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Haemodynamic effects of PAH-targeted therapies in pulmonary hypertension due to lung disease: A systematic review and meta-analysis.

Pulm Pharmacol Ther 2021 May 9:102036. Epub 2021 May 9.

Department of Cardiology, AHEPA University Hospital, Thessaloniki, Greece. Electronic address:

Background: Pulmonary hypertension (PH) is a negative predictor in patients with lung disease and/or hypoxia (group 3 PH). Current guidelines do not endorse the use of targeted therapies for pulmonary arterial hypertension (PAH) in patients with group 3 PH, due to lack of strong evidence. However, a variety of studies have examined the effect of PAH-targeted therapies in group 3 PH with mixed methods and conflicting results. Read More

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General practice responses to opioid prescribing feedback: a qualitative process evaluation.

Br J Gen Pract 2021 May 11. Epub 2021 May 11.

University of Leeds, Academic Unit of Primary Care, Leeds, United Kingdom.

Background: The rise in opioid prescribing in primary care represents a significant public health challenge, associated with increased psychosocial problems, hospitalisations and mortality. We developed and implemented an evidence-based bi-monthly feedback intervention to reduce opioid prescribing targeting 316 general practices in West Yorkshire over one year.

Aim: To understand how general practice staff received and responded to the feedback intervention. Read More

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Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma.

J Clin Oncol 2021 May 12:JCO2100612. Epub 2021 May 12.

James Graham Brown Cancer Center, University of Louisville, Louisville, KY.

Purpose: Effective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes has demonstrated efficacy in advanced melanoma. Lifileucel is an autologous, centrally manufactured tumor-infiltrating lymphocyte product. Read More

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A Within-Subject Pilot Feasibility Study of a Gambling Specific SBIRT Intervention Delivered in an Urban HIV/Primary Clinic.

J Gambl Stud 2021 May 12. Epub 2021 May 12.

College of Medicine, University of Kentucky, Lexington, USA.

Background: Although there are few interventions available to provide screening and brief intervention targeted toward problematic gambling, Screening, Brief Intervention and Referral to Treatment (SBIRT) is an evidence-based intervention that has demonstrated effectiveness in reducing gambling behaviors.

Methods: The goal of this pilot study was to evaluate the feasibility, acceptability and preliminary outcomes of a gambling specific SBIRT intervention in a medical setting. Fifteen participants were recruited from an urban HIV/Primary Care clinic to receive the gambling specific SBIRT intervention delivered by 3 clinicians. Read More

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A Global Vista of the Epigenomic State of the Mouse Submandibular Gland.

J Dent Res 2021 May 12:220345211012000. Epub 2021 May 12.

Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Read More

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Dual contrast agents for fluorescence and photoacoustic imaging: evaluation in a murine model of prostate cancer.

Nanoscale 2021 May 12. Epub 2021 May 12.

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21218, USA.

Prostate-specific membrane antigen (PSMA) is a promising diagnostic and therapeutic target for prostate cancer (PC). Poly(amidoamine) [PAMAM] dendrimers serve as versatile scaffolds for imaging agents and drug delivery that can be tailored to different sizes and compositions depending upon the application. We have developed PSMA-targeted PAMAM dendrimers for real-time detection of PC using fluorescence (FL) and photoacoustic (PA) imaging. Read More

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Limited brain metastases: a narrative review.

Ann Palliat Med 2021 Apr 26. Epub 2021 Apr 26.

Department of Radiation Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Limited brain metastases refer to an oligometastatic state in the brain for which focal therapy with stereotactic radiosurgery (SRS) is appropriate. The definition of what is considered "limited" for brain metastases, however, is not well defined. Multiple recent randomized trials show that metastasis-directed therapy with surgery or stereotactic radiation can prolong survival for patients with 1-5 metastases from various primary tumors, but patients with untreated brain metastases were largely excluded from these trials. Read More

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Cadmium inhibits neural stem/progenitor cells proliferation via MitoROS-dependent AKT/GSK-3β/β-catenin signaling pathway.

J Appl Toxicol 2021 May 11. Epub 2021 May 11.

School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, China.

Cadmium (Cd) is a toxic heavy metal widely found in the environment. Cd is also a potential neurotoxicant, and its exposure is associated with impairment of cognitive function. However, the underlying mechanisms by which Cd induces neurotoxicity are unclear. Read More

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Implementing Volume-targeted Ventilation to Decrease Hypocarbia in Extremely Low Birth Weight Infants during the First Week of Life: A Quality Improvement Project.

