tbuckley/cabot-search huggingface dataset:
Changes in IgA-targeted microbiota following fecal transplantation for recurrent <i>Clostridioides difficile</i> infection
Authors: Kelsey E Huus, Marcin Frankowski, Maja Pučić-Baković, Frano Vučković, Gordan Lauc, Benjamin H Mullish, Julian R Marchesi, Tanya M Monaghan, Dina Kao, B. Brett Finlay
Journal: Gut Microbes (2020)

Secretory immunoglobulin A (IgA) interacts with intestinal microbiota and promotes mucosal homeostasis. IgA-bacteria interactions are altered during inflammatory diseases, but how these interactions are shaped by bacterial, host, and environmental factors remains unclear. In this study, we utilized IgA-SEQ to profile IgA-bound fecal bacteria in 48 recurrent Clostridioides difficile patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, Escherichia coli was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple Firmicutes species. Post-FMT IgA-targeting was unaffected by the route of FMT delivery (colonoscopy versus capsule), suggesting that both methods lead to the establishment of healthy immune-bacterial interactions in the gut. Interestingly, IgA-targeting in FMT recipients closely resembled the IgA-targeting patterns of the donors, and fecal donor identity was significantly associated with IgA-targeting of the recipient microbiota. These data support the concept that intrinsic bacterial properties drive IgA recognition across genetically distinct human hosts. Together, this study suggests that IgA-bacterial interactions are reestablished in human FMT recipients to resemble that of the healthy fecal donor.
Increased advanced glycation end product and meat consumption is associated with childhood wheeze: analysis of the National Health and Nutrition Examination Survey
Authors: Jing Gennie Wang, Bian Liu, Francesca Kroll, Corrine Hanson, Alfin Vicencio, Steven Coca, Jaime Uribarri, Sonali Bose
Journal: Thorax (2020)

We examined 4388 children from the 2003 to 2006 National Health and Nutrition Examination Survey and used survey-design-adjusted multivariable logistic regression to evaluate associations between dietary advanced glycation end product (AGE) and meat consumption frequencies and respiratory symptoms. Higher AGE intake was significantly associated with increased odds of wheezing (adjusted OR 1.18; 95% CI 1.02 to 1.36), wheeze-disrupted sleep (1.26; 95% CI 1.05 to 1.51) and exercise (1.34; 95% CI 1.08 to 1.67) and wheezing requiring prescription medication (1.35; 95% CI 1.13 to 1.63). Higher intake of non-seafood meats was associated with wheeze-disrupted sleep (2.32; 95% CI 1.11 to 4.82) and wheezing requiring prescription medication (2.23; 95% CI 1.10 to 4.54).
Neural Organoids and the Precautionary Principle
Authors: Jonathan Birch, Heather Browning
Journal: The American Journal of Bioethics (2020)

It is a familiar idea that we should "apply the precautionary principle" when designing animal welfare regulations: we should not allow our uncertainty about the sentience of some animals to delay the adoption of proportionate measures to protect those animals from severe welfare threats.The same general idea should be applied to neural organoid research.If any of a set of neurological "warning signs" is found, proportionate measures should be taken to mitigate welfare risks.A measure likely to be proportionate is to bring the organoids in question within the scope of regulation that already exists for scientific research on sentient animals (such as, in a UK context, the "ASPA" regulatory framework).
Roles of ASH1 in DKK1 and E-cadherin repression and neuroendocrine differentiation in lung cancer
Authors: Hirotaka Osada, Shuta Tomida, Yasushi Yatabe, Yoshio Tatematsu, Toshiyuki Takeuchi, Hideki Murakami, Yutaka Kondo, Yoshitaka Sekido, Takashi Takahashi
Journal: Cancer Research (2008)

