tbuckley/cabot-search huggingface dataset:
Phase 1 study of the folic acid (FA) and tubulysin B hydrazide (TubBH) small molecule drug conjugate (SMDC) EC1456 in patients (pts) with advanced cancers (CA).
Authors: Daniela Matei, Martin J. Edelman, Jasgit C. Sachdev, Patrick Klein, Satish Rao, Shelly Burgess, Romnee Clark, Ramesh K. Ramanathan, Elizabeth A Morris, Wael A. Harb
Journal: Journal of Clinical Oncology (2015)

2551 Background: The folate receptor (FR) is expressed in many cancers, with limited expression in most normal tissues. EC1456, a potent SMDC of FA and the anti-tubulin cytotoxic TubBH, targets delivery of TubBH to FR-expressing cells. EC1456 demonstrated potent activity in paclitaxel- and cisplatin-resistant FR expressing cells. In murine models of FR-expressing xenografts, EC1456 caused complete tumor regression without significant toxicity. Enhanced anti-tumor activity was observed when EC1456 was combined with platinum, taxanes, and topotecan in preclinical models. These data led to this clinical evaluation of EC1456 in advanced CA pts. Methods: The primary objective is to determine the MTD of EC1456 administered on 2 schedules (BIW: days 1, 4, 8, 11 q 21 or 28 days [dosages: 0.5-6.0 mg/m2)], or QW: days 1, 8 q 21 days (dosage: 1.5-6.0 mg/m2). Key inclusion criteria: age ≥ 18 years, ECOG PS 0–1, and adequate organ function. 99mTc-etarfolatide scan to evaluate FR status is to be obtained on enrolled pts. Dose escalation follows the “3+3” protocol for BIW cohort, and continuous reassessment method for QW cohort. Cycle 1 DLT evaluation must be completed for each schedule cohort prior to dosing a new cohort. Results: 16 pts have been treated: median age: 67.5 (48-86), M/F: 7/16. 11 pts have received 50 cycles of EC1456 BIW (median 2; range: 1-16), and 5 pts have received 19 cycles of EC1456 QW (median 4; range: 1-8). The only DLT and treatment related (TR) SAE occurred at 4.5 mg/m2 QW schedule (Grade 3 infusion reaction). There have been no TR-deaths, Grade 4 toxicity, or toxicity causing dose delay, omission or reduction. Most TR-AEs have been Grade 1-2. Stable disease > 14 cycles has been observed in 2 pts with FR expression on 99mTc-etarfolatide SPECT scan (mesothelioma; GEJ CA) on BIW schedule, and SD > 6 cycles in 1 pt (leiomyosarcoma) on QW schedule. Conclusions: Due to the DLT on the QW schedule, cohort expansion is ongoing at 3.5 mg/m2. Dose escalation of EC1456 BIW is ongoing. EC1456 is generally well tolerated. PK data are anticipated in May 2015. Clinical trial information: 001999738.
A multidimensional problem-oriented review and evaluation system
Authors: S I Miller, R H Schlachter
Journal: American Journal of Psychiatry (1975)

The need for evaluation of psychiatric services is becoming more and more apparent as third-party coverage becomes more available. A variety of expensive and complex data and computer systems have been developed. Small institutions and programs, however, cannot afford them. The system described in this report uses diagnosis and a standardized problem list in order to define the treatment outcome of a variety of therapies delivered in an interdisciplinary setting. The system, which has been developed and is operating at low cost, satisfies a variety of needs.
Active Tumor Permeation and Uptake of Surface Charge-Switchable Theranostic Nanoparticles for Imaging-Guided Photothermal/Chemo Combinatorial Therapy
Authors: Chia-Chian Hung, Wen-Chia Huang, Yi-Wen Lin, Ting-Wei Yu, Hsin-Hung Chen, Sung-Chyr Lin, Wen-Hsuan Chiang, Hsin-Cheng Chiu
Journal: Theranostics (2015)

