tbuckley/cabot-search huggingface dataset:
A1.76 Higher proportions of pathogenic CCR6+ T cell subpopulations in ACPA+ compared to ACPA- patients with early rheumatoid arthritis
Authors: Sandra M J Paulissen, Jan Piet van Hamburg, Nadine Davelaar, Heleen Vroman, Johanna M W Hazes, Pascal H P de Jong, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Presence of serum anti-citrullinated protein antibodies (ACPAs) in patients with rheumatoid arthritis (RA) predicts worse disease course and a more erosive disease. In the pathogenesis of RA, inflammatory T cells play a central role. In this context, we recently found increased proportions of pathogenic peripheral CCR6+ memory T helper cells in patients with early RA compared to healthy individuals. However, it is unclear how T cell proportions are distributed between ACPA+ and ACPA- patients. Therefore alterations in peripheral T cell populations and their pathogenic potential were examined in ACPA+ and ACPA- patient groups. <h3>Materials and Methods</h3> A nested matched case control study was performed including 27 ACPA+ and 27 ACPA- patients with early RA. T cell profiles (Treg, Th1, Th2, Th17, Th22 and various less well classified populations) from these ACPA+ and ACPA- patients were generated based on chemokine receptor, cytokine and transcription factor expression. Differentially present T cell populations were isolated from peripheral blood and analysed for their pathologic potential in a co-culture system with RA derived synovial fibroblasts (RASF). <h3>Results</h3> In comparison to ACPA- patients, ACPA+ patients have higher proportions of regulatory T cells (Treg) and CD4+ memory CCR6+ T cells. Since the CCR6+ T cell population is still a heterogeneous population, four CCR6+ T cell subpopulations were distinguished by differential expression of CXCR3 and CCR4. All four CCR6+ subpopulations shared Th17 cell characteristics such as Rorγt and CCL20 expression, but IL-17A, IL-17F, IL-22 and IFN-γ expression differed greatly between these subpopulations. However, even the population with lowest expression of these cytokines showed high pathological potential as shown by stimulating IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression upon co-culture with RASF. Indeed, despite dissimilar Th17 and Th1 characteristics between the CCR6+ subpopulations, all four showed highly increased pathological potential in co-culture compared to naive and Th1 cells. <h3>Conclusions</h3> ACPA+ and ACPA- patients can be distinguished by the distribution of Treg and CCR6+ T cell subpopulations. These CCR6+ subpopulations exhibit dissimilar Th17 and Th1 characteristics, but all possess high pathological potential, including the population that has low IL-17A/F and IL-22 expression. These findings indicate a prominent role of CCR6+ T cells in the pathogenesis of ACPA+ patients with early RA and may contribute to the worse disease outcome in ACPA+ patients.
Late Improvement in Consciousness after Post-Traumatic Vegetative State
Authors: Nancy L. Childs, Walt N. Mercer
Journal: New England Journal of Medicine (1996)

