tbuckley/cabot-search huggingface dataset:
Phase I Trial Of Carfilzomib In Combination With Vorinostat (SAHA) In Patients With Relapsed/Refractory B-Cell Lymphomas
Authors: Beata Holkova, Maciej Kmieciak, Prithviraj Bose, Paul M. Barr, Mary Beth Tombes, Ellen Shrader, Erin Cebula, Emily Pierce, Megan M. Herr, Heidi Sankala, Changyong Feng, Richard I Fisher, Steven Grant, Jonathan W. Friedberg
Journal: Blood (2013)
The Important Role of Schools in the Prevention of Skin Cancer
Authors: Gery P. Guy, Dawn M. Holman, Meg Watson
Journal: JAMA Dermatology (2016)

The Important Role of Schools in the Prevention of Skin Cancer Sun exposure in childhood is an important risk factor for the future development of skin cancer.The risk of developing melanoma is strongly related to a history of sunburns (an indicator of intense UV radiation exposure) during childhood and adolescence. 1However, skin cancer risk can be greatly reduced if children and adolescents are protected from UV radiation, suggesting the importance of protecting young people from the sun beginning at an early age. 1 Given the amount of time children spend in school settings, schools can play an important role in protecting children and adolescents from UV exposure and the future development of skin cancer. 1,2 Skin cancer prevention can be addressed in schools through policy and environmental changes and educational programs. 2School-based efforts to change children's knowledge, attitudes, and behaviors regarding sun protection can play a vital role in saving lives, improving quality of life, and reducing avoidable costs from the treatment of skin cancers.Acknowledging the critical role of schools, key strategies outlined in the Surgeon General's Call to Action to Prevent Skin Cancer 2 include increasing the availability of sun protection in educational settings and supporting the inclusion of sun protection in school policies, construction of school facilities, and school curricula.The Guide to Community Preventive Services (The Community Guide) 3 specifically recommends interventions to prevent skin cancer in primary and middle schools as well as child care centers, based on strong evidence of their effectiveness in increasing sun-protective behaviors and decreasing UV exposure, sunburn incidence, and formation of new moles.Recommended interventions to promote sunprotective behaviors include educational interventions, supportive behavioral interventions, and environmental and policy changes. 3Educational and behavioral interventions include teaching children about sun safety and the effects of UV radiation.Environmental and policy changes include increasing the availability of sun protection (eg, sunscreen, sun-protective clothing), increasing the availability of shade, and implementing sunprotection policies (eg, clothing guidelines, restrictions on outdoor activities during peak sunlight hours). 3espite these recommendations and evidence of their effectiveness in preventing skin cancer, findings of the Centers for Disease Control and Prevention 4,5 reveal that the use of these policies and practices in schools throughout the United States remains low.The Centers for Disease Control and Prevention's School Health Policies and Practices Study (SHPPS) 6 is a national survey periodically conducted to assess school health policies and practices.The SHPPS collected data on policies and practices related to sun safety at the state and district levels in 2012,
PTH-325 Does preoperative chemotherapy and radiation adversely influence postoperative outcomes after colorectal resection?: Abstract PTH-325 Table 1
Authors: R Kiran, DE Estrada, R Pasam, AS van Dalen, A Murray, S Lee-Kong, D Feingold
Journal: Gut (2015)

