tbuckley/cabot-search huggingface dataset:
Conservation and Coevolution in the Scale-Free Human Gene Coexpression Network
Authors: I King Jordan, Leonardo Mariño-Ramírez, Yuri I Wolf, Eugene V Koonin
Journal: Molecular Biology and Evolution (2004)

The role of natural selection in biology is well appreciated. Recently, however, a critical role for physical principles of network self-organization in biological systems has been revealed. Here, we employ a systems level view of genome-scale sequence and expression data to examine the interplay between these two sources of order, natural selection and physical self-organization, in the evolution of human gene regulation. The topology of a human gene coexpression network, derived from tissue-specific expression profiles, shows scale-free properties that imply evolutionary self-organization via preferential node attachment. Genes with numerous coexpressed partners (the hubs of the coexpression network) evolve more slowly on average than genes with fewer coexpressed partners, and genes that are coexpressed show similar rates of evolution. Thus, the strength of selective constraints on gene sequences is affected by the topology of the gene coexpression network. This connection is strong for the coding regions and 3' untranslated regions (UTRs), but the 5' UTRs appear to evolve under a different regime. Surprisingly, we found no connection between the rate of gene sequence divergence and the extent of gene expression profile divergence between human and mouse. This suggests that distinct modes of natural selection might govern sequence versus expression divergence, and we propose a model, based on rapid, adaptation-driven divergence and convergent evolution of gene expression patterns, for how natural selection could influence gene expression divergence.
Presence of human papillomavirus DNA sequences in cervical intraepithelial neoplasia.
Authors: D J McCance, P G Walker, J L Dyson, D V Coleman, A Singer
Journal: BMJ (1983)

Twenty two patients referred to a district colposcopy clinic because of an abnormal cervical cytology report or a suspicious cervix and found to have a cervical epithelial abnormality were studied. The techniques of cytology, histology, immunohistochemistry, and DNA-DNA hybridisation were used to detect infection by human papillomavirus. Using an indirect immunoalkaline phosphatase technique human papillomavirus antigen was found in biopsy specimens from six of the 22 patients and DNA of papillomavirus type 6 in biopsy specimens from 13 of these women, including four out of six whose histological diagnosis was cervical intraepithelial neoplasia grade 3. In eight cases where cytological, colposcopical, and histological investigations all indicated the presence of wart virus infection, papillomavirus type 6 DNA was found in seven. Papillomavirus type 6 DNA was found in more than half of the proved cases of cervical intraepithelial neoplasia. The presence of this viral DNA in women with no cervical abnormality is to be studied.
Factors Associated With Intensification of Oral Diabetes Medications in Primary Care Provider-Patient Dyads: A Cohort Study
Authors: Shari Danielle Bolen, Eric Bricker, T. Alafia Samuels, Hsin-Chieh Yeh, Spyridon S. Marinopoulos, Maura McGuire, Marcela Abuid, Frederick L. Brancati
Journal: Diabetes Care (2008)

OBJECTIVE—Although suboptimal glycemic control is known to be common in diabetic adults, few studies have evaluated factors at the level of the physician-patient encounter. Our objective was to identify novel visit-based factors associated with intensification of oral diabetes medications in diabetic adults. RESEARCH DESIGN AND METHODS—We conducted a nonconcurrent prospective cohort study of 121 patients with type 2 diabetes and hyperglycemia (A1C ≥8%) enrolled in an academically affiliated managed-care program. Over a 24-month interval (1999–2001), we identified 574 hyperglycemic visits. We measured treatment intensification and factors associated with intensification at each visit. RESULTS—Provider-patient dyads intensified oral diabetes treatment in only 128 (22%) of 574 hyperglycemic visits. As expected, worse glycemia was an important predictor of intensification. Treatment was more likely to be intensified for patients with visits that were “routine” (odds ratio [OR] 2.55 [95% CI 1.49–4.38]), for patients taking two or more oral diabetes drugs (2.82 [1.74–4.56]), or for patients with longer intervals between visits (OR per 30 days 1.05 [1.00–1.10]). In contrast, patients with less recent A1C measurements (OR &amp;gt;30 days before the visit 0.53 [0.34–0.85]), patients with a higher number of prior visits (OR per prior visit 0.94 [0.88–1.00]), and African American patients (0.59 [0.35–1.00]) were less likely to have treatment intensified. CONCLUSIONS—Failure to intensify oral diabetes treatment is common in diabetes care. Quality improvement measures in type 2 diabetes should focus on overcoming inertia, improving continuity of care, and reducing racial disparities.
Improved Peripheral Perfusion During Endothelin-A Receptor Blockade in Patients With Type 2 Diabetes and Critical Limb Ischemia
Authors: Majid Kalani, John Pernow, Joakim Bragd, Gun Jörneskog
Journal: Diabetes Care (2008)

