tbuckley/cabot-search huggingface dataset:
Effects of adjunctive balloon angioplasty after intravascular ultrasound-guided optimal directional coronary atherectomy
Authors: Takahiko Suzuki, Hiroaki Hosokawa, Osamu Katoh, Tamotsu Fujita, Katsumi Ueno, Shinichi Takase, Kenshi Fujii, Hideo Tamai, Tadanori Aizawa, Tetsu Yamaguchi, Hiroyuki Kurogane, Mikihiro Kijima, Hirotaka Oda, Etsuo Tsuchikane, Tomoaki Hinohara, Peter J Fitzgerald
Journal: Journal of the American College of Cardiology (1999)
Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations
Authors: Ana Márquez, Martin Kerick, Alexandra Zhernakova, Javier Gutierrez-Achury, Wei-Min Chen, Suna Onengut-Gumuscu, Isidoro González-Álvaro, Luis Rodriguez-Rodriguez, Raquel Rios-Fernández, Miguel A. González-Gay, Maureen D. Mayes, Soumya Raychaudhuri, Stephen S. Rich, Cisca Wijmenga, Javier Martín
Journal: Genome Medicine (2018)

In recent years, research has consistently proven the occurrence of genetic overlap across autoimmune diseases, which supports the existence of common pathogenic mechanisms in autoimmunity. The objective of this study was to further investigate this shared genetic component.
Reflectance confocal microscopy terminology glossary for melanocytic skin lesions: A systematic review
Authors: Cristian Navarrete-Dechent, Konstantinos Liopyris, Jilliana Monnier, Saud Aleissa, Lindsay M. Boyce, Caterina Longo, Margaret Oliviero, Harold Rabinovitz, Ashfaq A. Marghoob, Allan C. Halpern, Giovanni Pellacani, Alon Scope, Manu Jain
Journal: Journal of the American Academy of Dermatology (2020)
Safety and Efficacy, Including Event-Free Survival, of Deferasirox Versus Placebo in Iron-Overloaded Patients with Low- and Int-1-Risk Myelodysplastic Syndromes (MDS): Outcomes from the Randomized, Double-Blind Telesto Study
Authors: Emanuele Angelucci, Junmin Li, Peter L Greenberg, Wu Depei, Ming Hou, Efreen Montaño Figueroa, Guadalupe Rodriguez, Xunwei Dong, Jagannath Ghosh, Orna Bornstein, Guillermo Garcia-Manero
Journal: Blood (2018)
Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study
Authors: Amanda J Cross, Kate Wooldrage, Emma C Robbins, Ines Kralj-Hans, Eilidh MacRae, Carolyn Piggott, Iain Stenson, Aaron Prendergast, Bhavita Patel, Kevin Pack, Rosemary Howe, Nicholas Swart, Julia Snowball, Stephen W Duffy, Stephen Morris, Christian von Wagner, Stephen P Halloran, Wendy S Atkin
Journal: Gut (2018)

Objective The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. Design Intermediate-risk patients (60–72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012–December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. Results 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. Conclusions Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%–40% of CRCs and 40%–70% of AAs. Trial registration number ISRCTN18040196 ; Results.
Treatment resistant depression: what are the options?
Authors: Greta McLachlan
Journal: BMJ (2018)

Some patients with treatment resistant depression have tried up to 12 antidepressants and waited 10 years before they are seen at specialist centres, a recent press briefing heard. The figures fall far short of targets set out in draft guidance from the National Institute for Health and Care Excellence, which says that all patients who have not responded to two antidepressants should be referred to specialists.1

NICE’s definition would mean that 2.7 million people in the UK have treatment resistant depression (between 10% and 30% of people with depression), an unmanageable number for the NHS’s psychiatric services.

Allan Young, honorary consultant at Maudsley and Bethlem Hospitals in south London, told the briefing that though GPs were good at identifying and treating depression, “TRD [treatment resistant depression] is a subgroup—and there isn’t the capacity in secondary mental health teams to deal with this.”

