tbuckley/cabot-search huggingface dataset:
<i>G72</i> and Its Association With Major Depression and Neuroticism in Large Population-Based Groups From Germany
Authors: Marcella Rietschel, Lars Beckmann, Jana Strohmaier, Alexander Georgi, Anna Karpushova, Frederike Schirmbeck, Katja V. Boesshenz, Christine Schmäl, Christin Bürger, Rami Abou Jamra, Johannes Schumacher, Susanne Höfels, Robert Kumsta, Sonja Entringer, Axel Krug, Valentin Markov, Wolfgang Maier, Peter Propping, Stefan Wüst, Tilo Kircher, Markus M. Nöthen, Sven Cichon, Thomas G. Schulze
Journal: American Journal of Psychiatry (2008)

Objective: G72 is among the most frequently replicated vulnerability genes for schizophrenia and bipolar disorder. The authors previously found identical haplotypes of markers M23 and M24 to be associated with schizophrenia, bipolar disorder, and panic disorder. Given both the well-recognized familial clustering across these disorders and recent linkage findings implicating the region harboring G72 in the etiology of major depression and panic disorder, we can hypothesize that G72 should also be involved in the etiology of major depression. Neuroticism, measuring trait anxiety, may be the endophenotypic link underlying genetic associations with G72 across diagnostic boundaries. The authors tested whether the previously observed risk haplotypes are also associated with major depression and neuroticism. Method: The authors performed a standard haplotype analysis in a group of 500 major depression patients and 1,030 population-based comparison subjects. The authors also performed an exploratory analysis on 10 additional G72 markers using a novel haplotype-sharing approach. They performed a quantitative trait haplotype analysis in an independent group of 907 individuals phenotyped for neuroticism. Results: The previously identified M23-M24 risk haplotype was significantly associated with major depression and high levels of neuroticism. The haplotype-sharing analysis also implicated the same region, whereas more proximal markers showed no association with major depression. Conclusions: This is the first study to the authors’ knowledge to implicate the G72 locus in the etiology of major depression and neuroticism. The results strengthen the notion of a genetic overlap between diagnoses, commonly conceptualized as distinct entities. Neuroticism may constitute the common underlying endophenotypic link.
Phase II Study of Oxaliplatin, Fluorouracil, and Folinic Acid in Locally Advanced or Metastatic Gastric Cancer Patients
Authors: C. Louvet, T. André, J.M. Tigaud, E. Gamelin, J.Y. Douillard, R. Brunet, E. François, J.H. Jacob, D. Levoir, A. Taamma, P. Rougier, E. Cvitkovic, A. de Gramont
Journal: Journal of Clinical Oncology (2002)

To evaluate the efficacy and safety of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FA) combination in patients with metastatic or advanced gastric cancer (M/AGC).Of the 54 eligible patients with measurable or assessable M/AGC, 53 received oxaliplatin 100 mg/m(2) and FA 400 mg/m(2) (2-hour intravenous infusion) followed by 5-FU bolus 400 mg/m(2) (10-minute infusion) and then 5-FU 3,000 mg/m(2) (46-hour continuous infusion) every 14 days.Patients (69% male, 31% female) had a median age of 61 years (range, 31 to 75 years), 89% had a performance status of 0 or 1, 70% had newly diagnosed disease, and 87% had metastatic disease. All had histologically confirmed adenocarcinoma. With a median of three involved organs, disease sites included the lymph nodes (67%), stomach (65%), and liver (61%). A median of 10 cycles per patient and 468 complete cycles were administered. Best responses in the 49 assessable patients were two complete responses and 20 partial responses, giving an overall best response rate of 44.9%. Eight patients underwent complementary treatment with curative intent (six with surgery and two with chemoradiotherapy). Median follow-up, time to progression, and overall survival were 18.6 months, 6.2 months, and 8.6 months, respectively. Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and anemia occurred in 38%, 19%, 4%, and 11% of patients, respectively, and febrile neutropenia occurred in six patients (one episode each). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity.This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable safety profile in M/AGC patients, and may prove to be a suitable alternative regimen in this indication.
A Stochastic Local Search Algorithm for Distance-Based Phylogeny Reconstruction
Authors: F. Tria, E. Caglioti, V. Loreto, A. Pagnani
Journal: Molecular Biology and Evolution (2010)

