tbuckley/cabot-search huggingface dataset:
Circulating ‘lncRNA OTTHUMT00000387022’ from monocytes as a novel biomarker for coronary artery disease
Authors: Yue Cai, Yujia Yang, Xiongwen Chen, Genze Wu, Xiaoqun Zhang, Yukai Liu, Junyi Yu, Xinquan Wang, Jinjuan Fu, Chuanwei Li, Pedro A. Jose, Chunyu Zeng, Lin Zhou
Journal: Cardiovascular Research (2016)

Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be established whether or not circulating lncRNAs can serve as biomarkers of CAD. Using a microarray-based lncRNA expression profiling, we found 86 lncRNAs that were differentially expressed in circulating peripheral blood monocytes and plasma from 15 CAD patients and 15 control subjects. After choosing a consistent criterion (average normalized intensity ≥7 with significance <0.005) and confirmed by quantitative PCR, only three lncRNAs (CoroMarker, BAT5, and IL21R-AS1) remained as candidate CAD biomarkers. Using the analysis of area under the curve (AUC) of the receiver-operating characteristic in another pilot group and another larger cohort, CoroMarker was found to be the best candidate biomarker for CAD with an AUC of 0.920 and 95% confidence interval of 0.892-0.947. CoroMarker was independent from known CAD risk factors and other cardiovascular diseases. In a prospective study, we found that the sensitivity and specificity of CoroMarker were 76 and 92.5%, respectively. Functional enrichment analysis showed CoroMarker to be clustered with genes positively associated with signal transduction, transmembrane transport, synaptic transmission, and innate immunity and negatively associated with inflammation. These findings were validated in THP-1 cells; CoroMarker siRNA treatment decreased the concentrations of proinflammatory cytokines [interleukin (IL)-1β, IL-6, and tumour necrosis factor α] in the culture medium. The present study suggests that CoroMarker is a novel and specific biomarker of CAD.
Netherlands tops European healthcare index
Authors: Rory Watson
Journal: BMJ (2016)

The Netherlands has been ranked as the most consumer friendly healthcare system in Europe in the latest annual Euro Health Consumer Index (EHCI), scoring 916 points out of a possible 1000.1 The UK came in 14th position—one place below the Czech Republic—in the survey of 35 countries.

The index, which began in 2005, ranks countries on 48 indicators in areas such as patient rights and information, access to care, …
An evaluation of cediranib as a new agent for alveolar soft part sarcoma (ASPS).
Authors: S. Kummar, A. Strassberger, A. Monks, S. P. Ivy, I. B. Turkbey, P. L. Choyke, S. M. Steinberg, R. Simon, J. H. Doroshow, L. J. Helman
Journal: Journal of Clinical Oncology (2011)

10001 Background: ASPS accounts for < 1% of soft tissue sarcomas. ASPS is associated with the t(X;17)(p11;q25) translocation, ASPL-TFE3 fusion protein. There is no effective systemic treatment for metastatic ASPS. Cediranib (C) is a potent oral inhibitor of vascular endothelial growth factor receptor (VEGFR-1,-2,-3) tyrosine kinases. Methods: Phase II trial to determine the response rate (PR + CR) of patients (pts) with ASPS to C; assess the effect of C on tumor angiogenesis using DCE-MRI and proliferation using FDG-PET; and compare gene expression profiles in pre- and post-treatment tumor biopsies. Eligible pts (≥ 18 years) had documented metastatic ASPS; ECOG 0-2; and adequate bone marrow, hepatic, and renal function. Pts received 30 mg C by mouth, once a day in 28-day cycles. Tumor response was assessed using RECIST 1.1. Biopsies were performed at baseline and after 3-5 days of treatment. Results: A total of 36 pts have been enrolled since July 2009; age range 19-59 yrs. Twenty-eight pts are evaluable for response (completed ≥ 2 cycles); 12 pts had PR (43%), 4 pts had > 20% reduction in target lesions, and 6 others (with sufficient follow-up) were stable at 6 months, for a disease control rate (DCR) at 6 months (PR + SD) of 22/28=78%. Common toxicities (grade ≥ 2) included transaminitis, hypertension, diarrhea, tumor pain, and proteinuria. DCE-MRI and PET showed reduction in tumor blood flow and SUVs of target lesions, respectively. Expression profiles (Affymetrix U133 plus 2 arrays) from pre- and post-treatment biopsies (5 pts) revealed C significantly (p < 0.01) modulated expression of approximately 1000 genes across the cohort. Reproducible down-regulation of certain pro-angiogenic or endothelial-specific genes, including FLT1 and KDR (but not FLT4), ANGPT2 (angiopoietin 2, but not ANGPT1), and ESM1 (endothelial specific molecule 1), and upregulation of genes involved in the inflammatory response, were observed. Conclusions: C has substantial single-agent activity in ASPS, with a > 40% response rate and a DCR of 78%. Gene expression profiling indicates an early effect of treatment on the angiogenesis pathway, concurrent with induction of a modest inflammatory response. Patient accrual is ongoing. Funded by NCI Contract No. HHSN261200800001E.
Reducing Indoor Tanning—An Opportunity for Melanoma Prevention
Authors: Gery P. Guy, Meg Watson, Lisa C. Richardson, Boris D. Lushniak
Journal: JAMA Dermatology (2016)

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Hydrogen gas inhalation ameliorates direct lung injury and indirect contralateral lung injury in a murine aspiration pneumonia model
Authors: Yuki Nishikawa, Kenichi Kokubo, Ryuji Hataishi, Toshihiro Shinbo, Minoru Hirose, Noriyuki Masuda, Hirosuke Kobayashi
Journal: European Respiratory Journal (2012)

[Aim] Accumulated leukocytes in the lungs produce several inflammatory cytokines and reactive oxygen and nitrogen species (ROS and RNS), which will induce ALI/ARDS. It has been reported that hydrogen (H2) gas has potential as eliminating highly reactive ROS and RNS. The aim of the present study was to clarify the effect of H2 gas inhalation on direct lung injury and indirect contralateral lung injury.

[Methods] Anesthetized C57BL/6J male mice were intubated, and 5 μl of 0.1N HCl was administered to the left lung. Mice were randomly grouped to saline treatment instead of HCl (Sham), HCl-treatment (HCl), and 2% H2 gas inhalation with the HCl-treatment (HCl-H2) groups. Extra-vascular wet to dry ratio, myeloperoxidase (MPO) activity in the treated left lung and untreated right lung, and serum IL-6 level were evaluated 4 hrs after the treatment.

[Results] This aspiration pneumonia model induced direct lung injury and contralateral lung injury. The extra-vascular wet to dry ratios of the left and right lungs were significantly larger in the HCl group compared to the Sham and the HCl-H2 group (n=10, P <0.01), suggesting that H2 gas was effective not only in the direct injured lung but also in contralateral lung. MPO activity of the left lung was also significantly larger in the HCl group compared to those in the Sham and HCl-H2 groups (n=3, P <0.05). IL-6 was increased in the HCl group, but it did not statistically differ to the level in the HCl-H2 group, suggesting H2 gas did not interfere in the cytokine production.

[Conclusion] H2 gas inhalation ameliorated direct lung injury and indirect contralateral lung injury in a murine aspiration pneumonia model.
간세포암종의 치료에 있어 고주파 소작술과 수술적 절제의 비교
Authors: 조창민 ( Chang Min Cho ), 탁원영 ( Won Young Tak ), 권영오 ( Young Oh Kweon ), 김성국 ( Sung Kook Kim ), 최용환 ( Yong Hwan Choi ), 황윤진 ( Yoon Jin Hwang ), 김양일 ( Yang Il Kim )
Journal: Clinical and Molecular Hepatology (2005)

목적: 간암의 치료법으로 수술적 절제가 비교적 양호한 완치의 기회를 제공하는 치료법으로 인정받고 있으나, 잔여 간기능의 여부에 따라 일부에서만 적응이 되어 제한된 환자에서 치료의 기회가 주어진다. 또한, 치료 후 잔여 간에서 간암의 재발이 빈번히 발생하고 있다. 최근 시술되는 고주파 소작술은 종양의 완전 괴사율이 높고 국소 재발률이 낮아 수술적 절제에 버금가는 치료 성적이 기대된다. 최근에 간암의 국소적인 치료로 고주파 소작술이 많이 보고되고 있으나,
Decompensated alcohol related liver disease: acute management
Authors: Stuart McPherson, Michael R Lucey, Kieran J Moriarty
Journal: BMJ (2016)

#### What you need to know

Alcohol related liver disease (ARLD) and liver cirrhosis are complications of long term excessive alcohol use and occur in 10-20% of chronic, heavy drinkers.1 2 Complications, including hepatic decompensation, variceal bleeding, and hepatocellular carcinoma, reduce life expectancy.1 3 Since 1970, there has been a 400% increase in liver related (mainly alcohol related) deaths across all ages in the UK (fig 1⇓).4 5 Liver disease is now the fifth commonest cause of death in the UK. The average age of death from ARLD is 59 years.6



Fig 1  Standardised mortality data for major causes of death in UK, 1970-2010. Reproduced with permission of Nick Sheron



In a report of UK hospitals only 47% of patients received “good” hospital care.7 This review provides guidance on the management of patients with decompensated ARLD, focusing on the first 24 hours after hospital admission.

Figure 2⇓ provides a summary of the clinical course of ARLD. Decompensation of cirrhosis occurs when liver function deteriorates, and the disease presents with jaundice …
HER-2 as a potential target for rectal cancer treatment: Positivity rate in patients of the CAO/ARO/AIO-94 and -04 trial.
Authors: Lena-Christin Conradi, Marcus Storch, Iris Nagelmeier, Hanna Styczen, Hendrik A. Wolff, Jochen Gaedcke, Thilo Sprenger, Kia Homayounfar, Michael Ghadimi, Josef Rüschoff, Tim Beissbarth, Claus Rödel, Torsten Liersch
Journal: Journal of Clinical Oncology (2015)

585 Background: Members of the EGFR family are established targets for specific therapy approaches in a variety of malignancies. Especially HER-2 has been targeted for more than a decade in breast cancer and more recently in gastric cancer and adenocarcinomas of the gastroesophageal junction. Applying the HER-2 scoring algorithm established in gastric cancer we here investigated HER-2 expression in rectal cancer using FFPE tumor samples from both large trials of the German Rectal Cancer Study Group (GRCSG)-(CAO/ARO/AIO-94 and -04). Methods: Overall, FFPE samples from 839 patients from 63 sites were available. All patients received standardized multidisciplinary treatment according to protocols of the phase-III-trials. 104 patients were treated by primary tumor resection followed by adjuvant CRT, all other patients (n=547) had preoperative CRT either with concomitant 5-FU mono therapy (n=329, 60.1%) or a combination of 5-FU and oxaliplatin (n=218, 39.9%). The HER-2-status was determined in resection specimens using immunohistochemistry scoring and S-ISH-amplification detection. Tumors with IHC 3+ or S-ISH ratios of ≥2.2 were classified HER-2-positive; these results were correlated with clinicopathological parameters (e.g., resection status, nodal-status ((y)pN)), time to recurrence (TTR) and cancer specific survival (CSS). Results: Positive HER-2-status was found in 13.8% of resected specimens. Positivity rate in primary resection specimens was 11.5% (n=12), while after preoperative CRT 13.2% (n=78 ) patients showed a HER-2 positive tumor; 13.1% (n=43) after 5-FU mono and 13.3% (n=35) after combination of 5-FU and oxaliplatin. There was no prognostic difference according to the HER-2 status regarding TTR (p=0.90) and CSS (p=0.68) overall. However in the 5-FU mono subgroup the HER-2 expression was of prognostic relevance as measured by CSS (p=0.034). Conclusions: Analysis of 839 patients from the GRCSG validated a relevant HER-2 amplification of 13.8% in samples of rectal adenocarcinoma. Besides its potential as an independent predictor of survival HER-2 may represent a promising target for innovative therapies and should be further assessed.
Disruption Of PML Nuclear Bodies Cooperates In The Pathogenesis Of Acute Promyelocytic Leukemia
Authors: Eva Moravcsik, Melanie Joannides, Edwige Voisset, Eva Wessel Stratford, Bernd B. Zeisig, Jo Morris, Ruth Densham, Chris Palgrave, Gordon Stamp, Emma Nye, Robert K. Hills, Paolo Salomoni, Chi Wai Eric So, Scott C. Kogan, Ellen Solomon, David Grimwade
Journal: Blood (2013)
Hepatitis C Drugs Top State Medicaid Pharmaceutical Expenditures
Authors: Rita Rubin
Journal: JAMA (2016)

Sovaldi, Gilead Sciences’ drug for treatment of hepatitis C, ranked among the top 5 pharmaceutical expenditures for 33 states’ Medicaid programs in 2014, according to data released recently by 2 members of the Senate Finance Committee (http://1.usa.gov/1Z0I2hM).
Abstract 140: Effect of Transendocardial Autologous Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and Restore Cardiac Function in a Heart Failure Swine Model
Authors: Viky Y Suncion, Vasileios Karantalis, Luiza L Bagno, Frederic McCall, Bo Wang, Samuel Golpanian, Jose E Rodriguez, Marcos Rosado, David Valdes, Samirah Gomes, Samirah Gomes, Jose Da Silva, Courtney Premer, Azorides Morales, Azorides Morales, Wayne Balkan, Muzammil Mushtaq, Juan Pablo Zambrano, Alan W Heldman, Joshua M Hare
Journal: Circulation Research (2014)

Background: A cell combination of human mesenchymal stem cells (MSCs) and c-kit+ cardiac stem cells (CSCs) improves left ventricular (LV) performance to a greater degree than MSCs alone in post myocardial infarction swine. To advance the development of cell combination therapy, we administered autologous swine cells, and tested the hypothesis that transendocardial autologous CSCs/MSCs produces greater improvement of performance than MSCs in a rigorous model of heart failure due to post infarct LV remodeling. Methods: Gottingen mini-swine (n=28) underwent LAD coronary artery occlusion followed by reperfusion, and allowed to undergo LV remodeling for 90 days. Autologous MSCs were amplified from bone marrow and CSCs from right ventricular biopsies in each swine, and injections of either CSC/MSC combo (1M/200M, n=7), MSCs (200M, n=7), or placebo (Plasmalyte, n=6) were injected to the infarct-border zone via the NOGA system. Cardiac MRI and pressure volume loops were obtained before and after therapy. Results: Both cell groups had substantially reduced scar size (Combo –37.2.9± 5.4% vs MSCs –38.8±7.5% vs placebo −7.2±6.3, P=0.0001) and increased viable tissue (Combo +30.9±7% vs MSCs +41.8±10.5% vs placebo +7.7±4.5, P&lt;0.0001) relative to placebo. Ejection Fraction (EF) improved only in the Combo group (Combo +7.0±2.8 vs MSCs +3.4±1.3 vs placebo +1.2±1.6 EF units, P=0.04). Accompanying this EF restoration was a substantial improvement in the Combo group in stroke volume (Combo +47.2±11.1% vs MSCs +32.6±12.0% vs placebo +10.8±4.5, P&lt;0.0001), cardiac output (Combo +35.9±7.6% vs MSCs 41.9±26.5% vs placebo −16.4±6.6%, P=0.01) and diastolic strain rate (Combo +18.9±8.6% vs MSCs 14.0±8.8% vs placebo −14.9±9.5%, P=0.03). Conclusions: Combination cell therapy and MSCs alone dramatically reduce scar size in a swine model of chronic ischemic cardiomyopathy. In contrast, combination therapy has much greater impact on functional recovery, increasing EF to [near normal] levels. These findings illustrate that interactions between ckit+ CSCs and MSCs result in substantial enhancement in cardiac performance, establish the safety of autologous cell combination strategies, and support the development of an advanced second generation cell therapeutic product.
A new method that simultaneously aligns and reconstructs ancestral sequences for any number of homologous sequences, when the phylogeny is given.
Authors: J Hein
Journal: Molecular Biology and Evolution (1989)

Among the fundamental problems in molecular evolution and in the analysis of homologous sequences are alignment, phylogeny reconstruction, and the reconstruction of ancestral sequences. This paper presents a fast, combined solution to these problems. The new algorithm gives an approximation to the minimal history in terms of a distance function on sequences. The distance function on sequences is a minimal weighted path length constructed from substitutions and insertions-deletions of segments of any length. Substitutions are weighted with an arbitrary metric on the set of nucleotides or amino acids, and indels are weighted with a gap penalty function of the form gk = a + (bxk), where k is the length of the indel and a and b are two positive numbers. A novel feature is the introduction of the concept of sequence graphs and a generalization of the traditional dynamic sequence comparison algorithm to the comparison of sequence graphs. Sequence graphs ease several computational problems. They are used to represent large sets of sequences that can then be compared simultaneously. Furthermore, they allow the handling of multiple, equally good, alignments, where previous methods were forced to make arbitrary choices. A program written in C implemented this method; it was tested first on 22 5S RNA sequences.
Abstract 209: Resistin Regulates Dynamin-Related Protein 1, a Mitochondrial Fission Protein in Vascular Smooth Muscle Cells
Authors: Takara A Scott, Sharon Francis
Journal: Circulation Research (2013)

Recent studies indicate increased mitochondrial fission and organ dysfunction in models of obesity. While the mechanisms for this morphological alteration are not completely understood it is likely that the altered adipokine profile that occurs during obesity may play a permissive role in enhanced mitochondrial fragmentation. In this study, we investigated the role of resistin, a pro-inflammatory adipokine that is elevated in the plasma of obese individuals, on regulation of the mitochondrial fission protein, dynamin-related protein 1(DNM1L) in vascular smooth muscle cells (VSMCs). We hypothesized that serum and glucocorticoid inducible kinase 1 (SGK1) plays a role in resistin-induced mitochondrial fission expression in VSMCs. In dose and time response studies, we found that resistin stimulated DNM1L protein levels in both rat and human aortic smooth muscle cells suggesting a role for resistin in regulation of mitochondrial fission. In addition, we observed that resistin enhances expression and activity of SGK1. To determine whether SGK1 regulates resistin-mediated expression of DNM1L, we examined the effect of SGK1 over-expression, or inhibition on resistin-induced expression of DNM1L. Over-expression of wildtype SGK1 potentiated resistin-mediated DNM1L expression, while dominant-negative SGK1 inhibited resistin-mediated expression of DNM1L in human VSMC. In conclusion, we have demonstrated for the first time that SGK1 is a potential downstream mediator of resistin. Interestingly, SGK1 activity has been linked to pathological vascular remodeling in various cardiovascular disease settings. Our data suggests that the elevated plasma levels of resistin that occur in obese individuals may lead to activation of SGK1. This in turn, could exacerbate mitochondrial fragmentation in VSMC and predispose to the development of vascular dysfunction that is evident during obesity. Together with further mitochondrial fission studies, additional elucidation of how resistin also alters components of mitochondrial fusion machinery may uncover novel mechanisms of potential theraputic targets for obesity-mediated vascular dysfunction.
Renal transplantation in the first year of life
Authors: J S Najarian, P S Almond, M Mauer, B Chavers, T Nevins, C Kashtan, A J Matas
Journal: Journal of the American Society of Nephrology (1992)

The treatment of choice for end-stage renal failure within the first year of life is controversial. Between September 1970 and February 1991, we performed 28 kidney transplants (27 primary, 1 retransplant, 23 living donor, 5 cadaver) in infants less than 1 yr of age (mean, 7 +/- 2 months; range, 6 wk to 12 months). The 1-yr patient survival rate for living donor recipients was 100% versus 20% for cadaver recipients (P = 0.0001). The 1-yr graft survival rate for living donor recipients was 96% versus 20% for cadaver recipients (P = 0.001). The 1-yr patient survival rate for cyclosporin A (CSA) recipients (N = 12) was 100% versus 75% for non-CSA recipients (P = 0.03). The 1-yr graft survival rate for CSA recipients was 92% versus 75% for non-CSA recipients (P = 0.08). There was no difference in the number of rejection episodes or serum creatinine levels in CSA versus non-CSA recipients. Compared with pretransplant values, the mean posttransplant standard deviation scores (SDS) for height (N = 18), weight (N = 22), and head circumference (N = 8) improved: height SDS from -1.9 to -1.5 (not significant); weight SDS from -2.5 to 0.6 (P less than 0.0005); head circumference SDS from -2.0 to -0.7 (P = 0.01). Because no other renal replacement therapy can match these results, we conclude that renal transplantation is the treatment of choice for infants with end-stage renal failure.
Screening for Depression in Adults
Authors: Albert L. Siu, Kirsten Bibbins-Domingo, David C. Grossman, Linda Ciofu Baumann, Karina W. Davidson, Mark Ebell, Francisco A. R. García, Matthew Gillman, Jessica Herzstein, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, Douglas K. Owens, William R. Phillips, Maureen G. Phipps, Michael P. Pignone
Journal: JAMA (2016)

DESCRIPTION Update of the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for depression in adults. METHODSThe USPSTF reviewed the evidence on the benefits and harms of screening for depression in adult populations, including older adults and pregnant and postpartum women; the accuracy of depression screening instruments; and the benefits and harms of depression treatment in these populations.POPULATION This recommendation applies to adults 18 years and older.RECOMMENDATION The USPSTF recommends screening for depression in the general adult population, including pregnant and postpartum women.Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.(B recommendation)