la mise en place des cellules spéciales d’écoute pour le personnel de santé pourraient être proposées.. Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of. During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (. In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.. Beyond age, cognitive impairment was associated with prior MI/stroke, higher hsCRP, statin use, less education, lower eGFR, BMI and LVEF.. These data demonstrate that even a short period of detraining is harmful for elderly women who regularly participate in a program of strength training, since it impairs physical performance, insulin sensitivity and cholesterol metabolism.. Exposure to PM. Respiratory sinus arrhythmia is reduced after PVI in patients with paroxysmal AF. Our findings suggest that this is related to a decrease in cardiac vagal tone. Whether and how this affects the clinical outcome including exercise capacity need to be determined.. BDNF and leptin were not associated with weight. We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG. The results indicated that the MGO injection reduced all CCl. The hepatoprotective effects of MGO might be due to histopathological suppression and inflammation inhibition in the liver.. OVEO showed moderate antifungal activity, whereas its main components carvacrol and thymol have great application potential as natural fungicides or lead compounds for commercial fungicides in preventing and controlling plant diseases caused by. PF trajectories were mainly related to income, pregestational BMI, birth weight, hospitalisation due to respiratory diseases in childhood, participant's BMI, report of wheezing, medical diagnosis and family history of asthma, gestational exposure to tobacco and current smoking status in adolescence and young adult age.. In chronic pain patients on opioids, administration of certain benzodiazepine sedatives induced a mild respiratory depression but paradoxically reduced sleep apnoea risk and severity by increasing the respiratory arousal threshold.. Quantitative measurements of sensory disturbances using the PainVision. The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.. The electrophysiological data and MD simulations collectively suggest a crucial role of the interactions between the HA helix and S4-S5 linker in the apparent Ca. Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes). Read the full text of the article at 10.1002/chem.202002067.. The optimal CRT pacing configuration changes during dobutamine infusion while LV and RV activation timing does not. Further studies investigating the usefulness of automated dynamic changes to CRT pacing configuration according to physiologic condition may be warranted.