In many interesting cases, the reconstruction of a correct phylogeny is blurred by high mutation rates and/or horizontal transfer events. As a consequence, a divergence arises between the true evolutionary distances and the differences between pairs of taxa as inferred from available data, making the phylogenetic reconstruction a challenging problem. Mathematically, this divergence translates in a loss of additivity of the actual distances between taxa. In distance-based reconstruction methods, two properties of additive distances have been extensively exploited as antagonist criteria to drive phylogeny reconstruction: On the one hand, a local property of quartets, that is, sets of four taxa in a tree, the four-points condition; on the other hand, a recently proposed formula that allows to write the tree length as a function of the distances between taxa, Pauplin's formula. Here, we introduce a new reconstruction scheme that exploits in a unified framework both the four-points condition and the Pauplin's formula. We propose, in particular, a new general class of distance-based Stochastic Local Search algorithms, which reduces in a limit case to the minimization of Pauplin's length. When tested on artificially generated phylogenies, our Stochastic Big-Quartet Swapping algorithmic scheme significantly outperforms state-of-art distance-based algorithms in cases of deviation from additivity due to high rate of back mutations. A significant improvement is also observed with respect to the state-of-art algorithms in the case of high rate of horizontal transfer.
Carvedilol Produces Dose-Related Improvements in Left Ventricular Function and Survival in Subjects With Chronic Heart Failure
Authors: Michael R. Bristow, Edward M. Gilbert, William T. Abraham, Kirkwood F. Adams, Michael B. Fowler, Ray E. Hershberger, Spencer H. Kubo, Kenneth A. Narahara, Henry Ingersoll, Steven Krueger, Sarah Young, Neil Shusterman
Journal: Circulation (1996)

Background We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a “third-generation” β-blocking agent with vasodilator properties, in chronic heart failure. Methods and Results Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P&lt; .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P&lt; .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects ( P &lt;.001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P= .01) and was generally well tolerated. Conclusions In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.
THE PSYCHOSOMATIC CONCEPT IN WORKING CLOTHES
Authors: GEORGE L. ROSS, THELMA E. BROWN
Journal: American Journal of Psychiatry (1950)

The term "rehabilitation" is a working definition of the psychosomatic concept. In order to carry out this Gestalt type of thinking, the emphasis of therapy must be changed from aggregation to integration of diagnostic, planning, and treatment services, The Fort Thomas staff is coordinating and integrating its functions as quickly and efficiently as possible to effect this change. Its interpretation of the psychosomatic concept in working clothes is presented in this paper through its three-step process: 1. The integrated diagnostic study; 2. Controlled planning; 3. Therapy and follow-through.
Abstract S1-01: The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06)
Authors: M Piccart-Gebhart, AP Holmes, E de Azambuja, S Di Cosimo, R Swaby, M Untch, C Jackisch, I Lang, I Smith, F Boyle, B Xu, C Barrios, R Gelber, H Eidtmann, J Baselga
Journal: Cancer Research (2013)

