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Background: Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed. Objectives: To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE‐BPC and three other databases. Methods: This study utilized GENIE‐BPC, SEER, SEER‐Medicare, and Merative MarketScan Research Databases. Women with invasive breast cancer were identified through EHR, cancer registries or ICD‐9/10‐CM codes. The ages were 18+ years or per database requirement. Treatments were based on EHR or HCPCS/NDC codes in claims. Overall survival was estimated as time from diagnosis to death. Results: Of female breast cancer patients in GENIE‐BPC (n = 775), SEER (n = 548 336), SEER‐Medicare (n = 68 914), and Marketscan (n = 109 499) databases, the median ages at initial diagnosis were 44, 62, 74, and 57 years, respectively. A greater proportion of patients in GENIE‐BPC, compared to SEER/SEER‐Medicare, had higher nuclear grades (%III–%IV: 57% vs. 26%/24%), advanced disease stage (%IV: 25.3% vs. 5%/3.6%), percent of triple negative breast cancer (19.7% vs. 10.2%/8.5%), and receipt of chemotherapy (85.0% vs. NA/22.3%). The 1‐, 3‐, and 5‐year overall survival rates were lower in GENIE‐BPC (78.5%, 60.5%, 55.5%) than in SEER (95.8%, 89.5%, 85.5%) and SEER‐Medicare (91.6%, 81.4%, 75.0%). Conclusion: Breast cancer patients in GENIE‐BPC were younger, had more advanced disease, had a higher proportion of triple negative breast cancer and recipients of chemotherapy, and had poorer overall survival. Researchers must use statistical adjustment when extrapolating results (e.g., biomarker prevalence) from GENIE‐BPC to the larger breast cancer population. [ABSTRACT FROM AUTHOR]

Abstract Background Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. Methods To investigate the association between a patient’s responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. Results We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection. Conclusion Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

Background: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. Methods: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. Results: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection. Conclusion: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options. [ABSTRACT FROM AUTHOR]

In the dynamic restaurant industry, we introduce ''Genie,'' an AI-powered chatbot, represents an advancement in customer service efficiency through technological innovation. Designed to enhance restaurant operations including order processing, reservations, and FAQs management, Genie leverages advanced Natural Language Processing (NLP) techniques. By converting input queries into word embeddings and applying a sophisticated tag classification system, Genie precisely interprets customer intents and generates accurate responses, thereby markedly improving the dining experience. Our thorough examination of various word embeddings and classifiers—Word2Vec, Glove, BERT, Gaussian Naive Bayes, XGB, Artificial Neural Networks (ANN), and Recurrent Neural Networks—revealed that the combination of Word2Vec and ANN is the most effective, achieving an impressive accuracy rate of 88.9 %. This discovery highlights Genie's capability to not only streamline restaurant operations but also enhance customer satisfaction by minimizing wait times and facilitating contactless service options. Additionally, this study enriches the understanding of AI's application in service industries and explores the potential future impact of generative AI technologies on chatbot interactions. As AI technology advances, its integration is essential for Genie to deliver increasingly personalized and dynamic customer experiences, aligning with the evolving demands of the digital era. This research emphasizes the transformative impact of AI in the restaurant industry, providing valuable insights into its practical applications and future prospects for automated customer service solutions.

Differences in cancer genomes between racial groups may impact tumor biology and health disparities. However, the discovery of race-associated mutations is constrained by the limited representation and sample size of different racial groups in prior genomic studies. We evaluated the influence of race on the frequency of gene mutations using the Genomics, Evidence, Neoplasia, Information, Exchange database, a large genomic dataset aggregated from clinical sequencing. Matched cohort analyses were used to identify histology-specific race-associated mutations including increased TERT promoter mutations in Black and Asian patients with gliomas and bladder cancers, and a decreased frequency of mutations in DNA repair pathway genes and subunits of the SWI/SNF chromatin complex in Asian and Black patients across multiple cancer types. The distribution of actionable mutations in oncogenes was also race-specific, demonstrating how targeted therapies may have a disparate impact on racial groups. Down-sampling analyses indicate that larger sample sizes are likely to discover more race-associated mutations. These results provide a resource to understand differences in cancer genomes between racial groups which may inform the design of clinical studies and patient recruitment strategies in biomarker trials. [ABSTRACT FROM AUTHOR]

Although driverless technology belongs to the frontier of science and technology, there is no sufficient actual data. From the lack of a comprehensive systematic evaluation method of traffic safety under driverless penetration, considering the impact of the three core systems of driverless perception, decision-making, control, and the complex road factors on the safety of driving, we review the main risk causal factors through the analysis of the accident causal model STAMP and put forward the fusion of the Leaky Noisy-OR Gate and Bayesian network model. The Bayesian network professional analysis tool GeNIe 2.0 was used to simulate, analyze, and evaluate the driverless traffic risk Bayesian network model, which accurately assessed the traffic safety risk under driverless penetration and diagnosed and identified the sensitive risk factors. The results of this study concluded that, in order to effectively deal with the future traffic safety risks of driverless vehicles, vehicle enterprises, research institutions, software and hardware suppliers in the field of driverless driving should strengthen the research and development and manufacturing of key components such as perception, and enhance the depth of research and development of AI decision-making software, which provides a new way of thinking about the management of the safety risk of driverless traffic and a theoretical basis for the development and implementation of risk control measures. [ABSTRACT FROM AUTHOR]

Abstract Backgorund Colorectal cancer (CRC) is among the leading causes of cancer‐related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients. Methods We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next‐generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan‐Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)‐Non‐Hispanic, and GENIE‐Hispanic datasets. Results Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE‐Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability‐high (MSI), wild‐type KRAS, wild‐type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients. Conclusion This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non‐Hispanic and USH populations.

