tbuckley/cabot-search huggingface dataset:
Abstract P405: Visceral Adipose Tissue Volume is Associated With Prevalent Coronary Plaque Independent of Total Adiposity in Psoriasis
Authors: Domingo E Uceda, Aarthi Reddy, Harry Choi, Sundus S Lateef, Khaled M Abdelrahman, Amit K Dey, Milena Aksentijevich, Colin Scott, Parag Shukla, Mohammed D Akbar, Jenis Argueta-Amaya, Justin Rodante, Heather Teague, Andrew Keel, Marcus Y Chen, Jianhua Yao, Wunan Zhou, Martin P Playford, Nehal N Mehta
Journal: Circulation (2020)

Introduction: Psoriasis (PSO) is a chronic inflammatory condition associated with accelerated atherosclerosis and increased risk of myocardial infarction in part mediated through high visceral adipose tissue (VAT) volume. VAT has been shown to be associated with increased coronary burden; however, the relationship with prevalent coronary plaque in PSO has not been explored. Hypothesis: We hypothesized that VAT would associate with coronary plaque in PSO beyond traditional risk factors. Methods: A total of 164 consecutive PSO patients underwent coronary computed tomography angiography (CCTA) as part of a large cohort study to assess presence of coronary plaque. Low-dose CT was utilized to quantify VAT and subcutaneous adipose tissue (SAT) volume from the level of the diaphragm to the pubic symphysis. Logistic regression was used to assess the association between the presence of coronary plaque and the ratio of VAT-to-total adiposity in adjusted models (STATA 12). Results: The cohort was middle-aged, predominantly male, relatively low CV risk by FRS and mild to moderate PSO (Table 1). Patients with increased VAT-to-total adiposity, had significantly increased coronary plaque presence (70% (45 of 65) vs. 31% (31 of 99), p&lt;0.001) compared to those with low VAT-to-total adiposity. Moreover, increased VAT-to-total adiposity was associated with 3-fold higher odds of having a prevalent coronary plaque (adjusted OR 2.96 (1.22 - 7.22), p=0.016) after adjustment for Framingham risk score, body-mass-index, waist-to-hip ratio and lipid treatment. Conclusions: Having higher VAT was associated with higher prevalence of coronary plaque independent of total adiposity and cardiovascular risk factors. These findings suggest VAT contributes to coronary plaque in psoriasis and that weight loss efforts may improve outcomes in this high-risk population.
Cancer Antigen Discovery Is Enabled by RNA Sequencing of Highly Purified Malignant and Nonmalignant Cells
Authors: Martin J. Scurr, Alex Greenshields-Watson, Emma Campbell, Michelle S. Somerville, Yuan Chen, Sarah L. Hulin-Curtis, Stephanie E.A. Burnell, James A. Davies, Michael M. Davies, Rachel Hargest, Simon Phillips, Adam D. Christian, Kevin E. Ashelford, Robert Andrews, Alan L. Parker, Richard J. Stanton, Awen Gallimore, Andrew Godkin
Journal: Clinical Cancer Research (2020)

Broadly expressed, highly differentiated tumor-associated antigens (TAA) can elicit antitumor immunity. However, vaccines targeting TAAs have demonstrated disappointing clinical results, reflecting poor antigen selection and/or immunosuppressive mechanisms.
Microglia in Alzheimer’s disease: Local heroes!
Authors: Nàdia Villacampa, Michael T. Heneka
Journal: The Journal of Experimental Medicine (2020)

In this issue of JEM, Reed-Geaghan et al. (https://doi.org/10.1084/jem.20191374) address the long-standing question about the primary source of myeloid cells located at β-amyloid deposits. Using genetic labeling experiments, the authors identify resident microglia as the only myeloid cells present at β-amyloid deposits.
Abstract P291: Effects of a Multidisciplinary Lifestyle Intervention on HDL Cholesterol Efflux Capacities in Adolescents With Obesity
Authors: Katherine Gagnon, Marjorie Boyer, Benoit J. Arsenault, Dominique Desrosiers, Johanne Harvey, Patricia Blackburn
Journal: Circulation (2020)

