tbuckley/cabot-search huggingface dataset:
δ Infection in asymptomatic carriers of hepatitis B surface antigen: Low prevalence of δ activity and effective suppression of hepatitis B virus replication
Authors: Pei-Jer Chen, Ding-Shinn Chen, Chiou-Rong Chen, Yu-Ying Chen, Hsu-Mei Hsu Chen, Ming-Yang Lai, Juei-Low Sung
Journal: Hepatology (1988)

We examined the prevalence of serum anti-δ antibody among 769 intravenous drug abusers in Taiwan. δ infection was found extremely common in the HBsAg-positive carriers with drug abuse, because 128 (85%) of 151 carriers were positive for anti-δ. However, most of antibody titers were low (&lt;1:5,000). By molecular hybridization, δ RNA genomes were detectable in only five (4%) of 128 asymptomatic carriers positive for anti-δ. The results suggested that most of them had previous, instead of ongoing, δ infection. We also studied the serum markers reflecting hepatitis B virus replication in these carriers and a control group. Hepatitis B e antigen was positive in only 12 (10%) of 115 anti-δ positive carriers in contrast to 22 (23%) of 95 age- and sex-matched HBsAg-positive, anti-δ negative volunteers donating blood (p &lt; 0.025). Furthermore, in contrast to the close association between HBeAg and hepatitis B virus DNA generally present in HBsAg carriers (concordance in this series: 79%), among the 12 HBeAg-positive subjects of the δ infected group, only two, or 17%, had serum hepatitis B virus DNA (p &lt; 0.003). Such suppressing effects did not require a simultaneous presence of the δ agent, as shown by the lack of δ RNA genomes in the serum by sensitive assay. We conclude that although δ superinfection is common in the asymptomatic HBsAg carriers with intravenous drug abuse in the nonendemic area of Taiwan, continuous δ activities are uncommon in them. In addition, the previous δ infection probably exerts effective suppression on the hepatitis B virus replication in these HBsAg carriers.
The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds
Authors: S.V. Tavtigian, J. Simard, J. Rommens, F. Couch, D. Shattuck-Eidens, S. Neuhausen, S. Merajver, S. Thorlacius, K. Offit, D. Stoppa-Lyonnet, C. Belanger, R. Bell, S. Berry, R. Bogden, Q. Chen, T. Davis, M. Dumont, C. Frye, T. Hattier, S. Jammulapati, T. Janecki, P. Jiang, R. Kehrer, J.-F. Leblanc, J.T. Mitchell, J. McArthur-Morrison, K. Nguyen, Y. Peng, C. Samson, M. Schroeder, S.C. Snyder, L. Steele, M. Stringfellow, C. Stroup, B. Swedlund, J. Swense, D. Teng, A. Thomas, T. Tran, M. Tranchant, J. Weaver-Feldhaus, A.K.C. Wong, H. Shizuya, J.E. Eyfjord, L. Cannon-Albright, M. Tranchant, F. Labrie, M.H. Skolnick, B. Weber, A. Kamb, D.E. Goldgar
Journal: Nature Genetics (1996)
Genetic landscape of esophageal squamous cell carcinoma
Authors: Yi-Bo Gao, Zhao-Li Chen, Jia-Gen Li, Xue-Da Hu, Xue-Jiao Shi, Zeng-Miao Sun, Fan Zhang, Zi-Ran Zhao, Zi-Tong Li, Zi-Yuan Liu, Yu-Da Zhao, Jian Sun, Cheng-Cheng Zhou, Ran Yao, Su-Ya Wang, Pan Wang, Nan Sun, Bai-Hua Zhang, Jing-Si Dong, Yue Yu, Mei Luo, Xiao-Li Feng, Su-Sheng Shi, Fang Zhou, Feng-Wei Tan, Bin Qiu, Ning Li, Kang Shao, Li-Jian Zhang, Lan-Jun Zhang, Qi Xue, Shu-Geng Gao, Jie He
Journal: Nature Genetics (2014)
Asthma outcomes: Pulmonary physiology
Authors: Robert S. Tepper, Robert S. Wise, Ronina Covar, Charles G. Irvin, Carolyn M. Kercsmar, Monica Kraft, Mark C. Liu, George T. O'Connor, Stephen P. Peters, Ronald Sorkness, Alkis Togias
Journal: Journal of Allergy and Clinical Immunology (2012)
Medical Humanities — A New Medical Adventure
Authors: Anthony R. Moore
Journal: New England Journal of Medicine (1976)

