tbuckley/cabot-search huggingface dataset:
<i>Staphylococcus aureus</i> Induces a Mucosal Type 2 Immune Response via Epithelial Cell–derived Cytokines
Authors: Feng Lan, Nan Zhang, Gabriele Holtappels, Natalie De Ruyck, Olga Krysko, Koen Van Crombruggen, Harald Braun, Sebastian L. Johnston, Nikos G. Papadopoulos, Luo Zhang, Claus Bachert
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Chronic rhinosinusitis with nasal polyps is characterized by a T-helper cell type 2-skewed upper airway inflammation. Mucosal Staphylococcus aureus colonization is found in the majority of patients with nasal polyps. S. aureus is known to induce type 2 cytokine release via enterotoxins.To investigate the impact of non-enterotoxin-producing S. aureus on type 2 cytokine release.TSLP (thymic stromal lymphopoietin), IL-33, and type 2 cytokines were assessed in a human mucosal tissue model upon S. aureus infection.S. aureus exposure increased the expression of IL-33, TSLP, IL-5, and IL-13 in nasal polyp tissue, accompanied by elevated expression levels of TSLP and IL-33 receptors, predominantly on CD3+ T cells. S. aureus infection led to the release of TSLP, but not IL-33, IL-5, or IL-13, from healthy inferior turbinate tissue. In contrast, S. epidermidis did not induce any epithelial cell-derived cytokines in nasal polyp or healthy tissue. S. aureus infection also increased the release of IL-33 and TSLP in BEAS-2B epithelial cells, accompanied by activation of NF-κB (nuclear factor κB) pathways. Incubation with CU-CPT22, a specific Toll-like receptor 2 antagonist, significantly reduced the S. aureus-induced release of TSLP and IL-33, and the activity of the NF-κB signal in BEAS-2B cells.This study demonstrates for the first time that S. aureus can directly induce epithelial cell-derived cytokine release via binding to Toll-like receptor 2, and may thereby propagate type 2 cytokine expression in nasal polyp tissue.
Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor–Positive Breast Cancer in Men
Authors: Sriram Venigalla, Ruben Carmona, David M. Guttmann, Varsha Jain, Gary M. Freedman, Amy S. Clark, Jacob E. Shabason
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)–positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. <h3>Objective</h3> To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. <h3>Design, Setting, and Participants</h3> This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. <h3>Exposures</h3> Receipt of adjuvant endocrine therapy. <h3>Main Outcomes and Measures</h3> Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. <h3>Results</h3> The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%,<i>P</i> &lt; .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63;<i>P</i> &lt; .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25;<i>P</i> = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15;<i>P</i> &lt; .001) or chemotherapy (odds ratio, 1.20; 95% CI, 1.07-1.34;<i>P</i> &lt; .001) were statistically significantly associated with adjuvant endocrine therapy use in men. A propensity score-weighted analysis indicated that relative to no use, adjuvant endocrine therapy use in men was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.63-0.77;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> There is a sex disparate underuse of adjuvant endocrine therapy among men with HR-positive breast cancer despite the use of this treatment being associated with improved overall survival. Further research and interventions may be warranted to bridge gaps in care in this population.
Ian Douglas Ramsay
Authors: Anna Ramsay
Journal: BMJ (2018)

Ian Douglas Ramsay, also known by friends and colleagues as “Muscles Ramsay” because of his pioneering research into thyroid disease and muscular dysfunction, was born in Manchester on 15 December 1935. As a consultant endocrinologist, Ian made a major contribution to the study of the thyroid and metabolic muscle disease, with his papers on the subject marking real advances in the understanding of metabolic muscle disease.