3459  The proneural basic-helix-loop-helix protein achaete-scute homolog 1 (ASH1) is expressed in a very limited spectrum of normal and cancerous cells in a lineage-specific manner, including normal pulmonary neuroendocrine cells (PNECs) and lung cancer cells with neuroendocrine (NE) features. Our previous results indicated that ASH1 may play a crucial role in the growth and survival of lung cancers with NE features, which prompted us to investigate the molecular function of ASH1 in relation to its involvement in carcinogenic processes. The ASH1 gene was introduced into a typical adenocarcinoma cell line, A549. Comparison of expression profiles resulted in the identification of 219 and 67 genes with up- and down-regulation. Up-regulated genes included those directly related to NE differentiation, such as chromogranin B (CHGB) and secretogranin II (SCG2), while down-regulated genes included such putative tumor suppressors as DKK1 and DKK3, negative regulators of Wnt/β-catenin signaling, as well as E-cadherin and integrin β1. DKK1 repression is unlikely to be a consequence of Wnt/β-catenin inactivation, because ASH1 is able to activate the Wnt/β-catenin signaling pathway. The results of a chromatin immunoprecipitation assay clearly demonstrated direct binding of ASH1 to the DKK1 and E-cadherin promoters, as well as transcription-repressing histone deacetylation and tri-methylation of lysine 27 (H3K27me3) of histone H3. In contrast, the transduction of ASH1 in A549 cells led to induction of H3 acetylation and a reduction of H3K27me3 in CHGB and SCG2 promoters, resulting in a strong induction of CHGB and SCG2 expression. In addition, ASH1-transduced A549 adenocarcinoma cells exhibited markedly altered morphology characteristics as compared to lung cancer cells with NE features both in vitro and in vivo, and also grew faster in vivo. Herein, we report for the first time that ASH1 functions as a dual transcription factor, by activating NE differentiation markers and also repressing putative tumor suppressors. Our results provide important clues for a better understanding of the molecular and cellular biological roles of ASH1 in the process of carcinogenesis of lung cancers with NE features, and warrant future investigations to shed light on the lineage-specific dependency of ASH1 gene.
米国におけるヘパリン誘発性血小板減少症の疾患負担,合併症率および健康管理コスト:集団ベース研究【JST・京大機械翻訳】
Authors: Dhakal Binod, Kreuziger Lisa Baumann, Rein Lisa, Kleman Ariel, Fraser Raphael, Aster Richard H, Hari Parameswaran, Padmanabhan Anand
Journal: The Lancet Haematology (2018)
Attenuation of Circuit Longevity in COVID-19 Critical Illness with AKI on Continuous Venovenous Hemodiafiltration Despite the Use of Regional Citrate Anticoagulation (RCA) and Heparin-Bonded AN 69 (Oxiris®) Filter
Authors: Tung Lin Lee, Zhong Hong Liew, Manish Kaushik, Li Choo Michelle Ng, Jiunn Wong, Hui-Lin Choong, Han K. Tan
Journal: Journal of the American Society of Nephrology (2020)

Lee, Tung Lin; Liew, Zhong Hong; Kaushik, Manish; Ng, Li Choo Michelle; Wong, Jiunn; Choong, Hui-Lin; Tan, Han K. Author Information
Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers
Authors: Dhivya R. Sudhan, Angel Guerrero-Zotano, Helen Won, Paula González Ericsson, Alberto Servetto, Mariela Huerta-Rosario, Dan Ye, Kyung-min Lee, Luigi Formisano, Yan Guo, Qi Liu, Lisa N. Kinch, Monica Red Brewer, Teresa Dugger, James Koch, Michael J. Wick, Richard E. Cutler, Alshad S. Lalani, Richard Bryce, Alan Auerbach, Ariella B. Hanker, Carlos L. Arteaga
Journal: Cancer Cell (2020)
Eruptions and related clinical course among 296 hospitalized adults with confirmed COVID-19
Authors: Sergey Rekhtman, Rachel Tannenbaum, Andrew Strunk, Morgan Birabaharan, Shari Wright, Nicole Grbic, Ashna Joseph, Stephanie K. Lin, Aaron C. Zhang, Eric C. Lee, Erika Rivera, Michael Qiu, John Chelico, Amit Garg
Journal: Journal of the American Academy of Dermatology (2020)
Polymer-conjugated glucosamine complexed with boric acid shows tumor-selective accumulation and simultaneous inhibition of glycolysis
Authors: Waliul Islam, Yoshitaka Matsumoto, Jun Fang, Ayaka Harada, Takuro Niidome, Katsuhiko Ono, Hiroyasu Tsutsuki, Tomohiro Sawa, Takahisa Imamura, Kazuo Sakurai, Nobuyoshi Fukumitsu, Hirofumi Yamamoto, Hiroshi Maeda
Journal: Biomaterials (2020)
21-Gene Assay and Breast Cancer Mortality in Ductal Carcinoma In Situ
Authors: Eileen Rakovitch, Rinku Sutradhar, Sharon Nofech-Mozes, Sumei Gu, Cindy Fong, Wedad Hanna, Lawrence Paszat
Journal: JNCI Journal of the National Cancer Institute (2020)

