tbuckley/cabot-search huggingface dataset:
New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: substantial changes for clinical practice
Authors: Andreas K Lindner, Veerle Lejon, François Chappuis, Jorge Seixas, Leon Kazumba, Michael P Barrett, Erick Mwamba, Olema Erphas, Elie A Akl, Gemma Villanueva, Hanna Bergman, Pere Simarro, Augustin Kadima Ebeja, Gerardo Priotto, Jose Ramon Franco
Journal: The Lancet Infectious Diseases (2019)
Targeting Mitochondrial Fission to Trigger Cancer Cell Death
Authors: V. Ashutosh Rao
Journal: Cancer Research (2019)

Abstract Carefully orchestrated interactions between mitochondrial proteins that facilitate cell death remain a topic of intense research, however, key steps remain to be elucidated, especially those that drive selective killing in cancer cells. How mitochondrial dysfunction and its regulation in cancer can be robustly leveraged for anticancer cell killing in a heterogeneous population of cells within a tumor also remains a promising but unfulfilled premise. Toward this goal, in this issue of Cancer Research, Seo and colleagues have identified the protein complex between mitochondrial fission factor (MFF1 and MFF2) and voltage-dependent anion channel (VDAC1) as a novel regulator of mitochondrial cell death and a potential target for selective cancer cell killing. See related article by Seo et al., p. 6215
Extracellular vesicle (ECV)-modified polyethylenimine (PEI) complexes for enhanced siRNA delivery in vitro and in vivo
Authors: Petro Zhupanyn, Alexander Ewe, Thomas Büch, Anastasia Malek, Phil Rademacher, Claudia Müller, Anja Reinert, Yarúa Jaimes, Achim Aigner
Journal: Journal of Controlled Release (2019)
Letter to the Editor: Might Denosumab Fit in Primary Biliary Cholangitis Treatment?
Authors: Ana Lleo, Xiong Ma, M. Eric Gershwin, Pietro Invernizzi
Journal: Hepatology (2019)

Potential conflict of interest: Dr. Lleo is on the speakers' bureau for Intercept, AbbVie, MSD, and Gilead. Dr. Gershwin has been an investigator to PBC trials sponsored by Arena Pharmaceuticals, Bristol‐Myers Squibb, Cymabay Pharmaceuticals, Genentech and Johnson and Johnson. Dr. Invernizzi received grants from Intercept, Gilead, and Bruschettini. TO THE EDITOR: We read with interest the recent communication1 reporting the efficacy and safety of 3‐year treatment with denosumab for osteoporosis in patients with primary biliary cholangitis (PBC). PBC is a chronic cholestatic liver disease characterized by progressive destruction of intrahepatic bile ducts, portal tract inflammation, and fibrosis that may eventually progress to end‐stage liver disease.2 Even though the exact etiology of PBC remains unknown, it is extensively accepted that development of PBC requires one or more environmental factors that initiate an autoimmune response in genetically predisposed individuals. Osteoporosis is a common extrahepatic complication in PBC patients that highly impairs quality of life. Denosumab, a fully human monoclonal antibody against the receptor activator of nuclear factor‐κB ligand (RANKL), is widely used for treatment of osteoporosis based on the fact that it increases bone mineral density by inhibiting development and activity of osteoclasts, thereby decreasing bone resorption. Accumulating evidence suggests the importance of RANKL signaling in autoimmunity, with the immune and skeletal systems being tightly interconnected. In addition, murine models lacking RANK or RANKL show defects in B‐cell number and homeostasis involving interleukin‐10 and CD40 signaling,3 and single‐nucleotide polymorphism SNP analysis has revealed that the RANKL gene is near a novel risk locus for PBC, suggesting a role of the RANKL‐RANK axis in PBC pathogenesis.4 Furthermore, our group has demonstrated that cholangiocytes from PBC patients express high levels of RANK and that the immune infiltrate within the portal areas around bile ducts in PBC are highly RANKL positive.5 Most important, hepatic level of RANKL was associated with disease severity. Our data therefore strongly suggested a role of the RANK‐RANKL axis in the innate immune activation in PBC, and we hypothesize that the damaged cholangiocytes, which express high levels of RANK, lead to the recruitment of RANKL‐positive cells and ultimately the classic portal tract infiltrates. Taken altogether, a number of old and new evidences suggests that denosumab might have a wide beneficial role in PBC treatment, besides osteoporosis.
Genomics of periodontal disease and tooth morbidity
Authors: Thiago Morelli, Cary S. Agler, Kimon Divaris
Journal: Periodontology 2000 (2019)

Abstract In this review we critically summarize the evidence base and the progress to date regarding the genomic basis of periodontal disease and tooth morbidity (ie, dental caries and tooth loss), and discuss future applications and research directions in the context of precision oral health and care. Evidence for these oral/dental traits from genome‐wide association studies first emerged less than a decade ago. Basic and translational research activities in this domain are now under way by multiple groups around the world. Key departure points in the oral health genomics discourse are: (a) some heritable variation exists for periodontal and dental diseases; (b) the environmental component (eg, social determinants of health and behavioral risk factors) has a major influence on the population distribution but probably interacts with factors of innate susceptibility at the person‐level; (c) sizeable, multi‐ethnic, well‐characterized samples or cohorts with high‐quality measures on oral health outcomes and genomics information are required to make decisive discoveries; (d) challenges remain in the measurement of oral health and disease, with current periodontitis and dental caries traits capturing only a part of the health‐disease continuum, and are little or not informed by the underlying biology; (e) the substantial individual heterogeneity that exists in the clinical presentation and lifetime trajectory of oral disease can be identified and leveraged in a precision medicine framework or, if unappreciated, can hamper translational efforts. In this review we discuss how composite or biologically informed traits may offer improvements over clinically defined ones for the genomic interrogation of oral diseases. We demonstrate the utility of the results of genome‐wide association studies for the development and testing of a genetic risk score for severe periodontitis. We conclude that exciting opportunities lie ahead for improvements in the oral health of individual patients and populations via advances in our understanding of the genomic basis of oral health and disease. The pace of new discoveries and their equitable translation to practice will largely depend on investments in the education and training of the oral health care workforce, basic and population research, and sustained collaborative efforts..
Abstract A51: Using single-cell gene expression profiles to determine the cellular landscape of pancreatic ductal adenocarcinoma
Authors: Veerin R. Sirihorachai, Samantha B. Kemp, Marina Pasca Di Magliano
Journal: Cancer Research (2019)

Abstract A key feature of pancreatic cancer is the extensive fibroinflammatory stroma that constitutes the bulk of the tumor volume. The stroma includes fibroblasts, extracellular matrix, and abundant infiltrating immune cells. The latter are largely suppressive immune cells, including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Data from our laboratory and many others show that immune cells are a key determinant of pancreatic cancer progression and metastasis. Previous data from the lab showed that the immune infiltration in the pancreas is regulated by signals deriving from oncogenic Kras-expressing epithelial cells. We tested the hypothesis that oncogenic Kras, through activation of its effector pathway MAPK/ERK, directly regulates the accumulation of suppressive myeloid and lymphoid cells at the premetastatic niche. We used a doxycycline-inducible, reversible iKras* cell line derived from genetically engineered mouse model to modulate expression of Kras in orthotopically implanted tumors. We used the 10X Genomics platform for single-cell RNAseq to distinguish populations of cells collected from the tumors in both the Kras-On and Kras-Off groups at single-cell resolution. Using the Seurat R package, we analyzed the data from the two groups using unsupervised clustering methods to define clusters of cells based on their gene expression data. We then broadly defined these populations using cell type-specific gene expression patterns. Our next step is to define subpopulations of cells on which we can perform differential expression analyses to determine the changes in gene expression between the Kras-On and Kras-Off groups. Citation Format: Veerin R. Sirihorachai, Samantha B. Kemp, Marina Pasca Di Magliano. Using single-cell gene expression profiles to determine the cellular landscape of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A51.
Defects in Signal Recognition Particle (SRP) Components Reveal an Essential and Non-Redundant Role for Granule Biogenesis and Differentiation of Neutrophil Granulocytes
Authors: Yoko Mizoguchi, Sebastian Hesse, Monika Linder, Natalia Zietara, Marcin Lyszkiewicz, Yanshan Liu, Megumi Tatematsu, Piotr Grabowski, Kaarin Ahomaa, Tim Jeske, Sebastian Hollizeck, Ejona Rusha, Megumu K Saito, Masao Kobayashi, Zahra Alizadeh, Zahra Pourpak, Sorin Iurian, Nima Rezaei, Ekrem Unal, Micha Drukker, Barbara Walzog, Fabian Hauck, Juri Rappsilber, Christoph Klein
Journal: Blood (2019)
Нейровегетативные и когнитивные нарушения у пациентов с неалкогольной жировой болезнью печени и сахарным диабетом 2 типа
Authors: Ye.S. Sirchak, O.O. Boldizhar, V.I. Griga, O.I. Petrichko
Journal: GASTROENTEROLOGY (2019)