Endothelin (ET)-1 levels are increased in patients with type 2 diabetes and may contribute to vascular complications and insulin resistance. Recently, we showed that ETA receptor blockade improves nutritive skin capillary circulation in patients with type 2 diabetes and microangiopathy (1).

In this study, we investigated the effect of ETA receptor blockade on peripheral micro- and macrocirculation in six patients (two female/four male; mean age 79 ± 6 years) with type 2 diabetes and critical limb ischemia (toe blood pressure …
Enhanced Killing of Primary Ovarian Cancer by Retargeting Autologous Cytokine-Induced Killer Cells with Bispecific Antibodies: A Preclinical Study
Authors: John K. Chan, Chad A. Hamilton, Michael K. Cheung, Mobin Karimi, Jeanette Baker, Jonathan M. Gall, Stephan Schulz, Steve H. Thorne, Nelson N. Teng, Christopher H. Contag, Lawrence G. Lum, Robert S. Negrin
Journal: Clinical Cancer Research (2006)

Abstract Cytokine-induced killer (CIK) cells are ex vivo activated and expanded CD8+ natural killer T cells that have been shown to have antitumor activity. This is the first study exploring cell killing of primary ovarian carcinoma cells with and without bispecific antibodies. Primary cancer cells and autologous CIK cells were collected from women with epithelial ovarian cancer. Bispecific antibodies against cancer antigen-125 (BSAbxCA125) and Her2 (BSAbxHer2) were developed using chemical heteroconjugation. On fluorescence-activated cell sorting analysis, the expansion of CIK cells resulted in a significant increase of CD3+CD8+ and CD3+CD56+ T cells. With enhancement by bispecific antibodies, the mean percent lysis in a 51Cr release assay of fresh ovarian cancer cells exposed to autologous CIK cells increased from 21.7 ± 0.3% to 89.4 ± 2.1% at an E:T ratio of 100:1 (P &amp;lt; 0.001). Anti-NKG2D antibodies attenuated the CIK activity by 56.8% on primary cells (P &amp;lt; 0.001). In a xenograft severe combined immunodeficient mouse model, real-time tumor regression and progression was visualized using a noninvasive in vivo bioluminescence imaging system. Four hours after CIK cell injection, we were able to visualize CD8+NKG2D+ CIK cells infiltrating Her2-expressing cancer cells on fluorescence microscopy. Mice that underwent adoptive transfer of CIK cells redirected with BSAbxCA125 and BSAbxHer2 had significant reduction in tumor burden (P &amp;lt; 0.001 and P &amp;lt; 0.001) and improvement in survival (P = 0.05 and P = 0.006) versus those treated with CIK cells alone. Bispecific antibodies significantly enhanced the cytotoxicity of CIK cells in primary ovarian cancer cells and in our in vivo mouse model. The mechanism of cytolysis seems to be mediated in part by the NKG2D receptor.
NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses
Authors: Frits van Rhee, Susann M. Szmania, Fenghuang Zhan, Sushil K. Gupta, Mindy Pomtree, Pei Lin, Ramesh B. Batchu, Amberly Moreno, Guilio Spagnoli, John Shaughnessy, Guido Tricot
Journal: Blood (2005)
Isomyosin distribution in normal and pressure-overloaded rat ventricular myocardium. An immunohistochemical study.
Authors: L Gorza, P Pauletto, A C Pessina, S Sartore, S Schiaffino
Journal: Circulation Research (1981)