To significantly promote tumor uptake and penetration of therapeutics, a nanovehicle system comprising poly(lactic-co-glycolic acid) (PLGA) as the hydrophobic cores coated with pH-responsive N-acetyl histidine modified D-α-tocopheryl polyethylene glycol succinate (NAcHis-TPGS) is developed in this work. The nanocarriers with switchable surface charges in response to tumor extracellular acidity (pHe) were capable of selectively co-delivering indocyanine green (ICG), a photothermal agent, and doxorubicin (DOX), a chemotherapy drug, to tumor sites. The in vitro cellular uptake of ICG/DOX-loaded nanoparticles by cancer cells and macrophages was significantly promoted in weak acidic environments due to the increased protonation of the NAcHis moieties. The results of in vivo and ex vivo biodistribution studies demonstrated that upon intravenous injection the theranostic nanoparticles were substantially accumulated in TRAMP-C1 solid tumor of tumor-bearing mice. Immunohistochemical examination of tumor sections confirmed the active permeation of the nanoparticles into deep tumor hypoxia due to their small size, pHe-induced near neutral surface, and the additional hitchhiking transport via tumor-associated macrophages. The prominent imaging-guided photothermal therapy of ICG/DOX-loaded nanoparticles after tumor accumulation induced extensive tumor tissue/vessel ablation, which further promoted their extravasation and DOX tumor permeation, thus effectively suppressing tumor growth.
Treatment of Gastric Cancer
Authors: John Fielding, David Peake
Journal: New England Journal of Medicine (2006)

To the Editor: In the study by Cunningham et al. (July 6 issue),1 the effect of down-staging of tumor is unclear. At surgery, there were more patients with advanced disease according to tumor stage and nodal status in the surgery group than in the perioperative-chemotherapy group. Also, 31% of patients did not have tumor size documented before randomization. It would therefore be interesting to know the clinical tumor stage and nodal status of patients before randomization and at restaging before surgical resection. A discrepancy in which patients with smaller tumors were disproportionately being assigned to the perioperative-chemotherapy group could account for the apparent down-staging. Jaswinder Singh, M.D. Stephen K. Williamson, M.D.
Phototherapy for seasonal affective disorder: a blind comparison of three different schedules
Authors: B Lafer, G S Sachs, L A Labbate, A Thibault, J F Rosenbaum
Journal: American Journal of Psychiatry (1994)

The authors investigated the outcome of an alternating time schedule versus two fixed schedules (either morning or evening) of bright light treatment for seasonal affective disorder. The subjects were 31 patients who met DSM-III-R criteria for major depression with a seasonal pattern. No statistically significant difference was observed among patients in the three groups for response criteria after 1 week of treatment. These results support the use of more flexible phototherapy schedules.
SP0247 Teaching is Not an Art: It is a Skill
Authors: J. Hafler
Journal: Annals of the Rheumatic Diseases (2015)

The shift in medical education towards an understanding that learning is a shared process in which the student is interacting with the learning environment can be guided by core principles.[1] Teaching is not an art. It is a skill and it is a skill that can be learned. You, the instructor, create the atmosphere for your students, whether it is in the lab, at the bedside or in a lecture. In academic settings we are always teaching: we teach our patients, we teach our peers, we teach our residents and we teach our students. How do you move from being a great scientist to being a great educator? In this talk I will ask that you think with me about how you can help students learn and how you can create an effective learning environment. I will present principle-based core teaching competencies, that when activated, can create a rich and effective learning environment. <h3>References</h3> Bing-You RG, Lee R, Trowbridge RL, Varaklis K, Hafler JP. Principle-based Teaching Competencies. J Grad Med Edu. Nov 2009. <h3>Disclosure of Interest</h3> None declared
Perspectives for a European Centre for Disease Prevention and Control
Authors: M Kokki, R Haigh
Journal: Eurosurveillance (2004)

