tbuckley/cabot-search huggingface dataset:
Abstract 59: Novel mechanisms-guided treatments for betel nuts-related head and neck squamous cell carcinoma in Taiwan
Authors: Jo-Pai Chen, Jui-Ying Chang, Ruey-Long Hong
Journal: Clinical Cancer Research (2017)

Abstract Background: Betel nuts-related HNSCCs in Taiwan will cause (1) strong inflammation, invasion, and angiogenesis; (2) poor response to chemotherapy, radiation, and epidermal growth factor receptor inhibitors. Methods: HNSCC cell lines (SCC4, SCC9, SCC15, SCC25, FaDu, KB, Cal27, SAS, and TW2.6, betel nuts-related) were used to evaluate (1) the in vitro drug sensitivity; (2) synergistic effects of different treatment combinations with MTT assay, colony formation, flow cytometry, and Western blotting; (3) invasion capacity by wound healing. TW2.6 had already been proved to possess defective p53, p16 loss, and increased Bcl2. Results: TW2.6 was resistant to chemotherapies, radiation, and EGFR inhibition, but sensitive to PI3K/mTOR dual inhibition (BEZ235), CDK4/6 inhibitor (palbociclib), Bcl2 inhibitor (ABT-199), WEE1 inhibitor(AZD1775), FGFR inhibitor(BGJ398), ALK/IGF-1R inhibitor (ceritinib), and eribulin. Polo-like kinase inhibitor (volasertib) with radiation, resulting in G2/M arrest in flow-cytometry and increased cyclin B levels in Western blotting, caused TW2.6 apoptosis. Nintedanib and regorafenib (VEGFR/PDGFR/FGFR inhibitor) and foretinib (VEGFR/c-MET/Axl inhibitor) would suppress HUVEC, block invasion capacity of TW2.6, inhibit TW2.6 growth, and resensitize TW2.6 to docetaxel, afatinib, and volasertib. Western blotting showed (1) mesenchymal markers (Slug, Snail, Axl, Twist, Vimentin, Claudin-1), PI3K/Akt/mTOR signaling (p-Akt and p70S6K), and BMI-1 dropped after nintedanib, regorafenib, and foretinib; (2) PDL1 drop after foretinib use. BYL719, ABT-199, and ceritinib also sensitize TW2,6 to docetaxel. Astragalus polysaccharides, minimally cytotoxic on TW2.6, could inhibit tumor migration, suppress epithelial-mesenchymal transformation and PI3K/AKT/mTOR pathway, and induce PDL1 drop. APS re-sensitizes TW2.6 to afatinib and volasertib. Olaparib (PARP inhibitor) also had poor effect on TW2.6, but volasertib, AZD1775, and foretinib could reverse olaparib resistance. Conclusions: TW2.6 might reflect treatment refractoriness of betel nuts-related HNSCC in Taiwan. Several novel mechanisms-guided treatment combinations should be tried in the future. Citation Format: Jo-Pai Chen, Jui-Ying Chang, Ruey-Long Hong. Novel mechanisms-guided treatments for betel nuts-related head and neck squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 59.
Staphylococcus aureus y MRSA en los hospitales austríacos, 1995
Authors: W Koller
Journal: Eurosurveillance (1997)

En 1996, el Ministerio Federal Austriaco de Sanidad y de Proteccion de consumidores solicito a 327 hospitales de enfermos agudos y a otras instituciones sanitarias que notificaran el numero de pacientes hospitalizados en 1995 que hubieran presentado un cultivo positivo de Staphylococcus aureus (SA). Tambien solicito la proporcion de SA resistentes a la meticilina (MRSA) y de EMRSA (MRSA epidemico caracterizado por su resistencia particular a multiples antibioticos*), al igual que la descripcion de los lugares en los que se habian aislado las cepas.
Cardiac βarrestin2 Improves Contractility and Adverse Remodeling in Heart Failure, But Is Underexpressed in Humans
Authors: Katie A. McCrink, Jennifer Maning, Angela Vu, Malika Jafferjee, Christine Marrero, Ava Brill, Ashley Bathgate-Siryk, Samalia Dabul, Walter J. Koch, Anastasios Lymperopoulos
Journal: Journal of the American College of Cardiology (2017)
Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial
Authors: Piet Ost, Dries Reynders, Karel Decaestecker, Valérie Fonteyne, Nicolaas Lumen, Aurélie De Bruycker, Bieke Lambert, Louke Delrue, Renée Bultijnck, Tom Claeys, Els Goetghebeur, Geert Villeirs, Kathia De Man, Filip Ameye, Ignace Billiet, Steven Joniau, Friedl Vanhaverbeke, Gert De Meerleer
Journal: Journal of Clinical Oncology (2017)

