tbuckley/cabot-search huggingface dataset:
Asthma drugs: industry and government look for greener methods of delivery
Authors: Lynn Eaton
Journal: BMJ (2019)

The UK government is working with the pharmaceutical industry to find new methods for delivering asthma drugs because of concerns over the effects of many commonly used inhalers on the climate.

Doctors have already been urged by the National Institute for Health and Care Excellence (NICE)1 to discuss with patients the type of asthma inhaler prescribed and other alternatives less damaging to the climate.

NICE’s patient decision aid says, “Where several inhalers could be viable options, patients can opt for the more environmentally friendly option, which may help to cut the health service’s carbon footprint.”

The most commonly used type, the metered dose inhaler, contains hydrofluorocarbons (HFCs), powerful greenhouse gases, whereas …
Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial
Authors: Josep M. del Campo, Ursula A. Matulonis, Susanne Malander, Diane Provencher, Sven Mahner, Philippe Follana, Justin Waters, Jonathan S. Berek, Kathrine Woie, Amit M. Oza, Ulrich Canzler, Marta Gil-Martin, Anne Lesoin, Bradley J. Monk, Bente Lund, Lucy Gilbert, Robert M. Wenham, Benedict Benigno, Sujata Arora, Sebastien J. Hazard, Mansoor R. Mirza
Journal: Journal of Clinical Oncology (2019)

In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.A total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (gBRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed gBRCAmut (non-gBRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to gBRCAmut status and response to their last platinum-based therapy. Ovarian cancer-specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy-Ovarian Symptom Index.Progression-free survival was improved in patients treated with niraparib compared with placebo in both the gBRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non-gBRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes.Patients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy.
Modelling the probability of erroneous negative lymph node staging in patients with colon cancer
Authors: Carlos Fortea‐Sanchis, Erica Forcadell‐Comes, David Martínez‐Ramos, Javier Escrig‐Sos
Journal: Cancer Communications (2019)

Abstract Background Patients in who with insufficient number of analysed lymph nodes (LNs) are more likely to receive an incorrect LN staging. The ability to calculate the overall probability of undiagnosed LN involvement errors in these patients could be very useful for approximating the real patient prognosis and for giving possible indications for adjuvant treatments. The objective of this work was to establish the predictive capacity and prognostic discriminative ability of the final error probability (FEP) among patients with colon cancer and with a potentially incorrectly‐staged LN‐negative disease. Methods This was a retrospective multicentric population study carried out between January 2004 and December 2007. We used a mathematical model based on Bayes’ theorem to calculate the probability of LN involvement given a FEP test result. Cumulative sum graphs were used to calculate risk groups and the survival rates were calculated, by month, using the Kaplan–Meier method. Results A total of 548 patients were analysed and classified into three risk groups according to their FEP score: low‐risk (FEP &lt; 2%), intermediate‐risk (FEP 2%–15%), and high‐risk (FEP &gt; 15%). Patients with LN involvement had the lowest overall survival rate when compared to the three risk groups. This difference was statistically significant for the low‐ and intermediate‐risk groups ( P = 0.002 and P = 0.004, respectively), but high‐risk group presented similar survival curves to pN+ group ( P = 0.505). In terms of disease‐free survival, the high‐risk group presented similar curves to the intermediate‐risk group until approximately 60 months’ follow‐up ( P = 0.906). After 80 months’ follow‐up, the curve of high‐risk group coincided with that of the pN+ group (P = 0.172). Finally, we summarized the FEP according to the number of analysed LNs and accompanied by a contour plot which represents its calculation graphically. Conclusions The application of Bayes’ theorem in the calculation of FEP is useful to delimit risk subgroups from among patients without LN involvement.
Annals Graphic Medicine - Dr. Mom: Rounds
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2019)

Web Exclusives4 June 2019Annals Graphic Medicine - Dr. Mom: RoundsFREEGrace E. Farris, MDGrace E. Farris, MDMount Sinai School of Medicine, New York, New York (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0046 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0042.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York. You can view her work at her Web site: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 June 2019Volume 170, Issue 11Page: W121-W122KeywordsConflicts of interestDisclosureHospital medicineHospitalists ePublished: 4 June 2019 Issue Published: 4 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis
Authors: Laura Turco, Candid Villanueva, Vincenzo La Mura, Juan Carlos García-Pagán, Thomas Reiberger, Joan Genescà, Roberto J. Groszmann, Barjesh C. Sharma, Carlo Merkel, Christophe Bureau, Edilmar Alvarado, Juan Gonzalez Abraldes, Agustin Albillos, Rafael Bañares, Markus Peck-Radosavljevic, Salvador Augustin, Shiv K. Sarin, Jaime Bosch, Guadalupe García-Tsao
Journal: Clinical Gastroenterology and Hepatology (2019)
Multiplexed promoterless gene expression with CRISPReader
Authors: Hengji Zhan, Qun Zhou, Qunjun Gao, Jianfa Li, Weiren Huang, Yuchen Liu
Journal: Genome biology (2019)