The vegetative state is a cognitively unresponsive state in which the patient's eyes are open.1 The diagnosis is made clinically in patients who are awake but have no behavioral evidence of awareness of self or the environment. The absence of communication, response to commands, behavioral response to stimulation, and intentional movement confirms the lack of awareness.2–5 The vegetative state is considered persistent if it lasts longer than 1 month after the injury,5,6 and permanent if it lasts for 12 months, since improvement after this time is extremely rare.4,6,7 We report a case of emergence from a . . .
Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder
Authors: Cora Braun, Tom Bschor, Jeremy Franklin, Christopher Baethge
Journal: Psychotherapy and Psychosomatics (2016)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; It is unclear whether antidepressants can prevent suicides or suicide attempts, particularly during long-term use. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We carried out a comprehensive review of long-term studies of antidepressants (relapse prevention). Sources were obtained from 5 review articles and by searches of MEDLINE, PubMed Central and a hand search of bibliographies. We meta-analyzed placebo-controlled antidepressant RCTs of at least 3 months' duration and calculated suicide and suicide attempt incidence rates, incidence rate ratios and Peto odds ratios (ORs). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Out of 807 studies screened 29 were included, covering 6,934 patients (5,529 patient-years). In total, 1.45 suicides and 2.76 suicide attempts per 1,000 patient-years were reported. Seven out of 8 suicides and 13 out of 14 suicide attempts occurred in antidepressant arms, resulting in incidence rate ratios of 5.03 (0.78-114.1; p = 0.102) for suicides and of 9.02 (1.58-193.6; p = 0.007) for suicide attempts. Peto ORs were 2.6 (0.6-11.2; nonsignificant) and 3.4 (1.1-11.0; p = 0.04), respectively. Dropouts due to unknown reasons were similar in the antidepressant and placebo arms (9.6 vs. 9.9%). The majority of suicides and suicide attempts originated from 1 study, accounting for a fifth of all patient-years in this meta-analysis. Leaving out this study resulted in a nonsignificant incidence rate ratio for suicide attempts of 3.83 (0.53-91.01). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Therapists should be aware of the lack of proof from RCTs that antidepressants prevent suicides and suicide attempts. We cannot conclude with certainty whether antidepressants increase the risk for suicide or suicide attempts. Researchers must report all suicides and suicide attempts in RCTs.
Impact of Fluorodeoxyglucose Positron Emission Tomography on the Clinical Management of Patients With Glioma
Authors: A Deshmukh, J A Scott, E L Palmer, F H Hochberg, M Gruber, A J Fischman
Journal: Clinical Nuclear Medicine (1996)

The past decade has seen the identification of many clinical settings in the treatment of primary brain tumors in which information from fluorodeoxyglucose positron emission tomography (FDG-PET) might be useful, if not essential, to therapeutic formulation. FDG-PET is currently used at referral centers in the management of primary brain tumors. The clinical pattern of FDG-PET use was assessed and its value compared to other information sources in clinical decision making. The clinical records of 75 glioma patients who were evaluated by FDG-PET were reviewed. The range of circumstances in which FDG-PET was employed included: pretherapeutic baseline studies for monitoring the effect of a therapy (1% of all cases), mapping of hypermetabolic regions before surgery or biopsy (2%), mapping of hypermetabolic regions before radiotherapy (2%), postsurgical evaluation for residual tumor (2%), assessment of the malignancy of a mass as a substitute for biopsy (11%), and distinguishing between radiation necrosis and recurrent tumor (87%). Other sources of information that contributed to the therapeutic management of patients included: gadolinium-enhanced MRI, contrast-CT, and clinical findings.
Abstract 697: Clinical and prognostic comparison between triple-negative and non-triple-negative breast cancer
Authors: Shian-Ling Ding, I Lee, Chun-Wen Cheng, Yu Hsin Lin, Jia-Ming Chang, Chen-Yang Shen
Journal: Cancer Research (2012)

Abstract Aim: The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of estrogen and progesterone receptors (ER/PR) and Her2/neu protein. The present study aimed to evaluate the five-year survival rates and clinico-pathological characteristics of patients with TNBCs and those with non-TNBCs in Taiwan. Methods: This study was conducted on 313 ethnic Chinese women with primary breast cancer using tissue microarrays to perform a standardized immunohistochemical analysis. Results: Of the 313 patients, 10.5% had the TNBC phenotype. The median age of the TNBC patients was lower than that of the non-TNBC patients (47 vs. 59 years). One of the more striking differences between the TNBC and non-TNBC women was tumor differentiation, with 29.6% of the non-TNBC group having a poorly differentiated tumor compared to 45.5% of the TNBC group (p=0.01). Cox proportional hazards model results showed that (a) ER, PR, or Her2/neu status was not associated with survival rate in early-stage patients and (b) ER negativity (p = 0.03, HR = 3.4) and Her2/neu negativity (p = 0.04, HR= 4.4) were two independent predictors of the five-year survival rate in advanced-stage (stage III-IV) women. Conclusion: The TNBC phenotype represents a specific molecular profile. However, it does not always lead to worse survival, especially in women with early breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 697. doi:1538-7445.AM2012-697
Abstract 2705: In search of a cost effective sentinel node biopsy technique: A randomized trial comparing the use of methylene blue and patent blue violet to identify sentinel node in breast cancer
Authors: seenu vuthaluru, Anurag Srivastava, Mahesh Misra
Journal: Cancer Research (2012)

