tbuckley/cabot-search huggingface dataset:
Функциональная диспепсия и синдром раздраженного кишечника: что общего?
Authors: Yu.M. Stepanov, I.Ya. Budzak
Journal: GASTROENTEROLOGY (2016)

В статье представлен анализ основных функциональных заболеваний пищеварительной системы — функциональной диспепсии и синдрома раздраженного кишечника. Показано сходство патогенетических факторов этих заболеваний. Помимо традиционных факторов (моторные нарушения, висцеральная гиперчувствительность), особое внимание уделено относительно новым факторам (желудочно-кишечная инфекция, минимальное воспаление слизистой, нарушение проницаемости слизистой и другие). Обращается внимание на частый оверлэп этих заболеваний.
An unhappy 10th birthday: Doctors of the World’s London clinic
Authors: Richard Hurley
Journal: BMJ (2016)

Jenny Lewis/Doctors of the World

For a decade the humanitarian charity Doctors of the World has been running a clinic in east London to help vulnerable people who are otherwise unable to access healthcare. The patients include refugees and undocumented migrants, some of whom have been trafficked or tortured.

For an exhibition to mark the occasion several photographers have contributed portraits of the clinic’s users and volunteer staff. The Sri Lankan man pictured escaped to London after being tortured and forced to leave his country. No general practice would register him despite his needing urgent medical help.

“I have a lot of pain on the body and I am not sleeping well, I have …
The Utility Of Newer Risk Models In Predicting Outcomes Of Patients (pts) With Higher-Risk (HR) Myelodysplastic Syndromes (MDS) Treated With Azactidine (aza)
Authors: Amer M. Zeidan, Najla H Al Ali, Mohamed A. Kharfan-Dabaja, Eric Padron, Ling Zhang, Pearlie K Epling-Burnette, Jeffrey E Lancet, Alan F List, Rami S Komrokji
Journal: Blood (2013)
Role of Allogeneic Stem Cell Transplantation (AlloSCT) in Patients Affected By Peripheral T-Cell Lymphomas (PTCL): No Difference in Outcome Between Patients Allografted at Diagnosis and in First Chemosensitive Relapse
Authors: Anna Dodero, Francesco Spina, Franco Narni, Francesca Patriarca, Fabio Benedetti, Donatella Baronciani, Alessandro Rambaldi, Attilio Olivieri, Serena Dalto, Benedetto Bruno, Umberto Vitolo, Paolo Corradini
Journal: Blood (2014)
Donor Cell Derived Leukemia: Description Of 38 Cases and a Case Control Study
Authors: Nicole Engel, Rafael F. Duarte, Myriam Labopin, Thomas Schroeder, Johanna Tischer, Per T. Ljungman, Nicolaas PM Schaap, Denis Guyotat, Yves Beguin, Arnon Nagler, Wilfried A. Schroyens, Grzegorz Wladyslaw Basak, Hans Jochem Kolb, Manuela Badoglio, Andre Tichelli, Alicia Rovo
Journal: Blood (2013)
Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion
Authors: Martin Chopra, Marlene Biehl, Tim Steinfatt, Andreas Brandl, Juliane Kums, Jorge Amich, Martin Vaeth, Janina Kuen, Rafaela Holtappels, Jürgen Podlech, Anja Mottok, Sabrina Kraus, Ana-Laura Jordán-Garrote, Carina A. Bäuerlein, Christian Brede, Eliana Ribechini, Andrea Fick, Axel Seher, Johannes Polz, Katja J. Ottmüller, Jeanette Baker, Hidekazu Nishikii, Miriam Ritz, Katharina Mattenheimer, Stefanie Schwinn, Thorsten Winter, Viktoria Schäfer, Sven Krappmann, Hermann Einsele, Thomas D. Müller, Matthias J. Reddehase, Manfred B. Lutz, Daniela N. Männel, Friederike Berberich-Siebelt, Harald Wajant, Andreas Beilhack
Journal: The Journal of Experimental Medicine (2016)