<h3>Introduction</h3> Controversy pertaining to whether or not preoperative chemo and radiotherapy worsen immediate postoperative outcomes after colorectal surgery continues to persist. Data for a large number of patients from a standardised national dataset may allow an adequate evaluation of their influence on postoperative outcomes after colorectal surgery. <h3>Method</h3> Patients who underwent colorectal surgery for cancer from 2012–2013 were identified from the NSQIP database. Patients who underwent preoperative chemotherapy (&lt;30 days prior to surgery) and/or radiotherapy (&lt;90 days prior to surgery) were compared to those who had surgery alone for complications classified as major and minor using chi-squared, Fisher’s Exact tests and logistic regression with p &lt; 0.05 being considered statistically significantly. <h3>Results</h3> Of the 2,936 CRC patients selected, 2,431 (82.8%) underwent colorectal resection alone, 127 (4.3%) received chemotherapy, 45 (1.5%) radiotherapy and 333 (11.3%) chemoradiotherapy. When comparing patients who underwent preoperative chemoradiotherapy to those who had surgery alone, the chemoradiotherapy group had a lower mean age (59 vs. 66 years, p &lt; 0.0001), a higher proportion of males (64% vs. 52%, p &lt; 0.0001) and rectal tumours (97% vs. 27%, p- &lt; 0.0001). Both groups had similar BMI and ASA class. Patients who received chemoradiation had a greater occurrence of deep vein thrombosis (OR: 2.66; 95% CI: 1.28–5.52, p = 0.02) and deep incisional SSI (OR: 2.76: 95% CI: 1.48–5.16, p = 0.0009). Other outcomes were similar (Table 1). <h3>Conclusion</h3> Patients who undergo preoperative chemotherapy and radiotherapy prior to surgery for colorectal cancer are at greater risk for postoperative thromboembolic complications and surgical site infection. Since both these complications are potentially preventable, an awareness of the increased risks in these patients along with greater scrutiny and adoption of preventive strategies will likely reduce these complications. <h3>Disclosure of interest</h3> None Declared.
Age dictates a steroid-resistant cascade of Wnt5a, transglutaminase 2, and leukotrienes in inflamed airways
Authors: Katharina Dietz, Marta de los Reyes Jiménez, Eva S. Gollwitzer, Adam M. Chaker, Ulrich M. Zissler, Olof P. Rådmark, Hoeke A. Baarsma, Melanie Königshoff, Carsten B. Schmidt-Weber, Benjamin J. Marsland, Julia Esser-von Bieren
Journal: Journal of Allergy and Clinical Immunology (2016)
Insulin and IGF-1 receptors regulate FoxO-mediated signaling in muscle proteostasis
Authors: Brian T. O’Neill, Kevin Y. Lee, Katherine Klaus, Samir Softic, Megan T. Krumpoch, Joachim Fentz, Kristin I. Stanford, Matthew M. Robinson, Weikang Cai, Andre Kleinridders, Renata O. Pereira, Michael F. Hirshman, E. Dale Abel, Domenico Accili, Laurie J. Goodyear, K. Sreekumaran Nair, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2016)

Diabetes strongly impacts protein metabolism, particularly in skeletal muscle. Insulin and IGF-1 enhance muscle protein synthesis through their receptors, but the relative roles of each in muscle proteostasis have not been fully elucidated. Using mice with muscle-specific deletion of the insulin receptor (M-IR–/– mice), the IGF-1 receptor (M-IGF1R–/– mice), or both (MIGIRKO mice), we assessed the relative contributions of IR and IGF1R signaling to muscle proteostasis. In differentiated muscle, IR expression predominated over IGF1R expression, and correspondingly, M-IR–/– mice displayed a moderate reduction in muscle mass whereas M-IGF1R–/– mice did not. However, these receptors serve complementary roles, such that double-knockout MIGIRKO mice displayed a marked reduction in muscle mass that was linked to increases in proteasomal and autophagy-lysosomal degradation, accompanied by a high-protein-turnover state. Combined muscle-specific deletion of FoxO1, FoxO3, and FoxO4 in MIGIRKO mice reversed increased autophagy and completely rescued muscle mass without changing proteasomal activity. These data indicate that signaling via IR is more important than IGF1R in controlling proteostasis in differentiated muscle. Nonetheless, the overlap of IR and IGF1R signaling is critical to the regulation of muscle protein turnover, and this regulation depends on suppression of FoxO-regulated, autophagy-mediated protein degradation.
Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings
Authors: Nicholas A Feasey, James Hadfield, Karen H Keddy, Timothy J Dallman, Jan Jacobs, Xiangyu Deng, Paul Wigley, Lars Barquist, Gemma C Langridge, Theresa Feltwell, Simon R Harris, Alison E Mather, Maria Fookes, Martin Aslett, Chisomo Msefula, Samuel Kariuki, Calman A Maclennan, Robert S Onsare, François-Xavier Weill, Simon Le Hello, Anthony M Smith, Michael McClelland, Prerak Desai, Christopher M Parry, John Cheesbrough, Neil French, Josefina Campos, Jose A Chabalgoity, Laura Betancor, Katie L Hopkins, Satheesh Nair, Tom J Humphrey, Octavie Lunguya, Tristan A Cogan, Milagritos D Tapia, Samba O Sow, Sharon M Tennant, Kristin Bornstein, Myron M Levine, Lizeth Lacharme-Lora, Dean B Everett, Robert A Kingsley, Julian Parkhill, Robert S Heyderman, Gordon Dougan, Melita A Gordon, Nicholas R Thomson
Journal: Nature Genetics (2016)
Epirubicin and cyclophosphamide (EC) followed by weekly paclitaxel with/without trastuzumab as primary systemic therapy in locally advanced breast cancer: Phase II study
Authors: A. Hirano, T. Shimizu, M. Kamimura, N. Goto, O. Watanabe, J. Kinoshita, K. Domoto, M. Aiba, K. Ogawa, D. Miura
Journal: Journal of Clinical Oncology (2009)

