tbuckley/cabot-search huggingface dataset:
The Evolution of Rhythm Processing
Authors: S.A. Kotz, A. Ravignani, W.T. Fitch
Journal: Trends in Cognitive Sciences (2018)

Behavioral and brain rhythms in the millisecond-to-second range are central in human music, speech, and movement. A comparative approach can further our understanding of the evolution of rhythm processing by identifying behavioral and neural similarities and differences across cognitive domains and across animal species. We provide an overview of research into rhythm cognition in music, speech, and animal communication. Rhythm has received considerable attention within each individual field, but to date, little integration. This review article on rhythm processing incorporates and extends existing ideas on temporal processing in speech and music and offers suggestions about the neural, biological, and evolutionary bases of human abilities in these domains.
Abstract 19979: Rapid ERα-AMPK Signaling Stimulates Vasorelaxation via ERK-Mediated Pathway
Authors: Seong C Kim, Milton H Hamblin
Journal: Circulation (2016)

Background: 17-β-estradiol has been shown to play an important role in regulating vascular function and vasomotor tone. We have previously demonstrated sex differences in rapid estrogen receptor signaling during vascular relaxation. We recently observed that estrogen activates AMPK-activated protein kinase (AMPK), suggesting that AMPK is a likely mediator of estrogen receptor (ER) signaling in vasomotor function. AMPK has been reported to participate in vascular relaxation. Furthermore, our recent studies found that incubating vascular rings with 5-aminoimidazole-4-carboxamide (AICAR), an AMPK activator, results in greater vasorelaxation of female C57BL/6J mouse vessels when compared with male vessels. However, the precise mechanisms involving estrogen receptor signaling and AMPK in promoting vascular relaxation remain unknown. Methods and Results: To elucidate a critical role of ERα-AMPK signaling and downstream targets involved in vascular relaxation, including the potential sex difference in the influe...
Abstract 13421: Liver T1 Mapping MRI and Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Mohammad R Ostovaneh, Tomoki Fuji, Hooman Bakhshi, Ravi V Shah, Venkatesh L Murthy, Russell P Tracy, Eliseo Guallar, Colin O Wu, David A Bluemke, Joao A Lima, Bharath A Venkatesh
Journal: Circulation (2016)

Introduction: Fatty liver disease and liver fibrosis are associated with cardiovascular disease (CVD) metabolic risk factors and events. However direct imaging of liver abnormalities using T1 mapping MRI in relation to CVD has not been investigated in large epidemiological cohorts. Hypothesis: Liver abnormalities (inflammation and/or fibrosis) by T1 mapping MRI are associated with CVD events. Methods: MESA enrolled 6814 participants free of clinical CVD at baseline, MESA1 (2000-2002). A subsample of participants underwent Modified Look-Locker T1 mapping MRI at the fifth follow-up exam, MESA5 (2010 -2012). T1 maps were analyzed avoiding vessels and biliary ducts, and pre- and post-contrast T1 times (25 minutes after injection) were calculated. Liver extracellular volume fraction (ECV) was calculated using the pre- and post-contrast T1 times of the liver and cardiac blood pool. Higher ECV and pre-contrast T1 time (PreT1) were indicative of liver abnormalities. Coronary heart disease (CHD), heart failure (HF) and atrial fibrillation (AF) events were ascertained between MESA 1 and MESA 5. Multivariable linear regression analysis evaluated the cross-sectional relationship between liver ECV and T1 time with cardiac events adjusted for ASCVD/AHA risk score, liver fat content by computed tomography, alcohol use, socioeconomic status and BMI. Results: In 888 participants (67.83±8 years, 51% female, 60% Caucasian, 4% Chinese, 26% African-American, 10% Hispanic) there were 63 cardiac events (44 CHD, 13 CHF and 18 AF) between MESA1 and 5. Compared to controls, PreT1 and ECV were significantly higher in those with any cardiac event and AF. In multivariable analysis, PreT1 (standardized β=0.08, p=0.018) and ECV (standardized β=0.09, p=0.008) were associated with composite cardiac events. Conclusion: Liver abnormalities (most likely inflammation and/or fibrosis) estimated by greater liver PreT1 and ECV, are associated with cardiac events in a multi-ethnic cohort.
Intrahepatic Cholangiocarcinoma: Continuing Challenges and Translational Advances
Authors: Alphonse E. Sirica, Gregory J. Gores, John D. Groopman, Florin M. Selaru, Mario Strazzabosco, Xin Wei Wang, Andrew X. Zhu
Journal: Hepatology (2018)