The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the overtreatment of DCIS. The 21-gene recurrence score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown.We performed a population-based analysis of 1362 individuals of DCIS aged 75 years or younger at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as >25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were 2-sided.With 16 years median follow-up, 36 (2.6%) died of BC, and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (hazard ratio = 11.27, 95% confidence interval [CI] = 3.00 to 42.33; P < .001) in women aged 50 years or younger at diagnosis treated with breast-conserving surgery alone, culminating in a 9.4% (95% CI = 2.3% to 22.5%) 20-year risk of BC death. For women with a high RS, treatment with radiotherapy was associated with a 71% (hazard ratio = 0.29, 95% CI = 0.10 to 0.89; P = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC.The 21-gene RS predicts BC mortality in DCIS and combined with age (50 years or younger) at diagnosis can identify individuals for whom radiotherapy reduces the risk of death from BC.
Abstract 9735: Accuracy of Commercial Heart Rate Monitors in Runners: A Prospective Study
Authors: Selena R Pasadyn, Mohamad Soudan, Marc Gillinov, Penny Houghtaling, Dermot Phelan, Nicole Gillinov, Barbara Bittel, Milind Desai
Journal: Circulation (2019)

Purpose: Elite athletes, particularly competitive runners, are using wrist worn devices with the heart rate (HR) feature to guide their training. However, few studies have assessed the effectivenes...
Preload Independence Is Associated with Extubation Failure in Simple Weaning Patients: A Multicenter Cohort Study
Authors: Diego B. Porto, Beatriz A. Beltrão, Fabricio S. Medeiros, José Augusto Santos Pellegrini, Márcio M. Boniatti
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Preload Independence Is Associated with Extubation Failure in Simple Weaning Patients: A Multicenter Cohort Study." American Journal of Respiratory and Critical Care Medicine, 203(7), pp. 916–918
Quality Improvement Project: Examining Urine Sediment and Microscopic Findings in COVID-19 AKI Patients
Authors: Abdulhadi T. Gelaidan, Ajai S. Rajabalan, Janice P. Lea, Jose E. Navarrete, Jason Cobb
Journal: Journal of the American Society of Nephrology (2020)