Backgorund: Colorectal cancer (CRC) is among the leading causes of cancer-related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients. Methods: We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next-generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan-Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)-Non-Hispanic, and GENIE-Hispanic datasets. Results: Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE-Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability-high (MSI), wild-type KRAS, wild-type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients. Conclusion: This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non-Hispanic and USH populations. [ABSTRACT FROM AUTHOR]

Although driverless technology belongs to the frontier of science and technology, there is no sufficient actual data. From the lack of a comprehensive systematic evaluation method of traffic safety under driverless penetration, considering the impact of the three core systems of driverless perception, decision-making, control, and the complex road factors on the safety of driving, we review the main risk causal factors through the analysis of the accident causal model STAMP and put forward the fusion of the Leaky Noisy-OR Gate and Bayesian network model. The Bayesian network professional analysis tool GeNIe 2.0 was used to simulate, analyze, and evaluate the driverless traffic risk Bayesian network model, which accurately assessed the traffic safety risk under driverless penetration and diagnosed and identified the sensitive risk factors. The results of this study concluded that, in order to effectively deal with the future traffic safety risks of driverless vehicles, vehicle enterprises, research institutions, software and hardware suppliers in the field of driverless driving should strengthen the research and development and manufacturing of key components such as perception, and enhance the depth of research and development of AI decision-making software, which provides a new way of thinking about the management of the safety risk of driverless traffic and a theoretical basis for the development and implementation of risk control measures.

Polytechnique Montréal s’est doté d’un portfolio numérique pour faire le suivi et l’évaluation des 12 compétences requises par le Bureau canadien d’agrément des programmes de génie. Cet article présente le contexte ayant mené à la mise en place de l’outil, nommé Polyfolio, ses principales fonctionnalités, ainsi que son processus de conception.

I attempt in this essay to shed new light on the origins of Louis Pasteur's uniquely progressive mind and spirit and the various factors in his background and upbringing that shaped them. There is, however, very limited documentation on the early period of Pasteur's life, apart from his son-in- law's (René Vallery-Radot) biographical account, and this is considered by many as more akin to a work of hagiography. We do have, on the other hand, Pasteur's correspondence with his parents and sisters as compiled and annotated by his grandson, Louis Pasteur Vallery-Radot. Using these limited sources, combined with what we know about Pasteur's home environment and early education, his cultural influences (like the books he read), and his drawings and etchings, I have attempted in this essay to hypothesize regarding the influences during Pasteur's childhood, adolescence, and very early adult years as a scientist and how they contributed to the formation of Pasteur's mind and spirit, while fully acknowledging the extent to which this is based on indirect evidence and, occasionally, outright speculation. [ABSTRACT FROM AUTHOR]

