tbuckley/cabot-search huggingface dataset:
A practice transformation model to improve lung cancer care.
Authors: Daisy E. Escobar, Mohd Khushman, Jennifer Young Pierce, Cathy Tinnea, Austin Cadden, Debra Wujcik, Susie Owenby, Sachin Gopalkrishn Pai
Journal: Journal of Clinical Oncology (2019)

92 Background: Lung cancer has the highest cause of cancer death, treatment of which is both complicated and expensive. Emerging actionable biomarkers and treatments provide both opportunity and treatment challenges. Adherence to evidence-based treatment and advanced care discussions add value to care. Oncology practices need to document the above to participate in value-based care reimbursement models. A Practice Transformation (PT) model was implemented to address quality and cost issues. Methods: After IRB approval, baseline data on lung cancer patients diagnosed during a 6-month period (Jul-Dec 2017) were collected through chart abstraction and treatment planning surveys. Rates of molecular testing ordered, results available at time of treatment decision-making, guideline concordant treatment decisions, and documentation of advanced care discussions were presented to the PT team. After education on recent clinical trial results and NCCN treatment guidelines, the PT team determined strategies for change. The PT team met after two 3-month periods of PT for education updates and progress reports. Data was compared on newly diagnosed patients during a 6-month period (Jul-Dec 2018), one year after the baseline period. Results: A total of forty-two patients were diagnosed in two 6-month periods, baseline and study period. Average age was 65 years, 57% male, 71% Caucasian, 95% ever smokers, 71% adenocarcinoma histology. Rate of ordering any molecular testing was (16/19) 84% in the baseline period vs (20/23) 86% in the study period. However, extended molecular testing increased from 16% (3/19) to 60% (12/20), p = .05 Fishers exact test. At treatment initiation, evidence-based treatment selections went from 47% to 52%. Documentation of advanced care discussions, 42% (8/19) to 56% (13/23), did not change significantly. Conclusions: A PT model that included education, and two cycles of implementation and feedback, resulted in increased molecular testing to inform evidence-based treatment selections. Increased awareness of the lack of documentation of advanced care discussions provides opportunity for continued improvement to effect quality care.
Inflammasome signaling and regulation of interleukin-1 family cytokines
Authors: Amy H. Chan, Kate Schroder
Journal: The Journal of Experimental Medicine (2019)

Specific IL-1 family cytokines are expressed by cells as cytosolic pro-forms that require cleavage for their activity and cellular release. IL-1β, IL-18, and IL-37 maturation and secretion is governed by inflammatory caspases within signaling platforms called inflammasomes. By inducing pyroptosis, inflammasomes can also drive the release of the alarmin IL-1α. Recent advances have transformed our mechanistic understanding of inflammasome signaling, cell death decisions, and cytokine activation and secretion. Here, we provide an updated view of inflammasome signaling; mechanisms underpinning IL-1α, IL-1β, IL-18, and IL-37 maturation and release; and the functions of these cytokines in protective and pathological inflammation.
Abstract 208: Reliable Biomimetic Culture System for Pig and Human Heart Slices
Authors: Riham Abouleisa, Qinghui Ou, Zoë Jacobson, Xian-Liang Tang, Sajedah M Hindi, Ashok Kumar, Kathryn N Ivey, Guruprasad Giridharan, Ayman Al-Baz, Kenneth Brittian, Benjamin Rood, Bradford G Hill, Steven P Jones, Roberto Bolli, Tamer M Mohamed
Journal: Circulation Research (2019)

