tbuckley/cabot-search huggingface dataset:
Commensal Fungi Recapitulate the Protective Benefits of Intestinal Bacteria
Authors: Tony T. Jiang, Tzu-Yu Shao, W.X. Gladys Ang, Jeremy M. Kinder, Lucien H. Turner, Giang Pham, Jordan Whitt, Theresa Alenghat, Sing Sing Way
Journal: Cell Host & Microbe (2017)
Changes In DNA repair gene expression induced by (-)-epi-gallocatechin-3-Gallate in human lymphoblastoid cells
Authors: Gisela C. Werle-Schneider, Markus Meinhardt, Andreas Wölfelschneider, Jörg Hümmerich, Barbara Bertram, Helmut Bartsch, Peter Schmezer
Journal: Cancer Research (2006)

2259   (-)-Epigallocatechin gallate (EGCG) is known to be the major bioactive polyphenol in green tea contributing to its cancer chemopreventive effects. Multiple mechanisms by which EGCG and other green tea ingredients can protect against cancer have been described  (Toxicol. Lett. 150: 43, 2004).  EGCG can modulate cell cycle regulatory proteins and by controlling intracellular signaling cascades EGCG seems to regulate cell growth. As we previously have shown that EGCG can also induce the formation of poly(ADP-ribose) in human lymphocytes ( Mutation Research 534: 77, 2003 ), we suggested that the chemopreventive effect of EGCG may be partly attributed to an interaction with the cellular DNA repair machinery. To further support this notion, we used a customized cDNA array ( DNA Repair 1: 237, 2002 ) and investigated EGCG-induced changes in gene expression in human lymphoblastoid cells of more than 130 human DNA repair or repair-related genes. Data generated by cDNA arrays were verified on 15 selected genes by real-time RT-PCR. Cells were treated with EGCG for 2-48 hours at different concentrations (1-200μM) in culture medium containing 2 or 15% serum (FCS). After treatment with 20μM EGCG at 2% FCS a number of DNA repair and repair-related genes showed a dose-dependent induction of mRNA expression reaching maximal values at 24 hours:  c-fos ,  p21 , and  TOP3a  were up-regulated more than 5-fold; expression of  BRCA1 ,  CDKN1C ,  ERCC5 ,  MPG ,  POLK1 ,  RAD23A  and  XPC  was 2-4 fold induced. This up-regulation decreased over time but was still detectable after 48 hours. Under the same experimental conditions but with 15% FCS-containing culture medium, no changes in gene expression were observed. At this high FCS content induction of gene expression was only seen at a concentration of ≥ 100μM EGCG, which already decreased cell viability. Our results demonstrate that EGCG is able to induce mRNA expression of a number of DNA repair or repair-related genes  in vitro . These data lend support for an interaction of EGCG with cellular DNA repair processes. This in part, may be responsible for the chemopreventive effects of EGCG possibly acting via a more efficient repair of damaged DNA.  (work conducted  i n cooperation with Axaron Bioscience AG, Heidelberg, Germany )
Meningococcal carriage within households in the African meningitis belt: A longitudinal pilot study
Authors: Nicole E. Basta, Abdoulaye Berthe, Mahamadou Keita, Uma Onwuchekwa, Boubou Tamboura, Awa Traore, Musa Hassan-King, Olivier Manigart, Maria Nascimento, James M. Stuart, Caroline Trotter, Jayne Blake, Anthony D. Carr, Stephen J. Gray, Lynne S. Newbold, Yangqing Deng, Julian Wolfson, M. Elizabeth Halloran, Brian Greenwood, Ray Borrow, Samba O. Sow
Journal: Journal of Infection (2017)

ObjectivesCarriers of Neisseria meningitidis are a key source of transmission. In the African meningitis belt, where risk of meningococcal disease is highest, a greater understanding of meningococcal carriage dynamics is needed.MethodsWe randomly selected an age-stratified sample of 400 residents from 116 households in Bamako, Mali, and collected pharyngeal swabs in May 2010. A month later, we enrolled all 202 residents of 20 of these households (6 with known carriers) and collected swabs monthly for 6 months prior to MenAfriVac vaccine introduction and returned 10 months later to collect swabs monthly for 3 months. We used standard bacteriological methods to identify N. meningitidis carriers and fit hidden Markov models to assess acquisition and clearance overall and by sex and age.ResultsDuring the cross-sectional study 5.0% of individuals (20/400) were carriers. During the longitudinal study, 73 carriage events were identified from 1422 swabs analyzed, and 16.3% of individuals (33/202) were identified as carriers at least once. The majority of isolates were non-groupable; no serogroup A carriers were identified.ConclusionsOur results suggest that the duration of carriage with any N. meningitidis averages 2.9 months and that males and children acquire and lose carriage more frequently in an urban setting in Mali. Our study informed the design of a larger study implemented in seven countries of the African meningitis belt.
Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets
Authors: Deepika Kanojia, Manoj Garg, Jacqueline Martinez, Anand M.T., Samuel B. Luty, Ngan B. Doan, Jonathan W. Said, Charles Forscher, Jeffrey W. Tyner, H. Phillip Koeffler
Journal: Journal of Hematology & Oncology (2017)

