tbuckley/cabot-search huggingface dataset:
Differentiation of tumour-stage mycosis fungoides, psoriasis vulgaris and normal controls in a pilot study using serum proteomic analysis
Authors: E.W. Cowen, C-W. Liu, S.M. Steinberg, S. Kang, E.C. Vonderheid, H.S. Kwak, S. Booher, E.F. Petricoin, L.A. Liotta, G. Whiteley, S.T. Hwang
Journal: British Journal of Dermatology (2007)

Serum proteomic analysis is an analytical technique utilizing high-throughput mass spectrometry (MS) in order to assay thousands of serum proteins simultaneously. The resultant 'proteomic signature' has been used to differentiate benign and malignant diseases, enable disease prognosis, and monitor response to therapy.This pilot study was designed to determine if serum protein patterns could be used to distinguish patients with tumour-stage mycosis fungoides (MF) from patients with a benign inflammatory skin condition (psoriasis) and/or subjects with healthy skin.Serum was analysed from 45 patients with tumour-stage MF, 56 patients with psoriasis, and 47 controls using two MS platforms of differing resolution. An artificial intelligence-based classification model was constructed to predict the presence of the disease state based on the serum proteomic signature.Based on data from an independent testing set (14-16 subjects in each group), MF was distinguished from psoriasis with 78.6% (or 78.6%) sensitivity and 86.7% (or 93.8%) specificity, while sera from patients with psoriasis were distinguished from those of nonaffected controls with 86.7% (or 93.8%) sensitivity and 75.0% (or 76.9%) specificity (depending on the MS platform used). MF was distinguished from unaffected controls with 61.5% (or 71.4%) sensitivity and 91.7% (or 92.9%) specificity. In addition, a secondary survival analysis using 11 MS peaks identified significant survival differences between two MF groups (all P-values <0.05).Serum proteomics should be further investigated for its potential to identify patients with neoplastic skin disease and its ability to determine disease prognosis.
Twenty-Year Follow-up of a Randomized Study Comparing Breast-Conserving Surgery with Radical Mastectomy for Early Breast Cancer
Authors: Umberto Veronesi, Natale Cascinelli, Luigi Mariani, Marco Greco, Roberto Saccozzi, Alberto Luini, Marisel Aguilar, Ettore Marubini
Journal: New England Journal of Medicine (2002)

We conducted 20 years of follow-up of women enrolled in a randomized trial to compare the efficacy of radical (Halsted) mastectomy with that of breast-conserving surgery.From 1973 to 1980, 701 women with breast cancers measuring no more than 2 cm in diameter were randomly assigned to undergo radical mastectomy (349 patients) or breast-conserving surgery (quadrantectomy) followed by radiotherapy to the ipsilateral mammary tissue (352 patients). After 1976, patients in both groups who had positive axillary nodes also received adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil.Thirty women in the group that underwent breast-conserving therapy had a recurrence of tumor in the same breast, whereas eight women in the radical-mastectomy group had local recurrences (P<0.001). The crude cumulative incidence of these events was 8.8 percent and 2.3 percent, respectively, after 20 years. In contrast, there was no significant difference between the two groups in the rates of contralateral-breast carcinomas, distant metastases, or second primary cancers. After a median follow-up of 20 years, the rate of death from all causes was 41.7 percent in the group that underwent breast-conserving surgery and 41.2 percent in the radical-mastectomy group (P=1.0). The respective rates of death from breast cancer were 26.1 percent and 24.3 percent (P=0.8).The long-term survival rate among women who undergo breast-conserving surgery is the same as that among women who undergo radical mastectomy. Breast-conserving surgery is therefore the treatment of choice for women with relatively small breast cancers.
Treatment of Complicated Grief
Authors: Katherine Shear, Ellen Frank, Patricia R. Houck, Charles F. Reynolds
Journal: JAMA (2005)

