tbuckley/cabot-search huggingface dataset:
Merging the Health System and Education Silos to Better Educate Future Physicians
Authors: Reshma Gupta, Vineet M. Arora
Journal: JAMA (2015)

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Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database
Authors: Pål Møller, Toni Seppälä, Inge Bernstein, Elke Holinski-Feder, Paola Sala, D Gareth Evans, Annika Lindblom, Finlay Macrae, Ignacio Blanco, Rolf Sijmons, Jacqueline Jeffries, Hans Vasen, John Burn, Sigve Nakken, Eivind Hovig, Einar Andreas Rødland, Kukatharmini Tharmaratnam, Wouter H de Vos tot Nederveen Cappel, James Hill, Juul Wijnen, Kate Green, Fiona Lalloo, Lone Sunde, Miriam Mints, Lucio Bertario, Marta Pineda, Matilde Navarro, Monika Morak, Laura Renkonen-Sinisalo, Ian M Frayling, John-Paul Plazzer, Kirsi Pylvanainen, Julian R Sampson, Gabriel Capella, Jukka-Pekka Mecklin, Gabriela Möslein
Journal: Gut (2015)

Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1 , MSH2 , MSH6 or PMS2 . Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.
The Concept of Euthymia
Authors: Giovanni A. Fava, Per Bech
Journal: Psychotherapy and Psychosomatics (2015)

Similar considerations apply to the use of the term euthymia in unipolar depression and dysthymia, where the overlap with the concept of recovery is considerable [9,10] .Again, euthymia is often defined essentially in negative terms, as a lack of a certain intensity of mood symptoms, and not as the presence of specific positive features that characterize recovery [9] .This introduces the need for a more comprehensive definition of euthymia.
Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis
Authors: Konstantinos Papamichael, Thomas Van Stappen, Niels Vande Casteele, Ann Gils, Thomas Billiet, Sophie Tops, Karolien Claes, Gert Van Assche, Paul Rutgeerts, Severine Vermeire, Marc Ferrante
Journal: Clinical Gastroenterology and Hepatology (2015)
Nova et Vetera
Authors: W H ARMYTAGE
Journal: BMJ (1957)

BRfDIcALTOURNALface value then the effect of television viewing on children's eyesight is a serious matter.The survey was carried out in Cardiff, no part of which is as much as 10 miles from the Wenvoe Television Transmitting Station, and where reception is therefore comparatively good.Summary 19,280 junior and secondary modern school children were asked whether or not they bad television sets in their own homes.According to the answers, they were divided into two groups, viewers and infrequent viewers.The number of children in each group wearing glasses or known to have been prescribed glasses was then determined.It was found that the incidence of children wearing glasses was somewhat lower in the viewer group in children aged 7 to 9, but was significantly higher in children aged 11 to 14.It is suggested that the only explanation that will meet the facts collected during this investigation is that many of the older schoolchildren watch television so often, so long, and under such adverse conditions that it causes eye strain sufficient to impair the vision of some of them.
Fluorescent Image–Guided Surgery with an Anti-Prostate Stem Cell Antigen (PSCA) Diabody Enables Targeted Resection of Mouse Prostate Cancer Xenografts in Real Time
Authors: Geoffrey A. Sonn, Andrew S. Behesnilian, Ziyue Karen Jiang, Kirstin A. Zettlitz, Eric J. Lepin, Laurent A. Bentolila, Scott M. Knowles, Daniel Lawrence, Anna M. Wu, Robert E. Reiter
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The inability to visualize cancer during prostatectomy contributes to positive margins, cancer recurrence, and surgical side effects. A molecularly targeted fluorescent probe offers the potential for real-time intraoperative imaging. The goal of this study was to develop a probe for image-guided prostate cancer surgery. Experimental Design: An antibody fragment (cys-diabody, cDb) against prostate stem cell antigen (PSCA) was conjugated to a far-red fluorophore, Cy5. The integrity and binding of the probe to PSCA was confirmed by gel electrophoresis, size exclusion, and flow cytometry, respectively. Subcutaneous models of PSCA-expressing xenografts were used to assess the biodistribution and in vivo kinetics, whereas an invasive intramuscular model was utilized to explore the performance of Cy5-cDb–mediated fluorescence guidance in representative surgical scenarios. Finally, a prospective, randomized study comparing surgical resection with and without fluorescent guidance was performed to determine whether this probe could reduce the incidence of positive margins. Results: Cy5-cDb demonstrated excellent purity, stability, and specific binding to PSCA. In vivo imaging showed maximal signal-to-background ratios at 6 hours. In mice carrying PSCA+ and negative (−) dual xenografts, the mean fluorescence ratio of PSCA+/− tumors was 4.4:1. In surgical resection experiments, residual tumors &amp;lt;1 mm that were missed on white light surgery were identified and resected using fluorescence guidance, which reduced the incidence of positive surgical margins (0/8) compared with white light surgery alone (7/7). Conclusions: Fluorescently labeled cDb enables real-time in vivo imaging of prostate cancer xenografts in mice, and facilitates more complete tumor removal than conventional white light surgery alone. Clin Cancer Res; 22(6); 1403–12. ©2015 AACR. See related commentary by van Leeuwen and van der Poel, p. 1304
The Neurobiology of “Food Addiction” and Its Implications for Obesity Treatment and Policy
Authors: Adrian Carter, Joshua Hendrikse, Natalia Lee, Murat Yücel, Antonio Verdejo-Garcia, Zane B. Andrews, Wayne Hall
Journal: Annual Review of Nutrition (2016)