e11590 Background: Primary systemic therapy (PST) has become a standard therapy for locally advanced breast cancer (LABC). The aim of this study was to evaluate the activity and toxicity of EC (epirubicin/cyclophosphamide) followed by weekly paclitaxel with/without trastuzumab as PST in LABC. Methods: Primary endpoint was pathologic complete response (pCR) rate in the breast and axilla, and secondary endpoints were breast conserving rate and toxicities. Patients with histologically diagnosed invasive breast cancer by core needle biopsy of the T2–4 (&gt;3 cm) or N1–3 were included in this study. Eligible patients were age &gt;20 years, had a performance status of 0 to 1, and had adequate organ functions. It was determined that the expected rate of pCR in the trial was 25%, and the sample size was calculated using the Simon method, with a type I error of 5% and a study power of 80%. The target enrollment was estimated to be 40 evaluable patients. Treatment: Patients received epirubicin (100 mg/m 2 ) and cyclophosphamide (600mg/m 2 ) every 3 weeks for four cycles followed by paclitaxel (80 mg/m 2 ) every week for 12 cycles. Trastuzumab (2mg/kg) was added to paclitaxel in HER2-positive patients. Results: Forty-three patients were enrolled into this study and 3 patients withdrew. pCR were observed in 8 patients and pCR rate was 20.0% (95% confidence interval, 7.6- 32.4). Twenty-four patients (60.0%) underwent breast conserving surgery. In particular, patients with HER2 positive tumor had significantly higher rate of pCR than the others (62.5% vs. 8.6%; p=0.0014). Grade 4 neutropenia was recorded in 27.5% of the patients, and febrile neutropenia occurred in 4 patients (10.0%). No heart failure was seen. Conclusions: EC followed by weekly paclitaxel with/without trastuzumab was an active and well-tolerated treatment for LABC. No significant financial relationships to disclose.
The Effect of Comedication With a Conventional Synthetic Disease‐Modifying Antirheumatic Drug on Drug Retention and Clinical Effectiveness of Anti–Tumor Necrosis Factor Therapy in Patients With Axial Spondyloarthritis
Authors: Michael J. Nissen, Adrian Ciurea, Jürg Bernhard, Giorgio Tamborrini, Ruediger Mueller, Bettina Weiss, Martin Toniolo, Pascale Exer, Cem Gabay, Axel Finckh
Journal: Arthritis & Rheumatology (2016)

To explore the effect of comedication with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) on drug retention and clinical effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (SpA).The study included all patients starting treatment with a TNFi in a large prospective cohort of axial SpA patients (Swiss Clinical Quality Management in axial SpA). Crude drug retention was analyzed using the Kaplan-Meier method, and in adjusted analyses, Cox proportional hazards regression was used to model TNFi discontinuation. We evaluated multiple disease activity measures and validated clinical response criteria over time.A total of 2,765 TNFi treatment courses were included from 1,914 patients with axial SpA, 20.4% in combination with a conventional synthetic DMARD. In unadjusted analyses, the monotherapy group had significantly shorter median TNFi retention time (32.7 months) compared to the cotherapy group (39.1 months) (P = 0.04). In multivariate adjusted analyses, the monotherapy group had significantly lower TNFi retention, with a hazard ratio (HR) of 1.17 (95% confidence interval [95% CI] 1.01-1.35). This effect was even larger when only infliximab-treated patients were considered, with an HR for monotherapy of 1.36 (95% CI 1.06-1.74). Clinical response rates were almost identical at 1 year, with a change in the Bath Ankylosing Spondylitis Disease Activity Index of -2.02 and -2.00 (P = 0.83) and a change in the Ankylosing Spondylitis Disease Activity Score using C-reactive protein of -1.14 and -1.12 (P = 0.45) in the monotherapy and cotherapy groups, respectively.We demonstrate an association between the combination of a TNFi with conventional synthetic DMARDs and improved drug retention in patients with axial SpA, particularly in the subgroup of patients with infliximab.
Bronchiectasis and the risk of cardiovascular disease: a population-based study
Authors: Vidya Navaratnam, Elizabeth R C Millett, John R Hurst, Sara L Thomas, Liam Smeeth, Richard B Hubbard, Jeremy Brown, Jennifer K Quint
Journal: Thorax (2016)

