13,398 results match your criteria lead substantial

Male and female reproductive fitness costs of an immune response in natural populations.

Evolution 2021 May 15. Epub 2021 May 15.

Department of Ecology & Evolutionary Biology, University of Connecticut, Storrs, CT, 06269.

Parasites can mediate host fitness both directly, via effects on survival and reproduction, or indirectly by inducing host immune defense with costly side-effects. The evolution of immune defense is determined by a complex interplay of costs and benefits of parasite infection and immune response, all of which may differ for male and female hosts in sexual lineages. Here, we examine fitness costs associated with an inducible immune defense in a fish-cestode host-parasite system. Read More

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On the robustness of latent class models for diagnostic testing with no gold standard.

Stat Med 2021 May 14. Epub 2021 May 14.

Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand.

It is difficult to estimate sensitivity and specificity of diagnostic tests when there is no gold standard. Latent class models have been proposed as a potential solution as they provide estimates without the need for a gold standard. Using a motivating example of the evaluation of point of care tests for leptospirosis in Tanzania, we show how a realistic violation of assumptions underpinning the latent class model can lead directly to substantial bias in the estimates of the parameters of interest. Read More

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Critical Review of Oncology Clinical Trial Design Under Non-proportional Hazards.

Crit Rev Oncol Hematol 2021 May 11:103350. Epub 2021 May 11.

Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, United States.

In trials of novel immuno-oncology drugs, the proportional hazards (PH) assumption often does not hold for the primary time-to-event (TTE) efficacy endpoint, likely due to the unique mechanism of action of these drugs. In practice, when it is anticipated that PH may not hold for the TTE endpoint with respect to treatment, the sample size is often still calculated under the PH assumption, and the hazard ratio (HR) from the Cox model is still reported as the primary measure of the treatment effect. Sensitivity analyses of the TTE data using methods that are suitable under non-proportional hazards (non-PH) are commonly pre-planned. Read More

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Improved efficiency and cost reduction in the emergency department by replacing contemporary sensitive with high-sensitivity cardiac troponin immunoassay.

Walter Serra

Acta Biomed 2021 May 12;92(2):e2021183. Epub 2021 May 12.

Cardiology Division, Cardio-Thoracic-Vascular Department, University Hospital of Parma, Parma, Italy..

The Authors planned this study to evaluate the impact of replacing a contemporary-sensitive with HS cTnI immunoassay on hospital and laboratory workload. The authors say that, 'Despite some evidence, the clinicians are still hesitant to replace the former so-called contemporary-sensitive methods with HS-cTn techniques, justifying this reluctance with concerns of overutilization, possible over diagnosis of cardiac injuries, overcrowding of emer-gency departments (EDs), and excess of cardiac invasive testing. Several factors have lead clinicians to use terms such as "troponin leak", "false-positive" troponin elevation, or "troponinemia". Read More

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The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on [Formula: see text] dynamics.

Sci Rep 2021 May 13;11(1):10268. Epub 2021 May 13.

Biomathematics Laboratory, Department of Applied Mathematics, School of Mathematical Sciences, Tarbiat Modares University, Tehran, Iran.

Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of [Formula: see text]-cell mass and alteration of [Formula: see text]-cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in [Formula: see text]-cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of [Formula: see text]-cell mass to [Formula: see text]-cell function in T2D, we make use of a comprehensive electrophysiological model of human [Formula: see text]-cell clusters. Read More

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Using a simple prescription gap to determine warfarin discontinuation can lead to substantial misclassification.

Thromb Haemost 2021 May 13. Epub 2021 May 13.

Brigham & Women's Hospital/Harvard Medical School, Boston, United States.

Background: Warfarin remains widely used and a key comparator in studies of other direct oral anticoagulants. As longer-than-needed warfarin prescriptions are often provided to allow for dosing adjustments according to International Normalized Ratios (INRs), the common practice of using a short allowable gap between dispensings to define warfarin discontinuation may lead to substantial misclassification of warfarin exposure. We aimed to quantify such misclassification and determine the optimal algorithm to define warfarin discontinuation. Read More

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Molecular scaffolds from mother nature as possible lead compounds in drug design and discovery against coronaviruses: A landscape analysis of published literature and molecular docking studies.

Microb Pathog 2021 May 10:104933. Epub 2021 May 10.

Department of Chemistry, Islamic University of Science and Technology, Awanti Pora, 192122, Jammu and Kashmir, India.

The recent outbreak of viral infection and its transmission has highlighted the importance of its slowdown for the safeguard of public health, globally. The identification of novel drugs and efficient therapies against these infectious viruses is need of the hour. The eruption of COVID-19 is caused by a novel acute respiratory syndrome virus SARS-CoV-2 which has taken the whole world by storm as it has transformed into a global pandemic. Read More

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Heme Detoxification in the Malaria Parasite: A Target for Antimalarial Drug Development.