Genes are comprised of DNA codes and contain promoters and other control elements for reading these codes. The rapid development of clustered regularly interspaced short palindromic repeats (CRISPR) technology has made possible the construction of a novel code-reading system with low dependency on the native control elements. We develop CRISPReader, a technology for controlling promoterless gene expression in a robust fashion. We demonstrate that this tool is highly efficient in controlling transcription and translation initiation of a targeted transgene. A notable feature of CRISPReader is the ability to "read" the open reading frames of a cluster of gene without traditional regulatory elements or other cofactors. In particular, we use this strategy to construct an all-in-one AAV-CRISPR-Cas9 system by removing promoter-like elements from the expression cassette to resolve the existing AAV packaging size problem. The compact AAV-CRISPR-Cas9 is also more efficient in transactivation, DNA cleavage, and gene editing than the dual-AAV vector encoding two separate Cas9 elements, shown by targeting both reporter and endogenous genes in vitro and in vivo. CRISPReader represents a novel approach for gene regulation that enables minimal gene constructs to be expressed and can be used in potential biomedical applications.
Emotional and behavioural reactions to melanoma genomic risk information
Authors: G.L. Fenton, A.K. Smit, L. Keogh, A.E. Cust
Journal: British Journal of Dermatology (2019)

Melanoma is the most deadly type of skin cancer, and in countries like Australia, the number of people who develop melanoma is high. A new approach to further improving the prevention and early detection of melanoma aims to better understand people's chances, or risk, of developing melanoma by looking at their genes and then providing them with their genetic risk of melanoma information. This Australian‐based study explored how people react to receiving this type of information. Thirty people were interviewed who had no personal history of melanoma and had previously received their genetic risk results, along with information on how to prevent melanoma and a telephone call from a genetic counsellor. Several considerations influenced how participants felt and behaved in response to their risk results, including their expectations for their genetic risk, their thoughts on their melanoma risk before testing and how they already protected themselves from the sun. There were many positive reactions and a number of participants said it had changed their behaviour in the sun for the better by increasing their knowledge and awareness of melanoma. While some participants described having negative emotions such as disappointment and worry, these improved with time. The results from this study improves our understanding of emotional and behavioural responses to melanoma genetic risk information and will assist in developing educational and support resources for people who have genetic testing.
SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse
Authors: Frank Koopmans, Pim van Nierop, Maria Andres-Alonso, Andrea Byrnes, Tony Cijsouw, Marcelo P. Coba, L. Niels Cornelisse, Ryan J. Farrell, Hana L. Goldschmidt, Daniel P. Howrigan, Natasha K. Hussain, Cordelia Imig, Arthur P.H. de Jong, Hwajin Jung, Mahdokht Kohansalnodehi, Barbara Kramarz, Noa Lipstein, Ruth C. Lovering, Harold MacGillavry, Vittoria Mariano, Huaiyu Mi, Momchil Ninov, David Osumi-Sutherland, Rainer Pielot, Karl-Heinz Smalla, Haiming Tang, Katherine Tashman, Ruud F.G. Toonen, Chiara Verpelli, Rita Reig-Viader, Kyoko Watanabe, Jan van Weering, Tilmann Achsel, Ghazaleh Ashrafi, Nimra Asi, Tyler C. Brown, Pietro De Camilli, Marc Feuermann, Rebecca E. Foulger, Pascale Gaudet, Anoushka Joglekar, Alexandros Kanellopoulos, Robert Malenka, Roger A. Nicoll, Camila Pulido, Jaime de Juan-Sanz, Morgan Sheng, Thomas C. Südhof, Hagen U. Tilgner, Claudia Bagni, Àlex Bayés, Thomas Biederer, Nils Brose, John Jia En Chua, Daniela C. Dieterich, Eckart D. Gundelfinger, Casper Hoogenraad, Richard L. Huganir, Reinhard Jahn, Pascal S. Kaeser, Eunjoon Kim, Michael R. Kreutz, Peter S. McPherson, Ben M. Neale, Vincent O’Connor, Danielle Posthuma, Timothy A. Ryan, Carlo Sala, Guoping Feng, Steven E. Hyman, Paul D. Thomas, August B. Smit, Matthijs Verhage
Journal: Neuron (2019)
Exploring Patient Preferences for Adjunct-to-Insulin Therapy in Type 1 Diabetes
Authors: Bruce A. Perkins, Julio Rosenstock, Jay S. Skyler, Lori M. Laffel, David Z. Cherney, Chantal Mathieu, Christianne Pang, Richard Wood, Ona Kinduryte, Jyothis T. George, Jan Marquard, Nima Soleymanlou
Journal: Diabetes Care (2019)

