tbuckley/cabot-search huggingface dataset:
Oxytocin alleviates cellular senescence through oxytocin receptor‐mediated extracellular signal‐regulated kinase/Nrf2 signalling
Authors: S.‐Y. Cho, A.Y. Kim, J. Kim, D.‐H. Choi, E.D. Son, D.W. Shin
Journal: British Journal of Dermatology (2019)

Oxytocin (OT) is a neuropeptide hormone that has many beneficial biological effects, including protection against age‐related disorders. However, less is known about its role in intrinsic skin ageing, which is accelerated by an increase in senescent cell fraction in skin tissue. To investigate the novel function and the underlying mechanism of OT in preventing cellular senescence in normal human dermal fibroblasts (NHDFs) isolated from the skin of female donors of different ages. NHDFs from young and old donors were exposed to conditioned medium from senescent or control NHDFs in the presence or absence of 10 nmol L−1 OT for 3 days, and were continuously subcultured for 12 days. Subsequently, various age‐associated signs of senescence including decreased proliferation rate, elevated p16 and p21 levels, and positivity for senescence‐associated β‐galactosidase expression were examined. We found that OT suppressed senescence‐associated secretory phenotype‐induced senescence in NHDFs, and its effect depended on the age of the donor's NHDFs. The inhibitory effects of OT required signalling by OT receptor‐mediated extracellular signal‐regulated kinase/Nrf2 (nuclear factor erythroid 2‐related factor 2). The age‐dependent antisenescence effects of OT are closely related to hypermethylation of the OT receptor gene (OXTR). Our findings bring to light the role of OT in the prevention of skin ageing, which might allow development of new clinical strategies. What's already known about this topic? Senescent keratinocytes and fibroblasts accumulate with age in the skin and contribute to the loss of skin function and integrity during ageing. Senescent cells secrete senescence‐associated secretory phenotype (SASP), which includes the release of proinflammatory cytokines such as interleukin (IL)‐6 and IL‐1, chemokines, extracellular matrix‐remodelling proteases and growth factors. The neuropeptide oxytocin (OT) and its receptor (OXTR) have protective effects against various age‐related disorders. What does this study add? OT suppressed SASP‐induced cellular senescence in normal human dermal fibroblasts (NHDFs), depending on the age of the NHDFs’ donor. The inhibitory effects of OT on cellular senescence required OXTR‐mediated phosphorylation of extracellular signal‐regulated kinase, which enhanced nuclear localization of Nrf2, a vital factor in the antioxidant defence system. The age‐specific antisenescent effects of OT were closely related to hypermethylation of OXTR. What is the translational message? Our results suggest that OT and OXTR agonists could be clinically promising agents for the improvement of age‐associated skin ageing, especially in women.
Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults
Authors: Michael S. Saag, Constance A. Benson, Rajesh T. Gandhi, Jennifer F. Hoy, Raphael J. Landovitz, Michael J. Mugavero, Paul E. Sax, Davey M. Smith, Melanie A. Thompson, Susan P. Buchbinder, Carlos del Rio, Joseph J. Eron, Gerd Fätkenheuer, Huldrych F. Günthard, Jean-Michel Molina, Donna M. Jacobsen, Paul A. Volberding
Journal: JAMA (2018)

<h3>Importance</h3> Antiretroviral therapy (ART) is the cornerstone of prevention and management of HIV infection. <h3>Objective</h3> To evaluate new data and treatments and incorporate this information into updated recommendations for initiating therapy, monitoring individuals starting therapy, changing regimens, and preventing HIV infection for individuals at risk. <h3>Evidence Review</h3> New evidence collected since the International Antiviral Society–USA 2016 recommendations via monthly PubMed and EMBASE literature searches up to April 2018; data presented at peer-reviewed scientific conferences. A volunteer panel of experts in HIV research and patient care considered these data and updated previous recommendations. <h3>Findings</h3> ART is recommended for virtually all HIV-infected individuals, as soon as possible after HIV diagnosis. Immediate initiation (eg, rapid start), if clinically appropriate, requires adequate staffing, specialized services, and careful selection of medical therapy. An integrase strand transfer inhibitor (InSTI) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) is generally recommended for initial therapy, with unique patient circumstances (eg, concomitant diseases and conditions, potential for pregnancy, cost) guiding the treatment choice. CD4 cell count, HIV RNA level, genotype, and other laboratory tests for general health and co-infections are recommended at specified points before and during ART. If a regimen switch is indicated, treatment history, tolerability, adherence, and drug resistance history should first be assessed; 2 or 3 active drugs are recommended for a new regimen. HIV testing is recommended at least once for anyone who has ever been sexually active and more often for individuals at ongoing risk for infection. Preexposure prophylaxis with tenofovir disoproxil fumarate/emtricitabine and appropriate monitoring is recommended for individuals at risk for HIV. <h3>Conclusions and Relevance</h3> Advances in HIV prevention and treatment with antiretroviral drugs continue to improve clinical management and outcomes for individuals at risk for and living with HIV.
NIMG-48. VOLUMETRIC RESPONSE TO TTFIELDS IN NEWLY DIAGNOSED GBM
Authors: Johannes Kerschbaumer, Daniel Pinggera, Claudius Thomé, Christian Freyschlag
Journal: Neuro-Oncology (2018)