Acc Chem Res 2021 May 13. Epub 2021 May 13.

Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa.

ConspectusOver the last century, malaria deaths have decreased by more than 85%. Nonetheless, there were 405 000 deaths in 2018, mostly resulting from infection. In the 21st century, much of the advance has arisen from the deployment of insecticide-treated bed nets and artemisinin combination therapy. Read More

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Genetics of atrial fibrillation - practical applications for clinical management: If not now, when and how?

Cardiovasc Res 2021 May 12. Epub 2021 May 12.

Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

The prevalence and economic burden of atrial fibrillation (AF) are predicted to more than double over the next few decades. In addition to anticoagulation and treatment of concomitant cardiovascular conditions, early and standardized rhythm control therapy reduces cardiovascular outcomes as compared with a rate control approach, favoring the restoration and maintenance of sinus rhythm safely. Current therapies for rhythm control of AF include anti-arrhythmic drugs (AAD) and catheter ablation (CA). Read More

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Ultralow contact resistance between semimetal and monolayer semiconductors.

Nature 2021 May 12;593(7858):211-217. Epub 2021 May 12.

Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.

Advanced beyond-silicon electronic technology requires both channel materials and also ultralow-resistance contacts to be discovered. Atomically thin two-dimensional semiconductors have great potential for realizing high-performance electronic devices. However, owing to metal-induced gap states (MIGS), energy barriers at the metal-semiconductor interface-which fundamentally lead to high contact resistance and poor current-delivery capability-have constrained the improvement of two-dimensional semiconductor transistors so far. Read More

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Implementing a digital health model of care in Australian youth mental health services: protocol for impact evaluation.

BMC Health Serv Res 2021 May 12;21(1):452. Epub 2021 May 12.

The University of Sydney, Brain and Mind Centre, 94 Mallett St, Camperdown, Sydney, NSW, 2050, Australia.

Background: The World Economic Forum has recently highlighted substantial problems in mental health service provision and called for the rapid deployment of smarter, digitally-enhanced health services as a means to facilitate effective care coordination and address issues of demand. In mental health, the biggest enabler of digital solutions is the implementation of an effective model of care that is facilitated by integrated health information technologies (HITs); the latter ensuring the solution is easily accessible, scalable and sustainable. The University of Sydney's Brain and Mind Centre (BMC) has developed an innovative digital health solution - delivered through the Youth Mental Health and Technology Program - which incorporates two components: 1) a highly personalised and measurement-based (data-driven) model of youth mental health care; and 2) an industrial grade HIT registered on the Australian Register of Therapeutic Goods. Read More

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Long-term impact of a ten-year intervention program on human and canine Trypanosoma cruzi infection in the Argentine Chaco.

PLoS Negl Trop Dis 2021 May 12;15(5):e0009389. Epub 2021 May 12.

Laboratorio de Eco-Epidemiología, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.

Background: Interruption of domestic vector-borne transmission of Trypanosoma cruzi is still an unmet goal in several American countries. In 2007 we launched a long-term intervention program aimed to suppress house infestation with the main domestic vector in southern South America (Triatoma infestans) and domestic transmission in Pampa del Indio, a resource-constrained, hyperendemic municipality with 1446 rural houses inhabited by Creole and indigenous people, in the Argentine Chaco ecoregion. Here, we assessed whether the 10-year insecticide-based program combined with community mobilization blocked vector-borne domestic transmission of T. Read More

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Racial/Ethnic Disparities In COVID-19 Exposure Risk, Testing, And Cases At The Subcounty Level In California.

Health Aff (Millwood) 2021 May 12:101377hlthaff202100098. Epub 2021 May 12.

Jeremy D. Goldhaber-Fiebert is an associate professor in the Centers for Health Policy and Primary Care and Outcomes Research, Stanford Health Policy, Freeman Spogli Institute for International Studies and the Stanford School of Medicine, Stanford University.

With a population of forty million and substantial geographic variation in sociodemographics and health services, California is an important setting in which to study disparities. Its population (37.5 percent White, 39. Read More

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Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype.

Nat Commun 2021 May 11;12(1):2678. Epub 2021 May 11.

Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.

Intellectual disability (ID) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders and are characterized by substantial impairment in intellectual and adaptive functioning, with their genetic and molecular basis remaining largely unknown. Here, we identify biallelic variants in the gene encoding one of the Elongator complex subunits, ELP2, in patients with ID and ASD. Modelling the variants in mice recapitulates the patient features, with brain imaging and tractography analysis revealing microcephaly, loss of white matter tract integrity and an aberrant functional connectome. Read More

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Specialty knowledge and competency standards for pharmacotherapy for adult obsessive-compulsive disorder.