In a formal medical syllabus it is difficult to provide an opportunity for the discussion of broader cultural, philosophical and personal issues relevant to doctorship. In particular, it is a delicate task to create an environment in which the students take the intellectual initiative in a consideration of human issues. In an attempt to provide such an opportunity, I designed a short course that is structured around a consideration of extracts from classic literary works, an adventure made possible by the teaching example of Dr. Theodore Redpath, fellow and director of English Studies, Trinity College, Cambridge University, and the encouragement . . .
Crisis in Care: Limited Treatment Options for Type 2 Diabetes in Adolescents and Youth
Authors: William V. Tamborlane, Georgeanna Klingensmith
Journal: Diabetes Care (2013)

Until two decades ago, children and adolescents were automatically assumed to have insulin-dependent type 1 diabetes. However, type 2 diabetes emerged as a “new type” of childhood diabetes in the 1990s in association with the epidemic of childhood obesity. It quickly became apparent that this new pediatric disease disproportionally affected disadvantaged minority children and was associated with comorbidities that increased the risk of future cardiovascular disease.

After more than 20 years, the optimal approach to the treatment of childhood type 2 diabetes remains largely unknown. Besides insulin, metformin remains the only other antidiabetic medication that is approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in youth with type 2 diabetes. Glimepiride and rosiglitazone failed noninferiority tests versus metformin as initial monotherapy in company-sponsored clinical trials. While the primary study results of the randomized phase of the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) study showed that combination therapy with metformin plus rosiglitazone was more effective than metformin plus intensive lifestyle intervention and metformin alone (1), rosiglitazone will not be used with any frequency in young patients with type 2 diabetes because of concerns about the cardiovascular and other adverse effects of this class of medications. Once again, pediatric diabetes practitioners are left with just metformin and insulin for adolescents with type 2 diabetes.

Why haven’t glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors that have been approved for use in adults with type 2 diabetes been approved for the treatment of adolescents …
The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with diabetes mellitus
Authors: Luis Gruberg, Ron Waksman, Andrew E Ajani, Han-Soo Kim, R.Lawrence White, Ellen E Pinnow, Lowell F Satler, Augusto D Pichard, Kenneth M Kent, Joseph Lindsay
Journal: Journal of the American College of Cardiology (2002)
Report fuels confusion over red meat and cancer
Authors: C. White
Journal: BMJ (1998)

Diet may have a significant impact on some of the cancers most common in Britain. This is the conclusion reached by the latest report from the Committee on Medical Aspects of Food and Nutrition Policy (COMA). Renewed confusion over the recommended consumption of red meat, however, threatens to subsume the overall message of The Nutritional Aspects of the Development of Cancer .

The report recommends an intake of fruits and vegetables of five or more servings a day—50% above the current British average. It also recommends increasing intake of dietary fibre and maintaining body mass index at 20­25 during adult life.

