tbuckley/cabot-search huggingface dataset:
The Landscape of Alterations in DNA Damage Response Pathways in Colorectal Cancer
Authors: Hiroyuki Arai, Andrew Elliott, Joanne Xiu, Jingyuan Wang, Francesca Battaglin, Natsuko Kawanishi, Shivani Soni, Wu Zhang, Joshua Millstein, Davendra Sohal, Richard M. Goldberg, Michael J. Hall, Aaron J. Scott, Moh'd Khushman, Jimmy J. Hwang, Emil Lou, Benjamin A. Weinberg, John L. Marshall, Albert C. Lockhart, Phillip Stafford, Jian Zhang, Roberto Moretto, Chiara Cremolini, W. Michael Korn, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2021)

Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and is associated with chemosensitivity. Although the mismatch repair system has been extensively studied, the clinical implications of other mechanisms associated with DDR alterations in patients with colorectal cancer remain unclear. This study aimed to understand DDR pathways alterations and their association with common clinical features in patients with colorectal cancer.Next-generation sequencing and whole-transcriptome sequencing were conducted using formalin-fixed paraffin-embedded samples submitted to a commercial Clinical Laboratory Improvement Amendments-certified laboratory. Samples with pathogenic or presumed pathogenic mutations in 29 specific DDR-related genes were considered as DDR-mutant (DDR-MT) and the remaining samples as DDR-wild type (DDR-WT).Of 9,321 patients with colorectal cancer, 1,290 (13.8%) were DDR-MT. The frequency of DDR-MT was significantly higher in microsatellite instability-high (MSI-H) cases than in microsatellite stable cases (76.4% vs. 9.5%). The DDR-MT genotype was higher in the right-sided, RAS-wild, BRAF-mutant, and CMS1 subgroups. However, these associations were primarily confounded by the distribution of MSI status. Compared with the DDR-WT tumors, the DDR-MT tumors had a higher mutational burden and gene expression levels in the immune-related pathway, which were independent of MSI status.We characterized a distinct subgroup of patients with colorectal cancer with tumors harboring mutations in the DDR-related genes. These patients more commonly had MSI-H tumors and exhibited an activated immune signature regardless of their tumor's MSI status. These findings warrant further investigations to develop personalized treatment strategies in this significant subgroup of patients with colorectal cancer.
Abstract 14393: Increased Arterial Stiffness Amplifies the Association Between Hemodynamic Stress and Cardiac Overload: The Japan Morning Surge-Home Blood Pressure Study
Authors: Yusuke Ishiyama, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2019)

Background: Increased blood pressure variability (BPV), which is used as an index of hemodynamic stress, induces change in left ventricular stroke volume and contractility, potentially leading to c...
Active case-finding of tuberculosis in general populations and at-risk groups: a systematic review and meta-analysis
Authors: Anders Solitander Bohlbro, Victor Schwartz Hvingelby, Frauke Rudolf, Christian Wejse, Cecilie Blenstrup Patsche
Journal: European Respiratory Journal (2021)

