tbuckley/cabot-search huggingface dataset:
IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways
Authors: Martijn L. Manson, Jesper Säfholm, Anna James, Anna-Karin Johnsson, Per Bergman, Mamdoh Al-Ameri, Ann-Charlotte Orre, Carina Kärrman-Mårdh, Sven-Erik Dahlén, Mikael Adner
Journal: Journal of Allergy and Clinical Immunology (2019)

Specific inflammatory pathways are indicated to contribute to severe asthma, but their individual involvement in the development of airway hyperresponsiveness remains unexplored.This experimental study in human small bronchi aimed to provide insight into which of the type 2 and type 17 cytokines cause hyperresponsiveness of airway smooth muscle.Explanted small bronchi isolated from human lung tissue and human airway smooth muscle cells were treated for 2 and 1 day(s), respectively, with 100 ng/mL of IL-4, IL-5, IL-13, or IL-17A, and contractile responses, Ca2+ mobilization, and receptor expression were assessed.Treatment with IL-13 increased the potency of histamine, carbachol, and leukotriene D4 as contractile agonists. IL-4, but not IL-5 or IL-17A, also increased the potency of histamine. In human airway smooth muscle cells, IL-13 and IL-4, but not IL-5 and IL-17A, enhanced the histamine-induced Ca2+ mobilization that was accompanied with increased mRNA expression of histamine H1 and cysteinyl leukotriene CysLT1 receptors. RNA sequencing of isolated bronchi confirmed the IL-13-mediated upregulation of H1 and CysLT1 receptors, without showing an alteration of muscarinic M3 receptors. Dexamethasone had no effects on IL-13-induced hyperresponsiveness in human bronchi, the increased Ca2+ mobilization, or the enhanced receptor expression. In contrast, antagonism of the common receptor for IL-13 and IL-4 by the biologic dupilumab prevented the effects of both IL-13 and IL-4 in human bronchi and human airway smooth muscle cells.The glucocorticoid-insensitive hyperrresponsiveness in isolated human airways induced by IL-13 and IL-4 provides further evidence that the IL-4Rα pathway should be targeted as a new strategy for the treatment of airway hyperresponsiveness in asthma.
U Distinct Roles of IL-12Rβ1 and IL-23R in the Development of Acute and Chronic Gvhd
Authors: David Bastian, Hung D Nguyen, Yongxia Wu, Steven Douglas Schutt, Anusara Daenthanasanmak, Mohammed Hanief Sofi, Supinya Iamsuwat, Mengmeng Zhang, Xue-Zhong Yu
Journal: Blood (2017)
Abstract 03: High-Dose Intranasal Insulin During CPR Improves Neurological Outcomes in a Rat Model of Cardiac Arrest
Authors: Tulasi Jinka, Adam D Chalek, Joseph M Wider, Kathleen J Maheras, Amanda Qvigstad, Erin Gruley, Sarita Raghunayakula, Jinhui Liao, Xiaodan Ren, Rui Zhang, Thomas H Sanderson, Robert W Neumar
Journal: Circulation (2019)