Although born and raised in the north of England, Ian was a true Scotsman and always ensured it was well known that he was British not English. During the second world war, Ian and his older brother, …
Spatial distribution and function of T follicular regulatory cells in human lymph nodes
Authors: Ismail Sayin, Andrea J. Radtke, Laura A. Vella, Wenjie Jin, E. John Wherry, Marcus Buggert, Michael R. Betts, Ramin S. Herati, Ronald N. Germain, David H. Canaday
Journal: The Journal of Experimental Medicine (2018)

T follicular regulatory (Tfr) cells are a population of CD4+ T cells that express regulatory T cell markers and have been shown to suppress humoral immunity. However, the precise mechanisms and location of Tfr-mediated suppression in the lymph node (LN) microenvironment are unknown. Using highly multiplexed quantitative imaging and functional assays, we examined the spatial distribution, suppressive function, and preferred interacting partners of Tfr cells in human mesenteric LNs. We find that the majority of Tfr cells express low levels of PD-1 and reside at the border between the T cell zone and B cell follicle, with very few found in the germinal centers (GCs). Although PD-1+ Tfr cells expressed higher levels of CD38, CTLA-4, and GARP than PD-1Neg Tfr cells, both potently suppressed antibody production in vitro. These findings highlight the phenotypic diversity of human Tfr cells and suggest that Tfr-mediated suppression is most efficient at the T-B border and within the follicle, not in the GC.
Association of <i>BRAF</i> Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer
Authors: Georgios Antonios Margonis, Stefan Buettner, Nikolaos Andreatos, Yuhree Kim, Doris Wagner, Kazunari Sasaki, Andrea Beer, Christoph Schwarz, Inger Marie Løes, Maria Smolle, Carsten Kamphues, Jin He, Timothy M. Pawlik, Klaus Kaczirek, George Poultsides, Per Eystein Lønning, John L. Cameron, Richard A. Burkhart, Armin Gerger, Federico N. Aucejo, Martin E. Kreis, Christopher L. Wolfgang, Matthew J. Weiss
Journal: JAMA Surgery (2018)

BRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied.To investigate the prognostic association of BRAF mutations with survival and recurrence independently and compared with other prognostic determinants, such as KRAS mutations.In this cohort study, all patients who underwent resection for CRLM with curative intent from January 1, 2000, through December 31, 2016, at the institutions participating in the International Genetic Consortium for Colorectal Liver Metastasis and had data on BRAF and KRAS mutational status were retrospectively identified. Multivariate Cox proportional hazards regression models were used to assess long-term outcomes.Hepatectomy in patients with CRLM.The association of V600E and non-V600E BRAF mutations with disease-free survival (DFS) and overall survival (OS).Of 853 patients who met inclusion criteria (510 men [59.8%] and 343 women [40.2%]; mean [SD] age, 60.2 [12.4] years), 849 were included in the study analyses. Forty-three (5.1%) had a mutated (mut) BRAF/wild-type (wt) KRAS (V600E and non-V600E) genotype; 480 (56.5%), a wtBRAF/wtKRAS genotype; and 326 (38.4%), a wtBRAF/mutKRAS genotype. Compared with the wtBRAF/wtKRAS genotype group, patients with a mutBRAF/wtKRAS genotype more frequently were female (27 [62.8%] vs 169 [35.2%]) and 65 years or older (22 [51.2%] vs 176 [36.9%]), had right-sided primary tumors (27 [62.8%] vs 83 [17.4%]), and presented with a metachronous liver metastasis (28 [64.3%] vs 229 [46.8%]). On multivariable analysis, V600E but not non-V600E BRAF mutation was associated with worse OS (hazard ratio [HR], 2.76; 95% CI, 1.74-4.37; P < .001) and DFS (HR, 2.04; 95% CI, 1.30-3.20; P = .002). The V600E BRAF mutation had a stronger association with OS and DFS than the KRAS mutations (β for OS, 10.15 vs 2.94; β for DFS, 7.14 vs 2.27).The presence of the V600E BRAF mutation was associated with worse prognosis and increased risk of recurrence. The V600E mutation was not only a stronger prognostic factor than KRAS but also was the strongest prognostic determinant in the overall cohort.
Complement-binding anti-HLA antibodies are independent predictors of response to treatment in kidney recipients with antibody-mediated rejection
Authors: Denis Viglietti, Yassine Bouatou, Vissal David Kheav, Olivier Aubert, Caroline Suberbielle-Boissel, Denis Glotz, Christophe Legendre, Jean-Luc Taupin, Adriana Zeevi, Alexandre Loupy, Carmen Lefaucheur
Journal: Kidney International (2018)
Osmotic Demyelination Syndrome With Evolving Movement Disorders
Authors: Ai Huey Tan, Shen-Yang Lim, Rong Xiang Ng
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Undifferentiated pleomorphic sarcoma: Factors predictive of adverse outcomes
Authors: Daniel Winchester, Julia Lehman, Tiffany Tello, Nicolette Chimato, Thomas Hocker, Sunhee Kim, Joseph Chang, Jeffrey Markey, Sue S. Yom, William Ryan, Thaddeus Mully, David Hodge, Clark Otley, Sarah T. Arron
Journal: Journal of the American Academy of Dermatology (2018)
Association of Statin Use With Overall and Cancer Survival
Authors: June M. Chan, Stacey A. Kenfield, Elizabeth A. Platz
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
Important considerations for interpreting biochemical tests in children
Authors: Khosrow Adeli, Victoria Higgins, Karin Trajcevski, Mark R Palmert
Journal: BMJ (2018)

