tbuckley/cabot-search huggingface dataset:
A comparison of cellular DNA repair rates of different cell lines using the TUNEL assay
Authors: Daniel R. Kennedy, Loretta S. Gawron, Jianhua Ju, Wen Liu, Ben Shen, Terry A. Beerman
Journal: Cancer Research (2006)

804  Cells possess several DNA repair systems to counteract the damage produced by endogenous and exogenous agents. Repair of DNA damage is significant in preventing genetic modifications involved in the progression of carcinogenesis. Inefficient repair systems facilitate an increased risk of developing cancer, supporting the prospective study of DNA repair in relation to the onset of cancer. The aim of this project was to develop a simple and accurate method of detecting DNA damage and measuring repair rate. Identification of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay is normally applied to investigate active cell death (apoptosis). Using this staining technique, we developed a method of measuring cellular DNA repair rates. We selected H202 as our primary damaging agent because of its reported ability to induce a large number of single-strand breaks (ssb>36000/cell) without impairing cell survival. (Int J Radiat Biol. 2000 Jan: 67-75). After damaging various lymphocyte cancer cell lines with H202, cells were allowed to repair in media at 37°C for 0, 5, 15, 30, or 60 minutes. Following the different repair incubation time points, the cells were fixed with 4% paraformaldahyde and then stained using TUNEL, followed by flow cytometry. The TUNEL repair assay was conducted on different mononuclear leukocyte cell lines, which revealed specific trends in DNA repair rates among the various cell lines. The Raji cell line with no repair time (0 minutes) had a damage population at 12.8 percent. As the time of repair increased, the damage population continued to decrease, reaching a percentage of 11.4 at a 15 minute repair time, and 8.4 at a 60 minute repair time. By analyzing the equation of the graphed line, the slope, or repair rate, was determined to be -.07 for Raji cells. The U937 cell line had a damage population of 4.7 percent at 0 minutes, 2.3 at 15 minutes, and 1.9 at 60 minutes, resulting in an overall repair rate of -.03 for U937 cells. Our results from the flow cytometer revealed a significant decrease in the amount of DNA damaged as the time for repair increased, indicating that TUNEL is an accurate method of determining and measuring DNA repair. This technique will be useful in further analysis of DNA repair and its contribution to the progression of cancer.
Prognostic Value of Initial Left Ventricular Remodeling in Patients With Reperfused STEMI
Authors: Jose F. Rodriguez-Palomares, Jose Gavara, Ignacio Ferreira-González, Filipa Valente, César Rios, Julián Rodríguez-García, Clara Bonanad, Bruno García del Blanco, Gema Miñana, Maria Mutuberria, Julio Nuñez, José Barrabés, Artur Evangelista, Vicente Bodí, David García-Dorado
Journal: JACC. Cardiovascular imaging (2019)

This study sought to establish the best definition of left ventricular adverse remodeling (LVAR) to predict outcomes and determine whether its assessment adds prognostic information to that obtained by early cardiac magnetic resonance (CMR).LVAR, usually defined as an increase in left ventricular end-diastolic volume (LVEDV) is the main cause of heart failure after an ST-segment elevated myocardial infarction; however, the role of assessment of LVAR in predicting cardiovascular events remains controversial.Patients with ST-segment elevated myocardial infarction who received percutaneous coronary intervention within 6 h of symptom onset were included (n = 498). CMR was performed during hospitalization (6.2 ± 2.6 days) and after 6 months (6.1 ± 1.8 months). The optimal threshold values of the LVEDV increase and the LV ejection fraction decrease associated with the primary endpoint were ascertained. Primary outcome was a composite of cardiovascular mortality, hospitalization for heart failure, or ventricular arrhythmia.The study was completed by 374 patients. Forty-nine patients presented the primary endpoint during follow-up (72.9 ± 42.8 months). Values that maximized the ability to identify patients with and without outcomes were a relative rise in LVEDV of 15% (hazard ratio [HR]: 2.1; p = 0.007) and a relative fall in LV ejection fraction of 3% (HR: 2.5; p = 0.001). However, the predictive model (using C-statistic analysis) failed to demonstrate that direct observation of LVAR at 6 months adds information to data from early CMR in predicting outcomes (C-statistic: 0.723 vs. 0.795).The definition of LVAR that best predicts adverse cardiovascular events should consider both the increase in LVEDV and the reduction in LV ejection fraction. However, assessment of LVAR does not improve information provided by the early CMR.
Comment on Scholtens et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism. Diabetes Care 2019;42:381–392
Authors: Adam Hulman
Journal: Diabetes Care (2019)