<h3>Background</h3> There are limited data on the burden of cardiovascular comorbidities in people with bronchiectasis. Our cross-sectional study estimates the burden of pre-existing diagnoses of coronary heart disease (CHD) and stroke in people with bronchiectasis compared with the general population. The historical cohort study investigates if individuals with bronchiectasis are at increased risk of incident CHD and stroke events. <h3>Methods</h3> We used primary care electronic records from the Clinical Practice Research Datalink. The cross-sectional study used logistic regression to quantify the association between bronchiectasis and recorded diagnoses of CHD or stroke. Cox regression was used to investigate if people with bronchiectasis experienced increased incident CHD and strokes compared with the general population, adjusting for age, sex, smoking habit and other risk factors for cardiovascular disease. <h3>Results</h3> Pre-existing diagnoses of CHD (OR 1.33, 95% CI 1.25 to 1.41) and stroke (OR 1.92, 95% CI 1.85 to 2.01) were higher in people with bronchiectasis compared with those without bronchiectasis, after adjusting for age, sex, smoking and risk factors for cardiovascular disease. The rate of first CHD and stroke were also higher in people with bronchiectasis (HR for CHD 1.44 (95% CI 1.27 to 1.63) and HR for stroke 1.71 (95% CI 1.54 to 1.90)). <h3>Conclusion</h3> The risk of CHD and stroke are higher among people with bronchiectasis compared with the general population. An increased awareness of these cardiovascular comorbidities in this population is needed to provide a more integrated approach to the care of these patients.
Advancing Survivors’ Knowledge (ASK) about skin cancer study: A randomized intervention within the Childhood Cancer Survivor Study (CCSS).
Authors: Robyn Keske, Gregory T. Armstrong, Jessica Davine, Todd M. Gibson, Ann Mertens, Aaron McDonald, Ashfaq A. Marghoob, Casey Daniel, Alan Geller
Journal: Journal of Clinical Oncology (2016)

255 Background: Adult survivors of childhood cancer who received radiation therapy have high rates of basal cell carcinoma and melanoma compared with the general population. Both the National Cancer Institute and Children’s Oncology Group Guidelines recommend regular skin self-checks and annual clinical skin exams for survivors. The ongoing ASK randomized intervention trial aims to identify strategies, including use of mobile health technology, which may improve early detection practices. Methods: Participants previously treated with radiation and had no previous history of skin cancer were identified, and eligible participants are currently being enrolled. 800 participants are being randomized into: (1) patient activation and education (PAE) including targeted print and web-based materials and monthly text messages prompting skin checks and driving participants to the ASK website; (2) PAE + physician activation (PAE + MD) adding targeted physician activation/educational materials about survivors’ increased skin cancer risk and recommendations for conducting full-body skin examinations; (3) PAE + MD + teledermoscopy (PAE + MD +TD). The TD group receives a dermatoscope that attaches to their smartphone to photograph suspect moles for review by the study dermatologist. Results: To date, 1,302 survivors are eligible. In the first five months of recruitment, 80% of the initial 400 eligible participants have responded to the study invitation and 248 participants (62%) have enrolled. Twenty-six percent of participants have visited the website and 12 images of suspicious moles have been submitted for review. Completion of recruitment is anticipated by spring 2016. Conclusions: The ASK study addresses screening barriers by providing educational and motivational information for both survivors and physicians on the value of regular and thorough skin examinations. It also determines whether use of innovative mobile health technology activates survivors to conduct skin self-examinations, request physician examinations, and obtain treatment when worrisome lesions are found. Clinical trial information: NCT 02046811.
Predicting bacteraemia or rapid identification of the causative pathogen in community acquired pneumonia: where should the priority lie?
Authors: Ricardo J. José, Jeremy S. Brown
Journal: European Respiratory Journal (2016)

