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Design Considerations for Macroencapsulation Devices for Stem Cell Derived Islets for the Treatment of Type 1 Diabetes.

Adv Sci (Weinh) 2021 Jun 21:e2100820. Epub 2021 Jun 21.

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Stem cell derived insulin producing cells or islets have shown promise in reversing Type 1 Diabetes (T1D), yet successful transplantation currently necessitates long-term modulation with immunosuppressant drugs. An alternative approach to avoiding this immune response is to utilize an islet macroencapsulation device, where islets are incorporated into a selectively permeable membrane that can protect the transplanted cells from acute host response, whilst enabling delivery of insulin. These macroencapsulation systems have to meet a number of stringent and challenging design criteria in order to achieve the ultimate goal of reversing T1D. Read More

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Efficacy of Daratumumab-Based Regimens Compared to Standard of Care in Transplant-Eligible Multiple Myeloma: A Meta-Analysis.

Cureus 2021 May 18;13(5):e15098. Epub 2021 May 18.

Critical Care, Mayo Clinic, Rochester, USA.

Daratumumab (dara) belongs to a class of monoclonal antibodies that target CD38 receptors expressed on multiple myeloma (MM) cells. It was first approved for MM treatment in 2015. The efficacy and safety of dara have been reported in many studies. Read More

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Phase Variation in HMW1A Controls a Phenotypic Switch in Haemophilus influenzae Associated with Pathoadaptation during Persistent Infection.

mBio 2021 Jun 22:e0078921. Epub 2021 Jun 22.

Instituto de Agrobiotecnología, Consejo Superior de Investigaciones Científicas (IdAB-CSIC)-Gobierno de Navarra, Mutilva, Spain.

Genetic variants arising from within-patient evolution shed light on bacterial adaptation during chronic infection. Contingency loci generate high levels of genetic variation in bacterial genomes, enabling adaptation to the stringent selective pressures exerted by the host. A significant gap in our understanding of phase-variable contingency loci is the extent of their contribution to natural infections. Read More

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2021 Update on airway management from the Anaesthesia Continuing Education Airway Management Special Interest Group.

Anaesth Intensive Care 2021 Jun 22:310057X20984784. Epub 2021 Jun 22.

Department of Anaesthesia, St James's Hospital, Dublin, Ireland.

Airway Management is the key for anaesthetists dealing with patients undergoing diagnostic procedures and surgical interventions. The present coronavirus pandemic underpins even more how important safe airway management is. It also highlights the need to apply stringent precautions to avoid infection and ongoing transmission to patients, anaesthetists and other healthcare workers (HCWs). Read More

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The East-West Divide in Response to COVID-19.

Engineering (Beijing) 2021 Jun 12. Epub 2021 Jun 12.

Independent consultant, Menlo Park, CA 94025, USA.

Coronavirus disease 2019 (COVID-19) death rates in the countries of the West exceed those in the countries of the East by factors ranging from 10-1 to 100-1. In this paper, we refer to the West as represented by United States plus the five most populous countries of Western Europe, and the East as the 15 countries of East Asia and Oceania that are members of the Regional Comprehensive Economic Partnership (RCEP). This paper argues that the currently available information points to the factors most responsible for this divide. Read More

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Initial Therapeutic Approaches to Patients with Multiple Myeloma.

Adv Ther 2021 Jun 18. Epub 2021 Jun 18.

Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, 200 First st SW, Rochester, MN, 55905, USA.

Multiple Myeloma (MM) is part of a spectrum of plasma cell disorders that may result in end organ damage. MM is subclassified into high and standard risk based on cytogenetic and laboratory markers. The treatment of newly diagnosed multiple myeloma is constantly changing with the advent of novel therapies. Read More

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Exposure to secondhand smoke is associated with increased left ventricular mass.

Tob Induc Dis 2021 4;19:43. Epub 2021 Jun 4.

Institute of Global Health and Human Ecology, School of Sciences and Engineering, The American University in Cairo, New Cairo, Egypt.

Introduction: Chronic hypertension is associated with left ventricular hypertrophy. Recent evidence suggests that secondhand smoke (SHS) exposure is associated with chronic hypertension, so we sought to examine the relationship between secondhand smoke exposure and electrocardiographic left ventricular (LV) mass among non-smokers.

Methods: This analysis included 4982 non-smoker participants from the Third National Health and Nutrition Examination (NHANES-III). Read More

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Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus.

PLoS One 2021 17;16(6):e0253393. Epub 2021 Jun 17.

Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, Bangladesh.

West Nile Virus (WNV) is a life threatening flavivirus that causes significant morbidity and mortality worldwide. No preventive therapeutics including vaccines against WNV are available for human use. In this study, immunoinformatics approach was performed to design a multi epitope-based subunit vaccine against this deadly pathogen. Read More

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SARS-CoV-2 variants and the so-called resistance to vaccines.