Intrahepatic cholangiocarcinoma (iCCA) has over the last 10‐20 years become the focus of increasing concern, largely due to its rising incidence and high mortality rates worldwide. The significant increase in mortality rates from this primary hepatobiliary cancer, particularly over the past decade, has coincided with a rapidly growing interest among clinicians, investigators, and patient advocates to seek greater mechanistic insights and more effective biomarker‐driven targeted approaches for managing and/or preventing this challenging liver cancer. In addition to discussing challenges posed by this aggressive cancer, this review will emphasize recent epidemiological, basic, and translational research findings for iCCA. In particular, we will highlight emerging demographic changes and evolving risk factors, the critical role of the tumor microenvironment, extracellular vesicle biomarkers and therapeutics, intertumoral and intratumoral heterogeneity, and current and emerging targeted therapies regarding iCCA. Specifically, recent evidence linking non–bile duct medical conditions, such as nonalcoholic fatty liver disease and nonspecific cirrhosis, to intrahepatic cholangiocarcinogenesis together with geographic and ethnic variation will be assessed. Recent developments concerning the roles played by transforming growth factor‐β and platelet‐derived growth factor D in driving the recruitment and expansion of cancer‐associated myofibroblasts within cholangiocarcinoma (CCA) stroma as well as their therapeutic implications will also be discussed. In addition, the potential significance of extracellular vesicles as bile and serum biomarkers and therapeutic delivery systems for iCCA will be described. An integrated systems approach to classifying heterogeneous iCCA subtypes will be further highlighted, and recent clinical trials and emerging targeted therapies will be reviewed, along with recommendations for future translational research opportunities. Established international CCA networks are now facilitating collaborations aimed at advancing iCCA translational and clinical research.
Implementation of a multifaceted program to improve uptake of guideline recommendations for adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL).
Authors: Erin Elizabeth Hahn, Nirupa R. Ghai, Robert Michael Cooper
Journal: Journal of Clinical Oncology (2018)

50 Background: ALL is one of the most common malignancies in the AYA population (age 15-39) and is associated with poor survival in AYAs when compared with children. There is compelling evidence demonstrating a survival benefit for AYAs treated with pediatric regimens vs adult regimens, and guidelines from the National Comprehensive Cancer Network now recommend consideration of pediatric inspired treatment. However, uptake has been suboptimal, with only 25%-35% of AYAs with ALL receiving a pediatric regimen in the U.S. There are several potential barriers to uptake, including lack of knowledge and guidance about the recommendations. For this study, we implemented and evaluated a multi-faceted program to improve uptake in a large health care system, Kaiser Permanente Southern California (KPSC), with 14 medical centers across the region. Methods: The program was initiated regionally in 2013 across all 14 medical centers. Content included education of clinical leaders, rapid identification of newly diagnosed AYA ALL patients by the hematopathology team, and guidance and support from a pediatric oncologist for adult oncology teams treating AYA ALL patients emphasizing a pediatric regimen when appropriate. We subsequently identified AYA ALL patients diagnosed and treated between 2012-2016. A detailed chart review was conducted to determine treatment regimens prior to implementation of the program and post-implementation. Results: We identified 58 patients, 11 in the period prior to implementation and 47 post-implementation. Overall, 18% of patients in the pre-intervention period were treated on a pediatric regimen vs. 77% post-implementation. We found an increasing trend over time in the post-intervention period, with 46% receiving a pediatric protocol in 2013, 64% in 2014, 92% in 2015, and 100% in 2016. Conclusions: We were successful at increasing the proportion of eligible patients who received pediatric protocols for treatment of AYA ALL. Implementing a multi-faceted approach to improve care for this rare condition was feasible and acceptable to oncology clinicians across the region, with potential for large-scale scale-up and spread.
The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p
Authors: Mu Xu, Xiaoxiang Chen, Kang Lin, Kaixuan Zeng, Xiangxiang Liu, Bei Pan, Xueni Xu, Tao Xu, Xiuxiu Hu, Li Sun, Bangshun He, Yuqin Pan, Huiling Sun, Shukui Wang
Journal: Molecular Cancer (2018)

