tbuckley/cabot-search huggingface dataset:
PTU-182 Specialist Care Of In-patients With Non-variceal Upper Gastrointestinal Bleeding Is Associated With A Significant Shorter Length Of Stay – A Prospective Analysis: Abstract PTU-182 Table 1
Authors: SV Venkatachalapathy, R Bright, G Chung-Faye, P Dubois, I Forgacs, RP Logan, B Hayee
Journal: Gut (2014)

<h3>Introduction</h3> Acute upper gastrointestinal bleeding (UGIB) is a common medical emergency that has a 10% mortality rate,<sup>1</sup> requiring specialist input and management.<sup>2</sup> We conducted a retrospective review last year which showed that the mean length of stay (days) was shorter in the GI group: 5.5 ± 5.7 vs 15.7 ± 20.8 (p = 0.02).<sup>3</sup> We conducted a prospective analysis to assess if the above results held true. <h3>Methods</h3> A prospective review of case-notes (Electronic patient record-EPR) was conducted for all patients admitted to Kings College hospital with suspected UGIB between January and September 2013. Patients were divided as to whether they came immediately under the care of Gastroenterologists (GI) or general physicians (non-GI) after initial evaluation in the Acute Admission Unit. Patients were assigned on the basis of bed availability in a ward-based system. Statistical comparisons were made as appropriate with two tailed t-test or chi- squared test. <h3>Results</h3> 138 patient episodes were reviewed of which 63 and 75 were treated by GI and Non-GI physicians. The two groups were broadly similar in their baseline characteristics. Mean length of stay (days) was significantly shorter in the GI group: 6.6 ± 5.6Vs 10.66 ± 11.3 (p = 0.006). Other comparators are shown in the table. <h3>Conclusion</h3> The length of stay of patients with UGIB is significantly shorter when receiving specialist care. In line with previous reports,<sup>4</sup> we found that the incidence of UGIB was higher in males. Patients managed by GI physicians received less blood transfusion compared to the Non-GI physicians. The time to endoscopy was significantly shorter when receiving specialist care. Mortality rates in both groups compared favourably to the national average. <h3>References</h3> CG141 Scope for improvement: A toolkit for a safer Upper Gastrointestinal Bleeding (UGIB) service. www.bsg.org.uk Venkatachalapathy SV, Grasso N, Hayee B <i>et al., </i>Specialist care of in-patients with non-variceal upper gastrointestinal bleeding is associated with a dramatically shorter length of stay. <i>Gut</i> 2013;62:A10 doi:10.1136 Lanas A, García-Rodríguez LA, Polo-Tomás M <i>et al</i>., <i>Am J Gastroenterol</i> 2009;104:1633-41 <h3>Disclosure of Interest</h3> None Declared.
A Patient with Migrating Polyarthralgias
Authors: Jonathan D. Casey, Daniel H. Solomon, Thomas A. Gaziano, Amy Leigh Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2013)

A 28-year-old woman with an unremarkable medical history presented for evaluation of fatigue and joint pain. She initially noted pain and swelling in her right foot and ankle; these symptoms then improved, but pain in both knees and hips and in her right elbow developed.
Comparison of sun protection modalities in parents and children.
Authors: Laurent Mortier, Philippe Saiag, Caroline Robert, Bruno Sassolas, Christine Lhomel, Celeste Lebbe, Florent Grange
Journal: Journal of Clinical Oncology (2012)

8601 Background: Routine sun protection is recommended to prevent skin cancer. Our aims were to examine and compare, in an observational survey, modalities of sun protection in parents and their children. Methods: This French nationwide observational survey, EDIFICE melanoma, was conducted through phone interviews among a representative sample of 1502 subjects aged ≥ 18 years old, using the quota method. The survey took place shortly after summer, from 28 Sep 2011 to 20 Oct 2011. Results: 1502 subjects were interviewed. Among them 1067 reported that they were sun-exposed (SE) at least ten days per year, 748 were parents, and 319 had no children. Sun protection measures seemed well done both in “parents” and “nonparents” groups: 74% used clothing; 43% used sunscreen, which was regularly renewed in 57% of cases. Sun protection measures used by SE parents for SE children were superior, both qualitatively and quantitatively to those used for themselves, ie 50% of parents reported using clothing, sunglasses and hat for their children vs 23% for themselves. In 87% of cases, parents reported regular re-application of sunscreen for their children vs 44% for themselves. The sunscreen SPF (Sun Protection Factor) was significantly lower for parents than for their children. Such data are in accordance with Buller et al. (Oncol Nurs Forum 1995), but contrast with the findings of Riordan et al. (J Pediatr 2003) with children being significantly less likely to wear sunglasses and to adopt sun avoidance habits than their parents. Conclusions: Sun protection awareness seems globally satisfying in the French population, with no difference between adult parents and nonparents, and is similar to that reported in Germany (Gambicher JEADV 2010), but seems better than in the US (Buller et al. JAAD 2011). Furthermore, French parents use sun protective measures qualitatively and quantitatively more efficiently for their children than for themselves.
Association of Dual-Task Gait With Incident Dementia in Mild Cognitive Impairment
Authors: Manuel M. Montero-Odasso, Yanina Sarquis-Adamson, Mark Speechley, Michael J. Borrie, Vladimir C. Hachinski, Jennie Wells, Patricia M. Riccio, Marcelo Schapira, Ervin Sejdic, Richard M. Camicioli, Robert Bartha, William E. McIlroy, Susan Muir-Hunter
Journal: JAMA Neurology (2017)

Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI.To determine whether a dual-task gait test is associated with incident dementia in MCI.The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016.Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity - dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition.Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (<0.8 m/second) was not associated with progression to dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized.Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI.clinicaltrials.gov: NCT03020381.
Associations of Nasopharyngeal Metabolome and Microbiome with Severity among Infants with Bronchiolitis. A Multiomic Analysis
Authors: Christopher J. Stewart, Jonathan M. Mansbach, Matthew C. Wong, Nadim J. Ajami, Joseph F. Petrosino, Carlos A. Camargo, Kohei Hasegawa
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity.Objectives: To determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis.Methods: We conducted a multicenter prospective cohort study of infants (age <1 yr) hospitalized with bronchiolitis. By applying metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation).Measurements and Main Results: Nasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P < 0.001). Among 254 metabolites identified, a panel of 25 metabolites showed high sensitivity (84%) and specificity (86%) in predicting the use of positive pressure ventilation. The intensity of these metabolites was correlated with relative abundance of Streptococcus pneumoniae. In the pathway analysis, sphingolipid metabolism was the most significantly enriched subpathway in infants with positive pressure ventilation use compared with those without (P < 0.001). Enrichment of sphingolipid metabolites was positively correlated with the relative abundance of S. pneumoniae.Conclusions: Although further validation is needed, our multiomic analyses demonstrate the potential of metabolomics to predict bronchiolitis severity and better understand microbe–host interaction.
Abstract 225: Pulmonary Hypertension Induced Right Ventricle Fibrosis is Associated With Male Gender
Authors: Olga Rafikova, Ruslan Rafikov, Mary L Meadows, Archana Kangath, Stephen M Black
Journal: Circulation Research (2015)

Pulmonary hypertension (PH) is a rare but incurable disease. The primary reason of PH mediated mortality is right ventricle (RV) failure. There is a well-established sexual dimorphism in regard to PH, with females generally associated with higher susceptibility to develop PH, while males possess lower survival rate. We hypothesized that sex difference in PH mediated mortality is associated with sex difference in mechanisms of RV failure development, with males being more prone to develop RV dysfunction. The angioproliferative PH was induced in 8 week old male and female rats by bolus injection of VEGF receptor 2 antagonist, SU5416 (20 mg/kg, s.c.) followed by 4 weeks of exposure to hypoxia (10%±0.5 O2) and 10 weeks of normoxia (21% O2). We found that PH induced a significantly higher mortality in males comparing to females, although the increase in RV peak systolic pressure (RVPSP) was similar in both genders (95.8±13.5 vs. 84.6±18.2; p=0.636; N=5). At the early stage of PH (4 weeks) both males and females had possessed the similar levels of PH induced increase in RV free wall (RVFW) thickness, assessed by Doppler echocardiography. However, starting from 8 week RV hypertrophy continues to progress in males only, while RVFW thickness in females was found to be preserved (RVFW at 12 week, mm: 2.1±0.2 vs. 1.2±0.1; p=0.003; N=5-6). After 14 weeks of study there was a significant impairment of RV relaxation and RV diastolic function in male group only (RV peak diastolic pressure (RVPDP), mmHg: -0.6±0.9 vs. -5.4±0.9; p=0.008; N=4-5). Finally, Masson’s trichrome staining revealed severe fibrosis in the RV of male, but not female rats with PH (fibrotic score: 2.5±0.3 vs. 0.7±0.2; p=0.0007; N=5-6), which was associated with endothelial nitric oxide synthase (eNOS) uncoupling, assessed by measuring caveolin expression (fold male Cont: 0.3±0.003 vs. 1.9±0.3; p=0.002; N=4) and eNOS dependent increase in superoxide generation. We conclude that males with PH have a high risk of mortality due to increased cardiac fibrosis development, which, in turn, leads to RV failure. The severe oxidative stress with subsequent injury of myocardial tissue may be responsible for RV fibrotic changes in males, which are lack of female sex hormones known to exert strong anti-oxidant protection.
Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease
Authors: Yiqiang Zhan, Ida K. Karlsson, Robert Karlsson, Annika Tillander, Chandra A. Reynolds, Nancy L. Pedersen, Sara Hägg
Journal: Circulation Research (2017)

