tbuckley/cabot-search huggingface dataset:
Синдром избыточного бактериального роста у больных с хроническими диффузными заболеваниями печени в зависимости от этиологии и морфологических особенностей
Authors: V.I. Didenko, E.V. Zigalo,, Yu.A. Gaidar, V.B. Yagmur
Journal: GASTROENTEROLOGY (2019)

Актуальность. Ряд исследований указывают на повышение риска появления нарушений со стороны печени при дисбиотических нарушениях в кишечнике. В свою очередь, изменение физиологических процессов в печени может стать толчком для возникновения синдрома избыточного бактериального роста (СИБР). Доказано, что СИБР в тонком кишечнике может играть определенную роль в патогенезе алкогольной болезни печени и осложнений, связанных с хроническим гепатитом С. Целью исследования было оценить частоту возникновения синдрома избыточного бактериального роста у больных хроническими диффузными заболеваниями печени (ХДЗП) с учетом степени стеатоза, стадии фиброза и степени активности воспалительного процесса в печени. Материалы и методы. 27 обследованных пациентов были распределены на 2 группы: I — 12 больных с хроническим гепатитом, ассоциированным с вирусом С (ХГС); II — 15 больных с алкогольной болезнью печени (АБП) в зависимости от этиологии при формировании и прогрессировании стеатоза и фиброза печени с использованием данных гистологических методов исследования, компьютерной морфометрии, транзиентной эластометрии и показателя степени стеатоза САР на аппарате FibroScan 502. Синдром избыточного бактериального роста определяли с помощью водородного дыхательного теста (ВДТ) с глюкозой. Результаты. СИБР был выявлен у 51,8 % больных с ХДЗП, достоверно почти в 1,5 раза преобладал у больных с АБП (60,0 %) по сравнению с ХГС, у которых только в 41,7 % случаев выявлен СИБР. Выявлено превалирование положительных случаев ВДТ в группе S3 (70,0 %), что достоверно отличалось от группы S1 (37,5 %). У больных ХГС с прогрессированием стеатоза увеличивается количество случаев СИБР, и наоборот, у большинства больных с АБП, у которых был выявлен гистологически подтвержденный микровезикулярный и мелкокапельный стеатоз печени, выявляли при ВДТ нарушения микробиоты в тонком кишечнике. Выводы. Между показателями водородного дыхательного теста и индексом гистологической активности, гистологическими показателями прогрессирования стеатоза печени у больных хроническим гепатитом С выявлена четкая взаимо­связь: с увеличением активности воспалительного процесса (9 баллов) и степени стеатоза печени (S3) повышается уровень нарушения микробиоты в тонком кишечнике (&gt; 20 ppm), то есть при ХГС уровень выделения водорода адекватно отображает степень активности воспалительного процесса в печени.
Improved Disease Free Survival Following Reduced Intensity Conditioned Allogeneic Stem Cell Transplantation Incorporating Alemtuzumab Compared with Autologous Stem Cell Transplantation in Follicular Lymphoma.
Authors: Wendy Ingram, Stephen Devereux, Juan Gonzalez, Aloysius Ho, Ghulam Mufti, Antonio Pagliuca
Journal: Blood (2005)
US could get access to UK health data, experts warn
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The US wants “free flow of data,” including health data, as part of any trade deal with the UK after Brexit, leaked negotiation documents have shown.

The documents, which were revealed by the Labour Party on 27 November, outlined six “secret talks” held between US trade representatives and the UK Department for International Trade from July 2017 to July 2019.1

As part of the discussions the US made it clear that access to UK data would be a priority and that it would be better for business if the UK moved closer to US regulations on data protection.

Experts have warned that such changes could lead to US technology companies using the data to build and to copyright algorithms that analyse the data and then charging the NHS to use them. Drug companies could also use the data for research.

Additionally, they warn, moving from EU to US data regulations could make it more difficult …
Effects of Andexanet Alfa on Thrombin Generation in Bleeding Associated with Factor Xa Inhibitors
Authors: Michiel Coppens, Lizhen Xu, Roisin Bavalia, Saskia Middeldorp, Peter Verhamme, John W. Eikelboom, Mark Crowther, Genmin Lu, Patrick Yue, Pamela B. Conley, Stuart J. Connolly
Journal: Blood (2019)
A Randomized Phase II Study of Single-Agent Imatinib Versus Chemotherapy Therapy in Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Including Analysis of Resistance Patterns.
Authors: Heike Pfeifer, Oliver G. Ottmann, Nicola Goekbuget, Lydia Wunderle, Patrick Brueck, Aristoteles Giagounidis, Michael Stelljes, Andreas Hochhaus, Harald Gschaidmeier, Dieter Hoelzer, Barbara Wassmann
Journal: Blood (2005)
A Tumor-in-Host DEB-Based Approach for Modeling Cachexia and Bevacizumab Resistance
Authors: Elena M. Tosca, Maurizio Rocchetti, Enrico Pesenti, Paolo Magni
Journal: Cancer Research (2019)

