50,122 results match your criteria trials experimental

Application of retention modeling in chiral method development. I. Selection of isocratic composition for preparative separation with SFC.

J Chromatogr A 2021 Jun 19;1651:462308. Epub 2021 Jun 19.

Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.

Preparative chiral separations are carried out using chiral stationary-phases (CSP) employing isocratic composition mode to take advantage of stacking multiple injections within a single continuous operation. Development of the separation method, however, is not conducted directly in the preparative systems. Chromatographic systems at analytical scale are set up to screen multiple CSPs with various mobile-phases (MP) to detect a suitable CSP-MP combination. Read More

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Immunogenicity and safety of a live attenuated varicella vaccine in children 1-12 years of age: A randomized, blinded, controlled, non-inferiority phase 3 clinical trial.

Contemp Clin Trials 2021 Jun 19:106489. Epub 2021 Jun 19.

Institute of Expanded Programme on Immunization, Guizhou Provincial Center for Disease Control and Prevention, Guiyang 550004, Guizhou Province, People's Republic of China. Electronic address:

Objectives: To evaluate the immunogenicity and safety of a live attenuated varicella vaccine produced using a cell factory process.

Methods: In this randomized, blinded, controlled, non-inferiority phase 3 clinical trial conducted in Guizhou, healthy children aged 1-12 years were randomly assigned in a 2: 1 ratio to receive one dose of experimental or control vaccine. Physical examination and first blood collection were performed preimmunization on day 0. Read More

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Effect of the mediterranean diet on histological indicators and imaging tests in non-alcoholic fatty liver disease.

Gastroenterol Hepatol 2021 Jun 19. Epub 2021 Jun 19.

Escuela de Nutrición y Dietética. Facultad de Farmacia Universidad de Valparaíso, Chile. Electronic address:

Aim: To analyze the scientific evidence regarding to the effect of the Mediterranean diet on the imaging tests and biopsy characteristics in subjects with non-alcoholic fatty liver disease.

Methods: A bibliographic search was carried out in this narrative review in Pubmed and Web of Science databases, considering studies published between 2011-2020, in english or spanish, randomized clinical trials and observational studies in patients with a diagnosis of non-alcoholic fatty liver disease, in subjects over 18 years of age of both sexes.

Results: In the observational studies found, an inverse association between adherence to a Mediterranean diet and liver damage stands out, while in the intervention studies with measurement of liver biopsy a 4. Read More

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Identification of sex-specific biomarkers predicting new-onset heart failure.

ESC Heart Fail 2021 Jun 22. Epub 2021 Jun 22.

Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, 6229 HX, The Netherlands.

Aims: Heart failure (HF) is common in both men and women, yet disease pathophysiology, presentation, and progression differ between sexes. Studies addressing whether biomarkers predict new onset HF sex-specifically are scarce. This study therefore aims to test the sex-specificity of 252 protein biomarkers for new-onset HF. Read More

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Integrated docking and enhanced sampling-based selection of repurposing drugs for SARS-CoV-2 by targeting host dependent factors.

J Biomol Struct Dyn 2021 Jun 22:1-12. Epub 2021 Jun 22.

Prescience Insilico Private Limited, Bangalore, India.

Since the onset of global pandemic, the most focused research currently in progress is the development of potential drug candidates and clinical trials of existing FDA approved drugs for other relevant diseases, in order to repurpose them for the COVID-19. At the same time, several high throughput screenings of drugs have been reported to inhibit the viral components during the early course of infection but with little proven efficacies. Here, we investigate the drug repurposing strategies to counteract the coronavirus infection which involves several potential targetable host proteins involved in viral replication and disease progression. Read More

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Subgroup discovery in non-inferiority trials.

Stat Med 2021 Jun 22. Epub 2021 Jun 22.

Division of Biostatistics, Department of Epidemiology and Population, Albert Einstein College of Medicine, Bronx, New York, USA.

