tbuckley/cabot-search huggingface dataset:
Abstract P484: The Role of Excessive Body Weight in Hypertension Risk Among Youth
Authors: Corinna Koebnick, Margo Sidell, Matthew Daley, Xia Li, Robert Riewerts, Beatriz Kuizon
Journal: Circulation (2020)

Objective: To determine the hypertension risk associated with elevated body mass index (BMI) for age in children. Study design: In a retrospective cohort of 706,903 children ages 3-18 years in an integrated health care system in Southern California between 2008 and 2017, Cox proportional hazard models with age as time scale were fitted to assess the risk of hypertension (based on 2017 Blood Pressure Guidelines by the American Academy of Pediatrics using 3 blood pressures of independent consecutive visits), by baseline BMI-for-age category (starting at their first available BMI) and BMI change over time, adjusted for sex, race, socioeconomic status and baseline year. Children were followed up until end of membership, onset of hypertension, death, or end of study period. Results: During 3,121,299 person-years, we identified 19,158 youth with incident hypertension. The adjusted hazard ratio (HR) for hypertension was 0.842 (95%CI 0.755, 0.938) for children with a baseline BMI-for-age &lt;5th percentile, 0.864 (95%CI 0.814, 0.917) for 5-39th percentile, 1.00 (reference) for 40-59th percentile, 1.216 (95%CI 1.153, 1.282) for 60-84th percentile, 1.721 (95%CI 1.629, 1.817) for 85-94th percentile, 2.418 (95%CI 2.261, 2.586) for 95-96th percentile, and 3.816 (95%CI 3.624, 4.019) for ≥97th percentile. The adjusted HR for change in BMI over time was 1.095 (95%CI 1.090, 1.100) per kg/m2. Conclusions: In this large cohort study, we found that even moderate elevations in BMI-for age percentile conferred an increased risk of hypertension in children. Results also indicate an escalation of hypertension risk as BMI increased over time. Our results suggest that normal body weight in children ranging from the 5th to the 85th percentile of BMI-for-age and modest increases in BMI over time may increase the risk for hypertension.
Abstract P547: The Relationship Between Alcohol Drinking Before Sleeping(Ne-Zake) or in the Morning(Mukae-Zake) and Sleeplessness Among Farmers
Authors: Rie Sato, Takashi Hisamatsu, Hideki Tsumura, Mari Fukuda, Yukio Esumi, Kaoru Mikajiri, Shusaku Tamura, Hideyuki Kanda
Journal: Circulation (2020)

Introduction: Drinking alcohol before sleeping (Ne-Zake) or in the morning (Mukae-Zake) is occasionally seen in Japan although it is well known that drinking alcohol have some negative effects on sleep. There have been studies which indicated that alcohol worsen sleep quality and quantity however few which investigated how alcohol before sleeping and no which noticed on how alcohol in the morning affects. The purpose of this study is to verify the relationship between Ne-Zake and/or Mukae-Zake and insomnia adjusting the influence of quality and frequency of drinking on the relationship. Hypothesis: We assessed the hypothesis that there is a significant association between Ne-Zake and/or Mukae-Zake and sleeplessness but this association can be confounded by quality and frequency of drinking. Method: Seven hundred and forty-six farmers who underwent annual medical checkups were analyzed. Ne-Zake was defined as “drinking as a sleeping aid” and Mukae-Zake was defined as “drinking in order to get calm down or to fix hungover”. Athene Insomnia Scale (AIS) was used to evaluate objective sleeplessness. AIS consists of 8 questions, which were evaluated from 0 (no sleeplessness) to 3 points (severe sleeplessness), asking the sleeping status in the previous 2 weeks. Insomnia was defined by AIS point more than 6. We conducted the multivariable logistic analysis, setting the presence of insomnia as a dependent variable and the presence of Ne-Zake and Mukae-Zake, quantity of alcohol at one time, frequency of drinking, sleeping related diseases (sleep apnea syndrome, restless leg syndrome, narcolepsy, limb movement disorder, depression), gender, and age as independent variables. Results: Among a total of 746 farmers (mean age 59.5 years; 74.1% men), insomnia, Ne-Zake, and Mukae-Zake were observed in 151 (20.2%), 140 (18.8%) and 37 (5.0%), respectively. Adjusted odds ratios (95% Confidence Intervals) of Ne-Zake and Mukae-Zake were 1.75 (1.07-2.88) and 3.01 (1.41-6.42). The association of Ne-Zake was consistent between men and women but that of Mukae-Zake was stronger in men than in women. (P-values for interaction = 0.98 and 0.03, respectively). Conclusion: Both Ne-Zake and Mukae-Zake had statistically positive significant association with insomnia independent of quantity and frequency of drinking. It may indicate that the timing of drinking alcohol has a stronger relationship with insomnia than quantity and frequency of drinking does. The feature of farmers’ lives in which they can decide their life style might give more opportunities to have Ne-Zake and/or Mukae-Zake than groups with well-scheduled working environment. This result can be utilized to improve farmers’ further physical and psychological health related to alcohol by encouraging to pay attention to not only the quantity or frequency of alcohol drinking but also the timing in a day.
New England Journal of Medicine reviews controversial stent study
Authors: Deborah Cohen, Ed Brown
Journal: BMJ (2020)

