tbuckley/cabot-search huggingface dataset:
UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response
Authors: LN Huiting, Y Samaha, GL Zhang, JE Roderick, B Li, NM Anderson, YW Wang, L Wang, FJF Laroche, JW Choi, CT Liu, MA Kelliher, H Feng
Journal: Leukemia (2018)
Solitary Breast Metastasis From Rhabdomyosarcoma Shown on FDG PET/CT
Authors: Xia Bai, Xuemei Wang
Journal: Clinical Nuclear Medicine (2018)

Rhabdomyosarcoma rarely metastasizes to breast. A 15-year-old adolescent girl underwent FDG PET/CT scan for staging a newly diagnosed alveolar rhabdomyosarcoma. The images showed not only the abnormal activity in the region of the right maxillary sinus, consistent with the known primary tumor, but also an intense focal activity in the right breast. The right breast lesion was excised, and the pathological results showed alveolar rhabdomyosarcoma.
GP who sexually assaulted patient who thought she was having a heart attack is jailed for 15 months
Authors: Clare Dyer
Journal: BMJ (2018)

A GP has been jailed for 15 months after being found guilty of sexually assaulting a patient who visited a walk-in centre fearing that she was having a heart attack.

Rajeshkumar Mehta, 64, was working as an ad hoc locum at Sparkhill Primary Care and Community Centre in May 2016, when the patient, who suffered from anxiety, told him she was feeling weakness on her left side.

After taking down her history he asked her to lie down for examination and she unbuttoned her blouse. But Mehta pulled down her bra, the …
TCTAP A-154 The Clinical Impact of Radial Versus Femoral Access in Patients underwent Percutaneous Coronary Interventions with DES
Authors: Sang-Cheol Cho, Yong-Hoon Yoon, Minsoo Kim, Hanbit Park, Sang Yong Om, Sangwoo Park, Tae-Oh Kim, Sun Hack Lee, Osung Kwon, Kyusup Lee, Do-Yoon Kang, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
Metformin prevents the development of severe chronic kidney disease and its associated mineral and bone disorder
Authors: Ellen Neven, Benjamin Vervaet, Kerstin Brand, Ulrike Gottwald-Hostalek, Britt Opdebeeck, Annelies De Maré, Anja Verhulst, Jean-Daniel Lalau, Said Kamel, Marc E. De Broe, Patrick C. D’Haese
Journal: Kidney International (2018)
A phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of idelalisib (GS-1101) in combination with bendamustine and rituximab for previously treated indolent non-Hodgkin lymphomas (iNHL).
Authors: Sven De Vos, Laurie Helen Sehn, Stephen P. Mulligan, Martin H. Dreyling, Mathias J. Rummel, Pier Luigi Zinzani, David Michael Johnson, Shelley Evans, Roger D. Dansey, Wayne R. Godfrey, Myron Stefan Czuczman
Journal: Journal of Clinical Oncology (2013)

TPS8618 Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). Phase I trials demonstrated that idelalisib is highly active in pts with heavily pretreated iNHL: pts experienced reductions in disease-associated chemokines, profound and rapid reductions in lymphadenopathy, and durable clinical benefit with an acceptable safety profile (de Vos et al, 2011). Methods: 450 pts with previously treated iNHL, who have measurable lymphadenopathy, require therapy for iNHL, have received prior anti-CD20-antibody-containing therapy and chemotherapy, and who have iNHL that is not refractory to bendamustine (B) are randomized in a 2:1 ratio into Arm A or B. In Arm A, pts receive idelalisib at 150 mg BID continuously + rituximab (R) at 375 mg/m 2 every 28 days for 6 cycles + B at 90 mg/m 2 on days 1 and 2 of each 28-d cycle. In Arm B, pts receive placebo BID instead of idelalisib. Stratification factors include tumor type (follicular lymphoma vs others), tumor burden (high vs low), and time since completion of last prior therapy for iNHL (&lt;18 months vs ≥18 months). The primary endpoint is PFS, and key secondary endpoints include CR rate, ORR, lymph node response rate, and OS. This is an event-driven trial and primary endpoint evaluation will be based on independent central review. For the primary efficacy analysis, the difference in PFS between the treatment arms will be assessed in the ITT analysis set using Kaplan-Meier methods and the stratified log-rank test. The study opened for enrollment in Dec 2012 (NCT01732926). Clinical trial information: NCT01732926.
Emergency doctor who imported drugs illegally is spared jail
Authors: Clare Dyer
Journal: BMJ (2018)

An emergency doctor who illegally imported drugs over the internet has been spared jail despite having previously received a suspended prison sentence for a different drugs offence.

