tbuckley/cabot-search huggingface dataset:
Do mucosal biomarkers reveal the immunological state associated with food allergy?
Authors: Eliete Neves Silva Guerra, Ana Carolina Acevedo, Isabela Porto de Toledo, Audrey Combes, Hélène Chardin
Journal: Allergy (2018)

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One hundred percent survival after transplantation of 34 patients with Wiskott-Aldrich syndrome over 20 years
Authors: Reem Ahmed Elfeky, Juliana M. Furtado-Silva, Robert Chiesa, Kanchan Rao, Persis Amrolia, Giovanna Lucchini, Kimberly Gilmour, Stuart Adams, Shahnaz Bibi, Austen Worth, Adrian J. Thrasher, Waseem Qasim, Paul Veys
Journal: Journal of Allergy and Clinical Immunology (2018)
BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer
Authors: Sen Chen, Changmeng Cai, Adam G. Sowalsky, Huihui Ye, Fen Ma, Xin Yuan, Nicholas I. Simon, Nathanael S. Gray, Steven P. Balk
Journal: Cancer Research (2018)

Abstract Prostate cancer responds to therapies that suppress androgen receptor (AR) activity (androgen deprivation therapy, ADT) but invariably progresses to castration-resistant prostate cancer (CRPC). The Tec family nonreceptor tyrosine kinase BMX is activated downstream of PI3K and has been implicated in regulation of multiple pathways and in the development of cancers including prostate cancer. However, its precise mechanisms of action, and particularly its endogenous substrates, remain to be established. Here, we demonstrate that BMX expression in prostate cancer is suppressed directly by AR via binding to the BMX gene and that BMX expression is subsequently rapidly increased in response to ADT. BMX contributed to CRPC development in cell line and xenograft models by positively regulating the activities of multiple receptor tyrosine kinases through phosphorylation of a phosphotyrosine-tyrosine (pYY) motif in their activation loop, generating pYpY that is required for full kinase activity. To assess BMX activity in vivo, we generated a BMX substrate–specific antibody (anti-pYpY) and found that its reactivity correlated with BMX expression in clinical samples, supporting pYY as an in vivo substrate. Inhibition of BMX with ibrutinib (developed as an inhibitor of the related Tec kinase BTK) or another BMX inhibitor BMX-IN-1 markedly enhanced the response to castration in a prostate cancer xenograft model. These data indicate that increased BMX in response to ADT contributes to enhanced tyrosine kinase signaling and the subsequent emergence of CRPC, and that combination therapies targeting AR and BMX may be effective in a subset of patients. Significance: The tyrosine kinase BMX is negatively regulated by androgen and contributes to castration-resistant prostate cancer by enhancing the phosphorylation and activation of multiple receptor tyrosine kinases following ADT. Cancer Res; 78(18); 5203–15. ©2018 AACR.
Prevalence of musculoskeletal injuries and a proposal for neuromuscular training to prevent lower limb injuries in Brazilian Army soldiers: an observational study
Authors: Michele Zukauskas de Andrade Gomes, Carlos Eduardo Pinfildi
Journal: Military Medical Research (2018)

The activities carried out by soldiers in the army involve great physical demands and require intense trainings to perform combat-specific tasks. Musculoskeletal injury is a potential threat to the health and physical integrity of the soldier. This study aimed to evaluate the prevalence of lower limb musculoskeletal injuries among soldiers and to propose a training protocol to prevent the most frequent injuries.
Monocyte/Macrophage Suppression in CD11b Diphtheria Toxin Receptor Transgenic Mice Differentially Affects Atherogenesis and Established Plaques
Authors: VictoriaStoneman, DeniseBraganza, NicholaFigg, JohnMercer, RichardLang, MartinGoddard, MartinBennett
Journal: Circulation Research (2007)