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.
Pembrolizumab (pembro) for relapsed malignant pleural mesothelioma (MPM): Outcomes in real-life setting in Australia (AUS) and Switzerland (CH)
Authors: L. Mauti, G. Rivalland, D. Klingbiel, S. Kao, S. Schmid, A. Nowak, O. Gautschi, B. Hughes, T. Bartnick, N. Pavlakis, H. Bouchaab, K. O'Byrne, S. Rothschild, P. Russell, S. Savic Prince, B. Thapa, M. Pless, R. von Moos, Y. Metaxas, T. John
Journal: Annals of Oncology (2017)
ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children
Authors: Athanasios G. Kaditis, Maria Luz Alonso Alvarez, An Boudewyns, Francois Abel, Emmanouel I. Alexopoulos, Refika Ersu, Koen Joosten, Helena Larramona, Silvia Miano, Indra Narang, Hui-Leng Tan, Ha Trang, Marina Tsaoussoglou, Nele Vandenbussche, Maria Pia Villa, Dick Van Waardenburg, Silke Weber, Stijn Verhulst
Journal: European Respiratory Journal (2017)

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1–23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms ( e.g. snoring) and/or conditions predisposing to SDB ( e.g. mandibular hypoplasia) as well as children with SDB and complex conditions ( e.g. Down syndrome, Prader–Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions ( e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1–23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.
The functional and developmental role of imitation in the (a)typical brain
Authors: Luca Casartelli, Valentina Parma
Journal: Behavioral and Brain Sciences (2017)

Keven & Akins (K&A) propose a biologically plausible view of neonatal imitation based on the analysis of sensorimotor development. Here, we consider imitation in the general context of motor cognition, taking examples from both typical and atypical development. Specifically, we will discuss the functional role of imitation, its multi-level nature, and its anomalous features in autism.
Trends in Cancer Survival by Health Insurance Status in California From 1997 to 2014
Authors: Libby Ellis, Alison J. Canchola, David Spiegel, Uri Ladabaum, Robert Haile, Scarlett Lin Gomez
Journal: JAMA Oncology (2017)

There have been substantial improvements in the early detection, treatment, and survival from cancer in the United States, but it is not clear to what extent patients with different types of health insurance have benefitted from these advancements.To examine trends in cancer survival by health insurance status from January 1997 to December 2014.California Cancer Registry (a statewide cancer surveillance system) data were used to estimate population-based survival by health insurance status in 3 calendar periods: January 1997 to December 2002, January 2003 to December 2008, and January 2009 to December 2014 with follow-up through 2014. Overall, 1 149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or melanoma in California were included in the study.Five-year all-cause and cancer-specific survival probabilities by insurance category and calendar period for each cancer site and sex; hazard ratios (HRs) and 95% CIs for each insurance category (none, Medicare, other public) compared with private insurance in each calendar period.According to data from 1 149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or melanoma gathered from the California Cancer Registry, improvements in survival were almost exclusively limited to patients with private or Medicare insurance. For patients with other public or no insurance, survival was largely unchanged or declined. Relative to privately insured patients, cancer-specific mortality was higher in uninsured patients for all cancers except prostate, and disparities were largest from 2009 to 2014 for breast (HR, 1.72; 95% CI, 1.45-2.03), lung (men: HR, 1.18; 95% CI, 1.06-1.31 and women: HR, 1.32; 95% CI, 1.15-1.50), and colorectal cancer (women: HR, 1.30; 95% CI, 1.05-1.62). Mortality was also higher for patients with other public insurance for all cancers except lung, and disparities were largest from 2009 to 2014 for breast (HR, 1.25; 95% CI, 1.17-1.34), prostate (HR, 1.17; 95% CI, 1.04-1.31), and colorectal cancer (men: HR, 1.16; 95% CI, 1.08-1.23 and women: HR, 1.11; 95% CI, 1.03-1.20).After accounting for patient and clinical characteristics, survival disparities for men with prostate cancer and women with lung or colorectal cancer increased significantly over time, reflecting a lack of improvement in survival for patients with other public or no insurance. To mitigate these growing disparities, all patients with cancer need access to health insurance that covers all the necessary elements of health care, from prevention and early detection to timely treatment according to clinical guidelines.
Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway
Authors: Cathleen Holze, Chloé Michaudel, Claire Mackowiak, Darya A. Haas, Christian Benda, Philipp Hubel, Friederike L. Pennemann, Daniel Schnepf, Jennifer Wettmarshausen, Marianne Braun, Daisy W. Leung, Gaya K. Amarasinghe, Fabiana Perocchi, Peter Staeheli, Bernhard Ryffel, Andreas Pichlmair
Journal: Nature Immunology (2017)
Initial signals of efficacy in cholangiocarcinoma from a phase Ib trial of varlitinib in combination with doublet chemotherapy (cisplatin + 5-fluororacil or capecitabine).
Authors: Chih-Yi Hsieh, Ming-Shiang Wu, Mark McHale, Bertil Lindmark, Lilian Chow, Yee Chao
Journal: Journal of Clinical Oncology (2017)