While sodium-glucose cotransporter inhibitor (SGLTi) therapy has been evaluated in type 1 diabetes (T1D) trials, patient reactions to benefits and risks are unknown. Using established methodology, we evaluated patient preferences for different adjunct-to-insulin therapy options in T1D.An online survey, completed by 701 respondents with T1D (231 U.S., 242 Canada, and 228 Germany), used conjoint analysis to present six hypothetical, masked, pairwise drug profile choices composed of different benefit-risk attributes and effect ranges. Data used in analyses were derived from actual phase 3 trials of a low-dose SGLTi (comparable to oral empagliflozin 2.5 mg q.d.), a high-dose SGLTi (comparable to oral sotagliflozin 400 mg q.d.), and an available adjunct-to-insulin therapy (comparable to subcutaneous pramlintide 60 μg t.i.d.).Conjoint analysis identified diabetic ketoacidosis risk as most important to patients (23% relative score; z test, P < 0.05); ranked second were HbA1c reduction (14%), risk of severe hypoglycemia (13%), oral versus injectable treatment (12%), and risk of genital infection (12%). Next was risk of nausea (11%), followed by weight reduction (8%) and the risk of diarrhea (7%). A low-dose SGLTi drug profile was identified by conjoint analysis as the top patient preference (83% of participants; z test, P < 0.05) versus high-dose SGLTi (8%) or pramlintide (9%). Separate from conjoint analysis, when respondents were asked to choose their preferred adjunct-to-insulin therapy (masked to drug name/dose), 69%, 17%, 6%, and 9% of respondents chose low-dose SGLTi, high-dose SGLTi, pramlintide, and insulin therapy alone, respectively.Low-dose SGLTi profile was the favored adjunct-to-insulin therapy by persons with T1D.
The effects of sleep on prospective memory: A systematic review and meta-analysis
Authors: Ruth L.F. Leong, Grand H.-L. Cheng, Michael W.L. Chee, June C. Lo
Journal: Sleep Medicine Reviews (2019)

Prospective memory (PM) enables us to execute previously conceived intentions at a later time and is used when remembering to call a friend or submitting a proposal on time. Evidence that sleep benefits PM is presently mixed. Further, when a benefit is observed, it is unclear if this is achieved through improvements in strategic monitoring (maintaining an intention in mind and searching for cues) or spontaneous retrieval (an automatic process occurring without preparatory attention). We conducted a meta-analysis of 24 independent samples (N = 165,432) to quantify the effect of sleep on PM and gain clarity regarding the retrieval process benefitted by sleep. Cohen's d with 95% confidence intervals (CI95) were derived using random-effects models. The benefit of sleep on PM was statistically significant and in the small to medium range (d = 0.41, CI95 = 0.25–0.56). Moreover, sleep did not appear to influence monitoring (d = −0.11, CI95 = −0.40–0.17). In contrast, the benefits of sleep are significantly greater when the likelihood of spontaneous retrieval is high (d = 0.94, CI95 = 0.44–1.44) versus low (d = 0.45, CI95 = −0.02–0.93), suggesting that sleep may leverage on spontaneous retrieval processes to improve PM. These findings inform theoretical models of sleep and PM that could sharpen strategies to improve memory function in vulnerable populations.
Functional impairment on admission and associated symptom burden and health outcomes among hospitalized patients with advanced cancer.
Authors: Daniel E Lage, Areej El-Jawahri, Charn-Xin Fuh, Richard Newcomb, Vicki Jackson, Joseph Greer, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2019)

