tbuckley/cabot-search huggingface dataset:
Genome-wide significant risk associations for mucinous ovarian carcinoma (vol 47, pg 888, 2015)
Authors: Linda E Kelemen, Kate Lawrenson, Jonathan Tyrer, Qiyuan Li, Janet M Lee, Ji-Heui Seo, Catherine M Phelan, Jonathan Beesley, Xiaoqing Chen, Tassja J Spindler, Katja Kh Aben, Hoda Anton-Culver, Natalia Antonenkova, Helen Baker, Elisa Bandera, Yukie Bean, Matthias W Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Ralf Butzow, Ian G Campbell, Karen Carty, Jenny Chang-Claude, Y Ann Chen, Zhihua Chen, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Joe Dennis, Ed Dicks, Jennifer A Doherty, Thilo Doerk, Andreas du Bois, Matthias Duerst, Diana Eccles, Douglas T Easton, Robert P Edwards, Ursula Eilber, Arif B Ekici, Svend Aage Engelholm, Peter A Fasching, Brooke L Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G Giles, Rosalind Glasspool, Ellen L Goode, Marc T Goodman, Jacek Grownwald, Patricia Harrington, Philipp Harter, Hanis Nazihah Hasmad, Alexander Hein, Florian Heitz, Michelle At Hildebrandt, Peter Hillemanns, Estrid Hogdall, Claus Hogdall, Satoyo Hosono, Edwin S Iversen, Anna Jakubowska, Allan Jensen, Bu-Tian Ji, Beth Y Karlan, Melissa Kellar, Joseph L Kelley, Lambertus A Kiemeney, Camilla Krakstad, Susanne K Kjaer, Jolanta Kupryjanczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Alice W Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas A Levine, Dong Liang
Journal: Nature Genetics (2015)
In search for novel functions of adenosine 5′-triphosphate (ATP) in the heart
Authors: Thomas Meyer, Niels Voigt
Journal: Cardiovascular Research (2017)

Ageing and age-related diseases have long been associated with the accumulation of misfolded proteins and protein aggregates. 2 Especially, age-related neurodegenerative pathologies, such as amyotrophic lateral sclerosis and Alzheimer's disease, have been linked to gradual derailment of proteostasis and protein aggregation.Furthermore, it has been shown that alterations in the proteostasis of cardiomyocytes may play an important role in the development of cardiovascular diseases. 35][6][7][8][9] Prevailing theories of impaired protein homeostasis mainly focus on disturbances of the fine-tuned balance of cellular production, folding, and degradation of proteins. 2,3In a recently published Science paper, Patel et al. 1 describe a mechanism which may play an important role in keeping proteins Dr.
Comparison of immunohistochemical and Western blot analyses of paraffin-embedded cell lines and xenografts for profiling cellular signaling
Authors: Katherine Crosby, Michael Lewis, Magdalene Laszczak, Qingfu Zeng, Angela Lightbown, Bradley L. Smith
Journal: Cancer Research (2005)

5470   Current development of targeted cancer therapeutics relies on the use of model cell lines and mouse xenografts. These samples are often analyzed by immunohistochemistry and Western blot to profile the activity of cell signaling proteins; however, the relative sensitivity and specificity of these methods for the profiling of cellular signaling has not been established. In this study we compared the results obtained by IHC with those obtained by Western blot analysis using a broad panel of total and phospho-specific antibodies on paraffin-embedded cell lines and xenografts or lysates from the same samples. The results demonstrate that the methods have limitations in sensitivity but do allow for consistent characterization of protein phosphorylation and pathway activation. In addition, the results suggest the most robust methods for tissue handling for IHC. Variable staining was observed with phospho-specific erk and Akt antibodies depending upon the time of tissue fixation or choice of fixative.
Individualized Glycemic Goals and an Expanded Classification of Severe Hypoglycemia in Diabetes
Authors: Philip E. Cryer
Journal: Diabetes Care (2017)

The view that a hemoglobin A1c (A1C) level <7% (55 mmol/mol) is the accepted glycemic goal for most people with diabetes sometimes conflicts with the view that glycemic goals should be individualized and, thus, that somewhat higher A1C levels are appropriate for some, particularly many at risk for iatrogenic hypoglycemia because of treatment with insulin, a sulfonylurea, or a glinide. The relationship between A1C and chronic complications of diabetes is curvilinear, A1C is a relatively weak predictor of cardiovascular disease, and minor elevations of A1C above 7% have not been found to be associated with increased mortality. Iatrogenic hypoglycemia causes recurrent morbidity in diabetes and is sometimes fatal. In those at risk for hypoglycemia, a reasonable individualized glycemic goal is the lowest A1C that does not cause severe hypoglycemia and preserves awareness of hypoglycemia, preferably with little or no symptomatic or even asymptomatic hypoglycemia, at a given stage in the evolution of the individual's diabetes. A somewhat higher A1C level is appropriate in those who have previously experienced hypoglycemia or have potential high risk for hypoglycemia, have a long duration of diabetes, and have a short life expectancy, among other traits. Given the importance of severe hypoglycemia in selecting glycemic goals, it is proposed to expand the classification of severe hypoglycemia beyond a hypoglycemic event requiring assistance from another person to include a measured glucose concentration <50 mg/dL (2.8 mmol/L), a level associated with sudden death.
Utilization of palliative care in intubated patients with metastatic cancer: A 10-year nationwide analysis.
Authors: Arjun Gupta, Avash Das, Nizar Bhulani, Raseen Tariq, Ryan D. Frank, Sahil Khanna, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2017)