There is a growing view that certain foods, particularly those high in refined sugars and fats, are addictive and that some forms of obesity can usefully be treated as a food addiction. This perspective is supported by a growing body of neuroscience research demonstrating that the chronic consumption of energy-dense foods causes changes in the brain's reward pathway that are central to the development and maintenance of drug addiction. Obese and overweight individuals also display patterns of eating behavior that resemble the ways in which addicted individuals consume drugs. We critically review the evidence that some forms of obesity or overeating could be considered a food addiction and argue that the use of food addiction as a diagnostic category is premature. We also examine some of the potential positive and negative clinical, social, and public policy implications of describing obesity as a food addiction that require further investigation.
Racial and Ethnic Disparities in Use of and Outcomes with Home Dialysis in the United States
Authors: Rajnish Mehrotra, Melissa Soohoo, Matthew B. Rivara, Jonathan Himmelfarb, Alfred K. Cheung, Onyebuchi A. Arah, Allen R. Nissenson, Vanessa Ravel, Elani Streja, Sooraj Kuttykrishnan, Ronit Katz, Miklos Z. Molnar, Kamyar Kalantar-Zadeh
Journal: Journal of the American Society of Nephrology (2015)

Home dialysis, which comprises peritoneal dialysis (PD) or home hemodialysis (home HD), offers patients with ESRD greater flexibility and independence. Although ESRD disproportionately affects racial/ethnic minorities, data on disparities in use and outcomes with home dialysis are sparse. We analyzed data of patients who initiated maintenance dialysis between 2007 and 2011 and were admitted to any of 2217 dialysis facilities in 43 states operated by a single large dialysis organization, with follow-up through December 31, 2011 (n =: 162,050, of which 17,791 underwent PD and 2536 underwent home HD for ≥91 days). Every racial/ethnic minority group was significantly less likely to be treated with home dialysis than whites. Among individuals treated with in-center HD or PD, racial/ethnic minorities had a lower risk for death than whites; among individuals undergoing home HD, only blacks had a significantly lower death risk than whites. Blacks undergoing PD or home HD had a higher risk for transfer to in-center HD than their white counterparts, whereas Asians or others undergoing PD had a lower risk than whites undergoing PD. Blacks irrespective of dialysis modality, Hispanics undergoing PD or in-center HD, and Asians and other racial groups undergoing in-center HD were significantly less likely than white counterparts to receive a kidney transplant. In conclusion, there are racial/ethnic disparities in use of and outcomes with home dialysis in the United States. Disparities in kidney transplantation evident for blacks and Hispanics undergoing home dialysis are similar to those with in-center HD. Future studies should identify modifiable causes for these disparities.
Weight increase in first year of life linked to type 1 diabetes
Authors: Jacqui Wise
Journal: BMJ (2015)

Weight increase during the first year of an infant’s life is positively associated with the risk of developing type 1 diabetes, an analysis of two large Scandinavian birth cohorts has found . 

