The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both and ; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated β-2 microglobulin (β2M) gene knockout (KO).
View Article and Find Full Text PDFData clustering plays a significant role in biomedical sciences, particularly in single-cell data analysis. Researchers use clustering algorithms to group individual cells into populations that can be evaluated across different levels of disease progression, drug response, and other clinical statuses. In many cases, multiple sets of clusters must be generated to assess varying levels of cluster specificity.
View Article and Find Full Text PDFApplications of synthetic biology spanning human health, industrial bioproduction, and ecosystem monitoring often require small molecule sensing capabilities, typically in the form of genetically encoded small molecule biosensors. Critical to the deployment of greater numbers of these systems are methods that support the rapid development of such biosensors against a broad range of small molecule targets. Here, we use a previously developed method for selection of RNA biosensors against unmodified small molecules (DRIVER) to perform a selection against a densely multiplexed mixture of small molecules, representative of those employed in high-throughput drug screening.
View Article and Find Full Text PDFNeutrophils, the most abundant white blood cell type in humans, play a crucial role in innate host defenses. Recent studies have revealed additional key roles in the pathogenesis of cancer and autoimmune diseases through multiple mechanisms including the formation of neutrophil extracellular traps (NETs). Further research to expand the understanding of neutrophils' role in health and diseases is limited by lack of techniques to quantify neutrophils undergoing NET formation in an objective, reproducible, and efficient manner.
View Article and Find Full Text PDFIsr J Health Policy Res
September 2022
Background: The breastfeeding initiation rate in Israel is approximately 90%, yet exclusive breastfeeding drops sharply in the early postnatal period. The study objective was to assess early postpartum professional breastfeeding support, its association with breastfeeding success and identification of risk factors for early breastfeeding discontinuation.
Methods: As part of a post-discharge newborn follow-up study, a convenience sample of 868 mothers attending Maternal and Child Health Centers (MCHCs) up to three months post-partum were interviewed using a 26-item questionnaire.
Introduction: Laparoscopic cholecystectomy (LC), one of the most common surgical procedures performed in the U.S., offers a window into the effects of the COVID-19 pandemic on routine surgical care.
View Article and Find Full Text PDFThe rates of and the factors influencing HER2 discordance in patients receiving neoadjuvant therapy for breast cancer are investigated. This study retrospectively examines the rates of HER2 and hormone receptor discordance between the biopsy and postoperative resection specimens of 400 female early-stage breast cancer patients. 133 (33.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19) is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over 500 million confirmed cases of COVID-19 have been recorded, with six million deaths. Thus, reducing the COVID-19-related medical burden is an unmet need.
View Article and Find Full Text PDFObjective: In this study, it was aimed to evaluate the demographic, clinical and laboratory characteristics of MIS-C patients in our hospital, to share our treatment approach, and to assess the outcomes of short- and long-term follow-up.
Methods: MIS-C patients who were admitted and treated in our hospital between July 2020 and July 2021 were evaluated. Demographic, clinical, laboratory, and follow-up data were collected from patient records retrospectively.
Objectives: In dermatomyositis (DM), autoantibodies are associated with unique clinical phenotypes. For example, anti-TIF1γ autoantibodies are associated with an increased risk of cancer. The purpose of this study was to discover novel DM autoantibodies.
View Article and Find Full Text PDFObjective: Regorafenib is a multikinase inhibitor, the effectiveness of which was demonstrated in metastatic colorectal cancer. This study aimed to investigate the factors that could predict the effectiveness of regorafenib.
Materials And Methods: This study retrospectively reviewed the clinical characteristics, tumor characteristics, and previous therapies in 62 patients who presented to our center between 2016 and 2020 and used regorafenib for metastatic colorectal cancer.
Background: The endothelium is crucial for the control of vascular homeostasis and plays a role in angiogenesis. Leptin, a protein released mainly by adipose tissue, plays a key role in the regulation of energy balance and angiogenesis. We aimed to investigate the changes of endothelial nitric oxide synthetase expression on human umbilical vein endo- thelial cells wound healing model after leptin treatment.