We have used affinity-purified antibodies reacting with guinea pig soleus muscle and ventricular myosin heavy chains to analyze the distribution of specific isomyosin in the ventricular myocardium of normal and renal hypertensive rats. Immunofluorescent staining of cardiac tissue sections with the two antimyosins revealed striking variations in reactivity among ventricular muscle fibers, reactive fibers being more numerous in the left compared to the right ventricle and in subendocardial compared to subepicardial layers. The response of the ventricular myocardium changed during development: all fibers were stained in the newborn rat, whereas most fibers were unreactive in 1-month-old animals. The number of reactive fibers increased again in subsequent stages leading to a mixed pattern in adult animals. The normal mixed pattern of reactivity was transformed into a uniformly positive pattern in hypertensive rats 2 months after surgery. This complete transformation was observed in 20 out of 23 hypertensive animals examined. These findings indicate that the two antimyosins cross-react with a particular type of ventricular myosin heavy chain, whose distribution varies in different muscle cells and whose relative concentration changes during development and during cardiac hypertrophy induced by systemic hypertension. We suggest that differences in pressure load may be responsible for both regional variations in isomyosin distribution and for isomyosin changes in hypertensive animals.
Effects of rugby sevens matches on human neutrophil-related non-specific immunity
Authors: I Takahashi, T Umeda, T Mashiko, D Chinda, T Oyama, K Sugawara, S Nakaji
Journal: British Journal of Sports Medicine (2006)

To evaluate the influences of the accumulative effect of two consecutive rugby sevens matches (Sevens) on aspects of human neutrophil-related non-specific immunity.
Large-scale Transcriptome Analyses Reveal New Genetic Marker Candidates of Head, Neck, and Thyroid Cancer
Authors: Eduardo M. Reis, Elida P.B. Ojopi, Fernando L. Alberto, Paula Rahal, Fernando Tsukumo, Ulises M. Mancini, Gustavo S. Guimarães, Gloria M.A. Thompson, Cleber Camacho, Elisabete Miracca, André L. Carvalho, Abimael A. Machado, Apuã C.M. Paquola, Janete M. Cerutti, Aline M. da Silva, Gonçalo G. Pereira, Sandro R. Valentini, Maria A. Nagai, Luiz Paulo Kowalski, Sergio Verjovski-Almeida, Eloiza H. Tajara, Emmanuel Dias-Neto
Journal: Cancer Research (2005)

Abstract A detailed genome mapping analysis of 213,636 expressed sequence tags (EST) derived from nontumor and tumor tissues of the oral cavity, larynx, pharynx, and thyroid was done. Transcripts matching known human genes were identified; potential new splice variants were flagged and subjected to manual curation, pointing to 788 putatively new alternative splicing isoforms, the majority (75%) being insertion events. A subset of 34 new splicing isoforms (5% of 788 events) was selected and 23 (68%) were confirmed by reverse transcription–PCR and DNA sequencing. Putative new genes were revealed, including six transcripts mapped to well-studied chromosomes such as 22, as well as transcripts that mapped to 253 intergenic regions. In addition, 2,251 noncoding intronic RNAs, eventually involved in transcriptional regulation, were found. A set of 250 candidate markers for loss of heterozygosis or gene amplification was selected by identifying transcripts that mapped to genomic regions previously known to be frequently amplified or deleted in head, neck, and thyroid tumors. Three of these markers were evaluated by quantitative reverse transcription–PCR in an independent set of individual samples. Along with detailed clinical data about tumor origin, the information reported here is now publicly available on a dedicated Web site as a resource for further biological investigation. This first in silico reconstruction of the head, neck, and thyroid transcriptomes points to a wealth of new candidate markers that can be used for future studies on the molecular basis of these tumors. Similar analysis is warranted for a number of other tumors for which large EST data sets are available.
VERTEBRATE NEURAL INDUCTION
Authors: A. Hemmati-Brivanlou, D. Melton
Journal: Annual Review of Neuroscience (1997)

▪ Abstract During early vertebrate development, the cells of the ectoderm choose between two possible fates: neural and epidermal. The process of neural induction was discovered nearly 70 years ago in vertebrates, and molecular analyses in recent years using Xenopus laevis embryos have identified several secreted factors with direct neural-inducing ability. There is considerable evidence that the mechanism of neuralization by these inducing factors is under inhibitory control and involves derepression. This review focuses on factors involved in the specification of neural fate within the frame of the default model of neural induction.
Rethinking learning and development in the Newell Test
Authors: Sylvain Sirois
Journal: Behavioral and Brain Sciences (2003)