Abstract One of the most significant breakthroughs in breast cancer management in recent times has been in the area of sentinel lymph node biopsy (SLNB), which is now an established staging technique for assessing regional lymph node status while minimizing the morbidity associated with conventional axillary lymph node dissection. Recommended technique of SLNBis the combination of blue dye (isosulfan blue or patent blue violet) and radiotracer. However, neither of the blue dyes are currently marketed in India &amp; are expensive. Thus, SLNB technique as practiced in the West is unlikely to be used widely in economically less developed nations. In India, some surgeons use methylene blue (MB) for identification of sentinel node in breast cancer with variable success rates. However, there are no large randomized trials comparing the efficacy of MB vis a vis isosulfan blue or patent blue violet (PBV) in identifying sentinel node in literature Objective To compare the sentinel node (SN) identification rate using patent blue violet (PBV) and methylene blue (MB) in combination with radiotracer in breast cancer. Sample size Assuming that MB identified SN in 60% cases and PBV in 85% of cases, a two group continuity corrected X2 test with 0.05 two sided test will have 80% power to detect the difference when the sample size is 57. Inclusion criteria Clinically axillary lymph node negative (N0) patients with breast cancer with tumor (T) stage T1, T2, Tx. willing to participate TechniqueCombination technique. Sentinel node: Any LN that is blue/ hot/ hot and blue is defined as SN. Any lymph node to which a blue stained lymphatic leads/ends will also be considered as SN. Results Study Period: Feb 2010-Nov 2011 No of Pts: 102 Age range: 31-82 yrs (mean: 41.4 yrs) Menopausal Status: Pre: 46 Post: 56 Side: R:L:: 50:52 T status: T1: 34; T2: 64; Tx SN identification rates: PBV: 46/49 MB: 51/53 (p value: NS) Conclusions Sentinel node can be identified with equal success rates using MB &amp; PBV. Methylene blue can be used as a cost effective sentinel node biopsy technique in breast cancer in economically less developed countries Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2705. doi:1538-7445.AM2012-2705
Case 1-2009
Authors: Daniel J. Costello, Florian S. Eichler, P. Ellen Grant, Pavan K. Auluck
Journal: New England Journal of Medicine (2009)

A 57-year-old man was transferred to this hospital because of progressive cognitive decline. Before admission, he had a generalized seizure, after which he was confused, incoherent, and intermittently agitated; he was admitted to another hospital and transferred 5 days later. His wife reported that he had had episodes of confusion for the past 5 years and worsening memory loss and performance problems for the preceding 2 months. He had a history of cutaneous melanoma, alcohol and drug abuse, and occupational exposure to organic solvents. Magnetic resonance imaging of the brain revealed diffuse signal abnormalities in the white matter. A diagnostic procedure was performed.
Abstract 230: A novel quantitative phosphoproteomic approach in mouse xenograft models to identify Src oncogenic signaling in colorectal cancer
Authors: Audrey Sirvent, Serge Urbach, Serge Roche
Journal: Cancer Research (2012)