Complicated grief is a debilitating disorder associated with important negative health consequences, but the results of existing treatments for it have been disappointing.To compare the efficacy of a novel approach, complicated grief treatment, with a standard psychotherapy (interpersonal psychotherapy).Two-cell, prospective, randomized controlled clinical trial, stratified by manner of death of loved one and treatment site.A university-based psychiatric research clinic as well as a satellite clinic in a low-income African American community between April 2001 and April 2004.A total of 83 women and 12 men aged 18 to 85 years recruited through professional referral, self-referral, and media announcements who met criteria for complicated grief.Participants were randomly assigned to receive interpersonal psychotherapy (n = 46) or complicated grief treatment (n = 49); both were administered in 16 sessions during an average interval of 19 weeks per participant.Treatment response, defined either as independent evaluator-rated Clinical Global Improvement score of 1 or 2 or as time to a 20-point or better improvement in the self-reported Inventory of Complicated Grief.Both treatments produced improvement in complicated grief symptoms. The response rate was greater for complicated grief treatment (51%) than for interpersonal psychotherapy (28%; P = .02) and time to response was faster for complicated grief treatment (P = .02). The number needed to treat was 4.3.Complicated grief treatment is an improved treatment over interpersonal psychotherapy, showing higher response rates and faster time to response.
mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation
Authors: Kristen N. Pollizzi, Chirag H. Patel, Im-Hong Sun, Min-Hee Oh, Adam T. Waickman, Jiayu Wen, Greg M. Delgoffe, Jonathan D. Powell
Journal: Journal of Clinical Investigation (2015)

Activation of mTOR-dependent pathways regulates the specification and differentiation of CD4+ T effector cell subsets. Herein, we show that mTOR complex 1 (mTORC1) and mTORC2 have distinct roles in the generation of CD8+ T cell effector and memory populations. Evaluation of mice with a T cell-specific deletion of the gene encoding the negative regulator of mTORC1, tuberous sclerosis complex 2 (TSC2), resulted in the generation of highly glycolytic and potent effector CD8+ T cells; however, due to constitutive mTORC1 activation, these cells retained a terminally differentiated effector phenotype and were incapable of transitioning into a memory state. In contrast, CD8+ T cells deficient in mTORC1 activity due to loss of RAS homolog enriched in brain (RHEB) failed to differentiate into effector cells but retained memory characteristics, such as surface marker expression, a lower metabolic rate, and increased longevity. However, these RHEB-deficient memory-like T cells failed to generate recall responses as the result of metabolic defects. While mTORC1 influenced CD8+ T cell effector responses, mTORC2 activity regulated CD8+ T cell memory. mTORC2 inhibition resulted in metabolic reprogramming, which enhanced the generation of CD8+ memory cells. Overall, these results define specific roles for mTORC1 and mTORC2 that link metabolism and CD8+ T cell effector and memory generation and suggest that these functions have the potential to be targeted for enhancing vaccine efficacy and antitumor immunity.
The Clinical COPD Questionnaire: response to pulmonary rehabilitation and minimal clinically important difference
Authors: Samantha S C Kon, Deniz Dilaver, Manvi Mittal, Claire M Nolan, Amy L Clark, Jane L Canavan, Sarah E Jones, Michael I Polkey, William D-C Man
Journal: Thorax (2013)

<h3>Background</h3> The Clinical COPD Questionnaire (CCQ) is a simple 10-item, health-related quality of life questionnaire (HRQoL) with good psychometric properties. However, little data exists regarding the responsiveness of the CCQ to pulmonary rehabilitation (PR) or the minimal clinically important difference (MCID). The study aims were to assess the responsiveness of the CCQ to PR, to compare the responsiveness of the CCQ to other HRQoL questionnaires and to provide estimates for the MCID. <h3>Methods</h3> The CCQ, St George9s Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ) and COPD Assessment Test (CAT) were measured in 261 patients with COPD before and after outpatient PR. Pre to post PR changes and Cohen9s effect size were calculated. Changes in CCQ were compared with changes in other HRQoL questionnaires. Using an anchor-based approach and receiver operating characteristic (ROC) curves, the CCQ change cutoffs that identified patients achieving the known MCID for other health status questionnaires with PR were identified. <h3>Results</h3> The CCQ, SGRQ, CRQ and CAT all significantly improved with PR with an effect size of −0.39, −0.33, 0.62 and −0.25, respectively. CCQ change correlated significantly with change in SGRQ, CRQ and CAT (r=0.48, −0.56, 0.54, respectively; all p&lt;0.001). ROC curves consistently identified a CCQ change cutoff of −0.4 as the best discriminating value to identify the MCID for the SGRQ, CRQ and CAT (area under curve: 0.71, 0.75 and 0.77, respectively; all p&lt;0.001). <h3>Conclusions</h3> The CCQ is responsive to PR with an estimated clinically important improvement of −0.4 points. The CCQ is a practical alternative to more time-consuming measures of HRQoL.
Gestational Diabetes Mellitus: Squaring the Circle
Authors: Gojka Roglic, Stephen Colagiuri
Journal: Diabetes Care (2014)