The Newell Test is an ambitious and promising project, but not without pitfalls. Some of the current criteria are not theoretically neutral, whereas others are unhelpful. To improve the test, the learning and development criteria are reviewed and revised, which suggests adding a maturation criterion as well. Such changes should make the Newell Test more general and useful.
p16INK4A Hypermethylation Is Associated with Hepatitis Virus Infection, Age, and Gender in Hepatocellular Carcinoma
Authors: Xin Li, Ai-Min Hui, Lin Sun, Kiyoshi Hasegawa, Guido Torzilli, Masami Minagawa, Tadatoshi Takayama, Masatoshi Makuuchi
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The tumor suppressor gene p16INK4A is mainly inactivated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. The possible clinical impact of p16INK4A methylation and the potential risk factors for this epigenetic alteration have not been thoroughly investigated. Experimental Design: We studied the methylation status and mRNA and protein expression of p16INK4A in 50 hepatocellular carcinomas and corresponding nonneoplastic liver lesions using methylation-specific PCR, reverse transcription-PCR, and immunohistochemical techniques. Results: p16INK4A hypermethylation was observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of the corresponding chronic hepatitis and cirrhosis tissue samples. p16INK4A methylation was significantly associated with mRNA and protein expression (P &amp;lt; 0.001 and P = 0.003, respectively). All of the p16INK4A-methylated tumors were positive for hepatitis B virus or hepatitis C virus markers, but none of the virus-negative tumors exhibited p16INK4A methylation (P = 0.006). The frequency of p16INK4A hypermethylation tended to be higher in hepatitis C virus-related tumors (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P = 0.1). Aberrant methylation of p16INK4A was also related significantly to increasing age, female gender, and normal levels of serum PIVKA-II (P = 0.02, 0.04, and 0.04, respectively). No statistically significant difference in survival was observed between patients with p16INK4A hypermethylation and those without. Conclusions: Our observations suggest that p16INK4A hypermethylation may contribute to hepatocarcinogenesis from an early stage and that multiple risk factors, such as viral infections, age, and gender, may be associated with p16INK4A hypermethylation in hepatocarcinogenesis.
Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium
Authors: V. Edefonti, M. Hashibe, F. Ambrogi, M. Parpinel, F. Bravi, R. Talamini, F. Levi, G. Yu, H. Morgenstern, K. Kelsey, M. McClean, S. Schantz, Z. Zhang, S. Chuang, P. Boffetta, C. La Vecchia, A. Decarli
Journal: Annals of Oncology (2011)
1161 INDUCTION OF HEME OXYGENASE-1 IN HUMAN HEPATOCYTES PROVIDES HEPATOPROTECTIVE EFFECTS AND SUPPRESSES HCV REPLICATION IN CHIMERIC uPA/SCID MICE
Authors: J. Kah, T. Volz, M. Lütgehetmann, N. Oehler, G. Tiegs, A.W. Lohse, G. Sass, M. Dandri
Journal: Journal of Hepatology (2013)
Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: A meta-analysis
Authors: Ruben Hernaez, Mariana Lazo, Susanne Bonekamp, Ihab Kamel, Frederick L. Brancati, Eliseo Guallar, Jeanne M. Clark
Journal: Hepatology (2011)

