tbuckley/cabot-search huggingface dataset:
Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence
Authors: Joan L. Luby, Andy C. Belden, Joshua J. Jackson, Christina N. Lessov-Schlaggar, Michael P. Harms, Rebecca Tillman, Kelly Botteron, Diana Whalen, Deanna M. Barch
Journal: JAMA Psychiatry (2015)

The trajectory of cortical gray matter development in childhood has been characterized by early neurogenesis and volume increase, peaking at puberty followed by selective elimination and myelination, resulting in volume loss and thinning. This inverted U-shaped trajectory, as well as cortical thickness, has been associated with cognitive and emotional function. Synaptic pruning-based volume decline has been related to experience-dependent plasticity in animals. To date, there have been no data to inform whether and how childhood depression might be associated with this trajectory.To examine the effects of early childhood depression, from the preschool age to the school age period, on cortical gray matter development measured across 3 waves of neuroimaging from late school age to early adolescence.Data were collected in an academic research setting from September 22, 2003, to December 13, 2014, on 193 children aged 3 to 6 years from the St Louis, Missouri, metropolitan area who were observed for up to 11 years in a longitudinal behavioral and neuroimaging study of childhood depression. Multilevel modeling was applied to explore the association between the number of childhood depression symptoms and prior diagnosis of major depressive disorder and the trajectory of gray matter change across 3 scan waves. Data analysis was conducted from October 29, 2014, to September 28, 2015.Volume, thickness, and surface area of cortical gray matter measured using structural magnetic resonance imaging at 3 scan waves.Of the 193 children, 90 had a diagnosis of major depressive disorder; 116 children had 3 full waves of neuroimaging scans. Findings demonstrated marked alterations in cortical gray matter volume loss (slope estimate, -0.93 cm³; 95% CI, -1.75 to -0.10 cm³ per scan wave) and thinning (slope estimate, -0.0044 mm; 95% CI, -0.0077 to -0.0012 mm per scan wave) associated with experiencing an episode of major depressive disorder before the first magnetic resonance imaging scan. In contrast, no significant associations were found between development of gray matter and family history of depression or experiences of traumatic or stressful life events during this period.This study demonstrates an association between early childhood depression and the trajectory of cortical gray matter development in late school age and early adolescence. These findings underscore the significance of early childhood depression on alterations in neural development.
Nilotinib in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis (CML-BC) who are resistant or intolerant to imatinib
Authors: F. J. Giles, R. A. Larson, H. M. Kantarjian, P. le Coutre, F. Palandri, A. Haque, N. Gallagher, O. G. Ottmann
Journal: Journal of Clinical Oncology (2008)

7017 Background: Patients (pts) with CML-BC, for whom prognosis remains poor, may benefit from treatment with the potent and highly selective BCR-ABL inhibitor nilotinib, which is approved for the treatment of chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome-positive (Ph+) CML pts who are resistant or intolerant to prior therapy including imatinib. Methods: This phase 2, open-label study evaluated the efficacy and safety of nilotinib in adult pts with Ph+ CML-BC who are resistant or intolerant to imatinib. The primary endpoint was confirmed hematologic response (HR). Imatinib resistance was defined as either treatment with imatinib > 600 mg/d with disease progression, no HR in bone marrow after 4 weeks. Imatinib intolerance was defined as grade 3/4 adverse events (AEs), or grade 2 AEs persisting for > 1 month while on imatinib. In the absence of safety concerns, the initial dose of nilotinib 400 mg twice daily (BID), could be escalated to 600 mg BID for: failure to achieve a return to CP, loss of an achieved hematologic or cytogenetic response, or progressive disease. Results: Safety and efficacy data are reported for 136 BC pts (myeloid, n = 105; lymphoid, n = 31). At study entry, 38% of pts had ≥ 95% Ph+ metaphases, and other chromosomal abnormalities were noted in 53% of pts. Confirmed HR occurred in 29 (21%) pts, and 15 (11%) achieved complete HR. Major cytogenetic response (MCyR) was achieved in 55 pts (40%), and 40 (29%) had complete cytogenetic response (CCyR). Overall survival at 12 months was 42%. Treatment with nilotinib is ongoing in 13 pts (10%). More than half of pts discontinued treatment due to disease progression. The most common grade 3/4 laboratory abnormalities were neutropenia (67%), thrombocytopenia (62%), and anemia (42%). Non-hematologic toxicities were mostly mild to moderate and included rash and nausea. Conclusions: Nilotinib has clinical activity in a group of CML pts with very advanced disease. Overall, nilotinib is well tolerated in imatinib-resistant or -intolerant CML-BC pts, with non-hematologic toxicity comparable to that observed for pts with CML- CP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Innovive, Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Novartis
Airway resistance and reactance in COPD patients and healthy smokers, and effect of bronchodilators
Authors: Linnea Svensson, Jaro Ankerst, Leif Bjermer, Ellen Tufvesson
Journal: European Respiratory Journal (2011)

