tbuckley/cabot-search huggingface dataset:
Depression and antiviral response to interferon-based therapy for hepatitis C virus infection
Authors: Jennifer M. Loftis, Benjamin J. Morasco, Peter Hauser
Journal: Hepatology (2010)

Within the context of published literature on interferon (IFN)-induced depression and hepatitis C virus, Leutscher et al.1 highlighted the complex relationships of mood, IFN, antidepressants, and sustained virological response (SVR). In agreement with previous studies, Leutscher et al. found that approximately 30% of patients receiving IFN-based therapy developed major depressive disorder (MDD). They also reported that IFN-induced depression was associated with a reduced likelihood of achieving SVR and stated that their study was the first to report this relationship. However, research has addressed this controversial topic.2-6 A prospective study (n = 394) analyzed the relationship between baseline and new-onset depression and treatment outcomes, and the SVR rates did not differ between patients who developed MDD and those who did not.6 Our retrospective cohort study supports and extends these findings by comparing the rates of antiviral therapy completion and SVR between patients with hepatitis C virus and MDD and those without MDD.7 We found that the MDD group had completion and SVR rates similar to those of patients without MDD. In our study, all patients with MDD were on antidepressant medications before and during antiviral therapy. Untreated IFN-induced depression may lead to dose reductions, premature IFN therapy termination, and compromised treatment outcomes. Leutscher et al.1 reported that almost half of their patients with MDD did not receive psychotropic medication and that their study was insufficiently powered to evaluate whether antidepressants affected viral clearance. Previous literature has shown that careful monitoring of neuropsychiatric symptoms during antiviral therapy and the initiation of antidepressants if significant symptoms of depression develop can be an effective strategy for optimizing treatment outcomes in patients with hepatitis C virus. Jennifer M. Loftis Ph.D.* , Benjamin J. Morasco Ph.D. , Peter Hauser M.D.§, * Research and Development Service, Portland Veterans Affairs Medical Center, Portland, OR, Mental Health and Clinical Neurosciences Division, Portland Veterans Affairs Medical Center, Portland, OR, Department of Psychiatry, Oregon Health and Science University, Portland, OR, § Long Beach Veterans Affairs Medical Center, Long Beach, CA.
[18F]-3′Deoxy-3′-Fluorothymidine Positron Emission Tomography and Breast Cancer Response to Docetaxel
Authors: Kaiyumars B. Contractor, Laura M. Kenny, Justin Stebbing, Lula Rosso, Rizvana Ahmad, Jimmy Jacob, Amarnath Challapalli, Federico Turkheimer, Adil Al-Nahhas, Rohini Sharma, R. Charles Coombes, Eric O. Aboagye
Journal: Clinical Cancer Research (2011)

To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [(18)F]-3'deoxy-3'-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer.This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II-IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles).Average and maximum tumor standardized uptake values at 60 minutes (SUV(60,av) and SUV(60,max)) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 × 10(-5) m(2)/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (P = 0.0003 for SUV(60,av) and P = 0.0002 for SUV(60,max)). Reduction in tumor SUV(60,av) was associated with target lesion size changes midtherapy (Pearson R for SUV(60,av) = 0.64; P = 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV(60,av) in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, K(i)). Docetaxel significantly reduced K(i) by 51.1% (±28.4%, P = 0.0009).Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non-FLT-PET response.
Pathological response to neoadjuvant chemotherapy for inflammatory breast cancer (IBC). Critical evaluation of Chevallier’s and Sataloff’s classifications
Authors: M. Baranzelli, V. Cabaret, L. Vanlemmens, C. Desauw, S. Giard, M. Chauvet, Y. Belkacemi, A. Mailliez, L. Deschildre, J. Bonneterre
Journal: Journal of Clinical Oncology (2006)

