tbuckley/cabot-search huggingface dataset:
Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcinoma
Authors: Karīna Siliņa, Alex Soltermann, Farkhondeh Movahedian Attar, Ruben Casanova, Zina M. Uckeley, Helen Thut, Muriel Wandres, Sergejs Isajevs, Phil Cheng, Alessandra Curioni-Fontecedro, Periklis Foukas, Mitchell P. Levesque, Holger Moch, Aija Linē, Maries van den Broek
Journal: Cancer Research (2017)

Abstract In solid tumors, the presence of lymph node–like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS develop in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multispectral microscopy, quantitative pathology, and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation in LSCC culminating in the formation of germinal centers (GC). In untreated patients, TLS density was the strongest independent prognostic marker. Furthermore, TLS density correlated with GC formation and expression of adaptive immune response–related genes. In patients treated with neoadjuvant chemotherapy, TLS density was similar, but GC formation was impaired and the prognostic value of TLS density was lost. Corticosteroids are coadministered with chemotherapy to manage side effects in LSCC patients, so we evaluated whether they impaired TLS development independently of chemotherapy. TLS density and GC formation were each reduced in chemotherapy-naïve LSCC patients treated with corticosteroids before surgery, compared with untreated patients, a finding that we confirmed in the experimental model of lung TLS induction. Overall, our results highlight the importance of GC formation in TLS during tumor development and treatment. Significance: Corticosteroid treatment during chemotherapy negatively affects the development of tertiary lymphoid structures and abrogates their prognostic value in patients with lung cancer. Cancer Res; 78(5); 1308–20. ©2018 AACR.
Heart Valves: Developing a Clinically Relevant Tissue Engineered Heart Valve—A Review of Current Approaches (Adv. Healthcare Mater. 24/2017)
Authors: Aline L. Y. Nachlas, Siyi Li, Michael E. Davis
Journal: Advanced Healthcare Materials (2017)

Heart valve tissue engineering has the potential to allow the development of living heart valves comprised of cells and biomaterials, and to make them be anatomically patient-specific. This Review (article No. 1700918) describes the current valve prosthesis and its design criteria, and discusses current strategies and future perspectives for valve tissue engineering. The cover image shows a patient with a “living valve implant” that was engineered using 3D bioprinting, biomaterial scaffold, and cells.
Healthcare provider perspectives on managing sexually transmitted infections in HIV care settings in Kenya: A qualitative thematic analysis
Authors: Kipruto Chesang, Sureyya Hornston, Odylia Muhenje, Teresa Saliku, Joy Mirjahangir, Amanda Viitanen, Helgar Musyoki, Christine Awuor, George Githuka, Naomi Bock
Journal: PLoS Medicine (2017)

Background The burden of sexually transmitted infections (STIs) has been increasing in Kenya, as is the case elsewhere in sub-Saharan Africa, while measures for control and prevention are weak. The objectives of this study were to (1) describe healthcare provider (HCP) knowledge and practices, (2) explore HCP attitudes and beliefs, (3) identify structural and environmental factors affecting STI management, and (4) seek recommendations to improve the STI program in Kenya. Methods and findings Using individual in-depth interviews (IDIs), data were obtained from 87 HCPs working in 21 high-volume comprehensive HIV care centers (CCCs) in 7 of Kenya's 8 regions. Transcript coding was performed through an inductive and iterative process, and the data were analyzed using NVivo 10.0. Overall, HCPs were knowledgeable about STIs, saw STIs as a priority, reported high STI co-infection amongst people living with HIV (PLHIV), and believed STIs in PLHIV facilitate HIV transmission. Most used the syndromic approach for STI management. Condoms and counseling were available in most of the clinics. HCPs believed that having an STI increased stigma in the community, that there was STI antimicrobial drug resistance, and that STIs were not prioritized by the authorities. HCPs had positive attitudes toward managing STIs, but were uncomfortable discussing sexual issues with patients in general, and profoundly for anal sex. The main barriers to the management of STIs reported were low commitment by higher levels of management, few recent STI-focused trainings, high stigma and low community participation, and STI drug stock-outs. Solutions recommended by HCPs included formulation of new STI policies that would increase access, availability, and quality of STI services; integrated STI/HIV management; improved STI training; increased supervision; standardized reporting; and community involvement in STI prevention. The key limitations of our study were that (1) participant experience and how much of their workload was devoted to managing STIs was not considered, (2) some responses may have been subject to recall and social desirability bias, and (3) patients or clients of STI services were not interviewed, and therefore their inputs were not obtained. While considering these limitations, the number and variety of facilities sampled, the mix of staff cadres interviewed, the use of a standardized instrument, and the consistency of responses add strength to our findings. Conclusions This study showed that HCPs understood the challenges of, and solutions for, improving the management of STIs in Kenya. Commitment by higher management, training in the management of STIs, measures for reducing stigma, and introducing new policies of STI management should be considered by health authorities in Kenya.
Abstract 14386: RNA Binding Protein HuR Regulates Cardiac Sodium Channel Gene (SCN5A) Expression Through Transcriptional and Post-Transcriptional Pathways
Authors: Anyu Zhou, Ning Jiang, Guangbin Shi, An Xie, Hong Liu, Man Liu, Euy-Myoung Jeong, Samuel Dudley
Journal: Circulation (2016)

