tbuckley/cabot-search huggingface dataset:
Psychiatric Risk Gene Transcription Factor 4 Regulates Intrinsic Excitability of Prefrontal Neurons via Repression of SCN10a and KCNQ1
Authors: Matthew D. Rannals, Gregory R. Hamersky, Stephanie Cerceo Page, Morganne N. Campbell, Aaron Briley, Ryan A. Gallo, BaDoi N. Phan, Thomas M. Hyde, Joel E. Kleinman, Joo Heon Shin, Andrew E. Jaffe, Daniel R. Weinberger, Brady J. Maher
Journal: Neuron (2016)
Increased Risk of Antituberculosis Drugs-Induced Maculopapular Eruption in Patients with Superoxide Dismutase 1 Gene Mutation
Authors: Sang-Heon Kim, Sang-Hoon Kim, Ji-Yong Moon, Dong Won Park, Jang Won Sohn, Ho Joo Yoon, Suk-Il Chang, Young-Koo Jee
Journal: Journal of Allergy and Clinical Immunology (2016)
A Broad RNA Virus Survey Reveals Both miRNA Dependence and Functional Sequestration
Authors: Troels K.H. Scheel, Joseph M. Luna, Matthias Liniger, Eiko Nishiuchi, Kathryn Rozen-Gagnon, Amir Shlomai, Gaël Auray, Markus Gerber, John Fak, Irene Keller, Rémy Bruggmann, Robert B. Darnell, Nicolas Ruggli, Charles M. Rice
Journal: Cell Host & Microbe (2016)
Secondary cytoreductive surgery for localized recurrent epithelial ovarian cancer: Analysis of prognostic factors and survival outcome
Authors: R. Salani, A. Santillan, M. Zahurak, R. Giuntoli, G. J. Gardner, D. K. Armstrong, R. E. Bristow
Journal: Journal of Clinical Oncology (2006)

5029 Background: To evaluate prognostic factors and survival outcome of patients undergoing secondary cytoreductive surgery for recurrent epithelial ovarian cancer with ≤ 5 sites of recurrence on pre-operative imaging studies. Methods: Patients undergoing secondary cytoreduction for recurrent epithelial ovarian carcinoma between 9/1997–3/2005 were retrospectively identified from tumor registry databases. Inclusion required: complete clinical response to primary therapy, ≥12 months between initial diagnosis and recurrence, and ≤5 recurrence sites on pre-operative imaging studies. Univariate and multivariate logistic regression analyses were used to evaluate the effect of clinico-pathologic variables on overall post-recurrence survival. Results: Fifty-five patients met study inclusion criteria. The median age at recurrence was 57.7 years and the median diagnosis-to-recurrence interval was 32 months (range 12 to 164 months). Complete cytoreduction was achieved in 41 patients (74.5%). On multivariate analysis, the statistically significant and independent predictors of overall survival were diagnosis-to-recurrence interval ≥18 months (median survival=49 months vs 3 months, p = 0.001), the number of radiographic recurrence sites (median survival: 1–2 sites=50.0 months vs 3–5 sites=12.0 months, p &lt; 0.03) and residual disease (median survival: no gross residual=50 months vs macroscopic residual=7.2 months, p &lt; 0.01). Age, tumor grade, histology, CA-125 level, ascites, and tumor size were not significantly associated with survival. Conclusions: These data support the definition of localized recurrent ovarian cancer as patients with 1–2 radiographic recurrence sites. In this select population, a diagnosis-recurrence interval ≥18 months and complete secondary surgical cytoreduction, which was achievable in the majority of cases, were associated with a median post-recurrence survival time of approximately 50 months. No significant financial relationships to disclose.
Coronary Artery Bypass Grafting Is Currently Underutilized
Authors: Mani Arsalan, Michael J. Mack
Journal: Circulation (2016)

C oronary artery disease (CAD) remains one of the lead- ing causes of death in the Western world.Three treatment options for CAD are currently available: medical therapy, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG).A long history of randomized controlled trials (RCTs), large observational registries, and a plethora of meta-analyses have demonstrated favorable outcomes with CABG in comparison with both medical therapy and PCI.However, because both techniques have developed further, there is still debate about the proper indications for each revascularization therapy.In this review, we will present recent studies and current practice in coronary revascularization, while making the case that, based on the available evidence, there should be a larger role for CABG in current clinical practice.Our aim is not to diminish PCI, because there are many patients with CAD in whom PCI is an appropriate treatment or even preferred alternative to CABG.Rather, the goal is to emphasize that, based on current evidence and guidelines, CABG is underutilized.
Turning the tide of antimicrobial resistance: Europe shows the way
Authors: D L Monnet, K G Kristinsson
Journal: Eurosurveillance (2008)

Preview this article: Turning the tide of antimicrobial resistance: Europe shows the way, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/13/46/art19039-en-1.gif
Reduced intensity allogeneic stem cell transplantation for follicular lymphoma relapsing after an autologous transplant achieves durable long-term disease control: an analysis from the Lymphoma Working Party of the EBMT
Authors: S.P. Robinson, A. Boumendil, H. Finel, H. Schouten, G. Ehninger, J. Maertens, C. Crawley, A. Rambaldi, N. Russell, W. Anders, D. Blaise, I. Yakoub-Agha, A. Ganser, L. Castagna, L. Volin, J.-Y. Cahn, S. Montoto, P. Dreger
Journal: Annals of Oncology (2016)
Abstract 1743: Pharmacological sequestration of Skp1 causes degradation of oncogenic E3 ligases and mitotic blockade
Authors: Guangbiao Zhou, Yong-Qiang Liu, Jinsong Liu
Journal: Cancer Research (2015)

Abstract Skp1 is an essential adaptor protein of the Skp1-Cul1-F-box protein complex and is able to stabilize the conformation of some ubiquitin E3 ligases. However, the role Skp1 plays during tumorigenesis remains unclear and Skp1-targeting agent is lacking. Here we showed that Skp1 was overexpressed in 33/56 (58.9%) non-small cell lung cancers, and elevated Skp1 was associated with poor prognosis. By structure-based high-throughput virtual screening, we found some Skp1-targeting compounds including 6-O-angeloylplenolin (6-OAP). 6-OAP could bind to Skp1 at sites critical to Skp1-Skp2 interaction, leading to dissociation and proteolysis of oncogenic E3 ligases NIPA, Skp2, and β-TRCP. Consequently, substrates of these E3 ligases Cyclin B1, P27 and E-Cadherin accumulated within the cells and caused prometaphase arrest. 6-OAP exhibited potent anti-lung cancer activity in two murine models and showed low adverse effect. These results indicate that Skp1 is critical to lung cancer pathogenesis, and targeting Skp1 can inactivate crucial oncogenic E3 ligases and exhibits significant therapeutic potentials. Citation Format: Guangbiao Zhou, Yong-Qiang Liu, Jinsong Liu. Pharmacological sequestration of Skp1 causes degradation of oncogenic E3 ligases and mitotic blockade. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1743. doi:10.1158/1538-7445.AM2015-1743
Central Nervous System Involvement in a Xenograft Model of Pre-B Acute Lymphoblastic Leukaemia Is Associated with Dysfunctional CXCR4 Expression and Upregulation of the Neurotropic Chemokine Receptors CCR6 and CX3CR1,
Authors: Christina Halsey, Mark TS Williams, Yasar Yousafzai, Klaus Rehe, Olaf Heidenreich, Josef Vormoor, Brenda Gibson, Gerard Graham
Journal: Blood (2011)
Divergent cancer pathways for early-onset and late-onset cutaneous malignant melanoma
Authors: W. F. Anderson, R. M. Pfeiffer, M. A. Tucker, P. S. Rosenberg
Journal: Journal of Clinical Oncology (2009)

9079 Background: Emerging data suggest that cutaneous malignant melanomas (CMM) may arise through divergent cancer pathways, linked to intermittent versus accumulated sun exposure. However, numerous questions remain regarding the timing and/or age of exposure. Methods: We, therefore, systematically examined the effect of aging upon CMM incidence in the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Standard descriptive epidemiology was supplemented with mathematical models. The impact of advancing age upon CMM incidence was assessed by gender, histopathological subtype (superficial spreading melanoma (SSM) or lentigo maligna melanoma [LMM]), and anatomic site (face, head, and neck [FHN] or lower extremity [LE]). Results: Gender, histopathological and anatomic site were age-specific effect modifiers for CMM, showing divergent (or bimodal) early- and late-onset cancer pathways. Early-onset melanomas were predominantly associated with female gender, SSM, and LE. Late- onset melanomas were correlated with male gender, LMM, and FHN. Early- and late-onset melanoma populations were confirmed with age-period-cohort models (adjusted for period and cohort effects) and two-component mixture models. Conclusions: These results are consistent with a divergent and age-dependent solar hypothesis for CMM. Early-onset melanomas may represent gene-sun exposure interactions occurring early (and/or intermittently) in life among susceptible individuals. Late-onset melanomas possibly reflect accumulated lifelong sun exposure in comparatively less susceptible individuals. Future analytical studies should be adequately powered to account for this age-dependent effect modification for acknowledged (gender, histopathology, and anatomic site) as well as suspected melanoma risk factors such as constituent genetic variants. No significant financial relationships to disclose.
World Health Organization and emergency health: if not now, when?:
Authors: Francesco Checchi, Ronald J Waldman, Leslie F Roberts, Alastair Ager, Ramin Asgary, Marie T Benner, Karl Blanchet, Gilbert Burnham, Emmanuel d’Harcourt, Jennifer Leaning, Moses B F Massaquoi, Edward J Mills, Rachel T Moresky, Preeti Patel, Bayard Roberts, Michael J Toole, Bradley Woodruff, Anthony B Zwi
Journal: BMJ (2016)