Introduction: Post-cardiac arrest brain injury is a major cause of mortality and morbidity. Insulin has well-established CNS neuroprotecive properties mediated by the AKT survival signaling pathway, and known transnasal transport mechanisms make it possible to rapidly achieve therapeutic brain insulin levels after intranasal delivery. Hypothesis: We hypothesize that high-dose intranasal insulin (HD-IN-I) administered during CPR, could improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Methods: Male Long Evans rats were subjected to 8-minute asphyxial cardiac arrest then block randomized to HD-IN-I (1.92 U/g brain wet weight) or placebo (PL) given at the onset of CPR by an experimental operator blinded to treatment. Sham operated rats were used as uninjured controls. For the long-term outcome study (n = 14/group), rats with return of spontaneous circulation (ROSC) were maintained at 37.0 ±0.5 °C for 72 hours and neurologic function was assessed on days 7 - 10. For the mechanistic study (n = 6/group), rats with ROSC were euthanized 30 minutes after ROSC and regional brain homogenates were analyzed by western blot for AKT phosporylation. Results: HD-IN-I during CPR had no statistically significant effect on ROSC rate (93% (13/14) HD-IN-I vs. 86% (12/14) PL, p &gt; 0.05) or 10-day survival (71% (10/14) HD-INI vs. 43% (6/14) PL, p &gt; 0.05). HD-IN-I had no significant impact on serum glucose concentrations. At 10 days post-ROSC, rats in the HD-IN-I group had significantly improved performance on rotarod (latency to fall 87±27 sec HD-IN-I vs. 41±18 sec PL, p &lt; 0.05), Barnes maze (latency to escape box 27±15 sec HD-IN-I vs. 298±5 sec PL, p &lt; 0.05), and passive avoidance (latency to re-enter shock chamber 300±0 sec HD-IN-I vs. 142±46 sec PL, p &lt; 0.05) testing. Hippocampal phosph-AKT/total AKT ratio increased 2-fold in the placebo group and 5.7-fold in the HD-IN-I group relative to shams (p &lt; 0.05). Conclusions: HD-IN-I administered during CPR causes rapid activation of brain AKT survival signaling and improves recovery of neurologic function in a rat cardiac arrest model. Additional studies are warranted to determine dose optimization, therapeutic window and effectiveness in large animal models to advance this novel therapy toward clinical trials.
Androgens have an anti‐inflammatory effect on human basophils in vitro
Authors: William Grobe, Wenming Peng, Jean‐Pierre Allam, Chun‐Feng Yu, Natalija Novak
Journal: Allergy (2019)

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Lead-in Dose Optimization to Mitigate Cytokine Release Syndrome in AML and MDS Patients Treated with Flotetuzumab, a CD123 x CD3 Dart® Molecule for T-Cell Redirected Therapy
Authors: Kenneth Jacobs, John Godwin, Matthew Foster, Norbert Vey, Geoffrey L. Uy, David A. Rizzieri, Martha L. Arellano, Michael P Rettig, Stephanie Christ, Max S. Topp, Geert Huls, Bob Lowenberg, Giovanni Martinelli, Stefania Paolini, Fabio Ciceri, Matteo Giovanni Carrabba, Jichao Sun, Daner Li, Kathy Tran, Karen Spohn, Jan Baughman, Sadhna Shankar, Helene Lelièvre, Ezio Bonvini, John F DiPersio, Jon Wigginton, Jan K davidson-Moncada
Journal: Blood (2017)
Natural Killer Cell Cytotoxicity Is a Predictor of Outcome for Patients with High Risk Myelodysplastic Syndrome and Oligoblastic Acute Myeloid Leukemia Treated with Azacytidine
Authors: Panagiotis Tsirigotis, Renata Grigoriou, Violetta Kapsimalli, Kleopatra Dagla, Evi Konsta, Konstantinos Gkirkas, Maria Stamouli, Aggeliki Karagiannidi, George Vassilopoulos, Konstantinos Gkodopoulos, Vassiliki Pappa, Maria Tsirogianni
Journal: Blood (2017)
Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples
Authors: Eleanor M. Scott, Egon J. Jacobus, Brian Lyons, Sally Frost, Joshua D. Freedman, Arthur Dyer, Hena Khalique, William K. Taverner, Alison Carr, Brian R. Champion, Kerry D. Fisher, Len W. Seymour, Margaret R. Duffy
Journal: Journal for ImmunoTherapy of Cancer (2019)

Tumour-associated macrophages (TAMs) are often implicated in cancer progression but can also exert anti-tumour activities. Selective eradication of cancer-promoting (M2-like) TAM subsets is a highly sought-after goal. Here, we have devised a novel strategy to achieve selective TAM depletion, involving the use of T cell engagers to direct endogenous T cell cytotoxicity towards specific M2-like TAMs. To avoid "on-target off-tumour" toxicities, we have explored localising expression of the T cell engagers to the tumour with enadenotucirev (EnAd), an oncolytic adenovirus in Phase I/II clinical trials.
Value of repeated blood pressure measurements in children
Authors: M de Swiet, E. A Shinebourne, P M Fayers
Journal: BMJ (1981)

