tbuckley/cabot-search huggingface dataset:
Comparison of the clinical treatment score with the adjuvant online score and the risk for recurrence score for estimating prognosis in early-stage high-risk breast cancer patients: A Hellenic Cooperative Oncology Group study.
Authors: Kyriaki Pliarchopoulou, Eleni P. Galani, Ralph M Wirtz, George Kouvatseas, Flora Zagouri, Helen Gogas, Angelos Koutras, George E. Pentheroudakis, Georgios Lazaridis, Nikolaos Pisanidis, Gerasimos Aravantinos, Pavlos Papakostas, Paris Makrantonakis, Konstantine T. Kalogeras, George Fountzilas, Flora Stavridi
Journal: Journal of Clinical Oncology (2014)

1077 Background: Early breast cancer is a heterogeneous disease, and, therefore, prognostic tools have been developed to evaluate the risk for distant recurrence. We compared the Clinical Treatment Score (CTS) with the Adjuvant Online Score (AOS) and the Risk for Recurrence Score (RRS) based on the expression of three proliferation markers (RACGAP1, Ki67 and TOP2A) in high-risk early breast cancer patients. Methods: A total of 1,681 patients, enrolled in two prospective phase III trials, were treated with anthracycline-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded primary tumor tissue samples with adequate material were obtained from 898 patients. Sufficient RNA was extracted from 875 samples (52.1% of the randomized patients) followed by multiplex RT-PCR for assessing RACGAP1, Ki67, TOP2A and CALM2 mRNA expression. The CTS integrated the prognostic information from nodal status, tumor size, histological grade and age. Results: CTS was prognostic for disease-free survival (DFS, p<0.0001), while CTS, AOS and RRS were all prognostic for overall survival (OS, p<0.0001, p<0.0001, p=0.036, respectively). The use of AOS in addition to CTS added prognostic information regarding DFS (LR-Δχ2 11.9592, p<0.0001). However, the use of RRS in addition to CTS was not proven to be a better prognostic tool in terms of DFS (LR-Δχ2 0.8495; p=0.357). For estimating OS, the use of either AOS or RRS in addition to CTS added significant prognostic information. Specifically, the use of both CTS and AOS had significantly better prognostic value vs CTS alone (LR-Δχ2 28.2266, p<0.0001), as well as the use of CTS and RRS vs CTS alone (LR-Δχ24.2057; p=0.040). Additionally, more patients were scored as high-risk by AOS than CTS. Conclusions: Using CTS, AOS or RRS provides prognostic information in high-risk early breast cancer patients, with more patients determined as high-risk by AOS. The combination of CTS and AOS adds significant prognostic information compared to CTS alone for DFS, while the combination of CTS with either AOS or RRS are better prognostic tools than CTS alone for OS.
Histamine enhances keratinocyte-mediated resolution of inflammation by promoting wound healing and response to infection
Authors: D Gutowska-Owsiak, T A Selvakumar, M Salimi, S Taylor, G S Ogg
Journal: British Journal of Dermatology (2014)

Summary Background. The role of the epidermis in the immune response is well known. While multiple cytokines are implicated in keratinocyte-mediated infection clearance and wound healing, little is known about the involvement of keratinocytes in promoting resolution of inflammation. Aim. To assess effects of histamine stimulation on keratinocyte function. Methods. We performed a combined microarray/Gene Ontology analysis of histaminestimulated keratinocytes. Functional changes were tested by apoptosis assessment and scratch assays. Histamine receptor involvement was also assessed by blocking wound closure with specific antagonists. Results. Histamine treatment had extensive effects on keratinocytes, including effects on proinflammatory responses and cellular functions promoting wound healing. At the functional level, there was reduced apoptosis and enhancement of wound healing in vitro. At the receptor level, we identified involvement of all keratinocyteexpressed histamine receptors (HRHs), with HRH1 blockage resulting in the most prominent effect. Conclusions. Histamine activates wound healing and infection clearance-related functions of keratinocytes. While enhancement of histamine-mediated wound healing is mediated predominantly via the HRH1 receptor, other keratinocyte-expressed receptors are also involved. These effects could promote resolution of skin inflammation caused by infection or superficial injury.
Polyarthralgia in a young woman
Authors: Raju Vaishya, Amit Kumar Agarwal, Sujeet Kumar Singh, Vipul Vijay, Raman Sardana
Journal: BMJ (2017)

A 22 year old Indian woman presented to the orthopaedic clinic with excruciating pain and swelling in multiple joints (knee, ankle, wrist, and elbow) for the past two weeks. She also had on and off high grade fevers for the past month, associated with a rash all over her body. There were no ophthalmic or urinary symptoms. Investigations on presentation to the clinic showed anti-chikungunya immunoglobulin M and G antibodies. She had been managed with simple analgesia. At the current presentation, on examination, her joints were mildly swollen and tender (fig 1). Plain radiographs of the hand, knee, and ankle did not show any juxta-articular osteopenia or bone erosion. Fig 1 Asymmetrical swelling of knees (right more than left) The results of a full blood count showed a haemoglobin of 120 g/L (reference range 135-180 g/L), total leucocyte count of 8700 cells/µL (3500 to 10 500 cells/µL). Her erythrocyte sedimentation rate (15 mm/h) and C reactive protein (0.5 mg/L) were found to be within normal limits. Rheumatoid arthritis factor, antibodies against the cyclic citrullinated protein, antinuclear antibodies, and human leucocyte antigen B27 were also negative.
Abstract 424: Activation of the S1P3 Receptors is Responsible for S1P-mediated RhoA Activation and Cardioprotection
Authors: Bryan S Yung, Sunny Y Xiang, Nicole Purcell, Hugh Rosen, Jerold Chun, Joan Heller Brown, Shigeki Miyamoto
Journal: Circulation Research (2015)

Sphingosine-1-phoshpate (S1P) is a bioactive lysophospholipid, generated and released at sites of tissue injury. S1P signals through a variety of G-protein coupled receptor subtypes and there are three major sub-types, S1P 1 , S1P 2 , and S1P 3 , to mediate cardiovascular responses. S1P 2 and S1P 3 receptors couple to Gα i , Gα 12 , Gα 13 and Gα q and we first examined the contribution of S1P 2 and S1P 3 to cardiac hypertrophy using S1P 2 and S1P 3 knockout (KO) mice and found that there is no difference in hypertrophy induced by pressure-overload. We previously showed that S1P provides cardioprotection against oxidative stress such as ischemia/reperfusion in which RhoA activation and its downstream effector PKD1 play an important role. It has not, however, been determined which S1P receptor subtype is responsible for S1P mediated cardioprotection. We knocked down the three major S1P receptors using siRNA in neonatal rat ventricular myocytes (NRVMs) and assessed RhoA and PKD1 activation induced by S1P. Knockdown of S1P 3 abolished RhoA activation and largely attenuated phosphorylation of PKD1 while knockdown of S1P 1 and S1P 2 did not. Using siRNA or pertussis toxin to inhibit different G-proteins, we further established that S1P regulates RhoA activation through Gα 13 , but not Gα 12 , Gα q , or Gα i . To investigate the role of S1P 3 receptors in the adult heart, hearts were isolated from wild-type or S1P 3 KO adult mice, perfused in the Langendorff mode and subjected to ex vivo ischemia/reperfusion. As previously reported, S1P perfusion significantly reduced infarct size induced by ischemia/reperfusion in WT hearts (by 50%), but this protection was abolished in the S1P 3 KO mouse heart. To further confirm the role of S1P 3 in cardioprotection we perfused WT mouse hearts with an S1P 3 -specific agonist CYM-51736. We observed that CYM-51736 attenuated the infarct size to a similar degree as that observed with S1P. Our findings reveal that activation of the S1P 3 receptor coupling to Gα 13 and subsequent RhoA activation is responsible for cardioprotection against ischemia/reperfusion. Accordingly specific drug targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease without the undesirable effects of global activation of other cardiac S1P receptors.
Indications for Psychotherapy in a Psychiatric Clinic Population
Authors: Astrid Heiberg
Journal: Psychotherapy and Psychosomatics (1975)

As a part of a larger project of trying to differentiate the therapies for inpatients in a psychiatric clinic, we have made a half year's survey of the patients' needs for short-term dynamic psychotherapy. Our findings point to less than 10 % of the inpatients being able to profit from this kind of therapy. These findings and their implications are discussed briefly.
単一生細胞と癌細胞の初期同定における二酸化炭素発生量へのモニタリングのための凝集誘起発光特性を有する蛍光バイオプローブ【Powered by NICT】
Authors: Chen Didi, Wang Huan, Dong Lichao, Liu Pai, Zhang Yahui, Shi Jianbing, Feng Xiao, Zhi Junge, Tong Bin, Dong Yuping
Journal: Biomaterials (2016)
Clinical Associations of Cytogenetic Abnormalities in Patients with Primary and Post-Essential Thrombocythemia and Post-Polycythemia Vera Myelofibrosis
Authors: Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Kate J Newberry, Carlos E Bueso-Ramos, Jorge E. Cortes, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2016)
Abstract 12592: Short-term Outcomes of Acute Myocardial Infarction in Patients with Acute Kidney Injury: A Report from the National Cardiovascular Data Registry
Authors: Caroline S Fox, Paul Muntner, Anita Y Chen, Karen P Alexander, Matthew T Roe, Stephen D Wiviott
Journal: Circulation (2010)

Background: Acute kidney injury (AKI) is a risk factor for long-term adverse outcomes including myocardial infarction (MI) and death. However, the relationship between severity of AKI and in-hospit...
Steering Against Wind: A New Network of NamiRNAs and Enhancers
Authors: Ying Liang, Qingping Zou, Wenqiang Yu
Journal: Genomics Proteomics & Bioinformatics (2017)

MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the 3'UTR of target genes to degrade mRNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus. Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expression by binding to the enhancer, and named them nuclear activating miRNAs (NamiRNAs). The discovery of NamiRNAs showcases a complementary regulatory mechanism of miRNA, demonstrating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accordingly, we propose a NamiRNA-enhancer-target gene activation network model to better understand the crosstalk between NamiRNAs and enhancers in regulating gene transcription. Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determination during development, although further study is needed to elucidate the underlying mechanisms in detail.
Immunometabolic profiling of T cells from patients with relapsing-remitting multiple sclerosis reveals an impairment in glycolysis and mitochondrial respiration
Authors: Claudia La Rocca, Fortunata Carbone, Veronica De Rosa, Alessandra Colamatteo, Mario Galgani, Francesco Perna, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Orefice, Ilaria Cerillo, Ciro Florio, Giorgia Teresa Maniscalco, Marco Salvetti, Diego Centonze, Antonio Uccelli, Salvatore Longobardi, Andrea Visconti, Giuseppe Matarese
Journal: Metabolism (2017)

Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression.In this report, we observed that extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), indicators of glycolysis and oxidative phosphorylation, respectively, were impaired during T cell activation in naïve-to-treatment relapsing remitting (RR)MS patients when compared with healthy controls. These results were also corroborated at biochemical level by a reduced expression of the glycolitic enzymes aldolase, enolase 1, hexokinase I, and by reduction of Krebs cycle enzymes dihydrolipoamide-S-acetyl transferase (DLAT) and dihydrolipoamide-S-succinyl transferase (DLST). Treatment of RRMS patients with interferon beta-1a (IFN beta-1a) was able to restore T cell glycolysis and mitochondrial respiration as well as the amount of the metabolic enzymes to a level comparable to that of healthy controls. These changes associated with an up-regulation of the glucose transporter-1 (GLUT-1), a key element in intracellular transport of glucose.Our data suggest that T cells from RRMS patients display a reduced engagement of glycolysis and mitochondrial respiration, reversible upon IFN beta-1a treatment, thus suggesting an involvement of an altered metabolism in the pathogenesis of MS.
Abstract 92: The Mitochondrial Calcium Uniporter is Necessary for Metabolic Matching of Contractile Demand During Acute Sympathetic Stress
Authors: Timothy S Luongo, Jonathan P Lambert, Ancai Yuan, Xueqian Zhang, Santhanam Shanmughapriya, Erhe Gao, Steven R Houser, Muniswamy Madesh, John W Elrod
Journal: Circulation Research (2015)

Contractility is mediated by a variable flux in intracellular calcium (Ca 2+ ), which is proposed to be integrated into mitochondria to regulate cardiac energetics. Moreover, m Ca 2+ -overload is known to activate the mitochondrial permeability transition pore (MPTP) and induce cell death. Recent studies have reported that the Mcu gene encodes the channel-forming portion of the mitochondrial calcium uniporter (MCU) and is required for m Ca 2+ uptake. To examine the role of m Ca 2+ in the heart, we generated a conditional, cardiac-specific knockout model and deleted Mcu in adult mice ( Mcu-cKO ). Loss of Mcu protected against myocardial ischemia-reperfusion (IR) injury by preventing the activation of the MPTP. In addition while we found no baseline phenotype, Mcu -cKO mice lacked contractile responsiveness to beta-adrenergic receptor stimulation as assessed by invasive hemodynamics (Fig 1) and in parallel were unable to activate mitochondrial dehydrogenases and increase cardiac NADH levels. Further experimental analyses in isolated adult cardiomyocytes confirmed a lack of energetic responsiveness to acute sympathetic stress (isoproterenol failure to mediate an increase in NADH, Fig 2), supporting the hypothesis that the physiological function of the MCU in the heart is to modulate Ca 2+ -dependent metabolism during the ‘fight or flight’ response.
Role of proton-coupled folate transporter in pemetrexed resistance of mesothelioma: clinical evidence and new pharmacological tools
Authors: E. Giovannetti, P.A. Zucali, Y.G. Assaraf, N. Funel, M. Gemelli, M. Stark, E. Thunnissen, Z. Hou, I.B. Muller, E.A. Struys, M. Perrino, G. Jansen, L.H. Matherly, G.J. Peters
Journal: Annals of Oncology (2017)
Alemtuzumab added to CHOP for treatment of peripheral T-cell lymphoma (pTNHL) of the elderly: Final results of 116 patients treated in the international ACT-2 phase III trial.
Authors: Lorenz H. Trumper, Gerald Wulf, Marita Ziepert, Francesco D'Amore, Gerhard Held, Richard Greil, Olivier Tournilhac, Thomas Relander, Andreas Viardot, Martin Wilhelm, Josee M Zijlstra, Johanna C. Kluin-Nelemans, Maike Nickelsen, Friederike Braulke, Bettina Altmann, Andreas Rosenwald, Philippe Gaulard, Markus Loeffler, Michael Pfreundschuh, Norbert Schmitz
Journal: Journal of Clinical Oncology (2016)

7500 Background: Standard treatment in pTNHL pts is unsatisfactory due to a high rate of early progression. Alemtuzumab (A), a monoclonal anti-CD52 antibody, has demonstrated efficacy in relapsed pTNHL pts, and phase II trials have shown feasibility of concomitant A+CHOP application. We report the final analysis of the international ACT-2 phase III randomized trial in elderly pts comparing standard CHOP to A-CHOP. Methods: Between 2007 and 2013, 116 pts from 52 centers were randomized to receive either 6 cycles of CHOP or A-CHOP at 14-day intervals with G-CSF support. Pts were to receive a total of 360 mgs A (until pt 39) or 120 mg. The protocol demanded stringent CMV / EBV monitoring and anti-infective prophylaxis. The study was powered to detect a 15% increase in EFS with the addition of A to CHOP. Results: 116 pts (median age 69 yrs, 58% male) were randomized (58/58). Histologies were 41% AITL, 39% pTNHL NOS , 6% ALCL , 14% other subtypes. Complete treatment as planned was applied in 79% (CHOP) resp 57% (A-CHOP) of pts. Hematotoxicity grade 3/4 was more frequent in A-CHOP (leukocytopenia 4: 70 vs 54%, thrombocytopenia 3/4: 19 vs 13%) resulting in more grade ≥ 3 infections (40 vs. 21%). Complete remissions were achieved in 43% of CHOP and 60% of A-CHOP pts. EFS, PFS and OS at 3 yrs showed no significant differences, also in multivariate analyses (hazard ratios HR 0.7 – 1.4) adjusted for strata and gender. Bulky disease (HR 2.2), extranodal disease > 1 (HR 2.3) and male gender (HR 2.5) were the most prominent risk factors for EFS. Conclusions: A added to CHOP in elderly pTNHL pts increases response rates. Survival was not improved mostly due to treatment related toxicity. Risk factor and biomarker analysis including data from the ACT-1 trial are ongoing and may identify pts who benefit from A, as may improvement of antiviral strategies. Identifying new agents that improve response without undue toxicity remains an unmet medical need. Clinical trial information: 00725231.Results in % with 95% confidence intervals. CHOP A-CHOP all pts CR 43 (30;57) 60 (47; 73) 52 (42; 61) Relapse 48 (28; 69) 43 (26; 61) 45 (32; 58) EFS 23 (12; 35) 26 (13; 38) 24 (16; 33) PFS 29 (17; 41) 26 (14; 38) 28 (19; 36) OS 56 (43; 69) 38 (24; 51) 48 (38; 57)
A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Authors: P. Bossi, R. Miceli, L.D. Locati, D. Ferrari, S. Vecchio, G. Moretti, N. Denaro, F. Caponigro, M. Airoldi, C. Moro, E. Vaccher, A. Sponghini, A. Caldara, G. Rinaldi, F. Ferrau, F. Nolè, S. Lo Vullo, F. Tettamanzi, L. Hollander, L. Licitra
Journal: Annals of Oncology (2017)
特集の紹介と概観「脳イメージングと老化」:加齢研究における神経画像の新時代【Powered by NICT】
Authors: Furukawa Katsutoshi, Ishiki Aiko, Tomita Naoki, Onaka Yuta, Saito Haruka, Nakamichi Tomoko, Hara Kazunari, Kusano Yusuke, Ebara Masamune, Arata Yuki, Sakota Miku, Miyazawa Isabelle, Totsune Tomoko, Okinaga Shoji, Okamura Nobuyuki, Kudo Yukitsuka, Arai Hiroyuki
Journal: Ageing Research Reviews (2016)
Phospholipid Phosphatase 4 promotes proliferation and tumorigenesis, and activates Ca2+-permeable Cationic Channel in lung carcinoma cells
Authors: Xin Zhang, Lan Zhang, Bihua Lin, Xingxing Chai, Ronggang Li, Yuehua Liao, Xinghui Deng, Qiongru Liu, Wenli Yang, Yubo Cai, Wei Zhou, Zhichao Lin, Wenhai Huang, Meigong Zhong, Fangyong Lei, Jinhua Wu, Shuaishuai Yu, Xiaoping Li, Shangren Li, Yueyue Li, Jincheng Zeng, Wansheng Long, Dong Ren, Yanming Huang
Journal: Molecular Cancer (2017)

Phospholipid phosphatase 4 (PPAPDC1A or PLPP4) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to investigate the clinical significance and biological roles of PLPP4 in lung carcinoma.PLPP4 expression was examined in 8 paired lung carcinoma tissues by real-time PCR and in 265 lung carcinoma tissues by immunohistochemistry (IHC). Statistical analysis was performed to evaluate the clinical correlation between PLPP4 expression and clinicopathological features and survival in lung carcinoma patients. In vitro and in vivo assays were performed to assess the biological roles of PLPP4 in lung carcinoma. Fluorescence-activated cell sorting, Western blotting and luciferase assays were used to identify the underlying pathway through which PLPP4 silencing mediates biological roles in lung carcinoma.PLPP4 is differentially elevated in lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SQC) tissues. Statistical analysis demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade, T category and stage, and poor overall and progression-free survival in lung carcinoma patients. Silencing PLPP4 inhibits proliferation and cell cycle progression in vitro and tumorigenesis in vivo in lung carcinoma cells. Our results further reveal that PLPP4 silencing inhibits Ca2+-permeable cationic channel, suggesting that downregulation of PLPP4 inhibits proliferation and tumorigenesis in lung carcinoma cells via reducing the influx of intracellular Ca2+.Our results indicate that PLPP4 may hold promise as a novel marker for the diagnosis of lung carcinoma and as a potential therapeutic target to facilitate the development of novel treatment for lung carcinoma.
Abstract 12041: Associations Between Acylcarnitine to Total Carnitine Ratio and Adverse Prognosis in Heart Failure Patients With Reduced or Preserved Ejection Fraction
Authors: Shunsuke Watanabe, Akiomi Yoshihisa, Yu Sato, Tetsuro Yokokawa, Shunsuke Miura, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2016)

Background: The failing heart is accompanied by disturbed energy metabolism with mitochondrial dysfunction. This metabolic change involves altered fatty acid metabolism. Carnitine is an essential cofactor for fatty acid oxidative metabolism, which is the predominant source of ATP in the normal aerobic condition. Decreased myocardial carnitine levels and increased plasma carnitine levels in heart failure (HF) have been reported. A plasma acylcarnitine to total carnitine ratio (AC/TC ratio) has been recently recognized as a marker of carnitine deficiency. We aimed to investigate the significance of the AC/TC ratio on prognosis of HF and compare its prognostic impact between HF patient with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods and Results: We analyzed 168 patients with HF who admitted to our hospital. These patients were divided into 3 groups based on the AC/TC ratio: 1 st (AC/TC ratio &lt;0.15, n = 56), 2 nd (0.15≤ AC/TC ratio &lt;0.25, n = 56) and 3 rd (0.25≤ AC/TC ratio, n = 56) tertiles. In the average follow-up of 1004 days, 23 cardiac deaths and 28 re-hospitalizations from worsening heart failure occurred. In the Kaplan-Meier analysis, cardiac event rates progressively increased from 1 st to 2 nd and 3 rd groups (21.4%, 26.8% and 42.9%, P = 0.022). In the Cox proportional hazard analysis, the AC/TC ratio was an independent predictor of cardiac event after adjusting for confounding factors (HR 1.33, 95% CI 1.01-1.74, P = 0.044). When analyzed separately between HFpEF (n = 66) and HFrEF (n = 168), the Kaplan-Meier analysis revealed that cardiac event rates progressively increased from 1 st to 2 nd and 3 rd groups in HFpEF (P = 0.008), but not in HFrEF (P = 0.321). In the Cox proportional hazard analysis, the AC/TC ratio was an independent predictor of cardiac event in HFpEF (HR 2.00, 95% CI 1.09-3.67, P = 0.025), but not in HFrEF (HR 1.27, 95% CI 0.95-1.70, P = 0.101). Conclusion: The AC/TC ratio can identify high risk HF patients, especially in HFpEF.