In light of the recent Ebola epidemic, <b>Francesco Checchi and colleagues</b> argue that the World Health Organization's response to health emergencies is not fit for purpose and put forward six proposals to reform WHO's crisis response
Outcomes of double-balloon enteroscopy-assisted direct percutaneous endoscopic jejunostomy tube placement
Authors: Badr Al-Bawardy, Emmanuel Gorospe, Jeffrey Alexander, David Bruining, Nayantara Coelho-Prabhu, Elizabeth Rajan, Louis Wong Kee Song
Journal: Endoscopy (2016)

<b>Background and study aims: </b>In a large series, conventional direct percutaneous endoscopic jejunostomy (DPEJ) tube placement with push endoscopes failed in approximately one-third of patients. In a pilot study, double-balloon enteroscopy (DBE)-assisted DPEJ tube placement was successful in all patients in whom attempted conventional DPEJ had failed. The study aim was to assess the technical success of and adverse events related to DBE-DPEJ tube placement in a large cohort of patients. <b>Patients and methods: </b>The medical records of all patients who underwent DBE-DPEJ tube placement between July 2010 and November 2013 were reviewed using a prospectively maintained electronic database. Data were abstracted for patient demographics, indications for DPEJ, gut anatomy, technical success rate, causes of failure, and adverse events. <b>Results: </b>The study comprised a total of 94 patients (39 men; mean age 56 years; body mass index [BMI] 23 ± 6.4 kg/m<sup>2</sup>). The most common indication for DPEJ was gastroparesis (n = 29). Altered gut anatomy was present in 36 patients (38 %). DBE-DPEJ tube placement was technically successful in 87 patients (93 %). The mean procedure duration was 33 minutes (range 15 – 88). DBE-DPEJ tube placement failed in seven patients (7 %), primarily because of limited instrument advancement in the setting of presumed surgical adhesions. Post-procedural adverse events occurred in eight patients (9 %), with one serious adverse event, which was a gastric interposition requiring surgical repair. <b>Conclusions:</b> Compared with the published outcomes of DPEJ by conventional endoscopy, DBE-DPEJ tube placement was technically successful in a high proportion of patients (93 %) and with a relatively low rate of significant adverse events.
Developmental history and object relations in psychiatrically disturbed adolescent girls
Authors: D Westen, P Ludolph, M J Block, J Wixom, F C Wiss
Journal: American Journal of Psychiatry (1990)

This study explored empirically the relationship between developmental history variables and several dimensions of object relations in a sample of 36 female adolescent inpatients. The results document the importance of preoedipal experience, the relationship with the mother, and continuity of attachments in shaping object relations. In addition, the data point to the importance of distinguishing different dimensions of object relations, such as the affective quality of the object world and the logic and accuracy of attributions, which may have different developmental correlates. The findings also suggest the impact of sexual abuse, typically a postoedipal experience, on enduring object-relational processes.
Reappraisal of risk factors for monoclonal gammopathy of undetermined significance
Authors: Ben Boursi, Brendan M. Weiss, Kevin Haynes, Ronac Mamtani, Yu‐Xiao Yang
Journal: American Journal of Hematology (2016)