requirements beyond the capabilities of most milk banks.For milk banks which depend on drip milk, an alternative approach to improve the quality of donated milk would be to collect expressed breast milk instead and to use the creamatocrit method for quality control.3The Nottingham study confirms in day-to-day practice previous research showing that expressed milk has a higher fat concentration than drip milk.4One major disadvantage of stocking a milk bank with expressed milk might be that the volume of milk collected would be insufficient, since the amount of milk which can usually be expressed seems to be less than can be collected by the "drip" method.(On this aspect we would welcome comments from colleagues who already organise milk banks which depend mainly on expressed milk.)Of course, if mothers can collect both expressed and drip milk, as indeed did one Nottingham mother, then perhaps both qualitative and quantitative requirements would be satisfied.
Efficacy and Safety of Zanubrutinib in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with del(17p): Follow-up Results from Arm C of the SEQUOIA (BGB-3111-304) Trial
Authors: Jennifer R. Brown, Tadeusz Robak, Paolo Ghia, Brad S. Kahl, Patricia Walker, Wojciech Janowski, Henry Chan, Mazyar Shadman, Peter S. Ganly, Luca Laurenti, Stephen Opat, Monica Tani, Hanna Ciepluch, Emma Verner, Martin Šimkovič, Anders Österborg, Marek Trněný, Alessandra Tedeschi, Piers Blombery, Jason C. Paik, Fangfang Yin, Shibao Feng, Vanitha Ramakrishnan, Jane Huang, Peter Hillmen, Constantine S. Tam
Journal: Blood (2020)
SAT0021 The incidence of varicoceles in patients with ankylosing spondyltis evaluated by physical examination and colour doppler sonography
Authors: S Ozgocmen, E Kocakoc, A Kiris, A Ardicoglu, O Ardicoglu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> A varicocele is an abnormal tortuosity and dilation of the testicular veins within the spermatic cord. The incidence of varicocele in AS, which affects predominantly young male individuals, is unknown. <h3>Objectives</h3> We proposed to assess the incidence of varicocele in AS evaluated by physical examination and colour doppler ultrasonography (CDU). Sperm parameters of these patients were also investigated and compared with controls. <h3>Methods</h3> Thirteen untreated male patients (ages 18–40) with AS and age matched healthy 12 male subjects (ages 18–39) included in the study. Testicular veins in both groups were studied with CDU and semen samples were analysed. <h3>Results</h3> Eight of the patients evaluated with physical examination had varicoceles (all grade II, 5 left side, 3 bilateral). Only two subjects in control group had grade II varicocele on the left side and both were asymptomatic. Colour doppler evaluation of the testicular vessels in patients with AS revealed grade II varicocele (6 left side, 3 bilateral) in 9 of the patients (69,2%) examined. Semen parameters were within normal limits in 7 patients, and there were altered sperm count and quality in 6 patients. <h3>Conclusion</h3> The high incidence of varicocele in patients with AS may be explained by chronic inflammatory low-back pain that brings about reduced extensor muscle strength that causes compensatory increase in intra-abdominal pressure. This may cause a mechanical overload to the testicular vessels. Secondly, vasodilator effect of nitric oxide that was activated by inflammatory process.
Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation
Authors: Lin-Hu Quan, Chuanhai Zhang, Meng Dong, Jun Jiang, Hongde Xu, Chunlong Yan, Xiaomeng Liu, Huiqiao Zhou, Hanlin Zhang, Li Chen, Fei-Liang Zhong, Zhao-Bo Luo, Sin-Man Lam, Guanghou Shui, Donghao Li, Wanzhu Jin
Journal: Gut (2019)