Mounting evidence demonstrates that long noncoding RNAs (lncRNAs) have critical roles during the initiation and progression of cancers. In this study, we report that the small nucleolar RNA host gene 1 (SNHG1) is involved in colorectal cancer progression.We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer. The effects of SNHG1 on colorectal cancer were investigated through in vitro and in vivo assays (i.e., CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, xenograft model, immunohistochemistry, and western blot). The mechanism of SNHG1 action was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay and RNA immunoprecipitation assay.Our analysis revealed that SNHG1 was upregulated in human colorectal cancer tissues, and high SNHG1 expression was associated with reduced patient survival. We also found that high SNHG1 expression was partly induced by SP1. Moreover, SNHG1 knockdown significantly repressed colorectal cancer cells growth both in vitro and in vivo. Mechanistic investigations demonstrated that SNHG1 could directly interact with Polycomb Repressive Complex 2 (PRC2) and modulate the histone methylation of promoter of Kruppel like factor 2 (KLF2) and Cyclin dependent kinase inhibitor 2B (CDKN2B) in the nucleus. In the cytoplasm, SNHG1 acted as a sponge for miR-154-5p, reducing its ability to repress Cyclin D2 (CCND2) expression.Taken together, the results of our studies illuminate how SNHG1 formed a regulatory network to confer an oncogenic function in colorectal cancer and suggest that SNHG1 may serve as a potential target for colorectal cancer diagnosis and treatment.
Advanced model systems and tools for basic and translational human immunology
Authors: Lisa E. Wagar, Robert M. DiFazio, Mark M. Davis
Journal: Genome Medicine (2018)

There are fundamental differences between humans and the animals we typically use to study the immune system. We have learned much from genetically manipulated and inbred animal models, but instances in which these findings have been successfully translated to human immunity have been rare. Embracing the genetic and environmental diversity of humans can tell us about the fundamental biology of immune cell types and the elasticity of the immune system. Although people are much more immunologically diverse than conventionally housed animal models, tools and technologies are now available that permit high-throughput analysis of human samples, including both blood and tissues, which will give us deep insights into human immunity in health and disease. As we gain a more detailed picture of the human immune system, we can build more sophisticated models to better reflect this complexity, both enabling the discovery of new immunological mechanisms and facilitating translation into the clinic.
Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study
Authors: Paul Tangermann, Federica Branchi, Alice Itzlinger, Jens Aschenbeck, Stefan Schubert, Jochen Maul, Thomas Liceni, Andreas Schröder, Frank Heller, Wolfgang Spitz, Ulrich Möhler, Ulrich Graefe, Michael Radke, Stefan Trenkel, Markus Schmitt, Christoph Loddenkemper, Jan C. Preiß, Reiner Ullrich, Severin Daum, Britta Siegmund, Christian Bojarski, Michael Schumann
Journal: Clinical Gastroenterology and Hepatology (2018)
Reply to Harshit Garg, Brusabhanu Nayak and Prabhjot Singh's Letter to the Editor Re: Tom J.H. Arends, Ofer Nativ, Massimo Maffezzini, et al. Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non–Muscle-invasive Bladder Cancer. Eur Urol 2016;69:1046–52
Authors: Tom J.H. Arends, J. Alfred Witjes
Journal: European Urology (2018)
Children with Heart Conditions and Their Special Health Care Needs — United States, 2016
Authors: Meng-Yu Chen, Tiffany Riehle-Colarusso, Lorraine F. Yeung, Camille Smith, Sherry L. Farr
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Children with heart conditions often use more health care services and specialized care than children without a heart condition (1); however, little is known about the number of U.S. children with heart conditions and their special health care needs. CDC used data from the 2016 National Survey of Children's Health (NSCH) to estimate the prevalence of heart conditions among U.S. children aged 0-17 years, which indicated that 1.3% had a current heart condition and 1.1% had a past heart condition (representing approximately 900,000 and 755,000 children, respectively). Sixty percent and 40% of children with current and past heart conditions, respectively, had one or more special health care needs, compared with 18.7% of children without a heart condition (adjusted prevalence ratios [aPRs] = 3.1 and 2.1, respectively). Functional limitations were 6.3 times more common in children with current heart conditions (30.7%) than in those without heart conditions (4.6%). Among children with current heart conditions, males, children with lower family income, and children living in other than a two-parent household had an increased prevalence of special health care needs. These findings highlight the importance of developmental surveillance and screening for children with heart conditions and might inform public health resource planning.
Abstract 18317: Activation of Autophagy Mediates Insulin-Like Growth Factor I (igf-1)-Induced Anti-Apoptotic Effect in Vascular Smooth Muscle Cells
Authors: Xuwei Hou, T Yoshida, Y Higashi, P Snarski, Z Li, P Delafontaine, S Danchuk, S Sukhanov
Journal: Circulation (2016)