Актуальность. Проводятся разнонаправленные исследования для лучшего понимания влияния когнитивных нарушений на лечение, мобильность, смертность пациентов, особенно лиц с полиморбидной патологией. Цель: изучить особенности когнитивных и нейровегетативных нарушений у пациентов с различными формами неалкогольной жировой болезни печени (НАЖБП) (неалкогольный жировой гепатоз (НАЖГ) и неалкогольный стеатогепатит (НАСГ)) и сахарным диабетом (СД) 2 типа. Материалы и методы. Обследовано 50 пациентов с НАЖБП (24 — с НАЖГ и 26 — с НАСГ). Группа сравнения включала 22 человека с СД 2 типа. Нарушения функций центральной и вегетативной нервной системы определяли с помощью нейропсихометрических тестов. Результаты. У обследованных пациентов по результатам анкетирования установлена вегетативная дисфункция. Когнитивные нарушения (преимущественно легкие и умеренные) выявлены в обеих группах больных. Максимально выраженные нарушения определялись в сфере внимания и концентрации, памяти, менее выраженные — в зрительно-конструктивной сфере, особенно у больных с НАСГ в сочетании с СД 2 типа. Стрессовые ситуации негативно влияют на жизнь этих пациентов, при этом они недостаточно критически реагируют на обнаруженные проблемы. У больных НАСГ в сочетании с СД 2 типа установлен наименьший уровень сопротивляемости стрессу — (56,7 ± 3,1) балла; p &lt; 0,01. У них определяется легкая уязвимость даже при незначительном негативном влиянии. Выводы. У пациентов с НАЖБП и СД 2 типа выявлены когнитивные нарушения и вегетативная дисфункция по результатам нейропсихометрического тестирования. Наиболее выраженными когнитивные нарушения были у больных НАСГ в сочетании с СД 2 типа и ожирением I степени по результатам Монреальской шкалы оценки когнитивных функций (r = 0,90; р &lt; 0,01), Бостонского теста (r = 0,94; р &lt; 0,01) и Висконсинского теста сортировки карточек (r = 0,92, р &lt; 0,01).
In STEMI with multivessel CAD, complete revascularization reduced CV death or MI more than culprit lesion–only PCI
Authors: Angela Lowenstern, L. Kristin Newby
Journal: Annals of Internal Medicine (2019)

