tbuckley/cabot-search huggingface dataset:
“PEAR-ing” Genomic and Epigenomic Analyses for Cancer Gene Discovery
Authors: Stephen C. Mack, Jeremy N. Rich, Peter C. Scacheri
Journal: Cancer Discovery (2015)

Abstract Summary: Somatic structural variants in tumor genomes can deregulate transcription through repositioning of enhancer elements. A new method, PEAR-ChIP, leverages paired-end H3K27ac chromatin immunoprecipitation combined with high-throughput sequencing and current computational methods to identify such events. Cancer Discov; 5(10); 1018–20. ©2015 AACR. See related article by Ryan et al., p. 1058.
The Impact of Nutrition on Thyroid Hormone Physiology and Action
Authors: E Danforth, A G Burger
Journal: Annual Review of Nutrition (1989)

In summary, nutritionally directed alterations in thyroid hormone metabolism appear to be adaptive and to serve important protective roles in the overall economy of the body. These adjustments to nutrition are found at practically every level of thyroid regulation, beginning in the CNS and ending with the final action of thyroid hormones in the nucleus of cells. The cellular actions of thyroid hormones modify, and are modified by, as yet poorly understood interrelationships with substrates and other hormones. The level and composition of the energy intake, including whether the organism is in energy balance, are important signals directing these hormonal adaptations.
Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. Millennium Cohort Study
Authors: D.C. Taylor-Robinson, H. Williams, A. Pearce, C. Law, S. Hope
Journal: British Journal of Dermatology (2015)

Summary Background Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. Objectives To identify early-life risk factors for eczema, and to explore how early-life risk factors explain any differences in eczema. Methods We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early-life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. Results Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree-level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31–1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1–6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early-life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03–1·50) in the group with the highest educational qualifications compared with the least. Conclusions In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early-life factors including not smoking during pregnancy, breastfeeding and having fewer siblings.
Thyroglobulin From Molecular and Cellular Biology to Clinical Endocrinology
Authors: Bruno Di Jeso, Peter Arvan
Journal: Endocrine Reviews (2015)

Thyroglobulin (Tg) is a vertebrate secretory protein synthesized in the thyrocyte endoplasmic reticulum (ER), where it acquires N-linked glycosylation and conformational maturation (including formation of many disulfide bonds), leading to homodimerization. Its primary functions include iodide storage and thyroid hormonogenesis. Tg consists largely of repeating domains, and many tyrosyl residues in these domains become iodinated to form monoiodo- and diiodotyrosine, whereas only a small portion of Tg structure is dedicated to hormone formation. Interestingly, evolutionary ancestors, dependent upon thyroid hormone for development, synthesize thyroid hormones without the complete Tg protein architecture. Nevertheless, in all vertebrates, Tg follows a strict pattern of region I, II-III, and the cholinesterase-like (ChEL) domain. In vertebrates, Tg first undergoes intracellular transport through the secretory pathway, which requires the assistance of thyrocyte ER chaperones and oxidoreductases, as well as coordination of distinct regions of Tg, to achieve a native conformation. Curiously, regions II-III and ChEL behave as fully independent folding units that could function as successful secretory proteins by themselves. However, the large Tg region I (bearing the primary T4-forming site) is incompetent by itself for intracellular transport, requiring the downstream regions II-III and ChEL to complete its folding. A combination of nonsense mutations, frameshift mutations, splice site mutations, and missense mutations in Tg occurs spontaneously to cause congenital hypothyroidism and thyroidal ER stress. These Tg mutants are unable to achieve a native conformation within the ER, interfering with the efficiency of Tg maturation and export to the thyroid follicle lumen for iodide storage and hormonogenesis.
Complement and Bacteria: Chemistry and Biology in Host Defense
Authors: K. A. Joiner, E. J. Brown, M. M. Frank
Journal: Annual Review of Immunology (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer
Authors: Yoshinaga Okugawa, Yuji Toiyama, Shusuke Toden, Hiroki Mitoma, Takeshi Nagasaka, Koji Tanaka, Yasuhiro Inoue, Masato Kusunoki, C Richard Boland, Ajay Goel
Journal: Gut (2015)

