Germline variants in androgen metabolism genes may influence clinical response to androgen deprivation therapy (ADT) in advanced prostate cancer. We sought to investigate the prognostic significance ...of germline variants in androgen metabolism genes with respect to overall survival (OS) after ADT, and to associate germline variants with tumor genomic features.
Germline and somatic whole-genome sequencing (WGS) data were evaluated in a cohort of 101 men with metastatic castration-resistant prostate cancer (mCRPC). Survival analyses were performed to identify polymorphisms associated with impaired OS after primary ADT. Germline variants found to be prognostic of OS were associated with tumor somatic DNA-sequence alterations based on WGS performed on paired metastasis biopsies from the same 101 patients. Gene set enrichment analysis was performed based on tumor RNA-sequencing data to identify genomic pathways differentially expressed in patients with germline variants.
A comprehensive literature review identified 17 candidate polymorphisms in nine androgen metabolism genes that have been previously shown to have an association with response to ADT in prostate cancer. Of these, the variant rs1856888 allele located 13 kb upstream of HSD3B1 was found to be significantly associated with impaired OS (P = 0.029). Variant rs1856888 was commonly co-inherited with the well-characterized HSD3B1(1245A>C) polymorphism, and there was a trend toward shorter median OS in patients with HSD3B1(1245A>C) compared with homozygous wild-type patients (P = 0.052). While HSD3B1 germline variants were not associated with common somatic tumor DNA alterations, they were associated with increased tumor expression of cell proliferation and cell cycle genes.
This study presents a comprehensive assessment of germline variants in androgen metabolism genes and highlights HSD3B1 polymorphisms as prognostic of OS after ADT and associated with an aggressive gene expression tumor profile in mCRPC.
Perfluorooctanoic acid (PFOA) is an artificially synthesized per-fluorinated chemical widely used in industry. It is often released into the environment without treatment and causes pollution in ...groundwater. In this paper, we employed a strip fountain dielectric barrier discharge (SF-DBD) plasma source to degrade PFOA from the water. The effects of power supply mode, discharge gases, pH, the conductivity of the solution, concentration, etc., on the degradation efficiency were studied. For a 200 mL sample of 75 mg/L PFOA, a 99% degradation efficiency with a 204.5 μg/kJ energy production rate was achieved using an average power of 43 W negative pulse argon plasma for 50 min at atmospheric pressure. The total organic carbon concentration (TOC) decreased by 63% after a 60 min treatment. The SF-DBD proves to be a promising and energy-saving technique to efficiently remove PFOA from water.
This study investigated the effect of educational board games and the creative thinking spiral teaching strategy (CTSTS) on the learning outcomes of beginner-level Chinese language learners. Two ...dimensions were measured: learning outcome and writing ability. A total of 82 learners from one university in Taiwan participated in this study. Participants were non-randomly selected using convenience sampling. The participants were divided into the control group (40 participants) and experimental group (42 participants). In the control group, the teacher used the board game “Conveyance GO” as a teaching tool; in the experimental group, both Conveyance GO and CTSTS were used to teach the Chinese language. The results indicate no significant difference in learning outcomes between the groups. However, the experimental group exhibited a significantly larger improvement in writing abilities than did the control group, especially in terms of cohesion, coherence, and grammatical accuracy.
For disorders with X-linked inheritance, variants may be transmitted through multiple generations of carrier females before an affected male is ascertained. Pathogenic
variants exclusively cause ...X-linked retinoschisis (XLRS). While
is constrained to variation, recurrent variants are frequently observed in unrelated probands. Here, we investigate recurrent pathogenic variants to determine the relative burden of mutational hotspot and founder allele events to this phenomenon. A cohort
variant analysis and standardized classification, including variant enrichment in the XLRS cohort and in
functional domains, were performed on 332 unrelated XLRS probands. A total of 108 unique
variants were identified. A subset of 19 recurrently observed
variants were evaluated in 190 probands by a haplotype analysis, using microsatellite and single nucleotide polymorphisms. Fourteen variants had at least two probands with common variant-specific haplotypes over ~1.95 centimorgans (cM) flanking
. Overall, 99/190 of reportedly unrelated probands had 25 distinct shared haplotypes. Examination of this XLRS cohort for common
haplotypes indicates that the founder effect plays a significant role in this disorder, including variants in mutational hotspots. This improves the accuracy of clinical variant classification and may be generalizable to other X-linked disorders.
The potential to enable unprecedented performance, durability, and safety has created the impetus to develop bulk-scale all-solid-state batteries employing metallic Li as the negative electrode. ...Owing to its low density, low electronegativity and high specific capacity, Li metal is the most attractive negative electrode. However, failure caused by the formation of dendrites has limited the widespread use of rechargeable batteries using metallic Li negative electrodes coupled with liquid electrolytes. One approach to mitigate the formation of dendrites involves the use of a solid electrolyte to physically stabilize the Li–electrolyte interface while allowing the facile transport of Li-ions. Though in principle this approach should work, it has been observed that at high Li deposition rates Li metal can propagate through relatively hard ceramic electrolytes and Li dendrite formation causing short circuit has been reported. Why this occurs is poorly understood, emphasizing the need to close the knowledge gap and facilitate the development of advanced batteries employing solid electrolytes. Here, through precise microstructural control, striking electron microscopy, and high-resolution surface spectroscopy, we directly observed for the first time the propagation of Li metal through a promising polycrystalline solid electrolyte based on the garnet mineral structure (Li6.25Al0.25La3Zr2O12). Moreover, we observed that Li preferentially deposits along grain boundaries (intergranularly). These results offer insight into the electrochemical-mechanical phenomena that govern the stability of the metallic Li–polycrystalline solid electrolyte interface and are essential to the maturation of solid-state batteries.