Psychiatry Res 2021 Mar 4;300:113853. Epub 2021 Mar 4.

Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, United States.

Obsessive-compulsive disorder (OCD) affects approximately one person in 40 and causes substantial suffering. Evidence-based treatments can benefit many; however, optimal treatment can be difficult to access. Diagnosis is frequently delayed, and pharmacological and psychotherapeutic interventions often fail to follow evidence-based guidelines. Read More

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Effect of community-led delivery of HIV self-testing on HIV testing and antiretroviral therapy initiation in Malawi: A cluster-randomised trial.

PLoS Med 2021 May 11;18(5):e1003608. Epub 2021 May 11.

Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.

Background: Undiagnosed HIV infection remains substantial in key population subgroups including adolescents, older adults, and men, driving ongoing transmission in sub-Saharan Africa. We evaluated the impact, safety, and costs of community-led delivery of HIV self-testing (HIVST), aiming to increase HIV testing in underserved subgroups and stimulate demand for antiretroviral therapy (ART).

Methods And Findings: This cluster-randomised trial, conducted between October 2018 and July 2019, used restricted randomisation (1:1) to allocate 30 group village head clusters in Mangochi district, Malawi to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. Read More

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Phylogeographic model selection using convolutional neural networks.

Mol Ecol Resour 2021 May 11. Epub 2021 May 11.

Department of Evolution, Ecology and Organismal Biology, The Ohio State University, 318 W. 12th Ave, Columbus, OH, 43210, USA.

The discipline of phylogeography has evolved rapidly in terms of the analytical toolkit used to analyze large genomic datasets. Despite substantial advances, analytical tools that could potentially address the challenges posed by increased model complexity have not been fully explored. For example, deep learning techniques are underutilized for phylogeographic model selection. Read More

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A Nutrition-Sensitive Agroecology Intervention in Rural Tanzania Increases Children's Dietary Diversity and Household Food Security But Does Not Change Child Anthropometry: Results from a Cluster-Randomized Trial.

J Nutr 2021 May 11. Epub 2021 May 11.

Department of Anthropology, Northwestern University, Evanston, IL, USA.

Background: There are urgent calls for the transformation of agriculture and food systems to address human and planetary health issues. Nutrition-sensitive agriculture and agroecology promise interconnected solutions to these challenges, but evidence of their impact has been limited.

Objectives: In a cluster-randomized trial (NCT02761876), we examined whether a nutrition-sensitive agroecology intervention in rural Tanzania could improve children's dietary diversity. 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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Forecasting transitions in the state of food security with machine learning using transferable features.

Sci Total Environ 2021 Apr 27;786:147366. Epub 2021 Apr 27.

Department of Experimental Psychology, Utrecht University, the Netherlands.

Food insecurity is a growing concern due to man-made conflicts, climate change, and economic downturns. Forecasting the state of food insecurity is essential to be able to trigger early actions, for example, by humanitarian actors. To measure the actual state of food insecurity, expert and consensus-based approaches and surveys are currently used. Read More

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The promise of crowdfunding to finance R&D of novel diagnostics and therapeutics for incurable diseases that are underfunded.

Drug Discov Today 2021 May 7. Epub 2021 May 7.

University College London, School of Pharmacy, London, UK.

The level of funding available for research and development (R&D) of diagnostics (D) and therapeutics (T) for underfunded incurable diseases varies and is not associated with the extent of their disease burden. Crowdfunding is a promising way to increase funding for R&D of D&T for incurable diseases such as Alzheimer's and Parkinson's disease that are underfunded, which has not been exploited to its full capacity. Investing into efforts to educate patients and researchers about its prospective is a worthwhile endeavor, which could lead to the generation of substantial new capital to finance the development of novel therapeutics for these diseases. Read More

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VEXAS Syndrome.

Blood 2021 May 10. Epub 2021 May 10.

NHLBI, NIH, Bethesda, Maryland, United States.

VEXAS syndrome is a monogenic disease of adulthood caused by somatic mutations in UBA1 in hematopoietic progenitor cells. Patients present with a range of inflammatory and hematologic symptoms (Visual Abstract). Myeloid-driven autoinflammation and progressive bone marrow failure lead to substantial morbidity and mortality. Read More

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Practical and Clinical Approaches Using Pacing to Improve Selfregulation in Special Populations such as Children and People with Mental Health or Learning Disabilities.

J Rehabil Med Clin Commun 2021 4;4:1000058. Epub 2021 May 4.

