tbuckley/cabot-search huggingface dataset:
CLO19-030: Duration of First Line Therapy in Metastatic Non-Small Cell Lung Cancer
Authors: Jeff Dang, Sang Chau, Jessy Delaisla, Divya Prakash, Andrew Hertler
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Lung cancer is the leading cause of death in the United States. We are challenged with finding the optimal treatment for patient subgroups in a real-world setting. Treatment options have expanded to include immunotherapies versus platinum-based therapies to improve the quality of cancer care. Platinum combinations are known to have overall response rates of 25%–35%, time to progression of 4–6 months, and a median survival of 8–10 months. The purpose of this study was to determine how long metastatic NSCLC patients were on first-line treatments and what characteristics potentially contribute to the duration of therapy prior to progression. Methods: All patients with a diagnosis of metastatic NSCLC that received first line treatment between January 1, 2016 and December 31, 2017 but later switched to a different treatment because of disease progression or intolerance were included in the study (n=1,222). The sample, obtained from a nationwide database of treatment requests, was stratified into 4 groups based on the type of treatment the patient received: single agent (n=66), PD-1/PDL-1 (n=157), platinum doublet (n=720), and platinum triplet (n=279). Chi-square and Kruskal-Wallis tests were performed as appropriate. Results: The findings suggested that the median duration to progression was shorter for single agents as compared to multiple agent treatments ( Χ 2 = 7.67 , P =.05). The median treatment duration for the groups were as follows: 90 days for single agent, 90 days for PD-1/PDL-1, 93 days for platinum doublet, and 111 days for platinum triplet. Additional analyses were conducted to understand whether pathway adherence and growth factor usage impact the duration of time to discontinuation within each group. Conclusions: These data provide insight into the duration of first line treatments for advanced lung cancer. Shorter duration times were found for single agent treatments as compared to multiple agent treatments.
Abstract 19704: Incomplete Left Atrial Appendage Closure Prediction Using Novel Three-Dimensional Computed Tomography Geometric Analysis
Authors: Hyung-bok Park, Byunghwan Jeon, Sanghoon Shin, Yoonmi Hong, Hyuk-Jae Chang
Journal: Circulation (2017)

Introduction: At times, peri-device leakage into the left atrial appendage (LAA) persists, after LAA device closure. We aimed to investigate whether novel three dimensional geometric computed tomography (CT) analysis would predict incomplete occlusion of LAA in advance. Hypothesis: Novel 3D geometric computed tomography (CT) analysis may predict incomplete LAA occlusion in advance. Methods: In this study, 64 patients who underwent LAA device closure were retrospectively enrolled. We defined peri-device leakage as the presence of a Doppler signal inside the LAA after device deployments (n=10). We compared this to patients without peri-device leakage (n=53). Distance was measured from the inferior vena cava (IVC) outlet to the interatrial septum (IAS, L1) and from the IAS to the LAA orifice (L2) respectively. The normal vector (perpendicular lines to planes) was acquired from the LAA orifice (LAA vector) and two vectors were acquired from centroid of the IVC outlet to the LAA (IVC vector) and from centroid ...
How uncertainty begets hope: A model of adaptive and maladaptive seeking behavior
Authors: Martin Zack
Journal: Behavioral and Brain Sciences (2019)

Abstract The “incentive hope” model creatively explains hoarding and fat accumulation by foragers under uncertainty and food seeking when food cues are present but food is not. The model has difficulty explaining why animals driven by cues fare better than animals driven by food reward itself, why human obesity exists when food is abundant, and why people enjoy gambling and care about winning.
Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation
Authors: Robert D. Kirkton, Maribel Santiago-Maysonet, Jeffrey H. Lawson, William E. Tente, Shannon L. M. Dahl, Laura E. Niklason, Heather L. Prichard
Journal: Science Translational Medicine (2019)

Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease. In rare cases, small samples of HAV were recovered during routine surgical interventions and used to examine the temporal and spatial pattern of the host cell response to the HAV after implantation, from 16 to 200 weeks. We observed a substantial influx of alpha smooth muscle actin (αSMA)-expressing cells into the HAV that progressively matured and circumferentially aligned in the HAV wall. These cells were supported by microvasculature initially formed by CD34+/CD31+ cells in the neoadventitia and later maintained by CD34-/CD31+ endothelial cells in the media and lumen of the HAV. Nestin+ progenitor cells differentiated into either αSMA+ or CD31+ cells and may contribute to early recellularization and self-repair of the HAV. A mesenchymal stem cell-like CD90+ progenitor cell population increased in number with duration of implantation. Our results suggest that host myogenic, endothelial, and progenitor cell repopulation of HAVs transforms these previously acellular vessels into functional multilayered living tissues that maintain blood transport and exhibit self-healing after cannulation injury, effectively rendering these vessels like the patient's own blood vessel.
Mediation of the influence of childhood maltreatment on depression relapse by cortical structure: a 2-year longitudinal observational study
Authors: Nils Opel, Ronny Redlich, Katharina Dohm, Dario Zaremba, Janik Goltermann, Jonathan Repple, Claas Kaehler, Dominik Grotegerd, Elisabeth J Leehr, Joscha Böhnlein, Katharina Förster, Susanne Meinert, Verena Enneking, Lisa Sindermann, Fanni Dzvonyar, Daniel Emden, Ramona Leenings, Nils Winter, Tim Hahn, Harald Kugel, Walter Heindel, Ulrike Buhlmann, Bernhard T Baune, Volker Arolt, Udo Dannlowski
Journal: The Lancet Psychiatry (2019)
Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association
Authors: Jacqueline E. Tamis-Holland, Hani Jneid, Harmony R. Reynolds, Stefan Agewall, Emmanouil S. Brilakis, Todd M. Brown, Amir Lerman, Mary Cushman, Dharam J. Kumbhani, Cynthia Arslanian-Engoren, Ann F. Bolger, John F. Beltrame
Journal: Circulation (2019)

Myocardial infarction in the absence of obstructive coronary artery disease is found in ≈5% to 6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition. As such, it is important that patients are appropriately diagnosed and an evaluation to uncover the correct cause is performed so that, when possible, specific therapies to treat the underlying cause can be prescribed. This statement provides a formal and updated definition for the broadly labelled term MINOCA (incorporating the definition of acute myocardial infarction from the newly released "Fourth Universal Definition of Myocardial Infarction") and provides a clinically useful framework and algorithms for the diagnostic evaluation and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.
AMSSM position statement update: blood-borne pathogens in the context of sports participation
Authors: Christopher McGrew, Daisy-Scarlett MacCallum, Dustymarie Narducci, Rathna Nuti, Leonard Calabrese, Robert J Dimeff, Stephen Paul, Sourav Poddar, Ashwin Rao, Douglas McKeag
Journal: British Journal of Sports Medicine (2019)

This American Medical Society for Sports Medicine position statement update is directed towards healthcare providers of patients involved in sport and exercise. There have been significant advances in clinical and scientific research in the understanding of blood-borne pathogens (BBPs), and this update incorporates these advancements. This document is intended as a general guide to clinical practice based on the current state of the evidence, while acknowledging the need for modification as new knowledge becomes available. Confirmed transmission of BBPs during sport is exceedingly rare. There are no well-documented reports of HIV, HCV or HDV transmission during sport. There is also no evidence for universal testing for BBPs as a specific requirement for participation in sports. Competitive athletes and non-athletes should follow appropriate general public health agency recommendations for screening for BBPs, considering their individual risk factors and exposures. Standard (universal) precautions must be followed by those providing care to athletes. Exercise and athletic participation can help promote a healthy lifestyle for persons living with BBPs. Those with acute symptomatic BBP infection should limit exercise intensity based on their current health status. Education is the key tool for preventing BBP transmission. Research gaps include evaluation of the prevalence of BBP infections in competitive athletes, the effects of long-term, intense training on infected athletes and the effects of BBP treatment therapies on performance.
Cerebral palsy in adults: summary of NICE guidance
Authors: Nathan Bromham, Katharina Dworzynski, Paul Eunson, Charlie Fairhurst
Journal: BMJ (2019)

