tbuckley/cabot-search huggingface dataset:
Beyond Margin Status: Population-Based Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification Recategorization
Authors: Raymond U. Osarogiagbon, Nicholas R. Faris, Walter Stevens, Carrie Fehnel, Cheryl Houston-Harris, Philip Ojeabulu, Olawale A. Akinbobola, Yu-Shen Lee, Meredith A. Ray, Matthew P. Smeltzer
Journal: Journal of Thoracic Oncology (2019)
Evaluation of Acute Mountain Sickness by Unsedated Transnasal Esophagogastroduodenoscopy at High Altitude
Authors: Heiko Fruehauf, Stephan R. Vavricka, Thomas A. Lutz, Max Gassmann, Kacper A. Wojtal, Annina Erb, Marco Maggiorini, Werner Schwizer, Michael Fried, Mark Fox, Oliver Goetze, Thomas Greuter
Journal: Clinical Gastroenterology and Hepatology (2019)
IMMU-26. PEPTIDE VACCINE IMMUNOTHERAPY BIOMARKERS AND RESPONSE PATTERNS IN PEDIATRIC GLIOMAS
Authors: Soren Muller, Sameer Agnihotri, Karsen Shoger, Max Myers, Aaron Diaz, Hideho Okada, Ian Pollack, Gary Kohanbash
Journal: Neuro-Oncology (2018)

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine which elicited consistent antigen-specific T-cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD;n=7), partial response (PR;n=3), and near-complete/complete response (CR;n=2) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA-sequencing on PBMC samples (n=54) collected at multiple time points. Patients who showed CR demonstrated elevated levels of T-cell activation markers accompanied by a cytotoxic T-cell response shortly after treatment initiation. At week 34, CR patients demonstrated both interferon signaling and poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T-cell activation markers were associated with prolonged PFS. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing Phase II LGG vaccine immunotherapy, should monitor these response patterns.
GPs are now outnumbered by wider clinical staff at practices, analysis shows
Authors: Gareth Iacobucci
Journal: BMJ (2019)

More non-GP clinical staff now work in general practice in England than GPs, an analysis has shown.1

The fourth annual NHS workforce report from the Health Foundation shows that the number of non-GP clinical staff has grown more quickly than the number of permanent qualified GPs over the past three years.

In March 2016 there were 6% fewer non-GP clinical staff than GPs, the report said. By March 2019, however, non-GP clinical staff had overtaken GPs to outnumber them by 8% (29 459 full time equivalent (FTE) other clinical staff including …
Results from a Phase 2 Study of Navitoclax in Combination with Ruxolitinib in Patients with Primary or Secondary Myelofibrosis
Authors: Claire N Harrison, Jacqueline S Garcia, Ruben A Mesa, Tim CP Somervaille, Rami S. Komrokji, Naveen Pemmaraju, Catriona Jamieson, Nikolaos Papadantonakis, James M. Foran, Casey L. O'Connell, Leanne Holes, Jia Jia, Jason Harb, Jessica Hutti, Josef T. Prchal
Journal: Blood (2019)
Smoking prevalence following tobacco tax increases in Australia between 2001 and 2017: an interrupted time-series analysis
Authors: Anna L Wilkinson, Michelle M Scollo, Melanie A Wakefield, Matthew J Spittal, Frank J Chaloupka, Sarah J Durkin
Journal: The Lancet Public Health (2019)

