tbuckley/cabot-search huggingface dataset:
L'injection haute pression est-elle utile pour la dissection sous-muqueuse? Résultats d'une étude randomisée prospective comparant deux couteaux de «seconde génération» sur un modèle porcin vivant
Authors: N Musquer, N Chapelle, M Le Rhun, E Metiver, Y Touchefeu, E Coron
Journal: Endoscopy (2018)

La dissection sous muqueuse est une technique initialement utilisée au Japon, et permettant la résection «en bloc» de large tumeurs superficielles. Plusieurs types de couteaux de dissection sous muqueuse (DSM) ont été commercialisés, mais peu d'études ont comparé leur efficacité. L'objectif de notre étude était de comparé, en termes d'efficacité et sureté, deux couteaux de DSM avec injection haute ou basse pression.
Quiescent Tissue Stem Cells Evade Immune Surveillance
Authors: Judith Agudo, Eun Sook Park, Samuel A. Rose, Eziwoma Alibo, Robert Sweeney, Maxime Dhainaut, Koichi S. Kobayashi, Ravi Sachidanandam, Alessia Baccarini, Miriam Merad, Brian D. Brown
Journal: Immunity (2018)
Surgeon who faked keyhole experience is jailed for six years
Authors: Clare Dyer
Journal: BMJ (2018)

A surgeon who lied about his work experience to land a job as consultant has been jailed for six years for fraud.

Sudip Sarker, 48, was appointed a general and colorectal surgeon at Alexandra Hospital in Redditch, Worcestershire, in August 2011. But after another surgeon blew the whistle, a review by the Royal College of Surgeons in 2012 expressed serious concern. He was stopped from operating, …
Toll-like receptor 3 in pancreatic cancer and malignant melanoma: a new paradigm for treatment
Authors: Anthony Schwartz, Kelly McCall, Eric Dickerson, Randall Moon, Andresz Slominski, Cesidio Giuliani, Leonard Kohn
Journal: Cancer Research (2008)

2762  It is now recognized that chronic inflammation is an important risk factor for the development of cancer. The proinflammatory cytokine IL6 is implicated in cancer because it is important for the activation of Stat3, a key regulator of cancer growth, survival, metastasis, immune evasion and angiogenesis. We have identified increased IL6 and Stat3 in vitro in pancreatic cancer and malignant melanoma cells with high basal expression of Toll-like receptor 3 (TLR3) and Wnt5a. We hypothesized that IL6/Stat3 activation, mediated by overexpressed TLR3 signaling, is important in the tumor growth process, that it may increase Wnt5a signaling, and be associated with increased cellular growth and migration. The link to TLR3 was established using siRNA inhibition. Additionally, using a novel inhibitor of pathologic TLR3 signaling, we have demonstrated decreases in these markers plus suppression of cell growth and migration in human pancreatic and malignant melanoma cancer cells in vitro, and have shown that this was relevant to cancer growth in vivo by demonstrating that the inhibitor suppressed the growth of pancreatic cancer and malignant melanoma in syngeneic mouse models.
Case 3-2018: A 5-Month-Old Boy with Hypoglycemia
Authors: Yee-Ming Chan, Rene Balza, Frances A. High
Journal: New England Journal of Medicine (2018)

A 5-month-old boy was admitted to the intensive care unit for evaluation of suspected hypoglycemia after several episodes of tachypnea in association with fasting. Examination revealed growth failure, doll-like facies, and a protuberant abdomen. A diagnosis was made.
Microhemorrhage-associated tissue iron enhances the risk for <i>Aspergillus fumigatus</i> invasion in a mouse model of airway transplantation
Authors: Joe L. Hsu, Olga V. Manouvakhova, Karl V. Clemons, Mohammed Inayathullah, Allen B. Tu, Raymond A. Sobel, Amy Tian, Hasan Nazik, Venkata R. Pothineni, Shravani Pasupneti, Xinguo Jiang, Gundeep S. Dhillon, Harmeet Bedi, Jayakumar Rajadas, Hubertus Haas, Laure Aurelian, David A. Stevens, Mark R. Nicolls
Journal: Science Translational Medicine (2018)