At a comprehensive, public university in Western Canada, a fourth-year course in risk and safety management was recently made a requirement for all engineering students; depending on their program, students may take this course in their second, third, fourth, or fifth year of their program. As a result of increasing class sizes, this course was shifted from traditional to blended instruction. Since blending and opening this course to students with varying years of undergraduate engineering experience, instructors noted a difference in students’ maturity (e.g., a change in quantity and quality of in-class discussion, questions, participation, student-teacher interactions, and problem solving capabilities) and questioned whether this impacted their interactions with online material. Research examining the impact of blended learning in Engineering has primarily focused on large first-year undergraduate courses; research about blended learning in upper-year engineering courses is sparse. Studies investigating courses with students of varying years of experience in the program are virtually non-existent. Therefore, to better understand students’ interactions with online material during blended learning as connected to years in their program, we examined the relationship between levels of interaction and performance of students by year in program. This study analyzed approximately 2000 students’ interactions with online material and performance across five sections of a risk-management course in engineering. We found that students who had completed more years of their program interacted less with online material than students earlier in their undergraduate careers. Academic performance, on the other hand, was higher for students who had interacted more with online material and slightly higher for students who had completed more years in their program. These results suggest that the delivery of instructional materials may need to be tailored to students’ year in their program. Further implications and areas of future study are discussed. Dans une université polyvalente publique de l’Ouest du Canada, un cours de quatrième année sur la gestion des risques et de la sécurité a été récemment déclaré obligatoire pour les étudiants et les étudiantes en génie. En fonction de leur programme, les étudiants et les étudiantes suivent ce cours dans la deuxième, la troisième, la quatrième ou la cinquième année de leur programme. Suite au nombre grandissant d’étudiants et d’étudiantes dans les classes, ce cours est passé d’un cours traditionnel à un cours en apprentissage hybride. Depuis que ce cours est offert en apprentissage hybride à des étudiants et à des étudiantes qui se trouvent dans diverses années de leur programme et dont l’expérience en génie du premier cycle varie, les professeurs et les professeures ont noté une différence dans la maturité des étudiants et des étudiantes (par ex. changement dans la quantité et la qualité des discussions en classe, questions, participation, interactions entre étudiants et professeurs et capacités de résolution de problèmes) et se demandent si cela a eu des effets sur leurs interactions avec le matériel en ligne. La recherche portant sur les effets de l’apprentissage hybride en génie s’est principalement penchée sur les grandes classes de première année du premier cycle universitaire. La recherche portant sur les cours de génie des années supérieures est peu abondante. Les études de recherche sur les cours où sont inscrits des étudiants et des étudiantes qui se trouvent dans diverses années de leur programme sont pratiquement inexistantes. C’est pourquoi, afin de mieux comprendre les interactions des étudiants et des étudiantes avec le matériel en ligne dans un cours hybride tel que connectées à l’année de leur programme, nous avons examiné la relation entre les niveaux d’interaction et la performance des étudiants et des étudiantes par année du programme. Cette étude a permis d’analyser environ 2000 interactions d’étudiants et d’étudiantes avec le matériel en ligne ainsi que leurs résultats académiques dans cinq sections d’un cours sur la gestion des risques en génie. Nous avons constaté que les étudiants et les étudiantes qui avaient complété davantage d’années dans leur programme interagissaient moins avec le matériel en ligne que les étudiants et les étudiantes qui se trouvaient au premier cycle de leur carrière. Les résultats académiques, par contre, était supérieurs parmi les étudiants et les étudiantes qui avaient interagi davantage avec le matériel en ligne et un peu plus élevés parmi les étudiants et les étudiantes qui avaient complété davantage d’années dans leur programme. Les résultats suggèrent que la fourniture de matériel didactique devrait peut-être être adaptée à l’année dans laquelle les étudiants et les étudiantes se trouvent dans leur programme. D’autres implications et des domaines d’études futures sont discutés.

Gustav Schilling charakterisierte Clara Wieck Schumann 1838 als geniale Virtuosin ebenso wie als geniale Komponistin, während sie selbst keinen Geniestatus für sich beanspruchte. Durch die im medizinisch-anthropologischen Diskurs im 19. Jahrhundert behauptete ›natürliche Ungleichheit‹ von Frauen und Männern wurde die Idee eines heldenhaften Genies, das unangestrengt und voraussetzungslos originelle Ideen produziert, verstärkt. Demgegenüber dokumentierte die Künstlerin, dass Komponieren harte Arbeit sein könne und sie das Handwerk systematisch gelernt habe. Heute hat sich der Fokus von der Diskussion des Genies auf die Erforschung von Kreativität verlagert. Einige zentrale Fragen, wie die nach den Akteur*innen, dem Publikum, den Aktionen, den Artefakten sowie den soziokulturellen und materiellen Entstehungsbedingungen musikalischer Werke können mit Kategorien der Genderforschung verbunden werden. Aus dieser Perspektive betrachte ich die Entstehung von Clara Wieck Schumanns Scherzo op. 10 und der Romanze op. 11/2. Die Kenntnis, wie und was unter Genie zu verschiedenen Zeiten verstanden wurde, konfrontiert uns damit, über eigene explizite wie implizite Überzeugungen nachzudenken und neue Zugänge zu ›post-genialistischen‹ Kunstwerken zu erarbeiten. In 1838 Gustav Schilling characterized Clara Wieck Schumann as a virtuoso and composer of genius; however, she never claimed genius for herself. The assumed naturalness of female inequality in medical and anthropological discourses of the nineteenth century reinforced the idea of a natural-born heroic genius who produces original ideas without effort and preconditions. In contrast, Clara Wieck Schumann documented that composing could be hard work and that she had received a systematic musical education. Today, the discussion of genius has given way to research on creativity. Some key questions of this research such as the actors, audiences, actions, artifacts, and sociocultural and material affordances of musical works can be connected to categories of gender studies. From this perspective I reflect on the compositional process of Clara Wieck Schumann’s Scherzo op. 10 and Romanze op. 11, no. 2. Understanding the concept of genius in different historical periods prompts us to re-think our own explicit and implicit assumptions and to find new approaches to “post-genius” art works.