BackgroundBuilding on substantial tobacco control action over the previous decade, Australia increased the taxes on tobacco by 25% without forewarning on April 30, 2010. Australia then became one of a few countries to pre-announce a series of increases in tobacco taxes, with annual 12·5% increases starting from December, 2013. We aimed to examine the effects of both tax increases on smoking prevalence.MethodsBy use of survey data from Australians aged 14 years and older in five capital cities, we did an interrupted time-series analysis to model the monthly prevalence of smoking (overall, of factory-made cigarettes [FMC], and of roll-your-own tobacco [RYO]), in the total sample and stratified by socioeconomic status subgroups. We measured outcomes in May, 2001–April, 2010; May, 2010–November, 2013; and December, 2013–April, 2017.FindingsThe 25% tax increase was associated with immediate (−0·745 percentage points; 95% CI −1·378 to −0·112) and sustained reductions in prevalence (monthly trend −0·023 percentage points; −0·044 to −0·003), which were driven by reductions in the prevalence of smoking of FMC. The prevalence of smoking of RYO increased between May, 2010, and November, 2013, after the 25% tax increase. At the start of the pre-announced annual 12·5% increases, we observed an immediate reduction in smoking (−0·997 percentage points; −1·632 to −0·362), followed by decreasing overall prevalence (monthly trend −0·044 percentage points; −0·063 to −0·026) due to ongoing decreases in the prevalence of FMC smoking and a cessation of increases in the prevalence of smoking of RYO. Immediate decreases in smoking and changing trends in the prevalence of smoking of RYO were most evident among groups with a lower socioeconomic status.InterpretationLarge tax increases are effective in reducing smoking prevalence, both as a single increase without forewarning and as a pre-announced series of increases. However, taxes on tobacco are best structured to apply equally to FMC and RYO products. Tobacco control policies should prohibit price marketing that otherwise erodes the full impact of such tax increases.FundingCancer Council Victoria.
Traumatic brain injury in homeless and marginally housed individuals: a systematic review and meta-analysis
Authors: Jacob L Stubbs, Allen E Thornton, Jessica M Sevick, Noah D Silverberg, Alasdair M Barr, William G Honer, William J Panenka
Journal: The Lancet Public Health (2019)

Homelessness is a global public health concern, and traumatic brain injury (TBI) could represent an underappreciated factor in the health trajectories of homeless and marginally housed individuals. We aimed to evaluate the lifetime prevalence of TBI in this population, and to summarise findings on TBI incidence and the association between TBI and health-related or functioning-related outcomes.For this systematic review and meta-analysis, we searched without date restrictions for original research studies in English that reported data on the prevalence or incidence of TBI, or the association between TBI and one or more health-related or function-related outcome measures. Studies were included if they had a group or clearly identifiable subgroup of individuals who were homeless, marginally housed, or seeking services for homeless people. With use of random-effects models, we calculated pooled estimates of the lifetime prevalence of any severity of TBI and the lifetime prevalence of moderate or severe TBI. We used meta-regression and subgroup analysis to evaluate potential moderators of prevalence estimates and the leave-one-out method for sensitivity analyses. We then summarised findings from all studies that evaluated TBI incidence and the association between TBI and health-related or functioning-related outcomes. All statistical analyses were done using R version 3.5.1. The study is registered with PROSPERO, number CRD42019119678.Of 463 potentially eligible studies identified by the search, 38 studies were included in the systematic review and 22 studies were included in the meta-analysis. The lifetime prevalence of any severity of TBI in homeless and marginally housed individuals (18 studies, n=9702 individuals) was 53·1% (95% CI 46·4-59·7; I2=97%) and the lifetime prevalence of moderate or severe TBI (nine studies, n=5787) was 22·5% (13·5-35·0; I2=99%). The method used to ascertain TBI history, the age of the sample, and the sample size significantly moderated estimated lifetime prevalence of any severity of TBI. TBI was consistently associated with poorer self-reported physical and mental health, higher suicidality and suicide risk, memory concerns, and increased health service use and criminal justice system involvement.The lifetime prevalence of TBI is high among homeless and marginally housed individuals, and a history of TBI is associated with poorer health and general functioning. Health-care providers and public health officials should have an increased awareness of the burden of TBI in this population. Prospective and longitudinal studies are needed to better understand how the health of this population is affected by TBI.Canadian Institutes of Health Research.
An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders
Authors: Nicholas J. Ashton, Abdul Hye, Anto P. Rajkumar, Antoine Leuzy, Stuart Snowden, Marc Suárez-Calvet, Thomas K. Karikari, Michael Schöll, Renaud La Joie, Gil D. Rabinovici, Kina Höglund, Clive Ballard, Tibor Hortobágyi, Per Svenningsson, Kaj Blennow, Henrik Zetterberg, Dag Aarsland
Journal: Nature Reviews Neurology (2020)
Amyloid-Beta (Aβ) Plaques Promote Seeding and Spreading of Alpha-Synuclein and Tau in a Mouse Model of Lewy Body Disorders with Aβ Pathology
Authors: Fares Bassil, Hannah J. Brown, Shankar Pattabhiraman, Joe E. Iwasyk, Chantal M. Maghames, Emily S. Meymand, Timothy O. Cox, Dawn M. Riddle, Bin Zhang, John Q. Trojanowski, Virginia M.-Y. Lee
Journal: Neuron (2019)
Boyd Tilak Batuwitage
Authors: Bisanth Batuwitage
Journal: BMJ (2019)