Topics: 3' Untranslated Regions; 5'-Nucleotidase; A549 Cells; Accidental Falls; Acetylcholinesterase; Acrylic Resins; Actinobacillus; Acute Disease; Acute Kidney Injury; Adaptor Proteins, Signal Transducing; Adenosine; Adenosine Triphosphate; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Advance Care Planning; Africa, Northern; Age Factors; Aged; Aged, 80 and over; Air Pollutants; Air Pollution; Air Pollution, Indoor; Albendazole; Aluminum Oxide; Anastomosis, Surgical; Ancylostoma; Ancylostomiasis; Androstadienes; Angiogenesis Inhibitors; Angiotensin II; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bispecific; Antibodies, Viral; Anticoagulants; Antihypertensive Agents; Antinematodal Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antiporters; Antiviral Agents; Apoptosis; Aptamers, Nucleotide; Aromatase Inhibitors; Asian People; Astrocytes; Atrial Fibrillation; Auditory Threshold; Aurora Kinase B; Australia; Autophagy; Autophagy-Related Protein 5; Autotrophic Processes; Bacillus cereus; Bacillus thuringiensis; Bacterial Proteins; Beclin-1; Belgium; Benzene; Benzene Derivatives; Benzhydryl Compounds; beta Catenin; beta-Arrestin 2; Biliary Tract Diseases; Biofilms; Biofuels; Biomarkers; Biomarkers, Tumor; Biomass; Biomechanical Phenomena; Bioreactors; Biosensing Techniques; Biosynthetic Pathways; Bismuth; Blood Platelets; Bone and Bones; Bone Regeneration; Bortezomib; Botulinum Toxins, Type A; Brain; Brain Injuries; Brain Ischemia; Brain Neoplasms; Breast Neoplasms; Breath Tests; Bronchodilator Agents; Calcium Phosphates; Cannabis; Carbon Dioxide; Carbon Isotopes; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiomyopathies; Cardiovascular Diseases; Cariostatic Agents; Case Managers; Case-Control Studies; Catalysis; Cation Transport Proteins; CD8-Positive T-Lymphocytes; Cecropia Plant; Cell Adhesion; Cell Count; Cell Differentiation; Cell Division; Cell Line; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Self Renewal; Cell Survival; Cells, Cultured; Cellular Reprogramming; Cellulose; Charcoal; Chemical and Drug Induced Liver Injury; Chemical Phenomena; Chemokines; Chemoradiotherapy; Chemoreceptor Cells; Child; Child Abuse; Child, Preschool; China; Chlorogenic Acid; Chloroquine; Chromatography, Gas; Chronic Disease; Clinical Competence; Coated Materials, Biocompatible; Cochlea; Cohort Studies; Color; Comorbidity; Computer Simulation; Computer-Aided Design; Contraception; Contraceptive Agents, Female; Contrast Media; COP-Coated Vesicles; Coronavirus Infections; Cost of Illness; Coturnix; COVID-19; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Culex; Curriculum; Cyclic N-Oxides; Cytokines; Cytoplasm; Cytotoxicity, Immunologic; Cytotoxins; Databases, Factual; Deep Learning; Delivery, Obstetric; Denitrification; Dental Caries; Denture, Complete; Dexamethasone; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dielectric Spectroscopy; Diet, High-Fat; Dietary Fiber; Disease Models, Animal; Disease Progression; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Dog Diseases; Dogs; Dopaminergic Neurons; Double-Blind Method; Down-Regulation; Doxorubicin; Drug Carriers; Drug Design; Drug Interactions; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Dry Powder Inhalers; Dust; E2F1 Transcription Factor; Ecosystem; Education, Nursing; Education, Nursing, Baccalaureate; Electric Impedance; Electricity; Electrocardiography; Electrochemical Techniques; Electrochemistry; Electrodes; Electrophoresis, Polyacrylamide Gel; Endoplasmic Reticulum; Endothelial Cells; Environmental Monitoring; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Estrogen Receptor Modulators; Europe; Evoked Potentials, Auditory, Brain Stem; Exosomes; Feasibility Studies; Female; Ferricyanides; Ferrocyanides; Fibrinogen; Finite Element Analysis; Fistula; Fluorescent Dyes; Fluorides, Topical; Fluorodeoxyglucose F18; Fluticasone; Follow-Up Studies; Food Contamination; Food Microbiology; Foods, Specialized; Forensic Medicine; Frail Elderly; France; Free Radicals; Fresh Water; Fungi; Fungicides, Industrial; Galactosamine; Gastrointestinal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Gingival Hemorrhage; Glioblastoma; Glioma; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucose; Glucose Transport Proteins, Facilitative; Glucosides; Glutamine; Glycolysis; Gold; GPI-Linked Proteins; Gram-Negative Bacteria; Gram-Positive Bacteria; Graphite; Haplotypes; HCT116 Cells; Healthy Volunteers; Hearing Loss; Heart Failure; Hedgehog Proteins; HEK293 Cells; HeLa Cells; Hemodynamics; Hemorrhage; Hepatocytes; Hippo Signaling Pathway; Histone Deacetylases; Homeostasis; Hospital Mortality; Hospitalization; Humans; Hydantoins; Hydrazines; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydroxylamines; Hypoglycemic Agents; Immunity, Innate; Immunoglobulin G; Immunohistochemistry; Immunologic Factors; Immunomodulation; Immunophenotyping; Immunotherapy; Incidence; Indazoles; Indonesia; Infant; Infant, Newborn; Infarction, Middle Cerebral Artery; Inflammation; Injections, Intramuscular; Insecticides; Insulin-Like Growth Factor I; Insurance, Health; Intention to Treat Analysis; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Intrauterine Devices; Intrauterine Devices, Copper; Iron; Ischemia; Jordan; Keratinocytes; Kidney; Kidney Diseases; Kir5.1 Channel; Klebsiella Infections; Klebsiella pneumoniae; Lab-On-A-Chip Devices; Laparoscopy; Lasers; 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Bladder cancer is a highly prevalent tumor, requiring the urgent development of novel therapies, especially for locally advanced and metastatic disease. Nintedanib is a potent antifibrotic angio-kinase inhibitor, which has shown clinical efficacy in combination with chemotherapy in patients with locally advanced muscle-invasive bladder cancer. Nintedanib inhibits fibroblast growth factor receptors (FGFRs), validated targets in patients with bladder cancer harboring FGFR3/2 genetic alterations. Here, we aimed at studying its mechanisms of action to understand therapy resistance, identify markers predictive of response, and improve the design of future clinical trials. We have used a panel of genetically well-characterized human bladder cancer cells to identify the molecular and transcriptomic changes induced upon treatment with nintedanib, in vitro and in vivo, at the tumor and stroma cell levels. We showed that bladder cancer cells display an intrinsic resistance to nintedanib treatment in vitro, independently of their FGFR3 status. However, nintedanib has higher antitumor activity on mouse xenografts. We have identified PI3K activation as a resistance mechanism against nintedanib in bladder cancer and evidenced that the combination of nintedanib with the PI3K inhibitor alpelisib has synergistic antitumor activity. Treatment with this combination is associated with cell-cycle inhibition at the tumoral and stromal levels and potent nontumor cell autonomous effects on α-smooth muscle actin-positive tumor infiltrating cells and tumor vasculature. The combination of nintedanib with PI3K inhibitors not only reversed bladder cancer resistance to nintedanib but also enhanced its antiangiogenic effects.

