tbuckley/cabot-search huggingface dataset:
Causes of Death and Conditional Survival Estimates of Medium- and Long-term Survivors of Pancreatic Adenocarcinoma
Authors: Douglas S. Swords, Sean J. Mulvihill, Matthew A. Firpo, Courtney L. Scaife
Journal: JAMA Oncology (2018)

Causes of Death and Conditional Survival Estimates of Medium-and Long-term Survivors of Pancreatic AdenocarcinomaMost patients who undergo resection of pancreatic ductal adenocarcinoma (PDAC) die within 5 years. [1]2][3][4][5] Five-year survivors remain at risk for PDAC-related death, 1,2,4,5 and recurrences more than 15 years after diagnosis are reported. 4 A study reporting conditional survival (CS) extended only 6.5 years after diagnosis. 3Reported 10-year survival rates range from 3.9% in a National Cancer Database (NCDB) study to 12% to 13% in singleinstitution studies. 1,5,6 In the NCDB study, the risk of death decreased for 6 years and then remained fairly constant at 10% per year in years 7 to 15, which was double that of an age-and sexmatched general population. 6 Limited prognostic information exists for 5-to 15-year survivors.We used the Surveillance, Epidemiology, and End Results (SEER) database (http://www.seer.cancer.gov) to quantify yearly risks of death due to PDAC vs other causes and calculate CS estimates extending 21 years after diagnosis.
Prejudice persists against black and ethnic minority doctors
Authors: Partha Das
Journal: BMJ (2018)

Menon’s article reminded me of my late father’s experiences as an ear, nose, and throat registrar in the 1970s and as an inner city general practitioner in the ’80s.1 The “local candidate” trope was so frequently used as justification for not appointing black and minority ethnic (BME) clinicians that it ceased being a euphemism. Support for foreign doctors from the establishment was …
Amifostine Inhibits Hematopoietic Progenitor Cell Apoptosis by Activating NF-κB/Rel Transcription Factors
Authors: Maria Fiammetta Romano, Annalisa Lamberti, Rita Bisogni, Corrado Garbi, Antonio M. Pagnano, Pasquale Auletta, Pierfrancesco Tassone, Maria Caterina Turco, Salvatore Venuta
Journal: Blood (1999)
Respuesta oncológica a largo plazo de las prótesis metálicas autoexpandibles en el tratamiento de la neoplasia de colon oclusiva
Authors: P Ruiz, X Andujar, B Arau, JC Espinos, M Esteve, F Fernandez Bañares, C Loras
Journal: Endoscopy (2017)

las prótesis metálicas autoexpandibles (PMA) se han utilizado en el tratamiento del cáncer de colon (CC) oclusivo como puente a la cirugía o como un tratamiento paliativo. La respuesta oncológica a largo plazo de las mismas sigue siendo controvertida.
Rentabilidad de la endoscopia urgente en la hemorragia digestiva baja
Authors: A Hidalgo Romero, D Rafael De La Cruz Esteban, M López-Cerón Pinilla, C Cuadrado Tiemblo, T Valdés Lacasa, J Diaz Tasende, G Castellano Tortajada
Journal: Endoscopy (2017)

La colonoscopia representa un rol indispensable en el manejo de la hemorragia digestiva baja (HDB). Sin embargo, el momento de su realización es controvertido. Nuestro estudio compara la rentabilidad de la endoscopia urgente (primeras 24 horas) vs. electiva (tras 24 horas).
Manejo laparoendoscópico (“Rendez-Vous”) de la cole-coledocolitiasis: Experiencia en nuestro centro
Authors: E Merino Gallego, C Molina Villalba, F Gallardo Sánchez, FJ Gallego Rojo
Journal: Endoscopy (2017)

La coledocolitiasis se encuentra asociada a colelitiasis en el 11 – 20%. Existen diversas opciones de manejo, siendo una de ellas la colecistectomía laparoscópica seguida de CPRE con técnica “Rendez-Vous” (RV) transcística en el mismo tiempo.
Of Mice and Men . . . and Microbes: Conclusions and Cautions from a Murine Study of the Lung Microbiome and Microbiome–Immune Interactions
Authors: John E. McGinniss, Ronald G. Collman
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