Although monocytes/macrophages are considered important in atherogenesis, their role in established plaques is unclear. For example, macrophage content is associated with plaque instability, but their loss through cell death is observed at sites of plaque rupture. To examine the role of monocytes/macrophages in atherosclerosis, we developed CD11b–diphtheria toxin (DT) receptor (DTR) transgenic mice, whereby administration of DT selectively kills monocytes/macrophages. DT treatment reduced peripheral blood monocytes and tissue macrophages and inhibited macrophage function in CD11b-DTR mice and apolipoprotein E–null (apoE−/−) mice transplanted with CD11b-DTR bone marrow. In atherogenesis experiments, DT markedly reduced plaque development and altered plaque composition, reducing collagen content and necrotic core formation. In mice with established plaques, acute DT treatment induced macrophage apoptosis and reduced macrophage content but did not induce plaque inflammation, thrombosis, or rupture. Furthermo...
Heat-related mortality trends under recent climate warming in Spain: A 36-year observational study
Authors: Hicham Achebak, Daniel Devolder, Joan Ballester
Journal: PLoS Medicine (2018)

Anthropogenic greenhouse gas emissions have increased summer temperatures in Spain by nearly one degree Celsius on average between 1980 and 2015. However, little is known about the extent to which the association between heat and human mortality has been modified. We here investigate whether the observed warming has been associated with an upward trend in excess mortality attributable to heat or, on the contrary, a decrease in the vulnerability to heat has contributed to a reduction of the mortality burden.
Provider Conscientious Refusal of Abortion, Obstetrical Emergencies, and Criminal Homicide Law
Authors: Lawrence Nelson
Journal: The American Journal of Bioethics (2018)

Catholic doctrine's strict prohibition on abortion can lead clinicians or institutions to conscientiously refuse to provide abortion, although a legal duty to provide abortion would apply to anyone who refused. Conscientious refusals by clinicians to end a pregnancy can constitute murder or reckless homicide under American law if a woman dies as a result of such a refusal. Such refusals are not immunized from criminal liability by the constitutional right to the free exercise of religion or by statutes that confer immunity from criminal homicide prosecution. Core principles of the rule of law require the state to protect the lives of all persons equally and to place the life and health of persons above any the interests of providers have in moral integrity or in respecting the moral status of prenatal humans. In some states criminal liability related to conscientious objection also applies to corporate hospital officials.
Metabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma
Authors: Richard Mair, Alan J. Wright, Susana Ros, De-en Hu, Tom Booth, Felix Kreis, Jyotsna Rao, Colin Watts, Kevin M. Brindle
Journal: Cancer Research (2018)

C MRI of hyperpolarized [1-
Specific Jagged-1 Signal From Bone Marrow Microenvironment Is Required for Endothelial Progenitor Cell Development for Neovascularization
Authors: Sang-MoKwon, MasamichiEguchi, MikaWada, YoIwami, KatsuhitoHozumi, HidekiIwaguro, HaruchikaMasuda, AtsuhikoKawamoto, TakayukiAsahara
Journal: Circulation (2008)

Background— Despite accumulating evidence that proves the pivotal role of endothelial progenitor cells (EPCs) in ischemic neovascularization, the key signaling cascade that regulates functional EPC kinetics remains unclear. Methods and Results— In this report, we show that inactivation of specific Jagged-1 (Jag-1)–mediated Notch signals leads to inhibition of postnatal vasculogenesis in hindlimb ischemia via impairment of proliferation, survival, differentiation, and mobilization of bone marrow–derived EPCs. Bone marrow–derived EPCs obtained from Jag-1−/− mice, but not Delta-like (Dll)-1−/− mice, demonstrated less therapeutic potential for ischemic neovascularization than EPCs from the wild type. In contrast, a gain-of-function study using 3T3 stromal cells overexpressing Notch ligand revealed that Jag-1–mediated Notch signals promoted EPC commitment, which resulted in enhanced neovascularization. The impaired neovascularization in Jag-1−/− mice was profoundly rescued by transplantation of Jag-1–stimulate...
Abstract 19562: The Relationship Between the Targeted Temperature of TTM and Neurological Outcome, the CRITICAL Study in Osaka, Japan
Authors: Taro Irisawa, Tasuku Matsuyama, Takeyuki Kiguchi, Tetsuhisa Kitamura, Kazuhisa Yoshiya, Taku Iwami, Takashi Kawamura, Takeshi Shimazu
Journal: Circulation (2017)