View Article and Find Full Text PDFRichter's Syndrome (RS) is an aggressive transformation of CLL, usually clonally-related diffuse large B-cell lymphoma (DLBCL), characterized by frequent TP53 mutations, intrinsic chemoresistance and poor survival. TP53-independent treatments are needed. We conducted a single center, phase 2, investigator-initiated study of high dose blinatumomab (maximum 112 mcg/d after initial, weekly dose escalation), NCT03121534, given for an 8-week induction and 4-week consolidation cycle.
View Article and Find Full Text PDFConjugated -glycans are considered next-generation bioactive prebiotic compounds due to their selective stimulation of beneficial microbes. These compounds are glycosidically attached to proteins through -acetylglucosamines specific asparagine residue (AsN-X-Ser/Thr). Certain bacteria such as () have been shown to be capable of utilizing conjugated -glycans, owing to their specialized genomic abilities.
View Article and Find Full Text PDFHidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder characterized by abscess-like nodules and boils resulting in fistulas and tissue scarring. We previously reported evidence of an autoimmune signature in HS, characterized by enhanced neutrophil extracellular trap (NET) infiltration in HS skin lesions and dysregulation of the adaptive immune system characterized by the presence of autoantibodies. Timely removal of NETs is critical for tissue homeostasis to prevent a dysregulated generation of modified autoantigens and tissue damage.
View Article and Find Full Text PDFPurpose: Determine the safety and specificity of a tumor-targeted radiotracer (89Zr-pan) in combination with 18F-FDG PET/CT to improve diagnostic accuracy in head and neck squamous cell carcinoma (HNSCC).
Experimental Design: Adult patients with biopsy-proven HNSCC scheduled for standard-of-care surgery were enrolled in a clinical trial and underwent systemic administration of 89Zirconium-panitumumab and panitumumab-IRDye800 followed by preoperative 89Zr-pan PET/CT and intraoperative fluorescence imaging. The sensitivity, specificity, and AUC were evaluated.
Objectives: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases.
View Article and Find Full Text PDFBovine milk is one of the best pre-and pro-workout sources for athletes owing to its rich nutritional content. Even though bovine milk consumption significantly benefits athletes' health and performance, many athletes cannot consume bovine milk since they struggle with gastrointestinal problems caused after milk consumption. Especially, the consumption of regular milk, which contains A1 β-casein, is associated with a variety of diseases ranging from gastrointestinal discomfort to ischemic heart diseases.
View Article and Find Full Text PDFBackground: Immunoglobulin A vasculitis with nephritis (IgAVN) is the most serious complication affecting long-term prognosis. Understanding the risk factors and markers for the development of IgAVN is essential. The aim of this study is to identify IgAVN-associated factors and to evaluate the usability of Pediatric Vasculitis Activity Score (PVAS) at diagnosis as an early marker for the development of IgAVN.
View Article and Find Full Text PDFAcute kidney injury (AKI) is a complication associated with vancomycin. Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin with meropenem or cefepime. These studies did not utilize area under the curve (AUC)-based dosing, which reduces vancomycin exposure and may decrease nephrotoxicity compared with trough-based dosing.
View Article and Find Full Text PDFThe bacterial flagellar type III secretion system (fT3SS) is a suite of membrane-embedded and cytoplasmic proteins responsible for building the flagellar motility machinery. Homologous nonflagellar (NF-T3SS) proteins form the injectisome machinery that bacteria use to deliver effector proteins into eukaryotic cells, and other family members were recently reported to be involved in the formation of membrane nanotubes. Here, we describe a novel, evolutionarily widespread, hat-shaped structure embedded in the inner membranes of bacteria, of yet-unidentified function, that is present in species containing fT3SS.
View Article and Find Full Text PDFObjectives: This study aims to determine whether COVID-19 patients with different initial reverse transcriptase-polymerase chain reaction (RT-PCR), computed tomography (CT) and laboratory findings have different clinical outcomes.
Materials And Methods: In this multi-center retrospective cohort study, 895 hospitalized patients with the diagnosis of COVID-19 were included. According to the RT-PCR positivity and presence of CT findings, the patients were divided into four groups.