On 30 March the Council finally put its seal on the Regulation setting up a new European Centre for Disease Prevention and Control. Negotiations, from the Commission's proposal in July 2003 to final agreement by both the European Parliament and the Council took just eight months. This might not be a record for agreeing new EU legislation, but in terms of the type of legislation involved - setting up a new Community body with all that entails for permanent funding and obligatory participation by Member States - it probably is. Now comes the next phase - the practical implementation of the Regulation. First amongst the priorities will be the choice of Director and the site in Stockholm. The Regulation sets out an ambitious series of requirements to make the Centre operational by May 2005 - making arrangements for the Management Board, organising the work programme for 2005, and putting in place many organisational requirements.
Association of tumor BRCA1 reversion mutation arising during neoadjuvant platinum-based therapy in breast cancer (BC) with therapy resistance.
Authors: Anosheh Afghahi, Kirsten Timms, Shaveta Vinayak, Kristin C. Jensen, Pei-Jen Chang, Anne-Renee Hartman, James M. Ford, Melinda L. Telli
Journal: Journal of Clinical Oncology (2015)

1094 Background: In germline BRCA1 or BRCA2 mutation carriers, restoration of tumor BRCA1/2 function by a secondary mutation in these genes has been recognized as a mechanism of acquired resistance to platinum and PARP inhibitors, primarily in ovarian cancer. We set out to evaluate this mechanism of resistance in newly diagnosed BRCA1/2-mutant BC patients (pts) with a poor response to platinum-based therapy. Methods: PrECOG 0105 was a single-arm phase II study in pts with clinical stage I-IIIA triple-negative (TN) or BRCA1/2 mutation-associated BC. Pts received neoadjuvant therapy with gemcitabine, carboplatin and iniparib every 21 days for 6 cycles (n = 80). The primary endpoint was pathologic complete response, defined as no invasive carcinoma in the breast and axilla. In addition to comprehensive germline BRCA1/2 testing, all pts underwent tumor BRCA1/2 genotyping using pre-treatment biopsies. For mutation carriers with unfavorable response (moderate or extensive residual disease at surgery), tumor BRCA1/2 status was re-sequenced in the residual surgical tissue. All testing was performed at Myriad Genetics. Results: 19 pts had a deleterious germline BRCA1/2 mutation, and of these 4 had moderate residual disease at surgery. BRCA1/2 sequencing of residual tissue was available in 2 of 4 pts (no consent in 1 case; inadequate DNA extraction in 1 case). These 2 pts had BRCA1 1479delAG and W1712X mutations with LOH at these loci in the pre-treatment tumor. In the first case, a new BRCA1 mutation (a 42 base pair [bp] deletion that overlapped with the original 2 bp deletion) was detected in the residual tissue. This resulted in a 14 amino acid deletion and restoration of the BRCA1 reading frame. A relapse biopsy 4 months later revealed the identical reversion mutation and the pt subsequently died of metastatic TNBC. No reversion mutation was observed in the residual tissue of the second BRCA1 carrier, who notably had ER/PR+ BC. Conclusions: We report a BRCA1 reversion mutation in a newly diagnosed TNBC pt that developed over the course of 18 weeks of platinum-based neoadjuvant therapy. This was associated with poor neoadjuvant therapy response, early relapse and death from metastatic BC.
How arousal influences neural competition: What dual competition does not explain
Authors: Steven G. Greening, Mara Mather
Journal: Behavioral and Brain Sciences (2015)