Abstract The non receptor tyrosine kinase (TyrK) Src mediates signal transduction induced by growth factors and integrins. Src also exhibits oncogenic activity when deregulated, a situation frequently observed in colorectal cancer (CRC). Moreover, the extent of kinase deregulation often correlates with malignant potential, in agreement with an important role Src in this tumorigenic process. However, the exact role of Src in CRC is only partially elucidated. Src has been implicated in growth and invasiveness of various CRC cells. A previous SILAC quantitative phosphoproteomic analysis allowed the characterization of Src signaling leading to CRC cells growth and invasion (Leroy et al, Cancer Res, 2009, 15:2279-86). Interestingly, Src also increased tumor growth in nude mice engraft with human SW620 CRC cells. This biological effect correlated with a strong increase of tyrosine phosphorylation (pTyr) content in Src-positive tumors. Here, we wished to characterize Src oncogenic signaling in these xenograft tumor models. To this end, we have developed an innovative quantitative phosphoproteomic analysis coupled to stable isotope labeling in mice named SILAX for Stable Isotope Labeling in mouse Xenografts. This method is based on tumor heavy isotope labeling in nude mice by addition of [13C]-Lysine into the food. An incorporation level &amp;gt;87% was obtained in subcutaneous tumors after 30 days of heavy lysine diet. This approach allowed the identification of 61 proteins which exhibited a significant increase in and/or association with pTyr upon Src expression in tumors. These mainly include vesicular trafficking, signaling and RNA binding proteins. Interestingly, we identified the novel vesicular trafficking protein TOM1L1 (Franco et al, Mol Cell Biol, 2006, 26:1932-47) as a specific regulator of Src oncogenic signaling of CRC cells in vivo. While TOM1L1 depletion poorly affected Src-induced CRC proliferation in vitro, it significantly inhibited tumor growth in nude mice. This data suggests that vesicular trafficking plays an important role in Src-induced CRC tumor growth and validate SILAX as a valuable approach to decipher TyrK signaling in mouse xenograft models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 230. doi:1538-7445.AM2012-230
A patient with muscle weakness
Authors: Bert Bravenboer, Lynn Debels
Journal: BMJ (2016)

A 29 year old woman presented with symptoms of muscle weakness and difficulty swallowing. Physical examination showed swollen upper eyelids with a violaceous eruption (fig 1⇓). The dorsal side of her fingers was covered with an erythematous eruption. She also had bilateral symmetric purple discoloration of her skin in the area of the sternocleidomastoid muscle (fig 2⇓) and difficulty raising her arms above her head. A full blood cell count was normal. Creatinine kinase was raised at 1577 U/L (reference range 30-135).



Fig 1 



Fig 2 

1.  What is the diagnosis?

2.  Does this disease have other skin specific manifestations?

3.  Which laboratory tests can help confirm this diagnosis?

4.  What should patients with this disease be screened for?

5.  How would you treat this patient?

### 1. What is the diagnosis?

#### Short answer

Acute dermatomyositis (with heliotrope rash).

#### Discussion

Dermatomyositis is, together with polymyositis and inclusion body myositis, an idiopathic inflammatory myopathy. It is characterised by proximal muscle weakness and evidence of muscle inflammation. Dermatomyositis, unlike polymyositis, is associated with a variety of skin manifestations, including a heliotrope eruption. It is …
What about politics and culture?
Authors: C. Dominik Güss
Journal: Behavioral and Brain Sciences (2013)