Introduction: In patients, deletions or loss-of-function mutations of SCN5A have been associated with a wide range of arrhythmias. Our previous results have shown that the expression of SCN5A decre...
Abstract 15197: Echocardiographic Evaluation of Paravalvular Regurgitation After Transarterial Valve Implantation Based on the Academic Valve Research Consortium 2 Recommendations
Authors: Dragos Alexandru, Simcha Pollack, Florentina Petillo, Dennis Mihalatos, Eddy Barasch
Journal: Circulation (2016)

Introduction: Recently, a simple scheme of semiquantitative evaluation of paravalvular regurgitation (PVR) severity on TTE in parasternal short axis (SAX) after transarterial valve replacement (TAV...
Annals Story Slam - I Don't Think It's a Good Fit
Authors: Kate Yun
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 December 2017Annals Story Slam - I Don't Think It's a Good FitFREEKate Yun, MD, MHSKate Yun, MD, MHSUniversity of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (K.Y.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0076 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - I Don't Think It's a Good Fit "I Don't Think It's a Good Fit," by Dr. Kate Yun (Duration 6:19)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (K.Y.)Current Author Address: Kate Yun, MD, MHS; e-mail, [email protected]chop.edu. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 December 2017Volume 167, Issue 12Page: SS1 ePublished: 19 December 2017 Issue Published: 19 December 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Inhibition of JAK-STAT Signaling Suppresses Pathogenic Immune Responses in Medium and Large Vessel Vasculitis
Authors: Hui Zhang, Ryu Watanabe, Gerald J. Berry, Lu Tian, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Circulation (2017)

Background: Giant cell arteritis, a chronic autoimmune disease of the aorta and its large branches, is complicated by aneurysm formation, dissection, and arterial occlusions. Arterial wall dendritic cells attract CD4 + T cells and macrophages to form prototypic granulomatous infiltrates. Vasculitic lesions contain a diverse array of effector T cells that persist despite corticosteroid therapy and sustain chronic, smoldering vasculitis. Transmural inflammation induces microvascular neoangiogenesis and results in lumen-occlusive intimal hyperplasia. We have examined whether persistent vessel wall inflammation is maintained by lesional T cells, including the newly identified tissue-resident memory T cells, and whether such T cells are sensitive to the cytokine-signaling inhibitor tofacitinib, a Janus kinase (JAK) inhibitor targeting JAK3 and JAK1. Methods: Vascular inflammation was induced in human arteries engrafted into immunodeficient mice that were reconstituted with T cells and monocytes from patients with giant cell arteritis. Mice carrying inflamed human arteries were treated with tofacitinib or vehicle. Vasculitic arteries were examined for gene expression (reverse transcription polymerase chain reaction), protein expression (immunohistochemistry), and infiltrating cell populations (flow cytometry). Results: Tofacitinib effectively suppressed innate and adaptive immunity in the vessel wall. Lesional T cells responded to tofacitinib with reduced proliferation rates (&lt;10%) and minimal production of the effector molecules interferon-γ, interleukin-17, and interleukin-21. Tofacitinib disrupted adventitial microvascular angiogenesis, reduced outgrowth of hyperplastic intima, and minimized CD4 + CD103 + tissue-resident memory T cells. Conclusions: Cytokine signaling dependent on JAK3 and JAK1 is critically important in chronic inflammation of medium and large arteries. The JAK inhibitor tofacitinib effectively suppresses tissue-resident memory T cells and inhibits core vasculitogenic effector pathways.
Abstract 14391: Mechanical Dyssynchrony Defined by Phase Analysis from GSPECT: Does it Predict Mortality?
Authors: Paul L Hess, Linda K Shaw, Mary L Shepherd, Michael MacKenzie, Robert Pagnanelli, Mona Fiuzat, Jonathan P Piccini, Sana M Al-Khatib, Christopher M O'Connor, Salvador Borges-Neto
Journal: Circulation (2012)