The study examines the effectiveness of using computer games for after-school remedial mastery learning. We incorporated instructional materials related to “area of a circle” into the popular ...Monopoly game to enhance the performance of sixth-grade students learning mathematics. The program requires that students enter the answers to avoid the shortcomings of multiple-choice questions. Throughout the game, whenever students are unable to answer questions correctly they receive immediate remedial instruction specifically for that question. This study sought to compare the effectiveness of game-based and video-based remedial instruction incorporated with elements of mastery learning. The results demonstrate that (a) both instructional videos and the proposed Monopoly game enhance the learning of mathematical concepts; and (b) the Monopoly game is more effective than instructional videos at leveraging the benefits of mastery learning. The goal of the research was to integrate games and mastery learning into after-school remedial instruction and design a game to practice the steps of mastery learning.
The purpose of this study is to examine the issues of students’ motivational beliefs in science learning and their relations with science achievement. Data of Taiwanese fourth and eighth graders from ...the Trends in International Mathematics and Science Study 2011 were examined. Students’ self-concept and intrinsic interest as motivational beliefs, and science scores in general and in different cognitive domains were used as measures in this study. A series of quantitative analyses along with statistical techniques accounting for the properties of international large-scale assessment data were utilized to investigate these issues. The results indicate that students’ motivational beliefs decrease over grades. The relations between the eighth graders’ motivational beliefs and science scores are positively stronger than those of the fourth graders. Meanwhile, students’ self-concept has a greater predictive power than intrinsic interest for science scores in both grades. Beyond documenting students’ motivational beliefs over grades, the conclusion also sheds light on the role of motivational beliefs, self-concept in particular, in explaining students’ science achievement.
The purpose of this study is to compare the impacts of flashcard and board games on the learning motivation, flow experience, and learning outcomes of learners of Chinese language. The subjects of ...this research were 34 learners who took beginner Chinese courses. Empirical research found out that both flashcard and board games have positively significant effects on learners’ learning motivation, flow experience and learning outcomes. In which, learners in the board game group have significantly higher learning outcomes than those in the flashcards group. However, the learning motivation and flow experience of the flashcard group are significantly higher than that of the educational board game group.
Over 150 000 Americans are diagnosed with colorectal cancer (CRC) every year, and annually over 50 000 individuals will die from CRC, necessitating improvements in screening, prognostication, disease ...management, and therapeutic options. Tumor metastasis is the primary factor related to the risk of recurrence and mortality. Yet, screening for nodal and distant metastasis is costly, and invasive and incomplete resection may hamper adequate assessment. Signatures of the tumor-immune microenvironment (TIME) at the primary site can provide valuable insights into the aggressiveness of the tumor and the effectiveness of various treatment options. Spatially resolved transcriptomics technologies offer an unprecedented characterization of TIME through high multiplexing, yet their scope is constrained by cost. Meanwhile, it has long been suspected that histological, cytological, and macroarchitectural tissue characteristics correlate well with molecular information (e.g., gene expression). Thus, a method for predicting transcriptomics data through inference of RNA patterns from whole slide images (WSI) is a key step in studying metastasis at scale. In this work, we collected tissue from 4 stage-III (pT3) matched colorectal cancer patients for spatial transcriptomics profiling. The Visium spatial transcriptomics (ST) assay was used to measure transcript abundance for 17 943 genes at up to 5000 55-micron (i.e., 1–10 cells) spots per patient sampled in a honeycomb pattern, co-registered with hematoxylin and eosin (H&E) stained WSI. The Visium ST assay can measure expression at these spots through tissue permeabilization of mRNAs, which are captured through spatially (i.e., x–y positional coordinates) barcoded, gene specific oligo probes. WSI subimages were extracted around each co-registered Visium spot and were used to predict the expression at these spots using machine learning models. We prototyped and compared several convolutional, transformer, and graph convolutional neural networks to predict spatial RNA patterns at the Visium spots under the hypothesis that the transformer- and graph-based approaches better capture relevant spatial tissue architecture. We further analyzed the model’s ability to recapitulate spatial autocorrelation statistics using SPARK and SpatialDE. Overall, the results indicate that the transformer- and graph-based approaches were unable to outperform the convolutional neural network architecture, though they exhibited optimal performance for relevant disease-associated genes. Initial findings suggest that different neural networks that operate on different scales are relevant for capturing distinct disease pathways (e.g., epithelial to mesenchymal transition). We add further evidence that deep learning models can accurately predict gene expression in whole slide images and comment on understudied factors which may increase its external applicability (e.g., tissue context). Our preliminary work will motivate further investigation of inference for molecular patterns from whole slide images as metastasis predictors and in other applications.
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