Background:  Little is known about the reversibility response of the obstructive patterns to therapies in COPD. Impulse oscillometry (IOS) is a method to measure resistance and reactance of both the central and peripheral airways.   Aim:  The aim of this study was to investigate how salbutamol and ipratropium, commonly used therapies in COPD, affect obstructive airway patterns measured by impulse oscillometry.   Methods:  Twenty two healthy smokers and 24 patients with COPD, with matched pack years were included in this study. Spirometry and impulse oscillometry were performed at baseline, after inhalation of salbutamol and after additional ipratropium.   Results:  Medication increased FEV1 as expected. COPD patients had significantly higher total (R5), central (R20) and peripheral (R5-R20) resistance (% predicted) at baseline compared to healthy smokers. After medication with salbutamol, R5, R20 decreased in both COPD patients and healthy smokers. Salbutamol only decreased R5-R20 in COPD patient, but after additional ipratropium the R5-R20 in healthy smokers also decreased. The COPD group showed a higher reactance (X5, AX and Fres) at baseline compared to the healthy smokers. After inhalation of salbutamol, X5, AX and Fres was significantly decreased in the COPD group as well as in healthy smokers. Additional inhalation of ipratropium showed a tendency of decreasing X5 and AX in both COPD patients and healthy smokers.   Conclusions:  COPD patient have higher resistance and reactance compared to healthy smokers at baseline. Both airway resistance and reactance was affected by inhalation of salbutamol and additional ipratropium, and more pronounced in COPD patients compared to healthy smokers.
Bullae and Erosions on Sun-Exposed Skin
Authors: Pooja Chitgopeker, Anthony J. Little, Brian L. Swick
Journal: JAMA Dermatology (2015)

A man in his 60s with a history of acute myeloid leukemia, for which he had received an allogeneic stem cell transplant that was complicated by graft-vs-host disease, presented with new-onset bullae and erosions over sun-exposed areas and bony prominences. What is your diagnosis?
The mechanism of anti-tumor immunity induced by varlilumab, a CD27 agonist mAb, is model dependent
Authors: Li-Zhen He, Anna Wasiuk, James Testa, Jeffrey Weidlick, Crsytal Sisson, Andrea Crocker, Jenifer Widger, Eirc Forsberg, Lauren Gergel, Lawrence Thomas, Henry Marsh, Tibor Keler
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The use of agonist antibodies to costimulatory receptors holds significant promise as a complementary approach to the already proven strategy of antibody mediated checkpoint blockade. This is in part due to the multiple mechanisms that have been associated with targeting
Endoplasmic Reticulum–Associated Degradation and Lipid Homeostasis
Authors: Julian Stevenson, Edmond Y. Huang, James A. Olzmann
Journal: Annual Review of Nutrition (2016)

The endoplasmic reticulum is the port of entry for proteins into the secretory pathway and the site of synthesis for several important lipids, including cholesterol, triacylglycerol, and phospholipids. Protein production within the endoplasmic reticulum is tightly regulated by a cohort of resident machinery that coordinates the folding, modification, and deployment of secreted and integral membrane proteins. Proteins failing to attain their native conformation are degraded through the endoplasmic reticulum-associated degradation (ERAD) pathway via a series of tightly coupled steps: substrate recognition, dislocation, and ubiquitin-dependent proteasomal destruction. The same ERAD machinery also controls the flux through various metabolic pathways by coupling the turnover of metabolic enzymes to the levels of key metabolites. We review the current understanding and biological significance of ERAD-mediated regulation of lipid metabolism in mammalian cells.
Different forms of exercise for chronic low back pain (PEDro synthesis)
Authors: Aimie Laura Peek, Matthew L Stevens
Journal: British Journal of Sports Medicine (2015)

This section features a synthesis of a recent systematic review that is indexed on PEDro, the Physiotherapy Evidence Database (http://www.pedro.org.au). PEDro is a free, web-based database of evidence relevant to physiotherapy.

▸ Searle A, Spink M, Ho A, et al . Exercise interventions for the treatment of chronic low back pain: a systematic review and meta-analysis of randomised controlled trials. Clin Rehabil 2015;29:1155–67.