Rationale: Heart failure is the number one killer and drug induced cardiotoxicity is a major cause of market withdrawal. The lack of availability of culture systems for human heart tissue that is functionally and structurally viable for more than 24 hours is a limiting factor in validation of novel heart failure therapies as well as reliable cardiotoxicity testing. Therefore, there is an urgent need to develop a reliable system for culturing human heart tissue for testing drug efficacy and toxicity. Objective: To develop a reliable method to culture pig and human heart slices under full physiological conditions for a period of time sufficient to test therapeutic efficacy and acute drug toxicity. Methods and Results: Here we describe a novel biomimetic culture system that maintains full viability and functionality of human and pig heart slices (300 μm thickness) for 6 days in culture through optimization of the medium and culture conditions with continuous electrical stimulation at 1.2 Hz and oxygenation of the medium. Functional viability of these slices over 6 days was confirmed by assessing their calcium homeostasis, twitch force generation, and response to β-adrenergic stimulation. Temporal transcriptome analysis using RNAseq at day 2, 6, and 10 in culture confirmed overall maintenance of normal gene expression for up to 6 days, while over 500 transcripts were differentially regulated after 10 days. Electron microscopy demonstrated intact mitochondria and Z-disc ultra-structures after 6 days in culture under our optimized conditions. This biomimetic culture system was successful in keeping human heart slices completely viable and functionally and structurally intact for 6 days in culture. We also used this system to demonstrate the effects of a novel gene therapy approach in human heart slices. Conclusions: We have developed and optimized a reliable and easily reproducible culture system for pig and human heart slices as a platform for testing the efficacy of novel heart failure therapeutics as well as reliable testing of cardiotoxicity in a 3D heart model.
Long Term Follow-up in Mantle Cell Lymphoma Patients Treated with R-GemOx Followed By Consolidation and Rituximab Maintenance
Authors: Marta Garcia Recio, Leyre Bento, Sandra Pérez-León, Sara Aida Jiménez-Julià, Jordi Gines, Jordi Martínez-Serra, Antonia Sampol, Antonio Gutiérrez
Journal: Blood (2018)
Abstract 901: Muscle-specific Stress Fibers Give Rise to Sarcomeres in Cardiomyocytes
Authors: Dylan T Burnette, Aidan M Fenix, Abigail C Neininger, Nilay Taneja, Karren Hyde, Mike R Visetsouk, Ryan Garde, Baohong Liu, Benjamin R Nixon, Annabelle E Manalo, Jason R Becker, Scott W Crawley, David M Bader, Matthew J Tyska, Qi Liu, Jennifer H Gutzman
Journal: Circulation Research (2019)

The sarcomere is the contractile unit that drives muscle contraction. Despite its importance, little is understood about how a disordered acto-myosin distribution converts into an ordered contractile array during sarcomere assembly. Here, we take advantage of a sarcomere assembly assay we developed using human induced pluripotent stem cell derived cardiomycytes to image the formation of sarcomeres, using live-cell high resolution microscopy. Our data show that a population of muscle specific stress fibers (MSFs) are essential sarcomere precursors. Interestingly, MSFs are formed at the leading edge of cells, undergo retrograde flow, and transition into sarcomere-containing myofibrils on the dorsal surface of cardiomyocytes. This is in direct contradiction to a recent report claiming sarcomeres are formed from adhesions on the ventral surface of cardiomyocytes. We have been able to recapitulate this other group's published experiments and definitively show that sarcomeres are not forming from the bottom of the cells or streaming out of adhesions. Instead, our 3D microscopy data shows that this group was imaging sarcomeres which were already formed on the dorsal surface and were traveling to the ventral surface of the cells. After this important clarification, we used our assay to show that the transition of MSFs to sarcomere-containing myofibrils requires formin-mediated actin polymerization and the non-muscle myosin IIA and myosin IIB. We conclude that sarcomeres form by a "templating" mechanism similar to that originally postulated by Howard Holtzer &gt;30 years ago. Furthermore, our data show short β cardiac myosin II filaments are themselves templated by "non-muscle" myosin II filaments. Subsequently, the short β cardiac myosin II filaments grow to form ~1.5 μm long filaments that then “stitch” together to form the stack of filaments at the core of the sarcomere (i.e., the A-band). Taken together, our data show that the differentiation of cardiomyocytes from stem cells is a powerful tool for dissecting the mechanisms controlling sarcomere assembly.
Utilization and costs of breast cancer screening for women in their 40s in a privately insured U.S. population.
Authors: Natalia R. Kunst, Jessica B. Long, Xiao Xu, Susan Busch, Ilana Richman, Kelly A. Kyanko, Cary Philip Gross
Journal: Journal of Clinical Oncology (2019)