Approaches and guidelines for performing subgroup analysis to assess heterogeneity of treatment effect in clinical trials have been the topic of numerous papers in the statistical and clinical literature, but have been discussed predominantly in the context of conventional superiority trials. Concerns about treatment heterogeneity are the same if not greater in non-inferiority (NI) trials, especially since overall similarity between two treatment arms in a successful NI trial could be due to the existence of qualitative interactions that are more likely when comparing two active therapies. Even in unsuccessful NI trials, subgroup analyses can yield important insights about the potential reasons for failure to demonstrate non-inferiority of the experimental therapy. Read More

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Borrowing from supplemental sources to estimate causal effects from a primary data source.

Stat Med 2021 Jun 22. Epub 2021 Jun 22.

Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

The increasing multiplicity of data sources offers exciting possibilities in estimating the effects of a treatment, intervention, or exposure, particularly if observational and experimental sources could be used simultaneously. Borrowing between sources can potentially result in more efficient estimators, but it must be done in a principled manner to mitigate increased bias and Type I error. Furthermore, when the effect of treatment is confounded, as in observational sources or in clinical trials with noncompliance, causal effect estimators are needed to simultaneously adjust for confounding and to estimate effects across data sources. Read More

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Physiologically Based Pharmacokinetic Modeling of Meropenem in Preterm and Term Infants.

Clin Pharmacokinet 2021 Jun 22. Epub 2021 Jun 22.

Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 301 Pharmacy Lane, Campus Box #7569, Chapel Hill, NC, 27599-7569, USA.

Background: Meropenem is a broad-spectrum carbapenem antibiotic approved by the US Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections in infants < 3 months of age. The impact of maturation in glomerular filtration rate and tubular secretion by renal transporters on meropenem pharmacokinetics, and the effect on meropenem dosing, remains unknown. We applied physiologically based pharmacokinetic (PBPK) modeling to characterize the disposition of meropenem in preterm and term infants. Read More

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Gut microbiota and microbiome in schizophrenia.

Curr Opin Psychiatry 2021 Jun 21. Epub 2021 Jun 21.

Department of Psychiatry, Pomeranian Medical University, Szczecin Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Wroclaw, Poland.

Purpose Of Review: Accumulating evidence indicates that there are bidirectional interactions between the gut microbiota and functioning of the central nervous system. Consequently, it has been proposed that gut microbiota alterations might play an important role in the pathophysiology of schizophrenia. Therefore, in this article, we aimed to perform a narrative review of studies addressing gut microbiota alterations in patients with schizophrenia that were published in the years 2019-2020. Read More

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The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER Trial).

Perioper Med (Lond) 2021 Jun 22;10(1):23. Epub 2021 Jun 22.

Anaesthesia and Critical Care Research Area, NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Road, Southampton, UK.

Background: The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health.

Methods: Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Read More

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COVID-19 vaccination in pregnancy and postpartum.

J Matern Fetal Neonatal Med 2021 Jun 21:1-21. Epub 2021 Jun 21.

Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy.

Pregnant women were excluded from the initial phase 3 clinical trials of COVID-19 vaccines resulting in limited data on their efficacy and safety during pregnancy and postpartum. As a result, since December 2020, there has been conflicting advice from public health, governmental, and professional authorities on this matter. From the end of 2020 up to now, some consensus guidance has been published with a prevalent precautionary approach on the administration of vaccines in pregnant women, in breastfeeding ones, or for those who are planning a pregnancy (either spontaneously or with assisted technologies). Read More

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Meta-analysis-based systematic review of effect of traditional Chinese medicine intervention in treatment of diabetic nephropathy on thyroid function.

Ann Palliat Med 2021 Jun 16. Epub 2021 Jun 16.

Department of Neurology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: This research sought to systematically evaluate the clinical effects of traditional Chinese medicine (TCM) intervention in the treatment of diabetic nephropathy (DN) and analyze changes in thyroid function in patients with DN.

