tbuckley/cabot-search huggingface dataset:
Comprehensive genomic profiling of primary and metastatic CDH1 mutated classic and pleomorphic invasive lobular breast carcinomas reveals markers of hormonal therapy resistance and opportunities for targeted therapies
Authors: J.S. Ross, L.M. Gay, J.A. Elvin, J. Suh, J-A. Vergilio, S. Ramkissoon, E. Severson, S. Daniel, G.M. Frampton, D. Fabrizio, A.B. Schrock, S.M. Ali, V.A. Miller, P. Stephens, J. Chung
Journal: Annals of Oncology (2017)
NHS staff who refuse flu vaccine this winter will have to give reasons
Authors: Gareth Iacobucci
Journal: BMJ (2017)

NHS staff members who refuse to have the flu vaccine this winter will have to give reasons to their employer, as leaders toughen their approach to improve take-up rates.

Amid concerns of a surge in numbers of flu cases this winter, national NHS leaders are to write to all staff working in the service urging them to be vaccinated against flu as soon as possible. The letter will make it clear that staff who refuse the vaccine will have to give reasons to their employing NHS trust, which will then be recorded. Trusts are also being …
Possible Therapeutic Potential of Recombinant Human Soluble Thrombomoduline Alpha for the Treatment of SOS/VOD: A Retrospective Study in Toranomon Hospital
Authors: Shinsuke Takagi, Mitsuhiro Yuasa, Naoyuki Uchida, Kyosuke Yamaguchi, Kosei Kageyama, Daisuke Kaji, Yuki Taya, Aya Nishida, Kazuya Ishiwata, Hisashi Yamamoto, Go Yamamoto, Yuki Asano-Mori, Atsushi Wake, Shigeyoshi Makino, Akiko Yoneyama, Koji Izutsu, Shuichi Taniguchi
Journal: Blood (2016)
Familial Mediterranean Fever and Incidence of Cancer
Authors: Ronen Brenner, Ilan Ben‐Zvi, Yael Shinar, Irena Liphshitz, Barbara Silverman, Nir Peled, Carmit Levy, Eldad Ben‐Chetrit, Avi Livneh, Shaye Kivity
Journal: Arthritis & Rheumatology (2017)

Objective Familial Mediterranean fever ( FMF ) is an autoinflammatory disease manifested as recurrent serosal inflammation. An association between FMF and malignancy has not been evaluated. The aim of this study was to estimate cancer risk in a large cohort of FMF patients from a single institution. Methods The study cohort consisted of 8,534 FMF patients registered at the National FMF Center in Tel Hashomer, Israel. We linked the study cohort to the database of the Israel National Cancer Registry using the national identity number. Cancer incidence in FMF patients was determined and then stratified by age and sex. Standardized incidence ratios ( SIR s) for cancers were calculated. Results Among 8,534 FMF patients (4,400 men, 4,134 women), 350 developed cancer during the years 1970–2011. The overall cancer risk among patients with FMF was significantly lower than was expected in specific sex and ethnic groups of the Israeli population: for males of Jewish ethnicity, SIR 0.66 (95% confidence interval [95% CI ] 0.55–0.77), P &lt; 0.001; for females of Jewish ethnicity, SIR 0.75 (95% CI 0.64–0.86), P &lt; 0.001; and for males of Arab ethnicity, SIR 0.34 (95% CI 0.07–0.99), P = 0.024. Conclusion FMF patients have a significantly lower incidence of cancer than the general population of Israel. This pattern was demonstrated in 2 ethnic populations: Jewish and Arab. We speculate that the lower cancer incidence could be attributed to a direct physiologic effect of FMF or to its treatment.
Adalimumab for nail psoriasis: Efficacy and safety from the first 26 weeks of a phase 3, randomized, placebo-controlled trial
Authors: Boni E. Elewski, Martin M. Okun, Kim Papp, Christopher S. Baker, Jeffrey J. Crowley, Gérard Guillet, Murali Sundaram, Yves Poulin, Yihua Gu, Ziqian Geng, David A. Williams, Phoebe A. Rich
Journal: Journal of the American Academy of Dermatology (2017)

Previous clinical trials have not evaluated improvement in nail psoriasis as a primary end point.This phase 3 trial evaluated the safety and efficacy of adalimumab in patients with moderate-to-severe fingernail psoriasis and moderate-to-severe plaque psoriasis.Patients were randomized 1:1 to 40 mg adalimumab every other week or placebo. The primary efficacy end point was at least 75% improvement in total-fingernail modified Nail Psoriasis Severity Index (NAPSI75) response rate at week 26. Ranked secondary end point scores evaluated at week 26 were total-fingernail NAPSI and modified NAPSI, nail pain, Nail Psoriasis Physical Functioning Severity, Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index, and Physician's Global Assessment (fingernail psoriasis).Of the 217 randomized patients (108 received placebo and 109 received adalimumab), 188 (86.6%) completed 26 weeks of treatment (period A) or escaped early to the open-label period. The study met the primary end point (response rate of 3.4% with placebo vs 46.6% with adalimumab [P < .001]) and all ranked secondary end points. The serious adverse event rates (placebo vs adalimumab) in period A were 4.6% versus 7.3%; the serious infections rates were 1.9% versus 3.7%.Patients with less than 5% BSA involvement were not eligible for enrollment.After 26 weeks of adalimumab treatment, significant improvements were seen in the primary and all ranked secondary end points and in signs and symptoms of moderate-to-severe nail psoriasis versus with placebo and no new safety risks were identified.
Épidémiologie de la méningite méningococcique et modifications du système de surveillance en Pologne entre 1970 et 2006
Authors: O Gryniewicz, J Kolbusz, M Rosinska, A Zielinski, P Stefanoff
Journal: Eurosurveillance (2007)

L’objectif de cette etude etait la description des caracteristiques generales de l’epidemiologie de la meningite meningococcique entre 1970 et 2006 en Pologne, dans le contexte des modifications apportees aux methodes de surveillance.
Clinical utility of quasi-monomorphic variation range (QMVR) on the determination of microsatellite instability (MSI) status in patients (pts) with colorectal cancer (CRC): GI-SCREEN-CRC-MSI sub-study 01
Authors: W. Okamoto, H. Bando, T. Fukui, T. Yamanaka, K. Akagi, T. Yoshino
Journal: Annals of Oncology (2017)
GW28-e0108 Homing of endogenous bone marrow mesenchymal stem cells (BMSCs) by UTMD-mediated recombinant SDF-1α adenovirus delivery to the infarcted myocardium
Authors: Yuming Mu, Lingjie Yang, Gaofeng Su, Lina Guan
Journal: Journal of the American College of Cardiology (2017)
Conditional survival analysis of stage IV colorectal cancer patients living &gt;24 months.
Authors: Nadia Dawn Ali, Shadi Zandieh, Kristen Donohue, Chunxia Chen, Dirk Moore, Elizabeth Poplin, Darren R. Carpizo
Journal: Journal of Clinical Oncology (2017)

3566 Background: The overall survival of patients with stage IV colorectal cancer (both in unresectable and resectable settings) has been increasing over recent decades due to improvements in chemotherapy, liver surgery and other liver-directed therapies. As a result of more patients living longer, there is a need to refine prognostic information to more accurately predict survival to assist multi-disciplinary cancer management teams in treatment decisions but also for patient quality of life. Methods: We performed a retrospective analysis of all patients with stage IV colorectal cancer seen at Rutgers Cancer Institute of New Jersey between Jan 1, 2005 to March 10, 2015 by ICD-9 code (N = 318 patients). This included patients who were deemed unresectable and patients who were resected with curative intent. Our study population was patients with documented survival for &gt; 24 months (N = 158). Variables gathered included patient demographics, disease related (primary location, KRAS status, metastasis location, interval to metastases) and treatment related (chemotherapy regimens, radiation and surgery) data. Survival curve estimates are conditional on having survived 24 months. Results: Complete data was available for 125 patients (75 were resected for cure and 50 were not). Median overall survival of resected patients was not reached. The median overall survival of non-resected patients was 75.9 months. Univariate and multivariate analysis for surgery and non-surgery groups was performed. No statistically significant covariates were found beyond surgical resectability. The conditional survival probabilities of living 1, 2 or 3 years longer after 24 months of survival are 91.7%, 71.6% and 51.6% respectively in the patients with unresectable disease, and 98.1%, 92.2% and 88.8% in patients who were able to be resected with curative intent. Conclusions: These results indicate that patients who survive 24 months with stage IV colorectal cancer have an excellent prognosis. For patients who are unresectable and survive 24 months, this study suggests that they may benefit from resection of remaining metastatic sites if feasible. For resected patients this information may propose a possible benefit from repeat metastasectomy.
Proprotein convertase furin regulates osteocalcin and bone endocrine function
Authors: Omar Al Rifai, Jacqueline Chow, Julie Lacombe, Catherine Julien, Denis Faubert, Delia Susan-Resiga, Rachid Essalmani, John W.M. Creemers, Nabil G. Seidah, Mathieu Ferron
Journal: Journal of Clinical Investigation (2017)

Osteocalcin (OCN) is an osteoblast-derived hormone that increases energy expenditure, insulin sensitivity, insulin secretion, and glucose tolerance. The cDNA sequence of OCN predicts that, like many other peptide hormones, OCN is first synthesized as a prohormone (pro-OCN). The importance of pro-OCN maturation in regulating OCN and the identity of the endopeptidase responsible for pro-OCN cleavage in osteoblasts are still unknown. Here, we show that the proprotein convertase furin is responsible for pro-OCN maturation in vitro and in vivo. Using pharmacological and genetic experiments, we also determined that furin-mediated pro-OCN cleavage occurred independently of its γ-carboxylation, a posttranslational modification that is known to hamper OCN endocrine action. However, because pro-OCN is not efficiently decarboxylated and activated during bone resorption, inactivation of furin in osteoblasts in mice resulted in decreased circulating levels of undercarboxylated OCN, impaired glucose tolerance, and reduced energy expenditure. Furthermore, we show that Furin deletion in osteoblasts reduced appetite, a function not modulated by OCN, thus suggesting that osteoblasts may secrete additional hormones that regulate different aspects of energy metabolism. Accordingly, the metabolic defects of the mice lacking furin in osteoblasts became more apparent under pair-feeding conditions. These findings identify furin as an important regulator of bone endocrine function.
Primary efficacy results and clinical impact of UGT1A1 genotype on safety from a Phase II study of FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer: The QUATTRO study
Authors: H. Bando, T. Kato, T. Yoshino, K. Muro, K. Yamazaki, T. Yamaguchi, E. Oki, S. Iwamoto, A. Tsuji, G. Nakayama, Y. Emi, T. Touyama, M. Nakamura, M. Kotaka, Y. Kagawa, H. Taniguchi, H. Sakisaka, T. Yamanaka, A. Kanazawa
Journal: Annals of Oncology (2017)
Sex-related differences in circadian-dependent tolerance of Irinotecan (I) added to chronomodulated (chrono) 5-Fluorouracil (F), Leucovorin (L) and Oxaliplatin (O): Final results from international randomised time-finding study in patients with metastatic colorectal cancer (MCC)
Authors: F. Levi, C. Garufi, A. Karaboué, C. Focan, P. Chollet, X-M. Li, P. INNOMINATO
Journal: Annals of Oncology (2017)
The interferon gene signature is increased in patients with early treatment-naive rheumatoid arthritis and predicts a poorer response to initial therapy
Authors: Faye A H Cooles, Amy E Anderson, Dennis W Lendrem, Julie Norris, Arthur G Pratt, Catharien M U Hilkens, John D Isaacs
Journal: Journal of Allergy and Clinical Immunology (2017)

The interferon gene signature (IGS) is of increasing interest in patients with autoimmune diseases. In patients with established rheumatoid arthritis (RA), an IGS is present in approximately 20% of patients and associates with poor response to rituximab.1,2 Nevertheless, in patients with established RA, the IGS does not associate with disease activity, and little is known regarding its role in RA pathogenesis.3 However, glucocorticoids, which are commonly administered in patients with RA, can modulate the IGS,2 potentially confounding reported findings.
Development of lamellar gel phase emulsion containing baru oil ( Dipteryx alata Vog.) as a prospective delivery system for cutaneous application
Authors: Cristhianne Moraes, Jorge L.V. Anjos, Monica Maruno, Antonio Alonso, Pedro Rocha-Filho
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The rational design of emulsions requires study of the main factors that influence their formation, physicochemical properties and, consequently, stability and performance. The use of vegetable oils in the pharmaceutical and cosmetic industries has recently become attractive. Dipteryx alata Vogel (D. alata) is an oleaginous species native to Brazil. The seeds of this species contain highly unsaturated oil with significant amounts of tocopherols and phytosterols, representing an important source of agents capable of combatting oxidative processes. In this work, a lamellar gel phase emulsion using oil extracted from the seeds of D. alata (baru) was developed. The steps involved in the development of this research were as follows: 1) development of formulations and 2) in vitro assays by simulating the evaporation of the final product after application to the skin and Electron paramagnetic resonance spectroscopy (EPR) of fatty acid spin labels was used to investigate the profile of interaction of the dispersed systems with stratum corneum (SC) lipids. The results indicate that the developed system shows no signs of instability during the storage period. Moreover, EPR studies indicated that D. alata oil and especially the developed formulation were able to increase SC lipid fluidity and extract a fatty-acid spin label from the lipid domain structures of SC, demonstrating its potential to act as a drug or skin care vehicle.
Impact on OS and PFS of 2nd and 3rd generation TKI in EGFR mt+ and ALK+ pts: Results of the NOWEL network
Authors: J. Roeper, A. Lueers, M. Netchaeva, M. Falk, C. Hallas, M. Tiemann, N. Neemann, L. Heukamp, C. Wesseler, G.H. Wiest, D. Ukena, S. Sackmann, F. Griesinger
Journal: Annals of Oncology (2017)
Abstract 10118: PCSK9 Inhibition Augments the Therapeutic Effect of Ezetimibe in Lowering Intestinal Apolipoprotein B Lipoprotein Production
Authors: Shirya Rashid, Harry R Davis, Xi Ai, David R Neff, Sergio Fazio
Journal: Circulation (2013)

Ezetimibe is an effective therapy to lower circulating low-density lipoprotein (LDL) cholesterol, a maneuver expected to reduce coronary heart disease (CHD) risk. However, ezetimibe concomitantly r...
A phase 1 study of oral LOXO 292 in adult patients with advanced solid tumors, including RET-fusion non-small cell lung cancer, medullary thyroid cancer and other tumors with increased RET activity
Authors: A.E. Drilon, T.M. Bauer, V. Subbiah, M. Cabanillas, N. Lahkani, L. Wirth, G. Oxnard, S. Smith, T. Eary, S. Cruickshank, M. Nguyen, S. Rothenberg
Journal: Annals of Oncology (2017)
Neo-adjuvant chemo/immunotherapy for the treatment of resectable stage IIIA non-small cell lung cancer (NSCLC): A phase II multicenter exploratory study” NADIM trial
Authors: V. Calvo de Juan, A. Insa Molla, M. Cobo Dols, B. Massuti Sureda, G. Lopez-Vivanco, J. Casal Rubio, J. de Castro, M. Majem Tarruella, R. Bernabe Caro, J. Gonzalez-Larriba, I.C. Barneto Aranda, E. Nadal, A. Martinez Marti, N. Vinolas Segarra, M. Guillot Morales, D. Vicente Baz, C. Camps Herrero, M. Domine Gomez, D. Rodriguez Abreu, M. Provencio Pulla
Journal: Annals of Oncology (2017)
Comparison of clinical efficacy of SST analogues therapy (lanreotide autogel vs. octreotide LAR) in treatment of patients with advance, non-resectable pancreatic neuroendocrine tumours (pNETs)
Authors: A. Kolasinska-Cwikla, A. Lewczuk, J. Palucki, L. Sawicki, K. Roszkowska-Purska, M. Kidd, L. Bodei, I. Modlin, J. Cwikla
Journal: Annals of Oncology (2017)
Presencia endémica de Salmonella enterica serotipo Cerro al sur de Italia
Authors: C Mammina, L Cannova, S CarfiPavia, A Nastasi
Journal: Eurosurveillance (2000)

La tipificacion molecular de cepas de salmonella aisladas entre 1997 y 1999 en la region sur de Italia y realizada por el Centro de Enteropatogenos de la Region Sur de Italia ha reflejado una alta frecuencia de Salmonella enterica del serotipo Cerro, serotipo muy poco frecuente en el hombre, con un predominio de ribotipo rt2. Los autores sostienen la hipotesis de una difusion de este serotipo por la region oriental de Sicilia y recomiendan una cuidadosa tarea de vigilancia.
Judge questions why GMC took three years to investigate sexual assault claim
Authors: Clare Dyer
Journal: BMJ (2017)

A High Court judge has called for an independent review of the General Medical Council’s delay in investigating a patient’s sexual assault claim against a foundation year 1 doctor, which was thrown out by a medical practitioners tribunal nearly three years after the investigation opened.1

Mr Justice Holgate made the call in a judgment quashing all the tribunal’s findings against Michael Brookman, along with the decision to strike him off the UK medical register.

The tribunal had rejected the patient’s evidence that Brookman had touched her genitalia while undertaking a sexually motivated inappropriate examination when he was working as a foundation year 1 doctor in October 2013. But it went on to strike Brookman off the register in February 2017 after finding him guilty of dishonesty in not immediately telling a locum agency and an NHS trust that were using his services about interim conditions placed on his registration. …
A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair
Authors: Alan J. Ryan, William A. Lackington, Alan J. Hibbitts, Austyn Matheson, Tijna Alekseeva, Anna Stejskalova, Phoebe Roche, Fergal J. O'Brien
Journal: Advanced Healthcare Materials (2017)

Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze-drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome.
Vigilância das infecções por E. coli enterohemorrágica (ECEH) e do síndroma hemolítico-urémico (SHU) na Europa
Authors: A Ammon
Journal: Eurosurveillance (1997)

Desde que foram descritas (1), as estirpes de Escherichia coli O157:H7 e outras E. coli enterohemorragicas tornaram-se conhecidas como os principais agentes causadores de diarreia hemorragica. Estas E. coli produzem uma ou mais shiga-toxinas (stx) ou Vero-citotoxinas. Em sentido estrito, o termo ECEH refere-se apenas aos serotipos que causam uma doenca clinica identica a causada pela E. coli O157:H7, nao existindo consenso sobre quando e que uma E. coli produtora de stx pode ser considerada uma ECEH.
Expression of breast cancer resistance protein (BCRP) in esophageal cancers (EC)
Authors: A. Bharthuar, T. Khoury, K. N. Haas, T. Mashtare, J. Black, M. Baer, G. Yang, N. Khushalani, R. V. Iyer
Journal: Journal of Clinical Oncology (2009)

e13529 Background: EC patients face a dismal outcome despite tri-modality management strategy. Median survival remains 15–18 months despite platinum, fluropyrimidine &amp; irinotecan based therapy. BCRP is an ATP-dependent efflux protein associated with chemotherapy (CT) (e.g. irinotecan) resistance. Role of BCRP expression in EC and normal esophageal cells is not known. We examined the expression of this protein and correlate it with survival (OS) in patients receiving irinotecan-based CT. Methods: With IRB approval, 40 cases of EC diagnosed between 2004 and 2008 were stained for BCRP expression by IHC &amp; scored by the pathologist blinded to clinical data. Baseline demographics, therapy given &amp; OS data were collected and correlated with BCRP expression. BCRP score (membrane or cytoplasm) &gt;/= 30 was considered positive (calculated by multiplying BCRP intensity and % staining). Fisher's exact test used to determine association between BCRP expression &amp; demographics. Cox proportional hazards model used for association of BCRP &amp; OS. Results: Baseline patient and tumor characteristics: Gender: M 35, F 5; Histology: 37 Adenoca &amp; 3 SCC; Stage 1-III 27, Stage IV 10, unknown 3; CT: cisplatin+irinotecan (n=16), oxaliplatin+fluoropyrimidine (n=8), other (n=16); IHC: 30 of 40 cancers (75%) expressed BCRP [strong (n=28) &amp; intermediate (n=3); membranous (n=17), cytoplasmic (n=27) &amp; both (n=14)]. Down-regulation of BCRP expression in tumor compared to normal cells seen in 40% of patients. Median OS was 19 months with no difference in OS between BCRP positive and negative patients (p=0.13). Estimated hazard ratio (HR) of death for BCRP positive patients was 2.29 (95% CI 0.79 - 6.64).There was no association between BCRP expression and stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line CT there was no difference in OS (p=0.39) of BCRP negative versus positive patients. Conclusions: BCRP expression is seen in a majority of EC &amp; normal esophageal mucosa. Response rates to irinotecan based therapies are seen in 30–40 % of EC, whether the 40% with low tumor BCRP constitute a majority of the responders needs to be prospectively validated in a larger dataset &amp; should include markers that predict response to 5-FU &amp; platinum based CT to allow individualizing therapy for this cancer. No significant financial relationships to disclose.
GW28-e0117 Impact of Gene Polymorphisms, Platelet Reactivity, and the SYNTAX Score on 1-Year Clinical Outcomes in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Rama Kumari, Sreenivasa Kumar, Sreedhar Kasturi, Sreedhar Reddy, Sarat Chandra, None Subbareddy, Ganesh Madhan, None Prakesh, None Ramesh, Vijay Kumar
Journal: Journal of the American College of Cardiology (2017)