tbuckley/cabot-search huggingface dataset:
Major vault protein in bladder tumor drug resistance and cell signaling.
Authors: Mikael C. Herlevsen, Dan Theodorescu
Journal: Cancer Research (2006)

5096   The vault complex is the largest known ribonuclear protein complex. To date, no function of vaults has been described, although their expression correlates in several tumor types, including bladder cancer, with drug resistance. Knockdown of the Major Vault Protein (MVP), the major constituent of the vault, in UMUC-3 human bladder cancer cells results in sensitization towards Doxorubicin. This is direct evidence for a role of vaults in de novo drug resistance. Our data indicate that MVP knockdown perturb the nuclear exclusion and subsequent lysosomal sequestration of Doxorubicin, providing novel data to the notion that vaults are important in cellular transport processes. MVP has further been suggested to function as a scaffold protein in EGF signaling and to directly interact with PTEN. An interaction between MVP and the tumor suppressor PTEN was identified in a mass spectroscopy based screen in UMUC-3 cells. To further analyze this interaction, we investigated the effect of MVP knockdown downstream of the EGF receptor in the PI3Kinase/AKT pathway as well as in the MAP Kinase pathway by assessing phospho-AKT and phospho-ERK1/2 levels respectively, through western blotting. No effect was seen on steady state levels of phospho-AKT. However, both phospho-AKT and phospho-ERK responses were initially lower directly after EGF signaling. We are hence seeing a disruption in EGFR signaling dynamics, that current efforts aim to explain. In summary these studies will increase the understanding of the role MVP, and in extension the vault complex, plays in de novo drug resistance.
A value-based approach to the management of patients with liver cirrhosis through the systematic measurement of clinical outcome and quality of life indicators
Authors: S Okolicsanyi, A Ciaccio, P Cortesi, M Rota, M Gemma, P Giani, L Scalone, L Mantovani, S Fagiuoli, M Valsecchi, G Cesana, L Belli, M Strazzabosco
Journal: Hepatology (2014)
The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia
Authors: Victor I. Reus, Laura J. Fochtmann, A. Evan Eyler, Donald M. Hilty, Marcela Horvitz-Lennon, Michael D. Jibson, Oscar L. Lopez, Jane Mahoney, Jagoda Pasic, Zaldy S. Tan, Cheryl D. Wills, Richard Rhoads, Joel Yager
Journal: American Journal of Psychiatry (2016)
Case 20-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Norman Geschwind, George M. Kleinman
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 79-year-old woman was admitted to the hospital because of weakness and falling.She was well until six years earlier, when a diagnosis of chronic lymphocytic leukemia was made. Lymphadenopathy was well controlled with prednisone and chlorambucil; chlorothiazide was prescribed because of slight peripheral edema. The white-cell count remained in the vicinity of 24,000, with 96 per cent lymphocytes; the hematocrit was 35 per cent, and the platelet count 120,000. Several months before admission she fell because of "weakness in the legs," without loss of balance. Two days before entry she complained to her physician of generalized . . .
Phase I/II trial of GM-CSF and lenalidomide in patients with hormone refractory prostate cancer (HRPC)
Authors: R. Dreicer, J. Garcia, S. Smith, P. Elson, P. Triozzi, S. Hodnick, B. Rini, E. Klein
Journal: Journal of Clinical Oncology (2007)