10666 Background: The aim of this study was to compare the two most frequently used pathological classifications to assess the response to chemotherapy (CT) in IBC. Methods: The pathological characteristics of 85 inflammatory breast cancers were reviewed. 52 patients (pts) had a post-CT mastectomy , 49 a tumor biopsy before CT and 16 both. Tumor types, grade, hormonal and Her status were evaluated before and after CT, when available. Results: Among 49 pts with initial biopsy, 1 had a high grade intraductular carcinoma and 48 an invasive carcinoma (42 ductular, 5 lobular, 1 mucinous). 27 (56%) invasive tumors were grade 3 and 21 (44%) grade 2, none was grade 1. Median value of mitotic index (Ki 67) was 23%. Hormone receptors (HR) were evaluable for 46 pts; 28 (61%) were negative. 13 (29%) out of 45 evaluable pts were Her2 3+. The pathological response was evaluated according to the Chevallier et Sataloff classifications in the 52 pts with post CT- mastectomy. According to Chevallier there were no grade 1(no microscopic invasive or in situ carcinoma) or 2 (microscopic in situ carcinoma without invasive carcinoma or axillary lymph node metastases), 44 (85%) were grade 3 (invasive carcinoma with fibrosis or sclerosis) and 8 grade 4 (no modification of initial tumor). There was no pathological complete response. According to Sataloff there were 4 grade TA (complete or nearly complete response), 15 (29%) TB (therapeutic response over 50%), 23 (44%) TC (therapeutic response above 50%), 10 TD (no evident therapeutic effect). There were 4 pathological complete responses out of 52 ( 8%). 16 pts had initial biopsy and post chemotherapy mastectomy. According to the OMS clinical classification there were 5 CR, 37 PR, 10 ST. Among the 4 pathological CR according to Sataloff (TA), 2 were CR and 2 PR. Conclusions: In our experience, there was a very poor correlation between the two pathological classifications and between pathological and clinical classifications. A clinical residual tumor can be due to fibrosis only. The classification used for the determination of the pathological response should always be given in clinical studies. No significant financial relationships to disclose.
Effect of Parent Training vs Parent Education on Behavioral Problems in Children With Autism Spectrum Disorder
Authors: Karen Bearss, Cynthia Johnson, Tristram Smith, Luc Lecavalier, Naomi Swiezy, Michael Aman, David B. McAdam, Eric Butter, Charmaine Stillitano, Noha Minshawi, Denis G. Sukhodolsky, Daniel W. Mruzek, Kylan Turner, Tiffany Neal, Victoria Hallett, James A. Mulick, Bryson Green, Benjamin Handen, Yanhong Deng, James Dziura, Lawrence Scahill
Journal: JAMA (2015)

Disruptive behavior is common in children with autism spectrum disorder. Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale randomized trials.To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior.This 24-week randomized trial compared parent training (n = 89) to parent education (n = 91) at 6 centers (Emory University, Indiana University, Ohio State University, University of Pittsburgh, University of Rochester, Yale University). We screened 267 children; 180 children (aged 3-7 years) with autism spectrum disorder and disruptive behaviors were randomly assigned (86% white, 88% male) between September 2010 and February 2014.Parent training (11 core, 2 optional sessions; 2 telephone boosters; 2 home visits) provided specific strategies to manage disruptive behavior. Parent education (12 core sessions, 1 home visit) provided information about autism but no behavior management strategies.Parents rated disruptive behavior and noncompliance on co-primary outcomes: the Aberrant Behavior Checklist-Irritability subscale (range, 0-45) and the Home Situations Questionnaire-Autism Spectrum Disorder (range, 0-9). On both measures, higher scores indicate greater severity and a 25% reduction indicates clinical improvement. A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression (range, 1-7), a secondary outcome, with a positive response less than 3.At week 24, the Aberrant Behavior Checklist-Irritability subscale declined 47.7% in parent training (from 23.7 to 12.4) compared with 31.8% for parent education (23.9 to 16.3) (treatment effect, -3.9; 95% CI, -6.2 to -1.7; P < .001, standardized effect size = 0.62). The Home Situations Questionnaire-Autism Spectrum Disorder declined 55% (from 4.0 to 1.8) compared with 34.2% in parent education (3.8 to 2.5) (treatment effect, -0.7; 95% CI, -1.1 to -0.3; P < .001, standardized effect size = 0.45). Neither measure met the prespecified minimal clinically important difference. The proportions with a positive response on the Clinical Global Impression-Improvement scale were 68.5% for parent training vs 39.6% for parent education (P < .001).For children with autism spectrum disorder, a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes, although the clinical significance of the improvement is unclear. The rate of positive response judged by a blinded clinician was greater for parent training vs parent education.clinicaltrials.gov Identifier: NCT01233414.
Diesel Exhaust Enhances Allergic Airway Inflammation and Hyperresponsiveness in Mice
Authors: YUICHI MIYABARA, HIROHISA TAKANO, TAKAMICHI ICHINOSE, HEUNG-BIN LIM, MASARU SAGAI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We previously reported that the intratracheal instillation of diesel exhaust particles enhances allergic airway inflammation and hyperresponsiveness in mice. However, it is not known whether the effects of such instillation differ from those obtained with the daily inhalation of diesel exhaust. We therefore examined whether the inhalation of diesel exhaust would also enhance allergic reactions. Mice were exposed to diesel exhaust or clean air for 5 wk. After the first week, the animals were sensitized to ovalbumin by intraperitoneal injection. At the end of the exposure period, they underwent an ovalbumin challenge. Control animals received saline instead of ovalbumin. Independently of ovalbumin sensitization, diesel exhaust caused an increase in the numbers of neutrophils and macrophages in bronchoalveolar lavage fluid, whereas a significant increase in eosinophil numbers occurred only after antigen challenge combined with diesel exhaust exposure. Furthermore, ovalbumin alone caused an increase in eosinophil numbers in lung tissue, and this was enhanced by diesel exhaust. Exposure to diesel exhaust combined with ovalbumin sensitization, but not diesel exhaust inhalation alone, enhanced the number of goblet cells in lung tissue, respiratory resistance, production of ovalbumin-specific immunoglobulin E and G1 in the serum, and expression of interleukin-5 in lung tissue.
Warm up practices of golfers: are they adequate?: Table 1
Authors: A J Fradkin, C F Finch, C A Sherman
Journal: British Journal of Sports Medicine (2001)