Introduction: We have previously shown that smooth muscle cell (SMC)-specific IGF-1 receptor (IGF1R) deficiency enhances plaque SMC apoptosis and increases atherosclerosis in Apoe-null mice, howeve...
Barriers and solutions to conducting patient-reported outcomes (PRO) research in patients with pain.
Authors: Jeannine M. Brant, Carrie Tompkins Stricker, Debra Wujcik
Journal: Journal of Clinical Oncology (2018)

227 Background: Cancer pain prevalence ranges from 52-77%. Poorly controlled pain contributes to patient suffering and increased health care utilization. Shared decision making (SDM), where patient preferences, goals, and concerns are discussed, can foster earlier identification and improved pain management. A study was proposed to determine if incorporating SDM into a pain care plan is feasible and effective. Methods: Patients with metastatic cancer reported their pain and symptom experiences on an electronic patient-reported outcome (ePRO) platform. A drill down pain assessment included questions on chronic and breakthrough pain and end of dose failure. The patient and provider jointly discussed ePROs; an individualized care plan was printed for each patient. One academic and two community sites planned to recruit 105 patients over 6 months. Accrual quickly fell behind predicted rates (1 vs 15 patients per month). Study teams met to identify and mitigate accrual barriers. Results: Using an implementation science framework, barriers were identified in study design, and patient, provider, and environmental issues. Literature reports challenges in accruing/ retaining patients with metastatic disease, such as uncontrolled symptoms, inability to complete measures, missed visits, hospice admission, and death. Researchers broadened eligibility requirements to include all cancer stages; study team members were re-educated to clarify the operational definition of pain (experiencing pain or controlled on opioids). Some patient-related barriers were solved with workflow modifications (pre-visit survey completion). Environmental issues such as privacy to complete ePRO measures and internet connection reliability were solved with clinical staff. Conclusions: Study accrual improved 500% (from 6 to 36 in 3 months) following design and process changes. While examining patients with metastatic disease is important, expanding eligibility allows researchers to still include these patients and yet answer research questions timelier with the expanded population. Applying implementation science principles during study design is relevant to broader studies of pain and symptom ePROs and SDM in cancer care. Clinical trial information: NCT03304145.
Quality improvement using new technology to assess and reduce FDG PET/CT radiotracer infiltrations.
Authors: Jackson William Kiser
Journal: Journal of Clinical Oncology (2018)