Rationale: Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention. Objective: To examine whether metabolic risk factors for CHD mediate the causal pathway from short TL to increased risk of CHD using a network Mendelian randomization design. Methods and Results: Summary statistics from several genome-wide association studies were used in a 2-sample Mendelian randomization study design. Network Mendelian randomization analysis—an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality—was performed to examine the causal association between telomeres and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D Consortium data were used (case=22 233 and control=64 762) for CHD, and other consortia data were used for metabolic traits (fasting insulin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip ratio). One-unit increase of genetically determined TL was associated with −0.07 (95% confidence interval, −0.01 to −0.12; P =0.01) lower log-transformed fasting insulin (pmol/L) and 21% lower odds (95% confidence interval, 3–35; P =0.02) of CHD. Higher genetically determined log-transformed fasting insulin level was associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01–3.41; P =0.04). Conclusions: Overall, our findings support a role of insulin as a mediator on the causal pathway from shorter telomeres to CHD pathogenesis.
Human CD62Ldim neutrophils identified as a separate subset by proteome profiling and in vivo pulse-chase labeling
Authors: Tamar Tak, Patrick Wijten, Marjolein Heeres, Peter Pickkers, Arjen Scholten, Albert J. R. Heck, Nienke Vrisekoop, Luke P. Leenen, José A. M. Borghans, Kiki Tesselaar, Leo Koenderman
Journal: Blood (2017)
Detection of clonal mitochondrial DNA mutation in airway mucosa of follow-up lung cancer patients
Authors: Santanu Dasgupta, Rex Yung, William Westra, David Sidransky
Journal: Clinical Cancer Research (2007)