The report also warns against the use of high doses of purified supplements and micronutrients—s carotene in particular—as a means of protecting against cancer. These, it says, cannot be assumed to …
Criteria for Diagnosis of Occupational Disease
Authors: Harriet L. Hardy
Journal: New England Journal of Medicine (1961)

CORRECT recognition of work-related illness is rarely easy. The exception is the epidemic occurrence of similar disease in a small group of workers — for example, clear-cut lead poisoning in certain storage-battery manufacturing operations. But the physician is usually called on to establish a diagnosis in a single worker, either as a private physician or in the role of part-time doctor for an industry.Occupational disease may be delayed in onset, the period from last exposure to demonstrable disease being as long as fifteen years or more as in some cases of silicosis, beryllium disease and cancer of the lung . . .
Further characterization of the natriuretic factor derived from kidney tissue of volume-expanded rats. Effects on short-circuit current and sodium-potassium-adenosine triphosphatase activity.
Authors: S D Hillyard, E Lu, H C Gonick
Journal: Circulation Research (1976)

Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.
The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease
Authors: Yaron Rotman, Christopher Koh, Joseph M. Zmuda, David E. Kleiner, Jake T. Liang
Journal: Hepatology (2010)

Abstract Genome-wide association studies identified single-nucleotide polymorphisms (SNPs) that are associated with increased hepatic fat or elevated liver enzymes, presumably reflecting nonalcoholic fatty liver disease (NAFLD). To investigate whether these SNPs are associated with histological severity of NAFLD, 1117 (894 adults/223 children) individuals enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network and National Institutes of Health Clinical Center studies with histologically confirmed NAFLD were genotyped for six SNPs that are associated with hepatic fat or liver enzymes in genome-wide association studies. In adults, three SNPs on chromosome 22 showed associations with histological parameters of NASH. After adjustment for age, sex, diabetes, and alcohol consumption, the minor allele of rs738409 C/G, a nonsynonymous coding SNP in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene encoding an Ile148Met change, was associated with steatosis ( P = 0.03), portal inflammation ( P = 2.5 × 10−4), lobular inflammation ( P = 0.005), Mallory-Denk bodies ( P = 0.015), NAFLD activity score (NAS, P = 0.004), and fibrosis ( P = 7.7 × 10−6). Two other SNPs in the same region demonstrated similar associations. Three SNPs on chromosome 10 near the CHUK (conserved helix-loop-helix ubiquitous kinase) gene were independently associated with fibrosis ( P = 0.010). In children, no SNP was associated with histological severity. However, the rs738409 G allele was associated with younger age at the time of biopsy in multivariate analysis ( P = 0.045). Conclusion: In this large cohort of histologically proven NAFLD, we confirm the association of the rs738409 G allele with steatosis and describe its association with histological severity. In pediatric patients, the high-risk rs738409 G allele is associated with an earlier presentation of disease. We also describe a hitherto unknown association between SNPs at a chromosome 10 locus and the severity of NASH fibrosis.
THE PHARMACOLOGIC ASSAY OF DRUGS AND ITS IMPORTANCE IN THERAPEUTICS.
Authors: E. M. HOUGHTON
Journal: JAMA (1901)

<h3>Note.</h3> —The word "pharmacology" is employed as meaning "the study of the changes induced in living organisms by the administration in a state of minute division of such unorganized substances as do not act merely as foods." After a correct diagnosis has been made, one of the most important questions to be considered by the physician is that of dosage. Especially is this true when, as often occurs, the patient's life depends upon prompt and efficient aid. But if the drugs prescribed are not of fixed and definite strength our efforts may prove utterly unavailing. Until a few years ago we were obliged to employ pharmaceuticals of uncertain and varying strength. This variation was due not alone to differences in the process of manufacture, but also to the fact that the amount of active constituents contained in the crude drug itself varies from season to season, is modified by habitat,
Policy for prevention of Asian rickets in Britain: a preliminary assessment of the Glasgow rickets campaign.
Authors: M G Dunnigan, W B McIntosh, G R Sutherland, R Gardee, B Glekin, J A Ford, I Robertson
Journal: BMJ (1981)