Methods: The PubMed, Embase, Medline, Ovid, Springer, and self-built databases were searched to screen literature on TCM intervention and the treatment of DN published from the establishment of the databases to January 1, 2021. The Cochrane Handbook for Systematic Reviews of Intervention 5. Read More

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Meta-analysis and systematic review of acupotomy combined with puncture and moxibustion in the treatment of knee osteoarthritis.

Ann Palliat Med 2021 Jun 21. Epub 2021 Jun 21.

Fourth Orthopedics, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.

Background: This study aimed to systematically evaluate the therapeutic effects of acupotomy combined with acupuncture and moxibustion on knee osteoarthritis (KOA), which was expected to provide a reference for clinical treatment of KOA using traditional Chinese medicine (TCM).

Methods: The databases PubMed, Embase, Medline, Ovid, and Springer were searched to retrieve randomized controlled trials (RCTs) on KOA treatment by acupotomy combined with acupuncture and moxibustion. The search time was set as from the date the database was established to 31 December 2020. Read More

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Underperformance of Contemporary Phase III Oncology Trials and Strategies for Improvement.

J Natl Compr Canc Netw 2021 Jun 21:1-7. Epub 2021 Jun 21.

1Richard A. and Susan F. Smith Cancer Center for Outcomes Research in Cardiology, Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center.

Background: Statistical testing in phase III clinical trials is subject to chance errors, which can lead to false conclusions with substantial clinical and economic consequences for patients and society.

Methods: We collected summary data for the primary endpoints of overall survival (OS) and progression-related survival (PRS) (eg, time to other type of event) for industry-sponsored, randomized, phase III superiority oncology trials from 2008 through 2017. Using an empirical Bayes methodology, we estimated the number of false-positive and false-negative errors in these trials and the errors under alternative P value thresholds and/or sample sizes. Read More

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Effect of hand loads on upper extremity muscle activity during pushing and pulling motions.

Appl Ergon 2021 Jun 19;96:103504. Epub 2021 Jun 19.

Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, South Korea. Electronic address:

Manual pushing or pulling with a hand tool is a coordinated action by various upper extremity muscles. The objective of this experimental study was to examine the effects of horizontal and vertical hand loads on upper extremity muscle activity during concentric pushing and pulling exertions. Twenty young female participants conducted repetitive pushing and pulling trials with three horizontal loads (1 kg, 2 kg, 3 kg) and two vertical loads (0. Read More

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Differences in oncological and toxicity outcomes between programmed cell death-1 and programmed cell death ligand-1 inhibitors in metastatic renal cell carcinoma: A systematic review and meta-analysis.

Cancer Treat Rev 2021 Jun 12;99:102242. Epub 2021 Jun 12.

Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Research Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. Electronic address:

Background: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients. Read More

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Neurosci Biobehav Rev 2021 Jun 18. Epub 2021 Jun 18.

Department of Neurology and ALS Centre, University of Piemonte Orientale, Maggiore della Carità Hospital, Corso Mazzini 18, Novara, 28100, Italy. Electronic address:

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease. Despite decades of research and many new insights into disease biology over the 150 years since the disease was first described, causative pathogenic mechanisms in ALS remain poorly understood, especially in sporadic cases. Our understanding of the role of the immune system in ALS pathophysiology, however, is rapidly expanding. Read More

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Acceptability of the oral hormonal male contraceptive prototype, 11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC), in a 28-day placebo-controlled trial.

Contraception 2021 Jun 18. Epub 2021 Jun 18.

Division of Endocrinology, Department of Medicine, The Lundquist Institute and Harbor UCLA Medical Center, Torrance, CA, USA.

Objective: To determine men's satisfaction with and the potential acceptability of 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) when used for 28 days as an experimental, once-daily, oral hormonal male contraceptive (HMC).