Abstract Background: The NeoALTTO study demonstrated a significantly higher breast pathological complete response (pCR) rate (NSABP definition – ypT0/is) with dual HER2 blockade using lapatinib and trastuzumab compared with single HER2 blockade using either lapatinib or trastuzumab (51.3% vs. 24.7% vs. 29.5%, respectively; p&amp;lt; 0.01 for both) in HER2 positive primary breast cancer (BC). A similar pattern was seen for locoregional pCR (ypT0/is ypN0) (Baselga J et al. Lancet 2012). Material and Methods: From January, 2008, to December, 2009, 455 patients were randomized from 99 participating sites in 23 countries. Patients were randomized to receive either lapatinib 1500 mg/d (154 pts), or trastuzumab 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly (149 pts), or lapatinib 1000 mg/d with trastuzumab for a total of 6 weeks (152 pts). After this biological window, patients continued on the same targeted therapy plus weekly paclitaxel 80 mg/m2 for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). After surgery, patients received 3 cycles of adjuvant FEC followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy), with on-going follow-up planned until 10 years after last randomised patient. Secondary objectives included disease-free survival and overall survival (OS). Following current practice and draft FDA recommendations for neoadjuvant trial endpoints, an amendment was made to the protocol secondary objectives (released in May 2013). DFS (from surgery) was replaced by event-free survival (EFS) from randomisation; OS from surgery was correspondingly replaced with OS from randomisation, and examination of the association between these survival endpoints and locoregional pCR (ypT0/is ypN0) was added as a secondary objective. EFS was defined as the time from randomization to first EFS event (breast cancer relapse, second primary malignancy or death without recurrence). OS was defined as the time from randomization to death from any cause. Results: The clinical cut-off date for the first planned analysis of these secondary objectives was on 26 May 2013, three years after the date of last surgery. Data cleaning is ongoing and analysis will be completed by November 2013. Results for EFS, OS and their association with pCR will be presented at the meeting. Funding: GlaxoSmithKline is the sponsor of this trial. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S1-01.
Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease
Authors: J. Dambacher, F. Beigel, J. Seiderer, D. Haller, B. Goke, C. J Auernhammer, S. Brand
Journal: Gut (2007)

<b>Background/aim:</b> Interleukin 31 (IL31), primarily expressed in activated lymphocytes, signals through a heterodimeric receptor complex consisting of the IL31 receptor alpha (IL31Rα) and the oncostatin M receptor (OSMR). The aim of this study was to analyse IL31 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal inflammation. <b>Methods:</b> Expression studies were performed by RT-PCR, quantitative PCR, western blotting, and immunohistochemistry. Signal transduction was analysed by western blotting. Cell proliferation was measured by MTS assays, cell migration by restitution assays. <b>Results:</b> Colorectal cancer derived intestinal epithelial cell (IEC) lines express both IL31 receptor subunits, while their expression in unstimulated primary murine IEC was low. LPS and the proinflammatory cytokines TNF-α, IL1β, IFN-γ, and sodium butyrate stimulation increased IL31, IL31Rα, and OSMR mRNA expression, while IL31 itself enhanced IL8 expression in IEC. IL31 mediates ERK-1/2, Akt, STAT1, and STAT3 activation in IEC resulting in enhanced IEC migration. However, at low cell density, IL31 had significant antiproliferative capacities (p&lt;0.005). IL31 mRNA expression was not increased in the TNFΔARE mouse model of ileitis but in inflamed colonic lesions compared to non-inflamed tissue in patients with Crohn's disease (CD; average 2.4-fold increase) and in patients with ulcerative colitis (UC; average 2.6-fold increase) and correlated with the IL-8 expression in these lesions (r = 0.564 for CD; r = 0.650 for UC; total number of biopsies analysed: n = 88). <b>Conclusion:</b> IEC express the functional IL31 receptor complex. IL31 modulates cell proliferation and migration suggesting a role in the regulation of intestinal barrier function particularly in intestinal inflammation.
THE MOTOR SHOW FROM THE MEDICAL MAN'S POINT OF VIEW: FRESH FEATURES AND HOW TO REGARD THEM
Authors: H. M. Buist
Journal: BMJ (1913)

THE MfOTOR SHOW.fNov u, T913.into consideration, and is calling a special miieeting to discuss it.Medical miien in England arc uarged to take niote of these facts and to beware of acceptina appointmenits to lodges in tllis State wvitlhout being fully assured that tlle appoint- ients whlichl they are accepting are approved by the New South AWales Branell of tlle Britislh MIcdical Association.
Exogenous ochronosis: an epidemiological study
Authors: N. HARDWICK, L.W. GELDER, C.A. MERWE, M.P. MERWE
Journal: British Journal of Dermatology (2006)

