tbuckley/cabot-search huggingface dataset:
Current Tobacco Smoking, Quit Attempts, and Knowledge About Smoking Risks Among Persons Aged ≥15 Years — Global Adult Tobacco Survey, 28 Countries, 2008–2016
Authors: Indu B. Ahluwalia, Tenecia Smith, René A. Arrazola, Krishna M. Palipudi, Isabel Garcia de Quevedo, Vinayak M. Prasad, Alison Commar, Kerstin Schotte, Paul David Garwood, Brian S. Armour
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Each year, tobacco use causes approximately 7 million deaths worldwide, including approximately 6 million among tobacco users and an estimated 890,000 among nonsmokers exposed to secondhand smoke (1). Tobacco use is a leading preventable cause of disease globally and has been determined to cause adverse health outcomes such as coronary heart disease, stroke, and multiple types of cancer, including lung cancer (2-4). Approximately 80% of the world's 1.1 billion tobacco smokers reside in low- and middle-income countries (4). Some persons do not fully understand the health risks associated with tobacco smoking (5-9), and studies have indicated that increasing knowledge about the adverse health effects of smoking can contribute to decreases in smoking, increases in cessation attempts, and increases in successful cessation (3,7,10). CDC analyzed 2008-2016 Global Adult Tobacco Survey (GATS) data from 28 countries to assess tobacco smoking prevalence, quit attempts, and knowledge about tobacco smoking risks among persons aged ≥15 years. Across countries, the median prevalence of tobacco smoking was 22.5%, and a median of 42.5% of tobacco smokers had made a quit attempt in the preceding 12 months. The median prevalences of knowing that tobacco smoking causes stroke, heart attack, and lung cancer were 73.6%, 83.6%, and 95.2%, respectively. Implementation of proven tobacco control interventions, including strategies that increase knowledge about the health risks posed by tobacco use, might help to reduce tobacco use and tobacco-related disease, including heart disease, stroke, and lung cancer (3-5).
Harnessing Androgen Receptor Pathway Activation for Targeted Alpha Particle Radioimmunotherapy of Breast Cancer
Authors: Daniel L.J. Thorek, Anson T. Ku, Nicholas Mitsiades, Darren Veach, Philip A. Watson, Dipti Metha, Sven-Erik Strand, Sai Kiran Sharma, Jason S. Lewis, Diane S. Abou, Hans G. Lilja, Steven M. Larson, Michael R. McDevitt, David Ulmert
Journal: Clinical Cancer Research (2018)

The impact of androgen receptor (AR) activity in breast cancer biology is unclear. We characterized and tested a novel therapy to an AR-governed target in breast cancer.Experimental Design: We evaluated the expression of prototypical AR gene products human kallikrein 2 (hK2) and PSA in breast cancer models. We screened 13 well-characterized breast cancer cell lines for hK2 and PSA production upon in vitro hormone stimulation by testosterone [dihydrotestosterone (DHT)]. AR-positive lines were further evaluated by exposure to estrogen (17β-Estradiol) and the synthetic progestin D-Norgestrel. We then evaluated an anti-hK2-targeted radiotherapy platform (hu11B6), labeled with alpha (α)-particle emitting Actinium-225, to specifically treat AR-expressing breast cancer xenografts under hormone stimulation.D-Norgestrel and DHT activated the AR pathway, while 17β-Estradiol did not. Competitive binding for AR protein showed similar affinity between DHT and D-Norgestrel, indicating direct AR-ligand interaction. In vivo production of hK2 was sufficient to achieve site-specific delivery of therapeutic radionuclide to tumor tissue at >20-fold over background muscle uptake; effecting long-term local tumor control.[225Ac]hu11B6 targeted radiotherapy was potentiated by DHT and by D-Norgestrel in murine xenograft models of breast cancer. AR activity in breast cancer correlates with kallikrein-related peptidase-2 and can be activated by D-Norgestrel, a common contraceptive, and AR induction can be harnessed for hK2-targeted breast cancer α-emitter radiotherapy.
A collaborative program for educating urban youth about HPV risk and cancer prevention.
Authors: Jennifer Jarvey Balistreri, Cathy Schulz, Anne Marie Barry-Weers, James L. Weese
Journal: Journal of Clinical Oncology (2018)