69 Background: Due to improved survival, an increasing number of patients with advanced cancer are eligible for aggressive ICU care, including intubation. The American Society of Clinical Oncology recommends early integration of palliative care in patients with advanced cancer. We analyzed 10-year trends in the utilization of palliative care, and predictors of palliative care use in patients with metastatic cancer undergoing intubation using the National Hospital Discharge Survey database from 2001-2010. Methods: Diagnosis and procedure codes were utilized to identify adult patients with metastatic cancer who underwent intubation, and received palliative care. Demographics, diagnoses, length of stay (LOS), and discharge information were extracted. T-tests and χ^2 tests were used to compare medians and proportions respectively in patients that did or did not receive palliative care. Multivariate regression models with weighted analysis were conducted to study predictors of palliative care use. Results: Over the 10-year study period, 200,350 patients with metastatic cancer and intubation were identified, mean age 65.3 years, 46.2% male. Of these, 6690 (3.3%) received palliative care. There was a significant increase in the use of palliative care from 2001 (0%) to 2010 (17.4%), p for trend &lt; 0.001. In multivariate analysis, patients who received palliative care were more likely to have age &gt; 65 years, be white vs non-white, be hospitalized in 2009-2010 vs 2000-2001, and be admitted to hospitals in the Western part of the US. The overall inpatient mortality rate was 57.3%, discharge to a care facility (DTCF) rate was 15.2%, and mean LOS was 11.1 days. The LOS and DTCF rates were similar in patients with and without palliative care. Patients with palliative care had higher rates of inpatient mortality (adjusted OR 9.6, 95% CI 2.2- 42.0). Conclusions: There was a dramatic increase in the use of palliative care in intubated patients with metastatic cancer. Studies to address the racial and geographic discrepancies in palliative care use are warranted. The higher mortality in palliative care group suggests it is being used for the sickest patients. Early (vs end of life) palliative care may be more beneficial.
Association between long sleep duration and increased risk of obesity and type 2 diabetes: A review of possible mechanisms
Authors: Xiao Tan, Colin D. Chapman, Jonathan Cedernaes, Christian Benedict
Journal: Sleep Medicine Reviews (2017)

For the last two decades research has revealed an alarming association between short sleep duration and metabolic disorders. In tandem, the hormonal, behavioral, and genetic mechanisms underlying this relationship have been extensively investigated and reviewed. However, emerging evidence is revealing that excessive sleep duration has remarkably similar deleterious effects. Unfortunately, to date there has been little attention to what drives this connection. This narrative review therefore aims to summarize existing epidemiological findings, experimental work, and most importantly putative molecular and behavioral mechanisms connecting excessive sleep duration with both obesity and type 2 diabetes mellitus. It will also address recent findings suggesting a worrisome bidirectional effect such that metabolic disorders create a positive feedback loop which further perpetuates excessive sleep.
Nils Albert Regan
Authors: Carolyn Regan
Journal: BMJ (2017)

Born in Berlin, Nils Albert Regan arrived in London with his family in 1936. He was educated at King’s College School in Wimbledon and Aberdeen University, following his father into medicine. After qualifying he did his national service in the Royal Air Force and spent two years stationed at RAF Hospital Rinteln, working in obstetrics and gynaecology. On his return to London, he continued in the specialty at West Middlesex, gaining his MRCOG in 1956, followed by a year’s service at the American Services Hospital in Ruislip.

