tbuckley/cabot-search huggingface dataset:
How house design affects malaria mosquito density, temperature, and relative humidity: an experimental study in rural Gambia
Authors: Ebrima Jatta, Musa Jawara, John Bradley, David Jeffries, Balla Kandeh, Jakob B Knudsen, Anne L Wilson, Margaret Pinder, Umberto D'Alessandro, Steve W Lindsay
Journal: The Lancet Planetary Health (2018)

IntroductionUnprecedented improvements in housing are occurring across much of rural sub-Saharan Africa, but the consequences of these changes on malaria transmission remain poorly explored. We examined how different typologies of rural housing affect mosquito house entry and indoor climate.MethodsFive typologies of mud-block houses were constructed in rural Gambia: four were traditional designs with poorly fitted doors and one was a novel design with gable windows to improve ventilation. In each house, one male volunteer slept under a bednet and mosquitoes were collected indoors with a light trap. Typologies were rotated between houses weekly. Indoor conditions were monitored with data loggers and the perceived comfort of sleepers recorded with questionnaires. We used pyschrometric modelling to quantify the comfort of the indoor climate using the logger data. Primary measurements were mean number of Anopheles gambiae and mean temperature for each house typology.FindingsIn thatched-roofed houses, closing the eaves reduced A gambiae house entry by 94% (95% CI 89–97) but increased the temperature compared with thatched-roofed houses with open eaves. In houses with closed eaves, those with metal roofs had more A gambiae, were hotter (1·5°C hotter [95% CI 1·3–1·7]) between 2100h and 2300 h, and had 25% higher concentrations of carbon dioxide (211·1 ppm higher [117·8–304·6]) than those with thatched roofs. In metal-roofed houses with closed eaves, mosquito house entry was reduced by 96% (91–98) by well fitted screened doors. Improved ventilation of metal-roofed houses made them as cool as thatched houses with open eaves. Metal-roofed houses with closed eaves were considered more uncomfortable than thatched ones with closed eaves. In metal-roofed houses, ventilated houses were more comfortable than unventilated houses before midnight, when people retired to bed.InterpretationClosing the eaves reduced vector entry in thatched houses but increased entry in metal-roofed houses. Metal-roofed houses with closed eaves were, however, protected against malaria vectors by well fitted screened doors and were made comfortable by increasing ventilation. House designs that exclude mosquitoes and are comfortable to live in should be a priority in sub-Saharan Africa.FundingSir Halley Stewart Trust, Global Clinical Trials, and Global Challenges Research Fund.
Abstract 18360: Predictors of Physician Under-recognition of Angina in Outpatients With Stable Coronary Artery Disease
Authors: Anna Grodzinsky, Mikhail Kosiborod, John Beltrame, Kensey Gosch, Philip G Jones, John A Spertus, Karen P Alexander, Ali Shafiq, Suzanne V Arnold
Journal: Circulation (2015)

Background: Under-recognition of angina by physicians may result in under-treatment with revascularization or medications that could improve patients’ quality of life. Patient and physician characteristics associated with under-recognition have never been described. Methods: Outpatients with stable CAD in a 24-site US registry completed the Seattle Angina Questionnaire (SAQ) and their physicians independently quantified patients’ angina in the month prior to their clinic visit. Angina frequency was categorized as none, monthly, and daily/weekly. Among patients who reported angina, under-recognition was defined as the physician reporting a lower frequency of angina than the patient. A hierarchical (for site and physician) logistic model examined patient and physician factors associated with under-recognition of angina. Physician variability was assessed with a median odds ratio (MOR), which compares the likelihood of 1 physician at 1 random site under-recognizing angina vs. another physician at another site. Results: Among 1203 patients with stable CAD, 304 patients reported angina in the prior month, of whom 122 (40%) were under-recognized by their physician. Physicians were more likely to under-recognize the frequency of angina in patients with heart failure and among patients with less frequent angina (Figure). No other patient or physician factors were associated with under-recognition. There was significant variability across physicians (MOR 2.6), indicating that some physicians were better than others at recognizing angina. Conclusions: Under-recognition of angina is common in routine clinical practice and was largely unrelated to standard patient and physician characteristics. The large variation across physicians suggests that a more systematic approach is needed to assess angina from patients with CAD. The use of a validated tool, such as the SAQ, should be tested for improving angina recognition and outcomes.
Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized with NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)
Authors: Leon Bernal-Mizrachi, Craig E. Cole, Leonard Heffner, Ajay K Nooka, Ravi Vij, Nyaya Kelkar, Akshata Sridhar, Munevver Cinar, Zhengjia Chen, Zhao Chang, Sagar Lonial, Jonathan L Kaufman
Journal: Blood (2018)
Association of Autism Spectrum Disorder With Prenatal Exposure to Medication Affecting Neurotransmitter Systems
Authors: Magdalena Janecka, Arad Kodesh, Stephen Z. Levine, Shari I. Lusskin, Alexander Viktorin, Rayees Rahman, Joseph D. Buxbaum, Avner Schlessinger, Sven Sandin, Abraham Reichenberg
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> Prenatal exposure to certain medications has been hypothesized to influence the risk of autism spectrum disorders (ASD). However, the underlying effects on the neurotransmitter systems have not been comprehensively assessed. <h3>Objective</h3> To investigate the association of early-life interference with different neurotransmitter systems by prenatal medication exposure on the risk of ASD in offspring. <h3>Design, Setting, and Participants</h3> This case-control study included children born from January 1, 1997, through December 31, 2007, and followed up for ASD until January 26, 2015, within a single Israeli health maintenance organization. Using publicly available data, 55 groups of medications affecting neurotransmitter systems and prescribed to pregnant women in this sample were identified. Children prenatally exposed to medications were compared with nonexposed children. Data were analyzed from March 1, 2017, through June 20, 2018. <h3>Main Outcome and Measures</h3> Hazard ratios (HRs) and 95% CIs of ASD risk associated with exposure to medication groups using Cox proportional hazards regression, adjusted for the relevant confounders (eg, birth year, maternal age, maternal history of psychiatric and neurologic disorders, or maternal number of all medical diagnoses 1 year before pregnancy). <h3>Results</h3> The analytic sample consisted of 96 249 individuals (1405 cases; 94 844 controls; mean [SD] age at the end of follow-up, 11.6 [3.1] years; 48.8% female), including 1405 with ASD and 94 844 controls. Of 34 groups of medications, 5 showed nominally statistically significant association with ASD in fully adjusted models. Evidence of confounding effects of the number of maternal diagnoses on the association between offspring exposure to medication and ASD was found. Adjusting for this factor, lower estimates of ASD risk among children exposed to cannabinoid receptor agonists (HR, 0.72; 95% CI, 0.55-0.95;<i>P</i> = .02), muscarinic receptor 2 agonists (HR, 0.49; 95% CI, 0.24-0.98;<i>P</i> = .04), opioid receptor κ and ε agonists (HR, 0.67; 95% CI, 0.45-0.99;<i>P</i> = .045), or α<sub>2C</sub>-adrenergic receptor agonists (HR, 0.43; 95% CI, 0.19-0.96;<i>P</i> = .04) were observed. Exposure to antagonists of neuronal nicotinic acetylcholine receptor α was associated with higher estimates of ASD risk (HR, 12.94; 95% CI, 1.35-124.25;<i>P</i> = .03). <h3>Conclusions and Relevance</h3> Most of the medications affecting neurotransmitter systems in this sample had no association with the estimates of ASD risk. Replication and/or validation using experimental techniques are required.
DNAX Activating Protein of 12 kDa/Triggering Receptor Expressed on Myeloid Cells 2 Expression by Mouse and Human Liver Dendritic Cells: Functional Implications and Regulation of Liver Ischemia–Reperfusion Injury
Authors: Toshimasa Nakao, Yoshihiro Ono, Helong Dai, Ryosuke Nakano, Angelica Perez‐Gutierrez, Geoffrey Camirand, Hai Huang, David A. Geller, Angus W. Thomson
Journal: Hepatology (2018)

Liver interstitial dendritic cells (DCs) have been implicated in the control of ischemia–reperfusion injury (IRI) and host immune responses following liver transplantation. Mechanisms underlying these regulatory functions of hepatic DCs remain unclear. We have shown recently that the transmembrane immunoadaptor DNAX‐activating protein of 12 kDa (DAP12) negatively regulates mouse liver DC maturation and proinflammatory and immune stimulatory functions. Here, we used PCR analysis and flow cytometry to characterize expression of DAP12 and its associated triggering receptor, triggering receptor expressed on myeloid cells 2 (TREM2), by mouse and human liver DCs and other immune cells compared with DCs in other tissues. We also examined the roles of DAP12 and TREM2 and their expression by liver DCs in the regulation of liver IRI. Injury was induced in DAP12 –/– , TREM2 –/– , or wild‐type (WT) mice by 1 hour of 70% clamping and quantified following 6 hours of reperfusion. Both DAP12 and TREM2 were coexpressed at comparatively high levels by liver DCs. Mouse liver DCs lacking DAP12 or TREM2 displayed enhanced levels of nuclear factor κB and costimulatory molecule expression. Unlike normal WT liver DCs, DAP12 –/– liver DC failed to inhibit proliferative responses of activated T cells. In vivo , DAP12 –/– and TREM2 –/– mice exhibited enhanced IRI accompanied by augmented liver DC activation. Elevated alanine aminotransferase levels and tissue injury were markedly reduced by infusion of WT but not DAP12 –/– DC. Conclusion: Our data reveal a close association between DAP12 and TREM2 expression by liver DC and suggest that, by negatively regulating liver DC stimulatory function, DAP12 promotes their control of hepatic inflammatory responses; the DAP12/TREM2 signaling complex may represent a therapeutic target for control of acute liver injury/liver inflammatory disorders.
Kidney Cancer: Toxicity Management, Symptom Control, and Palliative Care
Authors: Victoria J. Sinibaldi, Caroline F. Pratz, Olga Yankulina
Journal: Journal of Clinical Oncology (2018)

The challenges of managing the toxicities associated with the current armamentarium to combat kidney cancer continue to grow. It is therefore paramount for providers to not only have knowledge of the disease, but to also have an understanding of the potential adverse effects associated with the various treatments. In addition, it is important to incorporate palliative care strategies to help manage symptoms, improve quality of life, and support patients and their families throughout the continuum of the disease. This article will discuss the general toxicities and symptomatic issues encountered in patients with kidney cancer who are receiving targeted therapies and immunotherapies. It will also define the components of palliative care and its benefits. The recommendations in this article are from source documentation noted in various guidelines of the Oncology Nursing Society, ASCO, the National Comprehensive Cancer Network, and the Society for Immunotherapy of Cancer. We feel it is appropriate to modify and individualize management as deemed necessary to provide the best outcome for patients and their families.
Using HPV test in cervical screening may allow some women to stop earlier
Authors: Ingrid Torjesen
Journal: BMJ (2018)

Replacing traditional smear tests used in cervical cancer screening with a new test that detects human papillomavirus (HPV) DNA may allow regular testing to stop earlier for some women, a study published in Lancet Oncology suggests.1

The NHS invites women in England aged 25 to 49 for cervical screening every three years and those aged 50 to 64 every five years using cervical cytology (smear test). The new HPV test is being rolled out and will be the primary test used by the end of 2019. While more expensive than the current test, the HPV test has been shown to detect a higher proportion of women with high grade precancerous lesions (cervical intraepithelial …
Zika Virus Vaccine Development: Progress in the Face of New Challenges
Authors: Michael S. Diamond, Julie E. Ledgerwood, Theodore C. Pierson
Journal: Annual Review of Medicine (2018)

Zika virus (ZIKV) emerged at a global level when it spread to the Americas and began causing congenital malformations and microcephaly in 2015. A rapid response by academia, government, public health infrastructure, and industry has enabled the expedited development and testing of a suite of vaccine platforms aiming to control and eliminate ZIKV-induced disease. Analysis of key immunization and pathogenesis studies in multiple animal models, including during pregnancy, has begun to define immune correlates of protection. Nonetheless, the deployment of ZIKV vaccines, along with the confirmation of their safety and efficacy, still has major challenges, one of which is related to the waning of the epidemic. In this review, we discuss the measures that enabled rapid progress and highlight the path forward for successful deployment of ZIKV vaccines.
Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor
Authors: Chandrajit P. Raut, N. Joseph Espat, Robert G. Maki, Dejka M. Araujo, Jonathan Trent, Toni Faith Williams, D. Das Purkayastha, Ronald P. DeMatteo
Journal: JAMA Oncology (2018)

Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in patients with high-risk primary gastrointestinal stromal tumor (GIST) compared with patients who receive 1 year of treatment. The impact of a longer duration of therapy is unknown.To determine whether adjuvant treatment for primary GIST with imatinib for 5 years is tolerable and efficacious.This prospective, single-arm, phase 2 clinical trial (Postresection Evaluation of Recurrence-free Survival for Gastrointestinal Stromal Tumors With 5 Years of Adjuvant Imatinib [PERSIST-5]) included adult patients with primary GIST (expressing KIT) at 21 US institutions who underwent a macroscopically complete resection and were at intermediate or high risk of recurrence, defined as primary GIST at any site measuring 2 cm or larger with 5 or more mitoses per 50 high-power field or nongastric primary GIST measuring 5 cm or larger. Data were collected from August 5, 2009, through December 20, 2016.Imatinib, 400 mg once daily, orally for 5 years or until discontinuation of therapy because of progression or intolerance.The primary end point was recurrence-free survival (RFS). The secondary end point was overall survival.Of the 91 patients enrolled, 48 (53%) were men with a median age of 60 years (range, 30-90 years). Median tumor size was 6.5 cm (range, 2.3-30.0 cm). Median treatment duration was 55.1 months (range, 0.5-60.6 months); 46 patients (51%) completed 5 years of imatinib therapy. Estimated 5-year RFS was 90% (95% CI, 80%-95%), and overall survival was 95% (95% CI, 86%-99%). Recurrence was noted in 7 patients: 1 had disease recur while receiving imatinib (PDGFRA D842V mutation) and died; 6 had disease recur after discontinuation of imatinib therapy. Two additional deaths were unrelated to treatment or tumor progression. Forty-five patients (49%) stopped treatment early because of patient choice (10 [21%]), adverse events (15 [16%]), or other (11 [12%]). All 91 patients experienced at least 1 adverse event, and 17 (19%) experienced grade 3 or 4 adverse events.In this first adjuvant trial, to our knowledge, of patients with resected primary GIST who received 5 years of imatinib therapy, no patient with imatinib-sensitive mutations had disease recur during therapy. For patients in whom disease recurred, recurrence was within 2 years of discontinuation of imatinib therapy. Approximately half of the patients discontinued treatment early, most commonly because of patient choice, thus emphasizing the importance of close clinical monitoring to continue imatinib treatment for patients at appropriate risk.ClinicalTrials.gov identifier: NCT00867113.
Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screening
Authors: R. A. Smith, V. Cokkinides, O. W. Brawley
Journal: CA A Cancer Journal for Clinicians (2009)