Evidence of continuing hospital admissions of patients with Asian rickets and osteomalacia led to a further attempt to provide more effective preventive measures for the Glasgow Asian community. Dose-response studies showed that the equivalent of 10 microgram of vitamin D daily would provide effective prophylaxis, and a general practice survey showed that self-administered vitamin D supplements would reduce the prevalence and severity of Asian rickets. A multidisciplinary working group devised a preventive campaign based on the free issue of vitamin D supplements on demand to children who required them. Supported by a health education programme for community health personnel and the Asian community, the first 16 months of the campaign produced an eight-fold rise in the issue of supplements to older Asian children and a 33% increase in their issue to infants of all ethnic groups. Because more children are receiving vitamin D supplementation the campaign seems likely to reduce the prevalence of Asian rickets in Glasgow.
Recruiting High-Risk Individuals to a Diabetes Prevention Program
Authors: Toralph Ruge, Lennarth Nyström, Bernt Lindahl, Göran Hallmans, Margareta Norberg, Lars Weinehall, Olov Rolandsson
Journal: Diabetes Care (2007)

Lifestyle prevention programs in Finland (Diabetes Prevention Study [DPS]) (1,2) and the U.S. (Diabetes Prevention Program [DPP]) (3) have shown that the development of type 2 diabetes can be prevented. A cost-effectiveness study revealed that lifestyle intervention was effective in all ages (4). Whether lifestyle intervention will be cost-effective in the general population is determined by 1 ) the recruitment of the majority of high-risk individuals and 2 ) the compliance to lifestyle changes.

We studied the recruitment rate in an open, randomized, and controlled trial aiming to reduce the incidence of diabetes. Intervention consisted of physical activity and dietary information that was to be organized by a nonprofit organization for the intervention …
Industry’s push to woo nurse prescribers has been at “expense of nursing integrity”
Authors: Michael Day
Journal: BMJ (2008)

<h3>Abstract</h3> Neuroticism is a personality trait of fundamental importance for psychological wellbeing and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes and heterogeneity in the measurement of neuroticism. Here we report a genome-wide association study of neuroticism in 91,370 participants of the UK Biobank cohort and a combined meta-analysis which includes a further 7,197 participants from the Generation Scotland Scottish Family Health Study (GS:SFHS) and 8,687 participants from a Queensland Institute of Medical Research (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form’s Neuroticism scale. We found a SNP-based heritability estimate for neuroticism of approximately 15% (SE = 0.7%). Meta-analysis identified 9 novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (p = 1.28×10<sup>−15</sup>) spanning 4 Mb and containing at least 36 genes. Other associated loci included genes of interest on chromosome 1 (<i>GRIK3</i>, glutamate receptor ionotropic kainate 3), chromosome 4 (<i>KLHL2</i>, Kelch-like protein 2), chromosome 17 (<i>CRHR1</i>, corticotropin-releasing hormone receptor 1 and <i>MAPT</i>, microtubule-associated protein Tau), and on chromosome 18 (<i>CELF4</i>, CUGBP elav-like family member 4). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a large genetic correlation between neuroticism and MDD (0.64) and a smaller genetic correlation with schizophrenia (0.22) but not with bipolar disorder. Polygenic scores derived from the primary UK Biobank sample captured about 1% of the variance in trait liability to neuroticism. Overall, our findings confirm a polygenic basis for neuroticism and substantial shared genetic architecture between neuroticism and MDD. The identification of 9 new neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.
Abstract 3727: Phase 0 trials, obligation to research and ethical implications of health-care reform
Authors: Silvia Camporesi, Matteo Mameli
Journal: Cancer Research (2010)