Background The World Health Organization (WHO) recommends active case-finding (ACF) of tuberculosis (TB) in certain high-risk groups; however, more evidence is needed to elucidate the scope of ACF beyond the current recommendations. In this study we aimed to systematically review yields (the prevalence of active TB) of studies on ACF in general populations and at-risk groups. Methods A literature search in PubMed, Embase and the Cochrane Central Library (CENTRAL) was performed for studies concluded after 31 December 1999 and published before 1 September 2020. Screening yields were estimated and yield/prevalence ratios (ratio between yield of study and WHO estimated prevalence of TB) were calculated to assess which groups might especially benefit from ACF. Finally, risk of bias was assessed and heterogeneity was investigated using meta-regression and sensitivity analyses. Results We included 197 studies, with a total of 12 372 530 screened and 53 158 cases found. Yields were high among drug users, close contacts, the poor and marginalised, people living with HIV, and prison inmates across incidence strata, and estimated yield/prevalence ratios in screenings of general populations tended to be &gt;1 with an overall ratio of 1.4 and ranging between 1.0 and 1.5. Sensitivity analyses suggested that inclusion of studies at high risk of bias contributed to underestimation of yields. Conclusion Despite many studies using insensitive screening methods, these results suggest that more at-risk groups should be considered for inclusion in future screening recommendations and that screening of general populations may outperform current case-finding practices, providing evidence for extending ACF beyond the current recommendations.
Intranasal levels of lead as an exacerbation factor for allergic rhinitis in humans and mice
Authors: Huadong Xu, Nobutaka Ohgami, Masafumi Sakashita, Kazuhiro Ogi, Kazunori Hashimoto, Akira Tazaki, Keming Tong, Masayo Aoki, Shigeharu Fujieda, Masashi Kato
Journal: Journal of Allergy and Clinical Immunology (2021)
<i>Clostridioides difficile</i> Infection (Japanese Version)
Authors: Alice Y. Guh, Preeta K. Kutty
Journal: Annals of Internal Medicine (2018)

In the Clinic2 October 2018Clostridioides difficile Infection (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREEAlice Y. Guh, MD, MPH and Preeta K. Kutty, MD, MPHAlice Y. Guh, MD, MPHFrom the Centers for Disease Control and Prevention, Atlanta, Georgia. (A.Y.G., P.K.K.)Search for more papers by this author and Preeta K. Kutty, MD, MPHFrom the Centers for Disease Control and Prevention, Atlanta, Georgia. (A.Y.G., P.K.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201810020_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Clostridioides difficile Infection (Guh AY, Kutty PK. Clostridioides difficile Infection. Ann Intern Med. 2018;169:ITC49-ITC64. doi:10.7326/AITC201810020). Author, Article, and Disclosure InformationAffiliations: From the Centers for Disease Control and Prevention, Atlanta, Georgia. (A.Y.G., P.K.K.)Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Acknowledgment: The authors thank Margaret Trexler Hessen, MD, author of the previous version of this In the Clinic.Funding Source: American College of Physicians.Disclosures: Drs. Guh and Kutty, ACP Contributing Authors, have nothing to disclose. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1415.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoClostridioides difficile Infection Alice Y. Guh and Preeta K. Kutty Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the Clinic2’-Fucosyllactose inhibits proliferation of Clostridioides difficile ATCC 43599 in the CDi-screen, an in vitro model simulating Clostridioides difficile infection 2 October 2018Volume 169, Issue 7Page: JITC49-JITC64 ePublished: 16 March 2021 Issue Published: 2 October 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
<i>Porphyromonas gingivalis</i> Promotes Colorectal Carcinoma by Activating the Hematopoietic <i>NLRP3</i> Inflammasome
Authors: Xi Wang, Yiqun Jia, Liling Wen, Wenxin Mu, Xianrui Wu, Tao Liu, Xiangqi Liu, Juan Fang, Yizhao Luan, Ping Chen, Jinlong Gao, Ky-Anh Nguyen, Jun Cui, Gucheng Zeng, Ping Lan, Qianming Chen, Bin Cheng, Zhi Wang
Journal: Cancer Research (2021)

Abstract Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various digestive cancers. However, whether P. gingivalis can promote colorectal cancer and the underlying mechanism associated with such promotion remains unclear. In this study, we found that P. gingivalis was enriched in human feces and tissue samples from patients with colorectal cancer compared with those from patients with colorectal adenoma or healthy subjects. Cohort studies demonstrated that P. gingivalis infection was associated with poor prognosis in colorectal cancer. P. gingivalis increased tumor counts and tumor volume in the ApcMin/+ mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to P. gingivalis exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. P. gingivalis promoted colorectal cancer via NLRP3 inflammasome activation in vitro and in vivo. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on P. gingivalis pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that P. gingivalis contributes to colorectal cancer neoplasia progression by activating the hematopoietic NLRP3 inflammasome. Significance: This study demonstrates that the periodontal pathogen P. gingivalis can promote colorectal tumorigenesis by recruiting myeloid cells and creating a proinflammatory tumor microenvironment.
Bench to Bedside Discovery, Innovation, Global Health Equity, and Security
Authors: Victor J. Dzau
Journal: Circulation (2021)