This study calls attention to the strengths and weaknesses of reductionist model systems in the study of fibrosis.Laudably, the investigators used complementary approaches to clearly show that the IPF-ECM regulates miR-29 through mechanisms that are distinct from the mechanotransduction hierarchies reported using stiffnesscontrolled hydrogels.However, the results require that we reconcile the discordant findings generated from the different model systems.Matrix factors are critical to fibroblast biology, and incorporation of different matrix conditions into experimental design can provide important mechanistic insights (1, 6).However, it also demands appreciation of different levels of complexity.Hydrogels allow control of stiffness and ECM ligands, but lack dimensionality, matrix-protein interactions, and cross-linking.Decellularized matrices incorporate dimensionality, preserve native protein biochemistry, and maintain regional matrix mechanical properties.Nevertheless, they can be labor-intensive to produce and difficult to predict (14).Moreover, the effects of tissue processing on proteoglycans and glycosaminoglycans, on protein conformation, on matrisome protein interactions, and on the enzymes/growth factors harbored within the matrix are all poorly understood.Neither approach replicates the in vivo effects of stretch or recapitulates the effect of multiple resident and recruited cell types interacting in time and space in the context of a chemically and mechanically changing matrix.With increasing complexity, control of experimental variables diminishes, as does the ability to study specific mechanistic biology in depth.In time, tissue engineering may improve our ability to study intact systems ( 14).Nevertheless, the use of in vivo xenograft models in the current study provides confidence that the miRNA processing machinery can have a critical effect on fibrogenesis.Whether this represents "the" answer for IPF remains to be seen, but the evidence that it could represent "an" answer is indicative of ongoing progress in the field.
Case 21-2018: A 61-Year-Old Man with Grandiosity, Impulsivity, and Decreased Sleep
Authors: John B. Taylor, Laura M. Prager, Nadia V. Quijije, Pamela W. Schaefer
Journal: New England Journal of Medicine (2018)

A 61-year-old man with a history of stroke and alcohol-use disorder presented with grandiosity, impulsivity, and decreased sleep. An evaluation was notable for an expansive affect, emotional lability, and impaired memory. A diagnosis was made.
Myelin Plasticity and Nervous System Function
Authors: Michelle Monje
Journal: Annual Review of Neuroscience (2018)

Structural plasticity in the myelinated infrastructure of the nervous system has come to light. Although an innate program of myelin development proceeds independent of nervous system activity, a second mode of myelination exists in which activity-dependent, plastic changes in myelin-forming cells influence myelin structure and neurological function. These complementary and possibly temporally overlapping activity-independent and activity-dependent modes of myelination crystallize in a model of experience-modulated myelin development and plasticity with broad implications for neurological function. In this article, I consider the contributions of myelin to neural circuit function, the dynamic influences of experience on myelin microstructure, and the role that plasticity of myelin may play in cognition.
Immune sensitization during 1 year in the Antarctic high‐altitude Concordia Environment
Authors: Matthias Feuerecker, Brian E. Crucian, Roel Quintens, Judith‐Irina Buchheim, Alex P. Salam, Ales Rybka, Marjan Moreels, Claudia Strewe, Raymond Stowe, Satish Mehta, Gustav Schelling, Manfred Thiel, Sarah Baatout, Clarence Sams, Alexander Choukèr
Journal: Allergy (2018)

Antarctica is a challenging environment for humans. It serves as a spaceflight ground analog, reflecting some conditions of long-duration exploration class space missions. The French-Italian Concordia station in interior Antarctica is a high-fidelity analog, located 1000 km from the coast, at an altitude of 3232 m. The aim of this field study was to characterize the extent, dynamics, and key mechanisms of the immune adaptation in humans overwintering at Concordia for 1 year.This study assessed immune functions in fourteen crewmembers. Quantitative and phenotypic analyses from human blood were performed using onsite flow cytometry together with specific tests on receptor-dependent and receptor-independent functional innate and adaptive immune responses. Transcriptome analyses and quantitative identification of key response genes were assessed.Dynamic immune activation and a two-step escalation/activation pattern were observed. The early phase was characterized by moderately sensitized global immune responses, while after 3-4 months, immune responses were highly upregulated. The cytokine responses to an ex vivo stimulation were markedly raised above baseline levels. These functional observations were reflected at the gene transcriptional level in particular through the modulation of hypoxia-driven pathways.This study revealed unique insights into the extent, dynamics, and genetics of immune dysfunctions in humans exposed for 1 year to the Antarctic environment at the Concordia station. The scale of immune function was imbalanced toward a sensitizing of inflammatory pathways.
Community outbreak of serogroup B invasive meningococcal disease in Beaujolais, France, February to June 2016: from alert to targeted vaccination
Authors: Alexandra Thabuis, Karim Tararbit, Muhamed-Kheir Taha, Dominique Dejour-Salamanca, Vincent Ronin, Isabelle Parent du Chatelet, Guillaume Spaccaferri
Journal: Eurosurveillance (2018)