### What you need to know Rapid growth and development during childhood and adolescence pose challenges to paediatric healthcare, including blood test interpretation.1 Physicians may order blood tests in children and adolescents with signs and symptoms suggestive of a health condition. Blood tests can be used for screening, risk assessment, disease diagnosis or prognosis, and treatment initiation or monitoring (box 1). For example, newborns are commonly screened for metabolic disorders and genetic diseases, including phenylketonuria and congenital heart disease,9 and abnormal results are later confirmed by diagnostic testing.10 Additionally, measurement of bilirubin to test for jaundice is common in newborns. Reference intervals or clinical decision limits are widely used by clinical laboratories to flag results, thereby notifying physicians to potentially follow up with additional medical tests or specialist referral. Depending on an individual's risk, children and adolescents might also be screened for common conditions including type 2 diabetes, dyslipidaemia, and iron deficiency anaemia, which have all become more common with increased rates of obesity.111213 Box 1 ### Considerations for requesting blood tests in children • Laboratory medicine is integral to health assessment in the paediatric population, but important considerations for laboratory testing in this population can often be overlooked. • Pre-analytical factors can differ compared with an adult population. For example, automated laboratory equipment may not be able to handle small volume specimens, requiring manual processing, leading to difficulties in standardising specimen processing. Small sample volume might also pose challenges to repeat testing to … RETURN TO TEXT
Trametinib in Histiocytic Sarcoma with an Activating <i>MAP2K1</i> (MEK1) Mutation
Authors: Mrinal M Gounder, David B Solit, William D Tap
Journal: New England Journal of Medicine (2018)

Trametinib in Histiocytic Sarcoma In a patient with treatment-refractory follicular lymphoma, a biopsy showed a histiocytic sarcoma related to the lymphoma but with an activating mutation in MAPK2....
Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory
Authors: Laurie M. Robin, José F. Oliveira da Cruz, Valentin C. Langlais, Mario Martin-Fernandez, Mathilde Metna-Laurent, Arnau Busquets-Garcia, Luigi Bellocchio, Edgar Soria-Gomez, Thomas Papouin, Marjorie Varilh, Mark W. Sherwood, Ilaria Belluomo, Georgina Balcells, Isabelle Matias, Barbara Bosier, Filippo Drago, Ann Van Eeckhaut, Ilse Smolders, Francois Georges, Alfonso Araque, Aude Panatier, Stéphane H.R. Oliet, Giovanni Marsicano
Journal: Neuron (2018)
Arsenic Trioxide–Coated Stent Is an Endothelium‐Friendly Drug Eluting Stent
Authors: Yinping Zhao, Ruolin Du, Tian Zhou, Dongchuan Yang, Yuhua Huang, Yi Wang, Junli Huang, Xiaoyi Ma, Fugui He, Juhui Qiu, Guixue Wang
Journal: Advanced Healthcare Materials (2018)

Abstract An ideal vascular stent would both inhibit in‐stent restenosis (ISR) and promote rapid re‐endothelialization. In the current study, the performance of arsenic trioxide (ATO)‐drug eluting stent (AES) is compared with the bare metal stent, poly‐lactic‐ co ‐glycolic acid–coating metal stent, and rapamycin‐drug eluting stent (RES). In vivo AES is shown to prevent neointimal hyperplasia more efficiently than the others when implanted into the carotid arteries of rabbits. Moreover, AES promotes endothelial cells proliferation and re‐endothelialization more quickly than RES. In vitro ATO exposure significantly increases the viability, proliferation, adhesion, and spreading of primary porcine coronary artery endothelial cells (PCAECs), which are critical for endothelialization. However, ATO exposure reduces the viability of porcine coronary artery smooth muscle cells (PCASMCs). The evaluation of mitochondrial morphology, membrane potential, and function demonstrates that ATO at 2 µmol L −1 causes enlargement of the mitochondrion, enhancement of mitochondrial membrane potential, and adenosine triphosphate (ATP) production in PCAECs but not in PCASMCs. Thus, both in vivo and in vitro studies demonstrate that AES is an effective strategy for rapid re‐endothelialization and inhibition of ISR.
Regulatory T cell-targeted hybrid nanoparticles combined with immuno-checkpoint blockage for cancer immunotherapy
Authors: Wenquan Ou, Raj Kumar Thapa, Liyuan Jiang, Zar Chi Soe, Milan Gautam, Jae-Hoon Chang, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Journal: Journal of Controlled Release (2018)
Abstract 19165: Regional Changes in Cellular and Molecular Pathology in Children With End-stage Dilated Cardiomyopathy: Correlation With Cardiac Performance
Authors: Ching Kit Chen, Mei Sun, Cameron Slorach, Ryo Ishii, Andrew N Redington, Mark K Friedberg
Journal: Circulation (2015)

Dilated cardiomyopathy (DCM) carries poor prognosis in children, often needing heart transplant. Regional differences in left ventricular (LV) function suggest inhomogeneous expression of contractility related proteins. However, associations between myocardial performance and histological / molecular findings are poorly defined. We sought to investigate associations of regional myocardial performance with histological and molecular changes in hearts explanted from children with DCM, undergoing transplantation. Clinical and echo features (including tissue Doppler and strain) were correlated with histological and molecular findings in hearts explanted from 9 children [median age 2.8 years (range 4.4 months-17 years); 6 had LVAD]. Interstitial fibrosis, myocyte volume, and expression of proteins (western blot) implicated in fibrosis and function ( p38 , ERK , phospho- JNK , phospho- GSK , SMA , myosin heavy chain, cadherin, ILK , sarcoplasmic reticulum Ca 2+ -ATPase [SERCA2a], phospho- CamKII , phospholamban [PLN], and phospho-PLN) were correlated with speckle tracking strain from 11 regions per patient (basal and mid regions of anterior septum, anterior, lateral, posterior and inferior LV segments, and right ventricular [RV] free wall). On average, no significant difference was noted for the percentage of fibrosis and myocyte volume between the various LV segments, and between RV and LV. LV dimension, systolic and diastolic function were not related to interstitial fibrosis, myocyte volume or molecular signaling. Tricuspid annular plane systolic excursion was related to myocyte volume (r=0.89; p &lt;0.01). An inverse relationship between the extent of interstitial fibrosis and segmental longitudinal strain was present for LV basal and mid posterior segments (basal posterior, r=0.96, p &lt;0.01; mid posterior, r=0.74, p =0.05). Global longitudinal strain was related to expression of ILK and SERCA2a (ILK, r=0.78, p =0.02; SERCA2a, r=0.71, p =0.04). This study demonstrated association of regional cardiac function in children with DCM with expression of calcium-cycling and contractile proteins, as well as interstitial fibrosis. These findings have implications for diagnosis and therapeutic targets in pediatric DCM.
Abstract 15850: Stimulation of Soluble Guanylate Cyclase Activity With Riociguat Promotes Angiogenesis and Improves Neovascularization After Hindlimb Ischemia
Authors: Wahiba Dhahri, Sylvie Dussault, Michel Desjarlais, Raphaël Mathieu, Alain Rivard
Journal: Circulation (2016)

Background:  The NO-cGMP pathway has been shown to be essential for angiogenesis, vasculogenesis and post-natal neovascularization. The key enzyme responsible for the synthesis of cGMP following binding of NO is soluble guanylate cyclase (sGC). Riociguat is the first member of a novel class of compounds known as sGC stimulators. We tested the hypothesis that stimulation of sGC with riociguat might improve neovascularization in response to ischemia.   Methods/Results:  In a matrigel assay  in vitro , riociguat dose-dependently stimulated tubule formation in human umbilical vein endothelial cells (HUVECs). Cell migration (scratch assay) was also increased in HUVECs treated with riociguat. We used a mouse model of hindlimb ischemia to investigate the effect of riociguat on neovascularization  in vivo . C57Bl/6 mice were treated by gavage with 3 mg/kg/day of riociguat (or vehicle) for a total of 28 days. After two weeks of treatment, hindlimb ischemia was surgically induced by femoral artery removal. Treatment with riociguat led to improved blood flow recovery after ischemia (Laser Doppler imaging), and increased capillary density in ischemic muscles (CD31 immunostaining). Clinically, this was associated with a significant decrease of ambulatory impairment and ischemic damages. At the molecular level, we found that riociguat treatment is associated with an increased activation of sGC, PKG-α/β, Akt and ERK1/2 both in HUVECs and in ischemic muscles. Interestingly, mice treated with riociguat also showed a 94% increase in the number of bone marrow-derived pro-angiogenic cells (PACs) compared to control mice (p   Conclusions:  The sGC stimulator riociguat promotes angiogenesis and improves neovascularization after ischemia. The mechanism involves activation of angiogenic pathways such as Akt and ERK1/2, together with an improvement of PAC number and functions. sGC stimulation could constitute a novel therapeutic strategy to reduce tissue ischemia in patients with severe atherosclerotic diseases.
Serum α<sub>1</sub>-Antitrypsin Concentration in the Diagnosis of α<sub>1</sub>-Antitrypsin Deficiency
Authors: Killian Hurley, George T. O’Connor
Journal: JAMA (2018)

A 64-year-old man with a family history of early-onset lung disease, presented with dyspnea and recurrent pneumonia, emphysema changes on CT, and a serum α1-antitrypsin concentration of 14 mg/dL. How would you interpret the result?
Medicinal cannabis should not be used ahead of approved drugs, says German review
Authors: Ned Stafford
Journal: BMJ (2018)

The increasing number of German doctors prescribing cannabis is being fuelled in part by “hype,” concludes a review that contends that in most cases “tried and tested” drugs are better options.

The review says that research into the use of cannabis for medical treatment has been limited, in comparison with the intensive research process before traditional drugs receive regulatory approval. What limited research there is does not support the claims made by proponents medicinal cannabis, it says.

“Cannabis is not a miracle drug,” said the study coauthor Gerd Glaeske, an expert in healthcare economics and policy at the University of Bremen.

The 90 page cannabis report was commissioned by Techniker Krankenkasse (TK),1 one of Germany’s largest public sector health insurers, which regularly commissions studies …