Gelaidan, Abdulhadi T.; Rajabalan, Ajai S.; Lea, Janice P.; Navarrete, Jose E.; Cobb, Jason Author Information
Impact of COVID-19 Pandemic on Global Poliovirus Surveillance
Authors: Delayo J. Zomahoun, Ashley L. Burman, Cynthia J. Snider, Claire Chauvin, Tracie Gardner, Jacquelyn S. Lickness, Jamal A. Ahmed, Ousmane Diop, Sue Gerber, Abhijeet Anand
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On January 30, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern (1). On March 24, 2020, the Global Polio Eradication Initiative (GPEI) suspended all polio supplementary immunization activities and recommended the continuation of polio surveillance (2). In April 2020, GPEI shared revised polio surveillance guidelines in the context of the COVID-19 pandemic, which focused on reducing the risk for transmission of SARS-CoV-2, the virus that causes COVID-19, to health care workers and communities by modifying activities that required person-to-person contact, improving hand hygiene and personal protective equipment use practices, and overcoming challenges related to movement restrictions, while continuing essential polio surveillance functions (3). GPEI assessed the impact of the COVID-19 pandemic on polio surveillance by comparing data from January to September 2019 to the same period in 2020. Globally, the number of acute flaccid paralysis (AFP) cases reported declined 33% and the mean number of days between the second stool collected and receipt by the laboratory increased by 70%. Continued analysis of AFP case reporting and stool collection is critical to ensure timely detection and response to interruptions of polio surveillance.
The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury
Authors: Matt S. Zinter, Caroline A. Lindemans, Birgitta A. Versluys, Madeline Y. Mayday, Sara Sunshine, Gustavo Reyes, Marina Sirota, Anil Sapru, Michael A. Matthay, Sandhya Kharbanda, Christopher C. Dvorak, Jaap J. Boelens, Joseph L. DeRisi
Journal: Blood (2020)
Abstract 12033: Value of BNP in Prediction of Major Bleeding Events Among Patients With Atrial Fibrillation in the Era of Direct Oral Anticoagulants
Authors: Hiroshi Miyama, Seiji Takatsuki, Takehiro Kimura, Nobuhiro Ikemura, Yoshinori Katsumata, Ikuko Ueda, Kenji Hashimoto, Terumasa Yamashita, Taishi Fujisawa, Kazuaki Nakajima, Hideaki Kanki, Koji Negishi, Keiichi Nagami, Keiichi Fukuda, Shun Kohsaka
Journal: Circulation (2019)

Introduction: In the present era, the direct oral anticoagulants (DOACs) are prevailing for the stroke prevention of atrial fibrillation (AF) albeit the risk stratification for major bleeding is st...
Outcomes of Patients with Chronic Myeloid Leukemia Treated with Third-Line Tyrosine Kinase Inhibitors
Authors: Koji Sasaki, Elias Jabbour, Ghayas C. Issa, Guillermo Garcia-Manero, Tapan M. Kadia, William G. Wierda, Musa Yilmaz, Courtney D. DiNardo, Jeffrey Skinner, Maria Khouri, Naveen Pemmaraju, Patrice Nasnas, Sherry A. Pierce, Jorge E. Cortes, Hagop M. Kantarjian
Journal: Blood (2020)
Docosanoic acid conjugation to siRNA enables functional and safe delivery to skeletal and cardiac muscles
Authors: Annabelle Biscans, Jillian Caiazzi, Nicholas McHugh, Vignesh Hariharan, Manish Muhuri, Anastasia Khvorova
Journal: Molecular Therapy (2020)

Oligonucleotide therapeutics hold promise for the treatment of muscle- and heart-related diseases. However, oligonucleotide delivery across the continuous endothelium of muscle tissue is challenging. Here, we demonstrate that docosanoic acid (DCA) conjugation of small interfering RNAs (siRNAs) enables efficient (~5% of injected dose), sustainable (>1 month), and non-toxic (no cytokine induction at 100 mg/kg) gene silencing in both skeletal and cardiac muscles after systemic injection. When designed to target myostatin (muscle growth regulation gene), siRNAs induced ~55% silencing in various muscle tissues and 80% silencing in heart, translating into a ~50% increase in muscle volume within 1 week. Our study identifies compounds for RNAi-based modulation of gene expression in skeletal and cardiac muscles, paving the way for both functional genomics studies and therapeutic gene modulation in muscle and heart.
Progress in National Policies Supporting the Sustainable Development Goals: Policies that Matter to Income and Its Impact on Health
Authors: Amy Raub, Jody Heymann
Journal: Annual Review of Public Health (2020)