Boyd Tilak Batuwitage, better known as “Batu” to his friends, was born in Colombo, Sri Lanka, where he spent his formative years. He was the youngest of six brothers and identical twin to Brian. Boyd was schooled at Royal College, where he was a keen cricketer. He went on to …
Case 36-2019: A 34-Year-Old Man with Dyspnea, Odynophagia, and Abdominal Pain
Authors: Michael Saag, Dexter P. Mendoza, Marc S. Sherman, Gregory M. Cote, Angela R. Shih
Journal: New England Journal of Medicine (2019)

A 34-year-old man was admitted to the hospital because of dyspnea. An antibody differentiation assay confirmed a diagnosis of human immunodeficiency virus type 1 infection, and chest imaging was notable for diffuse ground-glass opacities. After treatment for Pneumocystis jirovecii pneumonia was initiated, acute abdominal pain developed. A diagnostic procedure was performed.
Endothelial Cell–Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production
Authors: Lufang Liu, Caodi Fang, Whitney Fu, Bo Jiang, Guangxin Li, Lingfeng Qin, Jacob Rosenbluth, Gavin Gong, Catherine B. Xie, Peter Yoo, George Tellides, Jordan S. Pober, Dan Jane-wit
Journal: Circulation (2019)

Ischemia reperfusion injury (IRI) predisposes to the formation of donor-specific antibodies, a factor contributing to chronic rejection and late allograft loss.
Curcumin analog CUR5–8 ameliorates nonalcoholic fatty liver disease in mice with high-fat diet-induced obesity
Authors: Eun Soo Lee, Mi-Hye Kwon, Hong Min Kim, Ho Bum Woo, Chan Mug Ahn, Choon Hee Chung
Journal: Metabolism (2019)

Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat storage in the liver and it is strongly linked with metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. Curcumin5-8 (CUR5-8) is a synthetic derivative of naturally active curcumin (CUR) that has anti-oxidative and anti-inflammatory properties. In the present study, we investigated the effects of CUR5-8, a novel CUR analog, on hepatic steatosis in mice with high-fat diet (HFD)-induced obesity.Based on their diets for 13 weeks, the mice were categorized into the following six groups: regular diet (RD, n = 10), RD with CUR (RD + CUR, 100 mg/kg/day, n = 10), RD with CUR5-8 (RD + CUR5-8, 100 mg/kg/day, n = 10), high-fat diet-induced obese mice (HFD, n = 10), HFD with CUR (HFD + CUR, 100 mg/kg/day, n = 10), and HFD with CUR5-8 (HFD + CUR5-8, 100 mg/kg/day, n = 10) for 13 weeks. Hematoxylin and eosin (H&E) staining of the sections revealed hepatic steatosis.CUR5-8 administration prevented increase in body and liver weights in mice with HFD-induced obesity. Compared to the HFD group, insulin resistance was significantly improved in the HFD + CUR5-8 group. Serum alanine aminotransferase level, which is an indicator of liver damage, was also decreased after CUR5-8 administration. H&E staining revealed that CUR5-8 treatment decreased hepatic steatosis in mice with HFD-induced obesity. Interestingly, CUR5-8, and not CUR, decreased the elevated liver triglyceride level induced by the HFD.These findings suggest that CUR5-8 ameliorates insulin resistance and hepatic steatosis in mice with HFD-induced obesity.
CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation
Authors: Zhaoqi Dong, Wenbing Chen, Chao Chen, Hongsheng Wang, Wanpeng Cui, Zhibing Tan, Heath Robinson, Nannan Gao, Bin Luo, Lei Zhang, Kai Zhao, Wen-Cheng Xiong, Lin Mei
Journal: Neuron (2019)
Antibodies against the erythroferrone N-terminal domain prevent hepcidin suppression and ameliorate murine thalassemia
Authors: João Arezes, Niall Foy, Kirsty McHugh, Doris Quinkert, Susan Benard, Anagha Sawant, Joe N. Frost, Andrew E. Armitage, Sant-Rayn Pasricha, Pei Jin Lim, May S. Tam, Edward Lavallie, Debra D. Pittman, Orla Cunningham, Matthew Lambert, John E. Murphy, Simon J. Draper, Reema Jasuja, Hal Drakesmith
Journal: Blood (2020)
The effects of canagliflozin on gout in type 2 diabetes: a post-hoc analysis of the CANVAS Program
Authors: JingWei Li, Sunil V Badve, Zien Zhou, Anthony Rodgers, Richard Day, Richard Oh, Mary Lee, Vlado Perkovic, Dick de Zeeuw, Kenneth W Mahaffey, Greg Fulcher, David R Matthews, Bruce Neal
Journal: The Lancet Rheumatology (2019)
Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial
Authors: Alison J Wimms, Julia L Kelly, Christopher D Turnbull, Alison McMillan, Sonya E Craig, John F O'Reilly, Annabel H Nickol, Emma L Hedley, Meredith D Decker, Leslee A Willes, Peter M A Calverley, Adam V Benjafield, John R Stradling, Mary J Morrell, Alison J Wimms, Julia L Kelly, Christopher D Turnbull, Alison McMillan, Sonya E Craig, John F O'Reilly, Annabel H Nickol, Sophie D West, Anita K Simonds, Shirmila Withana, Justin CT Pepperell, Neil R Ward, Brian D Kent, Timothy Quinnell, Mohammad Paracha, William Anderson, Emma L Hedley, Meredith D Decker, Leslee A Willes, Peter M A Calverley, Adam V Benjafield, John R Stradling, Mary J Morrell
Journal: The Lancet Respiratory Medicine (2019)
Identification of Two CAR T-Cell Populations Associated with Complete Response or Progressive Disease in Adult Lymphoma Patients Treated with Axi-Cel
Authors: Zinaida Good, Jay Y. Spiegel, Bita Sahaf, Meena B. Malipatlolla, Matthew J. Frank, John Baird, Lori S Muffly, Gursharan K. Claire, Juliana Craig, Katherine A. Kong, Sean Bendall, David B Miklos, Crystal L. Mackall
Journal: Blood (2019)
Improving together: collaboration needs to start with regulators
Authors: Nicola Burgess, Graeme Currie, Bernard Crump, John Richmond, Mark Johnson
Journal: BMJ (2019)

Nicola Burgess and colleagues argue for a move away from top-down regulation to a new approach that facilitates rather than hinders learning across organisations The regulatory landscape in the UK is changing again. From 1 April 2019 NHS England and NHS Improvement became what is effectively a single organisation with far reaching responsibility for the oversight of the system. The structural features of this change, which will eventually require legislative reform, have been widely debated, not least by those affected by plans for a collaborative approach to improvement in the NHS.12 But there has been less discussion about the style and approach to regulation that might be best suited to drive improvement in the NHS as set out in the long term plan.3 We contend that a major change is required in the way the system interacts with service providers if we are to be successful in developing a new service model for the 21st century. Currently the NHS relies on positional authority—a hierarchical system in which regulators use their power and leverage to drive change. Drawing on organisational theory we contend that structural change in the regulatory landscape is insufficient to drive interorganisational learning for improvement. Specifically, we argue that regulation needs to shift towards a more relational form of governance in which informal social systems foster learning across organisations. This relational authority emerges through interpersonal relationships characterised by trust and mutual respect and has to be earnt over time.4 To support our argument we draw on our experience analysing a major experiment in delivering service transformation in five NHS hospital trusts in partnership with NHS Improvement and the Virginia Mason Institute in the US (box 1).3 Box 1 ### NHS-Virginia Mason Institute partnership In 2015 a five year partnership was established between the NHS and US based Virginia Mason … RETURN TO TEXT
Intralymphatic immunotherapy in pollen-allergic young adults with rhinoconjunctivitis and mild asthma: A randomized trial
Authors: Jon R. Konradsen, Jeanette Grundström, Laila Hellkvist, Thi Anh Thu Tran, Niklas Andersson, Guro Gafvelin, M.B. Gea Kiewiet, Carl Hamsten, Jiaqian Tang, Rebecca V. Parkin, Mohamed H. Shamji, Gunilla Hedlin, Lars-Olaf Cardell, Marianne van Hage
Journal: Journal of Allergy and Clinical Immunology (2019)
Association between osteoporosis and statins therapy: the story continues
Authors: Andrea Michelle Burden, Stefan Weiler
Journal: Annals of the Rheumatic Diseases (2019)