169 Background: HPV infection is the most common sexually transmitted disease. Exposure to this infection is associated with cancer later in life. Public data regarding HPV vaccination rates and health disparity (as evidenced by low-income, high teen birth and STI rates) were identified. Methods: Based on the supposition that health disparity is associated with low socioeconomic status, a Wisconsin state map provided by the Center for Urban Population Health identified 29 zip codes in the City of Milwaukee, and are broken by low, medium, and high income brackets. An HPV education program, in partnership with Milwaukee Public Schools (MPS), was developed with a focus on the low income bracket to emphasize infection exposure and the safety and efficacy of the HPV vaccine in cancer prevention. This included education on safe relationships and emphasis on personal health advocacy. Program development was aimed at the health literacy of youth. Collaboration occurred with MPS leadership and their established health curriculum to ensure the HPV program accommodated the academic level of the freshman health classroom. Results: The data is reflective of HPV vaccine series completion rates within the zip codes where the HPV program was presented. Logistic regression was used and a significant rise for HPV completion rates by year (p = 0.0003) and by zip code (p &lt; 0.0001) were observed. Conclusions: As the program evolves, program evaluations and public data continue to be reviewed along with feedback from various stakeholders to maintain the quality and integrity of the program. Additionally, Aurora Health Care has received requests to share this HPV program best practice with other institutions to expand it throughout urban areas of Wisconsin and Illinois.[Table: see text]
Abstract A01: Stem cell signals in the initiation and progression of non-small cell lung cancer
Authors: Alison G. Barber, Hatim Husain, Mark A. Valasek, Miriam Scadeng, Tannishtha Reya
Journal: Clinical Cancer Research (2018)

Abstract Lung cancer is most commonly diagnosed at a late stage when the disease is in its most aggressive state. To define the key regulators of lung cancer, we have focused on how stem cell signals are hijacked to drive progression to an undifferentiated state. Using a novel reporter mouse designed to reflect expression of the stem cell fate determinant Musashi-2 (Msi2), we found that Msi2 is highly expressed in tumors derived from the KrasG12D/+; p53fl/fl (KP) mouse model of lung adenocarcinoma. To test if Msi2-expressing cells preferentially act as the cell of origin in lung cancer, we isolated lung epithelial cells and tested their tumorigenic potential in vitro and in vivo following activation of Kras and loss of p53. Importantly, Msi2+ cells preferentially formed tumorspheres in vitro as well as tumors in vivo, indicating that Msi2+ tumor cells have increased tumor-initiating capacity. To determine whether Msi2 is required for lung cancer growth and progression, we crossed KP mice to Msi2 knockout mice and monitored tumor growth over time. Loss of Msi2 led to a reduction in both the number of tumors that formed and in overall tumor burden. Moreover, the mice exhibited a reduced frequency of high-grade tumors and an increase in overall survival, suggesting that loss of Msi2 impairs tumor development and disease progression. Finally, inhibition of Msi2 in a primary lung adenocarcinoma cell line led to reduced tumor volume in vivo, suggesting that Msi2 continues to be a dependency in established disease. Collectively, our data identify Msi2 as a stem cell signal that is critically required in lung cancer development and progression. Citation Format: Alison G. Barber, Hatim Husain, Mark A. Valasek, Miriam Scadeng, Tannishtha Reya. Stem cell signals in the initiation and progression of non-small cell lung cancer [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr A01.
A nonrandomized study on compliance with IDSA guidelines on the choice and dosing of empiric antibiotics for patients with febrile neutropenia after implementation of a new Computerized Physician Order Entry (CPOE).
Authors: Kapil Meleveedu, Sai Kaza, Lisa Phuong, Edward Belk Perry, Susan Tannenbaum
Journal: Journal of Clinical Oncology (2018)

