tbuckley/cabot-search huggingface dataset:
Targeting protein and peptide therapeutics to the heart via tannic acid modification
Authors: Mikyung Shin, Hyang-Ae Lee, Mihyun Lee, Yoomi Shin, Ji-Joon Song, Sun-Woong Kang, Dae-Hwan Nam, Eun Je Jeon, Mira Cho, Minjae Do, SunHyun Park, Moon Sue Lee, Jae-Hyung Jang, Seung-Woo Cho, Ki-Suk Kim, Haeshin Lee
Journal: Nature Biomedical Engineering (2018)
Steroid-induced changes noted on trichoscopy of patients with frontal fibrosing alopecia
Authors: David Saceda-Corralo, Óscar M. Moreno-Arrones, Pablo Fonda-Pascual, Cristina Pindado-Ortega, Ángela Hermosa-Gelbard, Ana R. Rodrigues-Barata, Sergio Vañó-Galván
Journal: Journal of the American Academy of Dermatology (2018)
Incidental Detection of Meningioma by 18F-FMAU PET/CT in a Patient With Suspected Prostate Cancer
Authors: Bino Varghese, Erik Velez, Bhushan Desai, Hossein Jadvar
Journal: Clinical Nuclear Medicine (2018)

Abstract We report on an incidental detection of a meningioma on [ 18 F]-2′-fluoro-5-methyl-1-beta- d -arabinofuranosyluracil ( 18 F-FMAU) PET/CT scan that was performed during a prospective investigation of 18 F-FMAU PET/CT for targeted biopsy of potential sites of tumor in men with suspected prostate cancer based on elevated prostate-specific antigen level. Neither prostate multiparamteric MRI nor 18 F-FMAU PET/CT localized small volume Gleason 3 + 3 tumor deposits. However, an incidental focal high accumulation of 18 F-FMAU was observed in high right parietal lobe that displayed characteristics of a meningioma on a subsequent brain MRI.
Aryl hydrocarbon receptor activation by diesel exhaust particles mediates epithelium‐derived cytokines expression in severe allergic asthma
Authors: C.‐M. Weng, C.‐H. Wang, M.‐J. Lee, J.‐R. He, H.‐Y. Huang, M.‐W. Chao, K. F. Chung, H.‐P. Kuo
Journal: Allergy (2018)

Abstract Background Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium‐derived thymic stromal lymphopoietin ( TSLP ), interleukin ( IL )‐25, and IL ‐33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. Methods Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation ( NT ), cytokine expression, and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles ( DEP ) to determine AhR‐mediated IL ‐33, Il‐25, and TSLP synthesis and release. Results Primary bronchial epithelial cells exposed to DEP showed upregulation of IL ‐33, IL ‐25, and TSLP . These effects were abolished by knockdown of AhR by si RNA . Increased AhR/ ARNT binding to promoters of IL ‐33, IL ‐25, and TSLP was found using chromatin immunoprecipitation (Ch IP ) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL ‐33, IL ‐25, and TSLP . These patients derived clinical benefit from anti‐IgE treatment. Conclusion Aryl hydrocarbon receptor activation by DEP mediates upregulation of IL ‐33, IL ‐25, and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma.
Proof of concept study of an apoptosis-signal regulating kinase (ASK1) inhibitor (selonsertib) in combination with an acetyl-CoA carboxylase inhibitor (GS-0976) or a farnesoid X receptor agonist (GS-9674) in NASH
Authors: E. Lawitz, R. Herring, Z.H. Younes, E. Gane, P. Ruane, R.A. Schall, C. Jia, R. Xu, B. Mccolgan, S. Djedjos, M. Subramanian, J.G. Mchutchison, R. Myers, M. Middleton, K. Li, M. Hellerstein, P. Kwo, M. Noureddin, S. Harrison
Journal: Journal of Hepatology (2018)
Use of the Emergency Ambulance Service to an Inner City Accident and Emergency Department – a Comparison of General Practitioner and ‘999’ Calls
Authors: A G Pennycook, R M Makower, W G Morrison
Journal: Journal of the Royal Society of Medicine (1991)

Over a 2-week period a prospective study was undertaken of patients brought to an inner city accident and emergency department by the emergency ambulance service. Criteria for assessing the appropriateness of use of the emergency ambulance service are not well defined and at worst entirely subjective. The author's finding that, of patients attending after a ‘999’ call, 49.8% were discharged with no follow-up suggests that many of these journeys represented inappropriate use of the emergency ambulance service. Close liaison between senior medical staff and the emergency ambulance service may allow more appropriate and effective use of the service, improving patient care in the pre-hospital setting.
Abstract 15275: Effectiveness of Combination of Intracellular and Extracellular Aminothiols for Prediction of Cardiovascular Events
Authors: Nobuyuki Masaki, Bonpei Takase, Takeshi Adachi
Journal: Circulation (2016)