Objective Dietary fibre has beneficial effects on energy metabolism, and the majority of studies have focused on short-chain fatty acids produced by gut microbiota. Ginseng has been reported to aid in body weight management, however, its mechanism of action is not yet clear. In this study, we focused on the potential modulating effect of ginseng on gut microbiota, aiming to identify specific strains and their metabolites, especially long-chain fatty acids (LCFA), which mediate the anti-obesity effects of ginseng. Design Db/db mice were gavaged with ginseng extract (GE) and the effects of GE on gut microbiota were evaluated using 16S rDNA-based high throughput sequencing. To confirm the candidate fatty acids, untargeted metabolomics analyses of the serum and medium samples were performed. Results We demonstrated that GE can induce Enterococcus faecalis , which can produce an unsaturated LCFA, myristoleic acid (MA). Our results indicate that E. faecalis and its metabolite MA can reduce adiposity by brown adipose tissue (BAT) activation and beige fat formation. In addition, the gene of E. faecalis encoding Acyl-CoA thioesterases (ACOTs) exhibited the biosynthetic potential to synthesise MA, as knockdown (KD) of the ACOT gene by CRISPR-dCas9 significantly reduced MA production. Furthermore, exogenous treatment with KD E. faecalis could not reproduce the beneficial effects of wild type E. faecalis , which work by augmenting the circulating MA levels. Conclusions Our results demonstrated that the gut microbiota-LCFA-BAT axis plays an important role in host metabolism, which may provide a strategic advantage for the next generation of anti-obesity drug development.
Low 2018/19 vaccine effectiveness against influenza A(H3N2) among 15–64-year-olds in Europe: exploration by birth cohort
Authors: Esther Kissling, Francisco Pozo, Silke Buda, Ana-Maria Vilcu, Alin Gherasim, Mia Brytting, Lisa Domegan, Verónica Gómez, Adam Meijer, Mihaela Lazar, Vesna Višekruna Vučina, Ralf Dürrwald, Sylvie van der Werf, Amparo Larrauri, Theresa Enkirch, Joan O’Donnell, Raquel Guiomar, Mariëtte Hooiveld, Goranka Petrović, Elena Stoian, Pasi Penttinen, Marta Valenciano
Journal: Eurosurveillance (2019)

Introduction Influenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE). Aim The I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort. Methods We measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0–14, 15–64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32–54-year-olds (1964–86) sharing potential childhood imprinting to serine at haemagglutinin position 159. Results Influenza A(H3N2) VE among all ages was −1% (95% confidence interval (CI): −24 to 18) and 46% (95% CI: 8–68), −26% (95% CI: −66 to 4) and 20% (95% CI: −20 to 46) among 0–14, 15–64 and ≥ 65-year-olds, respectively. Among 15–64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: −34 to 50) and −74% (95% CI: −259 to 16), respectively. VE was −18% (95% CI: −140 to 41), −53% (95% CI: −131 to −2) and −12% (95% CI: −74 to 28) among 15–31-year-olds (1987–2003), 32–54-year-olds (1964–86) and 55–64-year-olds (1954–63), respectively. Discussion The lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964–86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15–64-year-olds and the public health impact of the I-REV hypothesis warrant further study.
Disgraced tracheal transplant surgeon is handed 16 month prison sentence in Italy
Authors: Michael Day
Journal: BMJ (2019)

Disgraced surgeon Paolo Macchiarini, who faked research relating to dangerous and largely discredited tracheal transplants, has been handed a 16 month prison sentence in Italy for forging documents and abuse of office.

Macchiarini made headlines around the world after claiming a major breakthrough for patients with failing windpipes, by “seeding” an artificial scaffold with a patient’s own stem cells, to generate a functioning trachea.

But excitement at the prospect of a genuine medical advance turned to scandal when it emerged that Macchiarini had falsified results and misled hospital authorities regarding the health of those receiving the experimental procedures. The revelation prompted his research centre, the Karolinska Institute, to eventually disown his …
Prediction, embodiment, and representation
Authors: István Aranyosi
Journal: Behavioral and Brain Sciences (2019)

First, I argue that there is no agreement within non-classical cognitive science as to whether one should eliminate representations, hence, it is not clear that Brette's appeal to it is going to solve the problems with coding. Second, I argue that Brette's criticism of predictive coding as being intellectualistic is not justified, as predictive coding is compatible with embodied cognition.
Reply to Jin et al.
Authors: Kirles Bishay, Nauzer Forbes
Journal: Endoscopy (2019)

See also: Endoscopic ultrasound-guided transmural approach versus ERCP-guided transpapillary approach for primary decompression of malignant biliary obstruction: a meta-analysisEndoscopy 2019; 51(10): 950-960DOI: 10.1055/a-0901-7343 See also: Malignant biliary obstruction: endoscopic ultrasound-guided versus endoscopic retrograde cholangiopancreatography-guided biliary drainageEndoscopy 2019; 51(12): 1185-1185DOI: 10.1055/a-0997-6582
Identification of Hypermutation and Defective Mismatch Repair in ctDNA from Metastatic Prostate Cancer
Authors: Elie Ritch, Simon Y.F. Fu, Cameron Herberts, Gang Wang, Evan W. Warner, Elena Schönlau, Sinja Taavitsainen, Andrew J. Murtha, Gillian Vandekerkhove, Kevin Beja, Yulia Loktionova, Daniel Khalaf, Ladan Fazli, Igal Kushnir, Cristiano Ferrario, Sebastien Hotte, Matti Annala, Kim N. Chi, Alexander W. Wyatt
Journal: Clinical Cancer Research (2019)