Medicina (B Aires) 2021 ;81(3):421-426

Comité de Redacción Medicina (B Aires), Buenos Aires, Argentina.

RNA viruses (except retroviruses) replicate by the action of an RNA-dependent RNA polymerase, which lacks a proofreading exonuclease and, consequently, errors may occur in each replication giving place to viral mutants. Depending on their fitness, these mutants either become extinct or thrive, spawning variants that escape the immune system. The most important SARS-CoV-2 mutations are those that alter the amino acid sequence in the viral S protein because this protein holds the key for the virus to enter the human cell. Read More

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The Serum Proteome and Ursodeoxycholic Acid Response in Primary Biliary Cholangitis.

Hepatology 2021 Jun 15. Epub 2021 Jun 15.

Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK.

Background And Aims: Stratified therapy has entered clinical practice in primary biliary cholangitis (PBC), with routine use of second-line therapy in non-responders to first-line therapy with ursodeoxycholic acid (UDCA). The mechanism for non-response to UDCA remains, however, unclear and we lack mechanistic serum markers. The UK-PBC study was established to explore the biological basis of UDCA non-response in PBC and to identify markers to enhance treatment. Read More

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Long-Term Effectiveness of Lurasidone in Pediatric Bipolar Depression: Response, Remission and Recovery.

CNS Spectr 2021 Apr;26(2):148

Sunovion Pharmaceuticals Inc., Marlborough, MA, USA.

Background: Bipolar disorder frequently has an early onset, with an estimated 1.8% prevalence of bipolar I disorder in children and adolescents. Childhood onset of bipolar disorder is typically associated with a chronic, severe, and disabling course of illness. Read More

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Deacylated tRNA Accumulation Is a Trigger for Bacterial Antibiotic Persistence Independent of the Stringent Response.

mBio 2021 Jun 15:e0113221. Epub 2021 Jun 15.

Department of Microbiology, The Ohio State University, Columbus, Ohio, USA.

Bacterial antibiotic persistence occurs when bacteria are treated with an antibiotic and the majority of the population rapidly dies off, but a small subpopulation enters into a dormant, persistent state and evades death. Diverse pathways leading to nucleoside triphosphate (NTP) depletion and restricted translation have been implicated in persistence, suggesting alternative redundant routes may exist to initiate persister formation. To investigate the molecular mechanism of one such pathway, functional variants of an essential component of translation (phenylalanyl-tRNA synthetase [PheRS]) were used to study the effects of quality control on antibiotic persistence. Read More

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RNA-Seq Transcriptome Analysis of Peripheral Blood From Cattle Infected With Across an Experimental Time Course.

Front Vet Sci 2021 28;8:662002. Epub 2021 May 28.

Animal Genomics Laboratory, UCD School of Agriculture and Food Science, UCD College of Health and Agricultural Sciences, University College Dublin, Dublin, Ireland.

Bovine tuberculosis, caused by infection with members of the complex, particularly , is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis of the host transcriptome to infection, particularly at the macrophage and peripheral blood level. In the present study, we have analysed the transcriptome of bovine whole peripheral blood samples collected at -1 week pre-infection and +1, +2, +6, +10, and +12 weeks post-infection time points. Read More

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Irradiation-induced sterility in an egg parasitoid and possible implications for the use of biological control in insect eradication.

Sci Rep 2021 Jun 10;11(1):12326. Epub 2021 Jun 10.

School of Biological Sciences, Auckland Mail Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.

Classical biological control is a pest control tool involving the release of imported natural enemies. The Sterile Insect Technique (SIT) comprises releasing sexually sterile insects of a pest into the wild population for suppression or eradication. Both these approaches are environmentally friendly and their combination can result in a synergistic impact on pest populations and improve eradication. Read More

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Disrupting hierarchical control of nitrogen fixation enables carbon-dependent regulation of ammonia excretion in soil diazotrophs.

PLoS Genet 2021 Jun 10;17(6):e1009617. Epub 2021 Jun 10.

Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom.

The energetic requirements for biological nitrogen fixation necessitate stringent regulation of this process in response to diverse environmental constraints. To ensure that the nitrogen fixation machinery is expressed only under appropriate physiological conditions, the dedicated NifL-NifA regulatory system, prevalent in Proteobacteria, plays a crucial role in integrating signals of the oxygen, carbon and nitrogen status to control transcription of nitrogen fixation (nif) genes. Greater understanding of the intricate molecular mechanisms driving transcriptional control of nif genes may provide a blueprint for engineering diazotrophs that associate with cereals. Read More

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Reply to Jindal et al.