48 Background: More than 80% of patients with hematologic malignancies and 10-50% of patients with solid tumors are expected to experience fever after one cycle of chemotherapy. Studies have shown all-cause mortality to be 15% higher in cancer patients with febrile neutropenia than comparably matched patients without febrile neutropenia and compliance for choice of empiric antibiotics in febrile neutropenia to be as low as 56%. Methods: We conducted a retrospective chart review of patients who presented with febrile neutropenia to our institution for one year prior to and after implementation of a CPOE set. Data was collected on basic demographics, oncological diagnosis, labs, choice of antibiotics and dosing frequency. Awareness sessions were conducted among admitting staff following the initial retrospective analysis followed by implementation of a CPOE set in order to improve guideline concordant management of febrile neutropenia patients. The IDSA risk was assessed based on the above data and the pre and post order set compliance with IDSA guidelines were compared. Fisher’s exact test was applied to assess the percentage of compliance before and after implementation of the order set, with significance set at two-sided p value &lt; 0.05. Results: Among the patients managed before order set, 15 of the total 26 (58%) were found to be non compliant with IDSA guidelines in terms of either antibiotic choice or dosing frequency. A post order set analysis showed that only 7/27 (26%) were non compliant with IDSA guidelines. The Fisher exact test showed a statistically significant value of 0.0267 (p &lt; 0.05). Conclusions: Education and implementation of a CPOE order set showed significant improvement in compliance with IDSA guidelines for management of febrile neutropenia. Based on the data from our study an IDSA concurrent institutional guideline for management of febrile neutropenia was formulated and further efforts are under way to incorporate results in our new EMR order set entries.[Table: see text]
Can administrative data improve the performance of clinical trial economic analyses?
Authors: Timothy Hanna, Paul Nguyen, Joe Pater, Christopher J. O'Callaghan, Nicole Mittmann, Craig Earle, Dongsheng Tu, Derek J. Jonker, Annette E. Hay
Journal: Journal of Clinical Oncology (2018)

2 Background: Economic analyses of trials often rely on trial-collected health resource utilization data, which is expensive and may be incompletely recorded. We investigated whether routinely collected health administrative data (RCD) can be utilized to improve trial economic analysis performance. Methods: Health administrative data was probabilistically linked to Ontario patient data from the Canadian Cancer Trials Group CO.17 trial (n = 572), evaluating cetuximab plus best supportive care (n = 75 linked Ontario patients) versus best supportive care alone (n = 73). Completeness of trial data was compared to RCD. Cost-effectiveness in 2007 Canadian dollars was determined using RCD up to trial date of last contact (DOLC), and up to RCD DOLC. Incremental cost effectiveness ratio (ICER) confidence intervals (CI) were determined using bootstrapping with 5000 iterations. Cost-effectiveness acceptability curves were determined. Sensitivity analyses were performed. Results: Among 148 Ontario patients, up to trial DOLC, RCD vital status was concordant in &gt; 96%. 29 deaths occurred after trial DOLC. Up to trial DOLC there were 34 net additional hospitalizations in RCD, and 28 net additional emergency room visits. Using RCD, total cetuximab group costs were $3,023,034, and $1,191,118 for best supportive care alone up to trial DOLC. Cost difference was driven by cetuximab drug costs ($1,531,370). Using RCD, the ICER was $211,128 per life-year gained (90% CI: $101,396, $694,950) when data was limited to trial DOLC, and $164,378 (90% CI: -$138,260, $644,555) using routinely collected data DOLC. ICER estimates were similar to the original economic analysis using trial-collected data ($199,742 (95% CI $125,973, $652,492)). Estimates were robust in sensitivity analysis. Conclusions: Administrative data were more complete than trial-collected utilization data, even under optimal conditions. There was also longer follow-up. We found that cost differences were robust to varying costing assumptions. Our findings demonstrate the potential of administrative data sources to relieve institutions, sponsors and patients from the burden of collecting key utilization information which requires considerable effort and cost.
Insights into pathogenesis of five novel GCK mutations identified in Chinese MODY patients
Authors: Limei Liu, Yanjun Liu, Xiaoxu Ge, Xipeng Liu, Chen Chen, Yanzhong Wang, Ming Li, Jun Yin, Juan Zhang, Yating Chen, Rong Zhang, Yanyan Jiang, Weijing Zhao, Di Yang, Taishan Zheng, Ming Lu, Langen Zhuang, Meisheng Jiang
Journal: Metabolism (2018)
Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma
Authors: Aurore Perrot, Valerie Lauwers-Cances, Jill Corre, Nelly Robillard, Cyrille Hulin, Marie-Lorraine Chretien, Thomas Dejoie, Sabrina Maheo, Anne-Marie Stoppa, Brigitte Pegourie, Lionel Karlin, Laurent Garderet, Bertrand Arnulf, Chantal Doyen, Nathalie Meuleman, Bruno Royer, Jean-Richard Eveillard, Lotfi Benboubker, Mamoun Dib, Olivier Decaux, Arnaud Jaccard, Karim Belhadj, Sabine Brechignac, Brigitte Kolb, Cecile Fohrer, Mohamad Mohty, Margaret Macro, Paul G. Richardson, Victoria Carlton, Martin Moorhead, Tom Willis, Malek Faham, Kenneth C. Anderson, Jean-Luc Harousseau, Xavier Leleu, Thierry Facon, Philippe Moreau, Michel Attal, Hervé Avet-Loiseau, Nikhil Munshi
Journal: Blood (2018)
Cytotoxic and antibacterial polyketide-indole hybrids synthesized from indole-3-carbinol by Daldinia eschscholzii
Authors: Liping Lin, Nan Jiang, Huimin Wu, Yaning Mei, Jie Yang, Renxiang Tan
Journal: Acta Pharmaceutica Sinica B (2018)