The New England Journal of Medicine has launched a review into a trial comparing stents with bypass surgery for blocked arteries, after a series of allegations made by the BBC’s Newsnight programme.

The EXCEL trial compared the outcomes from percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for the composite endpoint of death, myocardial infarction, and stroke in patients with left main disease at three and five years after their procedure.1

Newsnight alleged that important data about myocardial infarction had not been published and that the five year follow-up paper did not sufficiently emphasise that PCI patients had a higher mortality rate than those who had surgery.2

The trial was sponsored by the US stent …
Abstract P324: Differences in Incident Diabetes Mellitus and Atherosclerotic Cardiovascular Disease in Chronic Inflammatory Diseases
Authors: Simran Chadha, Adovich Rivera, Anna Pawlowski, Donald M Lloyd-jones, Matthew J Feinstein
Journal: Circulation (2020)

Introduction: Several chronic inflammatory diseases (CID) are associated with elevated risks for cardiovascular diseases (CVDs). However, the relative magnitude of elevated CVD risk may differ considerably between chronic inflammatory diseases. Hypothesis: We hypothesized that not all CIDs are associated with elevated risk for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD), and that magnitudes of increased CVD risk differ considerably across CIDs. Methods: We estimated the incidence of DM and ASCVD in 18,373 patients with any of six CIDs [human immunodeficiency virus infection (HIV), Irritable bowel disease (IBD), psoriasis, rheumatoid arthritis (RA), scleroderma, and systemic lupus erythematosus (SLE)] in regular outpatient care, as well as controls without CIDs in regular primary care, in a large metropolitan health system since January 1 st , 2000. We assessed incidence of outcomes in patients with each CID compared to controls using quasi-Poisson regression adjusting for age, sex, insurance status, and common CVD risk factors. A 90-day blanking period was applied for identifying incident cases. Results: Psoriasis, HIV, male sex, black race, Hispanic ethnicity, and being on public insurance were all associated with significantly elevated risks for DM (Figure). HIV, RA, scleroderma, SLE, male sex, and public insurance were all associated with significantly elevated risks for ASCVD. The magnitude of increased risk for ASCVD was similarly high for HIV (incidence rate ratio 1.79, 95% confidence interval 1.57-2.05), scleroderma (1.79, 1.42-2.27), and SLE (1.95, 1.59-2.39). Conclusion: Several, but not all, CIDs are associated with elevated risks for DM and ASCVD, but the magnitude of risk elevation differs depending on the CID. These data demonstrate the importance of nuanced approaches to understanding CID- and inflammation-associated CVD risks.
Evolution of an Amniote-Specific Mechanism for Modulating Ubiquitin Signaling via Phosphoregulation of the E2 Enzyme UBE2D3
Authors: Monica Roman-Trufero, Constance M Ito, Conrado Pedebos, Indiana Magdalou, Yi-Fang Wang, Mohammad M Karimi, Benjamin Moyon, Zoe Webster, Aida di Gregorio, Veronique Azuara, Syma Khalid, Christian Speck, Tristan Rodriguez, Niall Dillon
Journal: Molecular Biology and Evolution (2020)