Scholtens et al. (1) conducted an important study on the association between maternal glycemia and childhood glucose metabolism. In a subanalysis, the authors applied latent class trajectory modeling to assess the shape of maternal glucose response curves during the oral glucose tolerance test (OGTT). Even though I am in favor of this approach because it focuses on the shape of glucose curves rather than just individual time points, I have some concerns regarding how the analysis was conducted and reported.

The model is described as having random effects for linear, quadratic, and cubic terms for time. However, readers can only assume that the same terms were included and tested as fixed effects. …
Abstract 2094: B-type Natriuretic Peptide Is Useful In Detecting Asymptomatic Left Ventricular Dysfunction in Low-Income, Uninsured Hispanic Patients
Authors: Aurelia Macabasco-O’Connell, Sheba Meymandi, Robert Bryg
Journal: Circulation (2008)

BACKGROUND: Heart failure (HF) is a significant public health problem, particularly in low income Hispanics with multiple cardiovascular risk factors (CRFs). The effectiveness of B-type natriuretic...
AB1158 CLINICAL AND VISUAL US PARAMETERS IN SYMPTOMATIC KNEE OSTEOARTHRITIS AND ASYMPTOMATIC PATIENTS
Authors: Natalia Martusevitch, Katsiarina Gudkevich, Alexander Aleshkevich, Tatsiana Bondar
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Sonography is widely used because of its easy accessibility, relatively low cost. Sonography provides distinct information that bridges the gap between clinical and radiologic evaluation. There has been a growing interest in determining the sources of pain with ultrasound (US) findings in patients with knee osteoarthritis. <h3>Objectives</h3> The aim of this study was to determine the relationships between clinical parameters and features of US of the knee. <h3>Methods</h3> This was a cross-sectional study, recruiting 47 consecutive patients aged 47 (36- 54), 60,42% (n=29) were female. Those with recent trauma, rheumatic diseases were excluded from the study. Patients underwent assessment for knee pain (Visual Analog Scale (VAS)), US examination of the knee joints according to the 4-point scale (synovial proliferation, joint effusion, power Doppler signal (PD), patellofemoral joint cartilage (PFJ), medial femoral cartilage (MF), medial (MM) and lateral meniscus (LM), osteophytes, Baker cysts). US staging of knee OA was also performed. <h3>Results</h3> Patients were divided into 2 groups: those with knee pain (n=28) and asymptomatic patients (n=19). Pathological US features were found in both groups (Table). In 5 out of 19asymptomatic patients, degenerative changes of different degree of the joint structures were identified (PFJ, MF, osteophytes, MM, LM), in 4 patients – joint effusion. Prevalence of PFJ, MF, MM, LM changes, osteophytes and Baker cysts didn't differ between groupsG. roups differed in PD signal expression in the synovia (p=0,07). Functional association between VAS score and PD expression (R=1,0, p&lt;0,05) was revealed$ moderate correlation between VAS score and joint effusion (R=0,47, p&lt;0,05), PFJ (R=0,58, p&lt;0,05), osteophytes (R=0,66, p&lt;0,001) was observed. <h3>Conclusion</h3> In the patients under study, degenerative and inflammatory findings were common in the symptomatic group, but were also identified in the asymptomatic patients. Clinical parameters were more strongly associated with active inflammation (as verified by US) rather than with degenerative changes. <h3>Disclosure of Interests</h3> None declared
SP0106 LOOKING THROUGH MY BACK BONE
Authors: Matthias Gunzer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Because bone marrow is the source of all immune cells, knowing the blood supply of bones is essential to understand diverse mechanisms such as arthritic bone inflammation, anti-infectious immune defense or sterile inflammation. <h3>Objectives:</h3> We wanted to clarify, how immune cells are able to function inside of the bone and also leave bones for peripheral functions. <h3>Methods:</h3> Using an array of different imaging approaches and innovative animal models as well as insights from clinical studies in humans we have made the bone open to ways of studying, that have not previously possible. <h3>Results:</h3> Using these methods we have defined an entirely new concept of how a closed circulatory loop is established in long bones. Thereby we show the mechanistic role of osteoclasts and define, how T cells and neutrophils use the system to fight against viral infection or invade ischemic tissue. This allows an integrated view how the blood circulation inside and outside of bones are interconnected to mediate functional or dysfunctional immunity. <h3>Disclosure of Interests:</h3> None declared
PS1279 A PRACTICAL UPDATE ON THE EPIDEMIOLOGY AND RISK FACTORS FOR THE EMERGENCE AND MORTALITY OF BLOODSTREAM INFECTIONS IN 3014 PATIENTS WITH HEMATOLOGICAL MALIGNANCY RECEIVING CHEMOTHERAPY
Authors: J. Hu, S. Chen, T. Yang
Journal: HemaSphere (2019)