Liposarcoma, the most common soft tissue tumor, is understudied cancer, and limited progress has been made in the treatment of metastatic disease. The Achilles heel of cancer often is their kinases that are excellent therapeutic targets. However, very limited knowledge exists of therapeutic critical kinase targets in liposarcoma that could be potentially used in disease management. Large RNAi and small-molecule tyrosine kinase inhibitor screens were performed against the proliferative capacity of liposarcoma cell lines of different subtypes. Each small molecule inhibitor was either FDA approved or in a clinical trial. Screening assays identified several previously unrecognized targets including PTK2 and KIT in liposarcoma. We also observed that ponatinib, multi-targeted tyrosine kinase inhibitor, was the most effective drug with anti-growth effects against all cell lines. In vitro assays showed that ponatinib inhibited the clonogenic proliferation of liposarcoma, and this anti-growth effect was associated with apoptosis and cell cycle arrest at the G0/G1 phase as well as a decrease in the KIT signaling pathway. In addition, ponatinib inhibited in vivo growth of liposarcoma in a xenograft model. Two large-scale kinase screenings identified novel liposarcoma targets and a FDA-approved inhibitor, ponatinib with clear anti-liposarcoma activity highlighting its potential therapy for treatment of this deadly tumor.
Standardizing opioid prescribing practices for cancer-related pain via a novel interactive documentation template at a public hospital.
Authors: Maliha Nusrat, Amanda Marie Parkes, Bei Hu, Dalia Farhat, Alyssa G. Rieber, Hilary Y. Ma
Journal: Journal of Clinical Oncology (2017)

253 Background: Aberrant opioid use during treatment of cancer related pain poses serious risks for patients and society. Identifying and monitoring those at risk is challenging and time consuming. We aimed to standardize the process of managing opioids at a public hospital oncology clinic in compliance with Texas (TX) state regulations to improve patient safety. Methods: We gauged the current practices of assessing and documenting opioid efficacy, toxicity and misuse via provider survey and chart review. A process flowchart was then created and streamlined in the light of: published literature, TX Administrative Code on pain management, and practices of palliative care specialists at MD Anderson Cancer Center, TX. We made an interactive documentation template (SmartPhrase) in electronic medical record system (EPIC) to implement the standardized process. Results: Pre-intervention data showedhigh inter-provider variability in opioid misuse screening, safety monitoring and documentation. Of the 22 providers surveyed, 6 (22%) had a TX PMP Aware login; 8 (36%) ever checked the website; and 19 (86%) stated the need of a standardized process for prescribing opioids. Hence, we instituted baseline screening for aberrant behavior based on substance abuse history, TX PMP Aware query and urine drug screen; increased monitoring of high risk patients; universal screening for chemical coping at each visit; and timely referral of such patients to palliative care. We created a SmartPhrase that prompts providers to risk stratify and monitor for opioid misuse as above; assess analgesic efficacy; evaluate and manage uncontrolled pain and toxicities; and specify a refill plan. This SmartPhrase allows quick selection of options pertinent to a given patient from pre-populated lists before the encounter can be closed. Conclusions: We created a systematic approach to prescribing and monitoring opioid analgesics so as to ensure safe and judicious use of opioids to treat cancer related pain. We generated an interactive SmartPhrase for efficient documentation compliant with TX state regulations. Post-implementation review of efficacy and use of this intervention is ongoing to further refine it.
P1.05-058 Prognostic Factors of Post-Recurrence Survival in Resected Stage I Non-Small Cell Lung Cancer
Authors: Yasuaki Kubouchi, Yoshiteru Kidokoro, Takashi Oono, Yohei Yurugi, Makoto Wakahara, Ken Miwa, Kunio Araki, Yuji Taniguchi, Hiroshige Nakamura
Journal: Journal of Thoracic Oncology (2017)
Treatments for Food Allergies
Authors: Jill Jin
Journal: JAMA (2017)