A number of epidemiologic studies have demonstrated associations between obesity and diabetes and the risk of monoclonal gammopathy of undetermined significance (MGUS). However, since MGUS is an asymptomatic condition we evaluated whether these are true associations or the result of detection‐bias. We conducted a nested case–control study using a large primary‐care database. Cases were defined as those with incident diagnosis of MGUS. For every case, four eligible controls matched on age, sex, practice site, and duration of follow‐up were selected. Exposure variables included obesity and diabetes (including antidiabetic therapies) as well as other metabolic risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The study included 2363 MGUS patients and 9193 matched controls. In the primary analysis, obesity and diabetes were associated with higher MGUS risk with an adjusted ORs of 1.15 (95% CI 1.02–1.29) and 1.30 (95% CI 1.13–1.50), respectively. However, after adjustment to the number of laboratory tests prior to the MGUS diagnosis, there was no association between obesity and diabetes and MGUS risk (ORs of 1.08, 95% CI 0.96–1.22 and 1.08, 95% CI 0.93–1.25, respectively). In an additional analysis of antidiabetic therapies and MGUS risk, there was a nonsignificant decrease in MGUS risk among diabetes patients treated with metformin alone compared to subjects without diabetes (OR 0.77, 95% CI 0.56–1.05). In summary, while previously described risk factors for MGUS might be the result of detection bias, metformin should be further evaluated as a possible chemoprevention modality. Am. J. Hematol. 91:581–584, 2016. © 2016 Wiley Periodicals, Inc.
Mechanism of Persistent Herpes Simplex Virus Infection &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: Berge Hampar, Mary Alice K. Burroughs
Journal: JNCI Journal of the National Cancer Institute (1969)

Studies are reported relating to the mechanism of persistent herpes simplex virus (HSV) infection in Chinese hamster cells. Persistent infections were characterized by progressive changes with time in the properties of both the cells and the virus. Changes in the properties of the cells were evident by their increased resistance to HSV. Changes in the properties of the virus were host cell-induced, as evidenced by an increase in its virulence for resistant cells. It is suggested that changes in the infective and/or antigenic properties of HSV may be a normal sequelae following adaptation to less permissive cells. Persistent HSV infections were characterized by restrictive lesions, whereby cytopathic effects and virus synthesis were initiated but ultimately terminated. Termination of virus-induced lesions may have resulted from viral interference and/or the elaboration of an intracellular viral-interfering factor. The maintenance of persistent HSV infection apparently depended on a genetically determined cell-virus equilibrium, which precluded the requirement for external supportive factors. Finally, the properties of the persistent in vitro infections are discussed with relation to possible analogies to recurrent herpes infection in humans.
Multidrug-Resistant Organisms on Patients’ Hands
Authors: Jie Cao, Lillian Min, Bonnie Lansing, Betsy Foxman, Lona Mody
Journal: JAMA Internal Medicine (2016)

at risk), and 3.1% (11 of 347 at risk) of patients newly acquired VRE, MRSA, and RGNB colonization, respectively.MRSA and VRE colonization were more likely to be persistent, with 37.3% (22 of 59) and 22.5% (16 of 71) of patients colonized at multiple visits, whereas RGNB colonization on the same patient's hand was never obtained at follow-up.Overall, 67.2% of MDRO-colonized patients (82 of 122) remained colonized at discharge.
Phase I study of INC280 plus erlotinib in patients with MET expressing adenocarcinoma of the lung.
Authors: Caroline Elizabeth McCoach, Aiming Yu, David R. Gandara, Jonathan Riess, Tianhong Li, Primo Lara, Philip C. Mack, Laurel Beckett, Eric Daniel Slosberg, Karen Kelly
Journal: Journal of Clinical Oncology (2015)