### What you need to know Cerebral palsy is a non-progressive (though not unchanging) disorder of movement and posture pathology associated with an impairment of the developing fetal or infant brain (up to 2 years old)—when the maturation of the brain is most rapid and therefore most at risk from damage from, for example, prematurity, hypoxia, or infection. The prevalence remains at around 2-3 per 1000 live births, and most affected children live well into adult life.1 It is described in terms of topography (unilateral or bilateral), predominant motor subtype (usually spasticity and/or dyskinesis/dystonia), and severity (such as the Gross Motor Functional Classification System (GMFCS) see box 1). Box 1 ### Gross Motor Function Classification System (GMFCS)2 This five-level clinical classification system describes the gross motor function of people with cerebral palsy based on their self-initiated movement abilities. People assessed as level I are the most able, and people assessed as level V are dependent on others for all their mobility needs:RETURN TO TEXT
CLO19-059: A Systematic Review and Meta- Analysis of Randomized Controlled Trials to Evaluate the Risk of Health-Related Quality of Life Events in Patients With Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Treated With CDK 4/6 Inhibitors
Authors: Rachana Yendala, Kyaw Thein, Sriman Swarup, Anita Sultan, Somedeb Ball, Miguel Quirch, Myo H. Zaw, Yin M. Myat, Catherine Jones
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Pain, fatigue, hot flushes, and rash significantly contribute to quality of life in breast cancer patients undergoing chemotherapy. Hormone receptor-positive breast cancer is a common entity among women worldwide. In cancer cells, CDK4/6 activity is over expressed, which can lead to amplification or overexpression of the genes encoding for CDK 4/6 or the cyclin D, ultimately leading to endocrine therapy resistance. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of health-related quality of life (HRQOL) events associated with CDK 4/6 inhibitors. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018. RTCs that mention HRQOL events as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95%CI. Random effects model was applied. Results: 8 RCTs (7 phase III and 1 phase II) with a total of 4,557 patients were eligible. The study arms used palbociclib/ribociclib/abemaciclib with letrozole or anastrozole or fulvestrant or other hormonal agent while the control arms utilized placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agent. The RR of all-grade side effects were as follows: fatigue, 1.226 (95% CI: 1.079–1.393; P =.002); back pain, 0.971 (95% CI: 0.844–1.117; P =.681); arthralgia, 0.978 (95% CI: 0.830–1.152; P =.790); headache, 1.046 (95% CI: 0.928–1.179; P =.459); alopecia, 2.635 (95% CI: 1.966–3.533; P &lt;.001); hot flushes, 0.901 (95% CI: 0.766–1.060; P =.210); and rash, 2.068 (95% CI: 1.604–2.666; P &lt;.001). The RR of high-grade side effects were as follows: fatigue, 3.487 (95% CI: 1.765–6.889; P &lt;.001); back pain, 1.364 (95% CI: 0.695–2.679; P =.367); arthralgia, 1.148 (95% CI: 0.509–2.593; P =.740); headache, 0.807 (95% CI: 0.303–2.147; P =.667); and rash, 3.018(95% CI: 0.954–9.554; P =.060). Conclusions: Our study showed that the risk of developing all grades of fatigue and any-grade alopecia and rash was significantly with CDK 4/6 inhibitors. Prompt intervention with good supportive care is required.
Abstract O.17: Whole Genome Sequencing of a six-member African American family with two Kawasaki disease-affected siblings identifies novel susceptibility variants
Authors: Jihoon Kim, Chisato Shimizu, Hai Yang, Olivier Harismendy, Long Truong Hoang, Eric Levy, Rolando Cimaz, David Burgner, Rae S Yeung, Chiea C Khor, Sonia Davila, Michael Levin, Taco W Kuijpers, Martin L Hibberd, Lucila Ohno-Machado, Jane C Burns
Journal: Circulation (2015)