Hugh A. Sampson, MD; Wayne G. Shreffler, MD, PhD; William H. Yang, MD; Gordon L. Sussman, MD; Terri F. Brown-Whitehorn, MD; Kari C. Nadeau, MD, PhD; Amarjit S. Cheema, MD; Stephanie A. Leonard, MD; Jacqueline A. Pongracic, MD; Christine Sauvage-Delebarre, MD; Amal H. Assa'ad, MD; Frederic de Blay, MD, PhD; J. Andrew Bird, MD; Stephen A. Tilles, MD; Franck Boralevi, MD; Thierry Bourrier, MD; Jacques Hébert, MD; Todd D. Green, MD; Roy Gerth van Wijk, MD, PhD; André C. Knulst, MD, PhD; Gisèle Kanny, MD, PhD; Lynda C. Schneider, MD; Marek L. Kowalski, MD, PhD; Christophe Dupont, MD, PhD
Congenital Adrenal Hyperplasia
Authors: Po-Jui Ko, Ming-Lun Yeh
Journal: New England Journal of Medicine (2015)

A full-term infant was born with ambiguous genitalia. Ultrasonography revealed bilateral adrenal hypertrophy without visible testes, and chromosomal analysis revealed the 46 XX karyotype. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency in a female infant was diagnosed.
Diagnostic Accuracy of Pediatric Teledermatology Using Parent-Submitted Photographs
Authors: Daniel M. O’Connor, Olivia S. Jew, Marissa J. Perman, Leslie A. Castelo-Soccio, Flaura K. Winston, Patrick J. McMahon
Journal: JAMA Dermatology (2017)

Advances in smartphone photography (both quality and image transmission) may improve access to care via direct parent-to-clinician telemedicine. However, the accuracy of diagnoses that are reliant on parent-provided photographs has not been formally compared with diagnoses made in person.To assess whether smartphone photographs of pediatric skin conditions taken by parents are of sufficient quality to permit accurate diagnosis.A prospective study was conducted among 40 patient-parent dyads at a pediatric dermatology clinic at the Children's Hospital of Philadelphia from March 1 to September 30, 2016, to assess concordance between diagnoses made by an independent pediatric dermatologist based on in-person examination and those based on parental photographs. Half of the patient-parent dyads were randomized for a secondary analysis to receive instructions on how best to take photographs with smartphones. Clinicians were blinded to whether parents had received photography instructions.Half of the patient-parent dyads received a simple, 3-step instruction sheet on how best to take photographs using a smartphone (intervention group); the other half did not (control group).Concordance between photograph-based vs in-person diagnosis in the intervention vs control groups, as quantified using Cohen κ, a measure of interrater agreement that takes into account the possibility of agreement occurring by chance.Among the 40 patient-parent dyads (22 female children and 18 male children; mean [SD] age, 6.96 [5.23] years), overall concordance between photograph-based vs in-person diagnosis was 83% (95% CI, 71%-94%; κ = 0.81). Diagnostic concordance was 89% (95% CI, 75%-97%; κ = 0.88) in a subgroup of 37 participants with photographs considered of high enough quality to make a diagnosis. No statistically significant effect of photography instructions on concordance was detected (group that received instructions, 85%; group that did not receive instructions, 80%; P = .68). In cases of diagnostic disagreement, appropriate follow-up was suggested.Parent-operated smartphone photography can accurately be used as a method to provide pediatric dermatologic care.clinicaltrials.gov Identifier: NCT03246945.
Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations
Authors: Lei Huang, Lina Jansen, Yesilda Balavarca, Esther Molina-Montes, Masoud Babaei, Lydia van der Geest, Valery Lemmens, Liesbet Van Eycken, Harlinde De Schutter, Tom B Johannesen, Claus W Fristrup, Michael B Mortensen, Maja Primic-Žakelj, Vesna Zadnik, Nikolaus Becker, Thilo Hackert, Margit Mägi, Tiziana Cassetti, Romano Sassatelli, Robert Grützmann, Susanne Merkel, Ana F Gonçalves, Maria J Bento, Péter Hegyi, Gábor Lakatos, Andrea Szentesi, Michel Moreau, Tony van de Velde, Annegien Broeks, Milena Sant, Pamela Minicozzi, Vincenzo Mazzaferro, Francisco X Real, Alfredo Carrato, Xavier Molero, Marc G Besselink, Núria Malats, Markus W Büchler, Petra Schrotz-King, Hermann Brenner
Journal: Gut (2017)