The World Health Organization (WHO) has recently released a new classification and diagnostic criteria for hyperglycemia first diagnosed in pregnancy (1). These new criteria are an update of the 1999 WHO criteria, which defined gestational diabetes mellitus (GDM) as diabetes or impaired glucose tolerance with onset or first recognition in pregnancy. This definition was not based on a review of the evidence, but took into account the already recognized negative effect of uncontrolled diabetes on pregnancy outcome and a suspicion that milder hyperglycemia in pregnancy could also have a negative effect on maternal and child outcomes (2).

The ad hoc expert group convened for the update accepted the reasoning of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) (3) and decided to endorse the separation of diabetes and GDM. The WHO has accepted the same glucose diagnostic thresholds for GDM as proposed by IADPSG.

Globally, there is general agreement over how to diagnose diabetes in nonpregnant individuals, based on the relationship between glycemia and microvascular complications specific for diabetes. Such is …
Blood pressure and hypertension in athletes: a systematic review
Authors: H M Berge, C B Isern, E Berge
Journal: British Journal of Sports Medicine (2015)

Objective Hypertension is reported to be the most prevalent risk factor for cardiovascular disease in elite athletes. We aimed to review blood pressure (BP) and prevalence of hypertension in different elite athletes, and study whether there was an association between high BP and left ventricular hypertrophy (LVH). Methods A systematic review of studies reporting BP in athletes using search strategies developed for PubMed and EMBASE, including only studies with ≥100 participants. We collected data on BP, prevalence of hypertension, LVH and methods of BP measurement. Results Of 3723 records identified, 51 met the inclusion criteria. These included men and women (n=138 390), aged mostly between 18 and 40 years, from varied sports disciplines. Mean systolic BP varied from 109±11 to 138±7 mm Hg and mean diastolic BP from 57±12 to 92±10 mm Hg. Strength-trained athletes had higher BP than endurance-trained athletes (131.3±5.3/77.3±1.4 vs 118.6±2.8/71.8±1.2 mm Hg, p&lt;0.05), and there was a trend towards a higher BP in athletes training ≥10 h compared with others (121.8±3.8/73.8±2.5 vs 117.6±3.3/66.8±6.9, p=0.058), but overall there was no significant difference in BP between athletes and controls. The prevalence of hypertension varied from 0% to 83%. Some studies showed an association between high BP and LVH. Measurement methods were poorly standardised. Conclusions BP and prevalence of hypertension in athletes varied considerably partly because of variations in methodology, but type and intensity of training may contribute towards higher BP. High BP may be associated with LVH.
miRNA-200c inhibits invasion and metastasis of human non-small cell lung cancer by directly targeting ubiquitin specific peptidase 25
Authors: Jing Li, Qiang Tan, Mingxia Yan, Lei Liu, Hechun Lin, Fangyu Zhao, Guoliang Bao, Hanwei Kong, Chao Ge, Fanglin Zhang, Tao Yu, Jinjun Li, Xianghuo He, Ming Yao
Journal: Molecular Cancer (2014)

Growing evidence indicates that miR-200c is involved in carcinogenesis and tumor progression in non-small-cell lung cancer (NSCLC). However, its precise biological role remains largely elusive. The functions of miR-200c and USP25 in migration/invasion and lung metastasis formation were determined by transwell and tail vein injection assays, respectively. The potential regulatory targets of miR-200c were determined by prediction tools, correlation with target protein expression, and luciferase reporter assay. The mRNA expression levels of miR-200c and USP25 were examined in NSCLC cell lines and patient specimens using quantitative reverse transcription-PCR. The protein expression levels of USP25 were examined in NSCLC cell lines and patient specimens using western blot and immunohistochemical staining. We demonstrated that over-expression of miR-200c inhibited NSCLC cells migration, invasion, epithelial-mesenchymal transition (EMT) in vitro and lung metastasis formation in vivo. Further studies revealed that USP25 was a downstream target of miR-200c in NSCLC cells as miR-200c bound directly to the 3'-untranslated region of USP25, thus reducing both the messenger RNA and protein levels of USP25. Silencing of the USP25 gene recapitulated the effects of miR-200c over-expression. Clinical analysis indicated that miR-200c was negatively correlated with clinical stage, lymph node metastasis in NSCLC patients. Moreover, USP25 protein and mRNA level expressions were higher in NSCLC patients, compared to healthy control, and correlated with clinical stage and lymphatic node metastasis. These findings indicate that miR-200c exerts tumor-suppressive effects for NSCLC through the suppression of USP25 expression and suggests a new therapeutic application of miR-200c in the treatment of NSCLC.
STUDIES ON DELAYED HYPERSENSITIVITY
Authors: Bernard B. Levine
Journal: The Journal of Experimental Medicine (1965)