So what are GPs supposed to do? The answer it seems is, first, know the options …
Physician mothers’ experience of workplace discrimination: a qualitative analysis
Authors: Meghan C Halley, Alison S Rustagi, Jeanette S Torres, Elizabeth Linos, Victoria Plaut, Christina Mangurian, Esther Choo, Eleni Linos
Journal: BMJ (2018)

Abstract Objectives To report woman physicians’ experiences, in their own words, of discrimination based on their role as a mother. Design Qualitative analysis of physician mothers’ free-text responses to the open question: “We want to hear your story and experience. Please share” included in questions about workplace discrimination. Three analysts iteratively formulated a structured codebook, then applied codes after inter-coder reliability scores indicated high concordance. The relationships among themes and sub-themes were organized into a conceptual model illustrated by exemplary quotes. Participants Respondents to an anonymous, voluntary online survey about the health and wellbeing of physician mothers posted on a Facebook group, the Physician Moms Group, an online community of US physicians who identify as mothers. Results We analyzed 947 free-text responses. Participants provide diverse and vivid descriptions of experiences of maternal discrimination. Gendered job expectations, financial inequalities (including lower pay than equally qualified colleagues and more unpaid work), limited opportunities for advancement, lack of support during the pregnancy and postpartum period, and challenging work-life balance are some of the key themes identified. In addition, participants’ quotes show several potential structural drivers of maternal discrimination and describe the downstream consequences of maternal discrimination on the physician herself, her career, family, and the healthcare system. Conclusions These findings provide a view of maternal discrimination directly from the perspective of those who experience it. Women physicians report a range of previously uncharacterized ways in which they experience maternal discrimination. While certain aspects of these experiences are consistent with those reported by women across other professions, there are unique aspects of medical training and the medical profession that perpetuate maternal discrimination.
Large-scale wearable data reveal digital phenotypes for daily-life stress detection
Authors: Elena Smets, Emmanuel Rios Velazquez, Giuseppina Schiavone, Imen Chakroun, Ellie D’Hondt, Walter De Raedt, Jan Cornelis, Olivier Janssens, Sofie Van Hoecke, Stephan Claes, Ilse Van Diest, Chris Van Hoof
Journal: npj Digital Medicine (2018)

Physiological signals have shown to be reliable indicators of stress in laboratory studies, yet large-scale ambulatory validation is lacking. We present a large-scale cross-sectional study for ambulatory stress detection, consisting of 1002 subjects, containing subjects' demographics, baseline psychological information, and five consecutive days of free-living physiological and contextual measurements, collected through wearable devices and smartphones. This dataset represents a healthy population, showing associations between wearable physiological signals and self-reported daily-life stress. Using a data-driven approach, we identified digital phenotypes characterized by self-reported poor health indicators and high depression, anxiety and stress scores that are associated with blunted physiological responses to stress. These results emphasize the need for large-scale collections of multi-sensor data, to build personalized stress models for precision medicine.
Synergistic convergence of microbiota-specific systemic IgG and secretory IgA
Authors: Jehane Fadlallah, Delphine Sterlin, Claire Fieschi, Christophe Parizot, Karim Dorgham, Hela El Kafsi, Gaëlle Autaa, Pascale Ghillani-Dalbin, Catherine Juste, Patricia Lepage, Marion Malphettes, Lionel Galicier, David Boutboul, Karine Clément, Sébastien André, Florian Marquet, Christophe Tresallet, Alexis Mathian, Makoto Miyara, Eric Oksenhendler, Zahir Amoura, Hans Yssel, Martin Larsen, Guy Gorochov
Journal: Journal of Allergy and Clinical Immunology (2018)
Impact of different GMP media in the production of dendritic cells for next-generation cancer immunotherapy: Functional and metabolic characterization
Authors: J. Calmeiro, M. Carrascal, C. Gomes, A. Falcão, J. Serra, M.T. Cruz, B. Neves
Journal: Annals of Oncology (2018)