Michael Condon, 40, was sentenced at Bolton Crown Court to a community order of 12 months with a condition to serve 200 hours of unpaid work.

UK border control intercepted two parcels from the Netherlands addressed to Condon in December 2016 and March 2017. The first contained the class B drug methylone, also known as MDMC or M1, and the synthetic stimulant alpha PHP. The second contained the psychoactive substance flurophenmetrazine. The total quantity of all three drugs …
Impact on mortality of prompt admission to critical care for deteriorating ward patients: an instrumental variable analysis using critical care bed strain
Authors: Steve Harris, Mervyn Singer, Colin Sanderson, Richard Grieve, David Harrison, Kathryn Rowan
Journal: Intensive Care Medicine (2018)

To estimate the effect of prompt admission to critical care on mortality for deteriorating ward patients.We performed a prospective cohort study of consecutive ward patients assessed for critical care. Prompt admissions (within 4 h of assessment) were compared to a 'watchful waiting' cohort. We used critical care strain (bed occupancy) as a natural randomisation event that would predict prompt transfer to critical care. Strain was classified as low, medium or high (2+, 1 or 0 empty beds). This instrumental variable (IV) analysis was repeated for the subgroup of referrals with a recommendation for critical care once assessed. Risk-adjusted 90-day survival models were also constructed.A total of 12,380 patients from 48 hospitals were available for analysis. There were 2411 (19%) prompt admissions (median delay 1 h, IQR 1-2) and 9969 (81%) controls; 1990 (20%) controls were admitted later (median delay 11 h, IQR 6-26). Prompt admissions were less frequent (p < 0.0001) as strain increased from low (22%), to medium (15%) to high (9%); the median delay to admission was 3, 4 and 5 h respectively. In the IV analysis, prompt admission reduced 90-day mortality by 7.4% (95% CI 1.7-18.5%, p = 0.117) overall, and 16.2% (95% CI 1.1-31.3%, p = 0.036) for those recommended for critical care. In the risk-adjust survival model, 90-day mortality was similar.After allowing for unobserved prognostic differences between the groups, we find that prompt admission to critical care leads to lower 90-day mortality for patients assessed and recommended to critical care.
Safety, pharmacokinetics, and biomarkers of F-652, a recombinant human interleukin-22 dimer, in healthy subjects
Authors: Kai-Yang Tang, Jason Lickliter, Zhi-Hua Huang, Zong-Shu Xian, Han-Yang Chen, Cheng Huang, Chong Xiao, Yu-Peng Wang, Ying Tan, Lin-Feng Xu, Yu-Liang Huang, Xiao-Qiang Yan
Journal: Cellular and Molecular Immunology (2018)
Status, quality and specific needs of Ebola virus diagnostic capacity and capability in laboratories of the two European preparedness laboratory networks EMERGE and EVD-LabNet
Authors: Chantal B Reusken, Ramona Mögling, Pieter W Smit, Roland Grunow, Giuseppe Ippolito, Antonino Di Caro, Marion Koopmans
Journal: Eurosurveillance (2018)

From December 2013 to March 2016, West Africa experienced the largest Ebola virus (EBOV) outbreak to date, leading to a European-wide activation of laboratory preparedness and response. At the end of the outbreak, laboratories associated with the two European preparedness networks of expert laboratories EMERGE JA and EVD-LabNet were invited to participate in an assessment of the response of European laboratories to the EBOV outbreak, to identify learning points and training needs to strengthen future outbreak responses. Response aspects assessed included diagnostics, biorisk management and quality assurance. The overall coverage of EBOV diagnostics in the European Union/European Economic Area (EU/EEA) was found to be adequate although some points for quality improvement were identified. These included the need for relevant International Organization for Standardization (ISO) accreditation, the provision of EBOV external quality assessments (EQA) in periods where there is no emergency, facilitating access to controls and knowledge, biorisk management without compromising biosafety and a rapid public health response, and the need for both sustained and contingency funding for preparedness and response activities.
Breathless athlete: exercise-induced laryngeal obstruction
Authors: Steffan Arthur Griffin, Emil S Walsted, James H Hull
Journal: British Journal of Sports Medicine (2018)