Experiments carried out with several well defined antigenic systems (hapten conjugates of poly-L-lysine and guinea pig serum albumin) in guinea pigs demonstrated that: 1. Arthus reactions also manifest carrier specificity, although to a smaller extent than do delayed hypersensitivity reactions. 2. Desensitization by injection of minute doses of antigen results in moderate specific desensitization of delayed hypersensitivity without desensitization of Arthus reactivity to the same antigenic determinant. 3. Insoluble antigen-antibody complexes prepared from high affinity guinea pig antibodies can elicit specific delayed skin reactions in sensitized guinea pigs. 4. Homologous conjugates of structurally similar haptens show considerably less cross-reactivity in delayed reactions than in immediate hypersensitivity reactions to the same antigenic determinant. These experimental results are interpreted as indicating that delayed hypersensitivity reactions in the guinea pig are mediated by "antibodies" of comparatively high binding affinities. High binding affinities are achieved for these antibodies more likely by closer structural adaptation between antigen and antibody than by a larger area of specific contact.
HSC commitment–associated epigenetic signature is prognostic in acute myeloid leukemia
Authors: Boris Bartholdy, Maximilian Christopeit, Britta Will, Yongkai Mo, Laura Barreyro, Yiting Yu, Tushar D. Bhagat, Ujunwa C. Okoye-Okafor, Tihomira I. Todorova, John M. Greally, Ross L. Levine, Ari Melnick, Amit Verma, Ulrich Steidl
Journal: Journal of Clinical Investigation (2014)

Acute myeloid leukemia (AML) is characterized by disruption of HSC and progenitor cell differentiation. Frequently, AML is associated with mutations in genes encoding epigenetic modifiers. We hypothesized that analysis of alterations in DNA methylation patterns during healthy HSC commitment and differentiation would yield epigenetic signatures that could be used to identify stage-specific prognostic subgroups of AML. We performed a nano HpaII-tiny-fragment-enrichment-by-ligation-mediated-PCR (nanoHELP) assay to compare genome-wide cytosine methylation profiles between highly purified human long-term HSC, short-term HSC, common myeloid progenitors, and megakaryocyte-erythrocyte progenitors. We observed that the most striking epigenetic changes occurred during the commitment of short-term HSC to common myeloid progenitors and these alterations were predominantly characterized by loss of methylation. We developed a metric of the HSC commitment–associated methylation pattern that proved to be highly prognostic of overall survival in 3 independent large AML patient cohorts, regardless of patient treatment and epigenetic mutations. Application of the epigenetic signature metric for AML prognosis was superior to evaluation of commitment-based gene expression signatures. Together, our data define a stem cell commitment–associated methylome that is independently prognostic of poorer overall survival in AML.
Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis
Authors: Marieta Caganova, Chiara Carrisi, Gabriele Varano, Federica Mainoldi, Federica Zanardi, Pierre-Luc Germain, Laura George, Federica Alberghini, Luca Ferrarini, Asoke K. Talukder, Maurilio Ponzoni, Giuseppe Testa, Takuya Nojima, Claudio Doglioni, Daisuke Kitamura, Kai-M. Toellner, I-hsin Su, Stefano Casola
Journal: Journal of Clinical Investigation (2013)