15515 Background: Administration of GM-CSF in combination with thalidomide induces PSA responses in 20–25% of pts with HRPC. When administered in the neoadjuvant setting, this combination induces T cell and dendritic cell (DC) infiltration in prostate tumor tissue. Lenalidomide is an immunomodulatory analogue of thalidomide. In an effort to evaluate the clinical and immune activity of GM-CSF plus lenalidomide, we conducted a phase I/II trial in pts with HRPC. Methods: Pts had progressive asymptomatic HRPC by Consensus Criteria. Prior immunotherapy or chemotherapy was not permitted. A phase I safety phase followed by a phase II trial was undertaken. All pts received GM-CSF at 250 μg administered SC three times weekly along with lenalidomide 25 mg/day orally on days 1–21 of a 28-day cycle. Primary endpoints were safety and objective and PSA responses. Exploratory endpoints included activation of circulating DC, regulatory T cells (Treg) and cytokine production. Results: To date 19 of 34 planned pts are enrolled (13 with evidence of metastases; 6 with PSA-only disease). Seventeen pts are eligible for response (2 pts too early) Median age is 71 (49–80), median PSA is 19.1 (2.1–153.1). Median cycles of therapy is 4 (range: 1–14+). Overall, 13 of 17 pts (76%) experienced a reduction in PSA (&lt;20% 2/17; 20–40% 7/17,&gt;50% 4/17). Objective and PSA partial responses were observed in 2 and 4 of 17 pts respectively. Nine pts discontinued therapy (5 due to PD, 3 due to toxicity, and 1 withdrew consent). No pts on the phase I portion of the trial experienced a DLT. Grade (G) 1–2 toxicities for all 17 pts included neutropenia (20%), thrombocytopenia (13%), diarrhea (43%), dizziness, (25%), and fatigue (90%). Three pts developed G4 toxicities (PE, neutropenia, and emesis). The number of Treg cells decreased after 2 cycles of therapy. Similarly, Th1 cytokine and TNF-a production was increased after therapy. Although mean serum VEGF levels were decreased after therapy, changes in the mean serum levels of IL-8 and bFGF were not observed. Conclusions: The combination of GM-CSF and lenalidomide is relatively well tolerated with evidence of antitumor activity. Exploratory studies support the ability of this therapy to modulate immune cells. Accrual to this study is ongoing. [Table: see text]
TCTAP A-044 Single Versus Two-Stent Strategy for Unprotected Left Main Coronary Artery Disease in Patients with Acute Myocardial Infarction
Authors: Sung Hun Park, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Min Shim, Eun Jin Park, Jah Yeon Choi, Jae Joong Lee, Sunki Lee, Li Hu, Jin Oh Na, Cheolung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2016)
Gemcitabine-associated interstitial pneumonitis: Comprehensiveness and clinical characteristics of FDA and medical literature cases
Authors: N. Slimack, S. A. Klinge, V. Singh, T. Kuzel, S. Trifilio, S. M. Belknap, P. R. Yarnold, D. W. Raisch, M. S. Tallman, C. L. Bennett
Journal: Journal of Clinical Oncology (2004)

7229 Background: A debate exists over the extent to which gemcitabine is associated with potentially fatal pulmonary toxicities, namely interstitial pneumonitis. Methods: Herein, The Research on Adverse Drug reactions And Reports (RADAR) program evaluated 1) the quality and clinical characteristics of serious gemcitabine-associated pulmonary ADRs reported to the FDA (1997-present) and 2) reviewed medical literature cases (2001-present). Results: Completeness depending on whether reports were from the clinical trial (n=55) or routine care setting (n=95). Significantly more clinical trial reports reported the date of ADR onset (87% vs. 56%); days until onset (71% vs. 56%); pulmonary clinical signs such as dyspnea or hypoxia (82% vs. 69%), suspected drug relatedness (84% vs. 71%); and confirmed cause of death (83% vs. 67%) [p<.05 for all]. RADAR attributes better reporting in the clinical trial setting to prospective case reports forms mandated by IRBs and clinical trial sponsors. Gemcitabine was used for NSCLC (33%), pancreatic cancer (17%) and unspecified lung cancer (14%) and concomitant chemotherapy was used often (80% vs. 53%, clinical trial vs. not). These severe toxicities [pneumonitis (85%) & pneumonia (15%)] were diagnosed by CT or ultrasound (47%), more than one radiological exam (10%) or clinical means alone (43%); the median days until onset were 41 versus 55 days (clinical trial vs. not); 61% of patients were male; and 36 % of patients died. The medical literature indicates that concomitant chemotherapy significantly raises the risk of pulmonary toxicity. Conclusions: The lack of completeness in non-clinical trial versus clinical trial reports indicates that health professionals should strive to prospectively monitor and better report gemcitabine- associated pulmonary complications. No significant financial relationships to disclose.
PET as a predictor of metabolic response to antiangiogenic therapy in metastatic colorectal cancer (mCRC)
Authors: Nancy Van Damme, Sylvie De Bruyne, Liesbeth Ferdinande, Wim Ceelen, Jeroen Mertens, Christophe Van De Wiele, Stéphanie Laurent, Peter Smeets, Karen Geboes, Marc Peeters
Journal: Annals of Oncology (2011)
Effects on the Monocyte-Macrophage System and Antitumor Activity Against L1210 Leukemia of &lt;italic&gt;cis-bis&lt;/italic&gt;-Cyclopentenecarboxylato-&lt;italic&gt;trans-R,R&lt;/italic&gt;-1,2-Diaminocyclohexane-Platinum (II) Encapsulated in Multilamellar Vesicles&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Perez-Soler, A R Khokhar, P Claringbold, L P Kasi, G Lopez-Berestein
Journal: JNCI Journal of the National Cancer Institute (1986)