In 1957 Nils entered general practice with his father in law in Pimlico, where he remained until his retirement, also undertaking some 30 …
PTH-084 The use of budesonide in crohn’s disease: a national population based study
Authors: V Chhaya, C Alexakis, S Saxena, RC Pollok
Journal: Gut (2017)

Introduction  The preparations of budesonide, Budenofalk and Entocort are licensed and recommended for the treatment of mild to moderate ileo-caecal Crohn’s disease (CD) (1). Budesonide is advantageous in that systemic side effects are substantially reduced compared to conventional corticosteroids (CS). We hypothesised a reluctance to prescribe budesonide in the UK and aimed to compare the use of budesonide to overall CS use in CD.  Method  We constructed an incident cohort of CD patients diagnosed between 1990–2009 using the Clinical Practice Research Datalink (CRPD), a validated national primary care research database. We extracted prescribing data for any prescription of oral steroid therapy following the formal diagnosis of CD. Budesonide users were defined as any patient with at least one prescription of this medication during follow-up. CS users were defined as any patient with at least one prescription for any oral steroid medication (budesonide included) during follow-up. We divided our cohort by date of CD diagnosis into five time periods to analyse prescribing trends for steroid subtypes: era 1 (1990–1993), era 2 (1994–1997), era 3 (1998–2001), era 4 (2002–2005) and era 5 (2006–2009). We performed Kaplan-Meier survival analysis for the first four time era to quantify the 5 year probability of receiving budesonide or any oral CS. Significance levels were compared using the log-rank test.  Results  We identified 6997 patients with a diagnosis of CD. The median follow up time per patient was 4.2 years (IQR: 1.8–7.8). There were 474 (6.8%), 694 (9.9%), 1555 (22.2%), 2096 (30.0%) and 2178 (31.1%) incident cases in era 1, 2, 3, 4 and 5 respectively, reflecting the rising number of GP practices contributing to the database. A total of 4001 (57%) patients received a prescription for oral steroids within 5 years of diagnosis. Only 11.5% of patients with CD had received a prescription for budesonide within 5 years of diagnosis. The cumulative probability for receiving budesonide within 5 years was 0.8% (95%CI: 0.27%–2.5%), 11.5% (95%CI: 9.2%–14.4%), 12.6% (95%CI: 10.9%–14.5%), 10.6% (95%CI: 9.3%–12.1%), for era 1, 2, 3 and 4 respectively (log-rank p  Conclusion  Our findings demonstrate a potential underuse of budesonide in patients with CD, despite strong recommendations in guidelines for its use as a first line agent in mild to moderate ileo-caecal CD. Clinical guidelines should be reinforced at a primary care level to ensure wider use of budesonide over traditional oral CS treatment.  Reference  . Dignass, et al. J Crohns Colitis2010Feb;4(1):28–62  Disclosure of Interest  None Declared
The effect of message content and clinical outcome on patients' perceptions of physician compassion: A randomized controlled trial.
Authors: Kimberson Cochien Tanco, Ahsan Azhar, Wadih Rhondali, Alfredo Rodriguez-Nunez, Diane D Liu, Jimin Wu, Walter F. Baile, Eduardo Bruera
Journal: Journal of Clinical Oncology (2017)

27 Background: In a previous randomized cross-over study, patients perceived a physician delivering a more optimistic message as more compassionate and professional. However, the impact of the clinical outcome of patient on patients’ perception of physician’s level of compassion and professionalism has not been previously studied. Our aim was to determine if the reported clinical outcome modified the patient’s perception of physician compassion, professionalism, impression, and preference for physician. Methods: 128 advanced cancer patients in an outpatient Supportive Care Center were randomized to complete validated questionnaires about patients’ perception of physician’s level of compassion, professionalism, impression and preference of physician for themselves and their family after watching scripted videos depicting a physician delivering a more optimistic (MO) vs. a less optimistic (LO) message followed by a clinical vignette depicting a worse outcome. Results: Median age was 61 years and 55% were female. There was no difference in compassion score after the vignette for both the MO and LO groups respectively [mean difference (SD): 1.7(8.74) p = 0.4684 vs. 0.89(10.24) p = 0.1225] but there were worse overall impression [mean difference (SD): MO -0.79(1.62) p &lt; 0.0001 vs. LO -1.17(1.91) p &lt; 0.0001] and professionalism scores [MO -0.88(2.25) p = 0.0022 vs. LO -0.76(2.22) p = 0.0094]. In the MO group, preference for the physician for themselves [mean difference (SD) -0.29(0.77) p = 0.0049] and their family [mean difference (SD) -0.29(0.71) p = 0.0009] decreased after the vignette. Conclusions: Seeing a worse clinical outcome did not change the patients’ appraisal of an inappropriately optimistic physician. However, it reduced the overall impression of both physicians that conveyed a more or a less optimistic message and it also resulted in less likelihood of choosing the more optimistic physician for themselves and their family. Clinical trial information: NCT02498899.
Organ Bioprinting: Are We There Yet?
Authors: Guifang Gao, Ying Huang, Arndt F. Schilling, Karen Hubbell, Xiaofeng Cui
Journal: Advanced Healthcare Materials (2017)