11554 Background: Hospitalized patients with cancer often have impaired function, as measured by activities of daily living (ADLs), related to age, comorbidities, and both cancer and treatment-related morbidity. However, the relationship between functional impairment and patients’ symptom burden and clinical outcomes has not been well described. Methods: We prospectively enrolled patients with advanced cancer with unplanned hospitalizations at an academic medical center. Upon admission, nurses assessed patients’ ADLs (mobility, feeding, bathing, dressing, and grooming). We used the Edmonton Symptom Assessment Scale (ESAS) and Patient Health Questionnaire-4 to assess physical and psychological symptoms, comparing symptom burden between patients with and without ADL impairment. We used regression models adjusted for age, sex, education, Charlson comorbidity index, months since advanced cancer diagnosis, and cancer type to assess the relationship between any ADL impairment on admission and hospital length of stay, the composite outcome of death or readmission within 90 days of discharge, and survival. Results: Among 932 patients, 40.2% had at least one ADL impairment. Patients with ADL impairment were older (Mean = 67.2 vs 60.8 years, p &lt; 0.001), had higher Charlson comorbidity index (Mean = 1.1 vs 0.7, p &lt; 0.001), and higher physical symptom burden (ESAS Physical Mean = 35.2 vs 30.9, p &lt; 0.001). Those with ADL impairment were more likely to have moderate to severe constipation (46.7% vs. 36.0%, p &lt; 0.01), pain (74.9% vs. 63.1%, p &lt; 0.01), drowsiness (76.6% vs. 68.3%, p &lt; 0.01), as well as symptoms of depression (38.3% vs. 23.6%, p &lt; 0.01) and anxiety (35.9% vs. 22.4%, p &lt; 0.01). In adjusted models, ADL impairment was associated with longer hospital length of stay (B = 1.30, p &lt; 0.01), higher odds of death or readmission within 90 days (odds ratio = 2.26, p &lt; 0.01), and higher mortality (hazard ratio = 1.73, p &lt; 0.01). Conclusions: Hospitalized patients with advanced cancer who have functional impairment experience a significantly higher symptom burden and worse health outcomes compared to those without functional impairment. These findings highlight the need to assess and address functional impairment among this population to enhance their quality of life and care.
MYC-Driven Small-Cell Lung Cancer is Metabolically Distinct and Vulnerable to Arginine Depletion
Authors: Milind D. Chalishazar, Sarah J. Wait, Fang Huang, Abbie S. Ireland, Anandaroop Mukhopadhyay, Younjee Lee, Sophia S. Schuman, Matthew R. Guthrie, Kristofer C. Berrett, Jeffery M. Vahrenkamp, Zeping Hu, Marek Kudla, Katarzyna Modzelewska, Guoying Wang, Nicholas T. Ingolia, Jason Gertz, David H. Lum, Sabina C. Cosulich, John S. Bomalaski, Ralph J. DeBerardinis, Trudy G. Oliver
Journal: Clinical Cancer Research (2019)

Small-cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among SCLC subtypes is largely unexplored. In this study, we aimed to determine whether metabolic vulnerabilities exist between SCLC subtypes that can be therapeutically exploited.We performed steady state metabolomics on tumors isolated from distinct genetically engineered mouse models (GEMM) representing the MYC- and MYCL-driven subtypes of SCLC. Using genetic and pharmacologic approaches, we validated our findings in chemo-naïve and -resistant human SCLC cell lines, multiple GEMMs, four human cell line xenografts, and four newly derived PDX models.We discover that SCLC subtypes driven by different MYC family members have distinct metabolic profiles. MYC-driven SCLC preferentially depends on arginine-regulated pathways including polyamine biosynthesis and mTOR pathway activation. Chemo-resistant SCLC cells exhibit increased MYC expression and similar metabolic liabilities as chemo-naïve MYC-driven cells. Arginine depletion with pegylated arginine deiminase (ADI-PEG 20) dramatically suppresses tumor growth and promotes survival of mice specifically with MYC-driven tumors, including in GEMMs, human cell line xenografts, and a patient-derived xenograft from a relapsed patient. Finally, ADI-PEG 20 is significantly more effective than the standard-of-care chemotherapy.These data identify metabolic heterogeneity within SCLC and suggest arginine deprivation as a subtype-specific therapeutic vulnerability for MYC-driven SCLC.
Gene Variant Associated With Menthol Cigarette Smoking in Some African Americans
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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