A5  Mitochondrial DNA mutations were reported in various cancers but very little is known whether these mutations can be used for diagnostic or prognostic purposes. We examined 30 lesions from 5 follow-up lung cancer patients comprised of tumor, matched airway mucosa, metaplasia and tumor adjacent normal epithelium on high throughput Affymetrix Mitochip 2.0 array platform. The airway mucosal lesions were designated abnormal and suspicious for mild-moderate-severe dysplasia or carcinoma in situ based on Auto-Fluorescence-Bronchoscopy (AFB) and HUGO pathological classification. At least one somatic mutation was detected in each lesion analyzed. A total of 64 mutations were detected with 75% (48/64) from the coding regions and 25% (16/64) from the non-coding regions of the mtDNA. The mutational hot spots were at ND1 (14 mutation) and COI (10 mutations) and 2-4 identical mutations were noted among 4 patients. In 3 out of 5 patients, at least one identical mutation was evident in the tumor and one of the corresponding mucosal lesions. A range of 1-15 tumor matched mutations were detectable in mucosal lesions of the 3 patients. One patient was operated twice for tumor in the right and left lobe respectively within a span of two years and we detected multiple identical mtDNA mutations (20/20) in both the tumors from this patient. Fifteen out of twenty mtDNA mutations detected in the tumors of this patient were also detectable among the 5 corresponding mucosal lesions. Moreover, a significant correlation between smoking and number of mtDNA mutation in these patients were observed (P
Functional characterization of the UGT1A9183Gly and UGT2B7268Tyr polymorphic variants
Authors: Jean Bendaly, Jia-Long Fang, Doris Wiener, Philip Lazarus
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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UGT1A9 and UGT2B7 are human UDP-glucuronosyltransferases (UGTs) shown to play an important role in the phase II metabolism of procarcinogenic metabolites of benzo(a)pyrene (BaP) and 4–(methylnitrosamino)–1–(3–pyridyl)–1–butanone (NNK), as well as colon carcinogens like 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhiP). As both UGT1A9 and UGT2B7 are expressed in liver as well as in tissues of the digestive tract including colon and esophagus, these enzymes may play an important role as detoxifiers of digestive tract carcinogens. Prevalent missense polymorphisms have been previously identified at codon 183 of the UGT1A9 gene and codon 268 of the UGT2B7 gene. To determine whether these changes in amino acid sequence result in aberrant UGT1A9 or UGT2B7 enzyme activity, functional characterization of the wild-type- and variant-encoded UGT1A9 and UGT2B7 isoforms was performed in vitro after cloning and stable transfection of wild-type and variant UGT alleles into the non-UGT-expressing HK293 cell line. Cell homogenates were prepared from UGT1A9- and UGT2B7-transfected cells and glucuronidation assays were performed using equal amounts of total cell protein against various carcinogens/carcinogen metabolites including B[a]P-7,8-diol, PHIP, N -OH-PHIP, IQ, N -OH-IQ, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as well as other phenolic and steroidal compounds including 1-hydroxy (OH)-pyrene, 3-OH-BaP, 7-OH-BaP, 9-OH-BaP, 4-nitrophenol, 4-OH-acetophenone, estradiol, androsterone, and dihydrotestosterol. Levels of UGT enzyme activity were determined in three separate experiments by HPLC or TLC/densitometric analysis and calculated both before and after normalization for cell homogenate UGT1A9 or UGT2B7 protein levels as determined by Western blot analysis. A significant ( p <0.005) 3- to 15-fold decrease in activity was observed for the UGT1A9183Gly variant as compared to its wild-type counterpart for all substrates analyzed. Although high levels of activity were observed for the wild-type UGT1A9183Cys variant against NNAL, none was detected in assays with the UGT1A9183Gly variant. Significant ( p <0.05) decreases in UGT1A9 activity were observed prior to UGT protein normalization in assays using 3-OH-BaP, IQ, N -OH-IQ, or 4-nitrophenol as substrate. Similarly, significant ( p <0.02) decreases in glucuronidation activity (1.5- to 9.5-fold) were observed for the UGT2B7268Tyr variant as compared its wild-type counterpart for all substrates analyzed. Significant decreases in glucuronidation activity were observed for the UGT2B7268Tyr variant for all substrates both before and after UGT protein normalization. These results demonstrate that the UGT1A9 (Cys183Gly) and UGT2B7 (His268Tyr) polymorphisms significantly alter UGT1A9 and UGT2B7 function and could potentially play an important role as risk modifiers for digestive tract cancers.
Genetic regulation of the RUNX transcription factor family has antitumor effects
Authors: Ken Morita, Kensho Suzuki, Shintaro Maeda, Akihiko Matsuo, Yoshihide Mitsuda, Chieko Tokushige, Gengo Kashiwazaki, Junichi Taniguchi, Rina Maeda, Mina Noura, Masahiro Hirata, Tatsuki Kataoka, Ayaka Yano, Yoshimi Yamada, Hiroki Kiyose, Mayu Tokumasu, Hidemasa Matsuo, Sunao Tanaka, Yasushi Okuno, Manabu Muto, Kazuhito Naka, Kosei Ito, Toshio Kitamura, Yasufumi Kaneda, Paul P. Liu, Toshikazu Bando, Souichi Adachi, Hiroshi Sugiyama, Yasuhiko Kamikubo
Journal: Journal of Clinical Investigation (2017)

Runt-related transcription factor 1 (RUNX1) is generally considered to function as a tumor suppressor in the development of leukemia, but a growing body of evidence suggests that it has pro-oncogenic properties in acute myeloid leukemia (AML). Here we have demonstrated that the antileukemic effect mediated by RUNX1 depletion is highly dependent on a functional p53-mediated cell death pathway. Increased expression of other RUNX family members, including RUNX2 and RUNX3, compensated for the antitumor effect elicited by RUNX1 silencing, and simultaneous attenuation of all RUNX family members as a cluster led to a much stronger antitumor effect relative to suppression of individual RUNX members. Switching off the RUNX cluster using alkylating agent-conjugated pyrrole-imidazole (PI) polyamides, which were designed to specifically bind to consensus RUNX-binding sequences, was highly effective against AML cells and against several poor-prognosis solid tumors in a xenograft mouse model of AML without notable adverse events. Taken together, these results identify a crucial role for the RUNX cluster in the maintenance and progression of cancer cells and suggest that modulation of the RUNX cluster using the PI polyamide gene-switch technology is a potential strategy to control malignancies.
Infections Due to Adenovirus Type 8 in the United States
Authors: Chandler Dawson, Richard Darrell, Lavelle Hanna, Ernest Jawetz
Journal: New England Journal of Medicine (1963)

IN western countries outbreaks of epidemic keratoconjunctivitis have been limited largely to ophthalmic clinics of certain industries (such as shipyards), where minor eye trauma frequently occurs.1 2 3 Once introduced into an industrial dispensary or eye clinic, the virus is passed from one patient to the next by minor procedures such as tonometry and foreign-body removal.1 , 4 Secondary spread from adults thus infected to their immediate families is rare.2 , 5 In Japan, where there is a high endemic level of adenovirus Type 8, children are commonly infected.6 In young children the infection appears as a systemic disease, with fever, respiratory or gastrointestinal signs and . . .