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Imine reduction by an Ornithine cyclodeaminase/μ-crystallin homolog purified from ATCC 7330.

Biotechnol Rep (Amst) 2021 Sep 5;31:e00664. Epub 2021 Aug 5.

Laboratory of Bioorganic Chemistry, Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600 036, India.

We report a stereospecific imine reductase from ATCC 7330 (CpIM1), a versatile biocatalyst and a rich source of highly stereospecific oxidoreductases. The recombinant gene was overexpressed in and the protein CpIM1 was purified to homogeneity. This protein belongs to the Ornithine cyclodeaminase/ μ-crystallin (OCD-Mu) family of proteins which has only a few characterized members. Read More

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September 2021

Shotgun scanning glycomutagenesis: A simple and efficient strategy for constructing and characterizing neoglycoproteins.

Proc Natl Acad Sci U S A 2021 09;118(39)

Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;

As a common protein modification, asparagine-linked (linked) glycosylation has the capacity to greatly influence the biological and biophysical properties of proteins. However, the routine use of glycosylation as a strategy for engineering proteins with advantageous properties is limited by our inability to construct and screen large collections of glycoproteins for cataloguing the consequences of glycan installation. To address this challenge, we describe a combinatorial strategy termed shotgun scanning glycomutagenesis in which DNA libraries encoding all possible glycosylation site variants of a given protein are constructed and subsequently expressed in glycosylation-competent bacteria, thereby enabling rapid determination of glycosylatable sites in the protein. Read More

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September 2021

A Cre-driven allele-conditioning line to interrogate CD4 conventional T cells.

Immunity 2021 Sep 15. Epub 2021 Sep 15.

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA. Electronic address:

CD4 T cells share common developmental pathways with CD8 T cells, and upon maturation, CD4 T conventional T (Tconv) cells lack phenotypic markers that distinguish these cells from FoxP3 T regulatory cells. We developed a tamoxifen-inducible ThPOK line with Frt sites inserted on either side of the CreERT2-hCD2 cassette, and a Foxp3 strain, expressing Ametrine and FlpO in Foxp3 cells. Breeding these mice resulted in a CD4conv line that allows for the specific manipulation of a gene in CD4 Tconv cells. Read More

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September 2021

Poziotinib for Patients With Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial.

J Clin Oncol 2021 Sep 22:JCO2101113. Epub 2021 Sep 22.

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study.

Patients And Methods: Patients with advanced exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. Read More

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September 2021

Perspective: Opportunities and Challenges of Technology Tools in Dietary and Activity Assessment: Bridging Stakeholder Viewpoints.

Adv Nutr 2021 Sep 20. Epub 2021 Sep 20.

Center for Children's Healthy Lifestyles & Nutrition, Children's Mercy Kansas City, Kansas City, MO, USA.

The science and tools of measuring energy intake and output in humans have rapidly advanced in the last decade. Engineered devices such as wearables and sensors, software applications, and Web-based tools are now ubiquitous in both research and consumer environments. The assessment of energy expenditure in particular has progressed from reliance on self-report instruments to advanced technologies requiring collaboration across multiple disciplines, from optics to accelerometry. Read More

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September 2021

CREB regulates the expression of Type 1 Inositol 1,4,5-trisphosphate receptors.

J Cell Sci 2021 Sep 17. Epub 2021 Sep 17.

Department of Pharmacology and Physiology, University of Rochester, Rochester, NY, 14642, USA.

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) play a central role in regulating intracellular calcium signals in response to a variety of internal/external cues. Dysregulation of IP3R signaling is the underlying cause for numerous pathological conditions. It is well established that the activities of IP3Rs are governed by several post-translational modifications including phosphorylation by protein kinase A (PKA). Read More

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September 2021

IFN- Licensing Does Not Enhance the Reduced Immunomodulatory Potential and Migratory Ability of Differentiation-Induced Porcine Bone Marrow-Derived Mesenchymal Stem Cells in an Xenogeneic Application.

Biomed Res Int 2021 4;2021:4604856. Epub 2021 Sep 4.

College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.

IFN- licensing to mesenchymal stem cells (MSCs) is applied to enhance the therapeutic potential of MSCs. However, although the features of MSCs are affected by several stimuli, little information is available on changes to the therapeutic potential of IFN--licensed differentiated MSCs during xenogeneic applications. Therefore, the present study is aimed at clarifying the effects of adipogenic/osteogenic differentiation and IFN- licensing on the immunomodulatory and migratory properties of porcine bone marrow-derived MSCs in xenogeneic applications using human peripheral blood mononuclear cells (PBMCs). Read More

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September 2021

Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.

Cell Rep 2021 Sep;36(11):109689

The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.

Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. Read More

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September 2021

Downregulation of the Tem1 GTPase by Amn1 after cytokinesis involves both nuclear import and SCF-mediated degradation.

J Cell Sci 2021 Sep 14. Epub 2021 Sep 14.

CRBM, University of Montpellier, CNRS, 1919 Route de Mende, 34293 Montpellier, France.

At mitotic exit the cell cycle engine is reset to allow crucial processes, such as cytokinesis and replication origin licensing, to take place before a new cell cycle begins. In budding yeast, the cell cycle clock is reset by a Hippo-like kinase cascade called Mitotic Exit Network (MEN), whose activation is triggered at spindle pole bodies (SPBs) by the Tem1 GTPase. Yet, MEN activity must be extinguished once MEN-dependent processes have been accomplished. Read More

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September 2021

Pharmacodynamic measures within tumors expose differential activity of PD(L)-1 antibody therapeutics.

Proc Natl Acad Sci U S A 2021 Sep;118(37)

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287;

Macromolecules such as monoclonal antibodies (mAbs) are likely to experience poor tumor penetration because of their large size, and thus low drug exposure of target cells within a tumor could contribute to suboptimal responses. Given the challenge of inadequate quantitative tools to assess mAb activity within tumors, we hypothesized that measurement of accessible target levels in tumors could elucidate the pharmacologic activity of a mAb and could be used to compare the activity of different mAbs. Using positron emission tomography (PET), we measured the pharmacodynamics of immune checkpoint protein programmed-death ligand 1 (PD-L1) to evaluate pharmacologic effects of mAbs targeting PD-L1 and its receptor programmed cell death protein 1 (PD-1). Read More

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September 2021

Antigen modifications improve nucleoside-modified mRNA-based influenza virus vaccines in mice.

Mol Ther Methods Clin Dev 2021 Sep 12;22:84-95. Epub 2021 Jun 12.

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

Nucleoside-modified, lipid nanoparticle-encapsulated mRNAs have recently emerged as suitable vaccines for influenza viruses and other pathogens in part because the platform allows delivery of multiple antigens in a single immunization. mRNA vaccines allow for easy antigen modification, enabling rapid iterative design. We studied protein modifications such as mutating functional sites, changing secretion potential, and altering protein conformation, which could improve the safety and/or potency of mRNA-based influenza virus vaccines. Read More

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September 2021

By utilizing technology can nursing students gain more confidence and decrease anxiety when communicating with chronically ill patients about their sexual relationship?

Nurse Educ Today 2021 Aug 10;107:105084. Epub 2021 Aug 10.

The Valley Foundation School of Nursing, San Jose State University, United States of America.

Introduction: Effective communication is an essential part of nursing care. Nurses need to effectively communicate with patients, families, providers and staff. The purpose of this study was to show how the use of technology (i. Read More

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A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants.

Immunity 2021 09 17;54(9):2159-2166.e6. Epub 2021 Aug 17.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Read More

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September 2021

Comparison of domain adaptation techniques for white matter hyperintensity segmentation in brain MR images.

Med Image Anal 2021 Aug 17;74:102215. Epub 2021 Aug 17.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Australian Institute for Machine Learning (AIML), School of Computer Science, The University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.

Robust automated segmentation of white matter hyperintensities (WMHs) in different datasets (domains) is highly challenging due to differences in acquisition (scanner, sequence), population (WMH amount and location) and limited availability of manual segmentations to train supervised algorithms. In this work we explore various domain adaptation techniques such as transfer learning and domain adversarial learning methods, including domain adversarial neural networks and domain unlearning, to improve the generalisability of our recently proposed triplanar ensemble network, which is our baseline model. We used datasets with variations in intensity profile, lesion characteristics and acquired using different scanners. Read More

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The effects of graduated driver licensing on teenage body weight.

Health Econ 2021 Aug 26. Epub 2021 Aug 26.

Department of Economics, Andrew Young School of Policy Studies, Georgia State University, Atlanta, Georgia, USA.

The graduated driver licensing (GDL) program requires teenage drivers to pass through an intermediate stage, which contains specific driving restrictions such as a night curfew or a limit on the number of teen passengers to be carried, before earning full driving privileges. Using individual data from the 1999 to 2017 biennial Youth Risk Behavior Surveillance System (YRBS) combined with state-level GDL policy variations, we estimate the effects of GDL on teenage body weight in the United States. We find that the presence of GDL raises adolescents' body mass index Z-score and their likelihood of being overweight or obese. Read More

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Functional heterogeneity of IFN-γ-licensed mesenchymal stromal cell immunosuppressive capacity on biomaterials.