Genetic variation in the enzymes that catalyze posttranslational modification of proteins is a potentially important source of phenotypic variation during evolution. Ubiquitination is one such modification that affects turnover of virtually all of the proteins in the cell in addition to roles in signaling and epigenetic regulation. UBE2D3 is a promiscuous E2 enzyme, which acts as an ubiquitin donor for E3 ligases that catalyze ubiquitination of developmentally important proteins. We have used protein sequence comparison of UBE2D3 orthologs to identify a position in the C-terminal α-helical region of UBE2D3 that is occupied by a conserved serine in amniotes and by alanine in anamniote vertebrate and invertebrate lineages. Acquisition of the serine (S138) in the common ancestor to modern amniotes created a phosphorylation site for Aurora B. Phosphorylation of S138 disrupts the structure of UBE2D3 and reduces the level of the protein in mouse embryonic stem cells (ESCs). Substitution of S138 with the anamniote alanine (S138A) increases the level of UBE2D3 in ESCs as well as being a gain of function early embryonic lethal mutation in mice. When mutant S138A ESCs were differentiated into extraembryonic primitive endoderm, levels of the PDGFRα and FGFR1 receptor tyrosine kinases were reduced and primitive endoderm differentiation was compromised. Proximity ligation analysis showed increased interaction between UBE2D3 and the E3 ligase CBL and between CBL and the receptor tyrosine kinases. Our results identify a sequence change that altered the ubiquitination landscape at the base of the amniote lineage with potential effects on amniote biology and evolution.
Effect of celecoxib, a specific cyclooxygenase 2 inhibitor, on the apoptotic and mitotic indexes of breast cancer in patients with early stage disease
Authors: A. H. Tfayli, M. Cherry, J. Yang, K. Kojouri, M. Jafari, A. Thor, H. Ozer
Journal: Journal of Clinical Oncology (2007)

14132 Background: To assess whether the administration of celecoxib, a specific cyclooxegenease-2 (COX-2) inhibitor, to patients with breast cancer alters the proliferative and apoptotic indexes of their tumors. Methods: Women newly diagnosed with non metastatic breast cancer were enrolled into the study after undergoing a diagnostic core needle biopsy. Patients received celecoxib treatment at 400 mg orally twice a day for 14 days, and then underwent surgical excision of their tumor. Core biopsies obtained at the time of initial diagnostic procedure and surgical excision specimens were stained for Ki-67, as well as COX-2 and cleaved poly (ADP-ribose) polymerase (PARP) expression (as an apoptosis marker). Appropriate negative and positive controls were included. We assessed the difference in Ki- 67, COX-2 and cleaved PARP expression levels, before and after treatment using the Wilcoxon’s matched-pair ranks test and the McNemar’s test. Results: 16 patients were enrolled. The median age was 54.6 years. ER and/or PR expression was present in 81% of tumors; Her-2 neu overexpression was present in 25%. No significant change in COX-2 or cleaved PARP expression was noticed in the post intervention specimen compared to the core biopsies. Surprisingly, there was a significant increase in the Ki-67 expression (p &lt; 0.009). Conclusions: we have conducted a short term prospective study to assess the effects of celecoxib, on the proliferative and apoptotic indexes in patients with early stage breast cancer. We have found an increase in the Ki-67 activity, with no significant down regulation of COX-2 or increase in cleaved PARP expression with 14 days of therapy. This could be partly due to the small sample size. [Table: see text]
Abstract P373: Are Generic Drugs Used in Cardiology as Effective and Safe as Their Brand-name Counterparts? A Systematic Review and Meta-analysis
Authors: Jacinthe Leclerc, Magalie Thibault, Jennifer Midiani Gonella, Claudia Beaudoin, John Sampalis
Journal: Circulation (2020)