Backgrounds:  Disulfide bonds are formed from the oxidation of sulfhydryl (-SH) groups such as glutathione disulfide (GSSH) from glutathione (GSH), cystine from cysteine. The aminothiols indicate oxidative stress. But, the difference has not been fully investigated.   Hypothesis:  Combination of GSSG in red blood cells (RBC) and serum total cysteine (tCys) comprising mainly cystine may predict cardiovascular events.   Methods:  255 patients with cardiovascular disease (65±13 y/o) were prospectively followed up for 2.68±1.47 years. An oxidative stress test of d-ROMs was also performed.   Results:  In the follow-up, there were 8 (3%) of cardiovascular deaths, 12 (5%) of MACEs, 47 (18%) of cardiovascular events (MACEs plus hospitalization for heart failure, cardiovascular surgery, revascularization). There was a weak correlation between GSSG and tCys (r=0.167), but neither of them was associated with d-ROMs. tCys was negatively correlated to eGFR (r=-0.350). We classified the patients into four groups with combining the medians as cut-off points (tCys: 165.20 μM, GSSG: 34.61 μM); Group I (number of pts.=72): low tCys and low GSSG, Group II (57): high tCys and low GSSG, Group III (57): low tCys and high GSSG, Group IV (69): high tCys and high GSSG. Kaplan-Meier curves showed that Group II, IV had significantly higher rates of cardiovascular events and Group III tended to increase cardiovascular events (log-rank; p=0.050)  (Figure).  In univariate COX analysis, hazard ratios (HR) with setting Group I as reference were Group II 3.094 (CI 1.089-8.792, p=0.034), Group III 3.025 (CI 1.012-9.040, p=0.047), Group IV 5.210 (CI 1.962-13.830, p=0.001). After adjustment for age, sex, coronary risk factors, CRP, eGFR, d-ROMs, Group III, IV remained in high risk; Group III 3.598 (CI 1.183-10.945, p=0.024), Group IV 3.646 (CI 1.294-10.277, p=0.014).   Conclusions:  tCys partially depended on renal function, but GSSG did not. The combination was useful to stratify further cardiovascular risks.
Abstract 191: Paracrine Impact of Cardiac Progenitor Cells on Macrophage Phenotypes and Human Ipsc-derived Cardiomyocyte Survival
Authors: Michela Noseda, Chrystalla Constantinou, Sara Samari, Patricia Chaves, Kevin Cheng, Chiara Beretta, Tiago Rito, Marta Abreu-Paiva, Ana Pombo, Michael D Schneider
Journal: Circulation Research (2017)

The clinical progression of myocardial infarction, the foremost cause of death globally, to heart failure is proportionally higher with increasing infarct size. Thus, preventing cardiomyocyte loss at time of injury and stimulating self-repair are fruitful approaches to counteract the severity of cardiac damage. We previously found that intramyocardial injection of cardiac progenitor cells (CPCs) at time of ischemia improves cardiac function 12 weeks later. Given poor long-term engraftment in our studies and many others’, the consensus is that early paracrine effects are the probable cause of the benefits observed, including direct effects on cardiomyocytes but also macrophages as key players in the response to injury. Here, using transwell and conditioned medium experiments, we show that CPCs suppress the death of cardiomyocytes after oxidative stress. In this highly tractable model system, CPCs protect not only mouse cardiomyocytes, but also human iPSC-derived cardiomyocytes. Moreover, we show that CPC-conditioned medium affects macrophage differentiation and polarization. Cardioprotective CPCs disrupt the pro-inflammatory (“M1”) programme induced by GM-CSF/LPS/IFNγ, and promote instead the formation of anti-inflammatory (“M2”) macrophages as shown by single cell qRT-PCR. To identify the effectors of the cardioprotective paracrine cocktail, we performed RNA-Seq on unfractionated Sca1 + cardiac stromal cells, identified wound healing and immune response enriched GeneOntologies, then mapped noteworthy hits by single-cell qPCR to the PDGFRα + CPC subpopulation. By a combination of single-cell gene expression profiling in protective versus non-protective cells, plus highly multiplexed immunoassays (LEGENDplex, O-Link), we identified 6-8 candidates as potential mediators of cardiomyocyte protection and M2 macrophage induction. In summary, our data: (1) Define a consistent single-cell paracrine gene signature in adult CPCs; (2) Resolve specific benefits conferred by CPCs in the M1 versus M2 macrophage phenotypes; (3) Demonstrate the utility of iPSC-derived cardiomyocytes as a human platform for paracrine protection studies.
Gestational Diabetes Mellitus and Renal Function: A Prospective Study With 9- to 16-Year Follow-up After Pregnancy
Authors: Shristi Rawal, Sjurdur F. Olsen, Louise G. Grunnet, Ronald C. Ma, Stefanie N. Hinkle, Charlotta Granström, Jing Wu, Edwina Yeung, James L. Mills, Yeyi Zhu, Wei Bao, Sylvia H. Ley, Frank B. Hu, Peter Damm, Allan Vaag, Michael Y. Tsai, Cuilin Zhang
Journal: Diabetes Care (2018)

