tbuckley/cabot-search huggingface dataset:
Comparative Effectiveness and Safety of Bariatric Procedures for Weight Loss
Authors: David Arterburn, Robert Wellman, Ana Emiliano, Steven R. Smith, Andrew O. Odegaard, Sameer Murali, Neely Williams, Karen J. Coleman, Anita Courcoulas, R. Yates Coley, Jane Anau, Roy Pardee, Sengwee Toh, Cheri Janning, Andrea Cook, Jessica Sturtevant, Casie Horgan, Kathleen M. McTigue
Journal: Annals of Internal Medicine (2018)

Background: There has been a dramatic shift in use of bariatric procedures, but little is known about their long-term comparative effectiveness. Objective: To compare weight loss and safety among bariatric procedures. Design: Retrospective observational cohort study, January 2005 to September 2015. (ClinicalTrials.gov: NCT02741674) Setting: 41 health systems in the National Patient-Centered Clinical Research Network. Participants: 65 093 patients aged 20 to 79 years with body mass index (BMI) of 35 kg/m2 or greater who had bariatric procedures. Intervention: 32 208 Roux-en-Y gastric bypass (RYGB), 29 693 sleeve gastrectomy (SG), and 3192 adjustable gastric banding (AGB) procedures. Measurements: Estimated percent total weight loss (TWL) at 1, 3, and 5 years; 30-day rates of major adverse events. Results: Total numbers of eligible patients with weight measures at 1, 3, and 5 years were 44 978 (84%), 20 783 (68%), and 7159 (69%), respectively. Thirty-day rates of major adverse events were 5.0% for RYGB, 2.6% for SG, and 2.9% for AGB. One-year mean TWLs were 31.2% (95% CI, 31.1% to 31.3%) for RYGB, 25.2% (CI, 25.1% to 25.4%) for SG, and 13.7% (CI, 13.3% to 14.0%) for AGB. At 1 year, RYGB patients lost 5.9 (CI, 5.8 to 6.1) percentage points more weight than SG patients and 17.7 (CI, 17.3 to 18.1) percentage points more than AGB patients, and SG patients lost 12.0 (CI, 11.6 to 12.5) percentage points more than AGB patients. Five-year mean TWLs were 25.5% (CI, 25.1% to 25.9%) for RYGB, 18.8% (CI, 18.0% to 19.6%) for SG, and 11.7% (CI, 10.2% to 13.1%) for AGB. Patients with diabetes, those with BMI less than 50 kg/m2, those aged 65 years or older, African American patients, and Hispanic patients lost less weight than patients without those characteristics. Limitation: Potential unobserved confounding due to nonrandomized design; electronic health record databases had missing outcome data. Conclusion: Adults lost more weight with RYGB than with SG or AGB at 1, 3, and 5 years; however, RYGB had the highest 30-day rate of major adverse events. Small subgroup differences in weight loss outcomes were observed. Primary Funding Source: Patient-Centered Outcomes Research Institute.
British man with CJD gets experimental treatment in world first
Authors: Clare Dyer
Journal: BMJ (2018)

A High Court judge has given the go ahead for a middle aged man with sporadic Creutzfeldt-Jakob disease (CJD) to become the first human worldwide to be given the novel drug PRN100.1

The drug, a humanised monoclonal antibody, has been in development since 2007 and has been tested on animals, but researchers have been unable to raise the funds for a clinical trial.

Because of his condition the man, referred to as KG, lacks the full mental capacity to weigh up the risks and benefits of the treatment. But he, his family, the official solicitor as his representative, and University College London Hospitals NHS Foundation Trust have all …
Myocardial Edema After Ischemia/Reperfusion Is Not Stable and Follows a Bimodal Pattern: Imaging and Histological Tissue Characterization (vol 65, pg 315, 2015)
Authors: R Fernandez-Jimenez, J Sanchez-Gonzalez, J Aguero, J Garcia-Prieto, G J Lopez-Martin, J M Garcia-Ruiz, A Molina-Iracheta, X Rossello, L Fernandez-Friera, G Pizarro, A Garcia-Alvarez, E Dall'Armellina, C Macaya, R P Choudhury, V Fuster, B Ibanez
Journal: Journal of the American College of Cardiology (2018)
An Interleukin-23-Interleukin-22 Axis Regulates Intestinal Microbial Homeostasis to Protect from Diet-Induced Atherosclerosis
Authors: Aliia R. Fatkhullina, Iuliia O. Peshkova, Amiran Dzutsev, Turan Aghayev, John A. McCulloch, Vishal Thovarai, Jonathan H. Badger, Ravi Vats, Prithu Sundd, Hsin-Yao Tang, Andrew V. Kossenkov, Stanley L. Hazen, Giorgio Trinchieri, Sergei I. Grivennikov, Ekaterina K. Koltsova
Journal: Immunity (2018)
Doctors are cautioned against using Google Translate in consultations
Authors: Tom Moberly
Journal: BMJ (2018)