Dr Dzau was born in Shanghai. He received his Bachelor of Science in Biology and his MD degree from McGill University. He was a medical resident, Chief Resident, and the founding Chief of the Division of Vascular Medicine at the Peter Bent Brigham Hospital (now the Brigham and Women's Hospital). He moved to Stanford in 1990 as the Chief of the Division of Cardiovascular Medicine and later became Chairman of the Department of Medicine. Six years later, he returned to Harvard Medical School as the Hersey Professor of the Theory and Practice of Medicine and as Chairman of the Department of Medicine at Brigham and Women's Hospital. He then became the Chancellor for Health Affairs, President, and CEO of the Duke University Medical Center. In 2014, he was elected to become the President of the Institute of Medicine (now the National Academy of Medicine). He is a member of the National Academy of Medicine, the American Academy of Arts and Sciences, and the European Academy of Sciences and Arts.
Contribution of Long-Term Exposure to Outdoor Black Carbon to the Carcinogenicity of Air Pollution: Evidence regarding Risk of Cancer in the Gazel Cohort
Authors: Emeline Lequy, Jack Siemiatycki, Kees de Hoogh, Danielle Vienneau, Jean-François Dupuy, Valérie Garès, Ole Hertel, Jesper Heile Christensen, Sergey Zhivin, Marcel Goldberg, Marie Zins, Bénédicte Jacquemin
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Black carbon (BC), a component of fine particulate matter [particles with an aerodynamic diameter ≤2:5 lm (PM 2:5 )], may contribute to carcinogenic effects of air pollution.Until recently however, there has been little evidence to evaluate this hypothesis.OBJECTIVE: This study aimed to estimate the associations between long-term exposure to BC and risk of cancer.This study was conducted within the French Gazel cohort of 20,625 subjects.METHODS: We assessed exposure to BC by linking subjects' histories of residential addresses to a map of European black carbon levels in 2010 with back-and forward-extrapolation between 1989 and 2015.We used extended Cox models, with attained age as time-scale and time-varying cumulative exposure to BC, adjusted for relevant sociodemographic and lifestyle variables.To consider latency between exposure and cancer diagnosis, we implemented a 10-y lag, and as a sensitivity analysis, a lag of 2 y.To isolate the effect of BC from that of total PM 2:5 , we regressed BC on PM 2:5 and used the residuals as the exposure variable.RESULTS: During the 26-y follow-up period, there were 3,711 incident cancer cases (all sites combined) and 349 incident lung cancers.Median baseline exposure in 1989 was 2.65 10 -5 =m [interquartile range (IQR): 2.23-3.33],which generally slightly decreased over time.Using 10 y as a lag-time in our models, the adjusted hazard ratio per each IQR increase of the natural log-transformed cumulative BC was 1.17 (95% confidence interval: 1.06, 1.29) for all-sites cancer combined and 1.31 (0.93, 1.83) for lung cancer.Associations with BC residuals were also positive for both outcomes.Using 2 y as a lag-time, the results were similar.DISCUSSION: Our findings for a cohort of French adults suggest that BC may partly explain the association between PM 2:5 and lung cancer.Additional studies are needed to confirm our results and further disentangle the effects of BC, total PM 2:5 , and other constituents.
Machine Learning of Bone Marrow Histopathology Identifies Genetic and Clinical Determinants in Patients with MDS
Authors: Oscar E. Brück, Susanna E. Lallukka-Brück, Helena R. Hohtari, Aleksandr Ianevski, Freja T. Ebeling, Panu E. Kovanen, Soili I. Kytölä, Tero A. Aittokallio, Pedro M. Ramos, Kimmo V. Porkka, Satu M. Mustjoki
Journal: Blood Cancer Discovery (2021)

In myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN), bone marrow (BM) histopathology is assessed to identify dysplastic cellular morphology, cellularity, and blast excess. Yet, other morphologic findings may elude the human eye. We used convolutional neural networks to extract morphologic features from 236 MDS, 87 MDS/MPN, and 11 control BM biopsies. These features predicted genetic and cytogenetic aberrations, prognosis, age, and gender in multivariate regression models. Highest prediction accuracy was found for TET2 [area under the receiver operating curve (AUROC) = 0.94] and spliceosome mutations (0.89) and chromosome 7 monosomy (0.89). Mutation prediction probability correlated with variant allele frequency and number of affected genes per pathway, demonstrating the algorithms' ability to identify relevant morphologic patterns. By converting regression models to texture and cellular composition, we reproduced the classical del(5q) MDS morphology consisting of hypolobulated megakaryocytes. In summary, this study highlights the potential of linking deep BM histopathology with genetics and clinical variables. SIGNIFICANCE: Histopathology is elementary in the diagnostics of patients with MDS, but its high-dimensional data are underused. By elucidating the association of morphologic features with clinical variables and molecular genetics, this study highlights the vast potential of convolutional neural networks in understanding MDS pathology and how genetics is reflected in BM morphology.See related commentary by Elemento, p. 195.
Increased MHC Class I Expression on Platelets in Human and Murine Sepsis
Authors: Li Guo, Sikui Shen, Jesse W Rowley, Kyra Mccomas, Juan Su, Bhanu Kanth Manne, Ben Berger, Elizabeth Middleton, Robert A. Campbell, Andrew S. Weyrich, Matthew T. Rondina
Journal: Blood (2017)
US Hospital Capacity Managers’ Experiences and Concerns Regarding Preparedness for Seasonal Influenza and Influenza-like Illness
Authors: Gavin H. Harris, Kimberly J. Rak, Jeremy M. Kahn, Derek C. Angus, Olivia R. Mancing, Julia Driessen, David J. Wallace
Journal: JAMA Network Open (2021)

The 2017-2018 influenza season in the US was marked by a high severity of illness, wide geographic spread, and prolonged duration compared with recent previous seasons, resulting in increased strain throughout acute care hospital systems.To characterize self-reported experiences and views of hospital capacity managers regarding the 2017-2018 influenza season in the US.In this qualitative study, semistructured telephone interviews were conducted between April 2018 and January 2019 with a random sample of capacity management administrators responsible for throughput and hospital capacity at short-term, acute care hospitals throughout the US.Each participant's self-reported experiences and views regarding high patient volumes during the 2017-2018 influenza season, lessons learned, and the extent of hospitals' preparedness planning for future pandemic events. Interviews were recorded and transcribed and then analyzed using thematic content analysis. Outcomes included themes and subthemes.A total of 53 key hospital capacity personnel at 53 hospitals throughout the US were interviewed; 39 (73.6%) were women, 48 (90.6%) had a nursing background, and 29 (54.7%) had been in the occupational role for more than 4 years. Participants' experiences were categorized into several domains: (1) perception of strain, (2) effects of influenza and influenza-like illness on staff and patient care, (3) immediate staffing and capacity responses to influenza and influenza-like illness, and (4) future staffing and capacity preparedness for influenza and influenza-like illness. Participants reported experiencing perceived strain associated with concerns about preparedness for seasonal influenza and influenza-like illness as well as concerns about staffing, patient care, and capacity, but future pandemic planning within hospitals was not reported as being a high priority.The findings of this qualitative study suggest that during the 2017-2018 influenza season, there were systemic vulnerabilities as well as a lack of hospital preparedness planning for future pandemics at US hospitals. These issues should be addressed given the current coronavirus disease 2019 pandemic.
Enhancer Pleiotropy, Gene Expression, and the Architecture of Human Enhancer–Gene Interactions
Authors: Devika Singh, Soojin V Yi
Journal: Molecular Biology and Evolution (2021)