Hepatology 2021 Jun 10. Epub 2021 Jun 10.

University of Toronto, Toronto, ON, Canada.

We thank Jindal and Sharma for their letter, which raised several points that we will clarify in this response(1). We studied biofluids in non-consecutive patients because of several stringent criteria needed for inclusion into the study: one of these being sample collection as close to admission as possible to reduce the impact of in-hospital treatments on metabolomics. In any multi-center cohort, outside of a strict prospective clinical trial of a narrow highly selected patient population, it is not possible to expect all centers to follow the same diagnostic/treatment algorithm as suggested. Read More

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Up-to-Date Role of CT/MRI LI-RADS in Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 31;8:513-527. Epub 2021 May 31.

Liver Imaging Group, Department of Radiology, University of California San Diego, La Jolla, CA, USA.

Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide and a major healthcare burden in most societies. Computed tomography (CT) and magnetic resonance imaging (MRI) play a pivotal role in the medical care of patients with or at risk for hepatocellular carcinoma (HCC). When stringent imaging criteria are fulfilled, CT and MRI allow for diagnosis, staging, and assessment of response to treatment, without the need for invasive workup, and can inform clinical decision making. Read More

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Phenotypic and Multi-Omics Characterization of K-12 Adapted to Chlorhexidine Identifies the Role of MlaA and Other Cell Envelope Alterations Regulated by Stress Inducible Pathways in CHX Resistance.

Front Mol Biosci 2021 19;8:659058. Epub 2021 May 19.

Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.

Chlorhexidine (CHX) is an essential medicine used as a topical antiseptic in skin and oral healthcare treatments. The widespread use of CHX has increased concerns regarding the development of antiseptic resistance in Enterobacteria and its potential impact on cross-resistance to other antimicrobials. Similar to other cationic antiseptics, resistance to CHX is believed to be driven by three membrane-based mechanisms: lipid synthesis/transport, altered porin expression, and increased efflux pump activity; however, specific gene and protein alterations associated with CHX resistance remain unclear. Read More

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Establishing gold and platinum standards to 1 terapascal using shockless compression.

Science 2021 06;372(6546):1063-1068

Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

New techniques are advancing the frontier of high-pressure physics beyond 1 terapascal, leading to new discoveries and offering stringent tests for condensed-matter theory and advanced numerical methods. However, the ability to absolutely determine the pressure state remains challenging, and well-calibrated pressure-density reference materials are required. We conducted shockless dynamic compression experiments at the National Ignition Facility and the Z machine to obtain quasi-absolute, high-precision, pressure-density equation-of-state data for gold and platinum. Read More

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A partisan pandemic: state government public health policies to combat COVID-19 in Brazil.

BMJ Glob Health 2021 06;6(6)

Department of Social Sciences and Politics (currently listed in Spanish), Universidad Iberoamericana, Mexico City, Mexico.

Introduction: To present an analysis of the Brazilian health system and subnational (state) variation in response to the COVID-19 pandemic, based on 10 non-pharmaceutical interventions (NPIs).

Materials And Methods: We collected daily information on implementation of 10 NPI designed to inform the public of health risks and promote distancing and mask use at the national level for eight countries across the Americas. We then analyse the adoption of the 10 policies across Brazil's 27 states over time, individually and using a composite index. Read More

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Pathological Complete Response After Neoadjuvant Therapy in Rectal Adenocarcinoma: a 5-Year Follow-up.

Indian J Surg 2021 May 27:1-8. Epub 2021 May 27.

Clinical Research Centre, Selayang Hospital, Ministry of Health Malaysia, Selangor, Malaysia.

Neoadjuvant therapy is the gold standard treatment of locally advanced rectal cancer. It may induce complete sterilization of tumor cell and decreases its local recurrence rate. While 15-20% of patients were found to have pathological complete response (pCR) with combined multimodal therapy, Asian data were generally scarce. Read More

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Phylogeny Reveals Novel HipA-Homologous Kinase Families and Toxin-Antitoxin Gene Organizations.

mBio 2021 Jun 1:e0105821. Epub 2021 Jun 1.

Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.

Toxin-antitoxin modules function in the genetic stability of mobile genetic elements, bacteriophage defense, and antibiotic tolerance. A gain-of-function mutation of the Escherichia coli K-12 module can induce antibiotic tolerance in a subpopulation of bacterial cells, a phenomenon known as persistence. HipA is a Ser/Thr kinase that phosphorylates and inactivates glutamyl tRNA synthetase, inhibiting cellular translation and inducing the stringent response. Read More

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Capillary Electrophoresis Instruments for Medical Applications and Falsified Drug Analysis/Quality Control in Developing Countries.