In February and March 2016, four cases of serogroup B invasive meningococcal disease (IMD) occurred over 3 weeks in a small area north of Lyon in the Auvergne-Rhône-Alpes region, France. There were no deaths but two cases had sequelae. This community outbreak was caused by a rare meningococcal strain of the clonal complex ST-32, covered by the 4CMenB/Bexsero vaccine. The incidence rate for serogroup B IMD in this area was 22.5 per 100,000 inhabitants, which is above the epidemic threshold (10/100,000). The number of cases observed was significantly higher than expected in the age group of 0–24 year-olds (standardised incidence ratio: 96). These results suggested the potential emergence of this invasive strain in this sub-population. In accordance with French recommendations, it was decided to vaccinate the population aged between 2 months and 24 years, living, working or studying in the epidemic area. The vaccination campaign took place from April to September 2016. Vaccination coverage was estimated at 47% for one dose and 40% for two doses. The lowest coverage estimations were observed for the age groups younger than 3 and 15–19 years. Enhanced epidemiological and microbiological surveillance reported a fifth case in June 2016, outside the epidemic area.
Abstract 5170: The effect of vitamin K on aggressiveness, lipid metabolism and gene expression in triple-negative breast cancer cells
Authors: Leila Kokabee, Sarah Beaudin, JoEllen Welsh
Journal: Cancer Research (2018)

Abstract Vitamin K is an essential cofactor in the γ-carboxylation of glutamate (Glu) to γ-carboxyglutamate (Gla), a post-translational modification mediated by the gamma-glutamyl carboxylase enzyme (GGCX) and vitamin K oxidoreductases (VKORC1 or VCORC1L1). All three of these genes are expressed in most breast cancer cell lines and The Cancer Genome Atlas (TCGA) data indicate that upregulation of these genes is associated with reduced survival in breast cancer patients. Since vitamin K is not typically present in cell culture media, γ-carboxylation is limited in vitro despite the presence of GGCX and VKORs. To determine the functional significance of the vitamin K pathway in breast cancer cells, we assessed the effect of vitamin K treatment on cell survival, migration and mammosphere formation. SUM159 and Hs578T cells were maintained in vitamin K1 (5 ug/mL) for at least 3 passages for all assays. Cells passaged with vitamin K produced γ-carboxylated proteins and exhibited increased cell survival after 72h, increased mammosphere formation after 8 days and increased cell migration after 48h compared to cells passaged in ethanol vehicle. Inhibition of VKORC1 with 2 uM warfarin decreased the production of γ-carboxylated proteins and reduced the effects of vitamin K on cell survival and migration but not on mammosphere formation. Microarray profiling and pathway analysis indicated upregulation of several known oncogenic pathways, including PI3K-AKT, VEGF-VEGFR, RANK-RANKL and JAK/STAT in vitamin K-treated SUM159 and Hs578T cells. Thus, γ-carboxylation of proteins driven by vitamin K might indirectly activate these pathways to enhance cell survival, cell migration and mammosphere formation. Additional pathways upregulated in vitamin K-treated cells included adipogenesis, fatty acid biosynthesis and lipid metabolism. We therefore examined lipid droplet formation in cells exposed to vitamin K using Bodipy assays. We detected an increase in lipid droplet formation after 72 hours of vitamin K treatment, which was inhibited by warfarin. Since aggressive breast cancers are often associated with accumulation of cytoplasmic lipid droplets, further studies on the mechanism by which vitamin K increases lipid accumulation are warranted. In conclusion, our data indicate that vitamin K enhances γ-carboxylation, breast cancer aggressiveness and lipid metabolism, suggesting that blocking the vitamin K pathway might be of therapeutic value for patients whose tumors express GGCX and VKORs. Citation Format: Leila Kokabee, Sarah Beaudin, JoEllen Welsh. The effect of vitamin K on aggressiveness, lipid metabolism and gene expression in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5170.
Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer
Authors: Giulia Siravegna, Luca Lazzari, Giovanni Crisafulli, Andrea Sartore-Bianchi, Benedetta Mussolin, Andrea Cassingena, Cosimo Martino, Richard B. Lanman, Rebecca J. Nagy, Stephen Fairclough, Giuseppe Rospo, Giorgio Corti, Alice Bartolini, Pamela Arcella, Monica Montone, Francesca Lodi, Annalisa Lorenzato, Alice Vanzati, Emanuele Valtorta, Giovanni Cappello, Andrea Bertotti, Sara Lonardi, Vittorina Zagonel, Francesco Leone, Mariangela Russo, Antonella Balsamo, Mauro Truini, Federica Di Nicolantonio, Alessio Amatu, Erica Bonazzina, Silvia Ghezzi, Daniele Regge, Angelo Vanzulli, Livio Trusolino, Salvatore Siena, Silvia Marsoni, Alberto Bardelli
Journal: Cancer Cell (2018)
Secukinumab decreases serum Krebs von den Lungen 6 (KL-6) level in patients with psoriasis with elevated serum KL-6 level
Authors: C. Chijiwa, S. Takeoka, M. Kamata, H. Uchida, S. Fukaya, K. Hayashi, A. Fukuyasu, T. Tanaka, T. Ishikawa, T. Ohnishi, Y. Tada
Journal: British Journal of Dermatology (2018)
Uso de prótesis esofágicas cubiertas de doble malla en fístulas esofágicas post-quirúrgicas y perforaciones esofágicas: Experiencia en nuestro centro
Authors: P Sanz Segura, J Gotor Delso, P Garcia Cámara, E Sierra Moros, J Val Pérez, R Uribarrena Amezaga
Journal: Endoscopy (2017)