Studies have suggested that a reduced HDL cholesterol efflux capacities (CECs) may be associated with an increased risk of coronary heart disease. However, only few studies have evaluated the impact of a lifestyle modification program on HDL-CEC in adolescents with obesity. The objective of this study was to determine if a 16-week lifestyle modification program would improve HDL-CECs in adolescents with obesity. Twenty-nine adolescents with obesity (16 boys and 13 girls) from 11 to 16 years of age (14.0 ± 1.6 years) were selected to participate in this study. The aim of the lifestyle modification program was to improve eating habits and physical activity levels. During the study, each adolescent was followed by a multidisciplinary team and trained three sessions per week for 16 weeks. The exercise program focused on endurance type activities and all training sessions were supervised and performed in groups. Anthropometric data, metabolic variables and HDL-CECs were measured at baseline and at the end of the intervention. HDL-CECs were measured using ( 3 H)cholesterol-labeled J774 macrophages and HepG2 hepatocytes. Body mass index (33.6 to 32.7 kg/m 2 , p&lt;0.0001) and waist circumference (102.4 to 100.5 cm, p=0.001) were significantly reduced after the 16-week intervention program. We also found a significant decrease in triglyceride concentrations (1.28 to 1.04 mmol/L, p=0.02) as well as in total cholesterol/HDL cholesterol ratio (4.42 to 3.91, p=0.0007) whereas HDL cholesterol levels increased (1.03 to 1.14 mmol/L, p=0.002). J774-HDL-CECs and HepG2-HDL-CECs were not significantly modified after the intervention. In order to further explore the impact of intervention-induced changes in HDL cholesterol levels on exercise-induced changes in HDL-CECs, adolescents were divided into two groups according to their changes in HDL cholesterol levels during the study (low or high intervention-induced changes in HDL cholesterol levels). Adolescents with low HDL cholesterol levels intervention-induced changes did not show an increased in HepG2-HDL-CECs. However, a significant improvement in HepG2-HDL-CEC after the intervention was observed among adolescents characterized by the highest intervention-induced changes in HDL cholesterol levels (p=0.03). Intervention-induced changes in HDL cholesterol levels were also significantly associated with changes in HepG2-HDL-CEC (r=0.55; p=0.002). No association was found between changes in HDL cholesterol levels and changes in J774-HDL-CECs. In conclusion, we found that a structured lifestyle modification program leads to significant improvements in cardiometabolic risk profile and in HepG2-HDL-CEC in obese adolescents.
Erratum: Corrigendum: Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing
Authors: Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
Journal: Nature Medicine (2018)
Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system
Authors: Susanne Pfefferle, Svenja Reucher, Dominic Nörz, Marc Lütgehetmann
Journal: Eurosurveillance (2020)

Facing the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), high-volume respiratory testing is demanded in laboratories worldwide. We evaluated the performance of a molecular assay for the detection of SARS-CoV-2 on a high-throughput platform, the cobas 6800, using the ‘open channel’ for integration of a laboratory-developed assay. We observed good analytical performance in clinical specimens. The fully automated workflow enables high-throughput testing with minimal hands-on time, while offering fast and reliable results.
Abstract P248: Smoking, Smoking Cessation, and Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study
Authors: Ning Ding, Yingying Sang, Jeremy Van't Hof, Corey A Kalbaugh, Michael E Hall, Josef Coresh, Maya Salameh, Michael J Blaha, Weihong Tang, Kunihiro Matsushita
Journal: Circulation (2020)

Introduction: Smoking is the strongest risk factor for abdominal aortic aneurysm (AAA), and male ever smokers who are recommended for one-time screening for AAA with ultrasonography at age of 65 to 75 years. However, the proportion of eligible individuals who receive this screening remains small (~1%). Few studies have evaluated the association of key smoking parameters with incident AAA by sex. Methods: In 14,889 ARIC participants free of a history of AAA at baseline (1987-89), we quantified the associations of smoking parameters (pack-years, duration, and intensity [pack/day]) with incident AAA (hospitalizations with AAA diagnosis [ICD code: 441.3, 441.4, 38.44, 39.71] or a death certificate ICD code: 441.3, 441.4, I71.3, I71.4) using Cox models. Years since quitting in former smokers were explored as time-varying variables. Results: Over a median follow-up of 20 years, there were 567 cases of AAA. The incident rate of AAA was 5.98 per 1,000 person-years in male current smokers and 2.65 per 1,000 person-years in female current smokers. Pack-years was significantly associated with incident AAA (HR 7.31 [95% CI 5.48-9.74] for those smoked ≥40 pack-years vs. never smokers) and the association was stronger in women than men (8.53 [5.03-14.45] vs. 5.97 [4.21-8.47], p-for-interaction =0.02). Both smoking duration and intensity showed significant associations with AAA. Smoking cessation demonstrated a graded association with lower risk of AAA in both sexes, but significantly increased risk lasted longer in men (2.16 [1.39-3.36] in 30-&lt;40 years after cessation) than in women (1.84 [0.76-4.46] in 20-&lt;30 years after cessation) (Table). Conclusions: All smoking parameters tested consistently show significant associations with incident AAA in both sexes. After cessation, the residual risk lasted at least 40 years in men and 20 years in women. Our results further emphasize the importance of smoking prevention and early cessation for preventing AAA and the potential need of AAA screening in female current smokers and recent quitters.
Erratum. Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes Care 2019;42:2042–2049
Authors: Marie-Christine Vantyghem, Mikael Chetboun, Valéry Gmyr, Arnaud Jannin, Stéphanie Espiard, Kristell Le Mapihan, Violeta Raverdy, Nathalie Delalleau, François Machuron, Thomas Hubert, Marie Frimat, Eric Van Belle, Marc Hazzan, Pascal Pigny, Christian Noel, Robert Caiazzo, Julie Kerr-Conte, François Pattou
Journal: Diabetes Care (2020)