Despite recent advances in colorectal cancer (CRC) treatment, the prognosis of patients suffering from this malignancy still remains substandard, and metastatic recurrence following curative surgery is the leading cause of mortality. Therefore, it is imperative to identify prognostic markers to predict the clinical outcome of CRC patients. Recent evidence revealed the new role of small nucleolar RNAs (snoRNAs) in oncogenesis. Herein, we systematically evaluated dysregulation of snoRNAs in CRC and clarified their biomarker potential and biological significance in CRC.We analysed expression levels of 4 snoRNAs in 274 colorectal tissues from 3 independent cohorts and 6 colon cancer cell lines. The functional characterisation for the role of SNORA42 in CRC was investigated through a series of in vitro and in vivo experiments.In the screening phase, expression levels of all four snoRNAs were significantly elevated in CRC tissues than in corresponding normal mucosa. In the clinical validation cohort, increased SNORA42 expression was an independent prognostic factor for overall survival and disease-free survival, and was a risk factor for distant metastasis. SNORA42 expression negatively correlated with overall survival in an additional independent cohort and identified the patients with high risk for recurrence and poor prognosis in stage II CRC. Furthermore, in vitro and in vivo analyses showed that SNORA42 overexpression resulted in enhanced cell proliferation, migration, invasion, anoikis resistance and tumorigenicity.SNORA42 appears to be a novel oncogene and could serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC.
Immune biomarker correlates from a Phase II study of ipilimumab (IPI) with carboplatin and paclitaxel (CP) in patients with unresectable stage III or IV metastatic melanoma (MM)
Authors: Réjean Lapointe, Rahima Jamal, Leon van Kempen, Pamela Thebault, Karl Belanger, Jennifer Friedmann, Jean-Pierre Ayoub, Eftihia Cocolakis, Shirin Kazemi, Jeanne Dionne, Caroline Lambert, Huy Le, Cecile Grange, Jean-Francois Cailhier, Alan Spatz, Wilson Miller
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Pivotal studies with anti-CTLA-4 (Ipilimumab or IPI) demonstrated increased overall survival (OS) both as single agent (10.1 months) and with DTIC (11.2 months). We've previously reported an encouraging safety profile with IPI plus CP and early efficacy results. We now report
Transoral endoscopic surgical resection of a giant pedunculated polyp
Authors: Emilio Vicente, Yolanda Quijano, Benedetto Ielpo, Hipolito Duran, Eduardo Diaz, Susana Prados, Diego Juzgado
Journal: Endoscopy (2015)

Large pedunculated fibrovascular polyps are uncommon, mostly benign, intraluminal masses, which are usually located in the upper esophageal tract [1]. The most frequently reported clinical manifestation is dysphagia, followed by regurgitation, chest pain, and intestinal bleeding. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are key in the diagnostic work-up, revealing a sausage-shaped intraluminal mass. Endoscopy with ultrasonography and biopsy add important information for the diagnosis and pedicle location.
Probing the Human B-Cell Repertoire with EBV: Polyreactive Antibodies and CD5+ B Lymphocytes
Authors: P Casali, A L Notkins
Journal: Annual Review of Immunology (1989)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Chemical Senses in the Release of Gastric and Pancreatic Secretions
Authors: Joseph G. Brand, Robert H. Cagan, Michael Naim
Journal: Annual Review of Nutrition (1982)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Leptospirosis in man, British Isles, 1978
Authors: J D Coghlan
Journal: BMJ (1979)

Questions in the CommonsIncreased RHA costs.The following table the Clegg awards, the increased allocations to gives the estimated cost to regional health RHAs, and the gain to the Exchequer from authorities of increased value added tax and additionial VAT. 1979-80Cm Gain to Estimated Increase in Exchequer cost of Cost of allocation from increased Clegg towards additional RHA VAT awards extra cost VAT Northern.24-2-7 2-6 2-3 2-4-2-7Yorkshire.28-3-1 2-8 2-5 2-8-3 1Trent.34-3-9 3 3
Abstract 14738: Inflammasome Activation by Mitochondrial Oxidative Stress in Macrophages Leads to the Development of Angiotensin II-induced Aortic Aneurysm
Authors: Masafumi Takahashi, Fumitake Usui, Akira Kawashima, Tadayoshi Karasawa, Hiroaki Kimura
Journal: Circulation (2014)

Introduction: Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA formation remains unclear. The NLRP3 inflammasome is a multiprotein complex consisting of NLRP3, ASC, and caspase-1, and regulates caspase-1-dependent maturation of interleukin-1β (IL-1β). We previously showed that the NLRP3 inflammasome mediates the sterile cardiovascular inflammatory responses in vascular injury and myocardial ischemia-reperfusion injury.