Topics: Animals; Cell Line, Tumor; Humans; Lung Neoplasms; Mice; Phosphatidylinositol 3-Kinases; Stromal Cells; Urinary Bladder Neoplasms

The identification and targeting of actionable genomic alterations (AGA) have revolutionized the treatment of cancer in general and mostly for non-small cell lung cancer (NSCLC). We investigated whether in NSCLC patients PIK3CA mutations are actionable.. Chart review was performed of advanced NSCLC patients. PIK3CA mutated patients were analyzed as two groups: Group A: without any non-PIK3CA established AGA; Group B: with coexisting AGA. Group A was compared to a cohort of non-PIK3CA patients (group C), using t-test and chi-square. To evaluate the impact of PIK3CA mutation on outcome, we compared Group A survival to age/sex/histology matched cohort of non-PIK3CA mutated patients (group D) by Kaplan-Meier method. A patient with a PIK3CA mutation was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib).. Of a cohort of 1377 patients, 57 are PIK3CA mutated (4.1%). Group A: n-22, group B: n-35. Group A median age is 76 years, 16 (72.7%) men, 10 (45.5%) squamous, 4 (18.2%) never smokers. Two never-smoker female adenocarcinoma patients had solitary PIK3CA mutation. One of them was treated with a PI3Ka-isoform selective inhibitor BYL719 (Alpelisib), with rapid clinical and partial radiological improvement. Group B, compared with Group A, included younger patients (p = 0.030), more females (p = 0.028) and more adenocarcinoma cases (p < 0.001). Compared to group C, group A patients were older (p = 0.030) and had more squamous histology (p = 0.011).. In a small minority of NSCLC patients with PIK3CA mutation there are no additional AGA. PIK3CA mutations may be actionable in these cases.

Topics: Adenocarcinoma; Aged; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Catalytic Domain; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Lung Neoplasms; Male; Mutation

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Resistance, Neoplasm; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Mutation; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Quinazolines

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Death; Drug Administration Schedule; Drug Synergism; Erlotinib Hydrochloride; Female; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Quinolines; Software; Thiazoles; Triple Negative Breast Neoplasms

Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1.. We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3' mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines.. We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor.. Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.