Exercise-induced laryngeal obstruction (EILO) describes a condition in which the voice box closes inappropriately during vigorous exercise to precipitate respiratory symptoms, such as cough, wheeze and breathlessness.1 This can occur secondary to adduction of the vocal cords (glottic mechanism)±collapse of the arytenoid or aryepiglottic mucosa (supraglottic mechanism) with complete or incomplete obstruction of the larynx. The condition is highly prevalent in young athletes and estimated to affect between 5% and 10% of all adolescents.2 Despite this, EILO often remains overlooked as the cause of an athlete’s breathing difficulties and is often misdiagnosed as exercise-induced asthma.3 Failure to consider EILO in the differential diagnosis of a breathless athlete can result in delay to the initiation of effective treatment, and also to a potential inappropriate escalation in asthma therapy, with a deleterious impact on health and athletic performance. Research has shown that EILO may coexist with asthma, and distinguishing between these conditions can be challenging and often requires specialist investigation (figure 1). 



Figure 1 
Comparing EILO to EIB.  EIB, exercise-induced bronchoconstriction; EILO, exercise-induced laryngeal obstruction.



An 18-year-old female swimmer presents with a 3-year history of breathlessness that develops exclusively during high-intensity exercise. Inhaled asthma therapy, prescribed presumptively for a diagnosis …
HIV co-infection is associated with increased liver complications and reduced mental health among patients with chronic hepatitis B
Authors: M. Lu, N.P. Markowitz, Y. Zhou, K.-H. Wu, L.B. Rupp, S. Trudeau, J. Li, J.A. Boscarino, M.A. Schmidt, Y.G. Daida, S.C. Gordon
Journal: Journal of Hepatology (2018)
Novel protein biomarkers in serum extracellular vesicles for the diagnosis of primary sclerosing cholangitis (PSC) in patients with ulcerative colitis (UC)
Authors: A. Lapitz, A. Arbelaiz, M. Azkargorta, M. Krawczyk, Á. Santos-Laso, M.J. Perugorria, R. Jimenez-Aguero, A. Lacasta, C. Ibarra, A. Sanchez-Campos, E. Gonzalez, F. Lammert, P. Milkiewicz, M. Marzioni, J. Marin, T.H. Karlsen, J. Falcon-Perez, M. Chaparro, J. Gisbert, F. Elortza, L. Bujanda, J. Banales
Journal: Journal of Hepatology (2018)
The effect of primary prophylaxis therapy for large esophageal varices in patients with hepatocellular carcinoma
Authors: H.-S. Lu, C.-W. Su, M.-C. Hou, P.-H. Chen, P.-C. Lee, W.-Y. Kao, T.-I. Huo, Y.-H. Huang, H.-C. Lin, J.-C. Wu
Journal: Journal of Hepatology (2018)
Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant
Authors: Sarah Schillie, Aaron Harris, Ruth Link-Gelles, José Romero, John Ward, Noele Nelson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Hepatitis B (HepB) vaccination is the primary means of preventing infections and complications caused by hepatitis B virus (HBV). On February 21, 2018, the Advisory Committee on Immunization Practices (ACIP) recommended Heplisav-B (HepB-CpG), a yeast-derived vaccine prepared with a novel adjuvant, administered as a 2-dose series (0, 1 month) for use in persons aged ≥18 years. The ACIP Hepatitis Vaccines Work Group conducted a systematic review of the evidence, including data from four randomized controlled trials assessing prevention of HBV infection and six randomized controlled trials assessing adverse events in adults. Seroprotective antibody to hepatitis B surface antigen (anti-HBs) levels were achieved in 90.0%-100.0% of subjects receiving HepB-CpG (Dynavax Technologies Corporation), compared with 70.5%-90.2% of subjects receiving Engerix-B (GlaxoSmithKline Biologicals). The benefits of protection with 2 doses administered over 1 month make HepB-CpG an important option for prevention of HBV.
Hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil with systemic pegylated interferonα-2B for unresectable advanced intrahepatic cholangiocarcinoma.
Authors: Kei Sawara, Takayoshi Oikawa, Hidekatu Kuroda, Kazuhiro Kasai, Yasuhiro Takikawa
Journal: Journal of Clinical Oncology (2018)