Hypothesis: We hypothesized that the NLRP3 inflammasome is a key mediator of initial inflammation in AAA formation.

Methods: ASC is highly expressed in adventitial macrophages in human and murine AAA tissues. Using an established mouse model of AAA induced by continuous infusion of angiotensin II (AII) for 28 days in Apoe-/- mice, NLRP3, ASC, and caspase-1 deficiency in Apoe-/- mice was shown to significantly decrease the incidence, maximal diameter, and severity of AAA along with adventitial fibrosis and inflammatory responses, such as inflammatory cell infiltration and cytokine expression in the vessel wall. Blood pressures and lipid profiles were not influenced by the NLRP3 inflammasome deficiency. NLRP3, ASC, and caspase-1 deficiency in Apoe-/- mice also reduced elastic lamina degradation and metalloproteinase activation in the early phase of AAA formation. Further, AII stimulated generation of mitochondria-derived reactive oxygen species (mtROS) in the adventitial macrophages, and this mtROS generation was inhibited by NLRP3, ASC, and caspase-1 deficiency. In vitro experiments revealed that AII stimulated the NLRP3 inflammasome activation and subsequent IL-1β release in macrophages, and this activation was mediated through an AT1R/mtROS-dependent pathway.

Conclusions: Our results demonstrate the importance of the NLRP3 inflammasome in the initial inflammatory responses in AAA formation, indicating its potential as a novel therapeutic target for preventing AAA progression.
Microbiota studies in the bile duct strongly suggest a role for Helicobacter pylori in extrahepatic cholangiocarcinoma
Authors: F. Avilés-Jiménez, A. Guitron, F. Segura-López, A. Méndez-Tenorio, S. Iwai, A. Hernández-Guerrero, J. Torres
Journal: Clinical Microbiology and Infection (2015)
Paroxysmal Nocturnal Hemoglobinuria and Decay-Accelerating Factor
Authors: W F Rosse
Journal: Annual Review of Medicine (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Substance P as a Transmitter Candidate
Authors: R A Nicoll, C Schenker, S E Leeman
Journal: Annual Review of Neuroscience (1980)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Maintenance Therapy With Immunomodulatory Drugs in Multiple Myeloma: A Meta-Analysis and Systematic Review
Authors: Yucai Wang, Fang Yang, Yan Shen, Wenwen Zhang, Jacqueline Wang, Victor T. Chang, Borje S. Andersson, Muzaffar H. Qazilbash, Richard E. Champlin, James R. Berenson, Xiaoxiang Guan, Michael L. Wang
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Immunomodulatory drugs (IMiDs) and proteasome inhibitors have dramatically changed management of multiple myeloma (MM). While MM remains incurable, consolidation and maintenance therapy aimed at improving duration of response can potentially improve survival outcomes. A majority of randomized controlled trials (RCTs) have demonstrated benefit of IMiD-based maintenance therapy in delaying disease progression; however, whether this therapy can lead to improved survival remains controversial.
British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps
Authors: Matthew D Rutter, Amit Chattree, Jamie A Barbour, Siwan Thomas-Gibson, Pradeep Bhandari, Brian P Saunders, Andrew M Veitch, John Anderson, Bjorn J Rembacken, Maurice B Loughrey, Rupert Pullan, William V Garrett, Gethin Lewis, Sunil Dolwani
Journal: Gut (2015)

These guidelines provide an evidence-based framework for the management of patients with large non-pedunculated colorectal polyps (LNPCPs), in addition to identifying key performance indicators (KPIs) that permit the audit of quality outcomes. These are areas not previously covered by British Society of Gastroenterology (BSG) Guidelines.A National Institute of Health and Care Excellence (NICE) compliant BSG guideline development process was used throughout and the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to structure the guideline development process. A systematic review of literature was conducted for English language articles up to May 2014 concerning the assessment and management of LNPCPs. Quality of evaluated studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist System. Proposed recommendation statements were evaluated by each member of the Guideline Development Group (GDG) on a scale from 1 (strongly agree) to 5 (strongly disagree) with >80% agreement required for consensus to be reached. Where consensus was not reached a modified Delphi process was used to re-evaluate and modify proposed statements until consensus was reached or the statement discarded. A round table meeting was subsequently held to finalise recommendations and to evaluate the strength of evidence discussed. The GRADE tool was used to assess the strength of evidence and strength of recommendation for finalised statements.KPIs, a training framework and potential research questions for the management of LNPCPs were also developed. It is hoped that these guidelines will improve the assessment and management of LNPCPs.
Ablation Therapy for Patients with Supraventricular Tachycardia
Authors: M M Scheinman
Journal: Annual Review of Medicine (1986)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Advisory committee's conclusion was based on "absence of any credible alternative"
Authors: A. Wickham
Journal: BMJ (1996)