Community-acquired pneumonia (CAP) remains amongst the most common causes of infectious disease-related death worldwide. However, despite its clinical importance the existing routine microbiology tests for CAP pathogens have significant limitations, lacking sensitivity for identifying the causative pathogen and only altering management in a minority of patients. For example, blood cultures identify a pathogen in ≤10% of CAP cases [1, 2] and results are usually only available after 24 h. Therefore, clinicians are still required to prescribe broad-spectrum antibiotics for the first 24–72 h, which is the period of highest risk for clinical deterioration and death [3, 4]; even when bacteria are cultured this only rarely leads to a change in treatment and may miss co-infection [2, 5]. These limitations have led to suggestions that patients admitted with CAP do not require routine microbiological testing with management decisions based solely on clinical factors. However, not identifying the causative pathogens in CAP has important implications. From a public health perspective, not performing microbiological testing could result in failure to identify important changes in microbial aetiology or changes in anti-microbial resistance patterns. In the absence of microbiological testing all patients would be treated with prolonged broad-spectrum antibiotics that may not be required if, for example, Streptococcus pneumoniae was the causative pathogen, thereby unnecessarily increasing drug cost and potentially promoting the development of antimicrobial resistance or anti-microbial-related complications such as Clostridium difficile diarrhoea [6]. Finally, the relatively rare CAP patient infected with a drug-resistant pathogen, such as community-acquired methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa , may not be identified, thus increasing the chance of a poor outcome. Improved microbiological (molecular) diagnostic tests are needed to rapidly identify causative pathogens in CAP <http://ow.ly/6H0X300KBev>
Zika emergence in the French Territories of America and description of first confirmed cases of Zika virus infection on Martinique, November 2015 to February 2016
Authors: Elise Daudens-Vaysse, Martine Ledrans, Noellie Gay, Vanessa Ardillon, Sylvie Cassadou, Fatiha Najioullah, Isabelle Leparc-Goffart, Dominique Rousset, Cécile Herrmann, Raymond Cesaire, Marianne Maquart, Olivier Flusin, Séverine Matheus, Patricia Huc-Anaïs, Josiane Jaubert, Anne Criquet-Hayot, Bruno Hoen, Felix Djossou, Corinne Locatelli-Jouans, Alain Blateau, Anne-Marie McKenzie, Mathilde Melin, Patrick Saint-Martin, Frédérique Dorléans, Claudine Suivant, Luisiane Carvalho, Marion Petit-Sinturel, Audrey Andrieu, Harold Noël, Alexandra Septfons, Anne Gallay, Marie-Claire Paty, Laurent Filleul, André Cabié
Journal: Eurosurveillance (2016)

Following of the emergence of Zika virus in Brazil in 2015, an epidemiological surveillance system was quickly implemented in the French overseas Territories of America (FTA) according to previous experience with dengue and chikungunya and has detected first cases of Zika. General practitioners and medical microbiologists were invited to report all clinically suspected cases of Zika, laboratory investigations were systematically conducted (RT-PCR). On 18 December, the first autochthonous case of Zika virus infection was confirmed by RT-PCR on French Guiana and Martinique, indicating introduction of Zika virus in FTA. The viral circulation of Zika virus was then also confirmed on Guadeloupe and Saint-Martin. We report here early findings on 203 confirmed cases of Zika virus infection identified by RT-PCR or seroneutralisation on Martinique Island between 24 November 2015 and 20 January 2016. All cases were investigated. Common clinical signs were observed (maculopapular rash, arthralgia, fever, myalgia and conjunctival hyperaemia) among these patients, but the rash, the foundation of our case definition, may be absent in a significant proportion of patients (16%). These results are important for the implementation of a suspected case definition, the main tool for epidemiological surveillance, in territories that may be affected by ZIKV emergence, including Europe.
Numerous metallic foreign bodies in whole body after acupuncture
Authors: Yun-Seong Kang, Deog Kyeom Kim
Journal: Thorax (2016)

A 60-year-old man was referred to our clinic for the evaluation of numerous radio-opaque densities on a screening chest radiograph. He was a former smoker without any significant medical history, except for a history of pulmonary TB in his youth. On screening spirometry, he was diagnosed with mild COPD associated with smoking and previous TB. However, he did not report any symptoms, such as chest pain, shortness of breath, fever or chills. The laboratory results, including inflammatory markers, were not remarkable. After taking a detailed history, we found that he had been in a …