Background: Generic drugs constitute lower cost alternatives when the original drug patent expires. Two large systematic reviews and meta-analyses (2008; 2016) concluded to similarity in outcomes between brand-name and generic drugs in cardiology. These meta-analyses were possibly biased by the inclusion of ≥ 50% comparative bioavailability studies, not designed nor powered to detect a difference in efficacy or safety between drug types. We aimed to summarize best evidences regarding the effectiveness and safety of generic versus brand-name drugs used in cardiology. Methods: To conduct this systematic review of the literature, scientific databases (MEDLINE and EMBASE) were searched from the latest date among their inception or January 1984, to March 2018. Original research reports comparing the clinical impact of brand-name vs. generic cardiovascular drugs on humans treated in real-life setting were included. Meta-Analyses and subgroup analyses were performed. Heterogeneity (I 2 ) and risk of bias were tested. Results: Among the 3,148 screened abstracts, 72 met inclusion criteria. The studies included a total of 1,048,499 patients who used generic or brand-name cardiovascular drugs. Mean age was 65 +/- 10 years old and 42% were women. The most commonly studied therapeutic classes were antiplatelets, statins and anticoagulants. Platelet function, international normalized ratio and systolic blood pressure were similar in generic and brand-name groups. The risk of bias was modest to serious in the majority of studies. The overall relative risk of all-cause hospitalizations was 1.14 (95% Confidence interval: 1.06 to 1.23; I 2 : 98%), while it was 1.05 (0.98 to 1.14; I 2 : 68%) for cardiovascular hospitalizations (both pooled: 1.10 [1.04 to 1.15]; I 2 : 93%). Conclusion: The risk of hospitalization seemed higher for patients exposed to generics. However, evidences are insufficient and too heterogeneous to conclude that generics are as effective and safe as brand-name drugs in cardiology.
The impact of intra-operative high field magnetic resonance imaging on clinical decision making during oncologic neurosurgical procedures
Authors: J. S. Weinberg, K. Shah, G. Rao, E. F. Jackson, D. Suki, R. Sawaya, D. Schellingerhout
Journal: Journal of Clinical Oncology (2007)

19599 Background: Existing image guided surgical (IGS) technology used during resection of brain tumors is based on preoperative imaging modalities and are limited by their inability to demonstrate extent of resection (EOR) and compensate for anatomical changes which occur as a result of surgical manipulation (e.g. brain shift, tumor resection, spinal fluid loss). Having the ability to perform MRI during brain tumor surgery obviates many of these limitations. The purpose of this study was to determine the impact of intra-operative imaging with a high field MRI on brain tumor resection. Methods: Since September 2006, a total of 23 patients with brain tumors underwent resection at The University of Texas M. D. Anderson Cancer Center with intra-operative MR guidance (BrainLAB IGS system integrated with a 1.5T Siemens Espree scanner). For each patient, appropriate imaging was performed prior to craniotomy. Resection was then performed using image guidance. Surgeons completed a questionnaire documenting the reason for the scan and provided an estimation of EOR prior to and after the intraoperative scan. Multiple intraoperative scans were performed at the discretion of the operating surgeon. Results: In 23 patients, 25 scans were performed. The patients had a diagnosis of glioma (21), lymphoma (1), and schwannoma (1). Reasons for performing a scan included: evaluate EOR in 23 (92%) or update the IGS system in 2 (8%). Surgeons indicated in 21/23 (91%) scans performed to evaluate the extent of resection that they would have terminated the surgery prior to the scan. In 9/21 cases (43%), further surgery was performed after the scan to maximize EOR. In 10/24 (42%) cases, the pre-scan estimate of residual tumor matched the post-scan amount. The amount of residual tumor was correctly assessed (within 10%) prior to review of the MRI in 19/24 cases. The correlation between the pre-scan estimation of residual tumor and actual post-scan tumor was high (correlation coefficient 0.81, p&lt;0.05). Conclusions: High field intra- operative MRI with high spatial resolution is a useful adjunct to a neurosurgical oncology practice and alters surgical decision making in a significant number of cases. [Table: see text]
Graphdiyne nanoradioprotector with efficient free radical scavenging ability for mitigating radiation-induced gastrointestinal tract damage
Authors: Jiani Xie, Chengyan Wang, Ning Wang, Shuang Zhu, Linqiang Mei, Xiao Zhang, Yuan Yong, Lele Li, Chunying Chen, Changshui Huang, Zhanjun Gu, Yuliang Li, Yuliang Zhao
Journal: Biomaterials (2020)
Activity of Vincristine and Irinotecan in Diffuse Anaplastic Wilms Tumor and Therapy Outcomes of Stage II to IV Disease: Results of the Children’s Oncology Group AREN0321 Study
Authors: Najat C. Daw, Yueh-Yun Chi, John A. Kalapurakal, Yeonil Kim, Fredric A. Hoffer, James I. Geller, Elizabeth J. Perlman, Peter F. Ehrlich, Elizabeth A. Mullen, Anne B. Warwick, Paul E. Grundy, Arnold C. Paulino, Eric Gratias, Deborah Ward, James R. Anderson, Geetika Khanna, Brett Tornwall, Conrad V. Fernandez, Jeffrey S. Dome
Journal: Journal of Clinical Oncology (2020)