Proc Natl Acad Sci U S A 2021 Aug;118(35)

Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993;

Mesenchymal stromal cells (MSCs) are increasingly combined with biomaterials to enhance their therapeutic properties, including their immunosuppressive function. However, clinical trials utilizing MSCs with or without biomaterials have shown limited success, potentially due to their functional heterogeneity across different donors and among different subpopulations of cells. Here, we evaluated the immunosuppressive capacity, as measured by the ability to reduce T-cell proliferation and activation, of interferon-gamma (IFN-γ)-licensed MSCs from multiple donors on fibrin and collagen hydrogels, the two most commonly utilized biomaterials in combination with MSCs in clinical trials worldwide according to Variations in the immunosuppressive capacity between IFN-γ-licensed MSC donors on the biomaterials correlated with the magnitude of indoleamine-2,3-dioxygenase activity. Read More

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Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence -associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia.

PLoS One 2021 26;16(8):e0250133. Epub 2021 Aug 26.

Department of Large Animal Clinical Sciences, Equine Infectious Disease Laboratory, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, United States of America.

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Read More

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Phase I dose escalation safety and feasibility study of autologous WT1-sensitized T cells for the treatment of patients with recurrent ovarian cancer.

J Immunother Cancer 2021 Aug;9(8)

Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Background: This phase I dose escalation trial evaluated the feasibility of production, safety, maximum tolerated dose, and preliminary efficacy of autologous T cells sensitized with peptides encoding Wilms' tumor protein 1 (WT1) administered alone or following lymphodepleting chemotherapy, in the treatment of patients with recurrent WT1 ovarian, primary peritoneal, or fallopian tube carcinomas.

Methods: A 3+3 dose escalation design was used to determine dose-limiting toxicity (DLT). In cohort I, patients received WT1-sensitized T cells dosed at 5×10/m (level I) without cyclophosphamide lymphodepletion. Read More

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Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn's disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial.

Lancet Gastroenterol Hepatol 2021 Oct 11;6(10):816-825. Epub 2021 Aug 11.

Klinik für Innere Medizin I, Universitaetsklinikum Schleswig-Holstein, Kiel University, Kiel, Germany.

Background: BI 695501 is a biosimilar that has demonstrated similar efficacy, safety, and immunogenicity to adalimumab reference product in patients with rheumatoid arthritis and chronic plaque psoriasis. The VOLTAIRE-CD study aimed to compare the efficacy and safety of BI 695501 with adalimumab reference product in patients with Crohn's disease.

Methods: This phase 3, randomised, double-blind study was done at 92 centres in 12 countries across Europe and the USA in patients aged 18-80 years with moderately to severely active Crohn's disease (Crohn's Disease Activity Index [CDAI] score 220-450). Read More

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October 2021

Spine Surgeons Social Dilemma: Benefits and Risks of Social Media for Spine Surgery Practice in the 21st Century.

Global Spine J 2021 Aug 3:21925682211035716. Epub 2021 Aug 3.

Texas Back Institute, Plano, TX, USA.

Study Design: Cross-sectional observational.

Background: The use of social media by providers can enhance patient education, complement offline information, facilitate patient support, stimulate brand building, and strengthen the organization's market position. Risks of social media include, but are not limited to, a lack of quality, reliability, misrepresentation of credentials, influence of hidden and overt conflicts of interest, content that may jeopardize patient privacy, HIPAA regulations, and physicians' credentials and licensure. Read More

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GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy.

Theranostics 2021 26;11(16):7844-7868. Epub 2021 Jun 26.

German Cancer Research Center (DKFZ), Heidelberg, Germany.

Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity. Read More

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Triplanar ensemble U-Net model for white matter hyperintensities segmentation on MR images.

Med Image Anal 2021 10 18;73:102184. Epub 2021 Jul 18.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, UK; Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, UK.

White matter hyperintensities (WMHs) have been associated with various cerebrovascular and neurodegenerative diseases. Reliable quantification of WMHs is essential for understanding their clinical impact in normal and pathological populations. Automated segmentation of WMHs is highly challenging due to heterogeneity in WMH characteristics between deep and periventricular white matter, presence of artefacts and differences in the pathology and demographics of populations. Read More

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October 2021

IDEO energy-storing orthosis: Effects on lower extremity function and preservation.

Injury 2021 Jul 18. Epub 2021 Jul 18.

USU-WRNMMC Department of Surgery, Bethesda, MD, United States.