Background and Objectives: Target temperature management (TTM) for post cardiac arrest patients is recommended in international resuscitation guidelines. However the target temperature was still co...
Abstract 2002:Ganoderma lucidumextract (GLE) reduces stem cell markers in triple-negative breast cancer models via STAT3 regulation
Authors: Tiffany J. Rios, Alicia Marti, Gabriela Ortiz, Michelle M. Martínez-Montemayor
Journal: Cancer Research (2018)

Abstract Triple-negative breast cancer (TNBC) is a subtype of cancer described by the lack of estrogen receptor, progestogen receptor, and HER2 receptor. It accounts for approximately 15-20% of all breast cancer (BC) cases worldwide. TNBC aggressiveness might be explained by the presence of BC stem cells (BCSCs), which are a subpopulation of cancer cells involved in tumor initiation, metastasis, and therapy resistance. Interestingly, the signal transducer and activator of transcription 3 (STAT3) participates in the development and progression of BCSCs, but its role in TNBC progression remains unclear. Moreover, BCSCs can be identified by the CD44+/CD24- and ALDH+ phenotype, which correlates with a worse prognosis in TNBC patients. Furthermore, CSCs can be characterized based on the expression of transcription factors involved in stemness (Nanog, Sox2, and Oct4A), where activation of STAT3 leads to enhanced Nanog, Oct4 and Sox2 expression. Importantly, a major challenge arises to develop nontoxic targeted therapies to improve the outcome of TNBC patients. In this regard, our laboratory investigates the role of Ganoderma lucidum extract (GLE), a medicinal mushroom commonly used in complementary and alternative medicine. We hypothesize that GLE will decrease stem cell properties via STAT3 regulation in TNBC cells. Our in vitro results demonstrate that GLE significantly downregulates STAT3 and JAK2 in SUM-149 and MDA-MB-231, TNBC cell lines. In addition, GLE significantly decreases the secretion of IL-6 at 24hr in MDAMB231 cells. Further flow cytometry results show that GLE significantly decreases the CD44+/CD24- population at 24hr and 72hr in MDA-MB-231 cells. In this regard, GLE significantly decreases the expression of ALDH at 24hr and 72hr in MDAMB231 cells. Moreover, GLE decreases the expression of Nanog at 24hr, and all three transcription factors at 72hr. Additionally, our in vivo studies demonstrate that GLE significantly decreases tumor volume of mice injected with CD44+/CD24- sorted cells of the MDA-MB-231 cell line. Finally, tumor weight of GLE treated mice was marginally significantly lower (p=0.053) compared to vehicle. We can conclude that GLE decreases stemness of TNBC via STAT3 regulation. Citation Format: Tiffany J. Rios, Alicia Marti, Gabriela Ortiz, Michelle M. Martínez-Montemayor. Ganoderma lucidum extract (GLE) reduces stem cell markers in triple-negative breast cancer models via STAT3 regulation [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 2002.
HEPATITIS B ENVELOPE ANTIGEN SERONEGATIVITY PREDICTS INTRAHEPATIC RECURRENCE IN HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA AFTER LOCAL ABLATION THERAPY: PROSPECTIVE COHORT STUDY
Authors: Won Kim, Goh Eun Chung, Yong Jin Jung, Donghee Kim, Jung-Hwan Yoon, Bo Hyun Kim, Yoon Jun Kim
Journal: Hepatology (2010)
Patients like me manage lifelong illness with cannabis. For us, the UK is a hostile environment
Authors: Greg de Hoedt
Journal: BMJ (2018)

As a 30 year old with Crohn’s disease, I have lived my entire adult life dependent on drugs, both legal and illegal. I have learnt what works best to keep my symptoms under control and provide me with a good quality of life.

In 2010 I was told that I needed major surgery and chemotherapy or I would live two to five years before dying from malnutrition associated with short gut syndrome. For me this wasn’t an option. The side effects of chemotherapy can include all the symptoms of Crohn’s amplified, and potential impotence, leukaemia, and death. I was a mess.

Pharmaceutical drugs like the immunosuppressive azathioprine and the anti-inflamatory mesalamine nearly killed me, causing nausea, vomiting, and foaming at the mouth. I had worse diarrhoea with blood and mucus than my Crohn’s had ever given me.

Cannabis, however, drops my bowel movements from 20 …
Characterization of the nestin-driven-GFP (ND-GFP) nude mouse and its uses in cancer research
Authors: Yasuyuki Amoh, Lingna Li, Meng Yang, Jose Reynoso, A. R. Moossa, Kensei Katsuoka, David Tarin, Robert M. Hoffman
Journal: Cancer Research (2005)

1071  In stress responses induced by a wide variety of DNA-damaging treatments and other cellular stressors, transcription of the bZip transcription factor ATF3 is robustly induced. Transgenic overexpression of the human ATF3 gene in keratin 5 (K5)-expressing murine epithelia led to a sparse-hair phenotype and aberrantly large hair follicles, but no skin tumors were observed in female BK5.ATF3 mice monitored for 15 months. However, when female BK5.ATF3 mice were bred and allowed to raise progeny, mammary carcinomas arose after one or two litters; mammary tumor incidence reached about 80% by 15 months of age. At the same age, mammary tumor incidence was less than 5% in non-transgenic, biparous littermates and in virgin BK5.ATF3 females. The majority of mammary tumors were carcinomas with prominent squamous metaplasia. Both K5 and ATF3 were expressed in myoepithelial cells of the transgenic mammary gland; by immunohistochemistry the majority of the transgenic ATF3 was confined to the nucleus. Mammary tumor cells expressed keratins K5, K6 and K8, suggesting that the target cells for tumorigenesis were either myoepithelial cells which subsequently exhibited transdifferentiation, or that relatively undifferentiated “stem-like” cells were the targets for malignant conversion. In addition, immunohistochemistry demonstrated overexpression of the tumor suppressor protein p53 in all BK5.ATF3 mammary carcinomas. Global gene expression analyses in human breast tumor samples have demonstrated substantial overexpression of ATF3. Taken together, these results suggest the possibility that ATF3 acts as an oncogene in the genesis of human breast cancer.
Abstract 16036: Interest of Central Arterial Compliance in the Occurence of Discordant Grading in Aortic Stenosis
Authors: Marine Clisson, Lionel Tastet, Romain Capoulade, Louis Simard, Mylene Shen, Philippe Pibarot, Marie-Annick Clavel
Journal: Circulation (2016)

Introduction:  According to the current AHA/ACC guidelines, severe aortic stenosis (AS) is defined as a peak aortic jet velocity (Vpeak) >4m/sec, a mean gradient (MG) >40 mmHg, and/or an aortic valve area (AVA)  2 . However, cardiologists are often confronted to discordant echocardiographic findings that are unexplained by a reduction in transvalvular flow. Discordances may raise uncertainty about the actual severity of the disease and thus therapeutic management.   Aim:  The aim of this study was to identify the causes of such discordance by measuring systemic arterial compliance (SAC), which could interfere with the evaluation of AS.   Methods:  Fifty-two men with mild to moderate AS underwent Doppler-echocardiography, multidetector computed tomography (MDCT), and central and peripheral blood pressure were measured in the context of the prospective PROGRESSA study. SAC was calculated as the stroke volume (SV) divided by the systemic pulse pressure (systolic blood pressure [SBP] - diastolic blood pressure [DBP]).   Results:  The mean age was 63±13 years and MG 21±8 mmHg. There was a significant correlation between aortic valve calcification (AVC) and MG (r=0.62; p   Conclusions:  This study shows that for the same anatomic AS severity, patients with reduced SAC have a decreased MG. In these patients, AS severity could be underestimated and lead to an inappropriate treatment. In addition, patients may appear to have normal SAC when assessed in periphery despite decreased central SAC. Thus AS severity should be assessed by an alternative exam, such as MDCT, in any patient with discordant low gradient not obviously linked to measurement error.
Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans
Authors: Peter Ulrichts, Antonio Guglietta, Torsten Dreier, Tonke van Bragt, Valérie Hanssens, Erik Hofman, Bernhardt Vankerckhoven, Peter Verheesen, Nicolas Ongenae, Valentina Lykhopiy, F. Javier Enriquez, JunHaeng Cho, Raimund J. Ober, E. Sally Ward, Hans de Haard, Nicolas Leupin
Journal: Journal of Clinical Investigation (2018)

BACKGROUND. Intravenous Ig (IVIg), plasma exchange, and immunoadsorption are frequently used in the management of severe autoimmune diseases mediated by pathogenic IgG autoantibodies. These approaches modulating IgG levels can, however, be associated with some severe adverse reactions and a substantial burden to patients. Targeting the neonatal Fc receptor (FcRn) presents an innovative and potentially more effective, safer, and more convenient alternative for clearing pathogenic IgGs.
Dramatic Response to Lorlatinib in a Heavily Pretreated Lung Adenocarcinoma Patient Harboring G1202R Mutation and a Synchronous Novel R1192P ALK Point Mutation
Authors: Sara Baglivo, Biagio Ricciuti, Vienna Ludovini, Giulio Metro, Annamaria Siggillino, Andrea De Giglio, Rita Chiari
Journal: Journal of Thoracic Oncology (2018)
THU0205 The effect of certolizumab drug concentration and anti-drug antibodies on tnf neutralisation
Authors: L.C. Berkhout, E.H. Vogelzang, M.H. Hart, N.I. Derksen, R. Wieringa, W.A. van Leeuwen, C.L. Krieckaert, A. de Vries, M.T. Nurmohamed, G. Wolbink, T. Rispens
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although tumour necrosis factor- (TNF) inhibitors have proven to be a successful treatment option for patients with rheumatoid arthritis (RA), TNF-inhibitors, including certolizumab, elicit an immunogenic response leading to the formation of anti-drug antibodies (ADAs) (reported range ~5%–39% of the patients). <h3>Objectives</h3> We sought to investigate the relationship between certolizumab concentrations, ADAs, and the effective TNF neutralising capacity in sera of RA patients. TNF neutralising capacity of certolizumab was compared to the neutralising capacity of adalimumab. <h3>Methods</h3> Blood was collected of 35 consecutive certolizumab-treated RA patients at baseline and 4, 16, 28 and 52 weeks after treatment initiation. Certolizumab and ADA levels were quantified using a certolizumab bridging enzyme-linked immunosorbent assay (ELISA) and a drug-tolerant radioimmunoassay (RIA), respectively. TNF neutralisation of certolizumab and adalimumab in patient sera, in presence or absence of ADAs, was analysed using the TNF-sensitive WEHI bioassay. <h3>Results</h3> Despite a high incidence of ADAs during one year of follow-up (69%; 24/35 patients), certolizumab levels of ~&gt;10 µg/mL were measured in most patients (Spearman's r=−0.7155, p&lt;0.0001 (n=118); <b>figure 1A</b>). Furthermore, TNF neutralisation, expressed by EC50 values, was highly correlated with certolizumab serum concentration, while there was no association with ADAs (Pearson r=0.9087, p&lt;0.0001 (n=12) and Pearson r=−0.4712, p=0.1220 (n=12); <b>figure 1B and C</b>, respectively. Grey lines indicate log-log linear fit, weight by 1/Y^2). Similar results were obtained for adalimumab, although TNF neutralisation by adalimumab was less potent; the relative <i>in vitro</i>neutralising potency was 43 times higher for certolizumab compared to the neutralising potency of adalimumab. <h3>Conclusions</h3> Our study shows that certolizumab is highly immunogenic. In most cases where ADAs are detected, certolizumab is also present in high amounts, and can still potently neutralise TNF. Furthermore, TNF neutralisation is highly correlated with certolizumab concentrations. Therefore, measurement of certolizumab concentrations is the relevant parameter to assess clinically relevant immunogenicity. <h3>Disclosure of Interest</h3> L. Berkhout: None declared, E. Vogelzang: None declared, M. Hart: None declared, N. Derksen: None declared, R. Wieringa: None declared, W. van Leeuwen: None declared, C. Krieckaert Speakers bureau: Pfizer, A. de Vries: None declared, M. Nurmohamed Consultant for: Abbott, Roche, Pfizer, MSD, UCB, SOBI, BMS, Speakers bureau: Abbott, Roche, Pfizer, G. Wolbink Grant/research support from: Pfizer, Speakers bureau: Pfizer, UCB, AbbVie, Biogen, BMS, T. Rispens Grant/research support from: Genmab, Speakers bureau: Pfizer, AbbVie, Regeneron
Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen
Authors: Hwee Ying Lim, Sheau Yng Lim, Chek Kun Tan, Chung Hwee Thiam, Chi Ching Goh, Daniel Carbajo, Samantha Hui Shang Chew, Peter See, Svetoslav Chakarov, Xiao Nong Wang, Li Hui Lim, Louise A. Johnson, Josephine Lum, Chui Yee Fong, Ariff Bongso, Arijit Biswas, Chern Goh, Maximilien Evrard, Kim Pin Yeo, Ranu Basu, Jun Kit Wang, Yingrou Tan, Rohit Jain, Shweta Tikoo, Cleo Choong, Wolfgang Weninger, Michael Poidinger, Richard E. Stanley, Matthew Collin, Nguan Soon Tan, Lai Guan Ng, David G. Jackson, Florent Ginhoux, Véronique Angeli
Journal: Immunity (2018)
Addressing Unmet Clinical Needs with 3D Printing Technologies
Authors: Udayan Ghosh, Shen Ning, Yuzhu Wang, Yong Lin Kong
Journal: Advanced Healthcare Materials (2018)