Abstract Given Van de Vliert's impressive dataset and prognoses, I will discuss three limitations. First, the evolutionary argument does not adequately take into account how political changes influence freedoms. Second, the operationalizations of needs and freedoms are limited and questionable. Third, a direct relationship between climate, monetary resources, and psychological variables is a simplification neglecting various intervening variables.
AB0482 Takayasu arteritis and hla-b52 allele: a single-centre analysis from japanese population
Authors: T. Origuchi, T. Suzuki, Y. Nakashima, Y. Horai, A. Okada, S.-Y. Kawashiri, N. Iwamoto, K. Ichinose, K. Arima, M. Tamai, H. Nakamura, K. Eguchi, A. Kawakami
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Takayasu arteritis (TA) is a large vessel vasculitis affecting the aorta and its primary branches. The etiology of TA is still unknown, but recent studies have indicated that some genetic factors involve in its disease process. One of susceptible genes is HLA-B52 allele, however, its role to TA in Japanese populationhas not been well investigated. <h3>Objectives</h3> We have tried to investigate whether HLA-B52 allele associate with clinical characteristic of patients with TA from Japanese population. <h3>Methods</h3> We have retrospectively collected the patients with TA, diagnosed by the ACR classification criteria, in the medical record of Nagasaki University Hospital from 2003 to 2012. Twenty-five TA patients have been collected. All of patients gave their informed consent to be subjected to the protocol that was approved by the Institutional Review Board of Nagasaki University. <h3>Results</h3> Twenty-three out of 25 were female patients. Disease onset was 33.6 ± 18.5 y.o., and 15 patients were younger than 20 y.o. at onset. Initial laboratory data were WBC count 9238 ± 3838/mm<sup>3</sup>, CRP 5.8 ± 5.9 mg/dL, IgG 1,603 ± 520 mg/dL, fibrinogen 506 ± 129 mg/dL, respectively. Antinuclear antibody and rheumatoid factor were positive in two patients. Nineteen patients had been treated with glucocorticoids only whereas immunosuppressive agents were prescribed together with glucocorticoids in 12 patients. HLA typing was examined in 15 out of 25 TA patients. HLA-B52 allele was found in eleven TA patients (73.3%). Although statistical significance was not found, there was a trend that initial CRP (HLA-B52 allele-positive: 6.7 ± 4.1 mg/dL vs HLA-B52 allele-negative: 3.7 ± 3.7 mg/dL) and initial prednisolone dosage (HLA-B52 allele-positive: 37.8 ± 6.70 mg/day vs HLA-B52 allele-negative: 22.5 ± 17.1 mg/day) were high in HLA-B52 allele-positive patients as compared with negative patients. Additionally, five HLA-B52 allele-positive patients received methylprednisolone pulse therapy and eight received immunosuppressive agents whereas none of HLA-B52 allele-negative patients received such regime. <h3>Conclusions</h3> Most patients with TA were young female and HLA-B52 allele was frequently found. Presence of HLA-B52 allele might be a prognostic factor in Japanese patients with TA. <h3>References</h3> Sahin Z, Bıcakcıgil M, Aksu K, el al. Turkish Takayasu Study Group. Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey. Arthritis Res Ther. 2012 Feb 6;14(1):R27. doi: 10.1186/ar3730. Ohigashi H, Haraguchi G, Konishi M, et al. Improved prognosis of Takayasu arteritis over the past decade--comprehensive analysis of 106 patients. Circ J. 2012;76(4):1004-11. <h3>Disclosure of Interest</h3> None Declared
Abstract 760: Gene expression profiling in cancer vaccine: A new tool for cancer vaccine development
Authors: Satoko Matsueda, Tetsuro Sasada, Nobukazu Komatsu, Tetsuya Ioji, Shigeki Shichijo, Masanori Noguchi, Kosuke Tashiro, Satoru Kuhara, Kyogo Itoh
Journal: Cancer Research (2011)

Abstract (Introduction) Recently, cancer vaccines have emerged as one of the promising therapeutic options. However, it is still difficult to predict clinical responses in vaccinated patients prior to vaccination. For further development of this field, it would be of critical importance to identify biomarkers for selecting patients adequate for cancer vaccination. To identify reliable biomarkers, we characterized gene expression profiles by the DNA microarray technology (Illumina) in PBMC from prostate cancer patients that showed better or worse responses to the personalized peptide vaccination (survival time &amp;gt; 900 or &amp;lt; 300 days, respectively; n = 20 each). (Method) Total RNA was prepared from frozen-PBMCs prior to vaccination and hybridized. Detailed statistical analysis was performed to select genes that help predict patient clinical responses. In addition, to validate the result, 10 additional PBMC samples were analyzed in discriminant analysis. (Result) A combination of genes was selected as a predictive biomarker. In discriminant analysis, the identified genes clearly discriminated long-term survivors from short-term survivors to the peptide vaccination. (Conclusion) The identified gene set in PBMC may be useful as a biomarker in selecting patients adequate for personalized peptide vaccines. The detailed characterization of individual genes identified is currently underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 760. doi:10.1158/1538-7445.AM2011-760