Abstract Background Diet quality in older people with chronic obstructive pulmonary disease (COPD) is associated with better health and lung function. Social factors, such as social support, social networks and participation in activities, have been linked with diet quality in older age. A social network tool—GENIE (Generating Engagement in Network Involvement)—was implemented in a COPD community care context. The study aimed to assess the feasibility of the GENIE intervention to promote diet quality and other health behaviours in COPD. Methods Twenty-two community-dwelling older adults with COPD were recruited from a local COPD service. Participants were offered usual care or the GENIE intervention. Process evaluation methods were used to assess intervention implementation, context and mechanisms of impact; these included observations of patient interactions with the intervention, documented in observational field notes and in films of a patient group discussion. Diet quality was assessed by food frequency questionnaire; ‘prudent’ diet scores were used to describe diet quality at baseline and at 3-month follow-up. Change in diet quality was expressed per month, from baseline to follow-up. Results Feasibility data showed that the GENIE intervention could be implemented in this sample of community-living older people. The intervention was acceptable to clinicians and older people with COPD, especially for those with less severe disease, when facilitated appropriately and considering the levels of literacy of participants. There was no significant change in diet quality in the intervention group over the follow-up period (median change in prudent diet score per month (interquartile range (IQR), 0.03 (− 0.24–0.07)), whereas an overall fall in diet quality was observed in the control group (− 0.15 (− 0.24–0.03)). Conclusion The process evaluation findings suggest that this intervention is feasible and acceptable to both patients and clinicians. Although the sample size achieved in this study was small, findings suggest that the intervention may have a protective effect against declines in diet quality, and other health behaviours, in an older COPD population. Findings from this feasibility study indicate that further evaluation of the GENIE intervention is warranted in a larger study, with a longer follow-up. Trial registration ClinicalTrials.gov, NCT02935452 . NIH U.S. National Library of Medicine. Registered 17 October 2016.

Cet article propose d’explorer les statuts accordés aux compositeurs contemporains dans les premières années du XXe siècle en France, en comparant deux périodiques au format et aux lectorats très différents : d’un côté Musica (1902-1914), premier magazine musical français lancé par Pierre Lafitte, destiné à un lectorat issu de la bourgeoisie, essentiellement féminin et pratiquant la musique en amateur ; de l’autre, Le Mercure musical (1905-1906), une « petite revue » d’avant-garde dont la ligne éditoriale et les réseaux de circulation sont à l’opposé de ceux de Musica. Il s’agit de comprendre comment le format de ces deux périodiques a influencé la façon dont est conçu et véhiculé un objet commun, soit la grandeur culturelle des compositeurs contemporains. Il ressort que Musica mise sur le vedettariat et présente presque seulement des compositeurs déjà connus, alors que Le Mercure musical met principalement en avant des artistes émergents, souvent en marge ou en conflit avec les institutions officielles, en utilisant une rhétorique avant-courrière du génie qui sera un jour reconnu.

Abstract Background Significant numbers of variants detected in cancer patients are often left labeled only as variants of unknown significance (VUS). In order to expand precision medicine to a wider population, we need to extend our knowledge of pathogenicity and drug response in the context of VUS’s. Methods In this study, we analyzed variants from AACR Project GENIE Consortium APG (Cancer Discov 7:818-831, 2017) and compared them to the COSMIC database Forbes et al. (Nucleic Acids Res 43:D805-811, 2015) to identify recurrent variants that would merit further study. We filtered out known hotspot variants, inactivating variants in tumor suppressors, and likely benign variants by comparing with COSMIC and ExAC Lee et al. (Science 337:967-971, 2012). Results We have identified 45,933 novel variants with unknown significance unique to GENIE. In our analysis, we found on average six variants per patient where two could be considered as pathogenic or likely pathogenic and the majority are VUS’s. More importantly, we have discovered 730 recurrent variants that appear more than 3 times in GENIE but less than 3 in COSMIC. If we combine the recurrences of GENIE and COSMIC for all variants, 2586 are newly identified as occurring more than 3 times than when using COSMIC alone. Conclusions Although it would be inappropriate to blindly accept these recurrent variants as pathogenic, they may warrant higher priority than other observed VUS’s. These newly identified recurrent variants might affect the molecular profiles of approximately 1 in 6 patients. Further analysis and characterization of these variants in both research and clinical contexts will improve patient treatments and the development of new therapeutics.

Almond is an extendible open-source virtual assistant designed to help people access Internet services and IoT (Internet of Things) devices. Both are referred to as skills here. Service providers can easily enable their devices for Almond by defining proper APIs (Application Programming Interfaces) for ThingTalk in Thingpedia. ThingTalk is a virtual assistant programming language, and Thingpedia is an application encyclopedia. Almond uses a large neural network to translate user commands in natural language into ThingTalk programs. To obtain enough data for the training of the neural network, Genie was developed to synthesize pairs of user commands and corresponding ThingTalk programs based on a natural language template approach. In this work, we extended Genie to support Chinese. For 107 devices and 261 functions registered in Thingpedia, 649 Chinese primitive templates and 292 Chinese construct templates were analyzed and developed. Two models, seq2seq (sequence-to-sequence) and MQAN (multiple question answer network), were trained to translate user commands in Chinese into ThingTalk programs. Both models were evaluated, and the experiment results showed that MQAN outperformed seq2seq. The exact match, BLEU, and F1 token accuracy of MQAN were 0.7, 0.82, and 0.88, respectively. As a result, users could use Chinese in Almond to access Internet services and IoT devices registered in Thingpedia.