Adequate energy intake and homeostasis are fundamental for the appropriate growth and maintenance of an organism; the presence of a tumor can break this equilibrium. Tumor energy requests can lead to extreme weight loss in animals and cachexia in cancer patients. Angiogenesis inhibitors, acting on tumor vascularization, counteract this tumor-host energy imbalance, with significant results in preclinical models and more limited results in the clinic. Current pharmacokinetic-pharmacodynamic models mainly focus on the antiangiogenic effects on tumor growth but do not provide information about host conditions. A model that can predict energetic conditions that provide significant tumor growth inhibition with acceptable host body weight reduction is therefore needed. We developed a new tumor-in-host dynamic energy budget (DEB)-based model to account for the cytostatic activity of antiangiogenic treatments. Drug effect was implemented as an inhibition of the energy fraction subtracted from the host by the tumor. The model was tested on seven xenograft experiments involving bevacizumab and three different tumor cell lines. The model successfully predicted tumor and host body growth data, providing a quantitative measurement of drug potency and tumor-related cachexia. The inclusion of a hypoxia-triggered resistance mechanism enabled investigation of the decreased efficacy frequently observed with prolonged bevacizumab treatments. In conclusion, the tumor-in-host DEB-based approach has been extended to account for the effect of bevacizumab. The resistance model predicts the response to different administration protocols and, for the first time, the impact of tumor-related cachexia in different cell lines. Finally, the physiologic base of the model strongly suggests its use in translational human research. SIGNIFICANCE: A mathematical model describes tumor growth in animal models, taking into consideration the energy balance involving both the growth of tumor and the physiologic functions of the host.
The Combination of Pegylated Liposomal Doxorubicin and Bortezomib Significantly Improves Time to Progression of Patients with Relapsed/Refractory Multiple Myeloma Compared with Bortezomib Alone: Results from a Planned Interim Analysis of a Randomized Phase III Study.
Authors: Robert Z. Orlowski, Sen H. Zhuang, Trilok Parekh, Liang Xiu, Jean-Luc Harousseau
Journal: Blood (2006)
RANBP2/ALK Rearrangement Is a New Rare but Recurrent Fusion Gene in Childhood Myeloid Disorders.
Authors: Jochen Harbott, Jochen Bruch, Kerstin Busch, Ulrike A. Gammerdinger, Silja Rottgers, Andrea Teigler-Schlegel, Susanne Viehmann
Journal: Blood (2005)
The importance of adherence in tuberculosis treatment clinical trials and its relevance in explanatory and pragmatic trials
Authors: Andrew Vernon, Katherine Fielding, Rada Savic, Lori Dodd, Payam Nahid
Journal: PLoS Medicine (2019)

Points• Adherence to prescribed treatment remains a critical component of clinical trials in tuberculosis (TB) treatment.Recent evidence indicates that adherence strongly influences the outcome of therapy; attention to its quantification and measures to assure its implementation should increase.• In the context of a World Health Organization (WHO) Technical Consultation on "Advances in Clinical Trial Design for Development of New TB Treatments," we reviewed the challenges related to adherence confronting the trials community.• We discuss the importance of adherence to therapy in TB clinical trials, consider several definitions and measures of adherence, comment on the standard provided by directly observed therapy (DOT), and briefly review evolving electronic methods for the assessment of adherence.• Adherence affects both the outcome of therapy and the risk of acquired drug resistance.Assessment of adherence should consider not only overall adherence but also the timing and intensity of nonadherence.• Appropriate methods for pooling and analyzing electronic data on adherence are needed.• Better methods are needed for linking information on adherence to individual pharmacokinetics and pharmacodynamics and to individual patient outcomes.
上消化道疾病基础知识（三）——胃十二指肠溃疡和胃癌的病理生理
Authors: JohnCalam, JHBaron, 王玉珍, 夏志伟
Journal: BMJ (2003)

胃十二指肠溃疡和胃癌是常见的严重疾病,在感染幽门螺杆菌的人群中,只有少数人才会发病。由于需要资金的投入并且有导致耐药的危险,大规模地根除幽门螺杆菌是不现实的。而掌握幽门螺杆菌导致溃疡和胃癌形成机制方面的知识是很重要的。 很多因素影响幽门螺杆菌感染的结局,包括宿主反应,特
Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology
Authors: Timothy Gilligan, Daniel W. Lin, Rahul Aggarwal, David Chism, Nicholas Cost, Ithaar H. Derweesh, Hamid Emamekhoo, Darren R. Feldman, Daniel M. Geynisman, Steven L. Hancock, Chad LaGrange, Ellis G. Levine, Thomas Longo, Will Lowrance, Bradley McGregor, Paul Monk, Joel Picus, Phillip Pierorazio, Soroush Rais-Bahrami, Philip Saylor, Kanishka Sircar, David C. Smith, Katherine Tzou, Daniel Vaena, David Vaughn, Kosj Yamoah, Jonathan Yamzon, Alyse Johnson-Chilla, Jennifer Keller, Lenora A. Pluchino
Journal: Journal of the National Comprehensive Cancer Network (2019)

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.
Lymphoblastic Leukemia/Lymphoma in Mice Overexpressing the Mer Receptor Tyrosine Kinase.
Authors: Dana B. Salzberg, Amy K. Keating, Adil Anwar, Kelly Sawczyn, Kimberley Hill, Susan Sather, Jane Park, Deborah DeRyckere, Doug Everett, Douglas K. Graham
Journal: Blood (2005)
Specific Small‐Molecule NIR‐II Fluorescence Imaging of Osteosarcoma and Lung Metastasis
Authors: Hui Zhou, Wanrong Yi, Anguo Li, Bo Wang, Qihang Ding, Liru Xue, Xiaodong Zeng, Yanzhi Feng, Qianqian Li, Tian Wang, Yang Li, Xiaoding Cheng, Lin Tang, Zixin Deng, Mingfu Wu, Yuling Xiao, Xuechuan Hong
Journal: Advanced Healthcare Materials (2019)

Abstract Osteosarcoma is an aggressive tumor of mesenchymal origin that is more likely to spread to the lung than others, with a major impact on patients' prognosis. The optimal imaging method that can reliably detect or exclude pulmonary metastases from osteosarcoma is still scarce. Herein, two homologous types of fluorescent probes CH1055‐PEG‐PT and CH1055‐PEG‐Affibody , which show highly promising results for targeting imaging of osteosarcoma and its lung metastasis, respectively, are designed and synthesized. It is found that the NIR‐II imaging quality of CH1055‐PEG‐PT is far superior to that of computed tomography for the early in vivo 143B tumor imaging, and this probe‐guided surgery for accurate resection of 143B tumor is further performed. The high‐resolution visualization of primary and micrometastatic lung lesions of osteosarcoma by using CH1055‐PEG‐Affibody is also demonstrated. Therefore, the attractive imaging properties of CH1055‐PEG‐PT and CH1055‐PEG‐Affibody , including high levels of uptakes, and high spatial and temporal resolution, open up opportunities for molecular imaging and clinical translation of osteosarcoma and its lung metastasis in the unique second near‐infrared window.
Frank Dobson: Labour politician who became “best UK health secretary since Aneurin Bevan”
Authors: Matt Limb
Journal: BMJ (2019)

Photo credit: Glenn Corpus/Shutterstock

Frank Dobson was the first Labour health secretary for nearly 20 years when Tony Blair appointed him after the landslide general election victory of 1997. He served two and a half years, enough time to be judged the best health secretary since Aneurin Bevan, according to BMJ polling of top medical figures in 2013.

Dobson, a hero to many in the Labour party, was an MP in London for 36 years and held many of the top shadow cabinet posts.

But he admitted he made his worst career blunder when he quit as minister to stand for Labour as London mayor in 2000 and came a crushing third (Ken Livingstone won as an independent). He never returned to government.

At least by then he had already put in place “fairly fundamental things that have stood the test of time and are the bedrock of the NHS now,” his former adviser Joe McCrea told PA news agency.

Dobson set up two institutions that became central to the way it functions: the National Institute for Clinical Excellence (NICE, now the National Institute for Health and Care Excellence), and the Commission for Health Improvement (which evolved into the Care Quality Commission as the enforcer of clinical quality). Mike Rawlins, who was made NICE’s first chairman, knew him as a “shrewd” operator and a prolific user of the “f” word. Unusually, Dobson interviewed all NICE’s non-executive director candidates himself. When one asked him if the new body was going to work, he replied, “Probably not, but we’re going to give it a fucking good try,” recalls Rawlins.