School of Exercise and Nutrition Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.

For special populations such as people with a mental health issue or learning disability, a disconnect between the ability to accurately monitor and regulate exercise behaviour can lead to reduced levels of physical activity, which, in turn, is associated with additional physical or mental health problems. Activity pacing is a strategy used in clinical settings to address issues of pain amelioration, while self-pacing research is now well addressed in sport and exercise science literature. It has been proposed recently that these overlapping areas of investigation collectively support the development of self-regulatory, lifestyle exercise skills across broad population groups. Read More

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Cerebrotendinous Xanthomatosis: Molecular Pathogenesis, Clinical Spectrum, Diagnosis, and Disease-Modifying Treatments.

J Atheroscler Thromb 2021 May 8. Epub 2021 May 8.

Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder caused by mutations in the CYP27A1 gene, which encodes the mitochondrial enzyme sterol 27-hydroxylase. Decreased sterol 27-hydroxylase activity results in impaired bile acid synthesis, leading to reduced production of bile acids, especially chenodeoxycholic acid (CDCA), as well as elevated serum cholestanol and urine bile alcohols. The accumulation of cholestanol and cholesterol mainly in the brain, lenses, and tendons results in the characteristic clinical manifestations of CTX. Read More

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Localization of Deep Ischemia and Hemorrhage in Preterm Infants' Head with Near-Infrared Optical Tomography: A Numerical Case Study.

Adv Exp Med Biol 2021 ;1269:131-136

Biomedical Optics Research Laboratory (BORL), Department of Neonatology, University Hospital Zürich and University of Zürich, Zurich, Switzerland.

Background And Aim: Preterm infants have a high incidence of brain lesions that may lead to long-term disabilities. Early diagnosis of cerebral ischemia and hemorrhage may enable protection of the brain by prevention or neuroprotective treatment. Our recently developed time-domain near-infrared optical tomography (TD NIROT) system provides images to diagnose neonatal brain injury. Read More

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Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents.

Eur J Med Chem 2021 Apr 28;221:113480. Epub 2021 Apr 28.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. Electronic address:

With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. Read More

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Improving and calibrating channel erosion simulation in the Water Erosion Prediction Project (WEPP) model.

J Environ Manage 2021 May 5;291:112616. Epub 2021 May 5.

Purdue University, Agricultural & Biological Engineering Department, West Lafayette, IN, USA; USDA-Agricultural Research Service, National Soil Erosion Research Laboratory, West Lafayette, IN, USA. Electronic address:

The Water Erosion Prediction Project (WEPP) model has been widely used to assess the impacts of management practices and climate change on runoff and soil loss at both hillslope and watershed scales. However, the representation of channel erosion processes in WEPP has not been changed significantly since it was released. The current (WEPP v2012. Read More

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The Impact of Intensifying Prostate Cancer Screening in Black Men: A Model-Based Analysis.

J Natl Cancer Inst 2021 May 8. Epub 2021 May 8.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Black men in the United States have markedly higher rates of prostate cancer than the general population. National guidelines for prostate-specific antigen (PSA) screening do not provide clear guidance for this high-risk population. The purpose of this study is to estimate the benefit and harm of intensified PSA screening in Black men. Read More

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Suppression of Epithelial to Mesenchymal Transition Markers in Mouse Lens by a Smad7-based Recombinant Protein.

Chem Biol Interact 2021 May 4:109495. Epub 2021 May 4.

Department of Ophthalmology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, 80045, United States; Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, 80045, United States. Electronic address:

Cataracts, a clouding of the eye lens, are a leading cause of visual impairment and are responsible for one of the most commonly performed surgical procedures worldwide. Although generally safe and effective, cataract surgery can lead to a secondary lens abnormality due to transition of lens epithelial cells to a mesenchymal phenotype (EMT) and opacification of the posterior lens capsular bag. Occurring in up to 40% of cataract cases over time, posterior capsule opacification (PCO) introduces additional treatment costs and reduced quality of life for patients. Read More

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How Can Clinical Outcomes among Adolescents Living with HIV in Ethiopia be Improved? Healthcare Professionals' Perspectives.

Compr Child Adolesc Nurs 2021 May 7:1-10. Epub 2021 May 7.

Department of Health Sciences, Lund University, Lund, Sweden.

While successes in the prevention of mother-to-child transmission program are believed to lead to substantial reductions in new perinatal infections, new sexually acquired infections among the older adolescent group seem to fuel the HIV epidemic. That is why adolescents are the only age group in which an increase in new HIV infections was reported in the latest global HIV progress update. Increase in the number of perinatally HIV infected children growing to adolescence adds to this pool. Read More

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