Objective Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. Design Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003–2016 were analysed. Age-standardised resection rates for overall and stage I–II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. Results A total of 153 698 records were analysed. In population-based registries in 2012–2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I–II tumours, with great international variations. During 2003–2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I–II tumours: 0.05–0.18 and 0.01–0.06 across countries) and increasing age (ORs for patients 70–79 and ≥80 versus those &lt;60 years: 0.37–0.63 and 0.03–0.16 across countries). Patients with advanced-stage tumours (stage III–IV: 63.8%–81.2%) and at older ages (≥70 years: 52.6%–59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. Conclusion Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.
Neuroblastoma 3D cell culture: Proteomic differences between cancer spheroids and monolayers
Authors: John A. Sandoval, Derek J. Hoelz, Katharyn E. Turner, Frederick J. Rescorla, Robert J. Hickey, Linda H. Malkas
Journal: Cancer Research (2006)

4339   Single-agent fenretinide (4-HPR) is in current clinical evaluation for the treatment of pediatric neuroblastoma (NB). We have reported that 4-HPR induced large increases of ceramide by  de novo  synthesis in a wide variety of cancer cell lines  in vitro . 4-HPR cytotoxicity is synergized by modulators of ceramide metabolism, including D-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP), a glucosylceramide synthase (GCS) inhibitor that prevents the metabolism of dihydroceramides and ceramides into glycosylceramides and ganglioceramides. Here we report that combination treatment with 4-HPR+PPMP prolonged survival in three human NB murine xenograft models. Methods. We studied subcutaneous xenografts in athymic (nu/nu) mice of human NB cell lines CHLA-140, CHLA-136, and SMS-KCNR (all established at relapse) for tumor growth delay of treatment groups vs. controls, calculated as TGD = [(T - C)/C] × 100, where T and C are the median days for the tumors to attain a sacrifice size (1500 mm 3 ). Results. In two mass disease models, animals bearing CHLA-140 or KCNR were treated with 4-HPR (120 mg/kg/day), PPMP (80 mg/kg/day), or 4-HPR (80 or 120 mg/kg/day) + PPMP (80 mg/kg/day), divided BID, i.p., × 5 days, every other week, for 4 - 5 courses. In the CHLA-140 model, 4-HPR+PPMP prolonged survival in 7/12 mice compared to controls, including one durable complete response (CR). 4-HPR-alone prolonged survival in 3/12 mice (1 durable CR), and PPMP alone in 1/12 mice, demonstrated a survival benefit of 123% for 4-HPR+PPMP (P  3  and then tumors cytoreduced with cyclophosphamide (156 mg/kg/day) + topotecan (0.75 mg/kg/day), i.p., × 5 days. Animals were then treated with 4-HPR+PPMP (120 mg/kg/day 4-HPR and 88 mg/kg/day PPMP), divided BID, i.p., every other week, × 2 courses; or, in a second experiment, 4-HPR (80 mg/kg/day), PPMP (80 mg/kg/day), or 4-HPR+PPMP (80 mg/kg/day of each agent), divided BID, i.p., every other week, × 4 courses, both starting at Day +21. Prolonged survival was observed in 3/5 mice treated with the higher 4-HPR+PPMP doses, including one durable CR, and 3/6 prolonged survival in the lower dose 4-HPR+PPMP schedule, compared to controls. There was no survival advantage demonstrated by 4-HPR alone, or PPMP alone. 4-HPR+PPMP was well tolerated in all treatment groups. Conclusions. These results suggest that the combination of 4-HPR+PPMP warrants further pre-clinical development for the treatment of neuroblastoma. These experiments were partially supported by a NCI FLAIR grant to B.J.M. for the development of a cGMP production method and preliminary formulation of PPMP.
OV21/PETROC: a randomized Gynecologic Cancer Intergroup phase II study of intraperitoneal versus intravenous chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer
Authors: D.M. Provencher, C.J. Gallagher, W.R. Parulekar, J.A. Ledermann, D.K. Armstrong, M. Brundage, C. Gourley, I. Romero, A. Gonzalez-Martin, M. Feeney, P. Bessette, M. Hall, J.I. Weberpals, G. Hall, S.K. Lau, P. Gauthier, M. Fung-Kee-Fung, E.A. Eisenhauer, C. Winch, D. Tu, H.J. MacKay
Journal: Annals of Oncology (2017)
Core Outcome Set-STAndards for Development: The COS-STAD recommendations
Authors: Jamie J. Kirkham, Katherine Davis, Douglas G. Altman, Jane M. Blazeby, Mike Clarke, Sean Tunis, Paula R. Williamson
Journal: PLoS Medicine (2017)