About 15 years ago, bioprinting was coined as one of the ultimate solutions to engineer vascularized tissues, which was impossible to accomplish using the conventional tissue fabrication approaches. With the advances of 3D-printing technology during the past decades, one may expect 3D bioprinting being developed as much as 3D printing. Unfortunately, this is not the case. The printing principles of bioprinting are dramatically different from those applied in industrialized 3D printing, as they have to take the living components into account. While the conventional 3D-printing technologies are actually applied for biological or biomedical applications, true 3D bioprinting involving direct printing of cells and other biological substances for tissue reconstruction is still in its infancy. In this progress report, the current status of bioprinting in academia and industry is subjectively evaluated. The progress made is acknowledged, and the existing bottlenecks in bioprinting are discussed. Recent breakthroughs from a variety of associated fields, including mechanical engineering, robotic engineering, computing engineering, chemistry, material science, cellular biology, molecular biology, system control, and medicine may overcome some of these current bottlenecks. For this to happen, a convergence of these areas into a systemic research area "3D bioprinting" is needed to develop bioprinting as a viable approach for creating fully functional organs for standard clinical diagnosis and treatment including transplantation.
Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening
Authors: Linda J.W. Bosch, Meike de Wit, Thang V. Pham, Veerle M.H. Coupé, Annemieke C. Hiemstra, Sander R. Piersma, Gideon Oudgenoeg, George L. Scheffer, Sandra Mongera, Jochim Terhaar Sive Droste, Frank A. Oort, Sietze T. van Turenhout, Ilhame Ben Larbi, Joost Louwagie, Wim van Criekinge, Rene W.M. van der Hulst, Chris J.J. Mulder, Beatriz Carvalho, Remond J.A. Fijneman, Connie R. Jimenez, Gerrit A. Meijer
Journal: Annals of Internal Medicine (2017)

The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement.To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas.Case-control study.Colonoscopy-controlled referral population from several centers.315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples).Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples.In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001).Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples.Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening.Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.
P3.02c-024 Detection of Novel Activating FGFR Rearrangements, Truncations, and Splice Site Alterations in NSCLC by Comprehensive Genomic Profiling
Authors: Shirish Gadgeel, Adrienne Johnson, Leora Horn, Christine Lovly, Jonathan Riess, Paulo Campregher, Philip Stephens, Jeffrey Ross, Vincent Miller, Marcelo Cruz, Siraj Ali, Alexa Schrock
Journal: Journal of Thoracic Oncology (2017)
A validated antibody panel for the characterization of tau post-translational modifications
Authors: Ebru Ercan, Sameh Eid, Christian Weber, Alexandra Kowalski, Maria Bichmann, Annika Behrendt, Frank Matthes, Sybille Krauss, Peter Reinhardt, Simone Fulle, Dagmar E. Ehrnhoefer
Journal: Molecular Neurodegeneration (2017)

Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Aberrant PTMs such as hyperphosphorylation result in tau aggregation and the formation of neurofibrillary tangles, which are a hallmark of Alzheimer's disease (AD). In order to study the importance of PTMs on tau function, antibodies raised against specific modification sites are widely used. However, quality control of these antibodies is lacking and their specificity for particular modifications is often unclear. In this study, we first designed an online tool called 'TauPTM', which enables the visualization of PTMs and their interactions on human tau. Using TauPTM, we next searched for commercially available antibodies against tau PTMs and characterized their specificity by peptide array, immunoblotting, electrochemiluminescence ELISA and immunofluorescence technologies. We demonstrate that commercially available antibodies can show a significant lack of specificity, and PTM-specific antibodies in particular often recognize non-modified versions of the protein. In addition, detection may be hindered by other PTMs in close vicinity, complicating the interpretation of results. Finally, we compiled a panel of specific antibodies and show that they are useful to detect PTM-modified endogenous tau in hiPSC-derived neurons and mouse brains. This study has created a platform to reliably and robustly detect changes in localization and abundance of post-translationally modified tau in health and disease. A web-based version of TauPTM is fully available at http://www.tauptm.org .
P3.02a-005 The Association between the Percentage of Anaplastic Lymphoma Kinase(ALK)-Positive Cells and Efficacy of ALK Inhibitor
Authors: Tae Tanaka, Hiroshige Yoshioka, Koji Haratani, Hidetoshi Hayashi, Kunio Okamoto, Toshihiko Kaneda, Toshihide Yokoyama, Masayuki Takeda, Hiroyasu Kaneda, Kazuhiko Nakagawa, Tadashi Ishida
Journal: Journal of Thoracic Oncology (2017)
Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis
Authors: Madhav Kishore, Kenneth C.P. Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J. Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M. Smith, Robert Haas, Claudio Mauro, David C. Wraith, Klaus Okkenhaug, Alberico L. Catapano, Veronica De Rosa, Giuseppe D. Norata, Federica M. Marelli-Berg
Journal: Immunity (2017)

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene—leading to increased GCK activity—had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration.