tbuckley/cabot-search huggingface dataset:
Response to: ‘The role of temporal artery biopsy in patients with giant cell arteritis is debated’ by Moiseev <i>et al</i>
Authors: Christian Dejaco, Sofia Ramiro, Christina Duftner, Wolfgang A Schmidt
Journal: Annals of the Rheumatic Diseases (2018)

Moiseev et al 1 underlined the main message of the new European League Against Rheumatism (EULAR) recommendations for the use of imaging in large vessel vasculitis (LVV), namely the importance of imaging as a first-line test for the diagnosis of LVV.2 The EULAR task force also emphasised that the recommendations should not be understood as a recommendation against performing temporal artery biopsy (TAB) in giant cell arteritis (GCA), rather a biopsy still has its place when there is diagnostic doubt after having performed imaging or when imaging is not available or not performed with sufficient expertise. When a diagnosis can be …
Letter by Henni et al Regarding Article, “Aspirin Monotherapy Should Not Be Recommended for Cardioprotection in Patients With Symptomatic Peripheral Artery Disease”
Authors: Samir Henni, Nafi Ouedraogo, Pierre Abraham
Journal: Circulation (2018)

We read with interest Brass and Hiatt's 1 article, which proposes that aspirin monotherapy should not be recommended for cardioprotection in patients with symptomatic peripheral artery disease.Low-dose aspirin (75-325 mg) is a unique product on the market and in its application in clinical medicine.No other drug has such a large range of therapeutic recommended dose (from 1-4 times the minimal range).Using the lowest dose of aspirin seems to be associated with a high rate of persistent platelet reactivity. 2 Nevertheless, the prevalence of insufficient aspirin response can be significantly reduced and the risk for inadequate dual antiplatelet therapy minimized with a tailored treatment strategy and increased aspirin dose in case of persistent platelet reactivity. 3Increasing the aspirin dose decreases persistent platelet reactivity on plasma assays, but commonly used platelet assays show weak agreement with 1 another. 2To date, these platelet assays do not seem to directly correlate with clinical differences in terms of efficacy and bleeding risk.Several studies have reported positive results with tailored treatment for the prevention of thrombotic events.It could be argued that the CAPRIE trial (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events), which uses the highest aspirin dose within the recommended range, provided no evidence for increased benefit of aspirin compared with clopidogrel.However, this does not mean that aspirin is ineffective.Among other studies, a meta-analysis of randomized trials of antiplatelet therapy in patients with peripheral artery disease suggests that low-dose aspirin significantly reduces the incidence of vascular events by 26% compared with placebo. 4Considering the worldwide availability and low cost of aspirin, this issue is clearly important in low-income countries. 5Suggesting that aspirin monotherapy is not an optimal choice as a first-line treatment for cardioprotection in patients with peripheral artery disease in high-income countries appears to be a moderate and pragmatic conclusion.
SPECIFIC ADAPTIVE IMMUNE SYSTEM SIGNATURE AND PLAQUE FISSURE: AN OPTICAL COHERENCE TOMOGRAPHY STUDY IN ACUTE CORONARY SYNDROME
Authors: Aureliano Ruggio, Daniela Pedicino, Rocco Antonio Montone, Rocco Vergallo, Gianmarco Annibali, Davide Flego, Anna Severino, Ramona Vinci, Eugenia Pisano, Claudia Lucci, Italo Porto, Cristina Aurigemma, Giampaolo Niccoli, Filippo Crea, Giovanna Liuzzo
Journal: Journal of the American College of Cardiology (2018)
Use of seed gums from Tamarindus indica and Cassia fistula as controlled-release agents
Authors: Kampanart Huanbutta, Wancheng Sittikijyothin
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Most seed gums have been widely used in oral and topical pharmaceutical formulations, cosmetics, and food products because of their hydrophilic properties. Gums from Tamariudus indica and Cassia fistula seeds were chemically modified by carboxymethylation to improve their functionalities. The objective of the present study was to characterize and evaluate crude and carboxymethylated gums from T. indica and C. fistula seeds to achieve the controlled-release of diclofenac sodium (DS) in matrix tablet form. Both crude and carboxymethylated gums were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The results revealed that the gums were successfully modified by carboxymethylation and that the modified gums were amorphous in structure and had better flow properties. The carboxymethylated gums from both plant seeds did not exhibit cytotoxicity at concentrations lower than 0.5 mg/ml. All gum samples used as polymeric controlled-release agents were formulated into DS matrix tablets. Hardness and thickness tests were conducted as in-process tests. Drug content estimation and in vitro drug release studies were carried out to evaluate the matrix tablets. Increasing the concentration of gums increased compression time and hardness while it reduced the thickness. Furthermore, the results fitted well with the Korsmeyer-Peppas model. Moreover, the DS tablets were found to release the drug by super case II transport (relaxation). In summary, the carboxymethylated gum from T. indica and C. fistula seeds is an excellent, naturally sourced gum with high physicochemical and functional qualities, and can potentially be used in pharmaceutical applications as a disintegrant, diluent, and drug release-controlling agent.
Comorbidities of pyoderma gangrenosum: a retrospective multicentric analysis of 126 patients
Authors: M. Gillard, D. Anuset, H. Maillard, P. Senet, J. F. Cuny, E. Mahe, C. Sin, F. Dessiner, E. Goujon, J. Journet-Tollhupp, C. Debure, F. Dabouz, T. Develter, P. Bernard, C. Lok, P. Modiano
Journal: British Journal of Dermatology (2018)
Gpr97 Exacerbates AKI by Mediating Sema3A Signaling
Authors: Wei Fang, Ziying Wang, Quanxin Li, Xiaojie Wang, Yan Zhang, Yu Sun, Wei Tang, Chunhong Ma, Jinpeng Sun, Ningjun Li, Fan Yi
Journal: Journal of the American Society of Nephrology (2018)

Background G protein-coupled receptors (GPCRs) participate in a variety of physiologic functions, and several GPCRs have critical physiologic and pathophysiologic roles in the regulation of renal function. We investigated the role of Gpr97, a newly identified member of the adhesion GPCR family, in AKI. Methods AKI was induced by ischemia–reperfusion or cisplatin treatment in Gpr97-deficient mice. We assessed renal injury in these models and in patients with acute tubular necrosis by histologic examination, and we conducted microarray analysis and in vitro assays to determine the molecular mechanisms of Gpr97 function. Results Gpr97 was upregulated in the kidneys from mice with AKI and patients with biopsy-proven acute tubular necrosis compared with healthy controls. In AKI models, Gpr97-deficient mice had significantly less renal injury and inflammation than wild-type mice. Gpr97 deficiency also attenuated the AKI-induced expression of semaphorin 3A (Sema3A), a potential early diagnostic biomarker of renal injury. In NRK-52E cells subjected to oxygen–glucose deprivation, siRNA-mediated knockdown of Gpr97 further increased the expression of survivin and phosphorylated STAT3 and reduced toll-like receptor 4 expression. Cotreatment with recombinant murine Sema3A protein counteracted these effects. Finally, additional in vivo and in vitro studies, including electrophoretic mobility shift assays and luciferase reporter assays, showed that Gpr97 deficiency attenuates ischemia–reperfusion-induced expression of the RNA-binding protein human antigen R, which post-transcriptionally regulates Sema3A expression. Conclusions Gpr97 is an important mediator of AKI, and pharmacologic targeting of Gpr97-mediated Sema3A signaling at multiple levels may provide a novel approach for the treatment of AKI.
PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway
Authors: Yang Cheng, Yun Zhu, Jiajia Xu, Min Yang, Peiyu Chen, Wanfu Xu, Junhong Zhao, Lanlan Geng, Sitang Gong
Journal: Molecular Cancer (2018)

Protein kinase N2 (PKN2) is a PKC-related serine/threonine-protein kinase. PKN2 is required for tumor cell migration, invasion and apoptosis. However, the functional role of PKN2 in regulating tumor associated macrophages (TAMs) polarization in colon cancer has never been reported. PKN2 expression in human colon cancer tissues was examined with immunohistochemistry (IHC). M1/M2 macrophage signatures were evaluated by RT-PCR, IHC and flow cytometry. The effects of PKN2 on tumor growth and TAM polarization were investigated both in vitro and in vivo. PKN2 targeted cytokines/pathway were analyzed by gene expression analysis and further confirmed by PCR, luciferase assay or western blot. Correlations between PKN2 and transcriptional factors for IL4 and IL10 were confirmed by ChIP-qPCR. The catalytic activities of PKN2 and DUSP6 were determined by kinase activity assay. Interactions between PKN2 and DUSP6 were confirmed by Co-IP. The expression of PKN2 in colon cancer cells predicted a favorable prognosis and was associated with low M2 macrophage content in human colon cancer tissues. PKN2 inhibited tumor growth in mice xenograft model and inhibited M2 phenotype polarization both in vitro and in vivo. Mechanistically, PKN2 suppresses the expression of IL4 and IL10 from colon cancer cells by inhibiting Erk1/2 phosphorylation, which is required for phosphorylation and binding of CREB and Elk-1 to the promoters of IL4 and IL10. DUSP6, which is phosphorylated and activated through direct association with PKN2, suppresses Erk1/2 activation. The expression of PKN2 in colon cancer cells suppresses tumor associated M2 macrophage polarization and tumor growth. Targeting PKN2 signaling pathway may provide a potential therapeutic strategy for colon cancer.
Efficacy of Psychosocial Interventions for People with Multiple Sclerosis: A Meta-Analysis of Specific Treatment Effects
Authors: Amy-Lee Sesel, Louise Sharpe, Sharon L. Naismith
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Psychosocial interventions are often used as an adjunct to the medical management of multiple sclerosis (MS). However, the efficacy of such approaches for a range of psychosocial indications remains unclear. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To determine the efficacy of psychosocial therapies for people with MS (PwMS). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We searched 6 electronic databases (Medline, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, and Clinicaltrials.gov) until April 21, 2016, for randomized controlled trials reporting the effect of psychological interventions for depressive symptoms, anxiety, pain, fatigue, or health-related quality of life (HRQoL) in PwMS. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The search yielded 356 articles with 13 included studies (&lt;i&gt;n&lt;/i&gt; = 1,617). Benefits of psychological interventions were found for depressive symptoms (Cohen’s &lt;i&gt;d&lt;/i&gt; = 0.281), anxiety (&lt;i&gt;d&lt;/i&gt; = 0.285), fatigue (&lt;i&gt;d&lt;/i&gt; = 0.228), and mental (&lt;i&gt;d&lt;/i&gt; = 0.398) and total HRQoL (&lt;i&gt;d&lt;/i&gt; = 0.444), but not physical HRQoL. There were insufficient studies to meta-analyze posttreatment outcomes for pain. Interventions were more effective for HRQoL for patients with relapsing-remitting MS and when treatment doses were larger. Cognitive behavioral therapy (CBT) was not efficacious for PwMS when considered alone. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Psychosocial interventions have a significant, positive impact across a range of outcomes for PwMS with small, yet consistent, effect sizes. There was some indication that CBT was less efficacious than other interventions. However, this may be due to smaller treatment doses in CBT studies.
Plans for four year GP training outlined by RCGP
Authors: Helen Jaques
Journal: BMJ (2012)

General practitioner training should be extended to four years to allow trainees an extra 12 months in general practice placements, the Royal College of General Practitioners has recommended.

In evidence to the Medical Programme Board of Medical Education England, the college proposes that GP trainees should spend 24 months in general practice placements rather than the current 12 months.

Trainees should spend a further 12 months in placements in specialties relevant to general practice and the remaining 12 months in “innovative GP training placements” such as secondary care placements that provide relevant experience …
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma
Authors: Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen Rhodin, Hanna Kemeny, Cosette Dechant, S. Harrison Farber, Aladine A. Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina Jackson, Landon J. Hansen, Tanner M. Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei Andrea Yu, Darell D. Bigner, Amber Giles, Patrick Healy, Glenn Dranoff, Kent J. Weinhold, Gavin P. Dunn, Peter E. Fecci
Journal: Clinical Cancer Research (2018)

Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amid immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM.Experimental Design: Tumor-infiltrating and peripheral blood lymphocytes (TILs and PBLs) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and poststimulation levels of the cytokines IFNγ, TNFα, and IL2 were assessed by flow cytometry. T-cell receptor Vβ chain expansion was also assessed in TILs and PBLs. Similar analysis was extended to TILs isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers.Results: Our data reveal that GBM elicits a particularly severe T-cell exhaustion signature among infiltrating T cells characterized by: (1) prominent upregulation of multiple immune checkpoints; (2) stereotyped T-cell transcriptional programs matching classical virus-induced exhaustion; and (3) notable T-cell hyporesponsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations.Conclusions: Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlight the need to better understand this tumor-imposed mode of T-cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM. Clin Cancer Res; 24(17); 4175-86. ©2018 AACRSee related commentary by Jackson and Lim, p. 4059.
Practical cognition course
Authors: Jasvinder Singh
Journal: BMJ (2012)

This two day course is run by cognitive neurologists who are based in Newcastle upon Tyne and Oxford, and guest speakers come from the specialties of neurology, neuropsychology, and psychiatry. The course’s core aim is to develop skills and knowledge of cognitive assessment and relate this to the patient. The speakers this year included Jason Warren and Masud Husain, from the Institute of Neurology in London; Adam Zeman, from Peninsula Medical School; Andrew Larner, from the Walton Centre for Neurology in Liverpool; Roland Zahn, from Manchester University; and Tom Kelly, from Newcastle.

This course is aimed at consultants and trainees in adult neurology, psychiatry, clinical neuropsychology, and rehabilitation medicine who want to develop their clinical expertise in cognitive assessment and relate this to clinically relevant neuroscience.

The course is run at Newcastle University, usually in the autumn (planned dates for 2012 are 1-2 November). The morning of the first day begins with general principles of …
Characteristics, treatment and outcomes of nontuberculous mycobacterial pulmonary disease after allogeneic haematopoietic stem cell transplant
Authors: Takashi Hirama, Sarah K. Brode, Jenifer Beswick, Arjun D. Law, Wilson Lam, Fotios V. Michelis, Santhosh Thyagu, Auro Viswabandya, Jeffrey H. Lipton, Hans A. Messner, Dennis (Dong Hwan) Kim, Theodore K. Marras
Journal: European Respiratory Journal (2018)

Allogeneic haematopoietic stem cell transplant (alloHCT) recipients are at risk for a variety of opportunistic infections. While typical bacterial infections occur most frequently, nontuberculous mycobacteria (NTM) are becoming increasingly recognised as pathogens after alloHCT [1]. The prevalence of NTM pulmonary disease (NTM-PD) is increasing worldwide, with a rise in Ontario's period prevalence from 29.3 per 100 000 in 1998–2002 to 41.3 per 100 000 in 2006–2010 [2]. Likewise, the incidence of NTM-PD post alloHCT increased from 0.11–0.23% [3, 4] in early studies to 2.7–3.15% in recent investigations [5, 6]. Despite the incidence of NTM-PD after alloHCT being far higher than in the general population [6], there are few reports addressing management and treatment outcomes of NTM-PD after alloHCT. We reviewed the experience with NTM-PD among alloHCT recipients at our institution to better characterise clinical features and treatment outcomes. Nontuberculous mycobacterial pulmonary disease in allogeneic haematopoietic stem cell transplant recipients <http://ow.ly/5epj30j6bfy>
USPSTF Recommendations for Behavioral Counseling for Skin Cancer Prevention
Authors: Eleni Linos, Sherry Pagoto
Journal: JAMA Internal Medicine (2018)