Low back pain (LBP) is an extremely common health condition and the leading cause of disability worldwide. Exercise for the treatment of chronic LBP is widely recommended in current national and international guidelines,1 however, there is no consensus with regards to the type of exercise, duration or intensity.

To investigate the effectiveness of general exercise, and of specific types of …
Identification of p38 MAPK and JNK as new targets for correction of Wilson disease‐causing ATP7B mutants
Authors: Giancarlo Chesi, Ramanath N. Hegde, Simona Iacobacci, Mafalda Concilli, Seetharaman Parashuraman, Beatrice Paola Festa, Elena V. Polishchuk, Giuseppe Di Tullio, Annamaria Carissimo, Sandro Montefusco, Diana Canetti, Maria Monti, Angela Amoresano, Piero Pucci, Bart van de Sluis, Svetlana Lutsenko, Alberto Luini, Roman S. Polishchuk
Journal: Hepatology (2015)

Wilson disease (WD) is an autosomal recessive disorder that is caused by the toxic accumulation of copper (Cu) in the liver. The ATP7B gene, which is mutated in WD, encodes a multitransmembrane domain adenosine triphosphatase that traffics from the trans‐Golgi network to the canalicular area of hepatocytes, where it facilitates excretion of excess Cu into the bile. Several ATP7B mutations, including H1069Q and R778L that are two of the most frequent variants, result in protein products, which, although still functional, remain in the endoplasmic reticulum. Thus, they fail to reach Cu excretion sites, resulting in the toxic buildup of Cu in the liver of WD patients. Therefore, correcting the location of these mutants by leading them to the appropriate functional sites in the cell should restore Cu excretion and would be beneficial to help large cohorts of WD patients. However, molecular targets for correction of endoplasmic reticulum‐retained ATP7B mutants remain elusive. Here, we show that expression of the most frequent ATP7B mutant, H1069Q, activates p38 and c‐Jun N‐terminal kinase signaling pathways, which favor the rapid degradation of the mutant. Suppression of these pathways with RNA interference or specific chemical inhibitors results in the substantial rescue of ATP7B H1069Q (as well as that of several other WD‐causing mutants) from the endoplasmic reticulum to the trans‐Golgi network compartment, in recovery of its Cu‐dependent trafficking, and in reduction of intracellular Cu levels. Conclusion: Our findings indicate p38 and c‐Jun N‐terminal kinase as intriguing targets for correction of WD‐causing mutants and, hence, as potential candidates, which could be evaluated for the development of novel therapeutic strategies to combat WD. (H epatology 2016;63:1842‐1859)
Gynecological adverse events including hysterectomy with anastrozole tamoxifen: Data from the ATAC (‘Arimidex’, Tamoxifen, Alone or in Combination) trial
Authors: S. Duffy
Journal: Journal of Clinical Oncology (2005)

723 Background: The ATAC trial compared the efficacy and safety of anastrozole (‘Arimidex’) and tamoxifen in the primary adjuvant treatment of postmenopausal women (n=9366) with early-stage operable breast cancer. In this retrospective analysis of the ATAC data after the completed treatment analysis at a median follow-up of 68 months, we performed a direct comparison of the gynecological adverse events (AEs) experienced by patients treated with anastrozole with those experienced by patients treated with tamoxifen. Methods: Three specific gynecological AEs were predefined for analysis in the ATAC trial. Here, we further investigated all gynecological AEs and hysterectomies recorded on the ATAC main trial database. Results: Gynecological AEs were significantly less common with anastrozole compared with tamoxifen (20.5% vs 34.2%, p<0.0001). The incidence of the three predefined gynecological AEs continued to be significantly lower with anastrozole compared with tamoxifen: vaginal bleeding 5.4% vs 10.2%, p<0.0001; vaginal discharge 3.5% vs 13.2%, p<0.0001; endometrial cancer 0.2% vs 0.8%, p=0.02. Of those women with an intact uterus at baseline, substantially fewer had a hysterectomy (30 [1.3%) vs 115 [5.1%]) or a hysterectomy for malignancy (7 [0.3%] vs 20 [0.9%]) if treated with anastrozole than if treated with tamoxifen. Patients on anastrozole had a hysterectomy for a benign indication in 23/30 (77%) of the cases versus 95/115 (83%) on tamoxifen. Approximately 35% of the hysterectomies for benign indications were due to fibroids or polyps (8/23 [35%] and 1/23 [4%], respectively, in the anastrozole group and 16/95 [17%] and 15/95 [16%], respectively, in the tamoxifen group). Conclusions: Women on anastrozole are at a lower risk of having gynecological AEs on adjuvant hormonal treatment for breast cancer than women on tamoxifen. The substantially higher hysterectomy rate, due to benign or malignant diagnoses, in women treated with tamoxifen compared with those treated with anastrozole is a cause for concern. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Primary Low-Grade Lymphomas of the Intestine
Authors: Taner Demirer, Harika Çelebi, Ender Akçağlayan, Celalettin Üstün, Seher Demirer, Cemil Ekinci, Kadir Bahar, Haluk Koç
Journal: Journal of Clinical Oncology (1999)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.11.3682 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10550167 Primary Low-Grade Lymphomas of the Intestine Taner DemirerxTaner DemirerSearch for articles by this author , Harika ÇelebixHarika ÇelebiSearch for articles by this author , Ender AkçağlayanxEnder AkçağlayanSearch for articles by this author , Celalettin ÜstünxCelalettin ÜstünSearch for articles by this author , Seher DemirerxSeher DemirerSearch for articles by this author , Cemil EkincixCemil EkinciSearch for articles by this author , Kadir BaharxKadir BaharSearch for articles by this author , Haluk KoçxHaluk KoçSearch for articles by this author Show More Department of Hematology/Oncology and Bone Marrow Transplant Unit, Ankara University Medical School, Ibn-i Sina Hospital, Sihhiye 06100, Ankara, Turkey https://doi.org/10.1200/JCO.1999.17.11.3682 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial
Authors: Matthew Maddocks, Claire M Nolan, William D-C Man, Michael I Polkey, Nicholas Hart, Wei Gao, Gerrard F Rafferty, John Moxham, Irene J Higginson
Journal: The Lancet Respiratory Medicine (2015)

BackgroundSkeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy.MethodsIn this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed.FindingsBetween June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (−5·7 [–19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI −32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes.InterpretationNMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect.FundingNational Institute for Health Research.
Assessment of circulating tumor cell (CTC) patterns among disease-free breast cancer patients vaccinated with a preventive HER2/<i>neu</i> E75-peptide vaccine
Authors: A. Amin, A. Stojadinovic, J. P. Holmes, C. E. Storrer, A. M. Smith, Y. H. Jama, D. Craig, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2007)

3059 Background: The quantity of CTC and post-treatment reduction predict outcome in medically treated metastatic breast cancer patients (BCa); however, the impact on survival of CTC in patients at risk for recurrence rendered free of disease after multimodality treatment is unknown. We conducted a pilot study to assess CTC in clinically disease-free node-positive (NP) BCa patients, and to determine the effect on CTC of vaccination with the immunogenic HER2/neu peptide E75. Methods: The CellSearch System (Veridex, LLC Warren, NJ) was used to enumerate total CTC and HER2/neu + CTC in 20 ml of blood from selected samples obtained from patients (n=16) throughout and after the E75 vaccination series. Standard prognostic factors were collected on these patients as were measures of their immunologic response to the vaccine. Results: 14/16 patients (88%) had at least 1 CTC and 10/16 (63%) had 2 or more CTC identified. Standard clinical prognostic factors (tumor size, grade, lymph nodes and HER2/neu overexpression) did not correlate with number of CTC. Thus far, 9 patients have had multiple samples collected prior to, during and/or after the vaccine series. Early levels of CTC were significantly higher (mean±SE=5.2±0.5) vs. post-vaccination levels (0.3±0.1, p=0.005). Levels of HER2/neu + CTC were also significantly different (early 3.4±0.3 vs. post 0.4±0.1, p=0.01). All patients showed a decline in CTC from early to post levels while demonstrating HER2/neu immunity as measured by DTH to the E75 peptide post- vaccination (22.9±1.8 mm vs. control 4±0.9 mm, p=0.006). Conclusions: CTCs are readily demonstrated in clinically disease-free NP BCa patients. Prognostic indicators do not seem to correlate with the number of CTCs. CTCs decline during the course of vaccination. These data suggest a potential role for the CTC assay in assessing response to preventive vaccine-based immunotherapy. The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy or position of the Departments of Army or Navy, Department of Defense or the U.S. Government. No significant financial relationships to disclose.
Pet imaging of cytotoxic human T cells using an 89Zr-labeled anti-CD8 minibody
Authors: Tove Olafsen, Michael Torgov, Green G Zhang, Jason Romero, Charles Zampila, Filippo Marchioni, Karen Jiang, Jean Gudas, Daulet Satpayev
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Major challenges to advancing the new wave of cancer immunotherapies are to select patients who will respond to single immunotherapies, identify those who need more tailored combination regimens, and then, determine early during treatment whether the therapy is working. "