Anal Chem 2021 Jun 1;93(23):8107-8115. Epub 2021 Jun 1.

Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CH-1211 Geneva 4, Switzerland.

The implementation of integrated analytical techniques to meet stringent requirements in the life sciences requires a well-developed analytical capacity. New technology in analytical equipment for the analysis of large and small molecules is continuously being developed. However, developing countries frequently struggle to keep pace with technological advancements. Read More

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A data-driven metapopulation model for the Belgian COVID-19 epidemic: assessing the impact of lockdown and exit strategies.

BMC Infect Dis 2021 May 30;21(1):503. Epub 2021 May 30.

Data Science Institute, I-Biostat, Hasselt University, Agoralaan Gebouw D, Diepenbeek, 3590, Belgium.

Background: In response to the ongoing COVID-19 pandemic, several countries adopted measures of social distancing to a different degree. For many countries, after successfully curbing the initial wave, lockdown measures were gradually lifted. In Belgium, such relief started on May 4th with phase 1, followed by several subsequent phases over the next few weeks. Read More

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Government response moderates the mental health impact of COVID-19: A systematic review and meta-analysis of depression outcomes across countries.

J Affect Disord 2021 07 27;290:364-377. Epub 2021 May 27.

Mood Disorders Psychopharmacology Unit, Toronto Western Hospital, University Health Network, Toronto, ON, Canada M5T 2S8; Institute of Medical Science, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Psychiatry, University of Toronto, Toronto, ON, Canada M5S 1A8; Department of Pharmacology, University of Toronto, Toronto, ON, Canada M5S 1A8.

Background: The COVID-19 pandemic represents a public health, economic and mental health crisis. We hypothesized that timely government implementation of stringent measures to reduce viral transmission would benefit mental health, as evidenced by reduced rates of depressive symptoms (i.e. Read More

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Identification and characterization of long non-coding RNA and their response against citrus bark cracking viroid infection in Humulus lupulus.

Genomics 2021 May 27;113(4):2350-2364. Epub 2021 May 27.

Biology Centre, Czech Academy of Sciences, Institute of Plant Molecular Biology, Branišovská 31, 37005 České Budějovice, Czech Republic.

Long non-coding RNAs (lncRNAs) are a highly heterogeneous class of non-protein-encoding transcripts that play an essential regulatory role in diverse biological processes, including stress responses. The severe stunting disease caused by Citrus bark cracking viroid (CBCVd) poses a major threat to the production of Humulus lupulus (hop) plants. In this study, we systematically investigate the characteristics of the lncRNAs in hop and their role in CBCVd-infection using RNA-sequencing data. Read More

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Developability profile framework for lead candidate selection in topical dermatology.

Int J Pharm 2021 May 27;604:120750. Epub 2021 May 27.

GlaxoSmithKline, Dermatology Unit, 1250 South Collegeville Rd, Collegeville, PA 19426, USA. Electronic address:

The development of molecules for topical dermatology has primarily relied on drug repurposing or on combination therapies, leading to an average of only one New Chemical Entity (NCE) approved per year by the FDA. Topical products offer benefits to patients by enabling localized treatment, while minimizing systemic exposure and the likelihood of adverse events. New therapies are further justified by the burden skin diseases cause on patients' quality of life. Read More

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Characterization of microRNAs from neem () and their tissue-specific expression study in leaves and stem.

3 Biotech 2021 Jun 19;11(6):277. Epub 2021 May 19.

Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, 76130 Queretaro, CP Mexico.

Neem () is a very popular traditional medicinal plant used since ancient times to treat numerous ailments. MicroRNAs (miRNAs) are highly conserved, non-coding, short RNA molecules that play important regulatory roles in plant development and metabolism. In this study, deploying a high stringent genome-wide computational-based approach and following a set of strict filtering norms a total of 44 potential conserved neem miRNAs belonging to 21 families and their corresponding 48 potential target transcripts were identified. Read More

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The Development of Living, Rapid Practice Points: Summary of Methods From the Scientific Medical Policy Committee of the American College of Physicians.

Ann Intern Med 2021 May 25. Epub 2021 May 25.

Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (L.L.H.).

In response to the COVID-19 pandemic, the Scientific Medical Policy Committee (SMPC) of the American College of Physicians (ACP) began developing "practice points" to provide clinical advice based on the best available evidence for the public, patients, clinicians, and public health professionals. As one of the first organizations in the United States to develop evidence-based clinical guidelines, ACP continues to lead and advance the science of evidence-based medicine by implementing new methods to rapidly publish practice points and maintain them as living advice that regularly assesses and incorporates new evidence. The overarching aim of practice points is to answer targeted key questions for which there is a timely need to synthesize evidence for decision making. Read More

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