The names of the working groups that collaborated in the study reported in this article were inadvertently omitted from the byline. The corrected byline should …
Ventromedial hypothalamic nucleus neuronal subset regulates blood glucose independently of insulin
Authors: Jonathan N. Flak, Paulette B. Goforth, James Dell’Orco, Paul V. Sabatini, Chien Li, Nadejda Bozadjieva, Matthew Sorensen, Alec Valenta, Alan Rupp, Alison H. Affinati, Corentin Cras-Méneur, Ahsan Ansari, Jamie Sacksner, Nandan Kodur, Darleen A. Sandoval, Robert T. Kennedy, David P. Olson, Martin G. Myers
Journal: Journal of Clinical Investigation (2020)

To identify neurons that specifically increase blood glucose from among the diversely functioning cell types in the ventromedial hypothalamic nucleus (VMN), we studied the cholecystokinin receptor B–expressing (CCKBR-expressing) VMN targets of glucose-elevating parabrachial nucleus neurons. Activation of these VMNCCKBR neurons increased blood glucose. Furthermore, although silencing the broader VMN decreased energy expenditure and promoted weight gain without altering blood glucose levels, silencing VMNCCKBR neurons decreased hIepatic glucose production, insulin-independently decreasing blood glucose without altering energy balance. Silencing VMNCCKBR neurons also impaired the counterregulatory response to insulin-induced hypoglycemia and glucoprivation and replicated hypoglycemia-associated autonomic failure. Hence, VMNCCKBR cells represent a specialized subset of VMN cells that function to elevate glucose. These cells not only mediate the allostatic response to hypoglycemia but also modulate the homeostatic setpoint for blood glucose in an insulin-independent manner, consistent with a role for the brain in the insulin-independent control of glucose homeostasis.
The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark
Authors: A.Y.S. Wong, T. Frøslev, L. Dearing, H.J. Forbes, A. Mulick, K.E. Mansfield, R.J. Silverwood, A. Kjærsgaard, H.T. Sørensen, L. Smeeth, A. Lewin, S.A.J. Schmidt, S.M. Langan
Journal: British Journal of Dermatology (2020)

Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. This study aimed to evaluate the association between partner bereavement and (i) first‐time melanoma diagnosis and (ii) mortality in patients with melanoma. We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997–2017) and Danish nationwide registries (1997–2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random‐effects meta‐analysis. In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84–0·92] across the entire follow‐up period. In study 2, we observed increased melanoma‐specific mortality in people experiencing partner bereavement across the entire follow‐up period (HR 1·17, 95% CI 1·06–1·30), with the peak occurring during the first year of follow‐up (HR 1·31, 95% CI 1·07–1·60). We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self‐report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment:Talaganis et al. Br J Dermatol 2020; 183:607–608.
A multicenter phase II study of gemcitabine and S-1 combination therapy (GS therapy) in patients with metastatic pancreatic cancer
Authors: H. Ueno, T. Okusaka, J. Furuse, K. Yamao, A. Funakoshi, N. Boku, S. Ohkawa, A. Makimoto, T. Sato
Journal: Journal of Clinical Oncology (2007)

4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m 2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m 2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.
Abstract MP23: Interplay of Cognitive Impairment and Short Sleep Duration on Cardiovascular and Cerebrovascular Mortality
Authors: Julio Fernandez-Mendoza, Fan He, Susan L Calhoun, Duanping Liao, Alexandros N Vgontzas, Edward O Bixler
Journal: Circulation (2020)