Journal Article Exogenous ochronosis: an epidemiological study Get access N. HARDWICK, N. HARDWICK Departments of Dermatology, University of Pretoria, South Africa Dr N. Hardwick, No 3 Arrowhead House, Herts and Essex Hospital, Bishop's Stortford, Hertfordshire CM23 5JH, U.K. Search for other works by this author on: Oxford Academic Google Scholar L.W. VAN GELDER, L.W. VAN GELDER Departments of Family Medicine, University of Pretoria, South Africa Search for other works by this author on: Oxford Academic Google Scholar C.A. VAN DER MERWE, C.A. VAN DER MERWE Institute for Biostatistics, South African Medical Research Council, South Africa Search for other works by this author on: Oxford Academic Google Scholar M.P. VAN DER MERWE M.P. VAN DER MERWE Departments of Dermatology, University of Pretoria, South Africa Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 2, 1 February 1989, Pages 229–238, https://doi.org/10.1111/j.1365-2133.1989.tb07787.x Published: 01 February 1989
Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells
Authors: Xiang Dong Yang, Walden Ai, Samuel Asfaha, Govind Bhagat, Richard A Friedman, Guangchun Jin, Heuijoon Park, Benjamin Shykind, Thomas G Diacovo, Andras Falus, Timothy C Wang
Journal: Nature Medicine (2010)
Triangulocytes in Alcoholism
Authors: Sudhir Khanna
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The morphological red blood cell (RBC) abnormalities reported in alcoholism include macrocytes,<sup>1</sup>macro-ovalocytes,<sup>1</sup>target cells,<sup>2</sup>spur cells,<sup>3</sup>stomatocytes,<sup>4</sup>polychromasia,<sup>5</sup>and spherocytes as seen in the Zieve syndrome.<sup>6</sup>Macrocytes and macro-ovalocytes are usually associated with folic acid deficiency. Target and spur cells are secondary to an alteration in the cholesterol and lecithin in the RBC membrane.<sup>2,3</sup>Stomatocytes occur as a transient abnormality in acute alcoholics, but are also found in a rare inherited hemolytic disease with a defect in the protein kinase mediated phorphorylation of erythrocyte membrane proteins and associated disturbance in RBC cation content.<sup>7</sup>The polychromasia results from increased reticulocytosis and the spherocytes are probably related to the presence of abnormal lipids that seem to alter the RBC membrane making them more fragile.<sup>8</sup> Five hundred RBC from each of seven alcoholic patients were evaluated and compared with
Phase II Study: Integrated Palliative Care in Newly Diagnosed Advanced Non–Small-Cell Lung Cancer Patients
Authors: Jennifer S. Temel, Vicki A. Jackson, J. Andrew Billings, Constance Dahlin, Susan D. Block, Mary K. Buss, Patricia Ostler, Panos Fidias, Alona Muzikansky, Joseph A. Greer, William F. Pirl, Thomas J. Lynch
Journal: Journal of Clinical Oncology (2007)

To assess the feasibility of early palliative care in the ambulatory setting in patients with newly diagnosed advanced non-small-cell lung cancer (NSCLC).Patients were eligible if they had a performance status of 0 to 1 and were within 8 weeks of diagnosis of advanced NSCLC. Participants received integrated care from oncology and palliative care throughout the course of their disease. Participants were scheduled to meet with the palliative care team (PCT) and complete quality-of-life (QOL) and mood questionnaires monthly for 6 months. The study was deemed feasible if 64% of patients completed at least 50% of their scheduled visits and QOL assessments.Fifty-one patients were enrolled onto the trial. One died within 72 hours and was not assessable. Ninety percent (95% CI, 0.78 to 0.96) of study participants complied with at least 50% of the palliative care visits. Eight-six percent (95% CI, 0.73 to 0.94) of the participants met the full feasibility requirements by both meeting with the PCT and completing QOL assessments at least 50% of the time. QOL and mood analyses confirmed the high symptom burden in patients with newly diagnosed advanced NSCLC. At least 50% of participants experienced some degree of shortness of breath, cough, difficulty breathing, appetite loss, weight loss, or unclear thinking at their baseline assessment. More than one third of patients had a probable mood disorder at baseline.Integrated palliative and oncology care is feasible in ambulatory patients with advanced NSCLC.
The origin and possible time of divergence of the Hawaiian Drosophilidae: evidence from DNA sequences.
Authors: R DeSalle
Journal: Molecular Biology and Evolution (1992)