DNA mismatch repair defects (MMRd) and tumor hypermutation are rare and under-characterized in metastatic prostate cancer (mPC). Furthermore, because hypermutated MMRd prostate cancers can respond to immune checkpoint inhibitors, there is an urgent need for practical detection tools.We analyzed plasma cell-free DNA-targeted sequencing data from 433 patients with mPC with circulating tumor DNA (ctDNA) purity ≥2%. Samples with somatic hypermutation were subjected to 185 × whole-exome sequencing and capture of mismatch repair gene introns. Archival tissue was analyzed with targeted sequencing and IHC.Sixteen patients (3.7%) had somatic hypermutation with MMRd etiology, evidenced by deleterious alterations in MSH2, MSH6, or MLH1, microsatellite instability, and characteristic trinucleotide signatures. ctDNA was concordant with mismatch repair protein IHC and DNA sequencing of tumor tissue. Tumor suppressors such as PTEN, RB1, and TP53 were inactivated by mutation rather than copy-number loss. Hotspot mutations in oncogenes such as AKT1, PIK3CA, and CTNNB1 were common, and the androgen receptor (AR)-ligand binding domain was mutated in 9 of 16 patients. We observed high intrapatient clonal diversity, evidenced by subclonal driver mutations and shifts in mutation allele frequency over time. Patients with hypermutation and MMRd etiology in ctDNA had a poor response to AR inhibition and inferior survival compared with a control cohort.Hypermutated MMRd mPC is associated with oncogene activation and subclonal diversity, which may contribute to a clinically aggressive disposition in selected patients. In patients with detectable ctDNA, cell-free DNA sequencing is a practical tool to prioritize this subtype for immunotherapy.See related commentary by Schweizer and Yu, p. 981.
Young adults with squamous cell head and neck cancer: Ten years of a single institution’s experience (1999-2008).
Authors: Marcos Pantarotto Alves, Ana Filipa Martins Ferreira Castro, Liliana Lombo, Helena Rodrigues, Jose D. Silva, Isabel Azevedo
Journal: Journal of Clinical Oncology (2012)

5567 Background: Head and neck cancer of squamous cell type (SCHNC) is characterised by its aggressiveness and strong relationship with smoking and drinking habits. It is generally diagnosed in locally advanced stages, mainly in middle-aged men. People younger than 35yo are rarely affected by this disease, and little is known about its behaviour among young Portuguese adults. Our aim was to describe the clinical and epidemiological features of young adults with diagnosis of SCHNC in a single oncological centre in Portugal. Methods: Retrospective cohort including clinical registries’ databases for patients (pts) with diagnosis of SCHNC, with 3391 eligible pts from 1999 to 2008. Pts aged ≧18yo and ≤35yo at diagnosis with histopathological diagnosis in our Institution were included. Pts admitted to radiation therapy with no follow-up information were excluded. 39 pts fulfilled the criteria described, comprising the study population. Statistical analysis was carried out using SPSS v19.0 for Mac (IBM, 2010, EUA), with values of p&lt;0,05 considered significant. Results: Male sex predominance (82%) was observed. The median age of presentation was 33 yo [22; 35], with 90% smokers with a median of 18,5 package-years [1; 48]. Alcohol consumption was mild to moderate (n=9; 23%) or heavy (n=15; 38%). The median of follow-up time was of 24 months [1;151]. Locally advanced diseased was present at diagnosis in 24 pts, where localised disease was commonest among women (57%) than in men (29%). Median overall survival (OS) was not reached on this population, although K-M graphs seems to show a significant difference in survival between sexes. Alcohol consumption was the most significant variable to influence the survival (p&lt;0,01). Conclusions: SCHNC in young people is a rare condition, with distinct epidemiological and clinical features. Women seems to have greater survival rates, which may be explained by other risk factors already reported for this gender, namely HPV infection. The finding of an apparent relationship between alcohol consumption and OS, and the high prevalence of alcoholic intake habits on this parcel of the population, urge the need of development of public health programs addressed to this specific age group.