Study Design: We surveyed participants from a double-blind, randomized, placebo-controlled, phase 1 clinical trial, examining their experience with and willingness to use daily oral 11β-MNTDC for male contraception.

Results: Of 42 trial participants, 40 (30 11β-MNTDC, 10 placebo) completed baseline and end-of-treatment surveys. Read More

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[Realist protocol for implementing integrated care pathways in France (waivers 51)].

Ann Pharm Fr 2021 Jun 18. Epub 2021 Jun 18.

Réseau d'évaluation en économie de la santé (REES), 28 Rue D'Assas, Paris, France.

The paradox of real world researches supposedly conducted in real life is that they did not succeeded in freeing themselves from the techniques of the randomised trials which they pretended to escape. In the successionist perspective of classical experimental or quasi-experimental methods, the cause always precedes the effect in a linear manner, and any interference that is likely to threaten the stability of this relationship must be neutralised by mobilising the appropriate statistical techniques. In complex systems where everything moves at the same time due to multiple interrelationships that make it impossible to construct a counterfactual, these elements are no longer considered as confounding factors that need to be controlled, but as decisive factors in the smooth running of the experiment. Read More

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Prevalence and Phenotype Associations of Complement Factor I Mutations in Geographic Atrophy.

Hum Mutat 2021 Jun 21. Epub 2021 Jun 21.

Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Rare variants in the Complement Factor I (CFI) gene, associated with low serum Factor I (FI) levels, are strong risk factors for developing the advanced stages of Age-Related Macular Degeneration (AMD). No studies have been undertaken on the prevalence of disease-causing CFI mutations in patients with Geographic Atrophy (GA) secondary to AMD. A multi-centre, cross-sectional, non-interventional study was undertaken to identify the prevalence of pathogenic rare CFI gene variants in an unselected cohort of patients with GA and low FI levels. Read More

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Clinical and cost outcomes following genomics-informed treatment for advanced cancers.

Cancer Med 2021 Jun 21. Epub 2021 Jun 21.

Cancer Control Research, BC Cancer, Vancouver, Canada.

Background: Single-arm trials are common in precision oncology. Owing to the lack of randomized counterfactual, resultant data are not amenable to comparative outcomes analyses. Difference-in-difference (DID) methods present an opportunity to generate causal estimates of time-varying treatment outcomes. Read More

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Sensitive Measures of Cognition in Mild Cognitive Impairment.

J Alzheimers Dis 2021 Jun 14. Epub 2021 Jun 14.

Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.

Background: Sensitive measures of cognition are needed in preclinical and prodromal Alzheimer's disease (AD) to track cognitive change and evaluate potential interventions. Neurofibrillary tangle pathology in AD is first observed in Brodmann Area 35 (BA35), the medial portion of the perirhinal cortex. The importance of the perirhinal cortex for semantic memory may explain early impairments of semantics in preclinical AD. Read More

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Sodium-Glucose Co-transporter-2 Inhibitors and Nephroprotection in Diabetic Patients: More Than a Challenge.

Front Med (Lausanne) 2021 4;8:654557. Epub 2021 Jun 4.

Unit of Internal Medicine, Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Catanzaro, Italy.

Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Control of blood glucose and blood pressure (BP) reduces the risk of developing this complication, but once diabetic nephropathy is established, it is then only possible to slow its progression. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a novel class of oral hypoglycemic agents that increase urinary glucose excretion by suppressing glucose reabsorption at the renal proximal tubule. Read More

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Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia.

Front Oncol 2021 2;11:684396. Epub 2021 Jun 2.

Onco Hematology, Department of Oncology, Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.

Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related peptide family. It is secreted by endothelial cells and vascular smooth muscle cells, and is significantly upregulated by a number of stimuli. Moreover, ADM participates in the regulation of hematopoietic compartment, solid tumors and leukemias, such as acute myeloid leukemia (AML). Read More

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Hindsight: Review of Preclinical Disease Models for the Development of New Treatments for Uveal Melanoma.