The origins and times of divergence of the speciose Hawaiian Drosophilidae are examined using mtDNA sequences. The Hawaiian Drosophilidae are resolved as the sister group to the subgenus Drosophila. No one member of the subgenus Drosophila could be determined to be more closely related to the Hawaiian Drosophilidae than could any other. This result suggests that the Hawaiian Drosophilidae arose before the diversification of the subgenus Drosophila and after the divergence of the subgenus Sophophora. In light of fossil evidence, this phylogenetic scenario suggests that the Hawaiian Drosophilidae lineages are no younger than 30 Myr.
Synthesis of basement membrane collagen by cultured human endothelial cells.
Authors: E A Jaffe, C R Minick, B Adelman, C G Becker, R Nachman
Journal: The Journal of Experimental Medicine (1976)

Studies were performed to determine if cultured human endothelial cells synthesized basement membrane collagen. In culture, endothelial cells were attached to grossly visible membranous structures which on light microscopy were composed of ribbons of dense, amorphous material. On transmission electron microscopy, these membranous structures consisted of amorphous basement membrane, and material morphologically similar to microfibrils and elastic fibers. By immunofluorescence microscopy, these membranous structures stained brightly with antisera to human glomerular basement membrane. Cultured endothelial cells incorporated [3H]proline into protein; 18% of the incorporated [3H]proline was solubilized by purified collagenase. When endothelial cells were cultured with [14C]proline, 7.1% of the incorporated counts were present as [14C]hydroxyproline. Cultured endothelial cells were labeled with [3H]glycine and [3H]proline and digested with pepsin. The resulting fractions on analysis by SDS-polyacrylamide gel electrophoresis contained two radioactive protein peaks of mol wt 94,200 and 120,500. Both these peaks disappeared after digestion with purified collagenase. The peak of mol wt 120,500 corresponds to that of alpha1 (IV) collagen; the peak of the mol wt 94,200 probably corresponds to that of alpha1 (III) collagen. Thus, cultured human endothelial cells synthesize material which is morphologically and immunologically like amorphous basement membrane and biochemically like basement membrane collagen. Cultured endothelial cells probably also synthesize material which is morphologically similar to microfibrils and elastic fibers.
Causes of Death in Elderly Prostate Cancer Patients and in a Comparison Nonprostate Cancer Cohort
Authors: C. J. Newschaffer, K. Otani, M. K. McDonald, L. T. Penberthy
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Prostate cancer tends to affect older men and to progress relatively slowly. Since the prevalence of comorbidity increases with advancing age, competing causes of death are important contributors to death rates among prostate cancer patients. Accurate determination of the underlying causes of death in older men dying with prostate cancer may thus also be more difficult. Methods: We compared the distribution of underlying causes of death in decedents from a population-based cohort of elderly prostate cancer patients to that from a population-based comparison cohort of elderly men without prostate cancer. Among decedents from the prostate cancer patient cohort, we examined associations of patient demographics, disease stage, and initial treatment, with assignment of a prostate cancer underlying cause of death (versus any other cause) by use of multivariable logistic regression. In the subgroup of prostate cancer patient decedents having underlying causes of death other than prostate cancer, the underlying cause distribution was compared with that in nonprostate cancer cohort decedents. Results: Prostate cancer was the underlying cause for 39% (95% confidence interval [CI] = 36.3–41.9) of the decedents in the prostate cancer cohort. Causes of death among prostate cancer patients not dying of prostate cancer were similar to those among the nonprostate cancer cohort decedents. However, in those who were aggressively treated, the adjusted odds of other cancer causes of death were 51% higher (odds ratio [OR] = 1.51; 95% CI = 1.08–2.10) than that in nonprostate cancer patient decedents, while in those treated with watchful waiting the adjusted odds were 34% lower (OR = 0.66; 95% CI = 0.47–0.93). Conclusions: Initial treatment may influence the underlying cause of death reported in vital statistics for prostate cancer patients.