Background: The pathogenic epidemiology, antibiotic resistance, and risk factors of bloodstream infections (BSIs) in patients with hematologic malignancies (HMs) receiving chemotherapy is importment for clinican. Aims: To investigate the pathogenic epidemiology and antibiotic resistance of bloodstream infections (BSIs) in patients with hematologic malignancies (HMs) receiving chemotherapy, and to determine the risk factors for BSIs. Methods: Retrospective chart review of patients diagnosed with HMs (n = 3014) was performed (1/2013–12/2016), and patients classified as having BSIs (n = 725) or not (n = 2289). Clinical characteristics and pathogens were evaluated, and risk factors for BSIs identified by univariate and multivariate Logtistic and COX regression analyses. Results: BSI frequency was 24.1%, with 744 different isolated strains in 725 cases. Gram‐negative (G‐) represented 64.7% of the 744 isolated strains, while Gram‐positive (G+) and fungi were 27.7% and 7.7%, respectively. The most common isolates were Klebsiella pneumoniae (19.2%), and 90% of extended‐spectrum beta‐lactamases (ESBL)‐producing enterobacteria were multidrug‐resistant. Methicillin‐resistant Coagulase‐negative Staphylococci and Methicillin‐resistant Staphylococcus aureus accounted for 87.16% and 37.93% of the cases, respectively. Multivariate analysis revealed that male, age ≥ 45 and &lt;65 yr, hospital length of stay (LOS) ≥ 9d, neutropenia ≥ 7d before BSIs, ≥ 2 antibiotics, gastrointestinal, perirectal and urinary tract infections independently predicted BSIs emergence. Furthermore, age ≥ 65, neutropenia ≥ 7d before BSIs, no HM remission, lower white blood cell count, ≥ 3 antibiotics, respiratory infections, and Acinetobacter baumannii and Stenotrophomonas maltophilia BSIs were independent predictors of 30‐day mortality. Summary/Conclusion: Antibiotic resistance was high, outcome was poor, and mortality due to BSIs was high in this patient cohort. Therefore, close attention should be paid to the risk factors identified here during management of these patients with BSIs. image
Identifying Novel Types of Irritability Using a Developmental Genetic Approach
Authors: Lucy Riglin, Olga Eyre, Ajay K. Thapar, Argyris Stringaris, Ellen Leibenluft, Daniel S. Pine, Kate Tilling, George Davey Smith, Michael C. O’Donovan, Anita Thapar
Journal: American Journal of Psychiatry (2019)