Each year, the American Cancer Society (ACS) publishes a report summarizing its recommendations for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In 2008, the ACS, the American Gastroenterological Association, the American College of Gastroenterology, the Society for Gastrointestinal Endoscopy, and the American College of Radiology issued a joint update of guidelines for colorectal cancer screening in average-risk adults. In this issue, the current ACS guidelines and recent issues are summarized, updates of testing guidelines for early prostate cancer detection and colorectal cancer screening by the United States Preventive Services Task Force are discussed, and the most recent data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System and the National Health Interview Survey pertaining to participation rates in cancer screening are described.
FRI0242 Impairment in the rates of incidence, mortality, stays and annual costs of hospitalizations for gout in the spanish national health system
Authors: M. Hernández Hurtado, M. Á. Martínez Huedo, A. Balsa Criado, D. Peiteado López, E. De Miguel Mendieta
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Gout is the most common inflammatory articular disease in adults concerning a 1%–2% of the general population, and even a 4%–5% in older than 70 years. Recently, it has been reported an increase of the prevalence of gout, especially in developed countries. <h3>Objectives</h3> The principal purpose of our study is to describe the clinical and epidemiological characteristics of hospitalised patients with diagnosis of gout in Spain including mortality, comorbidities and healthcare costs in the last decade <h3>Methods</h3> Retrospective observational study based on data from the Database of Hospital from the Spanish National Health Service. The study was conducted in patients over eighteen years old with any gout diagnosis as principal or other diagnosis, who were admitted in the hospital between the years 2005–2015. The clinical characteristics analysed were sex, age, costs and length of hospital stay. Comorbidities as diabetes, congestive heart failure, acute myocardial infarction and cerebrovascular disease were identified with <i>International Classification of Diseases, ninth revision, common modification (</i>ICD-9-CM). <h3>Results</h3> The study cohort included 192.037 patients with gout, 82.6% of those were males. There was a progressive increase in the number of hospitalised patients with gout from 12 851 patients in 2005 to 23 318 in 2015; this was associated with an increase in mortality, reaching its highest value in 2015 with a 4.9% of gout hospitalised patients. The average age at dead in 2015 was 79.2 years and 85.16 years in male and female respectively, an age slightly lower than in the general population. The average cost in these hospitalised patients was 4931 €, reaching a peak of 5384 € in the last year. The hospital stay reached its lowest numbers in 2015 with an average of 8.9 days per patient. These comorbidities had statistical association with an added mortality risk in cerebrovascular disease (odds ratio [OR] 1.57, 95% confidence interval [CI]1.46–1.49), liver disease (OR 2.61 95% CI 2.34–2.9), kidney disease (OR 1.34 95% CI 1.28–1.41), dementia (OR 2.13 95% CI 1.88–2.42). On the contrary, in type 2 diabetes (OR 0.92 95% CI 0.87–0.96), we found a statistically significant lower mortality risk. Furthermore, it was found a statistically reduced mortality risk in females (OR 0.85 95% CI 0.8–0.9) <h3>Conclusions</h3> In Spain we have a progressive increase in the hospital admissions for gout, higher mortality rates and higher healthcare costs. This shows the need for changes in prevention and management of gout disease. <h3>Disclosure of Interest</h3> None declared
Questions to improve family–staff communication in the ICU: a randomized controlled trial
Authors: Elie Azoulay, Jean-Marie Forel, Isabelle Vinatier, Romain Truillet, Anne Renault, Sandrine Valade, Samir Jaber, Jacques Durand-Gasselin, Carole Schwebel, Hughes Georges, Sybille Merceron, Alain Cariou, Myriam Moussa, Sami Hraiech, Laurent Argaud, Marc Leone, J. Randall Curtis, Nancy Kentish-Barnes, Elisabeth Jouve, Laurent Papazian
Journal: Intensive Care Medicine (2018)
Ibrutinib Can Induce Complete Remissions and Sustained Responses in Refractory Cutaneous or Leg-Type Diffuse Large B-Cell Lymphoma
Authors: Johannes Bloehdorn, Stephanie Ellen Weissinger, Anca Sindrilaru, Stefan Schoensteiner, Thorsten Peters, Peter Moeller, Ralf Marienfeld, Andreas Viardot
Journal: Blood (2018)
Structure-based assessment and network analysis of targeting 14-3-3 proteins in prostate cancer
Authors: Alex Root, Azadeh Beizaei, H. Alexander Ebhardt
Journal: Molecular Cancer (2018)

Developing combination therapy for castrate-resistant prostate cancer (CRPC) may require exploiting new drug targets outside androgen receptor and PI3K / AKT / mTOR signal transduction pathways implicated in prostate cancer (PCa) progression. One such possible new target is YWHAZ of the 14-3-3 protein family as this gene has prognostic significance for metastatic CRPC patients. However, there are no small molecules targeting YWHAZ commercially available. Hence, we explored whether the small molecule BV02 targeting another 14-3-3 protein family member SFN also binds to YWHAZ. Using advanced docking algorithms we find that BV02 docks many other 14-3-3 family members. In addition, the amphipathic groove where drug binding occurs also has a high binding affinity for other drugs used to treat PCa such as docetaxel. The proteome of metastatic PCa models (LNCaP clone FGC and PC-3) was perturbed as a result of BV02 treatment. Through data integration of three proteomics data sets we found that BV02 modulates numerous protein-protein interactions involving 14-3-3 proteins in our PCa models.