Multilamellar vesicles (MLVs) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a molar ratio of 7:3 were used as carriers of cis-bis-cyclopentenecarboxylato-trans-R,R-1,2-diaminocyclohexane-p latinum (II) (CPDP). The encapsulation efficiency of liposomal CPDP (L-CPDP) was 87.6%, and its stability in normal saline at 14 days was 94.4%. The in vitro and in vivo effects on the function of the monocyte-macrophage system and the antitumor activity against L1210 leukemia were investigated in CD-1 and (C57BL/6J X DBA/2J)F1 mice. L-CPDP and cisplatin (CDDP) caused a comparable inhibition of murine-resident peritoneal macrophage (PM) protein and RNA synthesis and superoxide anion release. PM-mediated tumor cell cytotoxicity was completely inhibited at a concentration of 10 micrograms CDDP and L-CPDP/ml but not at concentrations of 1 and 5 micrograms/ml. The differences in plasma clearance of 99mTc-labeled MLV and phagocytic capacity of the liver among animals pretreated with the maximum tolerated doses of L-CPDP (25 mg/kg), empty liposomes, or CDDP (10 mg/kg) were not statistically significant (plasma clearance % of control: 105, 110, and 100, respectively: P greater than .05; liver uptake % of control: 87, 96, and 104, respectively: P greater than .05). At the maximum tolerated doses, the antitumor activity of L-CPDP against L1210 leukemia was similar to that of CDDP when a single dose was administered [median survival of treated mice/median survival of control mice X 100 (%T/C): 181 vs. 175] and slightly higher with the use of a triple-dose schedule (%T/C: 275 vs. 225). L-CPDP is easy to prepare, has a high-encapsulation efficiency and stability, is not more toxic than CDDP to the monocyte-macrophage system, and is at least as effective as CDDP against L1210 leukemia.
Abstract 12368: Impact of Weight Trends on Long-term Outcomes After Atrial Fibrillation Ablation in Obese Patients
Authors: T J Bunch, Heidi T May, Tami L Bair, Victoria Jacobs, Brian G Crandall, Michael Cutler, J P Weiss, Charles Mallender, Jeffrey S Osborn, Jeffrey L Anderson, John D Day
Journal: Circulation (2015)

Introduction: Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach in symptomatic patients. Obesity is a dominant driver of AF recurrence after ablation. Weight reduction strategies lower general AF burden and as such may be critical to long-term success rates after ablation. Hypothesis: Long-term outcomes after AF ablation will be better in obese patients with sustained weight loss. Methods: All patients that underwent an index ablation with a BMI recorded and &gt;30 kg/m 2 and at least 3 years of follow-up were included (n=407). The group was separated and compared by weight trends over the 3 years (1. Lost &gt;3% of index weight, n=141; 2. Maintained index weight ±3%, n=147; 3. Gained &gt;3% of index weight at 3 years, n=119). Long-term outcomes included AF recurrence and a composite defined as major adverse clinical events, MACE (stroke/TIA, heart failure (HF) hospitalization, and death). Results: The average age was 63.6±10.4 years, 59.3% were male and 51.7% had paroxysmal AF. AF comorbidities include: hypertension (79.5%), heart failure (36.0%), sleep apnea (35.2%), diabetes (28.9%), and stroke/TIA (5.9%). Those that maintained their weight (HR: 1.45, p=0.05) and those that gained weight (HR 1.54, p=0.07) were more likely to have AF recurrence compared to those that lost weight. Similarly, MACE increased from 18.4% in those that lost weight at 3 years compared to 18.6% (HR 1.32, p=0.29) in those that maintained their weight and 26.5% in those that gained weight (HR 2.01, p=0.02). A small group of patients (n=5), lost &gt;3% then gained it back and ultimately increased their weight by 3%. This group had the highest rates of AF recurrence (100%). Conclusion: Maintained weight loss is a critical component in reducing AF recurrence rates after index catheter ablation in obese patients. Sustained weight loss also results in a reduction in AF-related comorbidities and mortality.
Abstract 304: Crystal Structure Of Fak/mef2 Complex Reveals The Role Of Fak In The Regulation Of Mef2 Transcription Factor.
Authors: Alisson C Cardoso, Ana H Pereira, Andre L Ambrosio, Silvio R Consonni, Sandra M Dias, Kleber G Franchini
Journal: Circulation Research (2014)

