tbuckley/cabot-search huggingface dataset:
Soundings: Scaling up
Authors: Trisha Greenhalgh
Journal: BMJ (2002)

Regular readers of this column will know that I am convalescing from surgery. Under threat of splitting my stitches, I have agreed to do no strenuous sport, no unloading of shopping trolleys, and no gadding about the country giving lectures for 120 days.

My search for interim sedentary pursuits recently led me—don't laugh—to discover the joys of jigsaw puzzles. The family (to its eternal credit) embraced my new hobby with enthusiasm, and we initially spent many a happy hour gathered round the dining table completing some rustic scene or other, gradually progressing from the sort you can complete on a tea tray to a 4000 piece blockbuster only obtainable by mail order through Nerds Direct.

I can now tell you a thing or two about managing the production team for such an enterprise. Firstly, divide the pieces into seven or eight piles corresponding to grass, sky, buildings, and so on, and allocate a person to each. Ensure that each gets on with his or her own bloc, subcontracting smaller blocs to additional helpers if available. The boundary between blocs must be negotiated by the respective leaders of each bloc, and should be seamless from the viewer's perspective.

Initially, this arrangement worked extremely well, and we were amazed at the pace of progress once we had introduced role allocation, ground rules, and a strict division of labour. But in recent weeks the project has gone pear shaped. The sky expert was the first to abandon his post, on the grounds of intractable boredom. Even though he had responsibility for several varieties of clouds, he apparently felt that his work was less fulfilling than that of the tree expert or the flower expert. The rest of us pulled together in his absence, and recruited a string of temps who lacked commitment and demanded frequent coffee breaks. The original core team members have now begun to experience stress symptoms, claiming they've lost commitment to the big picture.

Increasingly, I try to identify the critical point at which a small, fun initiative became an incongruous unfinished jungle occupying what used to be our social space.

As with jigsaw puzzles, so with hospitals, primary care groups, academic departments. Perhaps the cure for our collective anomie is to acknowledge the downside of economies of scale.
Comprehensive analysis of radiographic, clinical, and inflammatory markers demonstrating changes in lean muscle correlate with outcome in patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) who undergo taxane-based chemotherapy (CT).
Authors: Daniel H. Ahn, Chul Ahn, Veena Nagar, Anne M. Noonan, Matthew Farren, Gregory B. Lesinski, Michael V. Knopp, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2016)

349 Background: MPDAC is associated with a poor prognosis. The mechanisms of carcinogenesis are complex; involve multiple signaling pathways and inflammatory cytokines that may promote cachexia, a major cause of morbidity and mortality in mPDAC. The purpose of this study is to understand factors related to skeletal muscle changes, and its effect on outcomes in pts with mPDAC. Methods: Pt and clinical data were obtained from a recent prospective clinical trial in mPDAC where all pts received first-line taxane-based CT. We examined changes in modified Glasgow prognostic score, neutrophil lymphocyte ratio, a 32-cytokine panel, weight, and skeletal muscle area (SMA), determined by validated methodology with computed tomography, at baseline and cycle 3. We defined &gt; 6cm2 in SMA, correlating to 1kg of skeletal muscle gain (SMG), as significant. Univariate and multivariate Cox regression models were used to determine the association between laboratory, radiographic and clinical findings with progression free survival (PFS) and overall survival (OS). Results: 66 evaluable pts were included. Independent of clinical response, an OS advantage was seen in pts who experienced significant SMG (p = 0.023) and in patients with nominal SMG (p = 0.012). A numerical benefit in PFS was observed with SMG. Decreases in IFN-a (p = 0.024), IFN-g (p = 0.001) and IL-6 (p = 0.042) were inversely associated with SMG. A comprehensive analysis incorporating all relevant laboratory, radiographic and clinical assessments demonstrated a 4.62-month OS advantage in pts with favorable characteristics vs. those with poor prognostic factors (11.47 versus 6.84 mos., p = 0.0029). Conclusions: SMG, or the reversal of cachexia confers an OS advantage in pts with mPDAC treated with taxane-based CT regardless of clinical response. A comprehensive assessment of muscle change is a precise measurement that can identify pts at greatest risk for muscle loss, which could predict for trmt response and pt outcomes. This merits further investigation as a tool and in trials directed at reversing the process of cachexia.
Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study
Authors: Marina Panova-Noeva, Andreas Schulz, M. Iris Hermanns, Vera Grossmann, Evgenia Pefani, Henri M. H. Spronk, Dagmar Laubert-Reh, Harald Binder, Manfred Beutel, Norbert Pfeiffer, Stefan Blankenberg, Tanja Zeller, Thomas Münzel, Karl J. Lackner, Hugo ten Cate, Philipp S. Wild
Journal: Blood (2015)
Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report
Authors: A Fischer, W Friedrich, A Fasth, S Blanche, F Le Deist, D Girault, F Veber, J Vossen, M Lopez, C Griscelli
Journal: Blood (1991)
Human case of autochthonous West Nile virus lineage 2 infection in Italy, September 2011
Authors: P Bagnarelli, K Marinelli, D Trotta, A Monachetti, M Tavio, R Del Gobbo, M R Capobianchi, S Menzo, L Nicoletti, F Magurano, P E Varaldo
Journal: Eurosurveillance (2011)