El uso de prótesis esofágicas para el manejo endoscópico de fístulas y perforaciones se ha convertido en un procedimiento habitual. Una de sus limitaciones es su alta tasa de migración. Para resolver esta situación, se ha propuesto el uso de prótesis cubiertas de doble malla.
Point-of-care production of therapeutic proteins of good-manufacturing-practice quality
Authors: Rajani Adiga, Mustafa Al-adhami, Abhay Andar, Shayan Borhani, Sheniqua Brown, David Burgenson, Merideth A. Cooper, Sevda Deldari, Douglas D. Frey, Xudong Ge, Hui Guo, Chandrasekhar Gurramkonda, Penny Jensen, Yordan Kostov, William LaCourse, Yang Liu, Antonio Moreira, KarunaSri Mupparapu, Chariz Peñalber-Johnstone, Manohar Pilli, Benjamin Punshon-Smith, Aniruddha Rao, Govind Rao, Priyanka Rauniyar, Sergei Snovida, Kanika Taurani, Dagmawi Tilahun, Leah Tolosa, Michael Tolosa, Kevin Tran, Krishna Vattem, Sudha Veeraraghavan, Brandon Wagner, Joshua Wilhide, David W. Wood, Adil Zuber
Journal: Nature Biomedical Engineering (2018)
DIFFERENTIATION OF PANCREATIC CYSTS BY CONTRAST-ENHANCED ENDOSCOPIC ULTRASONOGRAPHY
Authors: M Patricia Olar, O Mosteanu, I Rusu, A Seicean
Journal: Endoscopy (2018)

It is a great challenge to differentiate between the type and the malignant potential of a newly diagnosed pancreatic cyst. Our aim was to assess the role of contrast-enhanced endoscopic ultrasonography (EUS) for increasing diagnostic accuracy.
Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study
Authors: Dominique Baeten, Mikkel Østergaard, James Cheng-Chung Wei, Joachim Sieper, Pentti Järvinen, Lai-Shan Tam, Carlo Salvarani, Tae-Hwan Kim, Alan Solinger, Yakov Datsenko, Chandrasena Pamulapati, Sudha Visvanathan, David B Hall, Stella Aslanyan, Paul Scholl, Steven J Padula
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To evaluate the efficacy and safety of risankizumab, a humanised monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in patients with active ankylosing spondylitis (AS). Methods A total of 159 patients with biological-naïve AS, with active disease (Bath Ankylosing Spondylitis Disease Activity Index score of ≥4), were randomised (1:1:1:1) to risankizumab (18 mg single dose, 90 mg or 180 mg at day 1 and weeks 8, 16 and 24) or placebo over a 24-week blinded period. The primary outcome was a 40% improvement in Assessment in Spondylo Arthritis International Society (ASAS40) at week 12. Safety was assessed in patients who received at least one dose of study drug. Results At week 12, ASAS40 response rates were 25.5%, 20.5% and 15.0% in the 18 mg, 90 mg and 180 mg risankizumab groups, respectively, compared with 17.5% in the placebo group. The estimated difference in proportion between the 180 mg risankizumab and placebo groups (primary endpoint) was –2.5% (95% CI –21.8 to 17.0; p=0.42). Rates of adverse events were similar in all treatment groups. Conclusions Treatment with risankizumab did not meet the study primary endpoint and showed no evidence of clinically meaningful improvements compared with placebo in patients with active AS, suggesting that IL-23 may not be a relevant driver of disease pathogenesis and symptoms in AS. Trial registration number NCT02047110 ; Pre-results.
Elaboración y validación del cuestionario CCRSQ para medir la calidad y seguridad de la colonoscopia de cribado de cáncer colorrectal desde la experiencia del paciente
Authors: A Brotons Brotons, JJ Mira Solves, FJ Lacueva Gómez, M Guilabert Mora, MF García Sepulcre, G Belda Abad, BJ Lumbreras Lacarra, FJ Sola-Vera Sánchez
Journal: Endoscopy (2017)