Objective: Irritability, which is strongly associated with impairment and negative outcomes, is a common reason for referral to mental health services but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. The authors used a developmental approach to test the hypothesis that there are several forms of irritability, including a “neurodevelopmental/ADHD-like” type, with onset in childhood, and a “depression/mood” type, with onset in adolescence. Methods: Data were analyzed from the Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based cohort. Irritability trajectory classes were estimated for 7,924 individuals with data at multiple time points across childhood and adolescence (four possible time points from approximately ages 7 to 15). Psychiatric diagnoses were assessed at approximately ages 7 and 15. Psychiatric genetic risk was indexed by polygenic risk scores (PRSs) for attention deficit hyperactivity disorder (ADHD) and depression, derived using large genome-wide association study results. Results: Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%), and high-persistent (2.4%). The early-onset high-persistent trajectory was associated with male preponderance, childhood ADHD (odds ratio=108.64, 95% CI=57.45–204.41), and ADHD PRS (odds ratio=1.31, 95% CI=1.09–1.58). The adolescent-onset increasing trajectory was associated with female preponderance, adolescent depression (odds ratio=5.14, 95% CI=2.47–10.73), and depression PRS (odds ratio=1.20, 95% CI=1.05–1.38). Both the early-onset high-persistent and adolescent-onset increasing trajectory classes were associated with adolescent depression diagnosis and ADHD PRS. Conclusions: The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like. These findings have implications for treatment as well as nosology.
THU0264 ANALYSIS OF SURVIVAL ASSOCIATED WITH PULMONARY ARTERIAL HYPERTENSION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Chi Ho, Erik Fung, Lai-Shan Tam
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Identifying clinical variables that predict outcome of Systemic lupus erythematosus (SLE)-pulmonary arterial hypertension (PAH) is important.[1] Data focusing on SLE-PAH is lacking as previous studies were based on connective tissue disease (CTD)-PAH patients. <h3>Objectives:</h3> To examine clinical, serological and echocardiographic features that are 1) associated with SLE-PAH at baseline and 2) predictors of mortality in SLE-PAH. <h3>Methods:</h3> Data on SLE-PAH patients (SLE-PAH group, n=67) attending the Prince of Wales Hospital, from 2008 to 2018 was retrieved. Diagnosis of PAH was based on echocardiogram showing pulmonary artery systolic pressure (PASP) &gt; 30mmHg. Age-, sex- and disease duration-matched SLE patients with PASP &lt; 30mm Hg were selected from the same database as control (SLE-non PAH group, n=154). Clinical, serological, echocardiographic features and medication at baseline (PAH diagnosis) were collected. Censor date was death or last visit on or before 31<sup>st</sup> December 2018. PAH targeted therapy and immunosuppressant used for PAH were recorded after diagnosis of PAH. Hazard ratio were analysed by cox regression model, and adjusted by age-, sex-, disease-duration, comorbidities and baseline medication. <h3>Results:</h3> The cohort (n=221) mean age was 42.7 +/- 12.6 with 96.3% female, and a disease duration of 8.26 +/- 7.61 years. At baseline, the SLE-PAH group had higher anti-ds DNA titre; lower haemoglobin level; higher prevalence of renal impairment; but a lower prevalence of arthritis and thrombocytopenia/neutropenia and anti-phospholipid antibodies compared to the control (Table 1). SLE-PAH group's echocardiogram had a higher prevalence of reduced left ventricular ejection fractions, moderate-severe tricuspid regurgitation and pericardial effusion compared to the control (Table 1). Amongst the SLE-PAH group, 11/67 had a right heart catherization done and all were confirmed to have PAH. 8/11 patients received PAH specific treatment and 23/67 received escalated immunosuppressive therapy for presumed PAH, within 1 years of PAH diagnosis. The mortality rate of the SLE-PAH group was 3.82 (95% confident interval 1.50-9.83; p=0.005) compared to the control after adjusting for baseline parameters and medication used after the diagnosis of PAH. Poor prognostic factors at baseline are summarized in table 2. <h3>Conclusion:</h3> SLE-PAH had 3.8-fold increase in mortality despite treatment with PAH specific therapy and immunosuppressants. Hyponatremia and renal disease were associated with poor survival outcome in SLE-PAH patients. <h3>Reference:</h3> [1] Raina, A, et al. European Respiratory Review, 2016 <h3>Disclosure of Interests:</h3> None declared
Abstract 13098: Maternal Obesity and Insulin Resistance Lead to Endothelial and Myocardial Mircovascular Dysfunction in Nonhuman Primate Offspring
Authors: Scott M Chadderdon, J T Belcik, Jonathan Hattenhauer, Ashley M Crowley, Diana L Takahashi, Kevin L Grove, Sanjiv Kaul
Journal: Circulation (2013)

Background: There is a well-defined link between maternal under-nutrition and cardiovascular disease late in life. However, little is known about maternal over-nutrition and cardiovascular health i...
High rate of transmission in a pulmonary tuberculosis outbreak in a primary school, north-eastern Italy, 2019
Authors: Sandro Cinquetti, Maria Dalmanzio, Elisa Ros, Davide Gentili, Mauro Ramigni, Adriano Grossi, Xanthi D Andrianou, Leonardo Ermanno La Torre, Roberto Rigoli, Pier Giorgio Scotton, Angela Taraschi, Vincenzo Baldo, Giuseppina Napoletano, Francesca Russo, Patrizio Pezzotti, Giovanni Rezza, Antonietta Filia
Journal: Eurosurveillance (2019)