Increased ferric iron in allografts triggers a switch in the growth of the mold Aspergillus fumigatus from a colonizing to an invasive phenotype.
Immune Thrombocytopenia: A Monocentric Study of 113 Moroccan Cases
Authors: Zoubida Tazi Mezalek, Wafaa Ammouri, Hicham Harmouche, Mouna Maamar, Mohammed Adnaoui, Myriam Bourkia, Naima Mouatassim, Nisrine Bouigua
Journal: Blood (2017)
Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers
Authors: Min Yuen Teo, Kenneth Seier, Irina Ostrovnaya, Ashley M. Regazzi, Brooke E. Kania, Meredith M. Moran, Catharine K. Cipolla, Mark J. Bluth, Joshua Chaim, Hikmat Al-Ahmadie, Alexandra Snyder, Maria I. Carlo, David B. Solit, Michael F. Berger, Samuel Funt, Jedd D. Wolchok, Gopa Iyer, Dean F. Bajorin, Margaret K. Callahan, Jonathan E. Rosenberg
Journal: Journal of Clinical Oncology (2018)

Purpose Alterations in DNA damage response and repair (DDR) genes are associated with increased mutation load and improved clinical outcomes in platinum-treated metastatic urothelial carcinoma. We examined the relationship between DDR alterations and response to PD-1/PD-L1 blockade. Methods Detailed demographic, treatment response, and long-term outcome data were collected on patients with metastatic urothelial carcinoma treated with atezolizumab or nivolumab who had targeted exon sequencing performed on pre-immunotherapy tumor specimens. Presence of DDR alterations was correlated with best objective response per Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free and overall survival. Results Sixty patients with urothelial cancer enrolled in prospective trials of anti-PD-1/PD-L1 antibodies met inclusion criteria. Any DDR and known or likely deleterious DDR mutations were identified in 28 (47%) and 15 (25%) patients, respectively. The presence of any DDR alteration was associated with a higher response rate (67.9% v 18.8%; P < .001). A higher response rate was observed in patients whose tumors harbored known or likely deleterious DDR alterations (80%) compared with DDR alterations of unknown significance (54%) and in those whose tumors were wild-type for DDR genes (19%; P < .001). The correlation remained significant in multivariable analysis that included presence of visceral metastases. DDR alterations also were associated with longer progression-free and overall survival. Conclusion DDR alterations are independently associated with response to PD-1/PD-L1 blockade in patients with metastatic urothelial carcinoma. These observations warrant additional study, including prospective validation and exploration of the interaction between tumor DDR alteration and other tumor/host biomarkers of immunotherapy response.
Nine in 10 CCGs don’t know how long patients wait for talking therapies
Authors: Abi Rimmer
Journal: BMJ (2018)

Most clinical commissioning groups (CCGs) and mental health trusts have no idea how long patients with serious mental health problems are waiting for treatment, the BMA has found.

A freedom of information request, sent by the association, also revealed that some patients were waiting over a year for treatment.

The BMA asked all 207 CCGs and 54 mental health trusts in England about four talking therapies; dialectical behavioural therapy, cognitive behavioural therapy, family therapy, and dynamic psychotherapy. It …
Assessment and management of oesophago-gastric cancer: summary of NICE guidance
Authors: May Oo Khin, Nathan Bromham, Mark Harrison, Hilary Eadon
Journal: BMJ (2018)

### What you need to know

Oesophago-gastric cancer is the fourth commonest cause of cancer death in the UK, with 16 000 new cases each year, and its incidence is rising.1 Those affected by the disease often undergo a complex investigative pathway as a prelude to a variety of treatments with wide ranging short term and long term effects that require continued support throughout the initial period of care and beyond. Radical treatments for oesophago-gastric cancer are carried out in specialist centres where there will be access to a range of specialist healthcare professionals, but people with oesophago-gastric cancer will also require input from primary care. People whose cancer is suitable for palliative management will also benefit from the support of professionals from various disciplines, such as cancer care dietitians and palliative care professionals.

This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on diagnosis and management of oesophago-gastric cancer.2 The guidance was developed with the aim of improving and standardising care in all disciplines that treat people with oesophago-gastric cancer, including specialist centres, but some of the recommendations will affect non-specialist services too, and these are highlighted and summarised below.

NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal …
Induction of allergic responses in experimental murine model by long-term intranasal exposure of House Dust Mite(HDM) allergen
Authors: Jeom-Kyu Lee, Woo-Sung Chang, Sung-Hee Lee, Gyo Jeong Gu, Kyu-Tae Jeong, Ji-Hye Do
Journal: Journal of Allergy and Clinical Immunology (2018)
Rebooting Human Immunology
Authors: Mark M. Davis, Petter Brodin
Journal: Annual Review of Immunology (2018)

Recent progress in both conceptual and technological approaches to human immunology have rejuvenated a field that has long been in the shadow of the inbred mouse model. This is a healthy development both for the clinical relevance of immunology and for the fact that it is a way to gain access to the wealth of phenomenology in the many human diseases that involve the immune system. This is where we are likely to discover new immunological mechanisms and principals, especially those involving genetic heterogeneity or environmental influences that are difficult to model effectively in inbred mice. We also suggest that there are likely to be novel immunological mechanisms in long-lived, less fecund mammals such as human beings since they must remain healthy far longer than short-lived rodents in order for the species to survive.
Redirection to the bone marrow improves T cell persistence and antitumor functions
Authors: Anjum B. Khan, Ben Carpenter, Pedro Santos e Sousa, Constandina Pospori, Reema Khorshed, James Griffin, Pedro Velica, Mathias Zech, Sara Ghorashian, Calum Forrest, Sharyn Thomas, Sara Gonzalez Anton, Maryam Ahmadi, Angelika Holler, Barry Flutter, Zaida Ramirez-Ortiz, Terry K. Means, Clare L. Bennett, Hans Stauss, Emma Morris, Cristina Lo Celso, Ronjon Chakraverty
Journal: Journal of Clinical Investigation (2018)

A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that redirecting T cells to specialized niches in the BM that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration toward vascular-associated CXCL12+ cells in the BM and increased their local engraftment. Increased access of TCXCR4 to the BM microenvironment induced IL-15-dependent homeostatic expansion and promoted the differentiation of memory precursor-like cells with low expression of programmed death-1, resistance to apoptosis, and a heightened capacity to generate polyfunctional cytokine-producing effector cells. Following transfer to lymphoma-bearing mice, TCXCR4 showed a greater capacity for effector expansion and better tumor protection, the latter being independent of changes in trafficking to the tumor bed or local out-competition of regulatory T cells. Thus, redirected homing of T cells to the BM confers increased memory differentiation and antitumor immunity, suggesting an innovative solution to increase the persistence and functions of therapeutic T cells.
Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data
Authors: Stuart J Head, Milan Milojevic, Joost Daemen, Jung-Min Ahn, Eric Boersma, Evald H Christiansen, Michael J Domanski, Michael E Farkouh, Marcus Flather, Valentin Fuster, Mark A Hlatky, Niels R Holm, Whady A Hueb, Masoor Kamalesh, Young-Hak Kim, Timo Mäkikallio, Friedrich W Mohr, Grigorios Papageorgiou, Seung-Jung Park, Alfredo E Rodriguez, Joseph F Sabik, Rodney H Stables, Gregg W Stone, Patrick W Serruys, Arie Pieter Kappetein
Journal: The Lancet (2018)
Chlamydia pneumoniae enhances CD4+ and CD8 +T effector memory cell IL-2 and IL-4 responses in stimulated peripheral blood mononuclear cells in human subjects
Authors: Yitzchok M. Norowitz, Stephan Kohlhoff, Natalie Banniettis, Margaret R. Hammerschlag, Tamar A. Smith-Norowitz
Journal: Journal of Allergy and Clinical Immunology (2018)
HIV latency is reversed by ACSS2-driven histone crotonylation
Authors: Guochun Jiang, Don Nguyen, Nancie M. Archin, Steven A. Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M. Elsheikh, George R. Thompson, Dennis J. Hartigan-O’Connor, David M. Margolis, Joseph K. Wong, Satya Dandekar
Journal: Journal of Clinical Investigation (2018)

Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2). This reprogrammed the local chromatin at the HIV LTR through increased histone acetylation and reduced histone methylation. Pharmacologic inhibition or siRNA knockdown of ACSS2 diminished histone crotonylation-induced HIV replication and reactivation. ACSS2 induction was highly synergistic in combination with either a protein kinase C agonist (PEP005) or a histone deacetylase inhibitor (vorinostat) in reactivating latent HIV. In the SIV-infected nonhuman primate model of AIDS, the expression of ACSS2 was significantly induced in intestinal mucosa in vivo, which correlated with altered fatty acid metabolism. Our study links the HIV/SIV infection-induced fatty acid enzyme ACSS2 to HIV latency and identifies histone lysine crotonylation as a novel epigenetic regulator for HIV transcription that can be targeted for HIV eradication.
Abstract 13646: Electrical Stimulation Upregulates the miR-99 Family to Promote Cardiac Differentiation and Maturation of Human iPS Cells
Authors: Linlin Guo, Jialiang Liang, Wei Huang, Wenfeng Cai, Lei Wang, Jiapeng Wang, Christian Paul, Ronald W. Millard, Meifeng Xu, Yigang Wang
Journal: Circulation (2015)

Background: Electrical stimulation (ES) can efficiently promote cardiomyocyte differentiation and maturation of several cardiac progenitors, but the underlying mechanism has not yet been identified. This study aims to determine whether microRNAs (miRs) contribute to ES-induced cardiomyogenesis of human induced pluripotent stem cells (hiPSCs). Methods and Results: HiPSCs were induced into cardiomyocytes by our defined ES approaches (a biphasic square pulse (5ms) at 5 Hz frequency and with voltage of 0.5-1.0V/cm), and non-ES as treatment control. Cardiac markers (cTnT, Nkx2-5 and α-MHC) were significantly upregulated in hiPSCs with ES treatment as determined by qPCR (Fig.A), Western Blot, and immunostaining (Fig.B). The profile of miRs responsible for ES-induced cardiomyogenesis was analyzed by microarray and qPCR. Importantly, miR-99 family (Fig.C) (i.e., miR-99a and miR-100) were significantly upregulated in hiPSC-derived cardiac cells with ES treatment. Expression of cardiac genes in differentiated hiPSCs with ES treatment was decreased by miR-99a inhibition. Conversely, miR-99a overexpression enhanced sarcomeric maturation of hiPSC-derived cardiac cells under ES, as observed with immunostaining (Fig.E) and transmission electron microscopy. MiR-99a also enhanced the cardiac electrophysiological maturation as determined by patch clamp and calcium influx measurements. MiR-99a putatively targeted the 3'-UTR of BMPR2 mRNA (Fig.D) to facilitate cardiac maturation in hiPSCs, as identified by qPCR and the luciferase reporter assay. Conclusion: The miR-99 family appears to act as a crucial mediator for cardiogenic maturation of hiPSCs treated with ES. ES can enhance cardiac gene expression and structural maturation of hiPSCs for in vitro heart regeneration.
Unexplored therapeutic opportunities in the human genome.
Authors: Tudor I Oprea, Cristian G Bologa, Søren Brunak, Allen Campbell, Gregory N Gan, Anna Gaulton, Shawn M Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L Johnson, Anneli Karlson, Andrew R Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L Mathias, Michael T McManus, Terrence F Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L Roth, Stephan C Schürer, Anton Simeonov, Larry A Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dušica Vidovic, Anna Waller, David Westergaard, Jeremy J Yang, Gergely Zahoránszky-Köhalmi
Journal: Nature Reviews Drug Discovery (2018)
Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction
Authors: Øistein Svanes, Randi J. Bertelsen, Stein H. L. Lygre, Anne E. Carsin, Josep M. Antó, Bertil Forsberg, José M. García-García, José A. Gullón, Joachim Heinrich, Mathias Holm, Manolis Kogevinas, Isabel Urrutia, Bénédicte Leynaert, Jesús M. Moratalla, Nicole Le Moual, Theodore Lytras, Dan Norbäck, Dennis Nowak, Mario Olivieri, Isabelle Pin, Nicole Probst-Hensch, Vivi Schlünssen, Torben Sigsgaard, Trude D. Skorge, Simona Villani, Debbie Jarvis, Jan P. Zock, Cecilie Svanes
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described.Objectives: This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction.Methods: The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders.Measurements and Main Results: As compared with women not engaged in cleaning (ΔFEV1 = −18.5 ml/yr), FEV1 declined more rapidly in women responsible for cleaning at home (−22.1; P = 0.01) and occupational cleaners (−22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = −8.8 ml/yr; −13.1, P = 0.02; and −15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV1 decline (−22.0, P = 0.04; and −22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV1/FVC decline or airway obstruction.Conclusions: Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.
Socially awkward: how can we better promote walking as a social behaviour?
Authors: Ruth F Hunter, Kylie Ball, Olga L Sarmiento
Journal: British Journal of Sports Medicine (2018)