Es un requisito fundamental que las Unidades de Endoscopia con Programas de Cribado de Cáncer Colorrectal (CCR) sigan adecuados controles y programas de mejora de calidad. Para llevarlo a cabo es imprescindible conocer la experiencia del paciente. Hasta donde sabemos, no hay ningún cuestionario que se haya validado para esta finalidad, a pesar de que la guía de la Asociación Española de Gastroenterología lo recomienda.
Differences Between Randomized Clinical Trial Patients and Real-World Initiators of the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide
Authors: Jakob Schöllhammer Knudsen, Reimar Wernich Thomsen, Anton Pottegård, Filip Krag Knop, Henrik Toft Sørensen
Journal: Diabetes Care (2018)

Randomized controlled trials (RCTs) are considered the gold standard for determining efficacy and safety of new drugs. Successful randomization addresses known and unknown confounding when assessing a drug’s effect among trial patients selected on strict inclusion and exclusion criteria (1). However, treatment results have been shown on occasion to be much less favorable than expected outside trial populations, often related to differences in age, comorbidity, disease severity, drug compliance, and/or comedication among patients treated in everyday clinical practice (1). The risk of adverse drug effects may also be higher among patients treated in routine clinical care.

Liraglutide, a glucagon-like peptide 1 receptor agonist, was quickly adopted by clinicians following its approval by the European Medicines Agency in 2009 and by the U.S. Food and Drug Administration in 2010. Approval was based on a number of phase III RCTs called the Liraglutide Effect and Action in Diabetes (LEAD) 1–5 trials (2).

We used data from Danish population-based medical databases to examine whether routine clinical care liraglutide initiators would have been eligible for participation in …
Self-expandable metal stent placement for malignant esophageal strictures – changes in clinical outcomes over time
Authors: Agnes Reijm, Paul Didden, Sara Schelling, Peter Siersema, Marco Bruno, Manon Spaander
Journal: Endoscopy (2018)

Abstract Background Self-expandable metal stents (SEMSs) are effective for improving dysphagia in patients with incurable esophageal cancer but are also associated with recurrent dysphagia and adverse events. In the past decades, new SEMSs have been introduced, but also patients’ risk profiles have altered. It is unknown if these changes have affected SEMS outcomes. Methods This retrospective cohort study was conducted in a tertiary referral center in the Netherlands. Patients who underwent palliative esophageal SEMS placement for malignant dysphagia between 1994 and 2017 were included. The primary outcome was to assess shifts over time with respect to recurrent dysphagia and adverse events after SEMS placement. Results 997 patients who underwent SEMS placement were included. Recurrent dysphagia occurred in 309 patients (31 %) and remained stable, although with a trend towards an increase over time (hazard ratio [HR] 1.02 per 1-year increase; P = 0.05). Migration rate significantly increased over time (HR 1.04 per 1-year increase; P = 0.01). SEMS-related complications occurred in 461 patients (46.2 %), with 207 (20.7 %) major and 336 (33.7 %) minor complications. Prior chemoradiotherapy was significantly associated with major complications (HR 1.69; P &lt; 0.001). Pain was the most common adverse event and showed a significant increase over time (P &lt; 0.01). Factors associated with pain were prior chemoradiotherapy, absence of a fistula, axial and radial forces, and squamous cell carcinoma. Conclusions Despite the introduction of novel esophageal SEMS designs, recurrent dysphagia has not declined over the years. Stent-related complications have increased in recent years, which seems to be mainly associated with more frequent use of chemoradiotherapy prior to SEMS placement.