Topics: Afatinib; Benzamides; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Class I Phosphatidylinositol 3-Kinases; Drug Resistance, Neoplasm; Drug Synergism; ErbB Receptors; Gene Amplification; Humans; Imidazoles; Lung Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-met; Sequence Analysis, RNA; Thiazoles; Triazines

Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cytokines; Drug Discovery; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Myeloid, Acute; Lung Neoplasms; Mice; Molecular Targeted Therapy; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proteomics; Xenograft Model Antitumor Assays

KRAS is frequently mutated in non-small cell lung cancers (NSCLC), resulting in activation of the MEK/ERK pathway. Because there are currently no drugs that target oncogenic KRAS, MEK inhibitors have been tested clinically as a possible treatment option for patients with NSCLC. However, KRAS-mutant cancers exhibit resistance to MEK inhibitors. Therefore, a combinational strategy is necessary for effective therapy. To address this, we investigated the therapeutic effects of combining selumetinib, a MEK1/2 inhibitor, with BYL719, a PI3Kα inhibitor.. We evaluated the effects of selumetinib and BYL719 in vitro and in vivo in NSCLC cell lines.. The combination of BYL719 and selumetinib resulted in synergistic cytotoxic activity compared with the single agents alone in KRAS-mutant NSCLC cells. At the molecular level, we found that AKT activation strongly influenced the sensitivity of KRAS-mutant NSCLC cells to selumetinib. Selumetinib upregulated phospho-AKT and phosphorylated BAD at ser136, which is responsible for intrinsic drug resistance in KRAS-mutant NSCLC cells. In contrast, inhibition of the PI3K/AKT pathway by BYL719 hindered selumetinib-induced BAD phosphorylation and increased the antitumor efficacy of selumetinib. Furthermore, selumetinib and BYL719 combination therapy showed synergy in the suppression of A549 xenograft tumor growth. On analysis of the pharmacodynamics, selumetinib and BYL719 together resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue.. Taken together, these data suggest that combination treatment with selumetinib and BYL719 is a promising therapeutic approach to overcoming resistance to MEK inhibitors.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzimidazoles; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Survival; Class I Phosphatidylinositol 3-Kinases; Drug Synergism; Female; Humans; Lung Neoplasms; MAP Kinase Kinase Kinases; Mice, Inbred BALB C; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Thiazoles; Tumor Burden; Xenograft Model Antitumor Assays

A prominent role in the pathogenesis of squamous cell carcinoma of the lung (SQCLC) has been attributed to the aberrant activation of the PI3K signaling pathway, due to amplification or mutations of the p110α subunit of class I phosphatidylinositol 3-kinase (PIK3CA) gene. The aim of our study was to determine whether different genetic alterations of PIK3CA affect the biologic properties of SQCLC and to evaluate the response to specific targeting agents in vitro and in vivo. The effects of NVP-BEZ235, NVP-BKM120, and NVP-BYL719 on two-dimensional/three-dimensional (2D/3D) cellular growth, epithelial-to-mesenchymal transition, and invasiveness were evaluated in E545K or H1047R PIK3CA-mutated SQCLC cells and in newly generated clones carrying PIK3CA alterations, as well as in a xenograft model. PIK3CA mutated/amplified cells showed increased growth rate and enhanced migration and invasiveness, associated with an increased activity of RhoA family proteins and the acquisition of a mesenchymal phenotype. PI3K inhibitors reverted this aggressive phenotype by reducing metalloproteinase production, RhoA activity, and the expression of mesenchymal markers, with the specific PI3K inhibitors NVP-BKM120 and NVP-BYL719 being more effective than the dual PI3K/mTOR inhibitor NVP-BEZ235. A xenograft model of SQCLC confirmed that PIK3CA mutation promotes the acquisition of a mesenchymal phenotype in vivo and proved the efficacy of its specific targeting drug NVP-BYL719 in reducing the growth and the expression of mesenchymal markers in xenotransplanted tumors. These data indicate that PIK3CA mutation/amplification may represent a good predictive feature for the clinical application of specific PI3K inhibitors in SQCLC patients.

Topics: Aminopyridines; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Class I Phosphatidylinositol 3-Kinases; Disease Models, Animal; Epithelial-Mesenchymal Transition; Humans; Imidazoles; Lung Neoplasms; Morpholines; Mutation; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Quinolines; Signal Transduction; Thiazoles; Xenograft Model Antitumor Assays