OBJECTIVE To examine whether gestational diabetes mellitus (GDM), independent of subsequent diabetes, is an early risk factor for renal impairment long term after the index pregnancy. RESEARCH DESIGN AND METHODS In the Diabetes &amp; Women’s Health (DWH) study (2012–2016), we examined the independent and joint associations of GDM and subsequent diabetes with long-term renal function among 607 women with and 619 women without GDM in the Danish National Birth Cohort (DNBC) index pregnancy (1996–2002). At median follow-up of 13 years after the index pregnancy, serum creatinine (mg/dL) and urinary albumin (mg/L) and creatinine (mg/dL) were measured, from which estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) and urinary albumin-to-creatinine ratio (UACR) (mg/g) were derived. RESULTS Compared with women without GDM or subsequent diabetes, women with a GDM history had significantly higher eGFR even if they had not subsequently developed diabetes (adjusted β-coefficient [95% CI] = 3.3 [1.7, 5.0]). Women who had a GDM history and later developed diabetes (n = 183) also had significantly higher UACR [exponent β = 1.3 [95% CI 1.1, 1.6]) and an increased risk of elevated UACR (≥20 mg/g) [adjusted relative risk [95% CI] = 2.3 [1.1, 5.9]) compared with women with neither. After adjusting for potential confounders including prepregnancy BMI and hypertension, GDM without subsequent diabetes was not related to UACR. CONCLUSIONS Women who develop GDM in pregnancy were more likely to show increased eGFR levels 9–16 years postpartum, which could indicate early stages of glomerular hyperfiltration and renal damage. However, only those who subsequently developed diabetes showed overt renal damage as evidenced by elevated UACR.
Sarcopenia is not a predictor of survival or sorafenib toxicity in advanced hepatocellular carcinoma: A Dutch multicenter study
Authors: T. Labeur, J. van Vugt, D.T. Cate, B. Takkenberg, B.G. Koerkamp, R.D. Man, O. van Delden, J. Ijzermans, F. Eskens, H.-J. Klümpen
Journal: Journal of Hepatology (2018)
IOC Medical and Scientific Commission reviews its position on the use of dietary supplements by elite athletes
Authors: Ronald John Maughan
Journal: British Journal of Sports Medicine (2018)

Success in sport is determined by genetic endowment and by the modulation of that innate talent by an appropriate training programme. When athletes train to the limits of what is possible, they inevitably look for other factors that may help them to gain an advantage over the opposition. Of these, nutrition is often seen as an ‘easy’ option, and it is undoubtedly true that the food choices that an athlete makes will have profound effects on the ability to sustain consistent and intensive training and to amplify the training response. Although some of the details are unclear and are the subject of debate, there is little doubt that good nutrition strategies can also optimise performance in competition.1 

At the highest level of sport, competitors will all be genetically gifted, will have trained intensively and will have exploited all obvious performance-enhancement strategies. In the search for further gains, the use of dietary supplements is an attractive opportunity. Athletes may feel that …
Ex-vivo culture of normal and cancerous tissues: a tissue slice model
Authors: Valentina Vaira, Giuseppe Fedele, Ester Fasoli, Giorgia Zadra, Massimo Loda, Silvano Bosari
Journal: Cancer Research (2008)

