tbuckley/cabot-search huggingface dataset:
Impact of acute stress on itch sensation and scratching behaviour in patients with atopic dermatitis and healthy controls
Authors: H. Mochizuki, M.J. Lavery, L.A. Nattkemper, C. Albornoz, R. Valdes Rodriguez, C. Stull, L. Weaver, J. Hamsher, K.M. Sanders, Y.H. Chan, G. Yosipovitch
Journal: British Journal of Dermatology (2018)

Patients with atopic dermatitis (AD) often report that stress aggravates their itch. However, no study has investigated if and how acute stress influences itch sensation and scratching behaviour in these patients. We evaluated the impact of acute stress on experimentally induced cowhage itch perception and scratching behaviour in 16 healthy subjects and 15 patients with AD. The Trier Social Stress Test (TSST) was used to induce acute stress. The itch sensation, provoked by applying cowhage to the forearms, and off‐site scratching behaviour (not directed at the cowhage application site) were compared before and after performing the TSST or the control condition (watching a video of landscape scenes). In patients with AD, stress induced by TSST caused a significant reduction of cowhage‐evoked itch but significantly increased off‐site scratching behaviour. Such changes in itch perception and scratching behaviour were not observed in healthy controls. In addition, a significant positive correlation was noted between stress induced by TSST and clinical severity of eczema. We speculate that psychological stress increases spontaneous scratching in patients with AD, which may enhance the vicious cycle of itching and scratching, resulting in aggravation of the skin eczema. These results provide new insights on the mechanism of acute stress‐related exacerbation of itch in patients with AD.
Maternal diaphragmatic hernia in mid-pregnancy
Authors: Kenta Kawai, Hiroaki Itoh, Naomi Isomura-Furuta, Naohiro Kanayama
Journal: BMJ (2018)

A 34 year old woman at 25 weeks’ gestation presented to the emergency department with chest pain. A chest radiograph revealed a haemopneumothorax-like air-fluid interface and absent lung markings in …
The Significance of the Intestinal Microbiome for Vaccinology: From Correlations to Therapeutic Applications
Authors: Vanessa C. Harris
Journal: Drugs (2018)

Despite unprecedented advances in understanding the intestinal microbiome, its potential to improve fields such as vaccinology has yet to be realized. This review briefly outlines the immunologic potential of the intestinal microbiome for vaccinology and highlights areas where the microbiome holds specific promise in vaccinology. Oral rotavirus vaccine effectiveness in low-income countries is used as a case study to describe how the intestinal microbiome may be employed to improve a vaccine's immunogenicity. A top-down, evidence-based approach is proposed to identify effective microbiota-based applications for vaccine improvement. Applying evidence from field studies in pertinent populations that correlate microbiome composition with vaccine effectiveness to appropriate experimental platforms will lead to the identification of safe, vaccine-supporting microbiota targets that are relevant to populations in need of improvement in vaccine-induced immunity.
Abstract 3136: Comprehensive profiling the immune-status of a broad range of in vivo syngeneic models
Authors: Jingqi Huang, Shipzong Hu, Wentao Li
Journal: Cancer Research (2018)

Abstract Latterly with approval of PD-1, PD-L1 antibodies in clinical oncology, immunotherapy has gain recognition for cancer treatment for changing the way by joining chemotherapy, radiation and surgery. This type of cancer treatment aims to produce greater effectiveness with less toxicity than cancer chemotherapy and mainly acts by boosting the body's natural defenses to fight the cancer. It uses substances made by the body or laboratory agent to improve or restore the function of immune system. Therefore, understood the nature immune status and micro environment of in vivo tumor models is very important to assist exploring immunotherapy. As a results, nearly 40 tumor cell lines over a broad range of tumor type as well as corresponding in vivo syngeneic models were intensively studied on its immune status under two conditions when tumor volume were 100 mm3 and 500 to 600mm3 . The effort has been focus on the immune status including T cell status and levels of immune-suppression via FACS analysis of the population of CD4+, CD8+, Treg, MDSC, macrophage and DC cells. Furthermore, not only population of immune cells but also the expressions of immune related gene were analyzed by RE-PCR which are the genes related regulatory of T cells i.e., CD4, Foxp3, GITR; gene of tumor associated macrophage CSF1R, CD68, CX3CR1, ITGAM, CD163, MARC1; gene of co-stimulator receptors of T cells ICOS, CD137(Tnfrsf9), OX40(Tnfrsf4); co-inhibitory receptors of T cell BTLA, HAVCR2, CTLA4, LAG3, CD28, PDCD1; and gene of co-inhibitory ligands of tumor cells CD274, CD137L(Tnfsf9), PDCD1LG2, HVEM(Tnfsf14), OX40L(Tnfsf4). The profiling data illustrated, indeed, the expression of PD-L1 is different on different tumor cells; the immune status certainly pending on the tumor type but also related to the tumor progression. The bigger tumor size the higher level of expression of immune suppression which deterring the immune cell ability to conquer cancer. We believe that this profiling data will help many scientists to properly select correct model to support R&amp;D and to better understand how immune therapeutically agent acts in the immune system. With this comprehensive research data, we're now at a point where this information has started to become translated into treatment possibilities for cancer patients. Citation Format: Jingqi Huang, Shipzong Hu, Wentao Li. Comprehensive profiling the immune-status of a broad range of in vivo syngeneic models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3136.
Successful endoscopic lithotripsy using a new digital cholangioscope through an overtube placed by an enteroscope
Authors: Ryunosuke Hakuta, Hirofumi Kogure, Yousuke Nakai, Atsuo Yamada, Naminatsu Takahara, Suguru Mizuno, Kazuhiko Koike
Journal: Endoscopy (2018)