Source Citation Mehta SR, Wood DA, Storey RF, et al; COMPLETE Trial Steering Committee and Investigators. Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med. 20...
Toll-like Receptor Signaling Rewires Macrophage Metabolism and Promotes Histone Acetylation via ATP-Citrate Lyase
Authors: Mario A. Lauterbach, Jasmin E. Hanke, Magdalini Serefidou, Matthew S.J. Mangan, Carl-Christian Kolbe, Timo Hess, Maximilian Rothe, Romina Kaiser, Florian Hoss, Jan Gehlen, Gudrun Engels, Maike Kreutzenbeck, Susanne V. Schmidt, Anette Christ, Axel Imhof, Karsten Hiller, Eicke Latz
Journal: Immunity (2019)
Crack vs Inhaled Cocaine and Sentencing
Authors: Richard H. Hamilton
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Drs Hatsukami and Fischman<sup>1</sup>wrote a most interesting article. Their conclusion, however, is to be debated. They state that "those addicted individuals who are incarcerated for the sale or possession of cocaine are better served by treatment than prison." This is very likely true, but society is better served by getting these individuals out of a circumstance in which they might continue to sell these drugs. Society and the individuals would best be served by having the addicted individuals treated in prison.
Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes <i>p53</i> -deficient cancers to mTOR inhibition
Authors: Na Kong, Wei Tao, Xiang Ling, Junqing Wang, Yuling Xiao, Sanjun Shi, Xiaoyuan Ji, Aram Shajii, Silvia Tian Gan, Na Yoon Kim, Dan G. Duda, Tian Xie, Omid C. Farokhzad, Jinjun Shi
Journal: Science Translational Medicine (2019)

Loss of function in tumor suppressor genes is commonly associated with the onset/progression of cancer and treatment resistance. The p53 tumor suppressor gene, a master regulator of diverse cellular pathways, is frequently altered in various cancers, for example, in ~36% of hepatocellular carcinomas (HCCs) and ~68% of non-small cell lung cancers (NSCLCs). Current methods for restoration of p53 expression, including small molecules and DNA therapies, have yielded progressive success, but each has formidable drawbacks. Here, a redox-responsive nanoparticle (NP) platform is engineered for effective delivery of p53-encoding synthetic messenger RNA (mRNA). We demonstrate that the synthetic p53-mRNA NPs markedly delay the growth of p53-null HCC and NSCLC cells by inducing cell cycle arrest and apoptosis. We also reveal that p53 restoration markedly improves the sensitivity of these tumor cells to everolimus, a mammalian target of rapamycin (mTOR) inhibitor that failed to show clinical benefits in advanced HCC and NSCLC. Moreover, cotargeting of tumor-suppressing p53 and tumorigenic mTOR signaling pathways results in marked antitumor effects in vitro and in multiple animal models of HCC and NSCLC. Our findings indicate that restoration of tumor suppressors by the synthetic mRNA NP delivery strategy could be combined together with other therapies for potent combinatorial cancer treatment.
A Pilot Study of Colony Stimulating Factor-Primed Donor Leukocyte Infusion Using Cells Reserved at the Time of Transplantation after Allogeneic Stem Cell Transplantation in Patients with Advanced Hematological Malignancies
Authors: J. G. ang Kim, S. K. un Sohn, D. H. an Kim, J. S. o Suh, K. B. Lee
Journal: Blood (2002)
British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines
Authors: Matthew D Rutter, James East, Colin J Rees, Neil Cripps, James Docherty, Sunil Dolwani, Philip V Kaye, Kevin J Monahan, Marco R Novelli, Andrew Plumb, Brian P Saunders, Siwan Thomas-Gibson, Damian J M Tolan, Sophie Whyte, Stewart Bonnington, Alison Scope, Ruth Wong, Barbara Hibbert, John Marsh, Billie Moores, Amanda Cross, Linda Sharp
Journal: Gut (2019)