We performed Whole Genome Sequencing (WGS) of a 6-member African American (AA) family with 2 of the 4 children affected with KD. We identified 6,712,158 unique variants across all 6 individuals. We first analyzed the quartet of mother/father/affected sibs and then compared variants in the 2 affected vs. 2 unaffected sibs. Assuming a recessive inheritance model, we identified 49,591 transmitted candidate homozygous variants exclusively present in both affected sibs compared to their parents. The affected vs. unaffected sibling analysis generated 64,187 candidate homozygous variants exclusive to the affected sibs. The intersection of the two analyses identified 20,943 variants of which 303 - in 117 genes - were predicted to be deleterious. We validated the findings in a cohort of 405 KD subjects and 6,252 normal controls using 4,060,864 imputed genotypes. Association analysis of the imputed GWAS dataset for KD susceptibility using the allelic and recessive tests in PLINK found 438,343 SNPs (nominal P-value &lt; 0.05). Of these, 17 variants in 10 genes were also among the 303 variants from the family analysis. These genes were ANGPT1, AS3MT, C10orf32, CMIP, CNNM2, LRIG2, MMP1, NT5C2, SLK, and TLR6. Of these, ANGPT1, MMP1, and TLR6 have been previously associated with KD. For SLK (serine-threonine protein kinase 2) rs10786779 located in the promoter, the homozygous A allele (risk) genotype showed significantly higher expression (p=0.04) in a cohort of 141 acute vs. convalescent mixed ethnic KD subjects on the Illumina HumanRef-12 V4 BeadChip. Conclusion: This is the first analysis of WGS in KD and the first to focus on genetic susceptibility in AA children who are second only to Asian children in susceptibility to KD. This exploratory analysis provides new validated variants that may likely contribute to KD susceptibility in AA children.
Interim Analysis of Immunogenicity to the Vector Capsid and Transgene-Expressed Human FVIII in a Phase-1/2 Clinical Study of Bmn 270, an AAV5-Mediated Gene Therapy for Hemophilia a
Authors: Brian Long, Benjamin Kim, Wing Yen Wong, Ke Yang, Christian Vettermann, Nancy Pryer, Romain Hardet, Klaudia Kuranda, Philippe Veron, Federico Mingozzi, Glenn F. Pierce, Becky Schweighardt
Journal: Blood (2017)
Assessment of the effects of immunogenicity on the pharmacokinetics, efficacy and safety of tildrakizumab
Authors: A.B. Kimball, T. Kerbusch, F. Aarle, P. Kulkarni, Q. Li, A. Blauvelt, K.A. Papp, K. Reich, D. Montgomery
Journal: British Journal of Dermatology (2019)

We evaluated antidrug antibody (ADA) development in patients with chronic plaque psoriasis from three clinical trials of tildrakizumab, a humanized anti-interleukin-23p19 monoclonal antibody (P05495, reSURFACE 1 and reSURFACE 2).
Dioscin Alleviates Crystalline Silica-Induced Pulmonary Inflammation and Fibrosis through Promoting Alveolar Macrophage Autophagy
Authors: Sitong Du, Chao Li, Yiping Lu, Xue Lei, Yiting Zhang, Siyi Li, Fangwei Liu, Ying Chen, Dong Weng, Jie Chen
Journal: Theranostics (2019)