complacent.As doctors or scientists we are asked to give opinions about a range of issues, not all of which lie within our area of expertise.We will probably also be asked about issues that are at the boundaries of medical and scientific knowledge and about which considerable uncertainty exists.It is incumbent on us to be aware of all the arguments and to be able to communicate the levels of uncertainty associated with them in an understandable fashion.We need to work with the media so that we remain in control of the debates, and, above all, we must preserve our professional credibility at a time when those around us are losing theirs.
Treating young patients with breast cancer
Authors: J M Dixon
Journal: BMJ (2000)

Papers p 474

Breast cancer is uncommon in young women, but when it strikes it has a devastating effect on patients and their families. Several studies have shown that women who develop breast cancer in their 20s and 30s have worse survival and more biologically aggressive cancers with higher rates of proliferation and lymphovascular invasion and lower levels of oestrogen receptors than older patients with cancers of the same stage.1 Yet despite their apparently worse survival, younger women get more benefit from chemotherapy than older women. An overview of randomised trials showed that patients with operable breast cancer aged under 40 have a 37% (SD 7) proportional reduction in the odds of recurrence and a 27% (SD 8) reduced risk of death with adjuvant chemotherapy compared with reductions of 20.3% (SD 2.6) and 11.3% (SD 2.9) respectively for women aged 50-69.2 These proportionally greater benefits from adjuvant chemotherapy seem to be independent of node status.

There has been an increasing trend to give chemotherapy to almost all young patients with operable breast cancer regardless of lymph …
Active Transportation Surveillance — United States, 1999–2012
Authors: Geoffrey P. Whitfield, Prabasaj Paul, Arthur M. Wendel
Journal: MMWR Surveillance Summaries (2015)

Physical activity is a health-enhancing behavior, and most U.S. adults do not meet the 2008 Physical Activity Guidelines for Americans. Active transportation, such as by walking or bicycling, is one way that persons can be physically active. No comprehensive, multiyear assessments of active transportation surveillance in the United States have been conducted.1999-2012.Five surveillance systems assess one or more components of active transportation. The American Community Survey and the National Household Travel Survey (NHTS) both assess the mode of transportation to work in the past week. From these systems, the proportion of respondents who reported walking or bicycling to work can be calculated. NHTS and the American Time Use Survey include 1-day assessments of trips or activities. With that information, the proportion of respondents who report any walking or bicycling for transportation can be calculated. The National Health and Nutrition Examination Survey and the National Health Interview Survey both assess recent (i.e., in the past week or past month) habitual physical activity behaviors, including those performed during active travel. From these systems, the proportion of respondents who report any recent habitual active transportation can be calculated.The prevalence of active transportation as the primary commute mode to work in the past week ranged from 2.6% to 3.4%. The 1-day assessment indicated that the prevalence of any active transportation ranged from 10.5% to 18.5%. The prevalence of any habitual active transportation ranged from 23.9% to 31.4%. No consistent trends in active transportation across time periods and surveillance systems were identified. Among systems, active transportation was usually more common among men, younger respondents, and minority racial/ethnic groups. Among education groups, the highest prevalence of active transportation was usually among the least or most educated groups, and active transportation tended to be more prevalent in densely populated, urban areas.Active transportation is assessed in a wide variety of ways in multiple surveillance systems. Different assessment techniques and construct definitions result in widely discrepant estimates of active transportation; however, some consistent patterns were detected across covariates. Although each type of assessment (i.e., transportation to work, single day, and habitual behavior) measures a different active transportation component, all can be used to monitor population trends in active transportation participation.An understanding of the strengths, limitations, and lack of comparability of active transportation assessment techniques is necessary to correctly evaluate findings from the various surveillance systems. When used appropriately, these systems can be used by public health and transportation professionals to monitor population participation in active transportation and plan and evaluate interventions that influence active transportation.