428 Background: Cholangiocarcinoma is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepaticcholangiocarcinoma (ECC). The prognosis of ICC is far worse than that of ECC. In this study, the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) combined with subcutaneous administration of pegylated interferon (PEG-IFN) α-2b for patients with unresectable advanced ICC was evaluated. Methods: The subjects were 21 unresectable advanced ICC patients treated using subcutaneous PEG-IFN α-2b (50-100 μg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1-5 of every week, for 4 weeks). One treatment cycle lasted 4 weeks. Therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ≥ 1 cycle. Results: The objective early response rate was 60.0 %. Cumulative survival rates were 71.6 % at 6 months, 53.7 % at 12 months, 28.6 % at 18 months, and 14.3 % at 24 months. Median survival time was 14.6 months. All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment related deaths were not observed. Conclusions: The combination therapy of PEG-IFN α-2b and 5-FU for unresectable advanced ICC seems to be better than the results of the previous studies. In addition, most adverse effects are transient and well tolerated. Although a larger prospective study involving a larger population of patients with advanced ICC is needed to evaluate this combination therapy, this combination therapy may be useful for patients with unresectable advanced ICC as one of the therapeutic option.
Efficacy and safety of ticagrelor were similar in patients with past MI, regardless of multivessel coronary disease
Authors: Anupam Goel
Journal: Annals of Internal Medicine (2018)

Source Citation Bansilal S, Bonaca MP, Cornel JH, et al. Ticagrelor for secondary prevention of atherothrombotic events in patients with multivessel coronary disease. J Am Coll Cardiol. 2018;71:489-96. 29406853
Longitudinal Modeling of Lung Function Trajectories in Smokers with and without Chronic Obstructive Pulmonary Disease
Authors: James C. Ross, Peter J. Castaldi, Michael H. Cho, Craig P. Hersh, Farbod N. Rahaghi, Gonzalo V. Sánchez-Ferrero, Margaret M. Parker, Augusto A. Litonjua, David Sparrow, Jennifer G. Dy, Edwin K. Silverman, George R. Washko, Raúl San José Estépar
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The relationship between longitudinal lung function trajectories, chest computed tomography (CT) imaging, and genetic predisposition to chronic obstructive pulmonary disease (COPD) has not been explored.
Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction
Authors: Julie K. Allen, Guillermo N. Armaiz-Pena, Archana S. Nagaraja, Nouara C. Sadaoui, Tatiana Ortiz, Robert Dood, Merve Ozcan, Danielle M. Herder, Monika Haemmerle, Kshipra M. Gharpure, Rajesha Rupaimoole, Rebecca A. Previs, Sherry Y. Wu, Sunila Pradeep, Xiaoyun Xu, Hee Dong Han, Behrouz Zand, Heather J. Dalton, Morgan Taylor, Wei Hu, Justin Bottsford-Miller, Myrthala Moreno-Smith, Yu Kang, Lingegowda S. Mangala, Cristian Rodriguez-Aguayo, Vasudha Sehgal, Erika L. Spaeth, Prahlad T. Ram, Stephen T.C. Wong, Frank C. Marini, Gabriel Lopez-Berestein, Steve W. Cole, Susan K. Lutgendorf, Mariella De Biasi, Anil K. Sood
Journal: Cancer Research (2018)