From education to working conditions, from income to discrimination, social determinants of health (SDH) shape the majority of health outcomes. Governments are often best positioned to address the major SDH on a population-wide basis. In 2015, governments around the world committed to improving all core SDH when all countries agreed to a set of goals that would improve education, work, income, and equal opportunity, among other areas, in the Sustainable Development Goals (SDGs). Using data from the WORLD Policy Analysis Center, this article highlights how quantitative policy measures can be used to hold governments accountable for their commitments to the SDGs and thus to improve the SDH. Three areas are examined in detail to illustrate this approach to monitoring policy change: ensuring an adequate income, enhancing equal opportunities at work by prohibiting discrimination and sexual harassment, and enabling children and youth to complete their education.
Abstract 12540: Application of Knowledge-Based Reconstruction to Three Dimensional Echocardiography and Comparison With Semiautomatic Border Detection Method for Evaluating Ventricular Function in Tetralogy of Fallot
Authors: Ling Li, Andreas Schuster, Mary Craft, George Varghese, Shelby Kutty
Journal: Circulation (2018)

Background: The Knowledge-Based Reconstruction (KBR) technology has conventionally used 2D echocardiograms and positional data for processing into 3D representations and surface rendering for funct...
Aging Reprograms the Hematopoietic-Vascular Niche to Impede Regeneration and Promote Fibrosis
Authors: Yutian Chen, Qiang Pu, Yongyuan Ma, Hua Zhang, Tinghong Ye, Chengjian Zhao, Xiaojuan Huang, Yafeng Ren, Lina Qiao, Han-Min Liu, Charles T. Esmon, Bi-Sen Ding, Zhongwei Cao
Journal: Cell Metabolism (2020)
Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox
Authors: Peter Dubsky, Katja Pinker, Fatima Cardoso, Giacomo Montagna, Mathilde Ritter, Carsten Denkert, Isabel T Rubio, Evandro de Azambuja, Giuseppe Curigliano, Oreste Gentilini, Michael Gnant, Andreas Günthert, Nik Hauser, Joerg Heil, Michael Knauer, Mona Knotek-Roggenbauerc, Susan Knox, Tibor Kovacs, Henry M Kuerer, Sibylle Loibl, Meinrad Mannhart, Icro Meattini, Frederique Penault-Llorca, Nina Radosevic-Robin, Patrizia Sager, Tanja Španić, Petra Steyerova, Christoph Tausch, Marie-Jeanne T F D Vrancken Peeters, Walter P Weber, Maria J Cardoso, Philip Poortmans
Journal: The Lancet Oncology (2020)
Validation of orotate phosphoribosyltransferase (OPRT) as a predictive factor of 5-FU sensitivity by using RNAi technology
Authors: Etsuko Toda, Hideki Nagase, Kazuki Sakamoto, Yoshikazu Sugimoto, Toshinori Oka
Journal: Cancer Research (2006)

