tbuckley/cabot-search huggingface dataset:
Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription
Authors: Xince Huang, Min He, Shuai Huang, Ruirong Lin, Ming Zhan, Dong Yang, Hui Shen, Sunwang Xu, Wei Cheng, Jianxiu Yu, Zilong Qiu, Jian Wang
Journal: Molecular Cancer (2019)

Abstract Background CircRNAs are found to affect initiation and progression of several cancer types. However, whether circRNAs are implicated in gallbladder cancer (GBC) progression remains obscure. Methods We perform RNA sequencing in 10 pairs of GBC and para-cancer tissues. CCK8 and clone formation assays are used to evaluate proliferation ability of GBC cells. qPCR and Western blot are used to determine expression of RNAs and proteins, respectively. CircRNA-protein interaction is confirmed by RNA pulldown, RNA immunoprecipitation, and fluorescence in situ hybridization. Results We find that circRNA expression pattern is tremendously changed during GBC development. Among dozens of significantly changed circRNAs, a circRNA generated from the oncogene ERBB2, named as circERBB2, is one of the most significant changes. CircERBB2 promotes GBC proliferation, in vitro and in vivo. Other than being a miRNA sponge, circERBB2 accumulates in the nucleoli and regulates ribosomal DNA transcription, which is one of the rate-limiting steps of ribosome synthesis and cellular proliferation. CircERBB2 regulates nucleolar localization of PA2G4, thereby forming a circERBB2-PA2G4-TIFIA regulatory axis to modulate ribosomal DNA transcription and GBC proliferation. Increased expression of circERBB2 is associated with worse prognosis of GBC patients. Conclusions Our findings demonstrate that circERBB2 serves as an important regulator of cancer cell proliferation and shows the potential to be a new therapeutic target of GBC.
Who Pays in Medicare Part D? Giving Plans More Skin in the Game
Authors: Erin E. Trish, Paul B. Ginsburg, Geoffrey F. Joyce, Dana P. Goldman
Journal: New England Journal of Medicine (2019)

As U.S. policymakers debate proposals for reforming the prescription-drug marketplace, they should recognize the need to update the Medicare Part D benefit design to give the private plans that largely administer it more skin in the game.
Prevalence of germline BRCA1 and BRCA2 mutations and variants among ovarian, primary peritoneal and fallopian tube cancer patients: A multicentre Indian study
Authors: S. Gupta, S. Rajappa, S.H. Advani, A. Agarwal, S. Aggarwal, C. Goswami, S. Dattatreya Palanki, D. Arya, S. Patil, R. Kodagali
Journal: Annals of Oncology (2019)
Nutritional Support Among Medical Inpatients—Feed the Cold (and Malnourished) and Starve the Febrile
Authors: Paul E. Marik
Journal: JAMA Network Open (2019)

Filomena Gomes, PhD; Annic Baumgartner, MD; Lisa Bounoure, PhD; Martina Bally, MD; Nicolaas E. Deutz, MD; Jeffrey L. Greenwald, MD; Zeno Stanga, MD; Beat Mueller, MD; Philipp Schuetz, MD, MPH
Kydar Multicenter Trial of Quadruple Regimen for Induction Resistant Myeloma Combined with Translational Single-Cell Analysis Identifies Potential Drivers of Advanced Resistance, Including Novel Immune Checkpoints
Authors: Yael C Cohen, Mor Zada, Moshe E. Gatt, Noa Lavi, Chezi Ganzel, Shuang-Yin Wang, Assaf Weiner, Guy Ledergor, Evgeni Chubar, Ory Rouvio, Iuliana Vaxman, Mouna Ballan, Tamar Tadmor, Anatoly Nemets, Osnat Jarchowcky Dolberg, Olga Shvetz, Ofer Shpilberg, Nagib Deli, Irit Avivi, Ido Amit
Journal: Blood (2019)
Efficacy and Tolerability of Ixazomib, Daratumumab and Low Dose Dexamethasone (Ixa Dara dex) in Unfit and Frail Newly Diagnosed Multiple Myeloma (NDMM) Patients; Results of the Interim Efficacy Analysis of the Phase II HOVON 143 Study
Authors: Claudia A.M. Stege, Kazem Nasserinejad, Ellen van der Spek, Roel J.W. Van Kampen, Maaike Sohne, Noortje Thielen, Yavuz Bilgin, Esther G.M. De Waal, Inge Ludwig, Maria B.L. Leijs, Alain Kentos, Gert Jan Timmers, Koen de Heer, Matthijs Westerman, Marie Christiane Vekemans, Nazik Durdu-Rayman, Nicole C.H.P. van der Burg-de Graauw, Niels W. C. J. Van De Donk, Pieter Sonneveld, Saskia K. Klein, Mark-David Levin, Sonja Zweegman
Journal: Blood (2019)
Developing a Novel Anti-Bcma CAR-T for Relapsed or Refractory Multiple Myeloma
Authors: Xin Yao, Shigui Zhu, Jiaqi Huang, Xiaoyan Qu, Judy Zhu, Yutian Wei, Liping Lan, Xiaoteng LV, Junfeng Wu, Rirfei Wang, Dingzhu Yang, Chengxiao Zheng, DiJun Zhao, Lei Fan, Fei Huang, Hua Lu, Chaocan Zhang, Cheng Chen, Yanfeng Li, Jiaqiang Ren, Li Zhang, Michael Humphries, Jianyong Li, Yihong Yao
Journal: Blood (2019)
OCM community oncology palliative care program: Opioid analgesic utilization.
Authors: Adil Jamal Akhtar, Karna Sheth, Jeffrey H. Margolis, Andrew A. Muskovitz, Richard Philip Zekman, George Howard, Mitchell Folbe, Yusuf Qamruzzaman, Samer Ballouz, Tammy Scott-Barney, Karma Maxwell, Mohammed Ibrahim, Lexi Stortz, Maria Fabbiano
Journal: Journal of Clinical Oncology (2019)