The TempO-Seq S1500+ platform(s), now available for human, mouse, rat, and zebrafish, measures a discrete number of genes that are representative of biological and pathway co-regulation across the entire genome in a given species. While measurement of these genes alone provides a direct assessment of gene expression activity, extrapolating expression values to the whole transcriptome (~26 000 genes in humans) can estimate measurements of non-measured genes of interest and increases the power of pathway analysis algorithms by using a larger background gene expression space. Here, we use data from primary hepatocytes of 54 donors that were treated with the endoplasmic reticulum (ER) stress inducer tunicamycin and then measured on the human S1500+ platform containing ~3000 representative genes. Measurements for the S1500+ genes were then used to extrapolate expression values for the remaining human transcriptome. As a case study of the improved downstream analysis achieved by extrapolation, the "measured only" and "whole transcriptome" (measured + extrapolated) gene sets were compared. Extrapolation increased the number of significant genes by 49%, bringing to the forefront many that are known to be associated with tunicamycin exposure. The extrapolation procedure also correctly identified established tunicamycin-related functional pathways reflected by coordinated changes in interrelated genes while maintaining the sample variability observed from the "measured only" genes. Extrapolation improved the gene- and pathway-level biological interpretations for a variety of downstream applications, including differential expression analysis, gene set enrichment pathway analysis, DAVID keyword analysis, Ingenuity Pathway Analysis, and NextBio correlated compound analysis. The extrapolated data highlight the role of metabolism/metabolic pathways, the ER, immune response, and the unfolded protein response, each of which are key activities associated with tunicamycin exposure that were unrepresented or underrepresented in one or more of the analyses of the original "measured only" dataset. Furthermore, the inclusion of the extrapolated genes raised "tunicamycin" from third to first upstream regulator in Ingenuity Pathway Analysis and from sixth to second most correlated compound in NextBio analysis. Therefore, our case study suggests an approach to extend and enhance data from the S1500+ platform for improved insight into biological mechanisms and functional outcomes of diseases, drugs, and other perturbations. [ABSTRACT FROM AUTHOR]

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Background: Diet quality in older people with chronic obstructive pulmonary disease (COPD) is associated with better health and lung function. Social factors, such as social support, social networks and participation in activities, have been linked with diet quality in older age. A social network tool—GENIE (Generating Engagement in Network Involvement)—was implemented in a COPD community care context. The study aimed to assess the feasibility of the GENIE intervention to promote diet quality and other health behaviours in COPD. Methods: Twenty-two community-dwelling older adults with COPD were recruited from a local COPD service. Participants were offered usual care or the GENIE intervention. Process evaluation methods were used to assess intervention implementation, context and mechanisms of impact; these included observations of patient interactions with the intervention, documented in observational field notes and in films of a patient group discussion. Diet quality was assessed by food frequency questionnaire; 'prudent' diet scores were used to describe diet quality at baseline and at 3-month follow-up. Change in diet quality was expressed per month, from baseline to follow-up. Results: Feasibility data showed that the GENIE intervention could be implemented in this sample of community-living older people. The intervention was acceptable to clinicians and older people with COPD, especially for those with less severe disease, when facilitated appropriately and considering the levels of literacy of participants. There was no significant change in diet quality in the intervention group over the follow-up period (median change in prudent diet score per month (interquartile range (IQR), 0.03 (− 0.24–0.07)), whereas an overall fall in diet quality was observed in the control group (− 0.15 (− 0.24–0.03)). Conclusion: The process evaluation findings suggest that this intervention is feasible and acceptable to both patients and clinicians. Although the sample size achieved in this study was small, findings suggest that the intervention may have a protective effect against declines in diet quality, and other health behaviours, in an older COPD population. Findings from this feasibility study indicate that further evaluation of the GENIE intervention is warranted in a larger study, with a longer follow-up. Trial registration: ClinicalTrials.gov, NCT02935452. NIH U.S. National Library of Medicine. Registered 17 October 2016. [ABSTRACT FROM AUTHOR]

À partir de remarques sur Une promenade de Bélial, conte philosophique d'Alfred Le Poittevin, cet article tente de proposer quelques éléments de réflexion pour éclairer la "mystique du style" de Flaubert à partir de la notion de métempsycose, au cœur du texte de Le Poittevin, ainsi qu’à travers le concept de « conatus » dû à Spinoza, référence discutée par Alfred et Gustave.

Der Beitrag fokussiert die Paratexte des Populären. Ausgangspunkt ist die Frage, warum ein solch hoher Begründungsaufwand zu leisten ist, um das vermeintlich ohnehin Evidente — Volksdichtung ist gut, natürlich und damit auch authentisch — erneut zu erweisen. Eine der Strategien, Authentizität herzustellen, ist die zunehmende Anonymisierung von Dichtung, wie an Beispielen von Sammlungen um 1800 gezeigt werden soll. The article focuses on the paratexts of collections of popular songs. The fundamental question it poses is: why did authors insist upon such a high degree of justification in order to prove what was supposedly already evident, i.e. that popular poetry is good, natural, and therefore authentic? One of the strategies of producing authenticity is the increasing anonymization of poetry, as is shown here with the help of examples of collections from around 1800. [ABSTRACT FROM AUTHOR]