105 Background: Despite ongoing debate about the effectiveness of initiating breast cancer screening at age 40, there is less attention paid to costs implications associated with the alternative screening starting ages. We assessed the annual costs of different screening strategies for privately insured women aged 40-49, as well as regional cost variation. Methods: We used a limited data set from Blue Cross Blue Shield (BCBS) Axis, the largest source of commercial US claims data. We identified the unit costs and frequencies of screening and subsequent evaluation for beneficiaries with continuous coverage through 2017. A Monte Carlo simulation model was developed to evaluate the annual costs of three alternate screening strategies: 1) current clinical practice, 2) annual screening beginning at age 40, or 3) annual screening beginning at age 45. The following procedures were included: screening (2-D and 3-D mammogram), supplementary ultrasound, recall (diagnostic 2-D and 3-D mammogram and ultrasound), MRI, and biopsy. We examined variability in screening-related costs across hospital referral regions (HRRs), and identified the main contributors to regional variation. Results: Overall, 69% of women in their 40s received a mammogram in 2017, resulting in an annual cost of $200 per beneficiary. This cost varied nine-fold across HRRs (range: $60-550 per beneficiary). The median cost of mammograms varied substantially across regions (2-D median cost: $206; range: $100-463; 3-D median: $271; range: $104-676). Variability in the cost of 2-D and 3-D mammogram was the main contributor to the variation in annual screening-related costs across HRRs, explaining 37% and 27% of the total variation, respectively. Screening all women beginning at age 40 would be associated with an annual cost of $309 per beneficiary (range: $127-664). Initiating screening at age 45 would cost $153 per beneficiary (range: $61-319). Conclusions: In current practice, breast cancer screening in women ages 40-49 is common, and costs $200 per eligible female beneficiary annually. Screening all women beginning at age 40 would increase the median screening-related costs by over 50%, although the cost implications vary substantially across regions.
Effectiveness of a chronic cough management algorithm at the transitional stage from acute to chronic cough in children: a multicenter, nested, single-blind, randomised controlled trial
Authors: Kerry-Ann F O'Grady, Keith Grimwood, Paul J Torzillo, Sheree Rablin, Yolanda Lovie-Toon, Michelle Kaus, Daniel Arnold, Jack Roberts, Helen Buntain, Don Adsett, Alex King, Mark Scott, Jennie Anderson, Maree Toombs, Anne B Chang
Journal: The Lancet Child & Adolescent Health (2019)
Increased Longevity of Continuous Bone Marrow Cultures and Radioresistance of Bone Marrow Stromal Cells from SOD193A ALS (Amyotrophic Lateral Sclerosis) Mice
Authors: Andrew Henderson, Renee Fisher, Michael Epperly, Donna Shields, Lora Rigatti, Christopher Donnelly, Simon Watkins, Joel S. Greenberger
Journal: Blood (2018)
A baby with a widespread itchy rash
Authors: Michael J Lavery, Deborah Woodcock, Will Simmons, Ali Al-Sharqi
Journal: BMJ (2019)

A 7 month old baby presented to the dermatology clinic with a three month history of a widespread, itchy rash, predominantly on the trunk and limbs. The family’s general practitioner had prescribed topical steroids and oral antibiotics to treat the rash, to no avail. The baby was systemically well.

On examination there was a widespread florid polymorphic eruption with erythematous papules, nodules, and coalescing plaques (fig 1). On the hands there were crusted papules over the metacarpophalangeal joints and web spaces. On the soles of both feet there were serpiginous tracts, and dermoscopy showed black dots. There was also facial involvement with a unilateral eruption …
Improved Detection of the KIT D816V Mutation Using a Real-Time PCR Assay Allows a Finer Recognition of Patients with Indolent Systemic Mastocytosis
Authors: Massimiliano Bonifacio, Giovanna De Matteis, Caterina De Benedittis, Omar Perbellini, Alberto Zamò, Patrizia Bonadonna, Elisa Paviati, Anna Artuso, Simona Soverini, Giovanni Pizzolo, Giovanni Martinelli, Roberta Zanotti
Journal: Blood (2011)
Incorporation of Clinical Information to Decipher Driver Mutations in Myeloproliferative Neoplasms
Authors: Murtadha K. Al-Khabori, Shoaib Al-Zadjali, Mohamed Al-Rawahi, Iman Al Noumani, Khalil Al Farsi, Salam Al-Kindi, Mohamed Al Huneini, Al Lamki Sulayma, Mahdiya Al-Belushi, Khalid Al Hashmi, Muna Al Tarshi, Muhanna Almusalhi
Journal: Blood (2018)
Delayed Onset of T Cell-Mediated Xenogeneic Disease in Rag2−/− γc−/− mice after Co- Transplantation of in Vitro Expanded Human CD4+CD25highCD45RA+ Regulatory T Cells
Authors: Tina J Boeld, Ellen Obermann, Reinhard Andreesen, Petra Hoffmann, Matthias Edinger
Journal: Blood (2008)
Suicides in young US people increase 56% over a decade
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The suicide rate in the US rose by 56% among people aged 10-24 between 2007 (6.8 per 100 000) and 2017 (10.6 per 100 000), figures have shown.1