Members of MEF2 (Myocyte Enhancer Factor 2) family of transcription factors are major regulators of cardiac development and homeostasis. Their functions are regulated at several levels, including the association with a variety of protein partners. We have previously shown that FAK (Focal Adhesion Kinase) regulates the stretch-induced activation of MEF2 in cardiomyocytes. But, the molecular mechanisms, involved in this process, are unclear. Here, we integrated biochemical, imaging and structural analyses to characterize a novel interaction between MEF2 and FAK. An association between MEF2 and FAK was detected by co-immunoprecipitation in the extracts of stretched cardiomyocytes (10%, 60Hz, 2 hours). MEF2 and FAK staining were co-localized in the nuclei of stretched cells. Pull down assays indicated that the Focal Adhesion Targeting (FAT) domain is sufficient to confer FAK interaction with MEF2. Gene reporter assays indicated that the interaction with FAK enhances the MEF2C transcriptional activity in cultured cardiomyocytes. Also, we present a 2.9-Å X-ray crystal structure for the FAK_FAT domain bound to MEF2C (1-95), comprised by the MADS box/MEF2 domain. The structural information, when used in combination with biochemical studies, small-angle X-ray scattering (SAXS) data and reporter gene assay, lead to a mechanistic model describing how FAK binds to MEF2C and stimulates its transcription function in cardiomyocytes. We further validated this model by showing that the binding of FAK to MEF2C is essential for the hypertrophy of cardiomyocyte in response to mechanical stress. Our results present FAK as a new positive regulator of MEF2, implicated in the fine control of the signal transduction between focal adhesions and the nucleus of cardiac myocytes during mechanical stress.
Devolution of health budget to councils could see NHS spending eroded, expert warns
Authors: Nigel Hawkes
Journal: BMJ (2015)

Devolution of healthcare spending to local authorities could be a Trojan horse that would see the NHS budget eroded, a former permanent secretary at the Department of Health for England has warned.

Hugh Taylor, who now chairs the Guy’s and St Thomas’ NHS Foundation Trust in London, told a seminar at the think tank the King’s Fund that although he was an enthusiast for the devolution of powers exemplified by “devo Manc” (the new health and social care model being assembled in Greater Manchester1) he saw dangers.

He was sceptical that merging health and social care budgets and entrusting them to local authorities would work. How would the big decisions …
The incremental prognostic and clinical value of multiple novel biomarkers in heart failure
Authors: Colette E. Jackson, Caroline Haig, Paul Welsh, Jonathan R. Dalzell, Ioannis K. Tsorlalis, Alex McConnachie, David Preiss, Stefan D. Anker, Naveed Sattar, Mark C. Petrie, Roy S. Gardner, John J.V. McMurray
Journal: European Journal of Heart Failure (2016)
Next-Generation IgVH Sequencing of Monoclonal B-Cell Lymphocytosis Reveals Clonal Heterogeneity, Ongoing Mutation, and Repertoire Differences Relative to Chronic Lymphocytic Leukemia
Authors: Mark Klinger, Malek Faham, Jianbiao Zheng, Kojo S.J. Elenitoba-Johnson, Sherrie L. Perkins, David W Bahler
Journal: Blood (2014)
Stereotactic body radiation therapy for lung cancer with paraneoplastic limbic encephalitis: a case report
Authors: Yoshiaki Usui, Takao Fujisawa, Takafumi Koyama, Etsuko Fujisawa, Yoshiaki Nakamura, Yohei Harada, Kentaro Narita, Fumi Mitobe, Hidehiro Shibayama, Yu Oyama
Journal: Annals of Oncology (2015)
Is human albumin solution really the best resuscitation fluid for patients with advanced cirrhosis?
Authors: Alastair O'Brien, Louise China
Journal: Gut (2016)

Is Human Albumin Solution really the best fluid for advanced cirrhosis patients?Dear Sirs, We read with interest the revised consensus recommendations for management of acute kidney injury (AKI) ) in cirrhosis by the International Club of Ascites. 1 We are concerned that plasma volume expansion only with albumin is recommended for stage 2 and 3 AKI and do not believe that this represents a balanced view of the available evidence.No one doubts that fluid resuscitation is an integral part of the management of AKI; however, studies to date have not established class 1 evidence for an advantage of the use of albumin over other colloids or crystalloids.
Bronchogenic Carcinoma with Inappropriate Antidiuretic Activity in Plasma and Tumor
Authors: Bruce F. Bower, Donald M. Mason, Peter H. Forsham, Jean H. Hale
Journal: New England Journal of Medicine (1964)