Yorkshire born Dobson, a cheery and often fiery socialist of the “sane left,” was …
Hematologic Profiles in the Phase 3 APEX Trial.
Authors: Sagar Lonial, P. Richardson, P. Sonneveld, M. Schuster, D. Irwin, E. Stadtmauer, T. Facon, J. Harousseau, D. Ben-Yehuda, H. Goldschmidt, D. Reece, J. San Miguel, J. Blade, M. Boccadoro, J. Cavenagh, W. Dalton, A. Boral, D. Schenkein, K. Anderson
Journal: Blood (2005)
Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease
Authors: Hamzah Abu-Sbeih, David M. Faleck, Biagio Ricciuti, Robin B. Mendelsohn, Abdul R. Naqash, Justine V. Cohen, Maclean C. Sellers, Aanika Balaji, Guy Ben-Betzalel, Ibraheim Hajir, Jiajia Zhang, Mark M. Awad, Giulia C. Leonardi, Douglas B. Johnson, David J. Pinato, Dwight H. Owen, Sarah A. Weiss, Giuseppe Lamberti, Mark P. Lythgoe, Lisa Manuzzi, Christina Arnold, Wei Qiao, Jarushka Naidoo, Gal Markel, Nick Powell, Sai-Ching J. Yeung, Elad Sharon, Michael Dougan, Yinghong Wang
Journal: Journal of Clinical Oncology (2019)

PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P &lt; .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.
PsyMuKB: An Integrative <i>De Novo</i> Variant Knowledge Base for Developmental Disorders
Authors: Guan Ning Lin, Sijia Guo, Xian Tan, Weidi Wang, Wei Qian, Weichen Song, Jingru Wang, Shunying Yu, Zhen Wang, Donghong Cui, Han Wang
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract De novo variants (DNVs) are one of the most significant contributors to severe early-onset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Presently, a plethora of DNVs have been identified using next-generation sequencing, and many efforts have been made to understand their impact at the gene level. However, there has been little exploration of the effects at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues. Therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate a better usage and improve the isoform-level interpretation of variants, we developed NeuroPsychiatric Mutation Knowledge Base (PsyMuKB). It contains a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoform-specific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.
Blockage of TRAF6 Signaling Inhibits Osteoclast Formation and Tumor Cell through Blocking the NF-kB and JNK Pathways in Multiple Myeloma.
Authors: Haiming Chen, Mingjie Li, Jennifer Li, Richard A. Campbell, Cathy S. Wang, Eric Sanchez, Jeffrey Steinberg, Michael Share, Dror Shalitin, James Wang, Shi-Jason Xie, Benjamin Bonavida, James R. Berenson
Journal: Blood (2007)
Impact of MYD88<sup>L265P</sup> mutation status on histological transformation of Waldenström Macroglobulinemia
Authors: Saurabh Zanwar, Jithma P. Abeykoon, Eric Durot, Rebecca King, Gabriela E. Perez Burbano, Shaji Kumar, Morie A. Gertz, Anne Quinquenel, Alain Delmer, Wilson Gonsalves, Pascale Cornillet‐Lefebvre, Rong He, Rahma Warsame, Francis K. Buadi, Anne J. Novak, Patricia T. Greipp, David Inwards, Thomas M. Habermann, Ivana Micallef, Ronald Go, Eli Muchtar, Taxiarchis Kourelis, Angela Dispenzieri, Martha Q. Lacy, David Dingli, Grzegorz Nowakowski, Carrie A. Thompson, Patrick Johnston, Gita Thanarajasingam, N. Nora Bennani, Thomas E. Witzig, Jose Villasboas, Nelson Leung, Yi Lin, Robert A. Kyle, S. Vincent Rajkumar, Stephen M. Ansell, Jennifer G. Le‐Rademacher, Prashant Kapoor
Journal: American Journal of Hematology (2019)

Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88 L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88 L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88 L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88 WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P = .003). Additionally, the MYD88 WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P = .001]), with a 5-year transformation rate of 16% for MYD88 WT vs 2.8% with MYD88 L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P < .001). In conclusion, the MYD88 WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.
Myeloma Derived Extracellular Vesicles Containing Endoplasmic Reticulum Remodel the Bone Marrow Microenvironment Towards a Pro-Tumoral Senescent Phenotype
Authors: Yu Sun, Jayna J Mistry, Jamie A Moore, Charlotte Hellmich, Christopher R Marlein, Anna Haestier, Cesar A. Gomez, Christopher J Morris, Kristian M Bowles, Stuart A Rushworth
Journal: Blood (2019)