Pediatr Qual Saf 2021 May-Jun;6(3):e398. Epub 2021 May 5.

Department of Pediatrics, Brody School of Medicine, East Carolina University, Greenville, N.C.

Hypocarbia in neonates increases the risk of poor neurodevelopmental outcomes. Volume-targeted ventilation (VTV) is associated with decreased hypocarbia and other respiratory morbidities. We noticed a high incidence of hypocarbia in extremely low birth weight (ELBW; <1,000 g) neonates in our Neonatal Intensive Care Unit. Read More

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A pilot study on exertional tasks with physiological measures designed for the assessment of military concussion.

Concussion 2021 Apr 9;6(1):CNC88. Epub 2021 Apr 9.

Department of Allied Health Sciences, Curriculum in Human Movement Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Background: Guidelines for clinicians treating military concussion recommend exertional testing before return-to-duty, yet there is currently no standardized task or inclusion of an objective physiological measure like heart rate variability (HRV).

Methodology & Results: We pilot-tested two clinically feasible exertional tasks that include HRV measures and examined reliability of a commercially available heart rate monitor. Testing healthy participants confirmed that the 6-min step test and 2-min pushup test evoked the targeted physiological response, and the Polar H10 was reliable to the gold-standard electrocardiogram. Read More

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Clustering Complex Chronic Patients: A Cross-Sectional Community Study From the General Practitioner's Perspective.

Int J Integr Care 2021 Apr 19;21(2). Epub 2021 Apr 19.

University of Vic, Faculty of Medicine, Spain.

Objective: Characterize subgroups of Complex Chronic Patients (CCPs) with cluster analysis from the general practitioner's perspective.

Study Design: Cross-sectional population-based study.

Setting: Three Primary Care urban centres for a reference population of 43,647 inhabitants over 14 years old in Sabadell, Catalonia, Spain. Read More

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[Hygiene measures in antenatal care].

Gynakologe 2021 May 7:1-11. Epub 2021 May 7.

Klinik für Frauenheilkunde und Geburtshilfe, Klinikum Kempten und Immenstadt, Klinikverbund Allgäu, Robert-Weixler-Str. 50, 87439 Kempten, Deutschland.

Background: The prevention of infections in the obstetric care of pregnant women is paramount, on the one hand with regard to pathogens of congenital infections and on the other hand due to the association of maternal infections with premature delivery.

Objectives: Which measures are recommended for effective prevention of bacterial and viral diseases relevant to obstetrics?

Materials And Methods: Literature search on hygiene measures in terms of preventing transmission of infection.

Results: The physiological vaginal flora of the pregnant woman is a fundamental factor in natural defence against infection. Read More

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Combining radiomic phenotypes of non-small cell lung cancer with liquid biopsy data may improve prediction of response to EGFR inhibitors.

Sci Rep 2021 May 11;11(1):9984. Epub 2021 May 11.

Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Among non-small cell lung cancer (NSCLC) patients with therapeutically targetable tumor mutations in epidermal growth factor receptor (EGFR), not all patients respond to targeted therapy. Combining circulating-tumor DNA (ctDNA), clinical variables, and radiomic phenotypes may improve prediction of EGFR-targeted therapy outcomes for NSCLC. This single-center retrospective study included 40 EGFR-mutant advanced NSCLC patients treated with EGFR-targeted therapy. Read More

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Esophageal metastases from primary lung cancer: a case report.

J Med Case Rep 2021 May 12;15(1):265. Epub 2021 May 12.

Department of Cardiothoracic Surgery, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210000, Jiangsu, China.

Background: Primary lung cancer is one of the most frequently diagnosed cancers. The common metastatic sites are the liver, bones, brain, adrenal glands and central nervous system. However, gastrointestinal metastases, particularly esophageal metastases, from lung cancer are rare. Read More

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Medication risk management and health equity in New Zealand general practice: a retrospective cross-sectional study.

Int J Equity Health 2021 May 11;20(1):119. Epub 2021 May 11.

Department of General Practice and Rural Health, Otago Medical School - Dunedin Campus, University of Otago, Dunedin, New Zealand.

Background: Despite an overt commitment to equity, health inequities are evident throughout Aotearoa New Zealand. A general practice electronic alert system was developed to notify clinicians about their patient's risk of harm due to their pre-existing medical conditions or current medication. We aimed to determine whether there were any disparities in clinician action taken on the alert based on patient ethnicity or other demographic factors. Read More

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Estimated proportion of an urban academic emergency department patient population eligible for HIV preexposure prophylaxis.

Am J Emerg Med 2021 May 4;48:198-202. Epub 2021 May 4.