Background:  Phase analysis from gated single photon emission computed tomography myocardial perfusion imaging (GSPECT MPI) has emerged as an attractive means to assess left ventricular mechanical dyssynchrony. Whether dyssynchrony assessed by GSPECT MPI can identify patients at increased risk of mortality is unknown.   Methods:  We identified all patients with angiographically significant coronary disease and a GSPECT MPI in the Duke Databank for Cardiovascular Disease between July 2003 and August 2009. The range of time during which 95% of the left ventricle is initiating contraction (phase bandwidth) and the degree of heterogeneity in the distribution of segmental initiation of mechanical contraction (phase standard deviation (SD)) by GSPECT MPI were measured. To evaluate the relationship between each measure of dyssynchrony and long-term survival, unadjusted and adjusted Cox proportional hazards models were constructed.   Results:  A total of 1434 patients were identified.The median age was 64 (interquartile range (IQR) 55-72) years. A majority were male (69.6%), were white (73.8%), and had hypertension (HTN)(76.1%). A minority had chronic obstructive pulmonary disease (COPD) (6.6%), congestive heart failure (CHF) (24.3%), diabetes mellitus (DM)(36.2%), peripheral vascular disease (PVD)(10.5%), prior myocardial infarction (MI)(33.0%), or renal insufficiency (RI)(5.4%). The median duration follow-up was 4.2 (IQR 2.8-6.3) years. A total of 377 deaths were observed. After adjustment for age, sex, race, COPD, DM, HTN, PVD, cerebrovascular disease, prior MI, CHF, RI, and tobacco use, phase bandwidth and phase SD were significantly associated with mortality ( Table ).   Conclusions:  Dyssynchrony measured by GSPECT MPI is a significant predictor of mortality and provides information independent of clinical history.
Abstract 19463: Temporal Regulation of Retinoic Acid Enriches Left Ventricular Cardiomyocytes From Human Embryonic Stem Cells
Authors: Pengcheng Han, Jun Li, Heecheol Cho
Journal: Circulation (2016)

Retinoic acid (RA) plays a pivotal role during the heart development; RA needs to be inactive during the early cardiac mesoderm formation, but late-stage surplus of RA is critical for the cardiac looping and formation of the ventricular myocardium. We hypothesized that mimicking the  in vivo  RA signaling during human embryonic stem cell (hESC) differentiation could lead to enriched left ventricular myocytes.  H9 human ESCs were differentiated to cardiac lineage by treatment with Activin A, BMP4 and bFGF (ABF, control) for the first three days (d1-4). This lead to >70% brachyury+ mesoderm formation, and >80% of the mesodermal cells became cTnT+ cardiac myocytes. RA was inhibited for 24 hrs on d1 with a pan-retinoic acid receptor antagonist, and later activated with exogenous RA (1μM) for three days from d6-9 (Ri-ABF-RA). At d14, the Ri-ABF-RA cardiac myocytes showed >4-fold higher expression of ventricular markers,  IRX4  and  HRT2 , compared to control (n=3, p 29) at ≥d30. This is in line with enrichment of the left ventricular myocytes in Ri+ABF+RA compared to mixed populations of nodal, atrial and ventricular myocytes in ABF. Maximum upstroke velocity was faster in Ri-ABF-RA cardiomyocytes compared to ABF (540±460 vs. 36±26 μV/sec, n>31), pointing to higher Na channel density in Ri-ABF-RA compared to control.  Taken together, the data demonstrate that early RA inhibition followed by late RA activation of hESCs leads to enrichment of the left ventricular cardiomyocytes. The  de novo  cardiomyocytes better represent the left ventricle, and may serve as a specific platform for cardiac regeneration and drug screen for the left ventricular myocardium.
Low-Level Air Pollution Associated With Death
Authors: Junfeng Zhang
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effectiveness of WHO's pragmatic screening algorithm for child contacts of tuberculosis cases in resource-constrained settings: a prospective cohort study in Uganda
Authors: Leonardo Martinez, Ye Shen, Andreas Handel, Srijita Chakraburty, Catherine M Stein, LaShaunda L Malone, W Henry Boom, Frederick D Quinn, Moses L Joloba, Christopher C Whalen, Sarah Zalwango
Journal: The Lancet Respiratory Medicine (2017)
Abstract 17235: Physical Activity Reduces Cardiovascular Mortality in Albuminuria: The Strong Heart Study
Authors: Zaid Almazooq, Brian Salata, Mary Roman, Richard B Devereux, Parmanand Singh
Journal: Circulation (2016)

Background: Prior studies have established that albuminuria is associated with increased cardiovascular (CV) mortality. While it is known that physical activity (PA) improves CV clinical outcomes, ...
The accuracy of carboplatin area under the curve (AUC) estimated by Calvert formula using Cockcroft-Gault formula and Thai eGFR in Thai cancer patients.
Authors: Kokiet Kangwantas, Pannee Chinjarernpan, Virote Sriuranpong, Napa Parinyanitikul, Piyada Sitthideatphaiboon, Nattaya Poovorawan, Suebpong Tanasanvimon
Journal: Journal of Clinical Oncology (2016)

e14017 Background: In current practice, carboplatin dose is calculated by Calvert formula. Although, originally measured glomerular filtration rate (GFR) was used in the formula, creatinine clearance (CrCl) estimation by Cockcroft-Gault (CG) formula is widely accepted. The estimated GFR (eGFR) based on serum creatinine level has been established and endorsed to apply in clinical practice. We conducted a cross sectional study to compare the accuracy of estimated carboplatin AUC by Calvert formula using CG formula and Thai eGFR. Methods: Patients receiving carboplatin based regimens at King Chulalongkorn Memorial Hospital were enrolled. The doses of carboplatin were calculated by Calvert formula using CG formula. The actual carboplatin AUC was estimated by Ghazal-Aswad formula using measured plasma free carboplatin level at 24 hours after infusion. Based on the actual carboplatin AUC, we compared the accuracy of estimated carboplatin AUC by CG formula and Thai eGFR. Results: Of total 45 enrolled patients, 62% were male and the mean age was 60.5 years. The mean BMI was 21.9 (14.64 -32.27) kg/m2 and mean plasma creatinine levels was 0.82 (0.4-1.51) mg/dl. 95.6% received combination chemotherapy. The mean actual carboplatin AUC was 4.94 (±1.26) mg/ml·min. The mean estimated carboplatin AUC by CG and Thai eGFR were 4.07 (±1.17) and 3.50 (±1.12) mg/ml·min, respectively. The mean percentage error (MPE) of the estimated mean carboplatin AUC by CG and Thai eGFR were 16.1 (±22.5) % and 27.7 (±22.9) %, respectively, p < 0.001. For individual patients, the estimated carboplatin AUC by CG was more accurate in 37 (82.2%) patients. However, it dropped to 8 (57.1%) among patients with CrCl by CG more than 90 ml/min. Conclusions: The Calvert formula using CG formula is more accurate than using Thai eGFR in Thai patients. However, there might be certain subgroup that using Thai eGFR is better.
A Jagged1-Notch4 interaction between Alveolar Macrophages and Allergen-Specific T cells Mediates Airway Inflammation by Ultrafine Particles
Authors: Hani Harb, Mingcan Xia, Arian Saffari, Constantinos Sioutas, Talal A. Chatila
Journal: Journal of Allergy and Clinical Immunology (2018)
Precision design of nanomedicines to restore gemcitabine chemosensitivity for personalized pancreatic ductal adenocarcinoma treatment
Authors: Xiao Zhao, Xiuchao Wang, Wei Sun, Keman Cheng, Hao Qin, Xuexiang Han, Yu Lin, Yongwei Wang, Jiayan Lang, Ruifang Zhao, Xiaowei Zheng, Ying Zhao, Jian shi, Jihui Hao, Qing Robert Miao, Guangjun Nie, He Ren
Journal: Biomaterials (2017)
Drug Repurposing Screening Identifies Tioconazole as an ATG4 Inhibitor that Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy
Authors: Pei-Feng Liu, Kun-Lin Tsai, Chien-Jen Hsu, Wei-Lun Tsai, Jin-Shiung Cheng, Hsueh-Wei Chang, Chung-Wai Shiau, Yih-Gang Goan, Ho-Hsing Tseng, Chih-Hsuan Wu, John C. Reed, Lee-Wei Yang, Chih-Wen Shu
Journal: Theranostics (2017)