Background: Dendritic cells (DCs) are unique antigen presenting cells that are used in cancer immunotherapy, with more than 20 years of clinical trials in this field. The production of clinical grade monocyte-derived DCs is highly desired and globally performed, with a large space for improvement and development of clinical standard operating procedures (CSOP). This process is highly dependent on three constraints: used cytokines for cell differentiation, maturating agents and culture medium. There is a clear lack of studies focusing on how the used culture medium and its composition and components affect the process of ex-vivo generation of monocyte-derived DCs. This study aims to compare the effect of 4 culture media (3 GMP media and 1 medium widely used in research) during monocyte-derived DCs differentiation. Methods: We characterized DC viability, differentiation, maturation, internalization of tumor lysates, cytokines production and autologous T cell stimulatory capacity, as well as metabolomic profiles. Commercially available culture media for clinical use were tested, namely DendriMACS, AIM-V and X-VIVO 15. RPMI was also tested as a comparative term given that it is largely used in pre-clinical research. Results: In terms of differentiation, maturation, DC uptake capacity, and metabolic profiles, AIM-V and X-VIVO 15 present similar results. However, the use of X-VIVO 15 shows an enhanced DC production of IL-12. DCs cultured in X-VIVO 15 and AIM-V media are able to induce a superior stimulation of T cells, mainly CTLs and Th1 responses, while DCs cultured in DendriMACS are more prone to induce Treg polarization. Conclusions: Our data show that X-VIVO 15 and AIM-V culture media are preferable to support the differentiation of DC to be used in immunostimulatory approaches such as in cancer cell therapy. Overall, this study highlights the need of previously and carefully defining the culture medium to be used in DC cancer immunotherapy, for a better aim to the therapeutic goal and potentiating the clinical experiment and final patient output. Legal entity responsible for the study: Grupo Tecnimede. Funding: This study received funding from the project [email protected]: Cellular Immunotherapy towards the elimination of cancer stem cells (Ref.: POCI-01-0247-FEDER-033532), co-funded by the European Regional Development Fund (FEDER), Competitiveness and Internationalization Operational Program (COMPETE2020) and Own Revenues of the University of Coimbra. João Calmeiro is supported by the Portuguese Science and Technology Foundation (FCT) through an individual PhD fellowship (PD/BDE/135076/2017). Disclosure: All authors have declared no conflicts of interest.
Hospitals hit unsafe occupancy and divert ambulances in first week of winter
Authors: Matthew Limb
Journal: BMJ (2018)

Winter strain on the NHS in England is showing, with hospitals hitting “unsafe” occupancy levels and many ambulance crews being diverted from busy sites, figures show.

NHS England statistics—the first weekly report of this so far mild winter—showed that nearly 95% of beds were occupied and eight emergency departments had diverted ambulance crews elsewhere.1 To deliver safe care, occupancy rates should not exceed 85%.

Siva Anandaciva, chief analyst at the health think tank the King’s Fund, said, “These figures show little slack in a system which is operating consistently in the red zone.

“Hospital bed occupancy levels …
The orphan nuclear receptor NR4A1 promotes FcεRI‐stimulated mast cell activation and anaphylaxis by counteracting the inhibitory LKB1/AMPK axis
Authors: Fansi Jin, Xian Li, Yifeng Deng, Maheshwor Timilshina, Bin Huang, Dong‐Young Kim, Jae‐Hoon Chang, Hiroshi Ichinose, Suk‐Hwan Baek, Makoto Murakami, Youn Ju Lee, Hyeun Wook Chang
Journal: Allergy (2018)