Abstract Biomedical knowledge is a public good; and people have a right to it. These two widely accepted assumptions are also at the core of the US Health Care reform. On the one hand, a public good needs the community's contribution in order to exist. On the other hand, people have also duties concerning public goods. Indeed, current patients rest on the shoulders of previous patients who contributed to the advancement of biomedical knowledge. Therefore, it can be argued that participation to research should be considered a “moral duty,” based on the arguments of free riding, reciprocity and fairness; and that default option should be to “opt in” to clinical trials. While the debate revolving around a “obligation to research” dates back at least to the 1980s, it recently cropped up again, thanks to bioethicists John Harris and Ezekiel Emanuel (the latter, currently Special Advisor for Health Policy at the White House). The 2006 FDA guidelines concerning first-in human clinical studies, also known as Phase 0 trials, are relevant to this discussion. Phase 0 studies aim to reduce the gap of translational research, and at speeding up the drug rate of approval. They are not suitable for all drug candidates, but only for those agents for which the molecular target and mechanism of effect are known. As they offer no therapeutic benefits to the participants, it has been argued that they pose an ethical dilemma. But a broader outlook on the ethical aspects needs to be taken here. Indeed, the existence of a scientific rationale for the design of study is a necessary, even if not sufficient, condition for its ethical justification; and it can be argued that the current framework of Phase 1 studies is not suitable for molecularly targeted agents, for which the maximum tolerate toxicity does not correlate with maximum efficacy. Furthermore, if future trials will confirm the results of the first ABT-888 Phase 0 trial completed at NCI-NIH, and demonstrate that the risks of toxicity are negligible, it could be argued that Phase 0 trials represent the turning point for the envisaged cultural shift towards participation to research, as only in this context patients are offered the unique opportunity to contribute in a purely altruistic manner to the public good of biomedical knowledge. As a visiting PhD student at NCI-NIH sponsored by an UICC-ICRETT fellowship, I am currently developing a questionnaire to assess the comprehension of patients to Phase 0 clinical trials and their broader attitude towards participation to research. I will present my work in progress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3727.
Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1β protects against steatohepatitis
Authors: Elena Bellafante, Stefania Murzilli, Lorena Salvatore, Dominga Latorre, Gaetano Villani, Antonio Moschetta
Journal: Hepatology (2013)

Development of hepatic steatosis and its progression to steatohepatitis may be the consequence of dysfunction of several metabolic pathways, such as triglyceride synthesis, very low-density lipoprotein (VLDL) secretion, and fatty acid β-oxidation. Peroxisome proliferator-activated receptor γ coactivator-1β (PGC-1β) is a master regulator of mitochondrial biogenesis and oxidative metabolism, lipogenesis, and triglyceride (TG) secretion. Here we generated a novel mouse model with constitutive hepatic activation of PGC-1β and studied the role of this transcriptional coactivator in dietary-induced steatosis and steatohepatitis. Selective activation of PGC-1β within hepatocytes is able to protect the liver from lipid overload and from progression to fibrosis. The protective function exerted by PGC-1β is due to its ability to induce mitochondrial oxidative phosphorylation, fatty acid β-oxidation, and citrate cycle, as well as to decrease oxidative stress and promote TG secretion in the blood stream. These findings bolster the concept that a combined hepatic specific action of PGC-1β on lipid synthesis and secretion, as well as on mitochondrial biogenesis and function, could protect against steatohepatitis.
Comment on ''Interactions between endothelin-1 and the renin-angiotensin-aldosterone system''
Authors: S Gardiner
Journal: Cardiovascular Research (1999)

In a recent review, Rossi et al. [1] considered interactions between endothelin-1 and the renin angioten-sinaldosterone systems, and cited our work [2,3] on the super-additive vasodilator and hypotensive effects of the non-selective endothelin receptor antagonist, SB 209670, and …
Benign Breast Disorders
Authors: Richard J. Santen, Robert Mansel
Journal: New England Journal of Medicine (2005)

About 50 percent of women have histologic evidence of some degree of fibrocystic changes in the breast. This review article describes the spectrum of benign breast disorders, including those that increase the risk of malignant disease. The authors explain the evaluation and management of breast pain, breast discharge, and focal lesions, as well as the options that can prevent progression to breast cancer.