tbuckley/cabot-search huggingface dataset:
OC-074 Nutritional assessment and outcome in patients undergoing emergency abdominal surgery
Authors: P G Vaughan-Shaw, S Jones, J A Saunders, M A Stroud, T R Smith, A T King
Journal: Gut (2012)

<h3>Introduction</h3> Malnourished Surgical patients are at a significantly greater risk of post-operative complications and death than well-nourished patients. The “Malnutrition Universal Screening Tool” (MUST) is a validated tool for identifying at-risk patients. This paper studies the application of MUST in patients undergoing emergency abdominal surgery and the accuracy of this tool in predicting need for artificial nutritional support and clinical outcome. <h3>Methods</h3> A prospective cohort study of patients undergoing emergency abdominal surgery at a university surgical unit over a 2-month period was undertaken. MUST data were collected prospectively and <i>admission</i> and <i>highest</i> (maximum score during admission) MUST scores calculated independently by two researchers. Clinical outcome data were collected. <h3>Results</h3> 55 patients were included, median age 66. Median <i>admission</i> and <i>highest</i> MUST scores were 0. Eighteen patients had a highest MUST of ≥2. Post-operative complications included ileus (n=9), severe sepsis (n=6) and death (n=10), and were associated with increased <i>highest</i> MUST scores (2 vs 0, p=0.005). All patients with MUST ≥4 died (n=4). On multivariate analysis, both <i>admission</i> and <i>highest</i> MUST scores predicted need for artificial nutritional support (p=0.011 and p=0.005). A <i>highest</i> MUST score ≥4 independently predicted both artificial nutritional support requirement (p&lt;0.001) and death (p&lt;0.001). <h3>Conclusion</h3> <i>Admission</i> MUST scores predict requirement for artificial nutritional support. MUST scores repeated during admission offer utility in predicting both requirement for artificial nutritional support and survival. Clinicians have a responsibility to ensure accurate nutritional assessments are undertaken throughout hospital admission in order to identify those at risk and institute appropriate treatment. <h3>Competing interests</h3> None declared.
Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα
Authors: Robert C. Bauer, Makoto Sasaki, Daniel M. Cohen, Jian Cui, Mikhaila A. Smith, Batuhan O. Yenilmez, David J. Steger, Daniel J. Rader
Journal: Journal of Clinical Investigation (2015)

Variants near the gene TRIB1 are significantly associated with several plasma lipid traits, circulating liver enzymes, and the development of coronary artery disease in humans; however, it is not clear how its protein product tribbles-1 regulates lipid metabolism. Here, we evaluated mice harboring a liver-specific deletion of Trib1 (Trib1_LSKO) to elucidate the role of tribbles-1 in mammalian hepatic lipid metabolism. These mice exhibited increased hepatic triglyceride (TG) content, lipogenic gene transcription, and de novo lipogenesis. Microarray analysis revealed altered transcription of genes that are downstream of the transcription factor C/EBPα, and Trib1_LSKO mice had increased hepatic C/EBPα protein. Hepatic overexpression of C/EBPα in WT mice phenocopied Trib1_LSKO livers, and hepatic knockout of Cebpa in Trib1_LSKO mice revealed that C/EBPα is required for the increased lipogenesis. Using ChIP-Seq, we found that Trib1_LSKO mice had increased DNA-bound C/EBPα near lipogenic genes and the Trib1 gene, which itself was transcriptionally upregulated by C/EBPα overexpression. Together, our results reveal that tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα, which in turn transcriptionally upregulates Trib1. These data suggest an important role for C/EBPα in mediating the lipogenic effects of hepatic Trib1 deletion and provide insight into the association between TRIB1 and plasma lipids, and liver traits in humans.
Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation
Authors: Jyoti Das, Guangwen Ren, Liying Zhang, Arthur I. Roberts, Xin Zhao, Alfred L.M. Bothwell, Luc Van Kaer, Yufang Shi, Gobardhan Das
Journal: The Journal of Experimental Medicine (2009)

Interleukin (IL)-17–producing T helper (Th17) cells play a critical role in the pathophysiology of several autoimmune disorders. The differentiation of Th17 cells requires the simultaneous presence of an unusual combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) β, an antiinflammatory cytokine. However, the molecular mechanisms by which TGF-β exerts its effects on Th17 cell differentiation remain elusive. We report that TGF-β does not directly promote Th17 cell differentiation but instead acts indirectly by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. In contrast, TGF-β had no effect on the expression of retinoic acid receptor–related orphan nuclear receptor γt, a Th17-specific transcription factor. Interestingly, in Stat-6−/−T-bet−/− mice, which are unable to generate Th1 and Th2 cells, IL-6 alone was sufficient to induce robust differentiation of Th17 cells, whereas TGF-β had no effect, suggesting that TGF-β is dispensable for Th17 cell development. Consequently, BALB/c Stat-6−/−T-bet−/− mice, but not wild-type BALB/c mice, were highly susceptible to the development of experimental autoimmune encephalomyelitis, which could be blocked by anti–IL-17 antibodies but not by anti–TGF-β antibodies. Collectively, these data provide evidence that TGF-β is not directly required for the molecular orchestration of Th17 cell differentiation.
Therapeutic Effect of Vitamin C
Authors: Judy Z. Miller
Journal: JAMA (1977)

Three different dosages of vitamin C, dependent on body weight, were administered to 44 school-aged monozygotic twins for five months using a double-blind, co-twin control study design. The mothers recorded daily observations of cold symptoms, and multiple biochemical, anthropometric, and psychological measurements were made at the beginning and end of the study. Paired comparisons showed no significant overall treatment effect on cold symptoms, but the response was not uniform in all sub-groups. Treated girls in the youngest two groups had significantly shorter and less severe illness episodes, and an effect on severity was also observed in the youngest group of boys. The seven treated twins in the latter group also grew an average of 1.3 cm more than their untreated co-twins during the five-minth period of the study.
Long-Term Outcome After Drug-Eluting Versus Bare-Metal Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Anne Kaltoft, Henning Kelbæk, Leif Thuesen, Jens Flensted Lassen, Peter Clemmensen, Lene Kløvgaard, Thomas Engstrøm, Hans E. Bøtker, Kari Saunamäki, Lars R. Krusell, Erik Jørgensen, Hans-Henrik Tilsted, Evald H. Christiansen, Jan Ravkilde, Lars Køber, Klaus F. Kofoed, Christian J. Terkelsen, Steffen Helqvist
Journal: Journal of the American College of Cardiology (2010)
Salvage chemotherapy of relapsed or high-risk gestational trophoblastic neoplasia (GTN) with paclitaxel/cisplatin alternating with paclitaxel/etoposide (TP/TE)
Authors: J. Wang, D. Short, N.J. Sebire, I. Lindsay, E.S. Newlands, P. Schmid, P.M. Savage, M.J. Seckl
Journal: Annals of Oncology (2008)
Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes
Authors: Hirotaka Matsuo, Ken Yamamoto, Hirofumi Nakaoka, Akiyoshi Nakayama, Masayuki Sakiyama, Toshinori Chiba, Atsushi Takahashi, Takahiro Nakamura, Hiroshi Nakashima, Yuzo Takada, Inaho Danjoh, Seiko Shimizu, Junko Abe, Yusuke Kawamura, Sho Terashige, Hiraku Ogata, Seishiro Tatsukawa, Guang Yin, Rieko Okada, Emi Morita, Mariko Naito, Atsumi Tokumasu, Hiroyuki Onoue, Keiichi Iwaya, Toshimitsu Ito, Tappei Takada, Katsuhisa Inoue, Yukio Kato, Yukio Nakamura, Yutaka Sakurai, Hiroshi Suzuki, Yoshikatsu Kanai, Tatsuo Hosoya, Nobuyuki Hamajima, Ituro Inoue, Michiaki Kubo, Kimiyoshi Ichida, Hiroshi Ooyama, Toru Shimizu, Nariyoshi Shinomiya
Journal: Annals of the Rheumatic Diseases (2015)

Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Results Five gout susceptibility loci were identified at the genome-wide significance level (p&lt;5.0×10 −8 ), which contained well-known urate transporter genes ( ABCG2 and SLC2A9 ) and additional genes: rs1260326 (p=1.9×10 −12 ; OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10 −23 ; OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10 −9 ; OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case–control ORs for two distinct types of gout (r=0.96 [p=4.8×10 −4 ] for urate clearance and r=0.96 [p=5.0×10 −4 ] for urinary urate excretion). Conclusions Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics.
Open infarct artery, late potentials, and other prognostic factors in patients after acute myocardial infarction in the thrombolytic era. A prospective trial.
Authors: S H Hohnloser, P Franck, T Klingenheben, M Zabel, H Just
Journal: Circulation (1994)

BACKGROUND Successful reperfusion of the infarct-related artery in patients with acute myocardial infarction has been shown to reduce in-hospital as well as 1-year mortality. Besides the thrombolysis-induced myocardial salvage, there is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable long-term outcome of these patients. The exact incidence of arrhythmic events during the first year after myocardial infarction and the predictive value of different risk factors for these complications, however, have not been determined in patients in the thrombolytic era. METHODS AND RESULTS A total of 173 patients with acute myocardial infarction, 51% treated with thrombolysis, were prospectively entered into the study. At the time of hospital discharge, signal-averaged ECG, Holter monitoring, radionuclide angiography, coronary angiography, and levocardiography were performed in all patients. An open infarct-related artery was documented in 136 patients. The overall incidence of late potentials was 24% (41 patients). By multivariate analysis, an occluded infarct-related artery (P = .04) and the presence of regional wall motion abnormalities (P = .02) were the strongest independent predictors for the development of a late potential. Residual ischemia was treated by either percutaneous transluminal coronary angioplasty or surgery in 86 of 173 patients (50%). Seventy percent of the patients received beta-blocker therapy. During a mean follow-up of 12 +/- 5 months, 7 patients died suddenly or had ventricular fibrillation documented, while only 2 developed sustained monomorphic ventricular tachycardia. Overall 1-year mortality was 4.1%. Multivariate analysis revealed only an occluded infarct-related artery as an independent predictor of arrhythmic complications (P = .017). CONCLUSIONS In patients with acute myocardial infarction treated according to contemporary therapeutic guidelines, with a large proportion of individuals undergoing coronary artery revascularization, a low incidence of arrhythmic events, particularly of ventricular tachycardia, was observed in the first year after the index infarction. The presence or absence of an open infarct-related artery was the strongest independent predictor of these events, whereas other traditional risk factors, such as late potentials, were less helpful in identifying patients prone to sudden death. These findings emphasize the importance of the open artery hypothesis in patients recovering from acute myocardial infarction.
Implantable Cardioverter-Defibrillator Lead Performance
Authors: William H. Maisel, Daniel B. Kramer
Journal: Circulation (2008)

I mplantable cardioverter-defibrillators (ICDs) have revolu- tionized the treatment of patients at risk for sudden cardiac death.In the nearly 3 decades since the first human ICD implant, 1 millions of devices have been implanted worldwide and innumerable lives have been saved.Successful resuscitation of a potentially lethal ventricular arrhythmia by an ICD system depends on successful arrhythmia detection and timely delivery of therapy.Both the ICD generator and the ICD lead are critical components of this system.The lead, in particular, is literally a lifeline whose purpose is to convey critical information about the heart's rhythm to the ICD generator and, in turn, to deliver life-sustaining therapy when needed.Failure of an ICD lead may result in significant clinical events, including failure to pace, failure to defibrillate, inappropriate shocks, and even death.
Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study
Authors: Y. Tanaka, T. Takeuchi, T. Mimori, K. Saito, M. Nawata, H. Kameda, T. Nojima, N. Miyasaka, T. Koike
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Tumour necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons. <h3>Objective</h3> To determine whether infliximab might be discontinued after achievement of LDA in patients with RA and to evaluate progression of articular destruction during the discontinuation. <h3>Methods</h3> 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score, including a 28-joint count (DAS28) was &lt;3.2 (LDA) for 24 weeks, were studied. <h3>Results</h3> The mean disease duration of the 114 patients was 5.9 years, mean DAS28 5.5 and mean modified total Sharp score (mTSS) 63.3. After maintaining LDA for &gt;24 weeks by infliximab treatment, the drug was discontinued and DAS28 in 102 patients was evaluated at year 1. Fifty-six patients (55%) continued to have DAS28&lt;3.2 and 43% reached DAS&lt;2.6 at 1 year after discontinuing infliximab. For 46 patients remission induction by Remicade in RA (RRR) failed: disease in 29 patients flared within 1 year and DAS28 was &gt;3.2 at year 1 in 17 patients. Yearly progression of mTSS (ΔTSS) remained &lt;0.5 in 67% and 44% of the RRR-achieved and RRR-failed groups, respectively. The estimated ΔmTSS was 0.3 and 1.6 and Health Assessment Questionnaire-Disability Index was 0.174 and 0.614 in the RRR-achieved and RRR-failed groups, respectively, 1 year after the discontinuation. <h3>Conclusion</h3> After attaining LDA by infliximab, 56 (55%) of the 102 patients with RA were able to discontinue infliximab for &gt;1 year without progression of radiological articular destruction.
Therapeutic bronchoscopy with immediate effect revisited: "tissue is the issue"
Authors: E. E. McGrath, P. B. Anderson
Journal: European Respiratory Journal (2007)

To the Editors: 

In the paper by Bolliger et al. 1, the authors highlight that there have been very few multicentre trials and no randomised prospective trials on interventional stent insertion. They write that different centres have different levels of expertise at interventional bronchoscopy. With that in mind, the idea of management guidelines for treatment must surely be appealing, so that we all have a standard approach to treatment and diminish variability across centres.

This point was highlighted by a recent case at our unit. An elderly frail patient presented in respiratory failure …
The first whole genome and transcriptome of the cinereous vulture reveals adaptation in the gastric and immune defense systems and possible convergent evolution between the Old and New World vultures
Authors: Oksung Chung, Seondeok Jin, Yun Sung Cho, Jeongheui Lim, Hyunho Kim, Sungwoong Jho, Hak-Min Kim, JeHoon Jun, HyeJin Lee, Alvin Chon, Junsu Ko, Jeremy Edwards, Jessica A. Weber, Kyudong Han, Stephen J. O’Brien, Andrea Manica, Jong Bhak, Woon Kee Paek
Journal: Genome biology (2015)

The cinereous vulture, Aegypius monachus, is the largest bird of prey and plays a key role in the ecosystem by removing carcasses, thus preventing the spread of diseases. Its feeding habits force it to cope with constant exposure to pathogens, making this species an interesting target for discovering functionally selected genetic variants. Furthermore, the presence of two independently evolved vulture groups, Old World and New World vultures, provides a natural experiment in which to investigate convergent evolution due to obligate scavenging.We sequenced the genome of a cinereous vulture, and mapped it to the bald eagle reference genome, a close relative with a divergence time of 18 million years. By comparing the cinereous vulture to other avian genomes, we find positively selected genetic variations in this species associated with respiration, likely linked to their ability of immune defense responses and gastric acid secretion, consistent with their ability to digest carcasses. Comparisons between the Old World and New World vulture groups suggest convergent gene evolution. We assemble the cinereous vulture blood transcriptome from a second individual, and annotate genes. Finally, we infer the demographic history of the cinereous vulture which shows marked fluctuations in effective population size during the late Pleistocene.We present the first genome and transcriptome analyses of the cinereous vulture compared to other avian genomes and transcriptomes, revealing genetic signatures of dietary and environmental adaptations accompanied by possible convergent evolution between the Old World and New World vultures.
The thymic way to transplantation tolerance.
Authors: G Remuzzi, N Perico, C B Carpenter, M H Sayegh
Journal: Journal of the American Society of Nephrology (1995)