e15671 Background: Varlitinib (ASLAN001) is a potent, reversible, small molecule pan-HER inhibitor that selectively binds to HER1 (IC 50 7nM), HER2 (IC 50 2nM) and HER4 (IC 50 4nM). Clinical data in cholangiocarcinoma, gastric cancer, colorectal cancer and breast cancer indicate that varlitinib is a safe and well tolerated inhibitor of tumor growth and survival. Here we conducted a phase Ib trial to determine the safety and early efficacy signals of varlitinib in combination with cisplatin (CIS) and 5-fluorouracil (5-FU) or CIS and capecitabine (CAP). Methods: Eligible patients had metastatic solid tumors. Doses of varlitinib were escalated in a standard 3+3 design with corresponding chemotherapy for 6 cycles after which patients remained on varlitinib montherapy. Responses were defined using RECIST 1.1 criteria. Results: To date, 27 patients have been enrolled. Most common treatment related adverse events ( &gt; 10%) were nausea (56%; ≥G3 4%), vomiting (48%; ≥G3 4%), decreased appetite (44%; ≥G3 7%), diarrhea (37%; ≥G3 11%), anemia (26%; ≥G3 11%), fatigue (22%; ≥G3 0%), creatinine increase (19%; ≥G3 4%), stomatitis (15%; ≥G3 4%), acute kidney injury (11%; ≥G3 11%), bilirubin increase (11%; ≥G3 7%), leukopenia (11%; ≥G3 7%), abdominal pain (11%; ≥G3 0%), and neutropenia (11%; ≥G3 0%). All patients with diarrhea, including those with G3 diarrhea were well controlled with standard doses of loperamide. Of 15 patients evaluable for response, three had partial response (20%), ten had stable disease (67%), and two had progressive disease (13%). Of note were strong and durable responses in cholangiocarcinoma. One cholangiocarcinoma patient demonstrated an 87% reduction in liver tumor size by cycle 2 and a complete resolution in one liver lesion by cycle 4. Another cholangiocarcinoma patient without measurable lesions in the liver or biliary tract achieved long-term disease control for a total of 15.2 months with good tolerability on varlitinib as monotherapy. Conclusions: The combination of varlitinib and CIS + 5-FU or CAP doublet chemotherapy is safe, well tolerated and has demonstrated strong efficacy signals in cholangiocarcinoma. Clinical trial information: NCT02648425.
Abstract 15910: Ciprofloxacin Increases Susceptibility to Aortic Dissection and Rupture in Mice
Authors: Scott A LeMaire, Lin Zhang, Wei Luo, Pingping Ren, Chris Guardado, Joseph S Coselli, Ying H Shen
Journal: Circulation (2017)

Rationale and Objective:  Fluoroquinolones are among the most commonly prescribed antibiotics. Two observational clinical studies have indicated that fluoroquinolone use may be associated with an increased risk of aortic aneurysm and dissection (AAD). In this study, we tested the hypothesis that ciprofloxacin, the most commonly used fluoroquinolone, increases the risk of AAD in a mouse model of sporadic AAD.   Approach and Results:  Four-week-old male and female C57BL/6J mice were unchallenged or challenged with a high-fat diet (HFD) and low-dose angiotensin infusion (AngII, 1000 ng/min/kg). During the four-week period of AngII infusion, challenged mice also received either ciprofloxacin (100 mg/kg/day) (n=39) or vehicle (n=28) through daily gavage. While 75% of challenged mice developed aortic enlargement in thoracic and/or abdominal segments, only 18% developed aortic dissection and none had rupture. In contrast, challenged mice that received ciprofloxacin had a significantly increased incidence of aortic dissection (49%, p=0.01) and rupture (18%, p=0.035). Aortic tissues from challenged mice treated with ciprofloxacin showed markedly increased aortic destruction, elastic fiber fragmentation, matrix metalloproteinase (MMP) activity, and activation of the necroptosis pathway compared to controls. Experiments performed in male and female mice yielded similar results. To explore the direct effects of ciprofloxacin on the aortic wall, we treated aortic smooth muscle cells with ciprofloxacin and found that it reduced fibrilin-1, elastin, and TIMP-1 levels, and increased the level of MMP-9, suggesting that ciprofloxacin may reduce the biosynthesis of extracellular matrix (ECM) while promoting MMP activation and ECM destruction. Additionally, ciprofloxacin induced caspase-3 cleavage and apoptotic cell death.   Conclusions:  Our findings demonstrate that ciprofloxacin increases susceptibility to aortic dissection and rupture by promoting ECM destruction in a mouse model of sporadic AAD, supporting concerns raised in observational clinical studies and suggesting that this drug should be used with caution in patients with aortic dilatation.
Comprehensive Cardiac CT With Myocardial Perfusion Imaging Versus Functional Testing in Suspected Coronary Artery Disease
Authors: Marisa Lubbers, Adriaan Coenen, Marcel Kofflard, Tobias Bruning, Bas Kietselaer, Tjebbe Galema, Marc Kock, Andre Niezen, Marco Das, Marco van Gent, Ewout-Jan van den Bos, Leon van Woerkens, Paul Musters, Suze Kooij, Fay Nous, Ricardo Budde, Miriam Hunink, Koen Nieman
Journal: JACC. Cardiovascular imaging (2017)
Trends in, and projections of, indicators of universal health coverage in Bangladesh, 1995–2030: a Bayesian analysis of population-based household data
Authors: Md Shafiur Rahman, Md Mizanur Rahman, Stuart Gilmour, Khin Thet Swe, Sarah Krull Abe, Kenji Shibuya
Journal: The Lancet Global Health (2017)

Many countries are implementing health system reforms to achieve universal health coverage (UHC) by 2030. To understand the progress towards UHC in Bangladesh, we estimated trends in indicators of the health service and of financial risk protection. We also estimated the probability of Bangladesh's achieving of UHC targets of 80% essential health-service coverage and 100% financial risk protection by 2030.We estimated the coverage of UHC indicators-13 prevention indicators and four treatment indicators-from 19 nationally representative population-based household surveys done in Bangladesh from Jan 1, 1991, to Dec 31, 2014. We used a Bayesian regression model to estimate the trend and to predict the coverage of UHC indicators along with the probabilities of achieving UHC targets of 80% coverage of health services and 100% coverage of financial risk protection from catastrophic and impoverishing health payments by 2030. We used the concentration index and relative index of inequality to assess wealth-based inequality in UHC indicators.If the current trends remain unchanged, we estimated that coverage of childhood vaccinations, improved water, oral rehydration treatment, satisfaction with family planning, and non-use of tobacco will achieve the 80% target by 2030. However, coverage of four antenatal care visits, facility-based delivery, skilled birth attendance, postnatal checkups, care seeking for pneumonia, exclusive breastfeeding, non-overweight, and adequate sanitation were not projected to achieve the target. Quintile-specific projections showed wide wealth-based inequality in access to antenatal care, postnatal care, delivery care, adequate sanitation, and care seeking for pneumonia, and this inequality was projected to continue for all indicators. The incidence of catastrophic health expenditure and impoverishment were projected to increase from 17% and 4%, respectively, in 2015, to 20% and 9%, respectively, by 2030. Inequality analysis suggested that wealthiest households would disproportionately face more financial catastrophe than the most disadvantaged households.Despite progress, Bangladesh will not achieve the 2030 UHC targets unless the country scales up interventions related to maternal and child health services, and reforms health financing systems to avoid high dependency on out-of-pocket payments. The introduction of a national health insurance system, increased public funding for health care, and expansion of community-based clinics in rural areas could help to move the country towards UHC.Japan Ministry of Health, Labour, and Welfare.
Fertility treatment among women with asthma: a case–control study of 3689 women with live births
Authors: Anne Vejen Hansen, Zarqa Ali, Sara S. Malchau, Joan Blafoss, Anja Pinborg, Charlotte S. Ulrik
Journal: European Respiratory Journal (2018)