Background: Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy.However, this theory in clinical cancer research remains controversial due to the limited number of drugs that specifically inhibit autophagy-related (ATG) proteins.Methods: We screened FDA-approved drugs using a novel platform that integrates computational docking and simulations as well as biochemical and cellular reporter assays to identify potential drugs that inhibit autophagy-required cysteine proteases of the ATG4 family.The effects of ATG4 inhibitors on autophagy and tumor suppression were examined using cell culture and a tumor xenograft mouse model.Results: Tioconazole was found to inhibit activities of ATG4A and ATG4B with an IC50 of 1.3 µM and 1.8 µM, respectively.Further studies based on docking and molecular dynamics (MD) simulations supported that tioconazole can stably occupy the active site of ATG4 in its open form and transiently interact with the allosteric regulation site in LC3, which explained the experimentally observed obstruction of substrate binding and reduced autophagic flux in cells in the presence of tioconazole.Moreover, tioconazole diminished tumor cell viability and sensitized cancer cells to autophagy-inducing conditions, including starvation and treatment with chemotherapeutic agents.Conclusion: Tioconazole inhibited ATG4 and autophagy to enhance chemotherapeutic drug-induced cytotoxicity in cancer cell culture and tumor xenografts.These results suggest that the antifungal drug tioconazole might be repositioned as an anticancer drug or chemosensitizer.
LET's sponge: How the lncRNA PFL promotes cardiac fibrosis
Authors: Matthias S. Leisegang
Journal: Theranostics (2017)

Compared to their protein-coding counterparts, almost nothing is known about the role of long noncoding RNAs (lncRNAs) in cardiac fibrosis.In the current report, Liang and Pan et al. characterized the pro-fibrotic lncRNA PFL in respect to cardiac fibrosis in mice.PFL was upregulated in the hearts of mice after myocardial infarction and in fibrotic cardiac fibroblasts.Moreover, PFL competitively sponged the cardio-protective miRNA let-7d in cardiac fibroblasts.Knockdown of platelet activating factor receptor (PTAFR) was shown to affect the pro-fibrotic collagen production mediated by PFL.PTAFR overexpression also led to collagen production and RNA abundance of PTAFR was also regulated by miRNA let-7d.Therefore, the PFL/PTAFR/let-7d-dependent gene regulatory mechanism proposed by the authors manifests the hypothesis of competing endogenous RNAs to cardiac fibrosis.
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression
Authors: Ella J. Daly, Jaskaran B. Singh, Maggie Fedgchin, Kimberly Cooper, Pilar Lim, Richard C. Shelton, Michael E. Thase, Andrew Winokur, Luc Van Nueten, Husseini Manji, Wayne C. Drevets
Journal: JAMA Psychiatry (2017)

Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants.