tbuckley/cabot-search huggingface dataset:
Ethics Challenges in Forensic Psychiatry and Psychology Practice
Authors: Darren L. Lish
Journal: American Journal of Psychiatry (2018)

The field of ethics involves systematizing, defending, and recommending concepts of right and wrong behavior.The practice of forensic psychiatry and psychology has been described at times as an ethical minefield, as competing obligations at the interface of the justice and health care systems produce challenges regarding what is the "right" behavior and call for an ethical framework for guiding practice in this arena.In this book, Dr.
Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies
Authors: A. F. Behndig, Robert Linder, Jamshid Pourazar, A. Lindberg, Anders Blomberg
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies
Surveillance on speed: Being aware of infectious diseases in migrants mass accommodations - an easy and flexible toolkit for field application of syndromic surveillance, Germany, 2016 to 2017
Authors: Navina Sarma, Alexander Ullrich, Hendrik Wilking, Stéphane Ghozzi, Andreas K. Lindner, Christoph Weber, Alexandra Holzer, Andreas Jansen, Klaus Stark, Sabine Vygen-Bonnet
Journal: Eurosurveillance (2018)

Europe received an increased number of migrants in 2015. Housing in inadequate mass accommodations (MA) made migrants prone to infectious disease outbreaks. In order to enhance awareness for infectious diseases (ID) and to detect clusters early, we developed and evaluated a syndromic surveillance system in three MA with medical centres in Berlin, Germany. Healthcare workers transferred daily data on 14 syndromes to the German public health institute (Robert Koch-Institute). Clusters of ID syndromes and single cases of outbreak-prone diseases produced a signal according to a simple aberration-detection algorithm that computes a statistical threshold above which a case count is considered unusually high. Between May 2016-April 2017, 9,364 syndromes were reported; 2,717 (29%) were ID, of those 2,017 (74%) were respiratory infections, 262 (10%) skin parasites, 181 (7%) gastrointestinal infections. The system produced 204 signals, no major outbreak was detected. The surveillance reinforced awareness for public health aspects of ID. It provided real-time data on migrants' health and stressed the burden of non-communicable diseases. The tool is available online and was evaluated as being feasible and flexible. It complements traditional notification systems. We recommend its usage especially when laboratory testing is not available and real-time data are needed.
Nano-targeted relaxin impairs fibrosis and tumor growth in pancreatic cancer and improves the efficacy of gemcitabine in vivo
Authors: Deby F. Mardhian, Gert Storm, Ruchi Bansal, Jai Prakash
Journal: Journal of Controlled Release (2018)

Cancer-associated fibroblasts (CAFs), are the key effector cells in pancreatic ductal adenocarcinoma (PDAC), known to induce tumor growth and progression. Pancreatic stellate cells (PSCs) are the precursors of CAFs in PDAC that secrete abundant extracellular matrix, growth factors and cytokines. In this study, we targeted human relaxin-2 (RLX), an endogenous hormone, to PSCs to inhibit their differentiation into CAF-like myofibroblasts. RLX significantly inhibited TGF-β induced PSCs differentiation by inhibiting pSmad2 signaling pathway. In vitro in primary human PSCs (hPSCs), treatment with RLX dose-dependently inhibited the migration, contraction, and protein expression of alpha smooth muscle actin and collagen I These data demonstrate that RLX can regulate hPSCs activation in vitro. However, RLX has several drawbacks i.e. poor pharmacokinetics and systemic vasodilation, that limits its preclinical and clinical application. Thus, we designed and successfully synthesized a nanoparticle system by chemically conjugating RLX to superparamagnetic iron oxide nanoparticle (SPION) to improve its pharmacokinetics. Interestingly, we found RLX-SPION to be more efficacious compared to free RLX in vitro. Significantly, we observed RLX-SPION retarded the tumor growth by itself and also potentiated the effect of gemcitabine in a subcutaneous co-injection (Panc1 and hPSCs) tumor model. The treatment resulted in significant inhibition in tumor growth, which was attributed to reduced collagen I (ECM), desmin (hPSC marker) and CD31 (endothelial marker) expression. In contrast, free RLX showed no significant effects. Altogether, this study presents a novel therapeutic approach against tumor stroma using RLX-SPION to achieve an effective treatment against pancreatic tumor.
Apixaban for End-Stage Kidney Disease
Authors: Elaine M. Hylek
Journal: Circulation (2018)

Article, see p 1519 T he use of vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) among patients dependent on dialysis remains controversial.In this population, VKAs are associated with higher rates of major bleeding, particularly intracranial hemorrhage, and difficulty maintaining the international normalized ratio in the therapeutic range.A recent meta-analysis of 12 observational studies totaling 17 380 patients on hemodialysis (4010 of whom received VKAs) reported a nonsignificant reduction in the risk of ischemic stroke associated with VKAs (hazard ratio [HR], 0.74; 95% CI, 0.51-1.06),an increase in total bleeding risk (HR, 1.21; 95% CI, 1.03-1.43),and a numeric near doubling of the risk for hemorrhagic stroke (4 studies; HR, 1.93; 95% CI, 0.93-3.98). 1 In addition to the lack of convincing efficacy and more concerning harm, warfarin has been implicated in the accelerated decline of renal function either through parenchymal microbleeds in the setting of excessive anticoagulation or vascular calcifications that result from its inhibition of the vitamin K cycle and γ-carboxylation of matrix Gla protein. 2,3 Alternatives to VKAs are needed for this medically complex group of patients.Randomized trials to date of apixaban versus warfarin for AF excluded patients with severe and end-stage kidney disease, calculated creatinine clearance <25 mL per minute. 4,57][8] The recommended dose of apixaban was 5 mg twice daily with a reduction in dose to 2.5 mg twice daily for either ≥80 years of age or body weight ≤60 kg.The expectation or hope was that the favorable results of the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) would be translated to patients with AF dependent on dialysis, specifically less major hemorrhage, less intracerebral hemorrhage, and lower mortality compared to VKAs.Rates of major bleeding among patients enrolled in the ARISTOTLE trial were 2.13% per year in the apixaban group compared with 3.09% per year in the warfarin group (HR, 0.69; 95% CI, 0.60-0.80).In this issue of Circulation, Siontis et al 9 report their findings from a retrospective study of the use of apixaban versus warfarin among Medicare patients with AF identified in the US Renal Data System.Given the nonrandomized design, cohorts were matched using a prognostic score with patient factors derived from Medicare claims data.Drug exposure was determined using serial prescription refill data from Medicare Part D. Prespecified outcomes were determined from International Classification of Disease 9 and 10 codes in the primary or secondary diagnosis position of inpatient claims data.Bleeding was considered major if associated with
A novel long noncoding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by binding to YBX1
Authors: Erbao Zhang, Xuezhi He, Chongguo Zhang, Jun Su, Xiyi Lu, Xinxin Si, Jinfei Chen, Dandan Yin, Liang Han, Wei De
Journal: Genome biology (2018)

Recently, increasing evidence shows that long noncoding RNAs (lncRNAs) play a significant role in human tumorigenesis. However, the function of lncRNAs in human gastric cancer remains largely unknown.By using publicly available expression profiling data from gastric cancer and integrating bioinformatics analyses, we screen and identify a novel lncRNA, HOXC-AS3. HOXC-AS3 is significantly increased in gastric cancer tissues and is correlated with clinical outcomes of gastric cancer. In addition, HOXC-AS3 regulates cell proliferation and migration both in vitro and in vivo. RNA-seq analysis reveals that HOXC-AS3 knockdown preferentially affects genes that are linked to proliferation and migration. Mechanistically, we find that HOXC-AS3 is obviously activated by gain of H3K4me3 and H3K27ac, both in cells and in tissues. RNA pull-down mass spectrometry analysis identifies that YBX1 interacts with HOXC-AS3, and RNA-seq analysis finds a marked overlap in genes differentially expressed after YBX1 knockdown and those transcriptionally regulated by HOXC-AS3, suggesting that YBX1 participates in HOXC-AS3-mediated gene transcriptional regulation in the tumorigenesis of gastric cancer.Together, our data demonstrate that abnormal histone modification-activated HOXC-AS3 may play important roles in gastric cancer oncogenesis and may serve as a target for gastric cancer diagnosis and therapy.
Escorting α-globin to eNOS: α-globin–stabilizing protein paves the way
Authors: Adam C. Straub, Mark T. Gladwin
Journal: Journal of Clinical Investigation (2018)

In the vascular wall, endothelial nitric oxide synthase (eNOS) produces NO to regulate peripheral vascular resistance, tissue perfusion, and blood pressure. In resistance arteries, eNOS couples with α-globin and, through chemical reactions, modulates NO diffusion needed for vascular smooth muscle relaxation. While α-globin protein alone is known to be unstable, the mechanisms that enable α-globin protein expression remain elusive. Here, Lechauve et al. report that arterial endothelium expresses α hemoglobin-stabilizing protein, which acts as a critical chaperone protein for α-globin expression and vascular function.
Use of intrauterine device and ovarian cancer risk
Authors: Kathryn L. Terry, Linda Titus-Ernstoff, Olivera J. Finn, Daniel W. Cramer
Journal: Cancer Research (2006)

472  Introduction There is considerable evidence that the use of an intrauterine device (IUD) is associated with a decreased risk for endometrial cancer and some data that it may also lower ovarian cancer risk. The latter data indicate that IUD use may be part of a set of exposures which might lower ovarian cancer risk by inducing an inflammatory reaction in tissues that express the surface gylcoprotein and tumor antigen MUC1, exposing an unglycosylated form of MUC1 to immune recognition, and leading to the formation of protective anti-MUC1 antibodies. In this abstract, we examine the association between IUD use and ovarian cancer risk in a larger case-control data set and in greater detail than in our initial presentation of this association. Methods These data are from two phases of an ongoing population based ovarian cancer case control study. We identified ovarian cancer cases through hospital tumor boards and statewide cancer registries in New Hampshire and eastern Massachusetts between 1992 and 2003. We identified controls through a combination of random digit dialing, town book selection, and use of drivers9 license lists. We enrolled a total of 1231 epithelial ovarian cancer cases and 1244 controls. We interviewed all participants in person on a variety of reproductive and lifestyle characteristics. Anti-Muc1 antibodies were measured against a synthetic 100-mer MUC1 peptide corresponding to five tandem repeats of the MUC1 polypeptide core tandem repeat region in controls only from phase II. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. Risk for ovarian cancer associated with various descriptors of IUD use was calculated for all ovarian cancer cases and various histologic subtypes. Likelihood of antibodies (restricted to the phase 2 controls) was also assessed by the same descriptors of IUD use. Results Overall we observed an inverse association between IUD use and ovarian cancer risk (OR = 0.71, 95% CI: 0.56, 0.89). The association was attenuated when we additionally adjusted for parity, tubal ligation, and oral contraceptive use (covariate-adjusted OR= 0.86, 95% CI: 0.68, 1.08). Duration of IUD use had a U-shaped association with ovarian cancer risk. Women who had an IUD for  7 years had 0.72, 0.66, 0.61, and 0.84 times the risk of ovarian cancer as a women who never had an IUD, respectively. Similarly, the protective effect of IUD use was attenuated for women in the oldest age group at first IUD placement (>30 years). In general the likelihood of antibodies tracked in a manner similar to the odds ratios. Examination by histologic type revealed the strongest association to pertain to endometrioid tumor types (OR=0.40, 95% CI: 0.22, 0.71). Conclusions IUD use reduces the risk of ovarian cancer, especially for endometrioid types of ovarian cancer. The protective effect may be attenuated with older age at first use and longer lifetime duration of use.
Unraveling the Cause of Anuria Post Kidney Transplantation by Renal Scintigraphy
Authors: Ciska-Anne Van Keerberghen, Maarten Naesens, Olivier Gheysens, Ina Jochmans, Jacques Pirenne, Karolien Goffin
Journal: Clinical Nuclear Medicine (2018)

Abstract A dynamic renal scintigraphy is widely used after renal transplantation to evaluate transplant function and possible complications. We report the case of a 27-year-old man with persisting anuria after kidney transplantation. A renal scintigraphy using 99m Tc-ethylenedicysteine followed by SPECT/CT of the abdomen was performed showing tracer accumulation in the colon without any activity in the bladder, as a result of ureter reimplantation onto the sigmoid instead of onto the previously reconstructed bladder. Renal scintigraphy identified the cause and localization of the urinary leak, which led to immediate surgical reimplantation of the ureter onto the augmented bladder with onset of diuresis.
FRI0515 Effectiveness of direct-acting antiviral therapy on cryoglobulinemia associated with hepatitis c virus
Authors: S. Zegarra Mondragon, J.R. Quiñones, J. Bachiller Corral, M. Vazquez Diaz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hepatitis C virus (HCV) is the most frequent cause of mixed cryoglobulinemia, reaching up to 30%–50% of patients with chronic infection. Cryoglobulinemia can manifest as arthritis, vasculitis, hypocomplementemia, peripheral neuropathy or renal involvement. A new direct-acting antiviral therapy against HCV is available for 4 years, and it achieves a sustained virologic response, close to the definition of cure for this viral infection. <h3>Objectives</h3> To evaluate the effectiveness of treatment with direct-acting antivirals in HCV- associated cryoglobulinemia and its clinical manifestations. <h3>Methods</h3> In a retrospective cross-sectional observational study, we enrolled all consecutive patients with positive serum cryoglobulins and HCV infection with high viral load. Patients with or without associated rheumatological or systemic manifestations were included. All of them were treated with a combination of the new antivirals: sofosbuvir +ledipasvir, or ombitasvir +paritaprevir + ritonavir+dasabuvir; during 8 to 24 weeks, between January 2014 and December 2016. Post treatment blood studies were made in all patients during the first year. Seronegativization of cryoglobulins and improvement of associated clinical manifestations after treatment were analysed. <h3>Results</h3> Thirty patients were included, 24 (80%) women. The median age of was 61.4 years. The HCV genotype: 1B in 76.6%, 1A in 16.6% and type 4 in the rest. Eighteen (60%) patients had systemic manifestations: 11 had joint involvement, 11 hypocomplementemia, 8 had leukocytoclastic vasculitis or skin ulcers, 5 Raynaud's phenomenon, 5 sensory-motor peripheral neuropathy, 3 renal involvement with glomerulonephritis, 2 Sjögren's syndrome and 1 patient with autoimmune hemolytic anaemia. The sustained viral response was achieved in 29 patients (96.6%), maintaining an undetectable viremia after finishing the treatment. Cryoglobulins were negativized in 22 (73%) of patients, and complement was normalised in 36% of those who had hypocomplementemia before treatment. There was a clinical improvement in 54.2% of patients with previous associated rheumatologic or systemic manifestations. The artrhitis and cutaneous vasculitis had better response than the other manifestations. No significant correlations were found between the serological and clinical responses. <h3>Conclusions</h3> Direct-acting antiviral therapy is very effective against HCV infection. It is also useful for the treatment of mixed cryoglobulinemia, negativizing cryoglobulins in almost 3/4 of the cases, and with clinical response in more than half of the patients, being more favourable in the cases of joint involvement and cutaneous vasculitis. <h3>Disclosure of Interest</h3> None declared
Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial
Authors: Charlotte S Loozen, Hjalmar C van Santvoort, Peter van Duijvendijk, Marc GH Besselink, Dirk J Gouma, Grard AP Nieuwenhuijzen, Johannes C Kelder, Sandra C Donkervoort, Anna AW van Geloven, Philip M Kruyt, Daphne Roos, Kirsten Kortram, Verena NN Kornmann, Apollo Pronk, Donald L van der Peet, Rogier MPH Crolla, Bert van Ramshorst, Thomas L Bollen, Djamila Boerma
Journal: BMJ (2018)

To assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis.Multicentre, randomised controlled, superiority trial.11 hospitals in the Netherlands, February 2011 to January 2016.142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more.The primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year.The trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and the median length of hospital stay was longer (9 days v 5 days, P<0.001).Laparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis.Dutch Trial Register NTR2666.
The Ross Operation Comes of Age
Authors: Magdi Yacoub
Journal: JAMA Cardiology (2018)

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Abstract 12791: Heart Rate at One Minute Impact Neonatal Resuscitation & Clinical Outcomes in Infants
Authors: Vasantha H Kumar, Annie Skrobacz, Changxing Ma
Journal: Circulation (2016)

Introduction: Fetal hypoxia from intrapartum events can lead to absent heart rate (HR) or bradycardia (BC) at birth requiring neonatal resuscitation. Neonatal resuscitation guidelines do not differentiate infants with BC (HR<100/min) from absent HR at birth; Hypothesis: As HR is the primary determinant of resuscitation, we hypothesize that infants with no HR at 1min [determined by Apgar score (AS) of 0 @ 1min] would require more extensive resuscitation with worse clinical outcomes compared to infants with BC at 1min (determined by AS=1 @ 1 min). Methods: A retrospective analysis was done on infants born from 1/1/00 - 12/31/15 with AS of 0 (ASZ grp) or AS of 1 (ASN grp) at 1min. Patient demographics, resuscitation characteristics & clinical outcomes were analyzed in both the groups. Descriptive statistics & logistic procedure was performed (SAS System, Cary, NC). Results: Table.1 summarizes the resuscitation characteristics analyzed. AS were different between the groups over time (Fig.1). Death was higher ...