A report by the US Centers for Disease Control and Prevention found that, in 2017, suicide and homicide were the second and third leading causes of death in people aged 15-19 and 20-24 …
Abstract 140: Efficacy Evaluation of Transplantation of Three-Dimensional Adipose-derived Stem Cell Sheet With Enhanced Angiogenesis Into Cardiovascular Disease
Authors: Hyung Joon Joo, Jong-Ho Kim, Chi-Yeon Park, Soon Jun Hong, Do-Sun Lim
Journal: Circulation Research (2019)

Integration of adipose-derived stem cells (ASCs) and cell sheet engineering technology has received much interest in the regenerative medicine. First of all, sphere formation of ASCs (sph-ASCs) were successfully produced by poly-2-hydroxyethyl methacrylate (poly-HEMA)-coated plates as we previously reported. Sph-ASCs showed increased expression of angiogenic growth factors and cytokine secretion compared to adherent ASCs. Significantly increased expression of HIF-1α and decreased expression of cleaved caspase-3 were detected in sph-ASCs compared to adherent ASCs. Moreover, ASC sheets were formed using thermo-responsive plates and sph-ASCs were seeded to produce ASC sheets covered with sph-ASCs (sph-ASC sheets). After 48 hrs of incubation, the cross-section of sph-ASC sheets revealed mixed and multi-layered of sph-ASCs and ASC sheets. Sph-ASC sheets showed the positive expression of HIF-1α and angiogenic markers such as FGF-2, CD31, PDGFb, and CD144, especially higher in sph-ASC-covered sites. In addition, cytokine arrays of secretome revealed that sph-ASCs and sph-ASC sheets showed augmented angiogenic potential compared to adherent ASCs. Furthermore, four groups of AMI induction only (sham), intramyocardial injection of sph-ASC, ASC sheet transplantation, and sph-ASC sheet transplantation were compared using acute myocardial infarction (AMI) rat models. After 6 weeks of transplantation, echocardiography revealed that significantly improved ejection fraction and fraction shortening in sph-ASC sheet group compared to sham, sph-ASC, and ASC sheet groups. In conclusion, transplantation of sph-ASC sheets showed enhanced neovascularization in AMI animal models. These results indicated that the use of ASC sheets as a novel tissue engineering approach to improve the cardiac and vascular function.
CNS-Disease in Elderly Patients Treated with Modern Chemotherapy (CHOP-14) with or without Rituximab: An Analysis of CNS Events in the RICOVER-60 Trial of the German High-Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL).
Authors: Volkmar Boehme, Samira Zeynalova, Eva Lengfelder, Astrid Franke, Marcel Reiser, Hans Steinhauer, Michael Clemens, Christine Nickenig, Maike de Witt, Markus Loeffler, Michael Pfreundschuh, Norbert Schmitz
Journal: Blood (2007)
Rhob Overexpression Boosts Relapse of t(8;21) RUNX1-RUNX1T1 Rearranged Acute Myeloid Leukemia.
Authors: Pigazzi Martina, Zampini Matteo, Claudia Tregnago, Valeria Bisio, Luca Simula, Giulia Borella, Carlo Zanon, Valentina Serafin, Benedetta Accordi, Silvia Campello, Barbara Buldini, Andrea Pession, Franco Locatelli, Giuseppe Basso
Journal: Blood (2017)
Efficacy and Safety of Transcranial Direct Current Stimulation for Treating Negative Symptoms in Schizophrenia
Authors: Leandro da Costa Lane Valiengo, Stephan Goerigk, Pedro Caldana Gordon, Frank Padberg, Mauricio Henriques Serpa, Stephanie Koebe, Leonardo Afonso dos Santos, Roger Alberto Marcos Lovera, Juliana Barbosa de Carvalho, Martinus van de Bilt, Acioly L. T. Lacerda, Helio Elkis, Wagner Farid Gattaz, Andre R. Brunoni
Journal: JAMA Psychiatry (2019)