60 Background: Oncology Division of Michigan Health Professionals participates in Oncology Care Model (OCM ). A community oncology program for early and timely involvement of palliative care (PC) was launched in September 2017 to improve cancer pain management. Under-treatment of cancer pain leads to continued patient suffering and impaired quality of life. Appropriate dosing, rotation and frequent assessments are essential for better pain control. This study aims to see the effect of PC on opioid analgesic utilization. Methods: Retrospective claims review was performed with PC patients referred from September 2017 – December 2018 with an opioid class (as defined by CDC) Part D claim (within OCM data). Opioid utilization across agents was measured in morphine-milligram-equivalents (MME). MME per patient per opioid month (PPM) was compared between PC-referred and PC-not referred patients, pre- and post- PC start. Average MME PPM was compared between PC-Engaged and PC declined or unable to reach patients. Within these 2 cohorts, Long-Acting (LA) vs. Short-Acting (SA) opioid utilization was calculated. Results: PC-not referred patients appear to have little monthly variation in opioid dosing. PC-referred patients showed wide variation in opioid dosing before PC. After PC start, opioid dosing stabilized. PC-Engaged patients had more than double MME PPM vs PC declined or unable to reach (2481 MME PPM vs 1198 MME PPM respectively). PC-Engaged patients utilized a higher percentage of LA (43%) whereas PC declined or unable to reach used much less LA (8%). Conclusions: In patients with uncontrolled pain, PC-referral led to decreased variation in opioid dosing and better pain control. Better pain control may be the result of higher utilization of both SA &amp; LA opioids. Patients who do not engage in PC may be at-risk for under-treatment. Study was limited by OCM claims available as of June 2019. Results may be refreshed as more data becomes available.
Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis
Authors: Stephanie Lake, Zach Walsh, Thomas Kerr, Ziva D. Cooper, Jane Buxton, Evan Wood, Mark A. Ware, M. J. Milloy
Journal: PLoS Medicine (2019)

Background Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. Methods and findings This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3–54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34–0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. Conclusions We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain.
Competing interests in peer review
Authors: Hajira Dambha-Miller, Roger Jones
Journal: BMJ (2019)

We read John and colleagues’ paper and the accompanying editorial with interest.12 The trial findings indicate that authors’ financial conflict of interest (COI) disclosures have no effect on the quality of peer review. The study was limited to manuscripts submitted to the Annals of Emergency Medicine , and we are unclear about the extent to which financial COIs might contribute to …
WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating
Authors: Barbara A. Scholz, Noriyuki Sumida, Carolina Diettrich Mallet de Lima, Ilyas Chachoua, Mirco Martino, Ilias Tzelepis, Andrej Nikoshkov, Honglei Zhao, Rashid Mehmood, Emmanouil G. Sifakis, Deeksha Bhartiya, Anita Göndör, Rolf Ohlsson
Journal: Nature Genetics (2019)
Another hospital admission through the emergency room? Looking for a fragility pattern in advanced cancer patients.
Authors: Laura Velutti, Arianna Marinello, Antonella Cammarota, Maria Susanna Grimaudo, Annalisa Saetta, Santina Giuffrè, Diego Lopane, Nunzio Digiacomo, Chiara Provasoli, Frederico Gonçalves Pereira, Luca Cullia, Elisabetta Villa, Chiara Poggio, Stefano Ferrari, Carlotta Pavesi, Laura Giordano, Lorenza Rimassa, Armando Santoro
Journal: Journal of Clinical Oncology (2019)