Introduction: The Intrepid Dynamic Exoskeletal Orthosis (IDEO) brace is a custom energy-storing orthosis design meant to improve gait, stability, and function after lower extremity injury or limb salvage. Early studies demonstrated the potential for the IDEO to improve functional performance, in conjunction with its paired return to run (RTR) rehabilitation program, compared to other brace types, and an impressively decreased rate of late amputation. The current study aimed to investigate these functional and revision outcomes from our institution to determine which patients may benefit most from IDEO bracing and what factors of the IDEO design and rehabilitation program are most important for improved outcomes after lower extremity trauma and/or loss of function. Read More

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Global research publications on systemic use of off-label and unlicensed drugs: A bibliometric analysis (1990-2020).

Waleed M Sweileh

Int J Risk Saf Med 2021 Jul 14. Epub 2021 Jul 14.

Department of Physiology, Pharmacology/Toxicology, Division of Biomedical Sciences, College of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.

Background: Governmental regulations of drug registration and licensing are not always followed by healthcare providers.

Objective: To explore the global research growth and patterns on systemic use of off-label and unlicensed drugs to gain knowledge about the magnitude of the problem and the main research themes encountered in this field.

Methods: SciVerse Scopus was searched for papers on off-label and unlicensed drug use from 1990 until December 31, 2020, without any language limitations. Read More

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Management of neovascular age-related macular degeneration: Taiwan expert consensus.

J Formos Med Assoc 2021 Jul 14. Epub 2021 Jul 14.

Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan; College of Medicine, Chung-Shan Medical University, Taichung, Taiwan; Department of Optometry, College of Nursing and Health Science, Da-Yeh University, Changhua, Taiwan. Electronic address:

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss. The present consensus provides suggestions on diagnosis, evaluation, treatment, and follow-up strategies for nAMD from a panel of 11 practicing ophthalmologists. The experts suggest that the baseline visit for nAMD management should include a comprehensive ophthalmologic examination via a multimodal approach consisting of visual and anatomical evaluation. Read More

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A novel miR1983-TLR7-IFNβ circuit licenses NK cells to kill glioma cells, and is under the control of galectin-1.

Oncoimmunology 2021 28;10(1):1939601. Epub 2021 Jun 28.

Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.

Although pharmacological stimulation of TLRs has anti-tumor effects, it has not been determined whether endogenous stimulation of TLRs can lead to tumor rejection. Herein, we demonstrate the existence of an innate anti-glioma NK-mediated circuit initiated by glioma-released miR-1983 within exosomes, and which is under the regulation of galectin-1 (Gal-1). We demonstrate that miR-1983 is an endogenous TLR7 ligand that activates TLR7 in pDCs and cDCs through a 5'-UGUUU-3' motif at its 3' end. Read More

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Geodesic density regression for correcting 4DCT pulmonary respiratory motion artifacts.

Med Image Anal 2021 08 21;72:102140. Epub 2021 Jun 21.

Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA 52242 USA; Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242 USA. Electronic address:

Pulmonary respiratory motion artifacts are common in four-dimensional computed tomography (4DCT) of lungs and are caused by missing, duplicated, and misaligned image data. This paper presents a geodesic density regression (GDR) algorithm to correct motion artifacts in 4DCT by correcting artifacts in one breathing phase with artifact-free data from corresponding regions of other breathing phases. The GDR algorithm estimates an artifact-free lung template image and a smooth, dense, 4D (space plus time) vector field that deforms the template image to each breathing phase to produce an artifact-free 4DCT scan. Read More

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Determination of modification degree of polysialylated therapeutic proteins using H-NMR spectroscopy.

Int J Biol Macromol 2021 Aug 29;185:1015-1021. Epub 2021 Jun 29.

Department of Chemistry, University of Natural Resources and Life Sciences, Muthgasse 18, 1190 Vienna, Austria. Electronic address:

Water soluble polymers and their derivatives bound to proteins can dramatically favor the biological activity of new drugs and vaccines. Quantification of the modification degree of the protein is crucial during the development and licensing phase and later in order to monitor the industrial production process and to match product specification. In this work, we describe an innovative way to measure directly the modification degree of polysialylated proteins using proton NMR (Nuclear Magnetic Resonance) spectroscopy. Read More

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What Is the Best Evidence to Guide Management of Acute Achilles Tendon Ruptures? A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Clin Orthop Relat Res 2021 10;479(10):2119-2131

Centre for Practice-Changing Research, The Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Background: Uncertainty exists regarding the best treatment for acute Achilles tendon ruptures. Simultaneous comparison of the multiple treatment options using traditional study designs is problematic; multiarm clinical trials often are logistically constrained to small sample sizes, and traditional meta-analyses are limited to comparisons of only two treatments that have been compared in head-to-head trials. Network meta-analyses allow for simultaneous comparison of all existing treatments utilizing both direct (head-to-head comparison) and indirect (not previously compared head-to-head) evidence. Read More

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October 2021