Systematical Mutational Analysis of FRATtide against Osteoclast Differentiation by Alanine Scanning.

Osteoporosis, a global bone disease, results in decreased bone density, mass, and microarchitecture deterioration, increasing fracture risk. In previous research, FRATtide, a peptide derived from a glycogen synthase kinase-3 binding protein, effectively hindered osteoclast differentiation to yield therapeutically potent derivatives via single and double stapling. However, FRATtide's structure-activity relationship remains unclear.

Heat-Killed BBMN68 in Pasteurized Yogurt Alleviates Mugwort Pollen-Induced Allergic Airway Responses through Gut Microbiota Modulation in a Murine Model.

Many probiotic bacteria have been proven to prevent allergic airway responses through immunomodulation. This study was conducted to evaluate the effects of heat-killed BBMN68 (BBMN68) in pasteurized yogurt on the alleviation of mugwort pollen (MP)-induced allergic inflammation. BALB/c mice aged 5-6 weeks were randomly assigned and fed pasteurized yogurt containing heat-killed BBMN68 for 27 days, followed by allergic sensitization and challenge with MP extract.

Integrated UPLC-MS, network pharmacology, and intestinal flora analysis to determine the treatment effect of Qiangzhi decoction on comorbid Tourette syndrome and RRTI.

Background: Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics. Recurrent respiratory tract infection (RRTI), a commonly occurring disease in childhood, correlates with recurrent and severe course of tic symptoms. Qiangzhi decoction (QZD) is a traditional Chinese medicine that can alleviate TS symptoms while reducing the recurrence of RRTI.

Metformin: A Promising Antidiabetic Medication for Cancer Treatment.

Metformin is a widely used drug in patients with type 2 diabetes mellitus. Metformin inhibits hepatic gluconeogenesis and increases glucose utilization in peripheral tissues. In recent years, several studies have shown that metformin is a potential therapeutic agent against cancer, alone or combined with other anticancer treatments.

The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment.

Metformin is a widely-used anti-diabetic drug in patients with type 2 diabetic mellitus (T2DM) due to its safety and efficacy in clinical. The classic effect of metformin on lowering blood glucose levels is to inhibit liver gluconeogenesis that reduces glucose production as well as increases peripheral glucose utilization. However, the factors such as hyperglycemia, insulin deficiency, reduced serum levels of insulin-like growth factor-1 (IGF-1) and osteocalcin, accumulation of advanced glycation end products (AGEs), especially in collagen, microangiopathy, and inflammation reduced bone quality in diabetic patients.

Novel role and mechanism of glutathione peroxidase-4 in nutritional pancreatic atrophy of chicks induced by dietary selenium deficiency.

Nutritional pancreatic atrophy (NPA) is a classical Se/vitamin E deficiency disease of chicks. To reveal molecular mechanisms of its pathogenesis, we fed day-old chicks a practical, low-Se diet (14 μg Se/kg), and replicated the typical symptoms of NPA including vesiculated mitochondria, cytoplasmic vacuoles, and hyaline bodies in acinar cells of chicks as early as day 18. Target pathway analyses illustrated a > 90% depletion (P < 0.

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship.

Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI.

Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2.

Activating mutations in EZH2, the catalytic component of PRC2, promote cell proliferation, tumorigenesis, and metastasis through enzymatic or non-enzymatic activity. The EZH2-Y641 gain-of-function mutation is one of the most significant in diffuse large B-cell lymphoma (DLBCL). Although EZH2 kinase inhibitors, such as EPZ-6438, provide clinical benefit, certain cancer cells are resistant to the enzymatic inhibition of EZH2 because of the inability to functionally target mutant EZH2, or because of cells' dependence on the non-histone methyltransferase activity of EZH2.

missense mutations in Xia-Gibbs syndrome.

Xia-Gibbs syndrome (XGS; MIM: 615829) is a phenotypically heterogeneous neurodevelopmental disorder (NDD) caused by newly arising mutations in the AT-Hook DNA-Binding Motif-Containing 1 () gene that are predicted to lead to truncated AHDC1 protein synthesis. More than 270 individuals have been diagnosed with XGS worldwide. Despite the absence of an independent assay for AHDC1 protein function to corroborate potential functional consequences of rare variant genetic findings, there are also reports of individuals with XGS-like trait manifestations who have missense mutations and who have been provided a molecular diagnosis of the disorder.

Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications.

Non-surgical treatment options for low-grade endometrial cancer and precancerous lesions are a critical unmet need for women who wish to preserve fertility or are unable to undergo hysterectomy. The PI3K/AKT/mTOR pathway is frequently activated in endometrial cancers and has been associated with resistance to endocrine therapy, making it a compelling target for early stage disease. Oral everolimus, an inhibitor against mTORC1, has shown clinical benefit in advanced or recurrent disease but has severe adverse effects that may lead to treatment interruption or dose reduction.

Genome Sequence Analysis of the Fungal Pathogen Using Oxford Nanopore Technology.

is a plant pathogen of global importance which causes not only significant yield loss but also crop spoilage due to mycotoxins that render grain unsafe for human or livestock consumption. Although the full genome of several isolates from different parts of the world have been sequenced, there are no similar studies of isolates originating from China. The current study sought to address this by sequencing the isolate FG-12, which was isolated from the roots of maize seedlings exhibiting typical symptoms of blight growing in the Gansu province, China, using Oxford Nanopore Technology (ONT).

Network pharmacology study on the mechanism of Qiangzhifang in the treatment of panic disorder.

Background: Panic disorder (PD) is a kind of mental illness characterized by the symptom of recurring panic attacks. Qiangzhifang (QZF) is a novel decoction developed by Professor Zhaojun Yan based on a unique system of syndrome differentiation and clinical experience. It has achieved remarkable results after long-term clinical practice, but its mechanism of action is still unclear.

Comparing the Clinical Utility of Rapid Diagnostics for Treatment of Bloodstream Infections Using Desirability of Outcome Ranking Approach for the Management of Antibiotic Therapy (DOOR-MAT).

Decisions regarding which rapid diagnostic test (RDT) for bloodstream infections to implement remain challenging given the diversity of organisms detected by different platforms. We used the desirability of outcome ranking management of antimicrobial therapy (DOOR-MAT) as a framework to compare two RDT platforms on potential desirability of antimicrobial therapy decisions. An observational study was performed at University of Maryland Medical System comparing Verigene blood culture (BC) to GenMark Dx ePlex blood culture ID (BCID) (research use only) panels on blood cultures from adult patients.

Variable selection methods for identifying predictor interactions in data with repeatedly measured binary outcomes.

Introduction: Identifying predictors of patient outcomes evaluated over time may require modeling interactions among variables while addressing within-subject correlation. Generalized linear mixed models (GLMMs) and generalized estimating equations (GEEs) address within-subject correlation, but identifying interactions can be difficult if not hypothesized . We evaluate the performance of several variable selection approaches for clustered binary outcomes to provide guidance for choosing between the methods.

Day at the Races: Comparing BioFire FilmArray Blood Culture ID Panels With Verigene Blood Culture Panel in Gram-Negative Bloodstream Infections Using DOOR-MAT Analysis.

Three rapid diagnostic test panels (Verigene BC-GN, BioFire BCID, and BCID 2 [RUO]) were compared using the Desirability of Outcome Ranking Management of Antimicrobial Therapy (DOOR-MAT) to evaluate potential downstream antimicrobial prescribing decisions resulting from the panels' different organism and resistance detection. BioFire BCID 2 (RUO) had the best mean DOOR-MAT scores.

Biotransformation of Ginsenoside Rb1 to Ginsenoside CK by Strain XD101: a Safe Bioconversion Strategy.

Ginsenoside Rb1 is the main predominant component in Panax species. In this study, an eco-friendly and convenient preparation method for ginsenoside CK has been established, and five strains of β-glucosidase-producing microorganisms were screened out from the soil of a Panax notoginseng planting field using Esculin-R2A agar. Aspergillus niger XD101 showed that it has excellent biocatalytic activity for ginsenosides; one of the isolates can convert ginsenoside Rb1 to CK using extracellular enzyme from the mycelium.

Gadolinium-enhanced magnetic resonance versus computed tomography angiography for renal artery stenosis: A systematic review and meta-analysis.

Gadolinium-enhanced magnetic resonance angiography (MRA) and computed tomography angiography (CTA) are commonly used for diagnosing renal arterial stenosis (RAS); however, the diagnostic value is yet controversial. The aim of the study was to evaluate the diagnostic values of both methods. Electronic databases, including PubMed, Embase, and the Cochrane Library, were searched for studies, since inception until October 2017.

Calcium (Ca)-regulated exopolysaccharide biosynthesis in probiotic Lactobacillus plantarum K25 as analyzed by an omics approach.

Exopolysaccharide (EPS)-producing lactic acid bacteria have been widely used in dairy products, but how calcium, the main metal ion component in milk, regulates the EPS biosynthesis in lactic acid bacteria is not clear. In this study, the effect of Ca on the biosynthesis of EPS in the probiotic Lactobacillus plantarum K25 was studied. The results showed that addition of CaCl at 20 mg/L in a semi-defined medium did not affect the growth of strain K25, but it increased the EPS yield and changed the microstructure of the polymer.

A Statistical Review: Why Average Weighted Accuracy, not Accuracy or AUC?

Sensitivity and specificity are key aspects in evaluating the performance of diagnostic tests. Accuracy and AUC are commonly used composite measures that incorporate sensitivity and specificity. Average Weighted Accuracy (AWA) is motivated by the need for a statistical measure of diagnostic yield that can be used to compare diagnostic tests from the medical costs and clinical impact point of view, while incorporating the relevant prevalence range of the disease as well as the relative importance of false positive versus false negative cases.

Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT): A Framework for Assessing Antibiotic Selection Strategies in the Presence of Drug Resistance.

The complexities of antibiotic resistance mean that successful stewardship must consider both the effectiveness of a given antibiotic and the spectrum of that therapy to minimize imposing further selective pressure. To meet this challenge, we propose the Desirability of Outcome Ranking approach for the Management of Antimicrobial Therapy (DOOR MAT), a flexible quantitative framework that evaluates the desirability of antibiotic selection. Herein, we describe the steps required to implement DOOR MAT and present examples to illustrate how the desirability of treatment selection can be evaluated using resistance information.