Publications

Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation

Evaluation of the reporting quality of clinical practice guidelines on pancreatic cancer using the RIGHT checklist

The International Reporting Items for Practice Guidelines in Health Care (RIGHT) statement is a set of recommendations for the reporting in clinical practice guidelines (CPGs). We aimed to assess the reporting quality of CPGs for pancreatic cancer following the RIGHT checklist.Guidelines for pancreatic cancer were identified by searching electronic databases, guideline databases, and medical society websites. The reporting quality was evaluated by calculating the adherence to the items of the RIGHT checklist and summarizing them over the seven domains and the entire checklist. We also present results stratified by selected characteristics.A total of 22 guidelines were found eligible. Mean overall adherence to the RIGHT items was 60.0%. All guidelines adhered to the RIGHT items 3, 7a, 13a, while no guidelines reported the items 14c or 18b, which are some of the topics dealing with rationale for recommendations and funding source, respectively. Of the seven domains of the RIGHT checklist, "Review and quality assurance" and "Funding and declaration and management of interests" had the lowest reporting rates (25.0% and 43.2%, respectively); the remaining five domains had reporting rates >50%. CPGs that reported funding support, were published in higher-impact journals, and that applied a grading system for the quality of evidence, tended to have higher reporting rates.Our results show that reporting quality of pancreatic cancer CPGs still needs to be improved. The use of the RIGHT statement should be encouraged when developing new guidelines.

Evaluating the seismic performance of mid-rise composite modular buildings in low-to-moderate seismicity regions

Alterations in the gut virome are associated with type 2 diabetes and diabetic nephropathy

Although changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

A Novel Mechanism of Endoplasmic Reticulum Stress‐ and c‐Myc‐Degradation‐Mediated Therapeutic Benefits of Antineurokinin‐1 Receptor Drugs in Colorectal Cancer

The neurokinin-1 receptor (NK-1R) antagonists are approved as treatment for chemotherapy-associated nausea and vomiting in cancer patients. The emerging role of the substance P-NK-1R system in oncogenesis raises the possibility of repurposing well-tolerated NK-1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK-1R expression have poor survival, and NK-1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK-1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal-regulated kinase (ERK)-c-Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA-like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP-homologous protein (CHOP). Moreover, NK-1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5-fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK-c-Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK-1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.

Effect of steel fibers on the performance of an economical ultra‐high strength concrete

Abstract This study examines the use of steel fibers in enhancing the ductility of an economical ultra‐high strength concrete (UHSC). The addition of fibrous material with very small geometry in this mixture is an effective solution to improve its ductility and prevent its brittle failure which is a common characteristic of UHSC. Different mechanical properties of reinforced and unreinforced concrete (e.g., slump flow, compressive, splitting tensile strength tests, and failure modes) were taken into account to find out the efficiency of micro steel fibers. The test results showed that concrete containing 25 mm length and 0.20 mm diameter steel fibers at a volume fraction of 0.5% not only presented a reasonable improvement in ductility performance but also ensured cost‐effectiveness. The cost evaluation conducted on several existing mix designs is also introduced in this study to investigate the influence of various steel fiber contents on the total cost of concrete so that figure out the lowest budget solution. The evaluation shows the high price of fiber reinforcement in which an addition of steel fibers by 5% volume could increase 7% of the total concrete cost.

A novel unified model for laminated composite beams

Matrine protects retinal ganglion cells from apoptosis in experimental optic neuritis

<title>Abstract</title> Background: Inflammatory demyelination and axonal injury of the optic nerve are hallmarks of optic neuritis (ON), which often occurs in multiple sclerosis and is a major cause of visual disturbance in young adults. Although a high dose of corticosteroids can promote visual recovery, it cannot prevent permanent neuronal damage. Novel and effective therapies are thus required. Given the recently defined capacity of matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, in immunomodulation and neuroprotection, we tested in this study the effect of matrine on rats with experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Results: MAT administration, started at disease onset, significantly suppressed optic nerve infiltration and demyelination, with reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells, compared to those from vehicle-treated rats. Increased expression of neurofilaments, an axon marker, reduced numbers of apoptosis in retinal ganglion cells (RGCs), and reduced numbers of Iba1 + macrophages/microglia and CD4 + T cells were also observed in the retina after MAT treatment. Conclusions: Taken as a whole, our results demonstrate that MAT attenuated inflammation, demyelination and axonal loss in the optic nerve, and protected RGCs from inflammation-induced cell death. MAT may therefore have potential as a novel treatment for this disease that may result in blindness.

Investigation of Ultimate Strength and Behavior of Steel Suspension Bridge

(015) DEVELOPMENT OF A VAGINAL DILATOR DEVICE AND A HOME INSEMINATION DEVICE FOR CIS- AND TRANSGENDER PEOPLE, BASED ON THE ACTUAL ANATOMY OF THE PELVIS

Fire Behavior of Ultra-High Strength Concrete Filled Steel Tubular Columns Under Non-uniform Heating

Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer

Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure.Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest. The Prentice criteria were applied to test candidate biomarkers as surrogates for overall survival at the individual-patient level.A biomarker panel using CTC count and lactate dehydrogenase (LDH) level was shown to satisfy the four Prentice criteria for individual-level surrogacy. Twelve-week surrogate biomarker data were available for 711 patients. The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference (P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival. Overall, 2-year survival of patients with CTCs < 5 (low risk) versus patients with CTCs ≥ 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively.A biomarker panel containing CTC number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic CRPC. Additional trials are ongoing to validate the findings.

Data from γδ T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival

&lt;div&gt;Abstract&lt;p&gt;Merkel cell carcinomas (MCC) are immunogenic skin cancers associated with viral infection or UV mutagenesis. To study T-cell infiltrates in MCC, we analyzed 58 MCC lesions from 39 patients using multiplex-IHC/immunofluorescence (m-IHC/IF). CD4&lt;sup&gt;+&lt;/sup&gt; or CD8&lt;sup&gt;+&lt;/sup&gt; T cells comprised the majority of infiltrating T lymphocytes in most tumors. However, almost half of the tumors harbored prominent CD4/CD8 double-negative (DN) T-cell infiltrates (&gt;20% DN T cells), and in 12% of cases, DN T cells represented the majority of T cells. Flow cytometric analysis of single-cell suspensions from fresh tumors identified DN T cells as predominantly Vδ2&lt;sup&gt;−&lt;/sup&gt; γδ T cells. In the context of γδ T–cell inflammation, these cells expressed PD-1 and LAG3, which is consistent with a suppressed or exhausted phenotype, and CD103, which indicates tissue residency. Furthermore, single-cell RNA sequencing (scRNA-seq) identified a transcriptional profile of γδ T cells suggestive of proinflammatory potential. T-cell receptor (TCR) analysis confirmed clonal expansion of Vδ1 and Vδ3 clonotypes, and functional studies using cloned γδ TCRs demonstrated restriction of these for CD1c and MR1 antigen-presenting molecules. On the basis of a 13-gene γδ T–cell signature derived from scRNA-seq analysis, gene-set enrichment on bulk RNA-seq data showed a positive correlation between enrichment scores and DN T-cell infiltrates. An improved disease-specific survival was evident for patients with high enrichment scores, and complete responses to anti–PD-1/PD-L1 treatment were observed in three of four cases with high enrichment scores. Thus, γδ T–cell infiltration may serve as a prognostic biomarker and should be explored for therapeutic interventions.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related Spotlight on p. 600&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;

Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: A literature based meta-analysis of randomized trials

A Ritz type solution with exponential trial functions for laminated composite beams based on the modified couple stress theory

An analytical method for the vibration and buckling of functionally graded beams under mechanical and thermal loads

Receptor-mediated glutamate release from volume sensitive channels in astrocytes

Several lines of work have shown that astrocytes release glutamate in response to receptor activation, which results in a modulation of local synaptic activity. Astrocytic glutamate release is Ca 2+ -dependent and occurs in conjunction with exocytosis of glutamate containing vesicles. However, astrocytes contain a millimolar concentration of cytosolic glutamate and express channels permeable to small anions, such as glutamate. Here, we tested the idea that astrocytes respond to receptor stimulation by dynamic changes in cell volume, resulting in volume-sensitive channel activation, and efflux of cytosolic glutamate. Confocal imaging and whole-cell recordings demonstrated that astrocytes exhibited a transient Ca 2+ -dependent cell volume increase, which activated glutamate permeable channels. HPLC analysis revealed that glutamate was released in conjunction with other amino acid osmolytes. Our observations indicate that volume-sensitive channel may constitute a previously uncharacterized target for modulation of astrocyte-neuronal interactions.

Development and validation of a sensitive UHPLC–MS/MS method for quantitation of prucalopride in rat plasma and its application to pharmacokinetics study