Protection against deadly pathogens requires the production of high-affinity antibodies by B cells, which are generated in germinal centers (GCs). Alteration of the GC developmental program is common in many B cell malignancies. Identification of regulators of the GC response is crucial to develop targeted therapies for GC B cell dysfunctions, including lymphomas. The histone H3 lysine 27 methyltransferase enhancer of zeste homolog 2 (EZH2) is highly expressed in GC B cells and is often constitutively activated in GC-derived non-Hodgkin lymphomas (NHLs). The function of EZH2 in GC B cells remains largely unknown. Herein, we show that Ezh2 inactivation in mouse GC B cells caused profound impairment of GC responses, memory B cell formation, and humoral immunity. EZH2 protected GC B cells against activation-induced cytidine deaminase (AID) mutagenesis, facilitated cell cycle progression, and silenced plasma cell determinant and tumor suppressor B-lymphocyte–induced maturation protein 1 (BLIMP1). EZH2 inhibition in NHL cells induced BLIMP1, which impaired tumor growth. In conclusion, EZH2 sustains AID function and prevents terminal differentiation of GC B cells, which allows antibody diversification and affinity maturation. Dysregulation of the GC reaction by constitutively active EZH2 facilitates lymphomagenesis and identifies EZH2 as a possible therapeutic target in NHL and other GC-derived B cell diseases.
A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group
Authors: P. Pautier, A. Floquet, L. Gladieff, E. Bompas, I. Ray-Coquard, S. Piperno-Neumann, F. Selle, C. Guillemet, B. Weber, R. Largillier, F. Bertucci, P. Opinel, F. Duffaud, A. Reynaud-Bougnoux, C. Delcambre, N. Isambert, P. Kerbrat, G. Netter-Pinon, N. Pinto, P. Duvillard, C. Haie-Meder, C. Lhommé, A. Rey
Journal: Annals of Oncology (2012)
Case–control study to identify factors associated with mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia
Authors: D. Marchaim, K.S. Kaye, V.G. Fowler, D.J. Anderson, V. Chawla, Y. Golan, A.W. Karchmer, Y. Carmeli
Journal: Clinical Microbiology and Infection (2009)
NOTES ON THE TREATMENT OF ORAL AND RECTAL CANCER BY RADIUM
Authors: B. T. Rose
Journal: BMJ (1928)

RECTAL CANCER.[MEDICAL oa conisisting of agglutinated masses of the germs.In the case of a; negative reaction, the emulsion is smooth and fi ee from particles.In this manner tlle whole of the eighty-four serums wer-e quickly tested and those giving a positive reaction carefuilly note(l.
Head injuries in the female football player: incidence, mechanisms, risk factors and management
Authors: Jiri Dvorak, Paul McCrory, Donald T Kirkendall
Journal: British Journal of Sports Medicine (2007)

Although all injuries in sports are a concern for participants, head injuries are particularly troublesome because of the potential for long-term cognitive deficits. To prevent any specific injury, it is important to understand the basic frequency and incidence of injury and then the mechanism of injury. Once these are established, prevention programmes can be tested to see if the rate of injury changes. A primary problem with head injuries is recognising that the injury has occurred. Many athletes are not aware of the seriousness of concussive injury, thus this type of injury is probably under-reported. Once the diagnosis of a concussion is made, the next difficult decision is when to return a player to the game. These two management issues dominate the continuing development of understanding of concussive head injury. This paper explores the known gender differences between head injuries and highlights the areas that need to be considered in future research.
Angiotensin-converting enzyme inhibition is associated with reduced troponin release in non–ST-elevation acute coronary syndromes
Authors: Simon Kennon, Khalid Barakat, Graham A Hitman, Christopher P Price, Peter G Mills, Kulasegaram Ranjadayalan, Jackie Cooper, Heather Clark, Adam D Timmis
Journal: Journal of the American College of Cardiology (2001)
Facioskeletal changes in children with juvenile idiopathic arthritis
Authors: M Twilt, A J M Schulten, P Nicolaas, A Dülger, L W A van Suijlekom-Smit
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To investigate the facioskeletal morphology in patients with juvenile idiopathic arthritis (JIA) with and without temporomandibular joint (TMJ) involvement. <b>Methods:</b> Eighty five patients were included. TMJ involvement was defined by orthopantomogram alterations. Lateral cephalograms were used to determine linear and angular measurements and occlusion. <b>Results:</b> Patients regardless of their TMJ status had a 67% chance for retrognathia and a 52% chance for posterior rotation of the mandible and, respectively, 82% and 58% if TMJ involvement were present. Changes were not uniformly distributed among the different subtypes. <b>Conclusion:</b> Patients with JIA have an altered facial morphology, especially in the presence of TMJ involvement.
Reply
Authors: John Penders, Monique Mommers, Frederika A. van Nimwegen, Ellen E. Stobberingh, Dirkje S. Postma, Gerard H. Koppelman, Marjan Kerkhof, Naomi E. Reijmerink, Edward Dompeling, Piet A. van den Brandt, Isabel Ferreira, Carel Thijs
Journal: Journal of Allergy and Clinical Immunology (2011)