The study, published in JAMA Pediatrics , included 59 221 children from the Norwegian Mother and Child Cohort Study and 40 611 from the Danish National Birth Cohort who were born between February 1998 and July …
Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study
Authors: Asher Chanan-Khan, Paula Cramer, Fatih Demirkan, Graeme Fraser, Rodrigo Santucci Silva, Sebastian Grosicki, Aleksander Pristupa, Ann Janssens, Jiri Mayer, Nancy L Bartlett, Marie-Sarah Dilhuydy, Halyna Pylypenko, Javier Loscertales, Abraham Avigdor, Simon Rule, Diego Villa, Olga Samoilova, Panagiots Panagiotidis, Andre Goy, Anthony Mato, Miguel A Pavlovsky, Claes Karlsson, Michelle Mahler, Mariya Salman, Steven Sun, Charles Phelps, Sriram Balasubramanian, Angela Howes, Michael Hallek
Journal: The Lancet Oncology (2015)
Perinatal Phosphatidylcholine Supplementation and Early Childhood Behavior Problems: Evidence for <i>CHRNA7</i> Moderation
Authors: Randal G. Ross, Sharon K. Hunter, M. Camille Hoffman, Lizbeth McCarthy, Betsey M. Chambers, Amanda J. Law, Sherry Leonard, Gary O. Zerbe, Robert Freedman
Journal: American Journal of Psychiatry (2015)

Objective: α7-Nicotinic receptors are involved in the final maturation of GABA inhibitory synapses before birth. Choline at levels found in the amniotic fluid is an agonist at α7-nicotinic receptors. The authors conducted a double-blind placebo-controlled trial to assess whether high-dose oral phosphatidylcholine supplementation during pregnancy to increase maternal amniotic fluid choline levels would enhance fetal development of cerebral inhibition and, as a result, decrease childhood behavior problems associated with later mental illness. Method: The authors previously reported that newborns in the phosphatidylcholine treatment group have increased suppression of the cerebral evoked response to repeated auditory stimuli. In this follow-up, they report parental assessments of the children’s behavior at 40 months of age, using the Child Behavior Checklist. Results: At 40 months, parent ratings of children in the phosphatidylcholine group (N=23) indicated fewer attention problems and less social withdrawal compared with the placebo group (N=26). The improvement is comparable in magnitude to similar deficits at this age associated with later schizophrenia. The children’s behavior is moderated by CHRNA7 variants associated with later mental illness and is related to their enhanced cerebral inhibition as newborns. Conclusions: CHRNA7, the α7-nicotinic acetylcholine receptor gene, has been associated with schizophrenia, autism, and attention deficit hyperactivity disorder. Maternal phosphatidylcholine treatment may, by increasing activation of the α7-nicotinic acetylcholine receptor, alter the development of behavior problems in early childhood that can presage later mental illness.
Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes
Authors: D A Sallman, R Komrokji, C Vaupel, T Cluzeau, S M Geyer, K L McGraw, N H Al Ali, J Lancet, M J McGinniss, S Nahas, A E Smith, A Kulasekararaj, G Mufti, A List, J Hall, E Padron
Journal: Leukemia (2015)
First Incidence and Progression Study for Diabetic Retinopathy in Portugal, the RETINODIAB Study
Authors: Marco Dutra Medeiros, Edgar Mesquita, Luís Gardete-Correia, Joaquim Moita, Victor Genro, Ana Luísa Papoila, Antónia Amaral-Turkman, João Filipe Raposo
Journal: Ophthalmology (2015)
Even-Skipped+ Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude
Authors: Ellie S. Heckscher, Aref Arzan Zarin, Serge Faumont, Matthew Q. Clark, Laurina Manning, Akira Fushiki, Casey M. Schneider-Mizell, Richard D. Fetter, James W. Truman, Maarten F. Zwart, Matthias Landgraf, Albert Cardona, Shawn R. Lockery, Chris Q. Doe
Journal: Neuron (2015)
Seven Year Followup for Bystander Vaccine Therapy in Mantle Cell Lymphoma (MCL)
Authors: Bijal D. Shah, Jianguo Tao, Paul A. Chervenick, Marcie L Riches, Javier Pinilla-Ibarz, Lynn C. Moscinski, Scott Antonia, Eduardo M. Sotomayor, Sophie Dessureault
Journal: Blood (2014)
Abstract 190: Modulation of MiR-21 signaling by MPS1 in human glioblastoma
Authors: Uday Bhanu Maachani, Anita Tandle, Uma Shankavaram, Tamalee Kramp, Kevin A. Camphausen
Journal: Cancer Research (2015)

Abstract Monopolar spindle 1 (MPS1) is an essential spindle assembly checkpoint (SAC) kinase involved in determining spindle integrity. Beyond its mitotic functions, it has been implicated in several other signaling pathways. Its overexpression in cancer cells is known to contribute to genomic instability and tumorigenesis. Our earlier studies have elaborated on role of MPS1 in glioblastoma (GBM) radiosensitization. In this study using reverse phase protein arrays (RPPA), we assessed MPS1 mediated cell signaling pathways and demonstrated that inhibiting MPS1 could upregulate the expression of the tumor suppressor genes PDCD4 and MSH2 by downregulating micro RNA-21 (MiR-21). In GBMs MiR-21 expression is significantly elevated and is associated with chemo and radioresistance. Here, we show that MPS1 inhibition significantly repressed MiR-21 levels and elevated PDCD4 and MSH2 expression in GBM cells both in vitro and in vivo. Both MPS1 and MiR-21 depletion suppressed GBM cell proliferation, whereas, ectopic expression of MiR-21 rescued GBM cell growth from MPS1 inhibition. Further, we demonstrate that MPS1 mediates phosphorylation of SMAD3 but not SMAD2 in GBM cells; A possible mechanism behind MiR-21 modulation by MPS1. Collectively, our results shed light onto an important role of MPS1 in TGF-β/SMAD signaling via MiR-21 regulation. We also, evaluated the prognostic effect of MiR-21, PDCD4 and MSH2 expression on survival in GBM patients of different molecular subtypes from The Cancer Genome Atlas (TCGA) database, showing tumors with high MiR-21 expression and low PDCD4 and MSH2 expression were associated with significantly shorter survival times. To our knowledge this is the first report to demonstrate the role of MPS1 in MiR-21 modulation. This scenario in which MiR-21 is modulated by MPS1 inhibition may be exploited as a potential target for effective GBM therapy. Citation Format: Uday Bhanu Maachani, Anita Tandle, Uma Shankavaram, Tamalee Kramp, Kevin A. Camphausen. Modulation of MiR-21 signaling by MPS1 in human glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 190. doi:10.1158/1538-7445.AM2015-190
The rs2296651 (S267F) variant on NTCP (<i>SLC10A1</i>) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B
Authors: Hui-Han Hu, Jessica Liu, Yu-Ling Lin, Wun-Sheng Luo, Yu-Ju Chu, Chia-Lin Chang, Chin-Lan Jen, Mei-Hsuan Lee, Sheng-Nan Lu, Li-Yu Wang, San-Lin You, Hwai-I Yang, Chien-Jen Chen
Journal: Gut (2015)

<h3>Objective</h3> The sodium taurocholate co-transporting polypeptide (NTCP), encoded by <i>SLC10A1</i>, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB. <h3>Design</h3> The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant9s association with CHB, cirrhosis and HCC were estimated using logistic regression. <h3>Results</h3> In patients with CHB, the S267F variant was observed in 515 (18.5%) controls, 40 (17.2%) cirrhosis only cases, 49 (13.2%) non-cirrhotic HCC cases, and 52 (12.7%) cirrhotic-HCC cases. After adjustment for known risk factors, S267F was significantly associated with decreased risk for cirrhosis (OR 0.65 (95% CI 0.49 to 0.86), p=0.002) and HCC (OR 0.55 (95% CI 0.42 to 0.72), p&lt;0.001). This association persisted for non-cirrhotic and cirrhotic-HCC. Compared with patients with HBV DNA levels greater than 10<sup>5</sup> copies/mL who carried the GG genotype, patients who had undetectable HBV DNA and the GA or AA genotypes had a 25-fold decreased risk of developing HCC (OR 0.04 (95% CI 0.02 to 0.11), p&lt;0.001). The AA genotype was also associated with HBsAg seronegativity (OR 0.13 (95% CI 0.05 to 0.34), p&lt;0.001). <h3>Conclusions</h3> The <i>SLC10A1</i> (NTCP) S267F variant is independently associated with decreased risk of cirrhosis and HCC, and resistance to CHB infection. Together with serum HBV DNA levels, S267F may help to identify patients with CHB with very low risk of HCC.
Abnormalities of Vertebrobasilar Circulation Due to Subclavian Artery Disease
Authors: C M COUVES, J R HILLIARD, H F PRIBRAM
Journal: JAMA (1963)

The studies of Hutchinson and Yates on caroticovertebral stenosis have stimulated further interest in cerebrovascular disease. As a consequence, investigation of the four vessels, supplying the brain is now routine in the assessment of patients being considered for surgery for occlusive disease of the vessels. This has led to some interesting and unexpected findings.The effect of subclavian artery disease on the vertebrobasilar circulation was studied in two patients. Angiography showed the vertebral arteries to function as a collateral pathway when an occlusion of the subclavian artery was present proximal to the origin of the vertebral arteries. In one case both the carotid and the vertebral arteries were implicated in the collateral supply. A normal circulation was restored by subclavian endarterectomy.Studies of other workers have shown that such a circulation may reduce the cerebral blood flow by about 40%, but neither patient described in this report had signs or symptoms of cerebrovascular disease. It is evident that our understanding of the effects of cerebrovascular disease is far from complete.