Mounting clinical and preclinical evidence supports a key role for sustained adrenergic signaling in the tumor microenvironment as a driver of tumor growth and progression. However, the mechanisms by which adrenergic neurotransmitters are delivered to the tumor microenvironment are not well understood. Here we present evidence for a feed-forward loop whereby adrenergic signaling leads to increased tumoral innervation. In response to catecholamines, tumor cells produced brain-derived neurotrophic factor (BDNF) in an ADRB3/cAMP/Epac/JNK-dependent manner. Elevated BDNF levels in the tumor microenvironment increased innervation by signaling through host neurotrophic receptor tyrosine kinase 2 receptors. In patients with cancer, high tumor nerve counts were significantly associated with increased BDNF and norepinephrine levels and decreased overall survival. Collectively, these data describe a novel pathway for tumor innervation, with resultant biological and clinical implications.Significance: Sustained adrenergic signaling promotes tumor growth and metastasis through BDNF-mediated tumoral innervation. Cancer Res; 78(12); 3233-42. ©2018 AACR.
Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy
Authors: Ji Hyun Kim, Young Don Kim, Minjong Lee, Baek Gyu Jun, Tae Suk Kim, Ki Tae Suk, Seong Hee Kang, Moon Young Kim, Gab Jin Cheon, Dong Joon Kim, Soon Koo Baik, Dae Hee Choi
Journal: Journal of Hepatology (2018)
Efficacy and tolerability of triple drug therapy with albendazole, pyrantel pamoate, and oxantel pamoate compared with albendazole plus oxantel pamoate, pyrantel pamoate plus oxantel pamoate, and mebendazole plus pyrantel pamoate and oxantel pamoate against hookworm infections in school-aged children in Laos: a randomised, single-blind trial
Authors: Wendelin Moser, Somphou Sayasone, Syda Xayavong, Bangon Bounheuang, Maxim Puchkov, Jörg Huwyler, Jan Hattendorf, Jennifer Keiser
Journal: The Lancet Infectious Diseases (2018)
Nuclear IGF1R Interacts with Regulatory Regions of Chromatin to Promote RNA Polymerase II Recruitment and Gene Expression Associated with Advanced Tumor Stage
Authors: Tamara Aleksic, Nicki Gray, Xiaoning Wu, Guillaume Rieunier, Eliot Osher, Jack Mills, Clare Verrill, Richard J. Bryant, Cheng Han, Kathryn Hutchinson, Adam G. Lambert, Rajeev Kumar, Freddie C. Hamdy, Ulrike Weyer-Czernilofsky, Michael P. Sanderson, Thomas Bogenrieder, Stephen Taylor, Valentine M. Macaulay
Journal: Cancer Research (2018)

Internalization of ligand-activated type I IGF receptor (IGF1R) is followed by recycling to the plasma membrane, degradation or nuclear translocation. Nuclear IGF1R reportedly associates with clinical response to IGF1R inhibitory drugs, yet its role in the nucleus is poorly characterized. Here, we investigated the significance of nuclear IGF1R in clinical cancers and cell line models. In prostate cancers, IGF1R was predominantly membrane localized in benign glands, while malignant epithelium contained prominent internalized (nuclear/cytoplasmic) IGF1R, and nuclear IGF1R associated significantly with advanced tumor stage. Using ChIP-seq to assess global chromatin occupancy, we identified IGF1R-binding sites at or near transcription start sites of genes including
P259Up-regulation of myocardial connexin-43 is involved in compensatory response of the heart to acute injury
Authors: N Tribulova, C Viczenczova, B Kura, K K Chaudagar, B Szeiffova Bacova, T Egan Benova, V Knezl, M Barancik, T Ravingerova, J Slezak
Journal: Cardiovascular Research (2018)
Whole-Exome Sequencing in Age-Related Macular Degeneration Identifies Rare Variants in COL8A1, a Component of Bruch’s Membrane
Authors: Jordi Corominas, Johanna M. Colijn, Maartje J. Geerlings, Marc Pauper, Bjorn Bakker, Najaf Amin, Laura Lores Motta, Eveline Kersten, Alejandro Garanto, Joost A.M. Verlouw, Jeroen G.J. van Rooij, Robert Kraaij, Paulus T.V.M. de Jong, Albert Hofman, Johannes R. Vingerling, Tina Schick, Sascha Fauser, Eiko K. de Jong, Cornelia M. van Duijn, Carel B. Hoyng, Caroline C.W. Klaver, Anneke I. den Hollander
Journal: Ophthalmology (2018)

Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants.Genome-wide case-control association study of WES data.One thousand one hundred twenty-five AMD patients and 1361 control participants.A single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes.Genetic variants associated with AMD.We detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10-5). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch's membrane.This study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch's membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch's membrane, contributing to the accumulation of drusen and the development of AMD.
Presence of IgA isotype F-actin is frequent in patients with cirrhosis and consitutes the risk of progressive disease course
Authors: B. Balogh, T. Tornai, N. Sipeki, Z. Vitális, I. Tornai, P. Antal-Szalmás, T. Dinya, G.L. Norman, T. Bruns, M. Papp
Journal: Journal of Hepatology (2018)