On 10 September 2011, a patient in his 50s was admitted to hospital in Ancona, Italy, after six days of high fever and no response to antibiotics. West Nile virus (WNV) infection was suspected after tests to determine the aetiology of the fever were inconclusive. On 20 September, WNV-specific IgM and IgG antibodies were detected in the patient’s serum. Genomic sequencing of the viral isolate showed that the virus belonged to WNV lineage 2.
BMET-18ASSESSING CENTRAL NERVOUS SYSTEM (CNS) RESPONSE TO ALECTINIB IN TWO PHASE II STUDIES OF PRE-TREATED ALK+ NON-SMALL CELL LUNG CANCER (NSCLC): RECIST VERSUS RANO CRITERIA
Authors: Sai-Hong Ignatius Ou, Alice Shaw, Leena Gandhi, D. Ross Camidge, Dong-Wan Kim, Brett Hughes, James Chih-Hsin Yang, Hervé Lena, Sophie Golding, Walter Bordogna, Ali Zeaiter, Shirish Gadgeel
Journal: Neuro-Oncology (2015)

BACKGROUND: CNS progression results in frequent treatment failure for ALK+ NSCLC patients receiving the ALK inhibitor crizotinib. CNS efficacy is important in assessing new ALK inhibitors and accurate assessment of response/progression is vital in determining treatment efficacy. Data from two phase II studies in pre-treated ALK+ NSCLC were pooled to examine the CNS efficacy of the highly selective ALK inhibitor alectinib, using both Response Evaluation Criteria in Solid Tumors (RECIST) and Response Assessment in Neuro-Oncology (RANO) criteria to evaluate brain metastases. METHODS: The phase II, single-arm, multicenter studies both enrolled ALK+ NSCLC patients aged ≥18 years who had previously received crizotinib. NP28761 was conducted in North America only (NCT01871805); NP28673 was a global study (NCT01801111). All patients in both studies received 600mg oral alectinib twice daily. Patients underwent imaging at baseline to assess CNS metastases and CNS response was determined by an independent review committee (IRC) according to RECIST v1.1 or RANO criteria. RESULTS: Fifty-one patients had baseline measurable CNS disease by IRC according to RECIST v1.1, and 43 according to RANO criteria. The CNS objective response rate (ORR) was 60.8% by RECIST (95% CI 46.1–74.2; 9 CNS complete responses [CRs]; CNS disease control rate [DCR] 90.2%) and 51.2% by RANO (95% CI 35.5–66.7; 5 CNS CRs; CNS DCR 83.7%). Responses by RECIST included both confirmed and unconfirmed responses; those by RANO had to be confirmed. Median duration of CNS response was 9.1 months with RECIST (95% CI 5.8–NE; 39% of responders with event) and 9.1 months with RANO (95% CI 7.4–NE; 36% of responders with event). CONCLUSION: Alectinib demonstrated promising and durable efficacy in the CNS for ALK+ NSCLC patients previously treated with crizotinib, regardless of the assessment criteria used. Updated results from a later cut-off, plus correlative data and additional analyses, will be presented.
WHO warns of risk of Zika virus in Europe
Authors: Anne Gulland
Journal: BMJ (2016)

The overall risk of Zika virus transmission in Europe this spring and summer is low to moderate, the World Health Organization has warned, although three countries are at high risk of the disease.

A risk assessment published by WHO’s regional office for Europe found a high risk of spread on the Portuguese island of Madeira and in the northeastern Black Sea coast region—namely, Georgia and the southern part of the Russian Federation. These areas have the Aedes aegypti mosquito, the primary vector for the virus.