Background —Although it is widely recommended that golfers warm up before play or practice to enhance their physical performance and reduce their injury risk, it is not known to what extent they actually undertake such warm up procedures. Objective —To collect information about the proportion of golfers who actively warm up and to determine the types of warm up behaviours. Methods —This study was conducted over three weeks at three different golfing venues: a private golf course, a public golf course, and a golf driving range. Golfers' warm up behaviours, defined as any form of preparative exercise, were recorded by direct observation by two independent observers. Results —The sample consisted of 1040 amateur golfers (852 men and 188 women) aged at least 18 years. Only 54.3% (95% confidence interval 49.8 to 58.8) performed some form of warm up activity. Air swings on the tee were the most commonly observed warm up activity, with 88.7% (95% confidence interval 85.9 to 91.5) of golfers who warmed up performing these. Conclusions —Only a small proportion of amateur golfers perform appropriate warm up exercises. To improve on this, golfers should be educated about the possible benefits of warming up and be shown how to perform an appropriate warm up routine.
Experiences of hearing voices: analysis of a novel phenomenological survey
Authors: Angela Woods, Nev Jones, Ben Alderson-Day, Felicity Callard, Charles Fernyhough
Journal: The Lancet Psychiatry (2015)

Auditory hallucinations--or voices--are a common feature of many psychiatric disorders and are also experienced by individuals with no psychiatric history. Understanding of the variation in subjective experiences of hallucination is central to psychiatry, yet systematic empirical research on the phenomenology of auditory hallucinations remains scarce. We aimed to record a detailed and diverse collection of experiences, in the words of the people who hear voices themselves.We made a 13 item questionnaire available online for 3 months. To elicit phenomenologically rich data, we designed a combination of open-ended and closed-ended questions, which drew on service-user perspectives and approaches from phenomenological psychiatry, psychology, and medical humanities. We invited people aged 16-84 years with experience of voice-hearing to take part via an advertisement circulated through clinical networks, hearing voices groups, and other mental health forums. We combined qualitative and quantitative methods, and used inductive thematic analysis to code the data and χ(2) tests to test additional associations of selected codes.Between Sept 9 and Nov 29, 2013, 153 participants completed the study. Most participants described hearing multiple voices (124 [81%] of 153 individuals) with characterful qualities (106 [69%] individuals). Less than half of the participants reported hearing literally auditory voices--70 (46%) individuals reported either thought-like or mixed experiences. 101 (66%) participants reported bodily sensations while they heard voices, and these sensations were significantly associated with experiences of abusive or violent voices (p=0·024). Although fear, anxiety, depression, and stress were often associated with voices, 48 (31%) participants reported positive emotions and 49 (32%) reported neutral emotions. Our statistical analysis showed that mixed voices were more likely to have changed over time (p=0·030), be internally located (p=0·010), and be conversational in nature (p=0·010).This study is, to our knowledge, the largest mixed-methods investigation of auditory hallucination phenomenology so far. Our survey was completed by a diverse sample of people who hear voices with various diagnoses and clinical histories. Our findings both overlap with past large-sample investigations of auditory hallucination and suggest potentially important new findings about the association between acoustic perception and thought, somatic and multisensorial features of auditory hallucinations, and the link between auditory hallucinations and characterological entities.Wellcome Trust.
TRANSMISSION OF MYELOID LEUKEMIA OF MICE
Authors: J. Furth
Journal: The Journal of Experimental Medicine (1935)