Occupational exposure to crystalline silica (CS) particles leads to silicosis, which is characterized by chronic inflammation and abnormal tissue repair. Alveolar macrophages (AMs) play a crucial role in the process of silicosis. Previously, we demonstrated positive effect of dioscin on silicosis through modulating macrophage-elicited innate immune response. However, the concrete molecular mechanism remains to be discovered. Methods: We established experimental model of silicosis with wildtype and Atg5flox/floxDppa3Cre/+ mice and oral administrated dioscin daily to explore the effects of dioscin on macrophages and pulmonary fibrosis. AM cell line MH-S with Atg5 silence was used to explore specific function of dioscin on macrophage-derived inflammation and the underlying molecular mechanism. Results: Dioscin could promote autophagy in macrophages. Dioscin-triggered AMs autophagy limited mitochondrial reactive oxygen species (mtROS) mass stimulated by CS, reduced mitochondria-dependent apoptosis pathway activation and facilitated cell survival. Relieved oxidative stress resulted in decreased secretion of inflammatory factors and chemokines. Dioscin treatment alleviated macrophage-derived inflammation and subsequent abnormal collagen repair. All the dioscin's protective effects were diminished in Atg5flox/floxDppa3Cre/+ mice. Conclusion: Dioscin promoting autophagy leads to reduced CS-induced mitochondria-dependent apoptosis and cytokine production in AMs, which may provide concrete molecular mechanism for the therapy of silicosis.
Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation
Authors: Cristina Toffalori, Laura Zito, Valentina Gambacorta, Michela Riba, Giacomo Oliveira, Gabriele Bucci, Matteo Barcella, Orietta Spinelli, Raffaella Greco, Lara Crucitti, Nicoletta Cieri, Maddalena Noviello, Francesco Manfredi, Elisa Montaldo, Renato Ostuni, Matteo M. Naldini, Bernhard Gentner, Miguel Waterhouse, Robert Zeiser, Jurgen Finke, Maher Hanoun, Dietrich W. Beelen, Ivana Gojo, Leo Luznik, Masahiro Onozawa, Takanori Teshima, Raynier Devillier, Didier Blaise, Constantijn J. M. Halkes, Marieke Griffioen, Matteo G. Carrabba, Massimo Bernardi, Jacopo Peccatori, Cristina Barlassina, Elia Stupka, Dejan Lazarevic, Giovanni Tonon, Alessandro Rambaldi, Davide Cittaro, Chiara Bonini, Katharina Fleischhauer, Fabio Ciceri, Luca Vago
Journal: Nature Medicine (2019)
Effect of Wearable Digital Intervention for Improving Socialization in Children With Autism Spectrum Disorder
Authors: Catalin Voss, Jessey Schwartz, Jena Daniels, Aaron Kline, Nick Haber, Peter Washington, Qandeel Tariq, Thomas N. Robinson, Manisha Desai, Jennifer M. Phillips, Carl Feinstein, Terry Winograd, Dennis P. Wall
Journal: JAMA Pediatrics (2019)

Autism behavioral therapy is effective but expensive and difficult to access. While mobile technology-based therapy can alleviate wait-lists and scale for increasing demand, few clinical trials exist to support its use for autism spectrum disorder (ASD) care.To evaluate the efficacy of Superpower Glass, an artificial intelligence-driven wearable behavioral intervention for improving social outcomes of children with ASD.A randomized clinical trial in which participants received the Superpower Glass intervention plus standard of care applied behavioral analysis therapy and control participants received only applied behavioral analysis therapy. Assessments were completed at the Stanford University Medical School, and enrolled participants used the Superpower Glass intervention in their homes. Children aged 6 to 12 years with a formal ASD diagnosis who were currently receiving applied behavioral analysis therapy were included. Families were recruited between June 2016 and December 2017. The first participant was enrolled on November 1, 2016, and the last appointment was completed on April 11, 2018. Data analysis was conducted between April and October 2018.The Superpower Glass intervention, deployed via Google Glass (worn by the child) and a smartphone app, promotes facial engagement and emotion recognition by detecting facial expressions and providing reinforcing social cues. Families were asked to conduct 20-minute sessions at home 4 times per week for 6 weeks.Four socialization measures were assessed using an intention-to-treat analysis with a Bonferroni test correction.Overall, 71 children (63 boys [89%]; mean [SD] age, 8.38 [2.46] years) diagnosed with ASD were enrolled (40 [56.3%] were randomized to treatment, and 31 (43.7%) were randomized to control). Children receiving the intervention showed significant improvements on the Vineland Adaptive Behaviors Scale socialization subscale compared with treatment as usual controls (mean [SD] treatment impact, 4.58 [1.62]; P = .005). Positive mean treatment effects were also found for the other 3 primary measures but not to a significance threshold of P = .0125.The observed 4.58-point average gain on the Vineland Adaptive Behaviors Scale socialization subscale is comparable with gains observed with standard of care therapy. To our knowledge, this is the first randomized clinical trial to demonstrate efficacy of a wearable digital intervention to improve social behavior of children with ASD. The intervention reinforces facial engagement and emotion recognition, suggesting either or both could be a mechanism of action driving the observed improvement. This study underscores the potential of digital home therapy to augment the standard of care.ClinicalTrials.gov identifier: NCT03569176.