65 Background: Cancer patients (pts) are often treated with anticancer therapy (CT) even in the last months of life and are often hospitalized through an access to the emergency room (ERa). This is frequently the time when a palliative care (PC) service starts, or when pts die. Methods: We performed a retrospective analysis of pts admitted to our Oncology Unit through an ERa. We evaluated: pts’ characteristics, histology, date of diagnosis, sites of metastases, comorbidities, previous CT and radiotherapy (RT), imaging procedures and other exams in the last 90 days (90d), previous ERa and admissions for supportive care (SC), including transfusions, parenteral/enteral nutrition, high-cost antibiotics, in the last 90d. Pts were divided into 2 fragility groups: less fragile (LF), candidate after discharge to further CT or follow-up, and more fragile (MF), pts candidate to PC or who died in the Oncology Unit. Results: From August 2017 to May 2018 441/756 pts (58.3%) were admitted through an ERa: women/men 219/222, median age 65.4 years (y), range (r) 18.9 - 89.7. 328 pts had visceral metastases, 287 pts had ≥1 comorbidity, 318 pts received ≥1 line of CT (r 1-8), 121 pts received ≥1 RT (r 1-5), 240 pts had ≥1 prior admission for SC (r 1-6), 224 pts had an ERa (r 1-6) and 141 pts had ≥1 hospitalization for SC (r 1-4) in the last 90d, 386 pts received ≥1 diagnostic exam in the last 90d (r 1-12). Pts were grouped as follows: LF/MF 236/205. Differences between the 2 groups were: pts ≥70 y 31% in LF, 40% in MF, p=0.047; visceral metastases 70.1% in LF, 85.1% in MF, p&lt;0.001; ≥1 line of CT 64% in LF, 81% in MF, p&lt;0.001; ≥1 RT 23% in LF, 32% in MF, p=0.036; admissions for SC 47% in LF, 62.9% in MF, p&lt;0.001; ERa in the last 90d 39% in LF, 64% in MF, p&lt;0.001; admissions for SC in the last 90d 24.4% in LF, 39.4% in MF, p=0.004. No other differences were observed between the 2 groups. Conclusions: We identified a MF profile: pts ≥70 y, with visceral metastases, ≥1 line of CT and ≥1 RT course for advanced disease, ≥1 prior hospitalization for SC, ≥1 ERa and ≥1 admission for SC in the last 90d. The identification of this fragility profile may help oncologists timely offer a PC program to advanced stage pts. This could prevent some ERa and hospital admissions close to the end of life.
Stigma reduction interventions in people living with HIV to improve health-related quality of life
Authors: Galit Zeluf Andersson, Maria Reinius, Lars E Eriksson, Veronica Svedhem, Farhad Mazi Esfahani, Keshab Deuba, Deepa Rao, Goodluck Willey Lyatuu, Danielle Giovenco, Anna Mia Ekström
Journal: The Lancet HIV (2019)
Smoke-free prison policy development, implementation, and impact across the entire national prison service in Scotland (TIPs study): a three-phase, mixed methods natural experimental evaluation
Authors: Kate Hunt, Ashley Brown, Linda Bauld, Kathleen Boyd, Philip Conaglen, Peter Craig, Evangelia Demou, Ruaraidh Dobson, Douglas Eadie, Alastair Leyland, Nicola McMeekin, Jill Pell, Richard Purves, Helen Sweeting, Emily Tweed, Sean Semple
Journal: The Lancet (2019)
methylCC: technology-independent estimation of cell type composition using differentially methylated regions
Authors: Stephanie C. Hicks, Rafael A. Irizarry
Journal: Genome biology (2019)