Two skeletally undescribed polyketide-indole hybrids (PIHs), named indolchromins A and B, were generated from indole-3-carbinol (I3C) in the fungal culture (Daldinia eschscholzii). The indolchromin structures were elucidated mainly by their 1D and 2D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism (CD) spectra with the electronic CD (ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions, including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase (AONS), C(sp3)-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3–8.6 μmol/L, (2S,4R)- and (2R,4S)-indolchromin A and (2R,4S)-indolchromin B are inhibitory against Clostridium perfringens, Clostridium difficile, Veillonella sp., Bacteroides fragilis, and Streptococcus pyogenes. (2R,4S)-Indolchromin A and (2S,4S)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC50 values of 27.9 and 131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7 (IC50 94.4 nmol/L).
Dynamics of genetically engineered hematopoietic stem and progenitor cells after autologous transplantation in humans
Authors: Serena Scala, Luca Basso-Ricci, Francesca Dionisio, Danilo Pellin, Stefania Giannelli, Federica Andrea Salerio, Lorena Leonardelli, Maria Pia Cicalese, Francesca Ferrua, Alessandro Aiuti, Luca Biasco
Journal: Nature Medicine (2018)
<i>Staphylococcus aureus</i> from atopic dermatitis skin accumulates in the lysosomes of keratinocytes with induction of <scp>IL</scp>‐1α secretion via <scp>TLR</scp>9
Authors: Masaya Moriwaki, Kazumasa Iwamoto, Yoshie Niitsu, Ayako Matsushima, Yuhki Yanase, Junzo Hisatsune, Motoyuki Sugai, Michihiro Hide
Journal: Allergy (2018)

Abstract Background Staphylococcus aureus ( S. aureus ) is frequently detected in the skin of patients with atopic dermatitis (AD), and involved in the flare of AD. There are some evidence‐specific strains of S. aureus affect the severity of AD. However, the mechanism of predominant colonization and the aggravation of dermatitis by certain strains of S. aureus in the patients with AD are still unknown. Objective To reveal the characteristics of S. aureus from patients with AD ( S. aureus ‐AD), we analyzed the interaction of S. aureus ‐AD and keratinocytes in comparison with those of S. aureus laboratory strains ( S. aureus ‐stand.). Methods We stimulated HaCaT cells, keratinocyte cell line, and human epidermal keratinocytes by heat‐killed S. aureus strains, then evaluated immune response of keratinocytes by ELISA, immunofluorescence staining, and flow cytometry. Results Upon incubation with keratinocytes, three out of four strains of heat‐killed S. aureus ‐AD were strongly agglutinated inside the cytoplasm. In the cells, they are located in lysosomes and promoted the secretion of interleukin‐1α (IL‐1α). These reactions were not observed by any of four strains of S. aureus ‐stand. and S. epidermidis and were abolished by the treatment of S. aureus with proteinase K. Moreover, the IL‐1α secretion was diminished by the inhibition of Toll‐like receptor 9 (TLR9). Conclusion S. aureus ‐AD accumulates in lysosome of keratinocytes by means of bacterial cell wall proteins and induces IL‐1α via TLR9.
GJA1-20k Arranges Actin to Guide Cx43 Delivery to Cardiac Intercalated Discs
Authors: Wassim A. Basheer, Shaohua Xiao, Irina Epifantseva, Ying Fu, Andre G. Kleber, TingTing Hong, Robin M. Shaw
Journal: Circulation Research (2017)