1384  Purpose: 5-Fluorouracil (5-FU) is one of the most effective an anticancer drugs used in chemotherapy against a variety of solid tumors. It exerts its anticancer effects through the inhibition of thymidylate synthase (TS) and the incorporation of its metabolites into RNA. 5-FU is phosphorylated and activated by three pathways involving orotate phosphoribosyltransferase (OPRT), uridine phosphorylase (UP), or thymidine phosphorylase (TP); however, the OPRT pathway is considered as the major phosphorylation pathway of 5-FU. In this study, to verify the role of OPRT in metabolism and cytotoxic function of 5-FU, we inhibited OPRT mRNA by using RNAi technology, and examined the effect of OPRT knockdown on the chemosensitivity of 5-FU in MIAPaCa-2 human pancreatic cancer cells and WiDr human colon cancer cells. Method: MIAPaCa-2 and WiDr cells were transfected with siRNA (final 33nM) using Lipofectamine 2000. At 24h following siRNA treatment, cells were re-seeded into 96-well plates. Then after overnight incubation, cells were treated with 5-FU or gemcitabine for 4 days and cell growth was determined by MTT assay. OPRT mRNA and protein were detected using one-step real time RT-PCR method and ELISA kit. TS inhibition rate was quantified by detection of ternary complex using Western blotting. The amount of 5-FU incorporated into RNA was detected using [6-14C] 5-FU. Result: Four siRNA sequences were designed for OPRT and the one with the highest efficiency was selected. In MIAPaCa-2 cells, the siRNA for OPRT showed a 90% and 70% inhibitory effect on the OPRT mRNA and protein, respectively. Furthermore, OPRT knockdown had no effect on cell proliferation and resulted in a 15-fold decrease in the sensitivity of the cells to 5-FU. In WiDr cells, the siRNA for OPRT showed an 80% inhibitory effect on OPRT mRNA, and OPRT knockdown resulted in a 4.5-fold decrease in the sensitivity of the cells to 5-FU. In both cell lines, OPRT inhibition did not affect the sensitivity of the cells to other antimetabolite such as gemcitabine which does not require phosphorylation by OPRT. Moreover, OPRT knockdown by using siRNA did not influence TS, dihydropyrimidine dehydrogenase (DPD), TP, and UP mRNA levels, indicating that these factors were not responsible for the decrease in 5-FU sensitivity. We also found that TS inhibition rate by 5-FU and the amount of 5-FU incorporated into RNA were markedly decreased by the RNAi-medicated downregulation of OPRT in MIAPaCa-2. Conclusion: These results suggest that 5-FU is mainly phosphorylated by OPRT pathway in these cell lines and OPRT is an important predictive factor of 5-FU sensitivity.
Community Approaches for Integrating Environmental Exposures into Human Models of Disease
Authors: Anne E. Thessen, Cynthia J. Grondin, Resham D. Kulkarni, Susanne Brander, Lisa Truong, Nicole A. Vasilevsky, Tiffany J. Callahan, Lauren E. Chan, Brian Westra, Mary Willis, Sarah E. Rothenberg, Annie M. Jarabek, Lyle Burgoon, Susan A. Korrick, Melissa A. Haendel
Journal: Environmental Health Perspectives (2020)

A critical challenge in genomic medicine is identifying the genetic and environmental risk factors for disease. Currently, the available data links a majority of known coding human genes to phenotypes, but the environmental component of human disease is extremely underrepresented in these linked data sets. Without environmental exposure information, our ability to realize precision health is limited, even with the promise of modern genomics. Achieving integration of gene, phenotype, and environment will require extensive translation of data into a standard, computable form and the extension of the existing gene/phenotype data model. The data standards and models needed to achieve this integration do not currently exist.
Microvascular Injury in the Brains of Patients with Covid-19
Authors: Myoung-Hwa Lee, Daniel P Perl, Govind Nair, Wenxue Li, Dragan Maric, Helen Murray, Stephen J Dodd, Alan P Koretsky, Jason A Watts, Vivian Cheung, Eliezer Masliah, Iren Horkayne-Szakaly, Robert Jones, Michelle N Stram, Joel Moncur, Marco Hefti, Rebecca D Folkerth, Avindra Nath
Journal: New England Journal of Medicine (2020)

Microvascular Changes in the Brain in Covid-19 High-resolution MRI and histopathological study of the brains of patients who had died from Covid-19 showed punctate hyperintensities and punctate or ...
Demographic and Clinical Characteristics of Patients with CKD and SARS-CoV2 Undergoing Hemodialysis Treatment
Authors: Laura C Fuentes-Mendez, Angela M. Cordoba Hurtado, L. M. Perez-Navarro, Rafael Valdez-Ortiz, Maribel Merino
Journal: Journal of the American Society of Nephrology (2020)

Fuentes-Mendez, Laura C; Cordoba Hurtado, Angela M.; Perez-Navarro, L. M.; Valdez-Ortiz, Rafael; Merino, Maribel Author Information