A major challenge in the analysis of DNA methylation (DNAm) data is variability introduced from intra-sample cellular heterogeneity, such as whole blood which is a convolution of DNAm profiles across a unique cell type. When this source of variability is confounded with an outcome of interest, if unaccounted for, false positives ensue. Current methods to estimate the cell type proportions in whole blood DNAm samples are only appropriate for one technology and lead to technology-specific biases if applied to data generated from other technologies. Here, we propose the technology-independent alternative: methylCC, which is available at https://github.com/stephaniehicks/methylCC.
A decade of optimizing drug development for rare neuromuscular disorders through TACT
Authors: Kathryn R. Wagner, Annamaria De Luca, Didier Caizergues, James Dowling, Nathalie Goemans, Heather Gordish-Dressman, Miranda D. Grounds, Michael Kelly, Anna Mayhew, Elizabeth M. McNally, Tracey Zoetis, Joanne Lee, Cathy Turner, Dominic J. Wells, Cristina Csimma, Volker Straub
Journal: Nature Reviews Drug Discovery (2019)
Assessment of Unintentional Duplicate Orders by Emergency Department Clinicians Before and After Implementation of a Visual Aid in the Electronic Health Record Ordering System
Authors: Steven Horng, Joshua W. Joseph, Shelley Calder, Jennifer P. Stevens, Ashley L. O’Donoghue, Charles Safran, Larry A. Nathanson, Evan L. Leventhal
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Electronic health records allow teams of clinicians to simultaneously care for patients, but an unintended consequence is the potential for duplicate orders of tests and medications. <h3>Objective</h3> To determine whether a simple visual aid is associated with a reduction in duplicate ordering of tests and medications. <h3>Design, Setting, and Participants</h3> This cohort study used an interrupted time series model to analyze 184 694 consecutive patients who visited the emergency department (ED) of an academic hospital with 55 000 ED visits annually. Patient visits occurred 1 year before and after each intervention, as follows: for laboratory orders, from August 13, 2012, to August 13, 2014; for medication orders, from February 3, 2013, to February 3, 2015; and for radiology orders, from December 12, 2013, to December 12, 2015. Data were analyzed from April to September 2019. <h3>Exposure</h3> If an order had previously been placed during the ED visit, a red highlight appeared around the checkbox of that order in the computerized provider order entry system. <h3>Main Outcomes and Measures</h3> Number of unintentional duplicate laboratory, medication, and radiology orders. <h3>Results</h3> A total of 184 694 patients (mean [SD] age, 51.6 [20.8] years; age range, 0-113.0 years; 99 735 [54.0%] women) who visited the ED were analyzed over the 3 overlapping study periods. After deployment of a noninterruptive nudge in electronic health records, there was an associated 49% decrease in the rate of unintentional duplicate orders for laboratory tests (incidence rate ratio, 0.51; 95% CI, 0.45-0.59), from 4485 to 2731 orders, and an associated 40% decrease in unintentional duplicate orders of radiology tests (incidence rate ratio, 0.60; 95% CI, 0.44-0.82), from 956 to 782 orders. There was not a statistically significant change in unintentional duplicate orders of medications (incidence rate ratio, 1.17; 95% CI, 0.52-2.61), which increased from 225 to 287 orders. The nudge eliminated an estimated 17 936 clicks in our electronic health record. <h3>Conclusions and Relevance</h3> In this interrupted time series cohort study, passive visual cues that provided just-in-time decision support were associated with reductions in unintentional duplicate orders for laboratory and radiology tests but not in unintentional duplicate medication orders.
Treatment with the Bruton Tyrosine Kinase Inhibitor Zanubrutinib (BGB-3111) Demonstrates High Overall Response Rate and Durable Responses in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Updated Results from a Phase 1/2 Trial
Authors: Gavin Cull, David Simpson, Stephen Opat, Jan A. Burger, Judith Trotman, Paula Marlton, David Gottlieb, Javier Munoz, John F. Seymour, Andrew W. Roberts, Ken Wu, Siminder Atwal, William Novotny, Jane Huang, Constantine S. Tam
Journal: Blood (2019)
547 transcriptomes from 44 brain areas reveal features of the aging brain in non-human primates
Authors: Ming-Li Li, Shi-Hao Wu, Jin-Jin Zhang, Hang-Yu Tian, Yong Shao, Zheng-Bo Wang, David M. Irwin, Jia-Li Li, Xin-Tian Hu, Dong-Dong Wu
Journal: Genome biology (2019)