Résumé L'étrange rapport qui semble se nouer entre l'expression du génie et de la folie chez certains grands hommes, tout comme chez les malades, a marqué les esprits à travers notre histoire. De nombreuses hypothèses vont dans le sens d'un véritable lien de parenté, ou au moins de relative similitude, entre les processus mentaux pouvant conduire à l'émergence d'une psychose comme à la créativité. Or, si généralement les observations ne confirment pas l'avantage en matière de créativité chez les malades souffrant de troubles psychotiques, et notamment de schizophrénie, certaines découvertes récentes pourraient bien aller dans le sens de facteurs communs tant au plan génétique qu'au plan cognitif. Notre propos sera ici de discuter ces différents points de vue pour avancer quelques pistes de réflexion explicatives, notamment autour du concept de vulnérabilité ou sensibilité à la psychose. Abstract Throughout history, it is striking to observe a strange connection between the expression of genius and madness in certain great men, just as in sick people. Thus, the scientific literature has produced many hypotheses in the sense of kinship or, at least, a relative similarity between mental processes that can lead to psychosis and the ability to creativity. However, while research generally does not confirm increased creativity in psychosis, especially in schizophrenia, some recent findings may well be in favor of genetic and cognitive common factors. Our purpose will then be to discuss these different points of view in order to advance some explanatory lines of reflection, particularly around the concept of vulnerability or sensitivity to psychosis. [ABSTRACT FROM AUTHOR]

Background: Significant numbers of variants detected in cancer patients are often left labeled only as variants of unknown significance (VUS). In order to expand precision medicine to a wider population, we need to extend our knowledge of pathogenicity and drug response in the context of VUS's.Methods: In this study, we analyzed variants from AACR Project GENIE Consortium APG (Cancer Discov 7:818-831, 2017) and compared them to the COSMIC database Forbes et al. (Nucleic Acids Res 43:D805-811, 2015) to identify recurrent variants that would merit further study. We filtered out known hotspot variants, inactivating variants in tumor suppressors, and likely benign variants by comparing with COSMIC and ExAC Lee et al. (Science 337:967-971, 2012).Results: We have identified 45,933 novel variants with unknown significance unique to GENIE. In our analysis, we found on average six variants per patient where two could be considered as pathogenic or likely pathogenic and the majority are VUS's. More importantly, we have discovered 730 recurrent variants that appear more than 3 times in GENIE but less than 3 in COSMIC. If we combine the recurrences of GENIE and COSMIC for all variants, 2586 are newly identified as occurring more than 3 times than when using COSMIC alone.Conclusions: Although it would be inappropriate to blindly accept these recurrent variants as pathogenic, they may warrant higher priority than other observed VUS's. These newly identified recurrent variants might affect the molecular profiles of approximately 1 in 6 patients. Further analysis and characterization of these variants in both research and clinical contexts will improve patient treatments and the development of new therapeutics. [ABSTRACT FROM AUTHOR]

Background: Differences in DNA alterations in prostate cancer among White, Black, and Asian men have been widely described. This is the first description of the frequency of DNA alterations in primary and metastatic prostate cancer samples of self-reported Hispanic men., Methods: We utilized targeted next-generation sequencing tumor genomic profiles from prostate cancer tissues that underwent clinical sequencing at academic centers (GENIE 11th). We decided to restrict our analysis to the samples from Memorial Sloan Kettering Cancer Center as it was by far the main contributor of Hispanic samples. The numbers of men by self-reported ethnicity and racial categories were analyzed via Fisher's exact test between Hispanic-White versus non-Hispanic White., Results and Limitations: Our cohort consisted of 1412 primary and 818 metastatic adenocarcinomas. In primary adenocarcinomas, TMPRSS2 and ERG gene alterations were less common in non-Hispanic White men than Hispanic White (31.86% vs. 51.28%, p = 0.0007, odds ratio [OR] = 0.44 [0.27-0.72] and 25.34% vs. 42.31%, p = 0.002, OR = 0.46 [0.28-0.76]). In metastatic tumors, KRAS and CCNE1 alterations were less prevalent in non-Hispanic White men (1.03% vs. 7.50%, p = 0.014, OR = 0.13 [0.03, 0.78] and 1.29% vs. 10.00%, p = 0.003, OR = 0.12 [0.03, 0.54]). No significant differences were found in actionable alterations and androgen receptor mutations between the groups. Due to the lack of clinical characteristics and genetic ancestry in this dataset, correlation with these could not be explored., Conclusion: DNA alteration frequencies in primary and metastatic prostate cancer tumors differ among Hispanic-White and non-Hispanic White men. Notably, we found no significant differences in the prevalence of actionable genetic alterations between the groups, suggesting that a significant number of Hispanic men could benefit from the development of targeted therapies., (© 2023 Wiley Periodicals LLC.)