Ultrasonography is a widely accessible imaging technique for the detection of fatty liver, but the reported accuracy and reliability have been inconsistent across studies. We aimed to perform a systematic review and meta-analysis of the diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver. We used MEDLINE and Embase from October 1967 to March 2010. Studies that provided cross-tabulations of ultrasonography versus histology or standard imaging techniques, or that provided reliability data for ultrasonography, were included. Study variables were independently abstracted by three reviewers and double checked by one reviewer. Forty-nine (4720 participants) studies were included for the meta-analysis of diagnostic accuracy. The overall sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of ultrasound for the detection of moderate-severe fatty liver, compared to histology (gold standard), were 84.8% (95% confidence interval: 79.5-88.9), 93.6% (87.2-97.0), 13.3 (6.4-27.6), and 0.16 (0.12-0.22), respectively. The area under the summary receiving operating characteristics curve was 0.93 (0.91-0.95). Reliability of ultrasound for the detection of fatty liver showed kappa statistics ranging from 0.54 to 0.92 for intrarater reliability and from 0.44 to 1.00 for interrater reliability. Sensitivity and specificity of ultrasound was similar to that of other imaging techniques (i.e., computed tomography or magnetic resonance imaging). Statistical heterogeneity was present even after stratification for multiple clinically relevant characteristics.Ultrasonography allows for reliable and accurate detection of moderate-severe fatty liver, compared to histology. Because of its low cost, safety, and accessibility, ultrasound is likely the imaging technique of choice for screening for fatty liver in clinical and population settings.
Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids
Authors: M.E. Caplin, E. Baudin, P. Ferolla, P. Filosso, M. Garcia-Yuste, E. Lim, K. Oberg, G. Pelosi, A. Perren, R.E. Rossi, W.D. Travis, Detlief Bartsch, Jaume Capdevila, Frederico Costa, Jaroslaw Cwikla, Wouter de Herder, Gianfranco Delle Fave, Barbro Eriksson, Massimo Falconi, Diego Ferone, David Gross, Ashley Grossman, Tetsuhide Ito, Robert Jensen, Gregory Kaltsas, Fahrettin Kelestimur, Reza Kianmanesh, Ulrich Knigge, Beata Kos-Kudla, Eric Krenning, Emmanuel Mitry, Marianne Nicolson, Juan O'Connor, Dermot O'Toole, Ulrich-Frank Pape, Marianne Pavel, John Ramage, Eric Raymond, Guido Rindi, Andrea Rockall, Philippe Ruszniewski, Ramon Salazar, Aldo Scarpa, Eva Sedlackova, Anders Sundin, Christos Toumpanakis, Marie-Pierre Vullierme, Wolfgang Weber, Bertram Wiedenmann, Zeng Zheng-Pei
Journal: Annals of Oncology (2015)
The Significance of Basal Insulin Levels in the Evaluation of the Insulin Response to Glucose in Diabetic and Nondiabetic Subjects*
Authors: John D. Bagdade, Edwin L. Bierman, Daniel Porte
Journal: Journal of Clinical Investigation (1967)

The level of insulin after an overnight fast (basal) in 37 obese and nonobese male subjects with normal and abnormal carbohydrate tolerance was directly related to the increase in insulin concentration during a 3 hr 100 g oral glucose tolerance test. Obesity, but not diabetes, was associated with an elevation of this basal insulin level. Thus obesity predicted with the magnitude of the insulin response to glucose ingestion. When the individual insulin values were expressed as per cent change from the basal level, this effect of obesity was excluded. The insulin levels of all subjects with normal carbohydrate tolerance promptly rose 5-7-fold, and reached peak values 1 hr after oral glucose. In contrast, the diabetic response (as per cent increase) was markedly reduced during the 1st hr, and maximal (but still subnormal) insulin levels were not attained until 2 hr. In all subjects the insulin response (quantitated by calculation of the area circumscribed by a plot of the per cent change in insulin with time) showed a significant inverse correlation with the glucose response. Thus increasing degrees of carbohydrate intolerance were associated with decreasing insulin responses. Elevated levels of insulin, in both the basal state and in response to glucose, were related to obesity.
Smoking cessation determinants in STOP smoking program from Cluj Napoca, Romania
Authors: Doina Adina Todea, Alexandra Brinzaniuc, Andrrea Codruta Coman, Andreea Cristina Herescu, Loredana Elena Rosca
Journal: European Respiratory Journal (2013)

Cigarette smoking affects almost every system of the human body, thus causing multiple diseases. The risk of serious disease decreases rapidly after quitting.  The aim of the study was to establish which were the determinants in smoking cessation process.  Material and methods: We conducted a study from2008-2010. Study subjects included all smokers, outpatients, who visited Respiratory Medicine Department, University of Medicine and Pharmacy Iuliu Hatieganu Cluj Napoca in order to quit smoking. We collected Demographic data, detailed smoking history, detailed medical history with the presence of comorbidities, Fagerstrom test (FT) for nicotine dependence. Smoking history included pack-years (PYS), number of cigarettes per day, starting age, existence of quitting smoking attempt. The treatment options included counseling, bupropion SR, varenicline and nicotine patches.  Results: From 441 subjects 52,6 % were males, 47,4 % females; mean age 39,4, median 39; 34,9 % had a disease, FT mean was 6,28, median 6,00; PYS mean was 23,66 ; median 20,00; number of cigarettes per day mean=23,75; median =20,00; starting age mean -18,39; median-18,00; and 58,7 % had an anterior smoking attempt. At the end of the treatment 54,2 % were nonsmokers and 45,8 smokers. From treatment options varenicline (OR= 6,4) was superior to bupropion SR (OR=2,55) and nicotine patches (OR=0,38) ; existence of quitting smoking attempt and starting age also influence the final outcome.  Conclusions: The treatment but also other determinants are important in the smoking cessation process.