Delivery of Cx43 (connexin 43) to the intercalated disc is a continuous and rapid process critical for intercellular coupling. By a pathway of targeted delivery involving microtubule highways, vesicles of Cx43 hemichannels are efficiently trafficked to adherens junctions at intercalated discs. It has also been identified that actin provides rest stops for Cx43 forward trafficking and that Cx43 has a 20 kDa internally translated small C terminus isoform, GJA1-20k (Gap Junction Protein Alpha 1- 20 kDa), which is required for full-length Cx43 trafficking, but by an unknown mechanism.We explored the mechanism by which the GJA1-20k isoform is required for full-length Cx43 forward trafficking to intercalated discs.Using an in vivo Adeno-associated virus serotype 9-mediated gene transfer system, we confirmed in whole animal that GJA1-20k markedly increases endogenous myocardial Cx43 gap junction plaque size at the intercalated discs. In micropatterned cell pairing systems, we found that exogenous GJA1-20k expression stabilizes filamentous actin without affecting actin protein expression and that GJA1-20k complexes with both actin and tubulin. We also found that filamentous actin regulates microtubule organization as inhibition of actin polymerization with a low dose of latrunculin A disrupts the targeting of microtubules to cell-cell junctions. GJA1-20k protects actin filament from latrunculin A disruption, preserving microtubule trajectory to the cell-cell border. For therapeutic implications, we found that prior in vivo Adeno-associated virus serotype 9-mediated gene delivery of GJA1-20k to the heart protects Cx43 localization to the intercalated discs against acute ischemic injury.The internally translated GJA1-20k isoform stabilizes actin filaments, which guides growth trajectories of the Cx43 microtubule trafficking machinery, increasing delivery of Cx43 hemichannels to cardiac intercalated discs. Exogenous GJA1-20k helps to maintain cell-cell coupling in instances of anticipated myocardial ischemia.
Optimizing deep response assessment for AL amyloidosis using involved free light chain level at end of therapy: failure of the serum free light chain ratio
Authors: Eli Muchtar, Angela Dispenzieri, Nelson Leung, Martha Q. Lacy, Francis K. Buadi, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Wilson Gonsalves, Taxiarchis V. Kourelis, Rahma Warsame, Stephen J. Russell, John A. Lust, Yi Lin, Ronald S. Go, Steven R. Zeldenrust, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar, Morie A. Gertz
Journal: Leukemia (2018)
Load, capacity and health: critical pieces of the holistic performance puzzle
Authors: Evert Verhagen, Tim Gabbett
Journal: British Journal of Sports Medicine (2018)

Relationships between load, load capacity, performance and health are topics of contemporary interest. At what intensity should an athlete train to achieve the best physiological response? How much (or little) can an athlete train without detrimentally affecting health? Most studies addressing such questions have used a reductionist approach wherein factors were studied in isolation, thereby ignoring the complex inter-relationships and balance between factors. This editorial discusses the association between load and load capacity, and their relationship with athlete performance and health. We illustrate the practical use of a model for the management of athlete performance and health, and provide directions for future practice and research.

Figure 1 shows the intertwined relationships between load, load capacity, performance and health. To stimulate adaptation the basic principle of any training programme is to apply a load (ie, the amount of mechanical, physiological or mental stress) through training or competition that is greater than an athlete’s current load capacity (ie, the ability to tolerate load).1 With the optimal balance between both constructs, an appropriate training stimulus will …
Abstract 19699: Comparison Between Symptomatic and Asymptomatic Carotid Plaques in Patients With Bilateral Intraplaque Hemorrhage
Authors: Xianling Wang, Jie Sun, Xihai Zhao, Daniel S Hippe, Jin Liu, Thomas S Hatsukami, Rui Li, Gador Canton, Yan Song, Chun Yuan
Journal: Circulation (2016)

Introduction: Prospective studies have showed a strong association between intraplaque hemorrhage (IPH) on carotid MRI and increased risk of cerebrovascular ischemic events. However, it is also see...