SINCE the original description of the syndrome of bronchogenic carcinoma complicated by inappropriate antidiuresis in 1957,2 18 cases have been reported in detail.2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Because of the similarity between these patients and normal subjects who are chronically given large doses of exogenous antidiuretic hormone, it has been assumed that the antidiuresis results from inappropriate secretion of this hormone. However, this hypothesis has not been confirmed by direct demonstration of circulating plasma antidiuretic activity.Also uncertain is the source of the hypothesized antidiuretic activity. Possibilities include the inappropriate release of pituitary antidiuretic hormone by the tumor as a result of interference with . . .
Forced Fucosylation With ASC-101 Enhances The Binding Of Ex Vivo Expanded Human NK Cells To E-Selectin: A Novel Method To Improve The Homing Of Adoptively Transferred NK Cells To The Bone Marrow In Patients With Hematological Malignancies
Authors: Toshihiro Onishi, Maria Berg, Robert Reger, Leonard Miller, Steve Wolpe, Lynnet Koh, Richard Childs
Journal: Blood (2013)
Reply to Cebrián et al.
Authors: Uri Kopylov, Artur Nemeth, Anastasios Koulaouzidis, Ernest Seidman, Rami Eliakim, Ervin Toth
Journal: Endoscopy (2016)

We thank Cebrián et al. for their interest in our study; we agree with the points raised in their letter. Indeed, there is uncertainty regarding the optimal technique to detect the location of the patency capsule [1]. In our study, patency capsule location was verified using the hand-held scanner, plain abdominal film or abdominal computed tomography (CT). A recent, elegant, British study emphasized the inaccuracy of the plain abdominal film for this purpose, and suggested a dedicated low-radiation CT protocol for localization of the patency capsule [2]. This protocol involves a limited number of slices, does not require contrast material, and is associated with a lower level of radiation exposure (0.16 mSv) compared with plain abdominal film (0.4 mSv). In fact, in all patients with a “false-negative” patency capsule test in our study (i. e. excreted the patency capsule but retained the diagnostic capsule), the patency capsule location was verified by a plain abdominal film [3]. It is possible that some of these retention cases could have been avoided if a different modality was used, while enabling additional patients with a “false-positive” patency capsule test to proceed to diagnostic capsule endoscopy safely. Importantly, the accuracy of the hand-held scanner was never directly compared with any imaging modality.
ChromNet: Learning the human chromatin network from all ENCODE ChIP-seq data
Authors: Scott M. Lundberg, William B. Tu, Brian Raught, Linda Z. Penn, Michael M. Hoffman, Su-In Lee
Journal: Genome biology (2016)

A cell's epigenome arises from interactions among regulatory factors-transcription factors and histone modifications-co-localized at particular genomic regions. We developed a novel statistical method, ChromNet, to infer a network of these interactions, the chromatin network, by inferring conditional-dependence relationships among a large number of ChIP-seq data sets. We applied ChromNet to all available 1451 ChIP-seq data sets from the ENCODE Project, and showed that ChromNet revealed previously known physical interactions better than alternative approaches. We experimentally validated one of the previously unreported interactions, MYC-HCFC1. An interactive visualization tool is available at http://chromnet.cs.washington.edu.
A 5-Years Follow-up in Deferasirox Treatment: Improvement of Cardiac and Hepatic Iron Overload and Amelioration in Cardiac Function in Thalassemia Major Patients
Authors: Elena Cassinerio, Alberto Roghi, Nicola Orofino, Patrizia Pedrotti, Laura Zanaboni, Erika Poggiali, Marianna Giuditta, Dario Consonni, Maria Domenica Cappellini
Journal: Blood (2014)
Lyme Disease Serology
Authors: Paul M. Lantos, Paul G. Auwaerter, Christina A. Nelson
Journal: JAMA (2016)

A 10-year-old girl’s 2.0-cm annular lesion on the neck persists following 10 days of antifungal therapy, and she undergoes serologic testing for Lyme disease, which shows equivocal enzyme immunoassay results and negative immunoblots. How do you interpret results?