However, WHO also warned of a moderate risk of spread in 18 countries, primarily in the Mediterranean basin, where the Aedes albopictus mosquito, …
Extended sleep (hypersomnia) in young depressed patients
Authors: D R Hawkins, J M Taub, R L Van de Castle
Journal: American Journal of Psychiatry (1985)

To test the hypothesis that young depressed patients have prolonged rather than shortened sleep, 14 depressed patients aged 17-25 and age-matched normal control subjects were allowed to sleep as long as they wanted. All subjects increased their sleep over baseline values, but the extended sleep period of the depressed patients was almost twice as long as that of the control subjects. The distribution of sleep stages in the extended period did not differ. The depressed patients had changes in the length of REM periods similar to those of older subjects. The findings suggest an interaction between age, sleep, and depression.
Overview: the sex of the therapist
Authors: K M Mogul
Journal: American Journal of Psychiatry (1982)

Research studies about the relevance of therapist gender to assessment, duration of treatment, and satisfaction with treatment or its outcome provide no clear, replicable results salient to decision making. Psychoanalytic and other clinical writings deal with the impact of clinician gender on the course or outcome of psychotherapy. Effects appear to depend on many factors, including the type and goal of psychotherapy, the patient's developmental level, the early relationship with parents, and the nature of object relationships and specific conflictual areas, as well as the therapist' sensitivity and value system regarding gender issues. No specific conclusions as to optimal patient-therapist matches on the basis of therapist sex appear warranted.
The dying psychotherapist
Authors: A H Kaplan, D Rothman
Journal: American Journal of Psychiatry (1986)

A previously unpublished paper by a dying psychotherapist describes the therapeutic use of the ensuing grief reactions of five patients to his terminal illness to help them deal with the effects of their previous losses, deprivations, and abandonments. Follow-up interviews with these patients and their subsequent psychotherapists shed light on the efficacy of such therapeutic efforts, the character of the communication of the terminal illness, the transference and countertransference reactions that interfered with the inevitable separation, and conclusions by previous authors regarding patients' reactions to the deaths of their therapists.
As Opioid Prescribing Guidelines Tighten, Mindfulness Meditation Holds Promise for Pain Relief
Authors: Julie A. Jacob
Journal: JAMA (2016)

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Abstract B03: Identification of epigenetic regulated genes through simultaneous analysis of DNA methylation and chromatin structure in uncultured tumors
Authors: Elinne Becket, Sameer Chopra, Christopher Duymich, Lin J. Justin, Jueng Soo You, Kurinji Pandiyan, Peter W. Nichols, Kimberly D. Siegmund, Peter A. Jones, Gangning Liang
Journal: Cancer Research (2016)

Abstract The contribution of promoter DNA methylation to the alteration of caner related gene expression has been well studied, however, these genes can also potentially be altered by chromatin accessibility without involvement of DNA methylation and can be epigenetically inherited. In this study, we used an assay developed in our laboratory (AcceSssIble) that can simultaneously interrogate DNA methylation and chromatin accessibility allowing us to investigate the epigenetic changes in uncultured clear cell renal cell carcinoma (ccRCC) tumors and normal tissue to uncover genes that contribute to ccRCC tumorigenesis. AcceSssIble is both cost-effective and easily analyzed using simple and straightforward computational analysis. Our study revealed significant changes to the epigenome of ccRCC, especially identifying epigenetically up- (160) or down-regulated genes (180), which are dependent on accessibility changes with (30%) or without (70%) DNA methylation involvement, and which were validated by a cross-correlation of the identified genes with RNA-seq and DNA methylation data from larger cohorts of ccRCC samples from The Cancer Genome Atlas (TCGA). In addition, our findings also revealed these sets of genes not found to be commonly mutated in ccRCC and undergo epigenetic changes at higher frequencies than common ccRCC mutations. In addition, pathway analysis suggests that genetic and epigenetic alterations are independent events, and one such example includes a set of changes in HIF1α signaling pathway genes that are independent of the Von Hippel-Lindau (VHL) status. This suggests a novel epigenetic basis for HIF1αs role during tumorigenesis that may be a common occurrence in ccRCC. Thus, the AcceSssIble analysis on ccRCC samples revealed novel candidates for epigenetic driver genes which were previously undetectable by widely used methylation studies. Overall, this study provides a novel approach that can help identify new epigenetic therapeutic targets and treatment strategies complementing current approaches based primarily on the genetic makeup of primary tumors. Citation Format: Elinne Becket, Sameer Chopra, Christopher Duymich, Lin J. Justin, Jueng Soo You, Kurinji Pandiyan, Peter W. Nichols, Kimberly D. Siegmund, Peter A. Jones, Gangning Liang. Identification of epigenetic regulated genes through simultaneous analysis of DNA methylation and chromatin structure in uncultured tumors. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B03.
Are Gene Expression Microarray Analyses Reliable? A Review of Studies of Retinoic Acid Responsive Genes
Authors: Peter J. van der Spek, Andreas Kremer, Lynn Murry, Michael G. Walker
Journal: Genomics Proteomics & Bioinformatics (2003)