Doctors should not use Google Translate in consultations with patients because of the risk of introducing communication errors, medical defence organisations have said.

Last month The BMJ reported that researchers from the London School of Hygiene and Tropical Medicine had found that doctors were using Google Translate to overcome language barriers in consultations.1

“We would recommend extreme caution in using, and relying on, computer translation in everyday clinical practice,” said Naeem Nazem, medical adviser to the Medical and Dental Defence Union of Scotland. “In usual clinical practice, the risks of using computer translations, in the presence of validated alternatives, is likely to increase the risks …
Violence Victimization, Substance Use, and Suicide Risk Among Sexual Minority High School Students — United States, 2015–2017
Authors: Michelle M. Johns, Richard Lowry, Catherine N. Rasberry, Richard Dunville, Leah Robin, Sanjana Pampati, Deborah M. Stone, Laura M. Mercer Kollar
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Youths identifying as lesbian, gay, bisexual, or another nonheterosexual identity (sexual minority youths) report more violence victimization, substance use, and suicide risk than do heterosexual youths (1). These disparities are generally attributed to minority stress (the process through which stigma directed toward sexual minorities influences health outcomes) (2,3). Sexual minority youths might experience negative outcomes associated with minority stress differently across sexual identities, but to date, no nationally representative study has examined differences in victimization, substance use, and suicide risk within sexual minority youth. Using pooled data from the 2015 and 2017 national Youth Risk Behavior Surveys (YRBS), relationships between sexual identity groups and victimization, substance use, and suicide risk were evaluated with sex-stratified logistic regression models. Compared with heterosexual students, bisexual females and all sexual minority males reported more victimization; lesbian and bisexual females reported more use of alcohol, cigarettes, and marijuana; and all sexual minority youths reported elevated high-risk substance use and suicide risk. Programmatic efforts to reduce and prevent victimization, substance use, and suicide risk among sexual minority youths might benefit from consideration of issues within group differences.
Progress in Kidney Cancer Outcomes Through Collaboration, Innovation, and Discovery
Authors: David F. McDermott, Michael Carducci
Journal: Journal of Clinical Oncology (2018)

Over the last 3 years, investigators have leveraged a growing understanding of kidney cancer biology to target critical pathways and produce durable benefits, even rare remissions, for patients with advanced kidney cancer.2][3][4][5] In this Special Series issue of Journal of Clinical Oncology, kidney cancer experts describe how recent advances can be integrated into clinical management strategies and focus on important future priorities, including correlating genomic analyses with clinical outcomes to identify molecular predictive biomarkers, understanding the mechanisms by which kidney cancer develops and becomes resistant to standard therapies, and exploiting new discoveries to produce durable clinical benefits and maintain quality of life for patients with advanced disease.As editors for this issue, we summarize the contributions of the invited reviews and comment on the continued need for collaboration and resources to leverage the advances described.The comprehensive genetic analysis of clear-cell renal cell carcinoma (ccRCC) performed by the Cancer Genome Atlas Kidney Cancer Research Network (TCGA KCRN) investigators and others highlighted the importance of several pathways in kidney carcinogenesis, including von Hippel-Lindau (VHL)-hypoxia-inducible factor (HIF), chromatin remodeling/histone methylation, and tumor metabolism. 6,7These priority targets provided a roadmap for future translational research that is the focus of several of the articles in this special issue.The review by Hsieh et al 8 explore the consequences of the most common genetic alterations (eg, chromosome 3p loss, mutations in the VHL tumor suppressor gene and chromatin regulatory genes [eg, PBRM1, BAP1, and SETD2]) in ccRCCs. 91][12][13][14] Although drugs against one HIF-responsive gene product, vascular endothelial growth factor (VEGF), have contributed to significant progress over the past decade, the treatment of advanced kidney cancer remains inadequate. 15,16he authors explain how an improved understanding of the interrelationship between VHL inactivation and chromatin dysregulation may lead to improvements in risk stratification, treatment selection, and patient outcomes.Despite the fact that a master regulator of tumor metabolism, the mammalian target of rapamycin complex 1, is activated in most kidney cancer, only a subset
A Polygenic Genetic Architecture of Flowering Time in the Worldwide<i>Arabidopsis thaliana</i>Population
Authors: Yanjun Zan, Örjan Carlborg
Journal: Molecular Biology and Evolution (2018)