Data from a large autopsy series were analyzed to address questions pertinent to primary age-related tauopathy (PART) and Alzheimer's disease (AD): what factors are associated with increased severity of neurofibrillary degeneration in brains that lack neuritic amyloid plaques?; is there an association between Apolipoprotein E (APOE) alleles and PART pathologic severity independent of amyloid-β (Aβ) deposits?; and, how do the stains used to detect plaques and tangles impact the experimental results? Neuropathologic data were evaluated from elderly research volunteers whose brain autopsies were performed at University of Kentucky Alzheimer's Disease Center (UK-ADC; N = 145 subjects). All of the included subjects' brains lacked neuritic amyloid plaques according to the CERAD diagnostic criteria and the average final MMSE score before death was 26.8±4.6 stdev. The study incorporated evaluation of tissue with both silver histochemical stains and immunohistochemical stains to compare results; the immunohistochemical stains (Aβ and phospho-tau) were scanned and quantified using digital pathologic methods. Immunohistochemical stains provided important advantages over histochemical stains due to sensitivity and detectability via digital methods. When AD-type pathology was in its presumed earliest phases, neocortical parenchymal Aβ deposits were associated with increased medial temporal lobe neurofibrillary tangles. The observation supports the NIA-AA consensus recommendation for neuropathologic diagnoses, because even these "diffuse" Aβ deposits signal that AD pathobiologic mechanisms are occurring. Further, the data were most compatible with the hypothesis that the APOEɛ4 allele exerts its effect(s) via driving Aβ deposition, i.e., an "upstream" influence, rather than being associated directly with Aβ- independent PART pathology. [ABSTRACT FROM AUTHOR]

La formation continue va de pair avec la qualification des gens ciblés, vu que cette formation est toujours au service de l'organisation et de l'individu lui- même. En conséquence, la visée donc, de notre travail est de chercher dans quelle mesure le programme GENIE contribué à l'amélioration des apprentissages par l'intégration des TICE. En fait, ce programme a pour objectif de généraliser l'utilisation des technologies de l'information et de la communication dans les établissements scolaires et de qualifier les ressources humaines en la matiêre. Pour ceci, nous adoptons le modêle de Visi-Tic, développé par P.Coen et J.Schumacher (2006) [6], et qui sert à évaluer le degré de pénétration d'une innovation. Par ailleurs, nous avons conçu et réalisé une enquête sous forme de questionnaire, auprês de 52 enseignants et enseignantes de différentes disciplines.

The main objective of this paper is to analyze the dynamic response of floating bridges with transverse pontoons, when subjected to harmonic regular wave loads. As a result, a simplified beam model of the Bergsøysund floating bridge is established in the FEM software Abaqus. Additional “synthetic” floating bridge structures are subsequently built and analyzed in a similar manner. The pontoon model constructed in Genie is analyzed in HydroD to obtain the pontoon's structural model and hydrodynamic parameters. In addition to these parameters, by implementing the calculated data of mass and sectional properties of the bridge truss-work components, the simplified beam model of the bridge is built in Abaqus. Taking the Bergsøysund floating bridge model as the basis, “synthetic” bridge models are similarly assembled and studied. The effect of sideway mooring is also considered for the elongated bridge models. For each of the bridge models, eigenfrequency analysis is carried out in Abaqus in order to determine the natural frequency of the sway (lateral) and heave modes. For a natural frequency of a bridge model obtained from Abaqus, the updated added mass of each pontoon is obtained from HydroD by directing waves of the same frequency at the pontoon model. The eigenfrequency analysis is performed again with the updated added mass and this process is repeated until the natural frequency of the mode and the subsequent added mass are concurrent. The wave load amplitude on the pontoon model corresponding to the updated natural frequency of the mode is acquired from the hydrodynamic analysis in HydroD. The dynamic analysis is then carried out in Abaqus by applying the harmonic regular wave load on each pontoon of the bridge model. Efficient techniques are presented to calculate the phase difference at each pontoon. This arises due to the combined effect of changing wave direction and shapes of the models. A simplified method is employed to gauge the critical angle of wave heading. Limitations with regard to the non-application of full matrices of the pontoon's structural model and hydrodynamic parameters are highlighted. Negatively damped sway motions are controlled by the application of external lateral dampers. Mixed results are obtained at the estimated critical angles. Better result is obtained by iteration of the responses for growing angles of wave heading. [ABSTRACT FROM AUTHOR]

We analyzed all published reports of individuals not exposed to syntactic language until puberty: two feral children, who grew up without hearing any language, and eight deaf linguistic isolates, who grew up communicating to their families using homesign or kitchensign, a system of gestures which allows them to communicate simple commands but lacks much in the way of syntax. A common observation in these individuals is the lifelong difficulty understanding syntax and spatial prepositions, even after many years of rehabilitation. This debilitating condition stands in stark contrast to linguistic isolates' performance on memory as well as semantic tests: they could easily remember hundreds of newly learned words and identify previously seen objects by name. The lack of syntactic language comprehension in linguistic isolates may stem from inability to understand words and/or grammar or inability to mentally synthesize known objects into novel configurations. We have previously shown that purposeful construction of novel mental images is the function of the lateral prefrontal cortex (LPFC) ability to dynamically control posterior cortex neurons (Vyshedskiy et al. 2017). Here we have ranked all tests performed on linguistic isolates by their reliance on the LPFC control of the posterior cortex: a) the amount of posterior cortex territory that needs to be recruited by the LPFC and b) the number of disparate objects that have to be combined together by the LPFC in order to answer the test question. According to our analysis, linguistic isolates performed well in all tests that did not involve the LPFC control of the posterior cortex, showed decreasing scores in tests that involved greater recruitment of the posterior cortex by the LPFC, and failed in tests that involved greatest recruitment of posterior cortex necessary for mental synthesis of multiple objects. This pattern is consistent with inadequate frontoposterior connections in linguistic isolates. We discuss implications of these findings for the importance of early syntactic language exposure in formation of frontoposterior connections. [ABSTRACT FROM AUTHOR]