Abstract Microarray analyses of gene expression are widely used, but reports of the same analyses by different groups give widely divergent results, and raise questions regarding reproducibility and reliability. We take as an example recent published reports on microarray experiments that were designed to identify retinoic acid responsive genes. These reports show substantial differences in their results. In this article, we review the methodology, results, and potential causes of differences in these applications of microarrays. Finally, we suggest practices to improve the reliability and reproducibility of microarray experiments.
Polycystic ovary disease in two patients with Briquet's disorder
Authors: H Orenstein, M A Raskind
Journal: American Journal of Psychiatry (1983)

Luteinizing hormone, testosterone, and follicle-stimulating hormone were evaluated by radioimmunoassay in two patients with Briquet's disorder, secondary depression, and menstrual irregularity. In both patients a hormonal pattern consistent with polycystic ovary disease was documented. The ovaries of both patients showed the classic pathologic findings of this disease. These results suggest that the hormonal and ovarian pathologic abnormalities of polycystic ovary disease may be common in patients with menstrual irregularity and Briquet's disorder.
Abstract IA06: SWI/SNF chromatin remodeling complex mutations in cancer: Mechanisms and potential therapeutic insights
Authors: Charles W.M. Roberts
Journal: Cancer Research (2016)

Abstract Data emerging over the last several years implicate the SWI/SNF (BAF) chromatin remodeling complex as a major tumor suppressor as frequent inactivating mutations in at least eight SWI/SNF subunits have been identified in a variety of cancers. These include inactivating mutations of the gene encoding the ARID1A (BAF250a) subunit in ovarian, endometrioid, bladder, stomach, colorectal and pancreatic cancers; of the PBRM1 (BAF180) subunit in renal carcinomas; of the ARID2 subunit in hepatocellular, lung, and pancreas carcinomas as well as melanomas; of the BRD7 subunit in breast cancers; and of the BRG1 (SMARCA4) subunit in non-small cell lung cancers, medulloblastomas and ovarian small cell carcinomas. The SWI/SNF complex includes both core and lineage-specific subunits and utilizes the energy of ATP to modulate chromatin structure and regulate transcription. My laboratory began studying the SWI/SNF complex when the SNF5 (SMARCB1/INI1/BAF47) subunit was first identified as a tumor suppressor over a decade ago when it was found to be recurrently and specifically inactivated in a highly aggressive type of pediatric cancer called malignant rhabdoid tumor. We now study the complex using mouse models, cell lines and primary human tumor samples. Our goals are to elucidate the normal function of the complex, identify the mechanisms by which subunit mutations drive cancer formation, and utilize this insight to identify and develop novel therapeutic approaches. Insights into the normal function of SWI/SNF complexes, the mechanisms by which mutation of the complexes drive cancer formation, and potential therapeutic vulnerabilities created by mutation of the complex will be presented. Citation Format: Charles W.M. Roberts. SWI/SNF chromatin remodeling complex mutations in cancer: Mechanisms and potential therapeutic insights. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr IA06.
Cytologic Study of the gastric aspirate for Carcinoma Cells: Paraffin-Block Technic&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: A WOLLUM, D F GLASER, H C BRYANT, H M POOLARD
Journal: JNCI Journal of the National Cancer Institute (1952)
Organic mood syndrome associated with detoxification from methadone maintenance
Authors: P D Kanof, M J Aronson, R Ness
Journal: American Journal of Psychiatry (1993)

The authors delineate the clinical characteristics of mood state changes that occur in stable opioid-dependent patients undergoing therapeutic detoxification from methadone maintenance treatment.Twenty-four patients participated in a blinded protocol for gradual methadone dose reduction that included weekly assessments of affective state using the Profile of Mood States (POMS) as well as weekly assessments of signs and symptoms of opioid withdrawal. Data obtained before methadone dose reduction and during the 2-week period of maximal dysphoric symptoms were compared. Changes in affective and opioid withdrawal measures were compared in patients who differed in their success in completing the detoxification regimen.Sustained increases in POMS scores of greater than 20 points were observed in 12 of the 24 patients during the course of detoxification. The emergence of symptoms of dysphoria was accompanied by insomnia, loss of appetite, and somatic complaints consistent with symptoms of opioid withdrawal but only minimal levels of objective signs of withdrawal. Greater changes from baseline in mood state and opioid withdrawal measures occurred in patients who were unable to complete the detoxification regimen.The development of an organic mood syndrome is a common occurrence in patients undergoing slow detoxification from methadone maintenance treatment and is associated with a poor outcome.