University of Cincinnati, Department of Emergency Medicine, Cincinnati, OH, USA; Center for Addiction Research, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Objective: Pre-exposure prophylaxis (PrEP) is a highly effective but underutilized method of HIV prevention. Emergency departments (EDs) have access to at-risk populations meeting CDC eligibility criteria for PrEP. Characterizing this population could help motivate, develop, and implement ED interventions to promote PrEP uptake. Read More

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Cost-effectiveness evidence of mental health prevention and promotion interventions: A systematic review of economic evaluations.

PLoS Med 2021 May 11;18(5):e1003606. Epub 2021 May 11.

Deakin University, Deakin Health Economics, Institute for Health Transformation, School of Health and Social Development, Geelong, Australia.

Background: The prevention of mental disorders and promotion of mental health and well-being are growing fields. Whether mental health promotion and prevention interventions provide value for money in children, adolescents, adults, and older adults is unclear. The aim of the current study is to update 2 existing reviews of cost-effectiveness studies in this field in order to determine whether such interventions are cost-effective. Read More

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Using an electronic health record alert to prompt blood-borne virus testing in primary care.

AIDS 2021 May 10. Epub 2021 May 10.

Centre for Clinical Infection, The James Cook University Hospital, Middlesbrough TS4 3BW, UK Leadgate Medical Centre, Consett, DH8 6DP, UK Department of Psychology, Teesside University, Middlesbrough TS1 3BX, UK.

Background: Late diagnosis of HIV, hepatitis B (HBV) and hepatitis C (HCV) remains relatively common in the UK and many people who present late have missed opportunities for testing in primary care. The objective was to assess the effectiveness and acceptance of a prototype application (BBV_TP1), embedded in a primary care electronic health record (EHR), to increase real-time blood-borne virus (BBV) testing.

Methods: This prospective cohort study assessed BBV_TP1 in 14 general practices in North East England, in comparison to 54 similar practices in 2019. Read More

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The liver metastatic niche: modelling the extracellular matrix in metastasis.

Dis Model Mech 2021 Apr 15;14(4). Epub 2021 Apr 15.

CRUK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.

Dissemination of malignant cells from primary tumours to metastatic sites is a key step in cancer progression. Disseminated tumour cells preferentially settle in specific target organs, and the success of such metastases depends on dynamic interactions between cancer cells and the microenvironments they encounter at secondary sites. Two emerging concepts concerning the biology of metastasis are that organ-specific microenvironments influence the fate of disseminated cancer cells, and that cancer cell-extracellular matrix interactions have important roles at all stages of the metastatic cascade. Read More

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COVID-19 and the multidisciplinary care of patients with lung cancer: an evidence-based review and commentary.

Br J Cancer 2021 May 10. Epub 2021 May 10.

Lungs For Living Research Centre, University College London and Department of Thoracic Medicine, University College London Hospital, London, UK.

Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. Read More

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Outpatient prescribing pattern for acute bronchitis in primary healthcare settings in China.

NPJ Prim Care Respir Med 2021 May 10;31(1):24. Epub 2021 May 10.

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Inappropriate prescribing for acute bronchitis in primary healthcare settings (PHSs) is commonly seen worldwide. Here we describe the prescribing patterns and antibiotic use for acute bronchitis in PHSs across China. We conduct a nationwide cross-sectional survey to collect outpatient prescriptions from PHSs in 2017. Read More

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Establishment and preclinical application of a patient-derived xenograft model for uterine cancer.

Gynecol Oncol 2021 May 7. Epub 2021 May 7.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

Background: The patient-derived xenograft (PDX) model is a promising translational platform for duplicating the characteristics of primary tumors. Here, we established and characterized PDX models of uterine cancer to demonstrate their utility for preclinical drug testing.

Materials And Methods: We generated PDX tumors surgically derived from 58 cases of uterine cancer. Read More

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Whole School SEND (WSS) Review: study protocol for a two-arm pragmatic parallel cluster randomised controlled trial in 160 English secondary schools.

Trials 2021 May 10;22(1):333. Epub 2021 May 10.

Policy Evaluation and Research Unit, Manchester Metropolitan University, Manchester, UK.

Background: The trial will study the effects of the Whole School SEND Review on secondary school pupils in English mainstream education, to understand the impact of the intervention on academic attainment, wellbeing, and school attendance. The Review is designed to facilitate whole-school change through providing enhanced, intensive and sustained support and training in inclusive education for school special educational needs coordinators and leadership teams. The trial will have a specific focus on pupils designated as having special educational needs or disabilities. Read More

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Future of Allergic Rhinitis Management.

