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Background Immune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.Methods We undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.Results We identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).Conclusions The presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.

In this study, the production of titanium powder via hydrogen reduction of titanium tetrachloride by inductively coupled radio frequency plasma was investigated. While titanium tetrachloride is hard to be reduced by hydrogen thermodynamically, dissociated hydrogen radical which formed from hydrogen gas passing through the plasma can react with titanium tetrachloride to form hydrochloric acid and subsequently produce titanium. The frequency of generator used in this experiment was 13.56 MHz and input power was varied. The characteristics of the powder such as powder size, size distribution, and phases were analyzed with x-ray diffractometer, field emission scanning electron microscope, energy dispersive x-ray spectrometer and transmission electron microscope. The deposited height of titanium powders, after 4 minutes reaction, were 4.004 μm and loosely attached that could be easily collected. The morphology of powders was found to be more spherical with the increase in applied input power. Most of the powders were composed of titanium and oxygen. The average diameter of powders was approximately 200 nm.

Fetal rhabdomyomas are a rare neoplasm composed of immature striated muscle cells that resemble rhabdomesenchymal cells during weeks 6-10 of embryogenesis. This tumor, though well-described in many anatomic locations, is most commonly found in the head and neck region. We report a case that highlights the difficulty in diagnosing a fetal rhabdomyoma in the lacrimal gland of a 56 year old woman. This case report gives an overview of this rare neoplasm, detailing the presentation, diagnosis, and treatment.

Blood pressure (BP) is a typical complex trait, and the genetic susceptibility of individuals to changes in BP induced by air pollution exposure is different. Although interactions of exposure to air pollutants with several candidate genes have been identified, genome-wide interaction studies (GWISs) are needed to understand the association between them with BP. Therefore, we aimed to discover the unique genetic loci for BP that interact with exposure to air pollutants in Korean adults. We ultimately included 1868 participants in the discovery step and classified them into groups of those with low-to-moderate exposure and high exposure to average annual concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM10). Because none of the single nucleotide polymorphisms (SNPs) achieved a genome-wide level of significance of pint < 5 × 10–8 for either systolic BP (SBP) or diastolic BP (DBP), we considered the top 10 ranking SNPs for each BP trait. To validate these suggestive SNPs, we finally selected six genetic variants for SBP and five variants for DBP, respectively. In a replication result for SBP, only one SNP (rs12914147) located in an intergenic region of the NR2F2 showed a significant interaction. We also identified several genetic susceptibility loci (e.g., CHST11, TEK, and ITGA1) implicated in candidate mechanisms such as inflammation and oxidative stress in the discovery step, although their interaction effects were not replicated. Our study reports the first GWIS finding to our knowledge, and the association between exposure to PM10 and BP levels may be determined in part by several newly discovered genetic suggestive loci, including NR2F2. [ABSTRACT FROM AUTHOR]

A powerful carbon-based solid acid catalyst and furfural were obtained from rice straw (RS) biomass resource. The acid catalyst was prepared through the carbonization and sulfonation of RS. Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, scanning electron microscopy, N2 adsorption-desorption, and ammonia temperature-programmed desorption (NH3-TPD) were used to characterize the catalysts. The effect of sulfonation time (4 h to 16 h) on the structure and acidity of the catalysts was elucidated. After 16 h of sulfonation, the BET surface area and the total acidity of the catalyst reached 415 m2/g and 7.48 mmol/g, respectively. Moreover, strong acid sites accounted for more than 63% of acidity. The catalyst was then used for the conversion of RS into furfural in water. The influence of reaction temperature and time while using the catalyst on the conversion process was also investigated. The catalyst exhibited high activity in the conversion of RS, with a furfural yield of 68.3 g/kg RS at 160 °C in 5 h.

Abstract Pangenome inference is an indispensable step in bacterial genomics, yet its scalability poses a challenge due to the rapid growth of genomic collections. This paper presents PanTA, a software package designed for constructing pangenomes of large bacterial datasets, showing unprecedented efficiency levels multiple times higher than existing tools. PanTA introduces a novel mechanism to construct the pangenome progressively without rebuilding the accumulated collection from scratch. The progressive mode is shown to consume orders of magnitude less computational resources than existing solutions in managing growing datasets. The software is open source and is publicly available at https://github.com/amromics/panta and at 10.6084/m9.figshare.23724705 .

Abstract Whole genome analysis for microbial genomics is critical to studying and monitoring antimicrobial resistance strains. The exponential growth of microbial sequencing data necessitates a fast and scalable computational pipeline to generate the desired outputs in a timely and cost-effective manner. Recent methods have been implemented to integrate individual genomes into large collections of specific bacterial populations and are widely employed for systematic genomic surveillance. However, they do not scale well when the population expands and turnaround time remains the main issue for this type of analysis. Here, we introduce AMRomics, an optimized microbial genomics pipeline that can work efficiently with big datasets. We use different bacterial data collections to compare AMRomics against competitive tools and show that our pipeline can generate similar results of interest but with better performance. The software is open source and is publicly available at https://github.com/amromics/amromics under an MIT license.

Background/purpose: Platelet-rich fibrin (PRF) is a promising host-derived scaffold for regenerative endodontic treatment. This study investigated the effects of advanced PRF plus (A-PRF+) and injectable PRF (i-PRF) on the proliferation, migration, and differentiation of stem cells from apical papilla (SCAPs). Materials and methods: A-PRF+ and i-PRF were prepared using a DUO Quattro centrifuge following a standard protocol. A-PRF+ and i-PRF extract were diluted in Dulbecco's modified Eagle's medium and Ham's F-12 medium (DMEM/F12) to produce the experimental culture medium. DMEM/F12 and DMEM/F12 supplemented with 10% foetal bovine serum (FBS) were used as the negative control (NC) and positive control (PC) media, respectively. The proliferative ability of SCAPs was assessed using a counting method (haemocytometer). The migration ability was examined using a scratch-wound assay. Alkaline phosphatase, bone sialoprotein, dentin matrix protein 1, and dentin sialophosphoprotein expression were measured to determine the differentiation ability. Results: The proliferation, migration, and differentiation of SCAPs in the A-PRF+ group were similar to those of the PC group. In the i-PRF group, the cell number was significantly (p