Negative symptoms represent a substantial burden in schizophrenia. Although preliminary studies have suggested that transcranial direct current stimulation (tDCS) is effective for some clusters of symptoms, the clinical benefits for negative symptoms are unclear.To determine the efficacy and safety of tDCS vs sham as an add-on treatment for patients with schizophrenia and predominant negative symptoms.The double-blind Schizophrenia Treatment With Electric Transcranial Stimulation (STARTS) randomized clinical trial was conducted from September 2014 to March 2018 in 2 outpatient clinics in the state of São Paulo, Brazil. Patients with schizophrenia with stable negative and positive symptoms and a minimum score of 20 points in the negative symptoms subscale of the Positive and Negative Syndrome Scale (PANSS) were included.Ten sessions of tDCS performed twice a day for 5 days or a sham procedure. The anode and the cathode were positioned over the left prefrontal cortex and the left temporoparietal junction, respectively.Change in the PANSS negative symptoms subscale score at week 6 was the primary outcome. Patients were followed-up for an additional 6 weeks.Of the 100 included patients, 20 (20.0%) were female, and the mean (SD) age was 35.3 (9.3) years. A total of 95 patients (95.0%) finished the trial. In the intention-to-treat analysis, patients receiving active tDCS showed a significantly greater improvement in PANSS score compared with those receiving the sham procedure (difference, 2.65; 95% CI, 1.51-3.79; number needed to treat, 3.18; 95% CI, 2.12-6.99; P < .001). Response rates for negative symptoms (20% improvement or greater) were also higher in the active group (20 of 50 [40%]) vs the sham group (2 of 50 [4%]) (P < .001). These effects persisted at follow-up. Transcranial direct current stimulation was well tolerated, and adverse effects did not differ between groups, except for burning sensation over the scalp in the active group (43.8%) vs the sham group (14.3%) (P = .003).Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia.ClinicalTrials.gov identifier: NCT02535676.
Abstract 498: The Effects of Low-carbohydrate High-fat Diet on Vascular Remodeling
Authors: Haruka Yanagisawa, Haruhiro Toko, Mutsuo Harada, Jiaxi Guo, Satoshi Bujo, Masato Ishizuka, Issei Komuro
Journal: Circulation Research (2019)

Background: Low carbohydrate diet (LCD) has been reported to reduce body weight and cardiovascular risk factors, including diabetic mellitus and dyslipidemia. Therefore, LCD was once expected to prevent cardiovascular events. However, recent meta-analysis reported that LCD was related to an increase in cardiovascular events. Moreover, other cohort studies reported that higher all-cause and cardiovascular mortality were observed only in LCD with animal derived-fat (LCD-A), not in LCD with plant derived-fat (LCD-P). Precise mechanisms of these effects have not been clarified, so we explored the potential roles of LCD-A and LCD-P in blood vessel remodeling by using two types of vascular disease model mice, atherosclerotic model and vascular injury model. Method: We generated two types of LCDs, beef tallow-based LCD (LCD-A) and cacao butter-based LCD (LCD-P). Six-week-old male ApoE Knockout (ApoE KO) mice (atherosclerosis model mice) and wild-type mice were subjected to LCD-A, LCD-P or normal chow for 14 weeks, and %plaque area of aortic root and serum lipid profile were measured. For vascular injury model, mice were inserted with a wire in a femoral artery of male 10-week-old wild-type mice and subjected to the three-types chow. After 4 weeks, femoral arteries were excised and embedded in paraffin and assessed with the extent of vascular injury severity. The femoral artery without injury on the other side was served as control. Results: In ApoE KO mice, serum levels of total cholesterol (TC) and triglyceride (TG) were decreased in LCD group (TC: p&lt;0.01, TG: p&lt;0.05 vs normal chow), but there was no significant difference between LCD-A to LCD-P. In wild-type mice, serum TC level was increased in LCD-A group (p&lt;0.0001 vs normal chow). LCD had no effect on %plaque area of aortic root in ApoE KO mice. In vascular injury model mice, there was no significant difference in the extent of neointimal hyperplasia induced by wire-injury among groups. Conclusion: Our preliminary data showed that LCD had no effect on vascular remodeling despite the presence of significant alteration in lipid profiles. Additional experiments are needed to confirm the results and clarify the precise mechanisms.
Localized- and advanced-stage follicular lymphomas differ in their gene expression profiles
Authors: Annette M. Staiger, Eva Hoster, Vindi Jurinovic, Stefan Winter, Ellen Leich, Claudia Kalla, Peter Möller, Heinz-Wolfram Bernd, Alfred C. Feller, Karoline Koch, Wolfram Klapper, Harald Stein, Martin-Leo Hansmann, Sylvia Hartmann, Martin Dreyling, Oliver Weigert, Wolfgang Hiddemann, Klaus Herfarth, Andreas Rosenwald, Marianne Engelhard, German Ott, Heike Horn
Journal: Blood (2019)