Ann Allergy Asthma Immunol 2021 May 7. Epub 2021 May 7.

Allergy Research Unit, Kingston Health Sciences Center - KGH Site, Kingston, ON, Canada; Department of Medicine, Queen's University, Kingston, ON, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada. Electronic address:

Objective: To present a comprehensive, clinically focused scoping review of therapeutic agents and practices comprising the future of allergic rhinitis (AR) management.

Data Sources: A review of the published literature was performed using the PubMed database, published abstracts and virtual presentations from scientific meetings, and posted results on ClinicalTrials.gov. Read More

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oColonic delivery of metronidazole-loaded capsules for local treatment of bacterial infections: a clinical pharmacoscintigraphy study.

Eur J Pharm Biopharm 2021 May 7. Epub 2021 May 7.

Clinical Pharmacology & Toxicology, University Hospital Basel, Basel, Switzerland.

Drug delivery to the colon offers great promise for local treatment of colonic diseases as it allows bypassing systemic absorption in the small intestine, thereby increasing luminal drug concentrations in the colon. The primary objective of this in vivo pharmaco-scintigraphy study was to assess the colon drug targeting accuracy of a metronidazole benzoate colonic drug delivery system intended for local treatment of Clostridioides difficile infections. Additionally, it was assessed if the concept of mucoadhesion would increase colonic residence time and promote higher drug bioavailability. Read More

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Hydrophobic and polar interactions of FDA-approved small protein kinase inhibitors with their target enzymes.

Authors:
Robert Roskoski

Pharmacol Res 2021 May 7:105660. Epub 2021 May 7.

Blue Ridge Institute for Medical Research 3754 Brevard Road, Suite 116, Box 19 Horse Shoe, North Carolina 28742-8814, United States. Electronic address:

Dysregulation and mutations of protein kinases play causal roles in many diseases including cancer. The KLIFS (kinase-ligand interaction fingerprint and structure) catalog includes 85 ligand binding-site residues occurring in both the small and large protein kinase lobes. Except for allosteric inhibitors, all FDA-approved drug-target enzyme complexes display hydrophobic interactions involving catalytic spine residue-6 (KLIFS-77), catalytic spine residue-7 (KLIFS-11), and catalytic spine residue-8 (KLIFS-15) within the small lobe and residues within the hinge-linker region (KLIFS-46-52). Read More

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Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Gastroenterol Hepatol 2021 May 7. Epub 2021 May 7.

Department of Intervention, Fujian Cancer Hospital, Fuzhou, China.

Background: Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma.

Methods: AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Read More

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Attitudes and beliefs of parents about routine childhood vaccination in Greece.

Hum Vaccin Immunother 2021 May 10:1-7. Epub 2021 May 10.

Department of Paediatrics, Medical School, University of Patras, Patras, Greece.

Vaccine hesitancy remains one of the 10 major global threats as per the WHO report in 2019. The aim of the present study is to assess attitudes and perceptions of vaccine hesitant parents in Greece with a view to implementing strategies to increase vaccine uptake. A cross-sectional questionnaire-based prospective survey was conducted between September 2019 and June 2020 on parents of children attending primary education in the city of Patras in Western Greece. Read More

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Identification of as the Key Gene Associated with Antivascular Endothelial Growth Factor Therapy in Glioblastoma Multiforme.

Genet Test Mol Biomarkers 2021 May 10. Epub 2021 May 10.

Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Vascular endothelial growth factors (VEGFs) are important for glioblastoma multiforme (GBM) growth and development. However, the effects of VEGF-targeting drugs in primary GBM remain poorly understood. We aimed to explore the key genes correlated with VEGF expression and prognosis and elucidate their potential implications in GBM anti-VEGF therapy. Read More

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Recruitment of solid lipid nanoparticles for the delivery of CRISPR/Cas9: primary evaluation of anticancer gene editing.

Nanomedicine (Lond) 2021 May 10. Epub 2021 May 10.

Izmir Biomedicine & Genome Center, Izmir, 35340, Turkey.

The CRISPR/Cas9 system is a promising gene-editing tool for various anticancer therapies; however, development of a biocompatible, nonviral and efficient delivery of CRISPR/Cas9 expression systems remains a challenge. Solid lipid nanoparticles (SLNs) were produced based on pseudo and 3D ternary plots. Obtained SLNs and their complexes with PX458 plasmid DNA were characterized and evaluated in terms of cytotoxicity and transfection efficiency. Read More

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