Italy is a low-incidence country for tuberculosis (TB). We describe a TB outbreak in a primary school in north-eastern Italy, involving 10 cases of active pulmonary disease and 42 cases of latent infection. The index case was detected in March 2019, while the primary case, an Italian-born schoolteacher, was likely infectious since January 2018. Administration of a pre-employment health questionnaire to school staff with sustained contact with children should be considered in low-incidence countries.
THU0209 4-PHENYLBUTYRIC ACID AMELIORATES LUPUS HEPATITIS AND NEPHRITIS THROUGH SUPPRESSION OF NF-KB ACTIVATION IN EXPERIMENTAL LUPUS MODEL
Authors: Yun-Jung Choi, Ji-Hyun Jeong, Eun-Kyeong Lee, Chang-Hoon Lee, Myeung-Su Lee, Wan-Hee Yoo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease presenting diverse manifestation involving multiple organs, such as liver and kidney. Endoplasmic reticulum (ER) stress has been revealed as the one of the contributing factors of lupus pathogenesis. <h3>Objectives:</h3> The purpose of the present study was to investigate whether ER stress inhibition suppresses organ inflammation including liver and kidney in lupus murine model and the activation of mitogen activated protein kinases (MAPK) and NF-kB. <h3>Methods:</h3> A murine lupus model was induced through a 4-week treatment with Resiquimod, a toll-like receptor agonist 7. From the 8<sup>th</sup> week, the mice were treated with phosphate buffered saline, 4-phenylbutyric acid (4-PBA), and dexamethasone for 4 weeks. The increment of body weight, liver weight, inflammation mediator level, and the pathology of hepatitis and nephritis were analyzed at 12 weeks of age. The level of phosphorylated MAPK expression and activation of NF-kb were also evaluated. <h3>Results:</h3> 4-PBA-treated group showed lower level of body weight increment with liver to body weight ratio compared with vehicle-treated group. 4-PBA group showed decreased inflammatory cell infiltration and fibrosis in the histologic finding of liver and kidney and lower level of inflammatory mediators, including TNF-α and IL-6, compared to vehicle-group. GRP78 and CHOP expression was decreased in the spleen of 4-PBA treated mice compared to vehicle-treated mice and 4-PBA group showed the lower expression level of phosphorylated JNK, ERK, p38 and NF-kB of the spleen. <h3>Conclusion:</h3> Our results suggest that 4-PBA attenuates the inflammation on liver and kidney of experimental lupus model through suppression of MAPK and NF-kB activation. Thus, inhibition of ER stress could be function as anti-inflammatory therapeutics for SLE. <h3>References:</h3> [1] Navid F, Colbert RA. Causes and consequences of endoplasmic reticulum stress in rheumatic disease. Nat Rev Rheumatol2017;13:25-40 [2] Hosoi T, Ozawa K. Endoplasmic reticulum stress in disease: mechanisms and therapeutic opportunities. Clin Sci (Lond)2009;118:19-29 <h3>Disclosure of Interests:</h3> None declared
David Barrington Shaw
Authors: Brian J Kirby
Journal: BMJ (2019)

We readily forget travel problems once posed to rural patients with complex cardiac problems. David Barrington Shaw, who died on 15 March 2019, brought specialist cardiology to those who lived in the south west peninsula of England.

David Shaw was born in Barnstaple, north Devon. After his early schooling, he attended Oundle School and then entered Charing Cross Hospital Medical School. He was regarded as a sound student, making good progress, which was unfortunately interrupted by tuberculosis. This was particularly tiresome as he had just acquired a small boat but was told not to sail it. Fortunately within six months he had recovered from this setback. On qualifying in 1952, he took appointments at Charing Cross and associated hospitals. In 1956 he took the membership exam but, unsure whether he would pass it, he immediately took the train to Edinburgh as an insurance—thereby passing both examinations in the same year. He then took medical registrar appointments at Carshalton and Chase Farm hospitals. His interests in heart and …