Abstract Recent advances in 3D printing have enabled the creation of novel 3D constructs and devices with an unprecedented level of complexity, properties, and functionalities. In contrast to manufacturing techniques developed for mass production, 3D printing encompasses a broad class of fabrication technologies that can enable 1) the creation of highly customized and optimized 3D physical architectures from digital designs; 2) the synergistic integration of properties and functionalities of distinct classes of materials to create novel hybrid devices; and 3) a biocompatible fabrication approach that facilitates the creation and cointegration of biological constructs and systems. This progress report describes how these capabilities can potentially address a myriad of unmet clinical needs. First, the creation of 3D‐printed prosthetics to regain lost functionalities by providing structural support for skeletal and tubular organs is highlighted. Second, novel drug delivery strategies aided by 3D‐printed devices are described. Third, the advancement of medical research heralded by 3D‐printed tissue/organ‐on‐chips systems is discussed. Fourth, the developments of 3D‐printed tissue and organ regeneration are explored. Finally, the potential for seamless integration of engineered organs with active devices by leveraging the versatility of multimaterial 3D printing is envisioned.
A biodegradable synthetic graft for small arteries matches the performance of autologous vein in rat carotid arteries
Authors: Kee-Won Lee, Piyusha S. Gade, Liwei Dong, Zhaoxiang Zhang, Ali Mubin Aral, Jin Gao, Xiaochu Ding, Chelsea E.T. Stowell, Muhammad Umer Nisar, Kang Kim, Dieter P. Reinhardt, Mario G. Solari, Vijay S. Gorantla, Anne M. Robertson, Yadong Wang
Journal: Biomaterials (2018)