Within the past three decades, extensive research has been carried out with the aim to prevent graft rejection by minimizing the side effects related to the use of immunosuppressants. The major goal in transplantation research remains the development of strategies that would allow one to achieve a state of donor-specific unresponsiveness in order to promote a condition of true tolerance without the need of immunosuppressants. Recent evidence has been provided that this is a pursuing goal, at least in experimental animals. The thymus plays the major role in the development of self-tolerance, and initial work in the late 1960s indicated that the thymus also plays a critical role in the induction of acquired tolerance to exogenous antigens. Recently, the interest in acquired thymic tolerance has been renewed by the observation that, in the rat, the thymus is an immunologically privileged site in which isolated pancreatic islets can be engrafted and survive indefinitely. Moreover, intrathymic injection of the islets induced donor-specific unresponsiveness, which allowed survival of a second donor-strain islet cell allograft transplanted into an extrathymic site. These findings on cellular allografts have been extended to vascularized organ allografts.(ABSTRACT TRUNCATED AT 250 WORDS)
Monozygotic twins with Crohn’s disease and ulcerative colitis: a unique case report
Authors: N P Breslin, A Todd, C Kilgallen, C O’Morain
Journal: Gut (1997)

Background —A large number of monozygotic and dizygotic twin pairs with inflammatory bowel disease have been reported. To date no twin pair has developed phenotypically discordant inflammatory bowel disease. This case report is the first documented occurrence of discordant inflammatory bowel disease occurring in monozygotic twins. Case report —Twenty two year old identical male twins presented within three months of each other with inflammatory bowel disease that proved to be discordant in overall disease type, disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time of testing while twin 2 (Crohn’s disease) was ANCA positive. Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previously associated with extensive colitis. Conclusion —This case report confirms the important role played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undetermined environmental agents in dictating disease expression and phenotype.
Fine specificity of alloimmune cytotoxic T lymphocytes directed against H-2K. A study with Kb mutants.
Authors: C J Melief, L P de Waal, M Y van der Meulen, R W Melvold, H I Kohn
Journal: The Journal of Experimental Medicine (1980)

The fine specificity of alloimmune cytotoxic T lymphocytes (CTL) was investigated in CTL responses across the smallest known H-2 differences, those based on mutation at a single H-2 locus. CTL were generated in all possible mixed lymphocyte culture (MLC) combinations among seven H-2Kb mutants and the mouse strain of origin, C57BL/6 (B6-H-2b). CTL were also generated in all F1 hybrid responder/homozygous stimulator-cell combinations among four Kb mutants and B6-H-2b. CTL activity was measured in cell-mediated lympholysis (CML) against target cells from all Kb mutants and B6-H-2b. Cross-reactivity against targets other than the MLC stimulator was extensive and led to the distinction of 64 CML target determinants. Two Kb mutants (B6-H-2bm6 and B6.C-H-2bm9) showed identical typing for all 64 CML determinants. CML reactions after MLC between these two haplotypes were mutually negative. The mutants B6-H-2bm3 and B6.C-H-2bm11 showed identical typing for 47 of the 64 determinants. Their close relationship is in agreement with the finding that H-2bm3 anti-H-2bm11 CTL were the only ones that exclusively lysed target cells of stimulator-cell genotype. On the basis of CML typing, the sequence of relatedness of the mutants with H-2b is as follows: bm6/bm9-bm10-bm3-bm1-bm11, bm6/bm9 being the closest to, and bm11 the most distant from H-2b. The extensive cross-reactivity of alloimmune CTL appears to reflect immunogenetic complexity rather than lack of specificity. Comparison with other reports supports the notion that the system of Kb CML determinants, recognized by alloimmune CTL, is at least partially overlapping with the H-2Kb specificity repertoire involved in the associative T cell recognition of virus-infected cells.