Introduction: Epidemiological and experimental studies have shown that short sleep duration is associated with cognitive impairment as well as cardiovascular (CVD) and cerebrovascular (CBV) diseases. However, its role in predicting CVD/CBV mortality is still not well-established, particularly using objective sleep measures. Hypothesis: Polysomnography (PSG)-measured short sleep duration modifies the increased risk of CVD/CBV mortality associated with cognitive impairment in middle-age. Methods: We addressed this hypothesis in the Penn State Adult Cohort, a random, population-based sample studied in the sleep laboratory (N=1,524, 48.9±13.4y, 54% women) and followed-up after 20.5 ± 5.7 years to ascertain their cause of death. Cognitive impairment (n=155) was ascertained using a comprehensive neuropsychological battery including Mini-Mental State Examination, Symbol Digit Modalities Test, Trail Making Test parts A and B, Benton Visual Retention Test and Thurstone Word Fluency Test. PSG total sleep time classified subjects as normal (≥6 h) and short (&lt;6 h) sleepers. Out of the 563 subjects who were deceased as of December 31, 2018, 244 died of CVD/CBV. Cox proportional hazards regression controlling for age, sex, race, education, obesity, sleep apnea, mental health problems and physical health problems, including hypertension, diabetes, heart disease and stroke at baseline, was used to assess the association between cognitive impairment and mortality. Results: Cognitive impairment was associated with an increased risk of all-cause mortality [(HR: 1.72 (1.35-2.06)], which was significantly modified by objective sleep duration (p-interaction=0.01). The association between cognitive impairment and all-cause mortality was significantly stronger among subjects who slept &lt; 6 hours [HR: 2.00 (1.54-2.59)] than among those who slept ≥ 6 hours [HR: 1.00 (0.59-1.67)]. Despite the smaller sample size, we observed a similar pattern (p-interaction=0.18) that the association between cognitive impairment and CVD/CBV mortality was stronger among subjects who slept &lt; 6 hours [HR: 2.09 (1.43-3.05)] than among those who slept ≥ 6 hours [HR: 1.24 (0.60-2.57)]. Conclusions: The risk of mortality associated with cognitive impairment in middle-age is significantly increased in adults with objective short sleep duration. Middle-aged adults who sleep objectively short may be more vulnerable to the effect of clinical and subclinical cerebrovascular morbidity on cognitive impairment and, thus, early death from CVD/CBV.
Abstract P227: Psychosocial Predictors of Physical Capacity in Cardiac Rehabilitation
Authors: Binu Koirala, Bronwyn Everett, Yenna Salamonson, Robert Zecchin, Patricia Davidson
Journal: Circulation (2020)

Introduction: Despite the impressive gains achieved by those who attend cardiac rehabilitation, many patients fail to maintain the gains in physical capacity in the longer term. There are likely psychosocial characteristics that can be leveraged to sustain behavior change. Hypothesis: Patients with higher perceived cardiac control, social support, and exercise self-efficacy, without depression, and those who received motivational interviewing (MI) sessions, adjunctive to cardiac rehabilitation, will have a significantly higher physical capacity. Methods: This is a secondary analysis of the data from a randomized controlled trial of MI as a tool to enhance secondary prevention strategies in cardiovascular disease (MICIS study) conducted at three hospitals in Sydney, Australia who attended 6-week phase II cardiac rehabilitation. Two, 1-hour sessions of a nurse-delivered motivational interview focused on increasing physical capacity was implemented and the participants were followed at 6-weeks and 12-months. The outcome for the study was physical capacity measured by distance walked on the six-minute walk test (6MWT). Multiple imputations were used to handle missing data. Descriptive statistics, t-tests, chi-square tests and linear regression for cluster data were used for data analysis. Results: The mean (SD) age of participants (n=110) at baseline was 60.1 (10.57) years and the majority were male (71.8%). (Table). In the adjusted analysis, motivational interviewing (p =0.57), perceived cardiac control (p=0.30), self-efficacy for exercise (p = 0.06) and level of depressive symptoms were not related to 6MWT. With every unit increase in perceived social support score, there was a decrease in distance walked in 6MWT by 1.30 meters (b = -1.30; p= 0.007). Conclusion: In this sample, psychosocial predictors, except social support, were not likely to influence physical capacity. Investigating barriers and facilitators to sustaining the effects of cardiac rehabilitation are needed.
Towards the automatic detection of social biomarkers in autism spectrum disorder: introducing the simulated interaction task (SIT)
Authors: Hanna Drimalla, Tobias Scheffer, Niels Landwehr, Irina Baskow, Stefan Roepke, Behnoush Behnia, Isabel Dziobek
Journal: npj Digital Medicine (2020)

Social interaction deficits are evident in many psychiatric conditions and specifically in autism spectrum disorder (ASD), but hard to assess objectively. We present a digital tool to automatically quantify biomarkers of social interaction deficits: the simulated interaction task (SIT), which entails a standardized 7-min simulated dialog via video and the automated analysis of facial expressions, gaze behavior, and voice characteristics. In a study with 37 adults with ASD without intellectual disability and 43 healthy controls, we show the potential of the tool as a diagnostic instrument and for better description of ASD-associated social phenotypes. Using machine-learning tools, we detected individuals with ASD with an accuracy of 73%, sensitivity of 67%, and specificity of 79%, based on their facial expressions and vocal characteristics alone. Especially reduced social smiling and facial mimicry as well as a higher voice fundamental frequency and harmony-to-noise-ratio were characteristic for individuals with ASD. The time-effective and cost-effective computer-based analysis outperformed a majority vote and performed equal to clinical expert ratings.