313 Background: The reported aggregated PET/CT 18F-FDG radiotracer injection infiltration rate from 3 centers in 6 studies is 15.2% (425 infiltrations/2804 patients). Infiltrations can negatively affect cancer patient staging, therapy assessment, treatment planning, and can lead to unnecessary invasive procedures and patient radiation exposure. The radiotracer dose is essential to PET image quality and quantification. Efforts are made to ensure the exact dose administered is used to create the patient image; but, no measures ensure the administered dose completely enters the patient circulation. Our objective was to use new technology (Lara, Lucerno Dynamics) to assess our infiltration rate, determine potential causes, reduce our rate, and assess results sustainability. Methods: Our IRB determined the project did not meet the definition of research as defined by 45 CFR 46.102(d) and classified the initiative as “quality improvement”. In Phase 1, our PET/CT center monitored the injection process. Lara data were analyzed (SAS Enterprise Miner, v. 14.1 and v.9.4) and identified potential contributing factors. We then implemented a quality improvement plan to address these factors. In Phase 2 we remeasured our infiltration rate. After Phase 2, we assessed our rate over an extended period. Results: Lara added 30 seconds to patient imaging. In Phase 1, 263 injections were monitored, and 35 infiltrations were identified (13.3%). Five technologists’ rates ranged from 8%-19%. Patients less than 145lbs with non-antecubital fossa injection sites were highly associated with infiltrations. In Phase 2, 278 injections were monitored, and 8 infiltrations were identified (2.9%), a 78% decrease (p &lt; 0.0001). The same technologists’ rates ranged from 0%-4%. Eight technologists performed the next 504 injections and six were infiltrated (1.2%). Conclusions: Our findings supported published PET/CT infiltration rates. Using new technology provided technologists with feedback on injections and lead to significant and sustainable improvements quickly, with minimal patient/procedure disruption. Infiltrations are a quality and safety issue. As a result, the injection process requires ongoing monitoring.
Implementation of a low-cost standardized handoff system (IPASS) in a pediatric hematology/oncology unit: Lessons from a low-middle income country.
Authors: Sheri Pariha, Sana Saeed, Sonia Qureshi, Sadaf Altaf
Journal: Journal of Clinical Oncology (2018)

278 Background: Communication failure is the most common preventable cause of medical adverse event, and almost half of all sentinel events involve handoff failure. Inefficient handoff is labor intensive and time consuming, impacting the quality of patient care provided. A safe and efficient means of exchange of medical information between care teams via a standardized handoff system is essential, especially in high intensity fields such as Pediatric Hematology/Oncology. Methods: Pre-intervention, handoff entailed the physical handover of handwritten notes, carbon copied for various team members. A standardized electronic handoff tool (IPASS) was identified, and significantly modified to fit our needs, since we do not have a complete electronic medical record (EMR). Microsoft Sharepoint (Microsoft, Redmond, WA) was used to develop a tabulated online portal incorporating patient demographic, clinical and laboratory details with physician remarks. This allowed remote access, multiple simultaneous inputs, authenticated use and user-specific access control. Implementation included sensitizing residents to the IPASS template, hands-on training, weekly feedback from the residents, directly observed hand-off by the chief and/or senior resident. Following a four-week pilot this was expanded to other sub specialties, and a pre and post intervention survey was conducted to assess its impact. Results: Pre-implementation survey revealed 74% resident and 87% faculty dissatisfaction with the current handoff process. Weekly compliance audits after initial pilot demonstrated a 100% compliance. Post-Implementation results showed that the resident dissatisfaction has gone down to less than 5%. Conclusions: Implementation of an electronic handoff tool in the absence of an EMR with minimal resources is a major breakthrough and can be replicated in other low-resource settings. We successfully implemented IPASS without any added infrastructure cost. In the next phase of our project we will be measuring trends in reduction in medical errors since implementation.
European Monitoring Centre for Drugs and Drug Addiction has a vital role in the UK’s ability to respond to illicit drugs and organised crime
Authors: Andres Roman-Urrestarazu, Roy Robertson, Justin Yang, Alison McCallum, Christina Gray, Martin McKee, John Middleton
Journal: BMJ (2018)

Much attention has been devoted to the consequences of the European Medicines Agency’s departure from London because of Brexit.12 Yet exclusion from other EU agencies, including the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), will also have serious consequences for public health in the United Kingdom.

Founded in 1993 in Lisbon,3 the EMCDDA derives its mandate from Regulation (EC) No 1920/20063, which involves surveillance, establishing best practice, facilitating exchange of knowledge and data, providing leadership on new psychoactive substances, and assisting with policy making in countries and in the EU. By adopting certain “red lines,” including oversight by the Court of Justice of the European Union, the UK will exclude itself from full membership.34

The EMCDDA has provided the EU and its member states with accurate and timely intelligence and evidence based overviews of the European drug landscape …
CHARACTERIZATION OF CD4 T-CELL IMMUNE RESPONSE TO NUCLEOPORIN P62 IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS
Authors: Francesca Meda, Maria Serena Longhi, Dimitrios P. Bogdanos, Pietro Invernizzi, Yun Ma, Giorgina Mieli-Vergani, Jozefa Wesierska-Gadek, Massimo Zuin, Mauro Podda
Journal: Hepatology (2008)