Abstract We argue that although the “dual competition” model is useful when considering interactions between emotional and neutral stimuli, it fails to account for the influence of emotional arousal on perceptual or goal-directed behavior involving neutral stimuli. We present the “arousal-biased competition” framework as an alternative that accounts for both scenarios.
Recombinant human granulocyte-macrophage colony-stimulating factor accelerates neutrophil and monocyte recovery after allogeneic T-cell- depleted bone marrow transplantation
Authors: T De Witte, A Gratwohl, N Van Der Lely, A Bacigalupo, AC Stern, B Speck, A Schattenberg, C Nissen, E Gluckman, WE Fibbe
Journal: Blood (1992)
AB1030 Juvenile Idiopathic Arthritis in Central Tunisia: Clinical and Therapeutic Features (About 54 Cases)
Authors: Z. Alaya, N. El Amri, H. Zaghouani, K. Baccouche, D. Amri, S. Belghali, M. Bouzaouache, H. Zeglaoui, E. Bouajina, C. Kraiem
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) groups several entities having in common the presence of arthritis that begin before the age of 16, persist for more than six weeks and have no identified cause. <h3>Objectives</h3> The aim of our study was to determine the feature of the different clinical forms of JIA. <h3>Methods</h3> This is a retrospective study of 54 cases of JIA according to the criteria of the International League Association of Rheumatology in department of Rheumatology collected over a period of 16 years [1998-2014]. <h3>Results</h3> Our population consists of 28 men and 26 women (sex ratio of 1.12). The average age of symptoms onset was 10.4 years [4-15 years]. Late diagnosis in adulthood was noted in 8 patients (15% of cases). The polyarticular form was the most common, affecting 66% of cases (15.1% with rheumatoid factor and 50.9% without rheumatoid factor). The other forms were in descending order: oligoarticular form (15.1%), arthritis with enthesitis (9.4%), systemic form (7.6%) and psoriatic arthritis (1.9%). Stunting and hip disease were observed respectively in 30.2 and 32.1% of cases. Extra- articular signs were fever (18.9%), uveitis (3.8%), pericarditis (3.8%), pleurisy (1.9%), rash (1.9%), peripheral lymphadenopathy (1.9%) and myocarditis (1.9%). The treatments used were: corticosteroids (66%), non steroidal anti-inflammatory drugs (43.4%), aspirin (17%), methotrexate (47.2%) and biotherapy (anti-tnf alpha) (9.4%). <h3>Conclusions</h3> JIA is an heterogeneous group of diseases having in common the presence of arthritis. Our series is characterized by the prevalence of hip disease. The treatment depends on the form of the disease. <h3>Disclosure of Interest</h3> None declared
Abstract 3211: Diabetes is Associated with Greater Progression of Coronary Atherosclerosis than the Metabolic Syndrome: Insights from Serial Intravascular Ultrasound Studies
Authors: O Bayturan, T Hu, P Schoenhagen, S Kapadia, E.M Tuzcu, S E Nissen, S J Nicholls
Journal: Circulation (2008)

Background: While the metabolic syndrome (MetS) and diabetes (DM) share many pathophysiological features it remains to be determined if they influence coronary atherosclerotic disease progression to a similar degree. Methods : A systematic review of subjects participating in 7 clinical trials that monitored coronary atheroma progression with intravascular ultrasound was performed. Clinical characteristics, baseline atheroma burden and disease progression were compared in patients with the MetS (n=1119), DM (n=201) or their combination (n=878). Results: Patients with the MetS were younger, more likely to be female and had a greater risk factor burden than diabetics. At baseline the presence of DM was associated with a greater percent atheroma volume (PAV 41.0+/−8.5 vs 37.6+/−8.9 %, p&lt;0.001) and total atheroma volume (TAV 202.5+/−84.1 vs 190.73+−84.9 mm 3 , p&lt;0.001) than observed in patients with the MetS. Greater progression of PAV (+0.71+/−0.3 vs 0.28+/−0.2 % p=0.04) and TAV (−3.3+/−1.8 vs −1.0+/−2.1 mm 3 , p=0.1) was observed in the presence of DM compared with the MetS. The combination of MetS and DM was not associated with greater PAV (+0.82+/−0.2 vs +0.71+/−0.3 %, p=0.59) or TAV (−1.0+/−1.8 vs −1.0+/−2.1 mm 3 , p=0.98) than DM alone. Substantial progression rate were not differ between three groups (Table ). However, the combination of DM and the MetS did result in the lowest rate of patients undergoing substantial plaque regression (&gt;.0 % chg in PAV, 14.9% vs 18.4%, p=0.01) when compared with patients with DM, not meeting the criteria for the MetS. Conclusions: Despite the presence of more risk factors, meeting the criteria for the MetS is not associated with a greater rate of progression of coronary atherosclerosis in patients with DM. This highlights the accelerated nature of disease in the setting of established DM. Table. Baseline and changes in IVUS disease burden according to metabolic syndrome and diabetes
Cardiac denervation with aortocoronary bypass.
Authors: M P Kaye, W C Randall
Journal: Circulation (1980)