These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address: Which patients should commence surveillance post-polypectomy and post-cancer resection? What is the appropriate surveillance interval? When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG’s guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant. two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either : two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps This cohort should undergo a one-off surveillance colonoscopy at 3 years. Post-CRC resection patients should undergo a 1 year clearance colonoscopy, then a surveillance colonoscopy after 3 more years.
Optimal Timing for Removal of an Upper Extremity Central Catheter When Associated with a Deep Vein Thrombosis: A Venous Thromboembolism Network US Multicenter Retrospective Cohort Study
Authors: Damon E. Houghton, Henny Heisler H. Billett, Manila Gaddh, Oluwatomiloba Onadeko, Gemlyn George, Tzu-Fei Wang, Thein H. Oo, Yuanyue Sun, Mingen Feng, Michael Jaglal, Michael B. Streiff, Pippa Simpson, Radhika Gali, Lisa Baumann Kreuziger
Journal: Blood (2019)
Patient Characteristics and Product Use Behaviors Among Persons with E-cigarette, or Vaping, Product Use–Associated Lung Injury — Indiana, June ̶ October 2019
Authors: Kathryn L. Gaub, Sara Hallyburton, Claudine Samanic, Deanna Paddack, Charles R. Clark, Shawn Pence, Jennifer A. Brown, Eric Hawkins
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

As of December 4, 2019, a total of 2,291 cases of hospitalized e-cigarette, or vaping, product use-associated lung injury (EVALI) have been reported from 50 states, the District of Columbia, and two U.S. territories (Puerto Rico and the U.S. Virgin Islands) (1). State health departments, including the Indiana State Department of Health (ISDH), are working with their local health departments and with CDC, the Food and Drug Administration, and other clinical and public health partners in investigating this outbreak of EVALI. On August 7, 2019, ISDH issued an advisory regarding patients hospitalized in Wisconsin with severe acute lung injury who reported the use of e-cigarette, or vaping, products (2); health care providers were requested to notify ISDH of similar cases. On August 8, 2019, ISDH received reports of five similar cases among Indiana residents. Suspected cases EVALI reported to ISDH were investigated further only among patients who required hospitalization. Established case definitions were used to classify cases.* Medical record abstractions and patient interviews were completed using nationally standardized forms to ascertain patient characteristics, medical care received, and product-use behaviors.
Endoscopic Ultrasound/Fine Needle Aspiration Is Effective for Lymph Node Staging in Patients With Cholangiocarcinoma
Authors: Thomas Malikowski, Michael J. Levy, Ferga C. Gleeson, Andrew C. Storm, Eric J. Vargas, Mark D. Topazian, Barham K. Abu Dayyeh, Prasad G. Iyer, Elizabeth Rajan, Gregory J. Gores, Lewis R. Roberts, Vinay Chandrasekhara
Journal: Hepatology (2019)

Presence of malignant regional lymph nodes (MRLNs) precludes curative oncological resection or liver transplantation for cholangiocarcinoma (CCA). Limited data support the utility of endoscopic ultrasound (EUS)/fine needle aspiration (FNA) for detection of MRLNs in extrahepatic CCA, but there are no data for its role in intrahepatic CCA (iCCA). The aim of this study is to evaluate the staging impact of EUS for CCA, including analysis by subtype.We identified consecutive patients with CCA who underwent EUS staging at a single tertiary care center from October 2014 to April 2018. Among this cohort, we abstracted clinical demographic, radiographical, procedural, cytopathological, and surgical data. STATA 15 software was used for comparative analysis calculations (StataCorp LP, College Station, TX). The study cohort included 157 patients; 24 (15%), 124 (79%), and 9 (6%) with intrahepatic, perihilar, and distal CCA, respectively. EUS was able to identify regional lymph nodes (RLNs) in a higher percentage of patients compared to cross-sectional imaging (86% vs. 47%; P < 0.001). FNA was performed in 133 (98.5%) patients with RLNs, with a median of three passes per node. EUS-FNA identified MRLN in 27 of 31 (87.1%) patients ultimately found to have MRLNs. For iCCA, EUS detected a higher percentage of RLN compared to cross-sectional imaging (83% vs. 50%; P = 0.048), with MRLNs identified in 4 (17%) patients. Among the entire cohort, identification of at least one MRLN by EUS was associated with lower median survival (353 vs. 1,050 days; P < 0.001) and increased risk of death (hazard ratio = 4.1; P < 0.001).EUS-FNA is effective for identifying MRLN in patients with CCA, and should be routinely incorporated into staging of all CCA subtypes given the impact of MRLN on prognosis and management decisions.