A transmissible strain of myeloid leukemia of mice is described. It can be readily passed from diseased to healthy mice by the transfer of tissues that contain live cells; but inoculation fails when the latter are not present. Inoculation is successful in almost every mouse whose resistance is lowered by X-rays. It is often successful in mice related to the animal in which the spontaneous leukemia took its origin, and occasionally successful in mice unrelated to it. The systemic diffuse disease (myeloid leukemia) is produced only by intravenous inoculation with relatively large doses, whereas subcutaneous or intraperitoneal inoculation results in the formation of tumors composed of myelocytes with basophile granules, in other words malignant blood cells of the strain described. Intravenous inoculation with small doses in susceptible mice, or similar inoculation with larger doses in somewhat resistant mice, results in the formation of tumors composed of myelocytes (multiple myeloma).
Proximal Dominant Hereditary Motor and Sensory Neuropathy With Proximal Dominance Association With Mutation in the TRK-Fused Gene
Authors: Sang-Soo Lee, Hye Jin Lee, Jin-Mo Park, Young Bin Hong, Kee-Duk Park, Jeong Hyun Yoo, Heasoo Koo, Sung-Chul Jung, Hyung Soon Park, Ji Hyun Lee, Min Goo Lee, Young Se Hyun, Khriezhanou Nakhro, Ki Wha Chung, Byung-Ok Choi
Journal: JAMA Neurology (2013)

<h3>Importance</h3>Hereditary motor and sensory neuropathy with proximal dominance (HMSN-P) has been reported as a rare type of autosomal dominant adult-onset Charcot-Marie-Tooth disease. HMSN-P has been described only in Japanese descendants since 1997, and the causative gene has not been found.<h3>Objectives</h3>To identify the genetic cause of HMSN-P in a Korean family and determine the pathogenic mechanism.<h3>Design</h3>Genetic and observational analysis.<h3>Setting</h3>Translational research center for rare neurologic disease.<h3>Participants</h3>Twenty-eight individuals (12 men and 16 women) from a Korean family with HMSN-P.<h3>Main Outcome Measures</h3>Whole-exome sequencing, linkage analysis, and magnetic resonance imaging.<h3>Results</h3>Through whole-exome sequencing, we revealed that HMSN-P is caused by a mutation in the TRK-fused gene (TFG). Clinical heterogeneities were revealed in HMSN-P between Korean and Japanese patients. The patients in the present report showed faster progression of the disease compared with the Japanese patients, and sensory nerve action potentials of the sural nerve were lost in the early stages of the disease. Moreover, tremor and hyperlipidemia were frequently found. Magnetic resonance imaging of the lower extremity revealed a distinct proximal dominant and sequential pattern of muscular involvement with a clearly different pattern than patients with Charcot-Marie-Tooth disease type 1A. Particularly, endoneural blood vessels revealed marked narrowing of the lumen with swollen vesicular endothelial cells.<h3>Conclusions and Relevance</h3>The underlying cause of HMSN-P proves to be a mutation in TFG that lies on chromosome 3q13.2. This disease is not limited to Japanese descendants, and marked narrowing of endoneural blood vessels was noted in the present study. We believe that TFG can affect the peripheral nerve tissue.
Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.
Authors: S Mazel, D Burtrum, H T Petrie
Journal: The Journal of Experimental Medicine (1996)

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point.
Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.
Authors: M R Szewczuk, M Halliday, T W Soybel, D Turner, G W Siskind, M E Weksler
Journal: The Journal of Experimental Medicine (1977)

Tolerance can be induced in adult mice by a single intravenous injection of 0.5 mg dinitrophenylated bovine gamma globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody-forming cells in partially tolerant animals and a prompt reversibility on cell transfer. The overall properties of this unresponsive state are consistent with the hypothesis that it is mediated by the production of small amounts of high affinity antibody in response to the tolerance-inducing injection of antigen. In contrast, the unresponsiveness induced in reconstituted, irradiated mice by the same procedure was characterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected and mixed cell transfer studies were consitent with the view that this unresponsive state represented a B-lymphocyte clonal deletion. The presence or absence of T lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolernace induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible "high affinity"-type tolerance is obtained such as is typical of normal intact animals. Restorationof a "normal" response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. It is suggested that the structural integrity of the lymphoid tissue is critical in determining whether B cell will be rendered tolerant after exposure to antigen in vivo.