Donor CD4+Foxp3+ regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT [allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2- and T reg cell–dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo.
Hepatocyte growth factor as inducer of gefitinib resistance in non-small cell lung cancer harboring <i>EGFR</i> activating mutations
Authors: S. Yano, W. Wang, Q. Li, T. Yamada, K. Matsumoto, T. Mitsudomi, Y. Yatabe, M. Hanibuchi, Y. Nishioka, S. Sone
Journal: Journal of Clinical Oncology (2009)

e19034 Background: Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations (EGFRmu) responds favorably to the EGFR tyrosine kinase inhibitors (EGFR-TKIs), gefitinib or erlotinib. However, 25–30% of patients with EGFRmu show intrinsic resistance, and the responders invariably acquire resistance to EGFR-TKIs. Here, we examined the role of hepatocyte growth factor (HGF), a specific ligand of MET, in gefitinib resistance of NSCLC with EGFRmu. Methods: NSCLC cells, PC-9 and HCC827, with EGFRmu, but not T790M second mutation in EGFR or MET amplification, were used in this study. Sensitivity to gefitinib was determined by MTT assay. Phosphorylation of MET, EGFR, ERBB3, and the PI3K/Akt pathway were examined by Western blotting. HGF expression in 20 tumors from 16 NSCLC patients with EGFRmu who were treated with gefitinib was determined by immunohistochemistry. Results: HGF induced resistance to gefitinib by restoring Akt phosphorylation independently of ErbB3. Specific down-regulation of MET, but not ErbB3, reversed gefitinib resistance and Akt phosphorylation induced by HGF. Importantly, high levels of immunoreactivity for HGF were detected in cancer cells of 3 of 3 intrinsic resistant tumors and in one of 2 tumors with acquired resistance without T790M second mutation or MET amplification. Conclusions: The findings indicate that HGF-mediated MET activation is a novel mechanism of intrinsic and acquired gefitinib-resistance in NSCLC with EGFRmu. Therefore, inhibition of HGF-MET signaling may be considerable strategy for more successful treatment with EGFR-TKIs. [Table: see text]
Acetaminophen and Asthma — A Small Sigh of Relief?
Authors: Augusto A. Litonjua
Journal: New England Journal of Medicine (2016)

Acetaminophen is the drug of choice for fever in young children. Pediatricians, parents, and caregivers consider it to be safe for most children when it is administered in accordance with the manufacturer’s directions for use. In 2000, however, concern was raised about the safety of acetaminophen as a result of the findings of a case–control study by Shaheen et al.1 that suggested that frequent use of acetaminophen (also known as paracetamol in the United Kingdom) among adults was associated with asthma, and among those who already had asthma, with more severe disease. The mechanism for this association was thought to . . .
The Receptor for Hyaluronic Acid Mediated Motility (RHAMM/CD168) Is a Potential Target for Immunotherapy of Patients with B-Cell Chronic Lymphocytic Leukemia.
Authors: Krzysztof Giannopoulos, Iwona Hus, Li Li, Agnieszka Bojarska-Junak, Jochen Greiner, Jacek Rolinski, Anna Dmoszynska, Hartmut Doehner, Michael Schmitt
Journal: Blood (2005)
Implementation of clinical practice guidelines for newly diagnosed GBM patients in China.
Authors: Jianmin Zhang, Wenbin Li, Wenbin Ma, Taipeng Jiang, Bing Jiang, Zhongping Chen, Jingbo Kang, Songtao Qi, Yunjie Wang, Qichuan Zhu Ge, Hua Feng, Guodong Gao, Yuping Wu, Jinhuan Wang, Yirong Wang, Xiaopeng Yang, Hui Zhao, Gang Zhao, Hui Yang, Renzhi Wang
Journal: Journal of Clinical Oncology (2016)

e13532 Background: The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) after surgery, followed by TMZ maintenance chemotherapy (guideline regimen) is the guideline recommended standard of care for newly diagnosed glioblastoma (GBM), yet its clinical uptake remains broadly low in China. This study will provide information on the consistency of such practice in real-world setting among newly diagnosed GBM patients treated with temozolomide in China. Methods: A multi-center, prospective, observational study was conducted to collect data about routine clinical practice in the management of patients newly diagnosed GBM in China. No study specific visits or clinical intervention were included in the study protocol. Overall compliance was based on guideline consistency during both concomitant and at least 1 cycle of the maintenance phase. Results: A total of 201 eligible patients were enrolled from 30 study sites. Use of guideline regimen was 40.3% and 52.2% during concomitant and maintenance phases, respectively, and 24.9% for the overall study period (concomitant plus maintenance phases). 59.2% patients received radiotherapy and 81.6% patients received chemotherapy with temozolomide consistent with standard treatment during concomitant phase. Analysis of the effect of guideline-consistent therapy on newly diagnosed GBM is ongoing. Conclusions: Onlyone quarter patients in China received treatment are consistent with the guideline regimen in the patient population treated with temozolomide for newly diagnosed GBM. The guideline implementation needs to be improved. Additional research is warranted to understand the factors that might have resulted in patients not receiving guideline recommended standard therapy.
Atypical Hemoglobin H Disease Due to Compound Heterozygosity for -α3.7 and --SEA Deletions and Heterozygosity for the β-Chain Variant Hemoglobin Raleigh (β1 VAL→ALA).
Authors: Ferdane Kutlar, Mary Ann Knovich, Dedrey Elam, Daniel B. Jobe, David H. Buss, Jeanette Harbin, Deborah H. Davis, Hernon Sabio, Abdullah Kutlar
Journal: Blood (2005)
Response to Comment on Yang et al. Association of Statin Use and Reduced Risk of Lower-Extremity Amputation Among Patients With Diabetes: A Nationwide Population-Based Cohort Observation. Diabetes Care 2016;39:e54–e55
Authors: Tsung-Lin Yang, Liang-Yu Lin, Chin-Chou Huang, Po-Hsun Huang, Shing-Jong Lin, Jaw-Wen Chen, Wan-Leong Chan, Hsin-Bang Leu
Journal: Diabetes Care (2016)

We thank Fox et al. (1) for their noteworthy comments concerning the need for clinical trials regarding the role of statins in preserving the lower extremities of patients with diabetes mellitus (DM). Complications of the extremities, comprising peripheral artery disease, peripheral neuropathy, foot ulcer, critical limb ischemia, and ultimately limb loss, constitute a huge health burden for patients with DM. Our recent study (2) showed the beneficial effect of statins in patients with type 2 diabetes leading to a 52% reduction in …
WEDNESDAY 24TH MARCH
Authors: P Howard, L Maher, C Heading, Provoke Gastro-Oesophageal, J Sch6nfeld, Murphy Bt, Johnston Collins, P Sagar, C Stoddard, A Kingsnorth, A Corder, R Jones, C Johnson, J Calam, E Golodner, J Walsh, A Soil, Smith Turvey, A Keable, I J P, Pdl ^a, H Kenned3, J Gee', J Burton', I Jhnson
Journal: Gut (1993)

We have previously suggested that examination of oesophageal motility during eating may be useful in patients with dysphagia, particularly when conventional manometry is normal.The aim of this study was to examine distl oesophageal motility during eating in healthy subjects, as qntitative indices of normal fed motility!have not been established.METHODS: In 12 asymptomatic volunteers, distal oesopha*eal manometry was performed in both sitting and lying positions in response to ml water swallows at intervals of at least 20 seconds and again while the subjects ate a slice of bread.RESULTS: Contractions were almost all peristaltic in esponse to water swallows in both positions.The median percentages (range) of swallow types while eating bread were:-52.4%(15-77%) peristaltic, 17.3% (0-50%) synchronous and 27.5% (0-62.5%)non-conducted, sitting and 56.6% (25-92.6%)peristaltic, 24% (0-62.5%)synchronous and 14.2 (0-59.9%)non-conducted, lying (p<0.001compared to erect and supine water swallows).Mean (SD) peristaltic velocities (cm/sec) were greater for water compared to bread swallows in both erect and supine positions (4.15 (0.66) v. 3.06 (1.13) erect and 3.45 (0.65) v. 2.80 (0.67) supine; p<0.005).Velocities were also greater for erect compared to supine water swallows (p<0.005).Peristaltic amplitudes were not significantly different for bread and water swallows in either position (bread swallows 83.9 (SD) 34.0 mmHg sitting and 91.4 (31.0) lying; water swallows 75.2 (36.5) sitting and 76.4 (32.8) lying).CONCLUSIONS: Normal oesophageal motor patterns during eating differ significantly from those in response to standard water swallows.The nature of the swallowed bolus has a much greater effect than posture on resulting oesophageal peristalsis.
Sunitinib (SU)-related hypertension in a randomized placebo (P)-controlled trial of GIST patients (pts).
Authors: M. Ewer, T. M. Suter, D. J. Lenihan, L. Niculescu, A. Breazna, R. J. Motzer, G. D. Demetri
Journal: Journal of Clinical Oncology (2010)

10059 Background: Blood pressure (BP) changes are significantly associated with use of SU. We describe systolic/diastolic BP (SBP/DBP) variations and clinically meaningful hypertension (CMH) using P-controlled data. Methods: A phase III trial randomized 361 pts with advanced GIST following failure of imatinib to blinded SU, 50 mg daily, (n=243) in cycles (cy) of 4/2 weeks on/off SU vs. P (n=118). The previously reported primary endpoint of the trial was time to tumor progression. Crossover resulted in higher exposure for pts randomized initially to SU (8.98 cy) vs. P (1.7 cy). To maintain comparability between groups, we restricted the analysis of BP variation to the first three cy of study. BP data were available on day 1 and 28 of each cy. Additionally we conducted a separate analysis with the entire data set, censoring for crossover pts, in order to assess CMH events defined as 1) an increase of at least 25 mmHg for SBP or 15 mmHg for DBP, or an increase of at least 10 mmHg to a level over 150 for SBP and 95 for DBP lasting >2 weeks or requiring change in antihypertensive or study medication, or 2) severe hypertension (SH: SBP ≥180 or DBP ≥120 mmHg with evidence of target organ dysfunction). Three cardiologists assisted by a medical oncologist, all blinded to treatment allocation, adjudicated SH events. Results: Data for both study arms during the first three cy are presented in the Table. For the second analysis, the incidence rates (IR: events per 100 patient-cy) of CMH for SU/P were 11.82/9.32 (HR: 2.1; 95% CI: 1.24-3.57). All 16 adjudicated SH were in SU, none were fatal, and two were in patients with normal baseline BP. Conclusions: These P-controlled data, albeit limited by differential exposure, allow for quantification of early BP changes during exposure to SU, demonstrating BP elevation with partial resolution when off SU. Nonfatal SH were seen in patients on SU, most of whom had pre-existing abnormal baseline BP. These data emphasize the need to monitor BP carefully before and during SU or other VEGFR- targeting treatment. SBP/DBP (mmHg) Cy-Day P SU 1-1 129.8/76.3 128/75.2 1-28 128.7/76.9 137.5/82.1 2-1 128.4/77.4 131.4/77.3 2-28 129.9/78.7 140.2/84.3 3-1 126.5/72.7 132.1/77.8 3-28 125.6/78.5 141.2/83.8 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Alnylam Pharmaceuticals, Amgen, ARIAD, Bayer, Genentech, Genentech/Roche, GlaxoSmithKline, Infinity, Johnson & Johnson, MethylGene Canada, Novartis, Pfizer, Roche Kolltan Pharmaceuticals, Pfizer, Plexxikon Novartis, Pfizer, Roche, sanofi-aventis Amgen, ARIAD, Bristol-Myers Squibb, Genentech/Roche, Infinity, Johnson & Johnson, Novartis, Pfizer, Roche, Synta Ariad, Infinity, Johnson & Johnson Pfizer
On validation of cardiovascular risk scores
Authors: Mark Woodward
Journal: BMJ (2016)

Damen and colleagues present an interesting overview of prediction models for cardiovascular disease (CVD) risk, with recommendations for future practice.1 Unfortunately, although they make much of the so called “validation” of these scores in research articles, they say nothing about its relevance to current clinical practice.

In predictive modelling, as reviewed by these authors, historical data are used to predict a known future. Each model produces a risk score on a scale of 0-1 (or 0%-100%), but each outcome is either an event or a non-event, so the score …
BRCA1/2 mutations and hereditary breast cancer: clinical phenotype, type of mutation and founder effect
Authors: Z. Ballatore, R. Bracci, M. Pistelli, F. Bianchi, E. Maccaroni, L. Belvederesi, V. Panni, M. De Lisa, A. Della Mora, A. Pagliacci, N. Battelli, A. Santinelli, T. Biscotti, S. Cascinu
Journal: Annals of Oncology (2015)
Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial
Authors: Kirkwood F. Adams, Javed Butler, J. Herbert Patterson, Wendy Gattis Stough, Jerry L. Bauman, Dirk J. van Veldhuisen, Todd A. Schwartz, Hani Sabbah, John I. Mackowiak, Hector O. Ventura, Jalal K. Ghali
Journal: European Journal of Heart Failure (2016)
A Simple Disease-Guided Approach to Personalize ACC/AHA-Recommended Statin Allocation in Elderly People
Authors: Martin Bødtker Mortensen, Valentin Fuster, Pieter Muntendam, Roxana Mehran, Usman Baber, Samantha Sartori, Erling Falk
Journal: Journal of the American College of Cardiology (2016)

The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines recommend primary prevention with statins for individuals with ≥7.5% 10-year risk for atherosclerotic cardiovascular disease (ASCVD). Everyone living long enough will become eligible for risk-based statin therapy due to age alone.This study sought to personalize ACC/AHA risk-based statin eligibility using noninvasive assessment of subclinical atherosclerosis.In 5,805 BioImage participants without known ASCVD at baseline, those with ≥7.5% 10-year ASCVD risk were down-classified from statin eligible to ineligible if imaging revealed no coronary artery calcium (CAC) or carotid plaque burden (cPB). Intermediate-risk individuals were up-classified from optional to clear statin eligibility if CAC was ≥100 (or equivalent cPB).At a median follow-up of 2.7 years, 91 patients had coronary heart disease and 138 had experienced a cardiovascular disease event. Mean age of the participants was 69 years, and 86% qualified for ACC/AHA risk-based statin therapy, with high sensitivity (96%) but low specificity (15%). CAC or cPB scores of 0 were common (32% and 23%, respectively) and were associated with low event rates. With CAC-guided reclassification, specificity for coronary heart disease events improved 22% (p < 0.0001) without any significant loss in sensitivity, yielding a binary net reclassification index (NRI) of 0.20 (p < 0.0001). With cPB-guided reclassification, specificity improved 16% (p < 0.0001) with a minor loss in sensitivity (7%), yielding an NRI of 0.09 (p = 0.001). For cardiovascular disease events, the NRI was 0.14 (CAC-guided) and 0.06 (cPB-guided). The positive NRIs were driven primarily by down-classifying the large subpopulation with CAC = 0 or cPB = 0.Withholding statins in individuals without CAC or carotid plaque could spare a significant proportion of elderly people from taking a pill that would benefit only a few. This individualized disease-guided approach is simple and easy to implement in routine clinical practice.
Community Needs Assessment After Microcystin Toxin Contamination of a Municipal Water Supply — Lucas County, Ohio, September 2014
Authors: Carolyn L. McCarty, Leigh Nelson, Samantha Eitniear, Eric Zgodzinski, Amanda Zabala, Laurie Billing, Mary DiOrio
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On August 1, 2014, routine testing at the Collins Park Water Treatment Plant in Lucas County, Ohio, revealed microcystin toxin levels in drinking water had reached 3.19 μg/L, surpassing the Ohio Environmental Protection Agency (EPA) drinking water advisory threshold of 1.0 μg/L. Microcystin is a hepatoxin released by cyanobacteria in certain harmful algal blooms. Exposure to microcystin has been associated with gastrointestinal and hepatic illness in both humans and animals (1-3). On August 2, a do-not-drink advisory was issued, warning community members not to drink, boil, or use the water for cooking or brushing teeth. Public health officials used traditional and social media outlets to disseminate public health messages to affected communities. On August 4, 2014, the advisory was lifted after multiple water samples confirmed microcystin toxin levels had dropped below the advisory threshold. To assess communication strategies, water exposure, and household needs, the Ohio Department of Health (ODH) and Toledo-Lucas County Health Department (TLCHD) conducted a Community Assessment for Public Health Emergency Response (CASPER) in Lucas County. Most households (88.1%) reported hearing about the advisory the morning it was issued, but 11% reported drinking and 21% reported brushing teeth with municipal water during the advisory. Household members reported physical (16%) and mental (10%) health concerns that they believed were related to the advisory and activity disruptions including temporarily staying outside of the home (6%) during the advisory and continued use of alternative water sources after the advisory was lifted (82%). During a do-not-drink advisory, governmental agencies and community partners need to engage in joint prevention and response efforts to decrease water exposure and prevent activity disruptions.
Effect of Acute Inflammation Induced by Prolonged Exercise on Circulating Stem/Progenitor Cells That Mediate Tissue Repair.
Authors: Ioannis Papassotiriou, Antonia Spiropoulos, Maria Tsironi, Katerina Skenderi, Alexandra Margeli, Stelios Graphakos, Panayiotis Baltopoulos, Evgenios Goussetis
Journal: Blood (2007)
Response by Shirakabe et al to Letter Regarding Article, “Drp1-Dependent Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload–Induced Mitochondrial Dysfunction and Heart Failure”
Authors: Akihiro Shirakabe, Peiyong Zhai, Yoshiyuki Ikeda, Toshiro Saito, Yasuhiro Maejima, Chiao-Po Hsu, Masatoshi Nomura, Kensuke Egashira, Beth Levine, Junichi Sadoshima
Journal: Circulation (2016)
Bioactive extracellular matrix fragments in lung health and disease
Authors: Amit Gaggar, Nathaniel Weathington
Journal: Journal of Clinical Investigation (2016)

The extracellular matrix (ECM) is the noncellular component critical in the maintenance of organ structure and the regulation of tissue development, organ structure, and cellular signaling. The ECM is a dynamic entity that undergoes continuous degradation and resynthesis. In addition to compromising structure, degradation of the ECM can liberate bioactive fragments that cause cellular activation and chemotaxis of a variety of cells. These fragments are termed matrikines, and their cellular activities are sentinel in the development and progression of tissue injury seen in chronic lung disease. Here, we discuss the matrikines that are known to be active in lung biology and their roles in lung disease. We also consider the use of matrikines as disease markers and potential therapeutic targets in lung disease.
Distinct Profile and Epigenetic Modulation Of STAT Signaling In FOXP3+ T Regulatory Cells Among The Various MDS Subtypes
Authors: Eleftheria Lamprianidou, Costas Tsatalas, Paraskevi Miltiades, Theodoros Vassilakopoulos, Athanasios G. Galanopoulos, Sotirios G Papageorgiou, Vassilia Garypidou, Sofia Vakalopoulou, Emmanouil Spanoudakis, Dimitrios Margaritis, Ioannis Kotsianidis
Journal: Blood (2013)
P1213 : Adeno-associated virus vector-mediated liver gene therapy for Crigler-Najjar syndrome
Authors: P. Bosma, P. Labrune, N. Brunetti-Pierri, L. D’Antiga, M. Ott, M. Beinat, F. Ronchi, F. Mavilio, U. Beuers, A. Muro, U. Baumann, F. Mingozzi
Journal: Journal of Hepatology (2015)