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Entsprungen aus den viktorianischen Romanen von Sir Arthur Conan Doyle kehrt die Figur des Kriminalvirtuosen Sherlock Holmes in das 21. Jahrhundert mit der BBC-Serie Sherlock zurück. Der vorliegende Text geht dem Privatdetektiv Sherlock Holmes in dieser Neuinterpretation nach und untersucht Konzepte äußerlicher wie innerlicher Performanz. Denkfiguren wie das Genie, der Dandy oder der Held werden miteinander diskutiert, in Beziehung gesetzt und (neu) interpretiert. Dabei werden Techniken von Einsamkeit mit dem Attribut der Langeweile und des Spiels gelesen. Die filmästhetische Ebene bildet einen entscheidenden Faktor, um den genialen Kopf, die dandyhafte Attitüde und die heldenhaften Taten von Sherlock zu erkennen und nachzuvollziehen. Auf stilistischer Seite war es ein Anliegen die Spannungselemente sowie die Ausgänge der einzelnen Episoden von Sherlock nicht preiszugeben und alles auf die Figur Sherlock Holmes mit ihrer zeitlichen Transformation und vielseitigen Charakteristik, die die Bildung einer Hybridgestalt fordert, zu fokussieren.

Ann Jefferson, Genius in France: An Idea and its Uses (Princeton, Oxford: Princeton University Press, 2015), 273 S., 11 Abb.

We present a study of coherent pion production in neutrino-nucleus interactions using the formalism based on partially conserved axial current theorem which connects the neutrino-nucleus cross section to the pion-nucleus elastic scattering cross section. Pion-nucleus elastic scattering cross section is calculated using Glauber model which takes three inputs, nuclear densities, pion-nucleon cross section and α π N which is the ratio of real to imaginary part of πN forward scattering amplitude, for which the parametrizations are obtained from measured data. We calculate the differential and integrated cross sections for charge and neutral current coherent pion production in neutrino (anti-neutrino)-nucleus scattering for a range of nuclear targets from light to heavy materials such as lithium, carbon, hydrocarbon, oxygen, silicon, argon, iron and lead. The results of these cross section calculations are compared with the measured data and with the calculations from the Berger-Sehgal model and GENIE package. There is an excellent agreement between the calculated and measured cross sections with Glauber model. While GENIE and Berger-Sehgal model give a good description of the data in the lower energy range the present calculations describe the data in all energy ranges. Predictions are also made for upcoming experiments like INO and DUNE in the coherent region of neutrino cross section. [ABSTRACT FROM AUTHOR]

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Der Beitrag wendet sich gegen die Karriere des Begriff s ,Werte', der seit dem 18. und 19. Jahrhundert die traditionelle Sprache der Tugendethik ablöste. Der Begriff ,Wert' setzt Subjektivismus und Pluralismus voraus. Die Vorstellung, Werte ließen sich von Philosophen oder gar von einem Philosophen ,schaffen', impliziert eine Überschätzung des Philosophen und der Philosophie überhaupt. This contribution opposes the career of the term ,values', which has replaced the traditional language of virtue ethics since the 18th and 19th centuries. The term ,value' presupposes subjectivism and pluralism. The idea that philosophers or even one philosopher can create values implies a hubris of the philosopher and of philosophy in general. [ABSTRACT FROM AUTHOR]

Isabella von Ägypten treibt die Kritik am Künstlersubjekt auf einen Höhepunkt. Die phantastischen Figuren verweisen alle insofern auf den Text als eklektizistisches Konstrukt, als sie die Kritik am romantischen Genie- und Künstlersubjekt in eine Dekonstruktion des Originalitätspostulats überführen. Dem auf der Oberflächenstruktur postulierten Ideal steht auf einer subtextuellen Ebene eine durch das Phantastische evozierte Kritik entgegen, die das Primat des Schöpfers über sein Werk Lügen straft.

This study explores the identity and function of the mostly unnoticed figure of Sha'tiqatu, a creature who plays a pivotal role in the story of the Ugaritic King Kirta. The exploration of this under appreciated figure is situated in the context of Ugaritic apotropea and within the better documented Mesopotamian cultural backdrop. A counterpart article provides the philological and epigraphic analysis to the Sha'tiqatu Narrative found in KTU 1.16.5.10-1.16.6.14. [ABSTRACT FROM AUTHOR]

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The ubiquity of index-finger pointing, and its early emergence in child development, has suggested that such pointing may be biologically-determined. However, cross-cultural variation in the form of pointing has also been noted, with some observations of middle-finger pointing. Here we examine the limited corpus of publically-available video data on the signs and gestures of Genie, a child who suffered severe social and linguistic deprivation throughout her childhood. These data suggest that Genie favored the use of the middle finger in points, in ASL signs that have an index-finger target handshape, and in object exploration. We speculate that middle-finger pointing in children may reflect an articulatory preference that is not limited to pointing, but that may encompass a range of manual behaviors. [ABSTRACT FROM AUTHOR]