Nuclear receptor subfamily 4 group A member 1 (NR4A1), an orphan nuclear receptor, has been implicated in several biological events such as metabolism, apoptosis, and inflammation. Recent studies indicate a potential role for NR4A1 in mast cells, yet its role in allergic responses remains largely unknown.The aim of this study was to clarify the role of NR4A1 in mast cell activation and anaphylaxis.To evaluate the function of NR4A1 in mast cells, the impacts of siRNA knockdown, gene knockout, adenoviral overexpression, and pharmacological inhibition of NR4A1 on FcεRI signaling and effector functions in mouse bone marrow-derived mast cells (BMMCs) in vitro and on anaphylactic responses in vivo were evaluated.Knockdown or knockout of NR4A1 markedly suppressed degranulation and lipid mediator production by FcεRI-crosslinked BMMCs, while its overexpression augmented these responses. Treatment with a NR4A1 antagonist also blocked mast cell activation to a similar extent as NR4A1 knockdown or knockout. Moreover, mast cell-specific NR4A1-deficient mice displayed dampened anaphylactic responses in vivo. Mechanistically, NR4A1 promoted FcεRI signaling by counteracting the liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) axis. Following FcεRI crosslinking, NR4A1 bound to the LKB1/AMPK complex and sequestered it in the nucleus, thereby promoting FcεRI downstream signaling pathways. Silencing or knockout of LKB1/AMPK largely abrogated the effect of NR4A1 on mast cell activation. Additionally, NR4A1 facilitated spleen tyrosine kinase activation independently of LKB1/AMPK.Nuclear receptor subfamily 4 group A member 1 positively regulates mast cell activation by antagonizing the LKB1-AMPK-dependent negative regulatory axis. This finding may provide a novel therapeutic strategy for the development of anti-allergic compounds.
Anagrelide for Gastrointestinal Stromal Tumor
Authors: Olli-Pekka Pulkka, Yemarshet K. Gebreyohannes, Agnieszka Wozniak, John-Patrick Mpindi, Olli Tynninen, Katherine Icay, Alejandra Cervera, Salla Keskitalo, Astrid Murumägi, Evgeny Kulesskiy, Maria Laaksonen, Krister Wennerberg, Markku Varjosalo, Pirjo Laakkonen, Rainer Lehtonen, Sampsa Hautaniemi, Olli Kallioniemi, Patrick Schöffski, Harri Sihto, Heikki Joensuu
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Gastrointestinal stromal tumor (GIST) is a common type of soft-tissue sarcoma. Imatinib, an inhibitor of KIT, platelet-derived growth factor receptor alpha (PDGFRA), and a few other tyrosine kinases, is highly effective for GIST, but advanced GISTs frequently progress on imatinib and other approved tyrosine kinase inhibitors. We investigated phosphodiesterase 3 (PDE3) as a potential therapeutic target in GIST cell lines and xenograft models. Experimental Design: The GIST gene expression profile was interrogated in the MediSapiens IST Online transcriptome database comprising human tissue and cancer samples, and PDE3A and PDE3B expression was studied using IHC on tissue microarrays (TMA) consisting of 630 formalin-fixed human tissue samples. GIST cell lines were screened for sensitivity to 217 anticancer compounds, and the efficacy of PDE inhibitors on GIST was further studied in GIST cell lines and patient-derived mouse xenograft models. Results: GISTs expressed PDE3A and PDE3B frequently compared with other human normal or cancerous tissues both in the in silico database and the TMAs. Anagrelide was identified as the most potent of the PDE3 modulators evaluated. It reduced cell viability, promoted cell death, and influenced cell signaling in GIST cell lines. Anagrelide inhibited tumor growth in GIST xenograft mouse models. Anagrelide was also effective in a GIST xenograft mouse model with KIT exon 9 mutation that may pose a therapeutic challenge, as these GISTs require a high daily dose of imatinib. Conclusions: PDE3A and PDE3B are frequently expressed in GIST. Anagrelide had anticancer efficacy in GIST xenograft models and warrants further testing in clinical trials.
Abstract 18949: Comparison of Incidence of Transfusion-Requiring Bleeding After Percutaneous Coronary Intervention and In-hospital Mortality in Patients With ST-Segment Elevation Myocardial Infarction and Non ST-Segment Elevation Myocardial Infarction: A Nationwide Analysis Using the National Inpatient Database of 2014
Authors: Ahmadreza Moradi, Xin Wei, Parisa Toosi, Sung E Lee, Mariam Khabdaker, Bing Yue, Yuzhou Liu, Angela M Palazzo
Journal: Circulation (2017)

Background: Major bleeding requiring transfusion after percutaneous coronary intervention (PCI) for myocardial infarction (MI) is associated with high mortality and morbidity. Limited data is avail...
Epidermal Growth Factor–Releasing Radially Aligned Electrospun Nanofibrous Patches for the Regeneration of Chronic Tympanic Membrane Perforations
Authors: Hoon Seonwoo, Beomyong Shin, Kyoung‐Je Jang, Myungchul Lee, Oak‐Sung Choo, Sang‐Bae Park, Yeong Cheol Kim, Mi‐Jin Choi, Jangho Kim, Pankaj Garg, Jeong Hun Jang, Yun‐Hoon Choung, Jong Hoon Chung
Journal: Advanced Healthcare Materials (2018)

Abstract Chronic tympanic membrane (TM) perforations can cause otorrhea. To date, various types of tissue engineering techniques have been applied for the regeneration of chronic TM perforations. However, the application of nanofibers with radially aligned nanostructures and the simultaneous release of growth factors have never been applied in the regeneration of chronic TM perforations. Here, epidermal growth factor (EGF)–releasing radially aligned nanofibrous patches (ERA‐NFPs) are developed and applied for the regeneration of chronic perforated TMs. First, radial alignments and the presence of EGF in the ERA‐NFPs are analyzed. EGF is confirmed to be released from the ERA‐NFPs until 8 weeks. In an in vitro study, cell viability assay, immunocytochemistry, and wound‐healing assay indicate rational enhancement of healing by the combination of radial alignments and EGF release. The effect of ERA‐NFPs on TM cells is revealed by quantitative real‐time polymerase chain reaction. An in vivo animal study shows that the ERA‐NFPs effectively stimulates the healing of the chronic TM perforations. The TMs healed by ERA‐NFPs show histological properties similar to those of normal TMs. These results indicate that ERA‐NFPs may be an efficient platform for the regeneration of chronic TM perforations, laying the foundation for nonsurgical treatments of chronic otitis media.
Evaluation of biochemichal features of anemia in cancer patients.
Authors: Silvia Park, Jun Ho Jang, Chul Won Jung, Won Seog Kim, Seok Jin Kim, Kihyun Kim, Jeeyun Lee, Myung-Ju Ahn, Ji Yun Lee, Kwai Han Yoo, Sung Hee Lim
Journal: Journal of Clinical Oncology (2014)

e20698 Background: Multifactorial pathogenesis is involved in anemia of cancer patients. However, conventional laboratory evaluation such as iron, TIBC and ferritin has only limited value for distinguishing the causes of anemia. As more relevant biomarkers, hepcidin contributes to the development of anemia of chronic disease (ACD), and soluble transferring receptor (sTfR)is a good indicator of iron restricted erythropoiesis in patients with inflammation. Methods: Since July 2008, serum samples from cancer patients were achieved and stored at -70’C in Samsung Medical Center. Twenty-nine stored frozen serum samples from 4 types of cancer (gastric cancer, biliary tract cancer, lung cancer, and lymphoma) were used to analyze ferritin, soluble transferring receptor (sTfR), CRP, and hepcidin with commercial ELISA kits. For the analysis, anemia was defined as hemoglobin (Hb) ≤11g/dL. Results: The median age of all patients was 57 (27-72) years. There were 11 gastric cancer (37.9%), 6 biliary tract cancer (20.7%), 8 lung cancer (27.6%) and 4 lymphoma patients (13.8%). When comparing to the reference value from general population, cancer patients tended to show higher ferritin, sTfR and CRP level and lower hepcidin level. Among the cancer patients, anemic patients showed significantly higher level of sTfR compared to non-anemic patients (p=0.011). Although not statistically significant, the level of ferritin, CRP, and hepcidin was more elevated in anemic patients. We also evaluated the correlation between each parameter and clinical characteristics. The results showed that significant positive correlation between ‘metastatic disease’ and ‘CRP’ (p=0.038), between ‘chemotherapy within 6 months’ and ‘CRP’ (p=0.037), and ‘hepcidin’ (p=0.023). And CRP, ferritin and hepcidin were positively correlated with each other (p=0.033 for CRP_ferritin; p=<0.001 for hepcidin_ferritin; p=0.026 for hepcidin_CRP). Conclusions: Consistent with common belief, cancer anemia seems to be closely related to inflammatory process (ACD) according to higher ferritin, CRP and hepcidin level in this population. Of note, however, iron deficiency and/or iron restricted erythroiesis also contributes considerably to pathogenesis of anemia in cancer patient.
Neutropenia in the age of genetic testing: Advances and challenges
Authors: Elissa Furutani, Peter E. Newburger, Akiko Shimamura
Journal: American Journal of Hematology (2018)

Abstract Identification of genetic causes of neutropenia informs precision medicine approaches to medical management and treatment. Accurate diagnosis of genetic neutropenia disorders informs treatment options, enables risk stratification, cancer surveillance, and attention to associated medical complications. The rapidly expanding genetic testing options for the evaluation of neutropenia have led to exciting advances but also new challenges. This review provides a practical guide to germline genetic testing for neutropenia.
Multicenter Microbiota Analysis Indicates That Pre-HCT Microbiota Injury Is Prevalent across Geography and Predicts Poor Overall Survival
Authors: Jonathan U. Peled, Antonio LC Gomes, Christoph K. Stein-Thoeringer, John B. Slingerland, Ann E. Slingerland, Daniela Weber, Kate A Markey, Melody Smith, Doris Ponce, Annelie Clurman, Anthony D. Sung, Daigo Hashimoto, Molly Maloy, Niloufer Khan, Boglarka Gyurkocza, Sergio Giralt, Miguel-Angel Perales, Robert R. Jenq, Ying Taur, Xavier B. Joao, Eric G. Pamer, Takanori Teshima, Nelson J. Chao, Ernst Holler, Marcel R.M. van den Brink
Journal: Blood (2018)
Depression and self-harm from adolescence to young adulthood in sexual minorities compared with heterosexuals in the UK: a population-based cohort study
Authors: Madeleine Irish, Francesca Solmi, Becky Mars, Michael King, Glyn Lewis, Rebecca M Pearson, Alexandra Pitman, Sarah Rowe, Ramya Srinivasan, Gemma Lewis
Journal: The Lancet Child & Adolescent Health (2018)