EDITORwith autopsy series, stating, "Previous autopsy studies have reported vegetative valvular lesions in 53% of patients who died of active infective endocarditis.'`However,they misinterpreted the data from these studies.2 3 In fact, all patients in the necropsy studies cited by Stewart et al. had valvular vegetations.The fact that these vegetations were superimposed on previously normal valves in 53% of the cases may be the source of confusion.
The emergence of LGV in Western Europe: what do we know, what can we do?
Authors: M JW Van de Laar
Journal: Eurosurveillance (2006)

Lymphogranuloma venereum (LGV), a systemic sexually transmitted disease (STD) caused by a variety of the bacterium Chlamydia trachomatis, occurs rarely in the Western world [1]. However, in January 2004, public health officials in the Netherlands noted an outbreak of cases of LGV proctitis among men who have sex with men (MSM) [2]. Since then, cases have been reported from several European countries, and the United States of America and Canada. In this issue three countries report on the current status of LGV [3-5].
Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses
Authors: Emmanuel Balandya, Teri Reynolds, Stephen Obaro, Julie Makani
Journal: American Journal of Hematology (2016)

Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper: CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg ), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27 + IgM(high) IgD(low) memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research. Am. J. Hematol. 91:938-946, 2016. © 2016 Wiley Periodicals, Inc.
Abnormal upper body soft tissue uptake on skeletal scintigraphy: a sign of superior vena cava obstruction.
Authors: MATTHEW MONSON, DAVID KEADLE, JOHN BAUMAN, CHRIS COWAN
Journal: Clinical Nuclear Medicine (2001)

MONSON, MATTHEW D.O.; KEADLE, DAVID M.D.; BAUMAN, JOHN M.D.; COWAN, CHRIS M.D. Author Information
Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease
Authors: A Satlin, L Volicer, V Ross, L Herz, S Campbell
Journal: American Journal of Psychiatry (1992)

The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders.Ten inpatients with Alzheimer's disease on a research ward of a veterans' hospital were studied in an open clinical trial. All patients had sundowning behavior and sleep disturbances. After a week of baseline measurements, patients received 2 hours/day of exposure to bright light between 7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week, and a posttreatment week, patients were rated by nurses for agitation, sleep-wake patterns, use of restraints, and use of prescribed-as-needed medication. On the last 2 days of each week, patients wore activity monitors. Activity counts were analyzed for circadian rhythmicity.Clinical ratings of sleep-wakefulness on the evening nursing shift improved with light treatment in eight of the 10 patients. The proportion of total daily activity occurring during the nighttime decreased during the light-treatment week. The relative amplitude of the circadian locomotor activity rhythm, a measure of its stability, increased during the light-treatment week. More severe sundowning at baseline predicted greater clinical improvement.Evening bright light pulses may ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's disease. This effect may be mediated through a chronobiological mechanism.
Reversible Defect in Renal Ammonium Excretion in Patients With Hypercalcemia
Authors: H O HEINEMANN
Journal: JAMA (1963)

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J&amp;J Partners with Yale to Share Trial Data
Authors: Melissa Weber
Journal: Cancer Discovery (2014)

Abstract Johnson &amp; Johnson (J&amp;J) joins GlaxoSmithKline, Pfizer, Roche, and other pharmaceutical companies in sharing its clinical trial data with researchers. J&amp;J, however, is the only company to enlist an independent academic partner to review every request for data and decide who gets access.