2587 Background: MET dysregulation is one mechanism of EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) resistance in patients (pts) with EGFR mutated lung cancer. INC280 is a potent oral small molecular inhibitor of the MET kinase. Inhibiting both pathways may circumvent EGFR-TKI resistance. A phase I study of INC280 plus erlotinib (E) to determine the maximum tolerated dose, dose limiting toxicity (DLT), pharmacokinetics (PK) and preliminary antitumor activity of this combination was conducted. Methods: Using a 3 + 3, dose escalation design, INC280 was increased over 5 dose levels (DL) from 100 - 600 mg po bid. Daily E was given at 100 mg in DL1 and 150 mg in DL2- 5. Both agents were given for 28 days (1 cycle). Key eligibility included: lung adenocarcinoma with MET expression by a CLIA certified lab, age ≥ 18 years old, ECOG PS of ≤ 2, acceptable organ function, and > 1 systemic therapy for advanced disease. Results: 18 pts have been treated on 5 dose levels. Pt characteristics: median age 59, M/F (7/11), ECOG 0-1/2 (16/2), MET expression by IHC/FISH/RT-PCR/NGS (6/2/9/1), EGFR mutated tumors (8) and prior E treatment (12). 14 patients have completed at least 1 cycle. One DLT (grade (Gr) 3 neutropenia) occurred in DL 5 (INC280 600mg bid, E 150mg daily). Common drug-related adverse events (AE) of any Gr were diarrhea and rash (47% each), fatigue (40%), increased AST and ALT (27% each), nausea, anorexia and paronychia (27% each). Drug-related Gr 3/ 4 AE were anorexia, increased amylase or lipase and neutropenia (all 7%). PK analysis revealed that INC280 exhibited a linear PK and no interaction with E. Of the 12 evaluable pts, 6 had stable disease (3 EGFR mutated) and 2 with EGFR mutated tumors had a minor response (10-29% decrease in target lesion size). Seven pts received treatment for ≥ 3 months (5 EGFR mutated). Conclusions: In patients with MET-expressing lung adenocarcinoma, INC280 plus erlotinib is feasible, tolerable and demonstrates anti-tumor activity. Expansion cohorts will enroll pts with EGFR mutated tumors refractory to an EGFR-TKI or EGFR-TKI naïve in the first-line setting and in wild type EGFR pts who are EGFR-TKI naïve as second or third-line therapy. The recommended phase II dose and updated results will be presented. Clinical trial information: NCT01911507.
Overall and Intracranial (Ic) Efficacy Results and Time to Symptom Deterioration in Profile 1014: 1St-Line Crizotinib Vs Pemetrexed - Platinum Chemotherapy (Ppc) in Patients (Pts) with Advanced Alk-Positive Non-Squamous Non-Small Cell Lung Cancer (Nsclc)
Authors: B. Solomon, E. Felip, F.H. Blackhall, T.S.K. Mok, D. Kim, Y. Wu, K. Nakagawa, T. Mekhail, J. Paolini, T. Usari, S. Iyer, A. Reisman, K. Wilner, J. Tursi, F. Cappuzzo
Journal: Annals of Oncology (2014)
An Exponential Model Relating Censored Survival Data and Concomitant Information for Prostatic Cancer Patients2
Authors: David P. Byar, Robert Huse, John C. Bailar
Journal: JNCI Journal of the National Cancer Institute (1974)

An exponential survival model was developed and used to estimate the relative importance of presenting signs and symptoms in prediction of survival of patients with advanced (Stages III and IV) carcinoma of the prostate gland. Based on this information, one can predict survival for patients with various combinations of presenting signs and symptoms. Survival predictions based on the exponential model agreed remarkably well with observed survival rates.
Abstract 13666: Association of Paracardial Adipose Tissue With Plaque Composition in STEMI Patients Undergone Primary Percutaneous Coronary Interventions: Insight From Virtual Histology Intravascular Ultrasound Analysis
Authors: Wang-Soo Lee, YoungHwan Choi, Sang-Wook Kim, CheolWon Hyeon, JeeEun Kwon, EunYoung Kim, Seung-Yong Shin, KwangJe Lee, TaeHo Kim, CheeJeong Kim
Journal: Circulation (2013)

Background: The association between paracardial adipose tissue (PCAT), including epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT), and atherosclerosis is well know. The impact o...
Protein Kinase C-α is a Critical Protein for Antisense Oligonucleotide-mediated Silencing in Mammalian Cells
Authors: Daniela Castanotto, Min Lin, Claudia Kowolik, Troels Koch, Bo Rode Hansen, Henrik Oerum, Cy A Stein
Journal: Molecular Therapy (2016)

We have identified the existence of a productive, PKC-α-dependent endocytotic silencing pathway that leads gymnotically-delivered locked nucleic acid (LNA)-gapmer phosphorothioate antisense oligonucleotides (ASOs) into late endosomes. By blocking the maturation of early endosomes to late endosomes, silencing the expression of PKC-α results in the potent reduction of ASO silencing ability in the cell. We have also demonstrated that silencing of gene expression in the cytoplasm is vitiated when PKC-α expression is reduced. Restoring PKC-α expression via a reconstitution experiment reinstates the ability of ASOs to silence. These results advance our understanding of intracellular ASO trafficking and activity following gymnotic delivery, and further demonstrate the existence of two distinct silencing pathways in mammalian cells, one in the cytoplasmic and the other in the nuclear compartment. We have identified the existence of a productive, PKC-α-dependent endocytotic silencing pathway that leads gymnotically-delivered locked nucleic acid (LNA)-gapmer phosphorothioate antisense oligonucleotides (ASOs) into late endosomes. By blocking the maturation of early endosomes to late endosomes, silencing the expression of PKC-α results in the potent reduction of ASO silencing ability in the cell. We have also demonstrated that silencing of gene expression in the cytoplasm is vitiated when PKC-α expression is reduced. Restoring PKC-α expression via a reconstitution experiment reinstates the ability of ASOs to silence. These results advance our understanding of intracellular ASO trafficking and activity following gymnotic delivery, and further demonstrate the existence of two distinct silencing pathways in mammalian cells, one in the cytoplasmic and the other in the nuclear compartment.