Here, we report an empirical study of the polygenic basis underlying the evolution of complex traits. Flowering time variation measured at 10 and 16°C in the 1,001-genomes Arabidopsis thaliana collection of natural accessions were used as a model. The polygenic architecture of flowering time was defined as the 48 loci that were significantly associated with flowering time-at 10 and/or 16°C and/or their difference-in this population. Contributions from alleles at flowering time associated loci to global and local adaptation were explored by evaluating their distribution across genetically and geographically defined subpopulations across the native range of the species. The dynamics in the genetic architecture of flowering time in response to temperature was evaluated by estimating how the effects of these loci on flowering changed with growth temperature. Overall, the genetic basis of flowering time was stable-about 2/3 of the flowering time loci had similar effects at 10°C and 16°C-but many loci were involved in gene by temperature interactions. Globally present alleles, mostly of moderate effect, contributed to the differences in flowering times between the subpopulations via subtle changes in allele frequencies. More extreme local adaptations were, on several occasions, due to regional alleles with relatively large effects, and their linkage disequilibrium-patterns suggest coevolution of functionally connected alleles within local populations. Overall, these findings provide a significant contribution to our understanding about the possible modes of global and local evolution of a complex adaptive trait in A. thaliana.
Cilia-driven cerebrospinal fluid flow directs expression of urotensin neuropeptides to straighten the vertebrate body axis
Authors: Xiaoli Zhang, Shuo Jia, Zhe Chen, Yan Ling Chong, Haibo Xie, Dong Feng, Xiaotong Wu, Don Zhu Song, Sudipto Roy, Chengtian Zhao
Journal: Nature Genetics (2018)
Abstract 15370: Genetic Study Identifies Common Variation in PHACTR1 to Associate With Fibromuscular Dysplasia <i>(Best of Basic Science Abstract)</i>
Authors: Soto Romuald Kiando, Nathan Tucker, Alexander Katz, Cyrielle Tréard, Valentina D’Escamard, Luis J Castro-Vega, Zi Ye, Carin Y Smith, Erin Austin, Cristina Barlasina, Daniele Cusi, Pilar Galan, Jean-Philippe Empana, Xavier Jouven, Patrick Brunval, Jeffrey W Olin, Heather Gornik, Pierre-François Plouin, Iftikhar J Kullo, David J Milan, Santhi K Ganesh, Pierre Boutouyrie, Jason Kovacic, Xavier Jeunemaitre, Nabila Bouatia-Naji
Journal: Circulation (2015)

Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to arterial stenosis, aneurysm and dissection, mainly in renal and carotid arteries. FMD has higher prevalence in females (80-90%) and is associated with hypertension and stroke. The pathophysiology of FMD is unclear and a genetic origin is suspected. We performed a genetic association study in European ancestry individuals. The discovery included 249 cases and 689 controls, in which we analyzed ∼26K common variants (MAF&gt;0.05) using an exome-chip array. We followed up 13 loci (P&lt;10-4) in 393 cases and 2537 controls and replicated a signal on Chr6. Three additional studies (combined Ncases=512, Ncontrols=669) confirmed this association, with an overall OR of 1.39, (P=7.4х10e-10 , All Ncases=1154, All Ncontrols=3895). The FMD risk variant is intronic to the phosphatase and actin regulator 1 gene (PHACTR1), involved in angiogenesis and cell migration. PHACTR1 is a risk locus for coronary artery disease, migraine, and cervical artery dissection, which may occur in FMD. We found a significant association between the risk allele and higher central pulse pressure (P=0.0009), increased intima media thickness (P=0.001) and wall cross-sectional area (P=0.003) of carotids assessed by echotracking in 3800 population-based individuals. The correlation of genotypes with the expression of PHACTR1 in primary cultured human fibroblasts showed higher expression in FMD risk allele carriers, compared to non carriers (N=57, P=0.02). Finally, Phactr1 knockdown of zebrafish showed significantly dilated vessels (P=0.003) indicating impaired vascular development. In conclusion, we report the first risk locus for FMD with the largest genetic association study conducted so far. Our data reveal a common genetic variant at PHACTR1 providing indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases.
THU0243 Case fatality over 365 days after first acute coronary syndrome in patients with ankylosing spondylitis
Authors: A. Södergren, J. Askling, K. Bengtsson, H. Forsblad-D’Elia, T. Jernberg, U. Lindström, L. Ljung, Ä. Mantel, L.T. Jacobsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ankylosing spondylitis (AS) is characterised by systemic and local inflammation of the axial skeleton, joints, and entheses. Studies have suggested a higher risk of acute coronary syndrome (ACS) among patients with AS compared with the general population, but whether patients with AS also have an increased fatality following ACS is not known. <h3>Objectives</h3> Is AS associated with an increased case fatality after a first-time ACS compared with the general population? <h3>Methods</h3> From the Swedish National Patient Register (NPR) we identified all patients registered with AS Jan 2001 through Dec 2014 and a later registration of a first time ACS between Jan 2006 and Dec 2014 (n=292). As a general population comparator, we identified up to 5 individuals per index-patient (n=1276), matched on year of first ACS and birth, gender, and place of living. The follow-up period began at the date of admission for ACS and extended until death, emigration, 365 days of follow-up or 31 December 2014, whichever occurred first. Hazard ratios (HR) for death in the AS group vs. the general population comparator was assessed using Cox regression. We assessed HRs for death in two intervals: 30 day mortality (day 1 through 30), and mortality day 31 through 365. <h3>Results</h3> During the 365 days following the ACS, 56 (19%) of the 292 AS patients and 184 (14%) of the 1276 population controls died (table 1). Whereas the 30 day mortality in the AS group was not elevated (HR=0.9), the mortality day 31 through 365 was doubled compared with the general population (HR=2.2, table 1 and figure 1). <h3>Conclusions</h3> Patients with AS were at increased risk of death during the first year, though not during the first month, following ACS. It is yet not clear whether this could be due to factors associated with the AS disease <i>per se</i>, or differences in ACS characteristics or treatment. <h3>Disclosure of Interest</h3> A. Södergren: None declared, J. Askling Consultant for: JA and Karolinska Institutet had research agreements with Abbvie, BMS, MSD, Pfizer, Roche, Astra-Zeneca, Lilly, Samsung and UCB, mainly in the context of safety monitoring of biologics via ARTIS/The Swedish Biologics Register. For these, JA has been principal investigator. Karolinska Institutet has received remuneration for JA participating in ad boards arranged by Pfizer and Lilly, K. Bengtsson: None declared, H. Forsblad-D'Elia: None declared, T. Jernberg: None declared, U. Lindström: None declared, L. Ljung: None declared, Ä. Mantel: None declared, L. Jacobsson: None declared
Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer
Authors: Alexander Melamed, Daniel J. Margul, Ling Chen, Nancy L. Keating, Marcela G. del Carmen, Junhua Yang, Brandon-Luke L. Seagle, Amy Alexander, Emma L. Barber, Laurel W. Rice, Jason D. Wright, Masha Kocherginsky, Shohreh Shahabi, J. Alejandro Rauh-Hain
Journal: New England Journal of Medicine (2018)

Minimally invasive surgery was adopted as an alternative to laparotomy (open surgery) for radical hysterectomy in patients with early-stage cervical cancer before high-quality evidence regarding its effect on survival was available. We sought to determine the effect of minimally invasive surgery on all-cause mortality among women undergoing radical hysterectomy for cervical cancer.
The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration
Authors: Robert F. Mullins, Gerald McGwin, Karen Searcey, Mark E. Clark, Elizabeth L. Kennedy, Christine A. Curcio, Edwin M. Stone, Cynthia Owsley
Journal: Ophthalmology (2018)
Low Levels of Neurologic Toxicity with Retained Anti-Lymphoma Activity in a Phase I Clinical Trial of T Cells Expressing a Novel Anti-CD19 CAR
Authors: Jennifer Brudno, Steven Hartman, Norris Lam, David F. Stroncek, John M. Rossi, Yueh-wei Shen, Allen Xue, Adrian Bot, Jennifer A Kanakry, Steven Z. Pavletic, Lekha Mikkilineni, Mark Roschewski, Robert M. Dean, Jeremy J. Rose, Rashmika Patel, Brenna Hansen, Steve A. Rosenberg, Ronald E. Gress, James N. Kochenderfer
Journal: Blood (2018)
Immunoglobulin Lambda Translocations Identify Poor Outcome and IMiD Resistance in Multiple Myeloma and Co-Occur with Hyperdiploidy
Authors: Benjamin G Barwick, Paola Neri, Nizar Bahlis, Ajay K Nooka, Jonathan L Kaufman, Vikas A. Gupta, Daniel Auclair, Jonathan J Keats, Sagar Lonial, Paula M Vertino, Lawrence H. Boise
Journal: Blood (2018)
Accuracy, Safety, and Reliability of Novel Phase I Designs—Letter
Authors: Nolan A. Wages, Thomas M. Braun
Journal: Clinical Cancer Research (2018)

A recently published review (1) of the accuracy, safety, and reliability of novel phase I methods concluded that the Bayesian Optimal Interval (BOIN; ref. 2) method does not suffer from the issue of “irrational” dose assignment. This property is defined by the authors as failing to deescalate the dose when 2 of 3 or ≥3 of 6 patients had dose-limiting toxicities (DLT) at a dose. This letter examines the author's definition of irrational dose assignment in a simulated trial example using the BOIN method. We generated DLT outcomes under an assumed set of true DLT probabilities (0.18, 0.25, 0.32, 0.36, 0.60, 0.69; Scenario 2 in Supplementary Table S2 of Zhou and colleagues; ref. 1) for a trial of n = 36 patients in cohorts of size 1. The target DLT rate is 25%, which yields dose escalation and deescalation boundaries of 19.7% and 29.8%, respectively. The allocation decisions of the BOIN method for the simulated trial are reported in Fig. 1. Note that patient 15 is the third of 6 patients to have a DLT with dose 3. Thus, the dose assignment for patient 16 is deescalated to dose 2, a decision that is classified as “rational” by the authors (1). However, the BOIN method recommends returning to dose level 3 with patient 17 immediately after a DLT is observed at dose level 2 in patient 16. In fact, no matter what DLT outcome was observed for patient 16, the observed DLT rate at dose level 2, either 0 of 6 or 1 of 6, would guarantee that the BOIN method would return to dose level 3 for patient 17. Therefore, the information obtained from the participation of patient 16 in the study does not contribute to the dose assignment algorithm for patient 17. Overall, data observed for 8 of 36 (22%) patients accrued to the study (patients 9, 13, 16, 17, 19, 21, 23, and 30) do not inform the dosing decision for the following patient accrued to the study. It is not clinically sensible to view as irrational the failing to deescalate when ≥3 of 6 patients experienced DLTs, but then allow, as rational, returning to that dose when the very next patient has a DLT at the next lowest dose level. While this simulated trial constitutes only a single example of a behavior of the BOIN method that would not be clinically acceptable, we hope that it will encourage researchers to take a closer look at in-trial behavior of new phase I methods.See the Response, p. 5483No potential conflicts of interest were disclosed.
Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study
Authors: Joakim Esbjörnsson, Fredrik Månsson, Anders Kvist, Zacarias J da Silva, Sören Andersson, Eva Maria Fenyö, Per-Erik Isberg, Antonio J Biague, Jacob Lindman, Angelica A Palm, Sarah L Rowland-Jones, Marianne Jansson, Patrik Medstrand, Hans Norrgren, Babetida N'Buna, Antonio J. Biague, Ansu Biai, Cidia Camara, Joakim Esbjörnsson, Marianne Jansson, Sara Karlson, Jacob Lindman, Patrik Medstrand, Fredrik Månsson, Hans Norrgren, Angelica A. Palm, Gülsen Özkaya Sahin, Zacarias José da Silva, Sten Wilhelmson
Journal: The Lancet HIV (2018)