It was with great interest that we read the study conducted by Leutner et al 1 that investigated the relationship between the use of statins and osteoporosis. As identified in the correspondence by Shih-Wei Lai, there is a long-standing interest in the relationship between statins and bone, with numerous observational studies identifying a protective effect; however, results are inconsistent.2–4 In their study, Leutner et al identified that the use of statins was associated with an impressive 3.62-fold increased risk of being diagnosed with osteoporosis, and this association was observed in both men (OR 3.35) and women (OR 3.90. However, we note that if the crude ORs are calculated on the data matched for age and sex (derived from table 1 of …
Comment on Pilemann-Lyberg et al. Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes. Diabetes Care 2019;42:1088–1094
Authors: Wenrong Chen, Dan Lu, Zuoming Huang, Lin Xiao
Journal: Diabetes Care (2019)

Type 1 diabetes (T1D) is an important risk factor for development of chronic kidney disease (CKD) and cardiovascular disease (CVD). Earlier detection of risk factors for diabetic complications can improve the risk stratification of the patients with diabetes and allow targeted treatment.

Recently, Pilemann-Lyberg et al. (1) reported that a higher uric acid (UA) level is associated with a higher risk of CKD and CVD. Importantly, adding UA to the adjusted model including conventional risk factors can significantly improve the relative integrated discrimination index. This study was interesting and provided further support that UA should be regarded as a risk factor of CKD and CVD in T1D.

Epidemiologic studies have shown inconsistent conclusions about …
Canada’s Single-Payer Health Care System—Reply
Authors: Steffie Woolhandler, David U. Himmelstein
Journal: JAMA (2019)

In Reply Dr McKee’s complimentary and critical comments about Canada’s health care echo those of many Canadians, whose system is, in our view,1 properly structured but inadequately funded. In 2018, Canada spent $5445 less per capita on health care than the United States.
RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants
Authors: Hai Lin, Katherine A. Hargreaves, Rudong Li, Jill L. Reiter, Yue Wang, Matthew Mort, David N. Cooper, Yaoqi Zhou, Chi Zhang, Michael T. Eadon, M. Eileen Dolan, Joseph Ipe, Todd C. Skaar, Yunlong Liu
Journal: Genome biology (2019)

Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, and evolutionary conservation features. RegSNPs-intron showed excellent performance in evaluating the pathogenic impacts of iSNVs. Using a high-throughput functional reporter assay called ASSET-seq (ASsay for Splicing using ExonTrap and sequencing), we evaluate the impact of RegSNPs-intron predictions on splicing outcome. Together, RegSNPs-intron and ASSET-seq enable effective prioritization of iSNVs for disease pathogenesis.
Development and validation of M1 substages for previously untreated metastatic nasopharyngeal carcinoma
Authors: S.K. Chan, C.W. Choi, T.C. Chau, S.C. Chau, K.O. Lam, S.Y. Chan, C.C. Tong, W.L. Chan, D.L.W. Kwong, T.W. Leung, M.Y. Luk, A.W.M. Lee, V.H.F. Lee
Journal: Annals of Oncology (2019)