Walking—whether for exercise, recreation or transport—often occurs within the bounds of the families, communities and neighbourhoods in which we live. It is a behaviour shaped by our physical and social environment, including social norms and networks.1 Recent advocacy work has seen great strides made in calling for changing the physical (built) environment to support physical activity and walking behaviour. However, built environments are difficult and costly to change. Using inherent social structures in our societies may provide a cost-efficient way of encouraging people to walk and better use the built environment in which we live, work and play, and promote population-level change. These social factors may also have a key role to play in the maintenance of walking behaviour (as we are all embedded in these networks) and ‘scaling up’ nationwide and worldwide interventions (based on the principles of social norms).

Walking, as a social behaviour, is influenced by our social networks (ie, the people around us). Social norms—the standards of behaviour that are considered acceptable or appealing in a group or society—are also important for walking. Yet seldom are these networks or norms taken into account when promoting walking behaviour, and they are subsequently underutilised in our interventions.2 Promoting walking to individuals without considering these social constructs inherent in ‘social settings’ (such as schools, workplaces, parks, neighbourhoods, streets and public spaces) may risk missing opportunities to more effectively produce behaviour change or maintained behaviour change. We may also be missing …
No red blood cell damage and no hemolysis in G6PD-deficient subjects after ingestion of low vicine/convicine Vicia faba seeds
Authors: Valentina Gallo, Oleksii A. Skorokhod, Luigi Felice Simula, Tiziana Marrocco, Elisa Tambini, Evelin Schwarzer, Pascal Marget, Gérard Duc, Paolo Arese
Journal: Blood (2018)
Stromal cell signature in luminal breast cancer associated with response to neoadjuvant chemotherapy.
Authors: Maria Lucia H. Katayama, Rene A. da Costa Vieira, Rosimeire A. Roela, Victor P. Andrade, Luiz Guilherme C. A. de Lima, Giselly Encinas, Ligia M. Kerr, Simone Maistro, M. Mitzi Brentani, Maria A. A. Koike Folgueira
Journal: Clinical Cancer Research (2018)
Clinical and Genomic Characterization of Low–Prostate-specific Antigen, High-grade Prostate Cancer
Authors: Brandon A. Mahal, David D. Yang, Natalie Q. Wang, Mohammed Alshalalfa, Elai Davicioni, Voleak Choeurng, Edward M. Schaeffer, Ashley E. Ross, Daniel E. Spratt, Robert B. Den, Neil E. Martin, Kent W. Mouw, Peter F. Orio, Toni K. Choueiri, Mary-Ellen Taplin, Quoc-Dien Trinh, Felix Y. Feng, Paul L. Nguyen
Journal: European Urology (2018)