Background The use of core outcome sets (COS) ensures that researchers measure and report those outcomes that are most likely to be relevant to users of their research. Several hundred COS projects have been systematically identified to date, but there has been no formal quality assessment of these studies. The Core Outcome Set-STAndards for Development (COS-STAD) project aimed to identify minimum standards for the design of a COS study agreed upon by an international group, while other specific guidance exists for the final reporting of COS development studies (Core Outcome Set-STAndards for Reporting [COS-STAR]). Methods and findings An international group of experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives produced the COS-STAD recommendations to help improve the quality of COS development and support the assessment of whether a COS had been developed using a reasonable approach. An open survey of experts generated an initial list of items, which was refined by a 2-round Delphi survey involving nearly 250 participants representing key stakeholder groups. Participants assigned importance ratings for each item using a 1–9 scale. Consensus that an item should be included in the set of minimum standards was defined as at least 70% of the voting participants from each stakeholder group providing a score between 7 and 9. The Delphi survey was followed by a consensus discussion with the study management group representing multiple stakeholder groups. COS-STAD contains 11 minimum standards that are the minimum design recommendations for all COS development projects. The recommendations focus on 3 key domains: the scope, the stakeholders, and the consensus process. Conclusions The COS-STAD project has established 11 minimum standards to be followed by COS developers when planning their projects and by users when deciding whether a COS has been developed using reasonable methods.
P2.07-037 Developing a Predictive Clinical Outcome Model for Advanced Non-Small Cell Lung Cancer Patients Receiving Nivolumab
Authors: W. Park, D. Kwon, D. Saravia, A. Desai, J. Warsch, F. Vargas, M. El Dinali, R. Elias, Y. Chae, D.W. Kim, S. Warsch, A. Ishkanian, C. Ikpeazu, R. Mudad, G. Lopes, M. Jahanzeb
Journal: Journal of Thoracic Oncology (2017)
Doctor who grabbed nurse’s breast is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2017)

A doctor from Pakistan who blamed a misunderstanding about differences in “cultural norms” for blinding him to a “red light” from a student nurse whose breast he grabbed has been suspended for 12 months by a medical practitioners tribunal.

Imran Qureshi, 44, was a locum senior house officer at Manchester’s Trafford General Hospital in June 2015 when he told the nurse, who was 21, that he was unhappy in his marriage and wanted an affair. He followed her into a small room, closed the door, and backed her into a corner. She pushed him away, calling him a “disgrace” and …
Comparação dos sitios Internet das redes de vigilância das doenças na União Europeia
Authors: A Lenglet, G Hernández Pezzi
Journal: Eurosurveillance (2006)

Na Uniao Europeia (UE) hoje, a vigilância das doencas infecciosas esta realizada pela Rede Basica de Vigilância (Basic Surveillance Network, BSN) e por redes de vigilância especificas (disease specific surveillance networks, DSN). Cada rede tem o seu sitio no Internet. O objetivo do seguinte relatorio e de descrever as informacoes apresentadas em accesso publico em cada sitio de Internet, do ponto de vista da sua utilidade para a vigilância de um estado membro da UE. Foram incluidos no estudo o BSN e os DSN mencionados na Decisao Comunitaria 2003/542/CE. Cada sitio foi estudado tomando em consideracao : 1) as informacoes gerais, 2) os procedimentos de recolha de dados e 3) a presentacao dos mesmos. Na semana do 5 dezembro de 2005, foram visitados os sitios, e dez sitios foram analizados. 80% entre eles tinham incluido a lista dos paises participantes, os contactos do coordinador da rede, os participantes em cada pais e os objetivos da rede. A periodicidade das presentacoes, sejam dados brutos ou elaborados, e muito variavel. 
As informacoes accessiveis ao publico nos dez sitios de redes estudadas tambem sao heterogeneas. Recomendamos que todas as redes presentem no seu sitio um conjunto de caracteristicas basicas, incluindo as definicoes de casos, os procedimentos usados para a recolha de dados, e os relatorios periodicos que apresentam os dados elaborados para toda a Uniao Europeia.