A 29-year-old woman who had undergone extrahepatic bile duct resection and hepaticojejunostomy for congenital biliary dilation was admitted to our hospital with cholangitis. Magnetic resonance cholangiopancreatography revealed multiple large intrahepatic bile duct stones ([Fig. 1]). Most of the stones were fragmented and removed by extracorporeal shock wave lithotripsy and endoscopic mechanical lithotripsy (LithoCrush V; Olympus, Tokyo, Japan) during double-balloon endoscope-assisted endoscopic retrograde cholangiopancreatography (EI-580BT; Fujifilm, Tokyo, Japan). However, intrahepatic stones in the right posterior branch could not be removed owing to the acute angle of the duct ([Fig. 2]). To perform intraductal lithotripsy under direct visualization, the enteroscope was withdrawn while leaving the overtube in situ. The direct cholangioscope (SpyGlass DS Direct Visualization System; Boston Scientific Japan, Tokyo, Japan) was successfully advanced through the overtube into the right posterior branch. The intrahepatic stones were visualized ([Fig. 3]) and successfully fragmented by electrohydraulic lithotripsy using the Autolith EHL system and 1.9-Fr probe (Boston Scientific Japan). Finally, the cholangioscope was exchanged for the enteroscope, and fragmented stones were extracted using a balloon catheter ([Fig. 4], [Video 1]).
Dietary advanced glycation end products and their relevance for human health
Authors: Kerstin Nowotny, David Schröter, Monika Schreiner, Tilman Grune
Journal: Ageing Research Reviews (2018)

Due to their bioactivity and harmful potential, advanced glycation end products (AGEs) are discussed to affect human health. AGEs are compounds formed endogenously in the human body andexogenously, especially, in foods while thermal processing. In contrast to endogenous AGEs, dietary AGEs are formed in much higher extent. However, their risk potential is also depending on absorption, distribution, metabolism and elimination. For over 10 years an intense debate on the risk of dietary AGEs on human health is going on. On the one hand, studies provided evidence that dietary AGEs contribute to clinical outcomes. On the other hand, human studies failed to observe any association. Because it was not possible to draw a final conclusion, the call for new interdisciplinary approaches arose. In this review, we will give an overview on the current state of scientific knowledge in this field. In particular, we focus on (I) the occurrence of AGEs in foods and the daily uptake of AGEs, (II) contribution to endogenous levels and (III) the effect on health-/disease-related biomarkers in humans.
Quantitative proteomics of acutely-isolated mouse microglia identifies novel immune Alzheimer’s disease-related proteins
Authors: Srikant Rangaraju, Eric B. Dammer, Syed Ali Raza, Tianwen Gao, Hailian Xiao, Ranjita Betarbet, Duc M. Duong, James A. Webster, Chadwick M. Hales, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Journal: Molecular Neurodegeneration (2018)

Microglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into their molecular and functional diversity in homeostatic and neurodegenerative disease states. State-of-the-art mass spectrometry methods can comprehensively characterize proteomic alterations in microglia in neurodegenerative disorders, potentially providing novel functionally relevant molecular insights that are not provided by transcriptomics. However, comprehensive proteomic profiling of adult primary microglia in neurodegenerative disease conditions has not been performed. We performed quantitative mass spectrometry based proteomic analyses of purified CD11b+ acutely-isolated microglia from adult (6 mo) mice in normal, acute neuroinflammatory (LPS-treatment) and chronic neurodegenerative states (5xFAD model of Alzheimer's disease [AD]). Differential expression analyses were performed to characterize specific microglial proteomic changes in 5xFAD mice and identify overlap with LPS-induced pro-inflammatory changes. Our results were also contrasted with existing proteomic data from wild-type mouse microglia and from existing microglial transcriptomic data from wild-type and 5xFAD mice. Neuropathological validation studies of select proteins were performed in human AD and 5xFAD brains. Of 4133 proteins identified, 187 microglial proteins were differentially expressed in the 5xFAD mouse model of AD pathology, including proteins with previously known (Apoe, Clu and Htra1) as well as previously unreported relevance to AD biology (Cotl1 and Hexb). Proteins upregulated in 5xFAD microglia shared significant overlap with pro-inflammatory changes observed in LPS-treated mice. Several proteins increased in human AD brain were also upregulated by 5xFAD microglia (Aβ peptide, Apoe, Htra1, Cotl1 and Clu). Cotl1 was identified as a novel microglia-specific marker with increased expression and strong association with AD neuropathology. Apoe protein was also detected within plaque-associated microglia in which Apoe and Aβ were highly co-localized, suggesting a role for Apoe in phagocytic clearance of Aβ. We report a comprehensive proteomic study of adult mouse microglia derived from acute neuroinflammation and AD models, representing a valuable resource to the neuroscience research community. We highlight shared and unique microglial proteomic changes in acute neuroinflammation aging and AD mouse models and identify novel roles for microglial proteins in human neurodegeneration.
IFNγ-induced Chemokines Are Required for CXCR3-mediated T-Cell Recruitment and Antitumor Efficacy of Anti-HER2/CD3 Bispecific Antibody
Authors: Ji Li, Ryan Ybarra, Judy Mak, Aurelie Herault, Patricia De Almeida, Alfonso Arrazate, James Ziai, Klara Totpal, Melissa R. Junttila, Kevin B. Walsh, Teemu T. Junttila
Journal: Clinical Cancer Research (2018)

The response to cancer immune therapy is dependent on endogenous tumor-reactive T cells. To bypass this requirement, CD3-bispecific antibodies have been developed to induce a polyclonal T-cell response against the tumor. Anti-HER2/CD3 T-cell-dependent bispecific (TDB) antibody is highly efficacious in the treatment of HER2-overexpressing tumors in mice. Efficacy and immunologic effects of anti-HER2/CD3 TDB were investigated in mammary tumor model with very few T cells prior treatment. We further describe the mechanism for TDB-induced T-cell recruitment to tumors.The immunologic effects and the mechanism of CD3-bispecific antibody-induced T-cell recruitment into spontaneous HER2-overexpressing mammary tumors was studied using human HER2 transgenic, immunocompetent mouse models.Anti-HER2/CD3 TDB treatment induced an inflammatory response in tumors converting them from poorly infiltrated to an inflamed, T-cell abundant, phenotype. Multiple mechanisms accounted for the TDB-induced increase in T cells within tumors. TDB treatment induced CD8+ T-cell proliferation. T cells were also actively recruited post-TDB treatment by IFNγ-dependent T-cell chemokines mediated via CXCR3. This active T-cell recruitment by TDB-induced chemokine signaling was the dominant mechanism and necessary for the therapeutic activity of anti-HER2/CD3 TDB.In summary, we demonstrate that the activity of anti-HER2/CD3 TDB was not dependent on high-level baseline T-cell infiltration. Our results suggest that anti-HER2/CD3 TDB may be efficacious in patients and indications that respond poorly to checkpoint inhibitors. An active T-cell recruitment mediated by TDB-induced chemokine signaling was the major mechanism for T-cell recruitment.
Aβ-Clearing Drug Fails to Slow Alzheimer Disease
Authors: Anita Slomski
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington’s Disease Minipig Model
Authors: Melvin M. Evers, Jana Miniarikova, Stefan Juhas, Astrid Vallès, Bozena Bohuslavova, Jana Juhasova, Helena Kupcova Skalnikova, Petr Vodicka, Ivona Valekova, Cynthia Brouwers, Bas Blits, Jacek Lubelski, Hana Kovarova, Zdenka Ellederova, Sander J. van Deventer, Harald Petry, Jan Motlik, Pavlina Konstantinova
Journal: Molecular Therapy (2018)

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Previously, we showed strong huntingtin reduction and prevention of neuronal dysfunction in HD rodents using an engineered microRNA targeting human huntingtin, delivered via adeno-associated virus (AAV) serotype 5 vector with a transgene encoding an engineered miRNA against HTT mRNA (AAV5-miHTT). One of the challenges of rodents as a model of neurodegenerative diseases is their relatively small brain, making successful translation to the HD patient difficult. This is particularly relevant for gene therapy approaches, where distribution achieved upon local administration into the parenchyma is likely dependent on brain size and structure. Here, we aimed to demonstrate the translation of huntingtin-lowering gene therapy to a large-animal brain. We investigated the feasibility, efficacy, and tolerability of one-time intracranial administration of AAV5-miHTT in the transgenic HD (tgHD) minipig model. We detected widespread dose-dependent distribution of AAV5-miHTT throughout the tgHD minipig brain that correlated with the engineered microRNA expression. Both human mutant huntingtin mRNA and protein were significantly reduced in all brain regions transduced by AAV5-miHTT. The combination of widespread vector distribution and extensive huntingtin lowering observed with AAV5-miHTT supports the translation of a huntingtin-lowering gene therapy for HD from preclinical studies into the clinic.
Impact of turnaround time on outcome with point-of-care testing for respiratory viruses: a <i>post hoc</i> analysis from a randomised controlled trial
Authors: Nathan J. Brendish, Ahalya K. Malachira, Kate R. Beard, Sean Ewings, Tristan W. Clark
Journal: European Respiratory Journal (2018)

Respiratory viruses are detected in around 40–50% of adults hospitalised with acute respiratory illness (ARI) [1, 2]. Routine laboratory PCR testing for respiratory viruses generally takes several hours to several days to generate results for clinicians and so cannot be used to inform decision making in real time. Decisions about hospitalisation, antibiotics, antivirals and side room isolation therefore need to be made presumptively and reviewed when results are available. Newer rapid molecular test platforms are accurate, easy to use, and generate a result in 1 h or less, making them potentially deployable for point-of-care testing (POCT) in clinical areas [3]. Recently, we reported on a large pragmatic randomised controlled trial (ResPOC) [4] which evaluated the impact of POCT (using the FilmArray Respiratory Panel (BioFire Diagnostics, Salt Lake City, UT, USA) which tests for a comprehensive range of viruses) in adults presenting to hospital with ARI. The study showed that POCT was associated with reductions in hospital length of stay overall and reductions in antibiotics use in patients with exacerbation of airways disease. Although this evidence would suggest that rapid molecular testing needs to be performed within clinical areas for these improved clinical outcomes, it has been suggested that rapid molecular test platforms used within centralised laboratories might also be associated with these clinical benefits, although the turnaround times (TATs) are likely to be much longer. In this follow-on study we evaluate the impact of POCT TAT on clinical outcomes with a view to determining how rapid molecular testing for respiratory viruses should be best implemented in clinical practice. As very rapid turnaround times lead to better outcomes, virus diagnostics should be performed at the point-of-care <http://ow.ly/eD6p30koZGg> We thank all of the patients and clinical staff at the Southampton General Hospital, including clinicians, nurses and laboratory technicians. We thank the directors, research nurses, data managers, clinical trials assistants and laboratory staff at the NIHR Southampton Clinical Research Facility and the NIHR Southampton Biomedical Research Centre. We thank the staff at the R&D Department, University Hospital Southampton NHS Foundation Trust and the NIHR Clinical Research Network, Wessex for their support throughout the trial.
Abstract 168: Cancer stem-like properties and drug resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2
Authors: Noriko Gotoh, Tatsunori Nishimura, Asuka Nakata, Shin-ichi Horike, Susumu Kohno, Chiaki Takahashi, Tomoyoshi Soga, Arinobu Tojo
Journal: Cancer Research (2018)

Abstract Tumor recurrence is attributable to cancer stem-like cells (CSCs), the metabolic mechanisms of which currently remain obscure. Here, we uncovered the critical role of folate-mediated one-carbon (1C) metabolism involving mitochondrial methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and its downstream purine synthesis pathway. MTHFD2 knockdown greatly reduced tumorigenesis and stem-like properties, which were associated with purine nucleotide deficiency, and caused marked accumulation of 5-aminoimidazole carboxamide ribonucleotide (AICAR)—the final intermediate of the purine synthesis pathway. Lung cancer cells with acquired resistance to the targeted drug gefitinib exhibited increased stem-like properties and enhanced expression of MTHFD2. MTHFD2 knockdown or treatment with AICAR reduced the stem-like properties and restored gefitinib sensitivity in gefitinib-resistant cancer cells. Thus, MTHFD2-mediated mitochondrial 1C metabolism appears critical for cancer stem-like properties and resistance to drugs including gefitinib through consumption of AICAR, leading to depletion of the intracellular pool of AICAR. Because CSCs are dependent on MTHFD2, therapies targeting MTHFD2 may eradicate tumors and prevent recurrence. Citation Format: Noriko Gotoh, Tatsunori Nishimura, Asuka Nakata, Shin-ichi Horike, Susumu Kohno, Chiaki Takahashi, Tomoyoshi Soga, Arinobu Tojo. Cancer stem-like properties and drug resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 168.