Asthma has been linked with prolonged time to pregnancy. Our aim was to explore a possible association between asthma and need for fertility treatment among women with live births.All women enrolled in the Management of Asthma during Pregnancy (MAP) programme at Hvidovre Hospital, Denmark were each matched with the next three consecutive women giving birth at Hvidovre Hospital. Information from the Danish National Assisted Reproductive Technology (ART) registry was cross-linked with the Danish Medical Birth registry to identify live births. The primary outcome of interest was births following fertility treatment.Our sample comprised pregnancies from asthmatic mothers (n=932, described as "cases") and non-asthmatic mothers (n=2757, described as "controls"), with 12% (n=114) and 8% (n=212), respectively, having had fertility treatment (OR 1.67, 95% CI 1.32-2.13; p<0.001). This association remained statistically significant after adjusting for confounders, including body mass index (OR 1.31, 95% CI 1.00-1.70; p=0.047). In women ≥35 years, 25% of cases (n=63) and 13% of controls (n=82) received fertility treatment (OR 2.12, 95% CI 1.47-3.07; p<0.001), which also remained statistically significant after adjusting for confounders (OR 1.65, 95% CI 1.11-2.46; p=0.013).A higher proportion of the births from asthmatic mothers involved fertility treatment compared to non-asthmatic mothers, not least among women aged ≥35 years.
VEGFR2–Mediated Reprogramming of Mitochondrial Metabolism Regulates the Sensitivity of Acute Myeloid Leukemia to Chemotherapy
Authors: Sandrina Nóbrega-Pereira, Francisco Caiado, Tânia Carvalho, Inês Matias, Gonçalo Graça, Luís G. Gonçalves, Bruno Silva-Santos, Haakan Norell, Sérgio Dias
Journal: Cancer Research (2017)

Abstract Metabolic reprogramming is central to tumorigenesis, but whether chemotherapy induces metabolic features promoting recurrence remains unknown. We established a mouse xenograft model of human acute myeloid leukemia (AML) that enabled chemotherapy-induced regressions of established disease followed by lethal regrowth of more aggressive tumor cells. Human AML cells from terminally ill mice treated with chemotherapy (chemoAML) had higher lipid content, increased lactate production and ATP levels, reduced expression of peroxisome proliferator–activated receptor gamma coactivator 1α (PGC-1α), and fewer mitochondria than controls from untreated AML animals. These changes were linked to increased VEGFR2 signaling that counteracted chemotherapy-driven cell death; blocking of VEGFR2 sensitized chemoAML to chemotherapy (re-)treatment and induced a mitochondrial biogenesis program with increased mitochondrial mass and oxidative stress. Accordingly, depletion of PGC-1α in chemoAML cells abolished such induction of mitochondrial metabolism and chemosensitization in response to VEGFR2 inhibition. Collectively, this reveals a mitochondrial metabolic vulnerability with potential therapeutic applications against chemotherapy-resistant AML. Significance: These findings reveal a mitochondrial metabolic vulnerability that might be exploited to kill chemotherapy-resistant acute myeloid leukemia cells. Cancer Res; 78(3); 731–41. ©2017 AACR.