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Comparison of S-1 and S-1 plus cisplatin as post-operative chemotherapy for gastric carcinoma with peritoneal lavage cytology positive or localized peritoneum metastasis: A multicenter retrospective study.
Authors: Masaki Aizawa, Toshifumi Yamaguchi, Atsuo Takashima, Kengo Nagashima, Akira Ema, Yasuhiro Yuasa, Shusuke Haruta, Hiroki Taniguchi, Daisuke Kobayashi, Kazuhiro Nishikawa, Gen Yunome, Masakazu Takagi, Hirotaka Niwa, Takanobu Yamada, Shinji Hato, Takeo Fukagawa, Narikazu Boku, Hitoshi Katai
Journal: Journal of Clinical Oncology (2018)

109 Background: Peritoneal lavage cytology of class V and localized peritoneum metastasis of gastric cancer (GC) are defined as CY1 and P1 in the 14th edition of the Japanese Classification of GC. Because patients (pts) with CY1 and/or P1 have poor prognosis after resecting all macroscopically visible disease by standard surgical resection, post-operative chemotherapy (post-Cx) is commonly performed in the clinical practice in Japan. However, no standard chemotherapy has not been established. The aim of this study was to investigate the efficacy of post-Cx in patients with CY1 and/or P1. Methods: We retrospectively reviewed the GC pts who were diagnosed to have CY1 and/or P1 at 34 institutions participating in the Stomach Cancer Group of Japan Clinical Oncology Group between 2007 and 2012. Inclusion criteria were: PS 0-2, histology of adenocarcinoma, no distant metastasis other than CY1 or P1, no prior treatment for GC. The subject of this study was the patients who received surgery followed by post-Cx. Results: A total of 824 pts were collected from 34 institutions. Of the 506 eligible pts, 444 pts underwent standard gastrectomy followed by post-Cx: S-1 (n=267), S1 plus cisplatin (SP) (n=114) or others (n=63). 62 pts did not receive post-Cx (non-Cx). Median age for the S1/SP/Others/non-Cx group were 69/63/66/75. In the S-1 group, pts with P0CY1/P1CY0/P1CY1 were 197/44/26, and those were 81/21/12 in SP, 45/9/9 in Others, and 44/7/11 in non-Cx. Conclusions: Post-Cx may have survival benefit after surgery for GC with CY1 or P1, while there seems no additional benefit over S-1. [Table: see text]
Gene expression profiling of patient-matched initial and recurrent glioblastoma
Authors: Aideen Roddy, Peter Stewart, Theodore Hirst, Estelle Healy, Claire Lewis, Philip Dunne, Manuel Salto-tellez, Tom Flannery, Kevin Prise, Darragh McArt
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is an aggressive, malignant brain tumour with only 5% of patients surviving beyond 5 years. The only prognostic improvement for these patients over the past 2 decades came through transitioning treatment to the Stupp protocol. However, these patients still recur after 6.9 months on average. Here, we present our study of patient-matched gene expression profiles for 10 initial and their paired, post-treatment, recurrent GBM samples with an additional 2 initial and 3 recurrent unmatched samples. This study represents an opportunity to focus these advances in GBM to radically improve diagnosis, prognosis and patient outcomes. The Clariom D assay by Affymetrix provides a wealth of information from over 540,000 transcripts allowing a detailed analysis of gene expression and alternative splicing events which result in both coding RNA and long non-coding RNA isoforms. Differential expression analysis highlighted ADGRL4, a key regulator of angiogenesis and ABCG2, a member of the ATP-binding cassette transporters associated with multi-drug resistance as being downregulated in GBM recurrent samples. Where as, GAS5, a long non-coding RNA which has been identified as a potential tumour suppressor is upregulated in our post-treatment GBM samples. Through further analysis we have identified HBB and HOXB3 as being alternatively spliced in recurrent tumours compared to their initial counter parts, while Ingenuity Pathway Analysis has identified EIF2 signaling and Antigen Presentation Pathway as being key in GBM recurrence. We can see from our analysis that treatment is having an effect on key genes and pathways implicated in cancer. We will validate our results using quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Future work will involve identifying key groups and trends in our cohort according to mutational profile,survival and time to progression.