398  Purpose: Cell cultures are widely used in cancer research though correlation with in vivo research is often poor. We propose an ex-vivo model of human tissue cultures that more closely resemble the in vivo three-dimensional environment to evaluate biological mechanisms present in pathological conditions. Fresh tissue are cut at the desired thickness by a vibrating microtome to obtain organotypic cultures. For validation we assessed tissue viability and the expression of selected members of the PI3K/AKT pathway. Procedures: We investigated 14 samples of colorectal, lung and prostate carcinomas (K) and 5 matched normal (N) specimens. Slices (400μm thick) were cultured on permeable membrane inserts in complete Ham F-12 media up to 96h after resection. Slices were evaluated every 24h: for each time point, one slice was formalin-fixed for morphological and immunohistochemical (IHC) evaluation and one slice was snap-frozen for qPCR studies. Slices for baseline conditions (T0) were used as reference for all experiments. Tissues proliferative status was assessed by Mib1 staining. We investigated the PI3K/Akt pathway by phospho-specific antibodies and by qPCR (table 1). Results: Tissue viability was maintained across all time points. All tumor tissues displayed proliferative activity up to 96h in contrast to normal samples. FASN displayed the most stable expression among the whole dataset. In tumors we observed an increase in p-S6K at 24, 48 and 96h schedules. Normal cultures showed stable low levels of p-AKT and p-S6K. Results of qPCR are presented in table 1. Normal samples were remarkably stable across all time points regardless of tissue origin. In tumors, a general increase in mRNA synthesis was appreciated. FAK and PI3K were upregulated from T24 to T96 whereas only BIRC5 was reduced. Conclusions: This tissue slice model represents a simple and suitable method to maintain tissue architecture with preservation of tumor-stroma interactions. This model can be used to evaluate dynamically pathological processes.
Deptor Is a Novel Target of Wnt/β-Catenin/c-Myc and Contributes to Colorectal Cancer Cell Growth
Authors: Qingding Wang, Yuning Zhou, Piotr Rychahou, Jennifer W. Harris, Yekaterina Y. Zaytseva, Jinpeng Liu, Chi Wang, Heidi L. Weiss, Chunming Liu, Eun Y. Lee, B. Mark Evers
Journal: Cancer Research (2018)

Abstract Activation of the Wnt/β-catenin signaling pathway drives colorectal cancer growth by deregulating expression of downstream target genes, including the c-myc proto-oncogene. The critical targets that mediate the functions of oncogenic c-Myc in colorectal cancer have yet to be fully elucidated. Previously, we showed that activation of PI3K/Akt/mTOR contributes to colorectal cancer growth and metastasis. Here, we show that Deptor, a suppressor of mTOR, is a direct target of Wnt/β-catenin/c-Myc signaling in colorectal cancer cells. Inhibition of Wnt/β-catenin or knockdown of c-Myc decreased, while activation of Wnt/β-catenin or overexpression of c-Myc increased the expression of Deptor. c-Myc bound the promoter of Deptor and transcriptionally regulated Deptor expression. Inhibition of Wnt/β-catenin/c-Myc signaling increased mTOR activation, and the combination of Wnt and Akt/mTOR inhibitors enhanced inhibition of colorectal cancer cell growth in vitro and in vivo. Deptor expression was increased in colorectal cancer cells; knockdown of Deptor induced differentiation, decreased expression of B lymphoma Mo-MLV insertion region 1 (Bmi1), and decreased proliferation in colorectal cancer cell lines and primary human colorectal cancer cells. Importantly, our work identifies Deptor as a downstream target of the Wnt/β-catenin/c-Myc signaling pathway, acting as a tumor promoter in colorectal cancer cells. Moreover, we provide a molecular basis for the synergistic combination of Wnt and mTOR inhibitors in treating colorectal cancer with elevated c-Myc. Significance: The mTOR inhibitor DEPTOR acts as a tumor promoter and could be a potential therapeutic target in colorectal cancer. Cancer Res; 78(12); 3163–75. ©2018 AACR.
Addressing Continued Disparities in Access to Breast Reconstruction on the 20th Anniversary of the Women’s Health and Cancer Rights Act
Authors: Nicholas L. Berlin, Edwin G. Wilkins, Amy K. Alderman
Journal: JAMA Surgery (2018)

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Rational design of silicon structures for optically controlled multiscale biointerfaces
Authors: Yuanwen Jiang, Xiaojian Li, Bing Liu, Jaeseok Yi, Yin Fang, Fengyuan Shi, Xiang Gao, Edward Sudzilovsky, Ramya Parameswaran, Kelliann Koehler, Vishnu Nair, Jiping Yue, KuangHua Guo, Yin Fang, Hsiu-Ming Tsai, George Freyermuth, Raymond C. S. Wong, Chien-Min Kao, Chin-Tu Chen, Alan W. Nicholls, Xiaoyang Wu, Gordon M. G. Shepherd, Bozhi Tian
Journal: Nature Biomedical Engineering (2018)
High virological cure rate and low rate of reinfection in a project to eradicate HCV in people who inject drugs at risk for non-adherence to direct-acting antivirals in Vienna
Authors: A. Schütz, C. Schwanke, E. Gutic, T. Lang, R. Schubert, J. Luhn, S. Moser, H. Haltmayer, M. Gschwantler
Journal: Journal of Hepatology (2018)
Detection of Cerebrospinal Fluid Dissemination of Recurrent Glioblastoma Using TSPO-PET With 18F-GE-180
Authors: Marcus Unterrainer, Daniel F. Fleischmann, Simon Lindner, Matthias Brendel, Rainer Rupprecht, Joerg C. Tonn, Claus Belka, Peter Bartenstein, Maximilian Niyazi, Nathalie L. Albert
Journal: Clinical Nuclear Medicine (2018)

PET targeting the translocator protein (TSPO) represents an interesting approach for glioma visualization, as TSPO is highly expressed in tumor cells. We present a 32-year-old man with recurrent glioblastoma after multimodal treatment. PET with the novel TSPO ligand F-GE-180 was performed after reirradiation. Here, the previously reirradiated tumor showed a remaining circular TSPO expression. Moreover, cerebrospinal fluid dissemination was detected by a high focal uptake at the right lateral and at the fourth ventricle, whereas only a faint contrast enhancement was present in MRI. This case demonstrated the diagnostic potential of TSPO-PET for glioma imaging by visualizing even minimal disease burden.
Soluble CD146 is a predictive marker of pejorative evolution and of sunitinib efficacy in clear cell renal cell carcinoma
Authors: Maeva Dufies, Marie Nollet, Damien Ambrosetti, Wael Traboulsi, Julien Viotti, Delphine Borchiellini, Renaud Grépin, Julien Parola, Sandy Giuliano, Dominique Helley-Russick, Karim Bensalah, Alain Ravaud, Jean-Christophe Bernhard, Renaud Schiappa, Nathalie Bardin, Françoise Dignat-George, Nathalie Rioux-Leclercq, Stephane Oudard, Sylvie Négrier, Jean-Marc Ferrero, Emmanuel Chamorey, Marcel Blot-Chabaud, Gilles Pagès
Journal: Theranostics (2018)

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Radiation-induced inflammation and autoimmune diseases
Authors: Rasoul Yahyapour, Peyman Amini, Saeed Rezapour, Mohsen Cheki, Abolhasan Rezaeyan, Bagher Farhood, Dheyauldeen Shabeeb, Ahmed Eleojo Musa, Hengameh Fallah, Masoud Najafi
Journal: Military Medical Research (2018)

Currently, ionizing radiation (IR) plays a key role in the agricultural and medical industry, while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern. Exposure to IR has various detrimental effects on normal tissues. Although an increased risk of carcinogenesis is the best-known long-term consequence of IR, evidence has shown that other diseases, particularly diseases related to inflammation, are common disorders among irradiated people. Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people. Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR. However, the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated, and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role. Thus, cytokines, including interleukin-1(IL-1), tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to IR. Additionally, these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH). It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster. In the present study, we reviewed the evidence of radiation-induced diabetes and thyroid diseases, as well as the potential roles of inflammatory responses. In addition, we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.
Thromboxane A 2 facilitates IL-17A production from Vγ4 + γδ T cells and promotes psoriatic dermatitis in mice
Authors: Yuri Ueharaguchi, Tetsuya Honda, Nobuhiro Kusuba, Sho Hanakawa, Akimasa Adachi, Yu Sawada, Atsushi Otsuka, Akihiko Kitoh, Teruki Dainichi, Gyohei Egawa, Chisa Nakashima, Saeko Nakajima, Teruasa Murata, Sachiko Ono, Makoto Arita, Shuh Narumiya, Yoshiki Miyachi, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2018)
Schrödinger's Disease and the Ethics of (Non)Diagnosis: The Problem of Medically Unexplained Symptoms in Contemporary Medical Practice
Authors: Louise Stone
Journal: The American Journal of Bioethics (2018)

"Schrödinger's Disease and the Ethics of (Non)Diagnosis: The Problem of Medically Unexplained Symptoms in Contemporary Medical Practice." The American Journal of Bioethics, 18(5), pp. 18–19