AREN0321 evaluated the activity of vincristine and irinotecan (VI) in patients with newly diagnosed diffuse anaplastic Wilms tumor (DAWT) and whether a regimen containing carboplatin (regimen UH1) in addition to regimen I agents used in the National Wilms Tumor Study 5 (NWTS-5; vincristine, doxorubicin, cyclophosphamide, and etoposide plus radiotherapy) would improve patient outcomes.Patients with stage II to IV DAWT without measurable disease received regimen UH1. Patients with stage IV measurable disease were eligible to receive VI (vincristine, 1.5 mg/m2 per day intravenously on days 1 and 8; irinotecan, 20 mg/m2 per day intravenously on days 1-5 and 8-12 of a 21-day cycle) in an upfront window; those with complete (CR) or partial response (PR) had VI incorporated into regimen UH1 (regimen UH2). The study was designed to detect improvement in outcomes of patients with stage II to IV DAWT compared with historical controls treated with regimen I.Sixty-six eligible patients were enrolled. Of 14 patients with stage IV measurable disease who received VI, 11 (79%) achieved CR (n = 1) or PR (n = 10) after 2 cycles. Doses of doxorubicin, cyclophosphamide, and etoposide were reduced midstudy because of nonhematologic toxicity. Four patients (6%) died as a result of toxicity. Four-year event-free survival, relapse-free survival, and overall survival rates were 67.7% (95% CI, 55.9% to 79.4%), 72.9% (95% CI, 61.5% to 84.4%), and 73.7% (95% CI, 62.7% to 84.8%), respectively, compared with 57.5% (95% CI, 47.6% to 67.4%; P = .26), 57.5% (95% CI, 47.6% to 67.4%; P = .048), and 59.2% (95% CI, 49.4% to 69.0%; P = .08), respectively, in NWTS-5.VI produced a high response rate in patients with metastatic DAWT. AREN0321 treatment seemed to improve outcomes for patients with stage II to IV DAWT compared with NWTS-5, but with increased toxicity. The UH2 regimen warrants further investigation with modifications to reduce toxicity.
Abstract P134: PR Interval Length is Associated With Presence of the White Matter Lesions: Insights From the Epidemiological LIFE-Adult Study
Authors: Jelena Kornej, Katrin Friedrich, Matthias L Schroeter, Veronika Witte, Arno Villringer, Markus Löffler, Samira Zeynalova
Journal: Circulation (2020)

Background: PR interval prolongation is associated with increased risk for atrial fibrillation (AF). AF is a known risk factor for cerebrovascular complications including microbleeds and stroke. This might explain the occurrence of white matter lesions (WML) and consequent cognitive dysfunction. The aim of the current study was to analyze the relationship between PR interval and WML in an epidemiological study. Methods: The LIFE-Adult-Study is a population-based cohort study of randomly selected participants from Leipzig, Germany. In this cross-sectional analysis, individuals without AF, with available brain MRI and ECG were included. The Fazekas scale was used to quantify the amount of WML and was graded into four Fazekas stages: 0=none; 1=punctate foci; 2= beginning confluence; 3=large confluent areas. Stages 2-3 were considered as advanced WML. Results: The study population comprised 2421 individuals (age 59±15 years, 1287 (53.2%) males). The median PR interval was 160 ms (IQR 143; 179). There were 319 (13.2%) individuals with advanced WML (stages 2 and 3). These probands were significantly older, had more often cardiovascular comorbidities, diabetes and stroke than patients without WML (all p&lt;0.005). On univariable analysis, PR interval (OR 1.012, 95%CI 1.008-1.016, p≤0.001) and PR interval ≥160 ms (OR 2.1, 95%CI 1.6-2.7, p≤0.001) were significantly associated with advanced WML. On multivariable analysis, age, arterial hypertension, stroke and PR interval (OR 1.005, 95%CI 1.000-1.009, p=0.044) demonstrated significant association with advanced WML. Furthermore, in other multivariable model PR interval ≥160ms demonstrated significant association with WML (OR 1.431, 95%CI 1.089-1.881, p=0.010). Conclusions: The PR interval is associated with advanced WML.