Abstract Enhancers are often studied as noncoding regulatory elements that modulate the precise spatiotemporal expression of genes in a highly tissue-specific manner. This paradigm has been challenged by recent evidence of individual enhancers acting in multiple tissues or developmental contexts. However, the frequency of these enhancers with high degrees of “pleiotropy” out of all putative enhancers is not well understood. Consequently, it is unclear how the variation of enhancer pleiotropy corresponds to the variation in expression breadth of target genes. Here, we use multi-tissue chromatin maps from diverse human tissues to investigate the enhancer–gene interaction architecture while accounting for 1) the distribution of enhancer pleiotropy, 2) the variations of regulatory links from enhancers to target genes, and 3) the expression breadth of target genes. We show that most enhancers are tissue-specific and that highly pleiotropy enhancers account for &amp;lt;1% of all putative regulatory sequences in the human genome. Notably, several genomic features are indicative of increasing enhancer pleiotropy, including longer sequence length, greater number of links to genes, increasing abundance and diversity of encoded transcription factor motifs, and stronger evolutionary conservation. Intriguingly, the number of enhancers per gene remains remarkably consistent for all genes (∼14). However, enhancer pleiotropy does not directly translate to the expression breadth of target genes. We further present a series of Gaussian Mixture Models to represent this organization architecture. Consequently, we demonstrate that a modest trend of more pleiotropic enhancers targeting more broadly expressed genes can generate the observed diversity of expression breadths in the human genome.
Symptom cluster is associated with prolonged return-to-play in symptomatic athletes with acute respiratory illness (including COVID-19): a cross-sectional study—AWARE study I
Authors: Martin Schwellnus, Nicola Sewry, Carolette Snyders, Kelly Kaulback, Paola Silvia Wood, Ishen Seocharan, Wayne Derman, James H Hull, Maarit Valtonen, Esme Jordaan
Journal: British Journal of Sports Medicine (2021)

There are no data relating symptoms of an acute respiratory illness (ARI) in general, and COVID-19 specifically, to return to play (RTP).To determine if ARI symptoms are associated with more prolonged RTP, and if days to RTP and symptoms (number, type, duration and severity) differ in athletes with COVID-19 versus athletes with other ARI.Cross-sectional descriptive study.Online survey.Athletes with confirmed/suspected COVID-19 (ARICOV) (n=45) and athletes with other ARI (ARIOTH) (n=39).Participants recorded days to RTP and completed an online survey detailing ARI symptoms (number, type, severity and duration) in three categories: 'nose and throat', 'chest and neck' and 'whole body'. We report the association between symptoms and RTP (% chance over 40 days) and compare the days to RTP and symptoms (number, type, duration and severity) in ARICOV versus ARIOTH subgroups.The symptom cluster associated with more prolonged RTP (lower chance over 40 days; %) (univariate analysis) was 'excessive fatigue' (75%; p<0.0001), 'chills' (65%; p=0.004), 'fever' (64%; p=0.004), 'headache' (56%; p=0.006), 'altered/loss sense of smell' (51%; p=0.009), 'Chest pain/pressure' (48%; p=0.033), 'difficulty in breathing' (48%; p=0.022) and 'loss of appetite' (47%; p=0.022). 'Excessive fatigue' remained associated with prolonged RTP (p=0.0002) in a multiple model. Compared with ARIOTH, the ARICOV subgroup had more severe disease (greater number, more severe symptoms) and more days to RTP (p=0.0043).Symptom clusters may be used by sport and exercise physicians to assist decision making for RTP in athletes with ARI (including COVID-19).