Brain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates.Here, we explore non-human primate brain aging using 547 transcriptomes originating from 44 brain areas in rhesus macaques (Macaca mulatta). We show that expression connectivity between pairs of cerebral cortex areas as well as expression symmetry between the left and right hemispheres both decrease after aging. Although the aging mechanisms across different brain areas are largely convergent, changes in gene expression and alternative splicing vary at diverse genes, reinforcing the complex multifactorial basis of aging. Through gene co-expression network analysis, we identify nine modules that exhibit gain of connectivity in the aged brain and uncovered a hub gene, PGLS, underlying brain aging. We further confirm the functional significance of PGLS in mice at the gene transcription, molecular, and behavioral levels.Taken together, our study provides comprehensive transcriptomes on multiple brain regions in non-human primates and provides novel insights into the molecular mechanism of healthy brain aging.
Anti-Apoptotic MCL-1 Plays a Critical Role in Maintenance of Normal and Malignant Human Hematopoietic Stem Cells through FLT3 Signaling.
Authors: Goichi Yoshimoto, Toshihiro Miyamoto, Tadafumi Iino, Yoshikane Kikushige, Hiroaki Niiro, Hiromi Iwasaki, Mine Harada, Koichi Akashi
Journal: Blood (2006)
Loss of Phospholipase C Gamma 1 (PLCG1) Impairs AML1-ETO Induced Leukemia Stem Cell Self-Renewal
Authors: Tina M. Schnoeder, Adrian Schwarzer, Florian Perner, Joanna Kirkpatrick, Anna Dolnik, Konstanze Döhner, Patricia Arreba-Tutusaus, Salam A. Assi, Claudia Bruedigam, Carolin Kathner, Theresa Eifert, Marcus Buschbeck, Monica Nafria I Fedi, Anetta Ptasinska, Andrew Elefanty, Elizabeth Ng, Holger Bierhoff, Florian Gras, Georg Matziolis, Klaus-Dieter Fischer, Olaf Heidenreich, Steven W. Lane, Lars Bullinger, Björn von Eyss, Alessandro Ori, Constanze Bonifer, Florian H. Heidel
Journal: Blood (2019)
Ibrutinib and Venetoclax Target Distinct Subpopulation of CLL Cells: Rationale for Drug Combination and Implication of Minimal Residual Disease Eradication
Authors: Y. Lynn Lynn Wang, Carrie Franzen, Shengchun Wang, Girish Venkataraman, Lei Li, Nifang Niu, Madina Sukhanova, Yifan Tu, Juehua Gao, Yi-Hua Chen, Shuo Ma, Richard A. Larson, Lu Pin
Journal: Blood (2019)
An Open‐Label, Dose‐Escalation Study to Assess the Safety and Efficacy of IL‐22 Agonist F‐652 in Patients With Alcohol‐associated Hepatitis
Authors: Juan P. Arab, Tejasav S. Sehrawat, Douglas A. Simonetto, Vikas K. Verma, Dechun Feng, Tom Tang, Kevin Dreyer, Xiaoqiang Yan, William L. Daley, Arun Sanyal, Naga Chalasani, Svetlana Radaeva, Liu Yang, Hugo Vargas, Mauricio Ibacache, Bin Gao, Gregory J. Gores, Harmeet Malhi, Patrick S. Kamath, Vijay H. Shah
Journal: Hepatology (2019)

Background and Aims Interleukin‐22 has beneficial effects on inflammation and impaired hepatic regeneration that characterize alcohol‐associated hepatitis (AH). F‐652 is a recombinant fusion protein of human interleukin‐22 and immunoglobulin G2 fragment crystallizable. This study aims to assess the safety and efficacy signals of F‐652 in patients with moderate and severe AH. Approach and Results A phase‐2 dose‐escalating study was carried out. F‐652 (10 μg/kg, 30 μg/kg, or 45 μg/kg) administered on days 1 and 7 was tested in 3 patients each with moderate (Model for End‐Stage Liver Disease [MELD] scores: 11‐20) and severe AH (MELD scores: 21‐28). Safety was defined by absence of serious adverse events and efficacy was assessed by Lille score, changes in MELD score, and serum bilirubin and aminotransferases at days 28 and 42. Three independent propensity‐matched comparator patient cohorts were used. Plasma extracellular vesicles and multiplex serum cytokines were measured to assess inflammation and hepatic regeneration. Eighteen patients (9 moderate and 9 severe AH) were enrolled, 66% were male, and the mean age was 48 years. The half‐life of F‐652 following the first dose was 61‐85 hours. There were no serious adverse events leading to discontinuation. The MELD score and serum aminotransferases decreased significantly at days 28 and 42 from baseline ( P &lt; 0.05). Day‐7 Lille score was 0.45 or less in 83% patients as compared with 6%, 12%, and 56% among the comparator cohorts. Extracellular vesicle counts decreased significantly at day 28 ( P &lt; 0.013). Cytokine inflammatory markers were down‐regulated, and regeneration markers were up‐regulated at days 28 and 42. Conclusions F‐652 is safe in doses up to 45 μg/kg and associated with a high rate of improvement as determined by Lille and MELD scores, reductions in markers of inflammation and increases in markers of hepatic regeneration. This study supports the need for randomized placebo‐controlled trials to test the efficacy of F‐652 in AH.