Optune TTField treatment is an established, non-invasive therapy for patients with newly diagnosed or recurrent glioblastoma (GBM). Treatment efficacy was evaluated, showing significant improvement of both, overall and progression free survival. For analysis, the MacDonald criteria were used. We performed a 3D volumetric analysis of patients with newly diagnosed GBM who underwent resection and chemoradiation with additional TTFields treatment. Between February 2016 and April 2017, 14 patients were initiated with TTField treatment. For analysis of volumetric response rates, we were able to include 7 patients (newly diagnosed GBM, device usage over 60%, treatment duration over 3 months). Segmentation and volumetric analysis was done for contrast enhancing tumor on T1 imaging (MPRAGE, 1mm slice thickness). The median age was 48 years (range 17–68 years) at the date of prescription. Median preoperative volume was 20.3 cc (range: 1.12–58.6cc), postoperative volume was 6.3 cc (range: 0–14.2cc) and volume upon analysis was 1.2 cc (range: 0–7.1cc). Average device usage (ADU) of these patients was 89.47%. The median change of volume from postoperative to posttreatment volume was 4cc (range: 0–7.1cc) in patients with a median device usage of over 80%; whereas in patients with lesser than 80%, the mean volume change was 2.2cc (range 0–3.2cc). TTFields are generally accepted and efficacious for treatment of GBM. Our analysis showed that the combination of radiation, Temozolomide and TTFields lead to a reduction in contrast enhancing tumor volume. The effect seemed to be related to treatment duration.
Abstract 3138: Stat3 signaling in thyroid cancer
Authors: Joana Silva, Paula Soares, Vitor Trovisco, Jeffrey Knauf, James Fagin, Jacqueline Bromberg
Journal: Cancer Research (2010)

Abstract In this study, we addressed the relevance and regulation of Stat3 activation in thyroid cancer. Papillary Thyroid Carcinoma (PTC) comprises almost 80% of thyroid neoplasias and 70% of PTC present activating alterations of components of the ERK-MAPK pathway, either BRAF mutations, RET/PTC rearrangements or RAS mutations. PTCs often display a strong desmoplastic reaction, where tumor is surrounded by a dense stroma and infiltrated with inflammatory cells. To examine the role of Stat3 in thyroid tumours and its putative relation to the associated inflammatory reaction, we analysed Stat3 activation (i.e. Y705-phosphorylation) by IHC in 58 samples of PTC. Approximately 50% of the tumors express pStat3. Frequently, nuclear positivity is only observed in the edge of the tumor as well as in the thyroid cells within tumor stroma. The inner part of the tumor is generally negative. Using multiple cell line models of PTC we observe that both RET/PTC and BRAFV600E expression can lead to Stat3 activation. Similarly, transgenic models of both BRAFV600E and RET/PTC also demonstrate high levels of pStat3 in particular on the inflammatory/leading edge of the tumor. We hypothesize that Stat3 activation, particularly in BRAFV600E tumors, may result from a paracrine effect of stromal cells-derived factors in the adjacent tumor cells. Stat3 is principally activated by autocrine/paracrine IL-6/Jak signaling in lung and breast tumors. Similarly, here we demonstrate that pan-Jak inhibitors block Stat3 activation in PTC cell lines. Furthermore, IL-6 signaling appears to mediate Stat3 activation in RET/PTC, BRAFV600E and RAS expressing cell lines. BRAFV600E knockdown led to a significant decrease of IL-6 levels, as well as of pStat3. In conclusion, we have found that Stat3 is activated in PTC, and that, particularly in BRAFV600E tumors, such activation may result from a paracrine effect of stromal cells through upregulation of IL-6/Jak pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3138.
Efficacy of Rituximab Maintenance for Diffuse Large B Cell Lymphoma with Transformation
Authors: Hideki Uryu, Yuko Mishima, Masahiro Yokoyama, Noriko Nishimura, Yoshiharu Kusano, Norihito Inoue, Anna Nishihara, Takanori Fukuta, Yuko Shirouchi, Naoko Tsuyama, Kengo Takeuchi, Yasuhito Terui
Journal: Blood (2018)
Abstract 1404: A red-shifted fluorescent substrate for aldehyde dehydrogenase, AldeRed 588-A, for labeling viable ALDH-positive cells
Authors: Vi Chu, Konstantin Taganov, D Ramesh, Nick Asbrock, Martin Pomper
Journal: Cancer Research (2015)

Abstract Normal and cancer stem cells can be isolated based upon the enzymatic activity of aldehyde dehydrogenase I (ALDH1), a detoxifying enzyme responsible for oxidation of hazardous aldehyde byproducts. ALDH1 has been used to isolate cancer stem cells of various human malignancies including bladder, breast, cervical, colon, head and neck, liver, lung, pancreas, prostate and ovary. Currently, the ALDEFLUORTM assay which uses a fluorescent substrate is the only commercially available reagent for ALDH detection. The substrate used in this assay primarily emits in the green region of the electromagnetic spectrum (512nm). For researchers with valuable cell and transgenic animal models in which the target gene of interest has been tagged with eGFP, ALDEFLUOR therefore cannot be used. Selection of cells positive for aldehyde dehydrogenase (ALDH) activity from a green fluorescent background is thus difficult with existing reagents. We now describe a red-shifted fluorescent substrate for ALDH, AldeRed 588-A, that provides additional flexibility for utilizing ALDH as a marker for stem cell and cancer stem cell isolation. The activity of AldRed 588-A was compared with the ALDEFLUOR reagent and demonstrated similar ability to fractionate ALDHpos cells in a number of cell lines tested. Citation Format: Vi Chu, Konstantin Taganov, D Ramesh, Nick Asbrock, Martin Pomper. A red-shifted fluorescent substrate for aldehyde dehydrogenase, AldeRed 588-A, for labeling viable ALDH-positive cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1404. doi:10.1158/1538-7445.AM2015-1404
Neofunctionalization of Mitochondrial Proteins and Incorporation into Signaling Networks in Plants
Authors: Sbatie Lama, Martyna Broda, Zahra Abbas, Dries Vaneechoutte, Katharina Belt, Torbjörn Säll, Klaas Vandepoele, Olivier Van Aken
Journal: Molecular Biology and Evolution (2019)

Because of their symbiotic origin, many mitochondrial proteins are well conserved across eukaryotic kingdoms. It is however less obvious how specific lineages have obtained novel nuclear-encoded mitochondrial proteins. Here, we report a case of mitochondrial neofunctionalization in plants. Phylogenetic analysis of genes containing the Domain of Unknown Function 295 (DUF295) revealed that the domain likely originated in Angiosperms. The C-terminal DUF295 domain is usually accompanied by an N-terminal F-box domain, involved in ubiquitin ligation via binding with ASK1/SKP1-type proteins. Due to gene duplication, the gene family has expanded rapidly, with 94 DUF295-related genes in Arabidopsis thaliana alone. Two DUF295 family subgroups have uniquely evolved and quickly expanded within Brassicaceae. One of these subgroups has completely lost the F-box, but instead obtained strongly predicted mitochondrial targeting peptides. We show that several representatives of this DUF295 Organellar group are effectively targeted to plant mitochondria and chloroplasts. Furthermore, many DUF295 Organellar genes are induced by mitochondrial dysfunction, whereas F-Box DUF295 genes are not. In agreement, several Brassicaceae-specific DUF295 Organellar genes were incorporated in the evolutionary much older ANAC017-dependent mitochondrial retrograde signaling pathway. Finally, a representative set of DUF295 T-DNA insertion mutants was created. No obvious aberrant phenotypes during normal growth and mitochondrial dysfunction were observed, most likely due to the large extent of gene duplication and redundancy. Overall, this study provides insight into how novel mitochondrial proteins can be created via "intercompartmental" gene duplication events. Moreover, our analysis shows that these newly evolved genes can then be specifically integrated into relevant, pre-existing coexpression networks.
Legionnaires’ disease in Europe: 2005-2006
Authors: K D Ricketts, C A Joseph, None on behalf of the European Working G
Journal: Eurosurveillance (2007)

Once a year, every country that participates in the European Surveillance Scheme for Travel Associated Legionnaires' Disease (EWGLINET) is asked to submit a dataset comprising all cases of Legionnaires' disease (not only travel-associated) with date of onset in the previous year. This paper presents the data collected for 2005 and 2006. In this period, 11,980 cases were reported by 35 countries, showing a continued increase compared with earlier years. 214 outbreaks or clusters were reported, involving 1028 cases. 377 cases died, giving a case fatality rate of 6.6%. The highest incidence rates in both years were recorded in Spain, while six countries reported a rate of less than one case per million population in at least one of the years. Incidence rates by age group were included in the dataset for the first time, showing an increase of the overall rate with age. Main method of diagnosis was the urinary antigen test (76.0%), whilst the percentage of cases diagnosed by culture fell from 10.0% in previous years to 8.9% in 2005-2006. .
Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline
Authors: Shlomo A. Koyfman, Nofisat Ismaila, Doug Crook, Anil D'Cruz, Cristina P. Rodriguez, David J. Sher, Damian Silbermins, Erich M. Sturgis, Terance T. Tsue, Jared Weiss, Sue S. Yom, F. Christopher Holsinger
Journal: Journal of Clinical Oncology (2019)

The aim of the current work is to provide evidence-based recommendations to practicing physicians and others on the management of the neck in patients with squamous cell carcinoma of the oral cavity and oropharynx.ASCO convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2018. Outcomes of interest included survival, regional disease control, neck recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.The literature search identified 124 relevant studies to inform the evidence base for this guideline. Six clinical scenarios were devised; three for oral cavity cancer and three for oropharynx cancer, and recommendations were generated for each one.For oral cavity cancers, clinical scenarios focused on the indications for and the hallmarks of a high-quality neck dissection, indications for postoperative radiotherapy or chemoradiotherapy, and whether radiotherapy alone is sufficient elective treatment of an undissected neck compared with high-quality neck dissection. For oropharynx cancers, clinical scenarios focused on hallmarks of a high-quality neck dissection, factors that would favor operative versus nonoperative primary management, and clarifying criteria for an incomplete response to definitive chemoradiation for which salvage neck dissection would be recommended. Consensus was reached and recommendations were made for all six clinical scenarios. Additional information is available at www.asco.org/head-neck-cancer-guidelines .
Large-scale Circulating microRNA Profiling for the Liquid Biopsy of Prostate Cancer
Authors: Fumihiko Urabe, Juntaro Matsuzaki, Yusuke Yamamoto, Takahiro Kimura, Tomohiko Hara, Makiko Ichikawa, Satoko Takizawa, Yoshiaki Aoki, Shumpei Niida, Hiromi Sakamoto, Ken Kato, Shin Egawa, Hiroyuki Fujimoto, Takahiro Ochiya
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsies. Therefore, the United States Preventive Services Task Force recommends that decisions regarding PSA-based screening of prostate cancer should be made with caution in men ages 55–69 years, and that men ≥70 years should not undergo PSA screening. Here, we investigated the potential of serum miRNAs as an accurate diagnostic method in patients with suspected prostate cancer. Experimental Design: Serum samples of 809 patients with prostate cancer, 241 negative prostate biopsies, and 500 patients with other cancer types were obtained from the National Cancer Center, Japan. Forty-one healthy control samples were obtained from two other hospitals in Japan. Comprehensive microarray analysis was performed for all samples. Samples were divided into three sets. Candidate miRNAs for prostate cancer detection were identified in the discovery set (n = 123). A diagnostic model was constructed using combinations of candidate miRNAs in the training set (n = 484). The performance of the diagnostic model was evaluated in the validation set (n = 484). Results: In the discovery set, 18 candidate miRNAs were identified. A robust diagnostic model was constructed using the combination of two miRNAs (miR-17-3p and miR-1185-2-3p) in the training set. High diagnostic performance with a sensitivity of 90% and a specificity of 90% was achieved in the validation set regardless of the Gleason score and clinical tumor–node–metastasis stage. Conclusions: The model developed in this study may help improve the diagnosis of prostate cancer and reduce the number of unnecessary prostate biopsies.
Usefulness of Home Blood Pressure Measurement in the Morning in Type 2 Diabetic Patients
Authors: Kyuzi Kamoi, Masashi Miyakoshi, Satoshi Soda, Susumu Kaneko, Osamu Nakagawa
Journal: Diabetes Care (2002)

Recently, repeated home blood pressure (HBP) measurements in the morning for a long period have been shown to have a stronger predictive power for mortality in patients with hypertension than occasional casual/clinic blood pressure (CBP) measurements. We studied whether HBP in the morning in type 2 diabetic patients is useful for prediction of diabetic complications.The occurrence of diabetic complications (nephropathy, retinopathy, coronary heart disease [CHD], and cerebrovascular disease [CVD]) were examined in relation to morning HBP as well as to CBP in 170 type 2 diabetic patients treated with antidiabetic and antihypertensive drugs. Blood pressure was measured at the clinic during the day and at home after awakening in the morning. Clinic hypertension (CH) and morning hypertension (MH) were defined as systolic blood pressure (SBP) > or =130 mmHg and/or diastolic blood pressure (DBP) > or =85 mmHg. The relation of CH and MH to the prevalence of these events was examined.There were no significant differences in the prevalence of nephropathy, retinopathy, CHD, and CVD between the two groups with (n = 131) and without CH (n = 39), whereas the prevalences of these events in the patients with MH (n = 97) were significantly higher (P < 0.05) than in those without MH (n = 73). The prevalence of nephropathy was highly associated with systolic MH.Elevations of HBP in the morning in diabetic patients are strongly related to microvascular and macrovascular complications, especially nephropathy. It is concluded that the control of MH may prevent vascular complications in type 2 diabetic patients.
Sensitization in Heart Transplantation: Emerging Knowledge: A Scientific Statement From the American Heart Association
Authors: Monica M. Colvin, Jennifer L. Cook, Patricia P. Chang, Daphne T. Hsu, Michael S. Kiernan, Jon A. Kobashigawa, JoAnn Lindenfeld, S. Carolina Masri, Dylan V. Miller, E. Rene Rodriguez, Dolly B. Tyan, Adriana Zeevi
Journal: Circulation (2019)

Sensitization, defined as the presence of circulating antibodies, presents challenges for heart transplant recipients and physicians. When present, sensitization can limit a transplantation candidate's access to organs, prolong wait time, and, in some cases, exclude the candidate from heart transplantation altogether. The management of sensitization is not yet standardized, and current therapies have not yielded consistent results. Although current strategies involve antibody suppression and removal with intravenous immunoglobulin, plasmapheresis, and antibody therapy, newer strategies with more specific targets are being investigated.
SP0029 Improving Your Graphs and Tables for Publication and Presentation
Authors: M. Boers
Journal: Annals of the Rheumatic Diseases (2015)

This workshop is an introduction to the principles of good graph and table design as pioneered by Cleveland<sup>1</sup> and Tufte<sup>2</sup> and updated by Few<sup>3</sup> so that the participant can better answer the following questions: Which of the messages in my research results requires a graph or table? Recognizing how graphs improve on simple statistics and convey much more information. Knowing when a table is better, or keeping the data in the body text. How can I best convey the message? Striving for clear vision by choice of graph, scaling, discrimination of data series, minimizing non-data ink, avoiding chart junk.Striving for clear understanding through a balance between data and explanation. Using order, subheadings, formatting and rules to guide your reader through your table data. Is my graph/table truthful? Creating a direct proportion between graph and data quantities, avoiding forms prone to misinterpretation, labels to prevent ambiguity; keeping data in context, avoiding more dimensions in the graph than in the data. This year9s course will have an extra focus on matrix graphs, and showcase the brand-new YouTube clips on the ARD website (ard.com)! Cleveland WS. The elements of graphing data: Hobart Press, Summit, NJ, U.S.A.; 1994. Tufte E. The visual display of quantitative information. 2nd ed: Graphics Press, Cheshire, CT, U.S.A.; 2001. Few S. Show me the numbers. Designing tables and graphs to enlighten. Analytics Press, Oakland, CA, U.S.A.; 2004. <h3>Disclosure of Interest</h3> None declared