J Cancer 2021 4;12(15):4672-4685. Epub 2021 Jun 4.

National Institute for Cellular Biotechnology, School of Biotechnology, Dublin City University, Dublin, Ireland.

The molecular, histopathological, genomic and transcriptomic characteristics of uveal melanoma (UM) have identified four molecular subgroups with different clinical outcomes. Despite the improvements in UM classification and biological pathology, current treatments do not reduce the occurrence of metastasis. The development of effective adjuvant and metastatic therapies for UM has been slow and extremely limited. Read More

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Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study.

Front Immunol 2021 2;12:624821. Epub 2021 Jun 2.

Renal Division, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States.

Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gluten-free and dairy-free (GF/DF) diet in children with SRNS. Read More

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Roles of Cholecystokinin in the Nutritional Continuum. Physiology and Potential Therapeutics.

Front Endocrinol (Lausanne) 2021 2;12:684656. Epub 2021 Jun 2.

Drug Discovery Biology theme, Monash Institute for Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.

Cholecystokinin is a gastrointestinal peptide hormone with important roles in metabolic physiology and the maintenance of normal nutritional status, as well as potential roles in the prevention and management of obesity, currently one of the dominant causes of direct or indirect morbidity and mortality. In this review, we discuss the roles of this hormone and its receptors in maintaining nutritional homeostasis, with a particular focus on appetite control. Targeting this action led to the development of full agonists of the type 1 cholecystokinin receptor that have so far failed in clinical trials for obesity. Read More

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Adverse Effects Associated With the Use of Antimalarials During The COVID-19 Pandemic in a Tertiary Care Center in Mexico City.

Front Pharmacol 2021 3;12:668678. Epub 2021 Jun 3.

Department of Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Antimalarial drugs were widely used as experimental therapies against COVID-19 in the initial stages of the pandemic. Despite multiple randomized controlled trials demonstrating unfavorable outcomes in both efficacy and adverse effects, antimalarial drugs are still prescribed in developing countries, especially in those experiencing recurrent COVID-19 crises (India and Brazil). Therefore, real-life experience and pharmacovigilance studies describing the use and side effects of antimalarials for COVID-19 in developing countries are still relevant. Read More

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Temporal Fluctuation of Mood in Gaming Task Modulates Feedback Negativity: EEG Study With Virtual Reality.

Front Hum Neurosci 2021 3;15:536288. Epub 2021 Jun 3.

Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology and Osaka University, Kobe, Japan.

Feedback outcomes are generally classified into positive and negative feedback. People often predict a feedback outcome with information that is based on both objective facts and uncertain subjective information, such as a mood. For example, if an action leads to good results consecutively, people performing the action overestimate the behavioral result of the next action. Read More

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Modeling colorectal cancers using multidimensional organoids.

Adv Cancer Res 2021 26;151:345-383. Epub 2021 Mar 26.

Department of Cellular and Molecular Medicine, University of California, San Diego, CA, United States; Rebecca and John Moore Comprehensive Cancer Center, University of California, San Diego, CA, United States; Department of Medicine, University of California, San Diego, CA, United States; Veterans Affairs Medical Center, San Diego, CA, United States; HUMANOID Center of Research Excellence (CoRE), University of California, San Diego, CA, United States. Electronic address:

Organoids have revolutionized cancer research as highly adaptable models that enable an array of experimental techniques to interrogate tissue morphology and function. Because they preserve the genetic, phenotypic, and behavioral traits of their source tissue, organoids have gained traction as the most relevant models for drug discovery, tracking therapeutic response and for personalized medicine. As organoids are indisputably becoming a mainstay of cancer research, this review specifically addresses how colon-derived organoids can be perfected as multidimensional, scalable, reproducible models of healthy, pre-neoplastic and neoplastic conditions of the colon and for use in high-throughput "Phase-0" human clinical trials-in-a-dish. Read More

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