tbuckley/cabot-search huggingface dataset:
Atlas and Abstract of the Diseases of the Larynx.
Journal: JAMA (1898)

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
Discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USP28 inhibitors
Authors: Zhenzhen Liu, Taoqian Zhao, Zhonghua Li, Kai Sun, Yundong Fu, Ting Cheng, Jimin Guo, Bin Yu, Xiaojing Shi, Hongmin Liu
Journal: Acta Pharmaceutica Sinica B (2019)

Ubiquitin specific peptidase 28 (USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date, only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28 (IC50 = 1.10 ± 0.02 μmol/L, Kd = 40 nmol/L), showing selectivity over USP7 and LSD1 (IC50 > 100 μmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition (EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19. Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers.
High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer
Authors: Erminia Massarelli, Vincent K. Lam, Edwin R. Parra, Jaime Rodriguez-Canales, Carmen Behrens, Lixia Diao, Jing Wang, Jorge Blando, Lauren A. Byers, Niranjan Yanamandra, Sara Brett, Peter Morley, Padmanee Sharma, James Allison, Ignacio I. Wistuba, John V. Heymach
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Introduction</h3> OX-40 co-stimulatory signaling plays a role in mounting anti-tumor immune responses and clinical trials targeting this pathway are ongoing. However, the association of with OX-40 protein expression with clinical outcomes and pathological features in non-small cell lung cancer (NSCLC) are largely unknown. <h3>Methods</h3> Surgically-resected stage I-III NSCLC specimens (<i>N</i> = 100) were stained by immunohistochemistry (IHC) for the following immune markers: OX-40, PD-L1, PD-1, CD3, CD4, CD8, CD45RO, CD57, CD68, FOXP3, granzyme B, and ICOS. Immune-related markers mRNA expression were also assessed. We evaluated the association of OX-40 levels with major clinicopathologic variables, including molecular driver mutations. <h3>Results</h3> OX-40 IHC expression was observed in all tested tumors, predominantly localized in the membrane of the tumor immune infiltrate, and was not associated with a specific clinicopathologic or molecular subtype. High OX-40 expression levels measured by IHC median score were associated with better overall survival (OS) (<i>p</i> = 0.002), independent of CD3/CD8, PD-L1, and ICOS expression. High OX-40 IHC score was associated with increased expression of immune-related genes such as CD3, IFN-gamma, ICOS, CD8, CXCL9, CXCL10, CCL5, granzyme K. <h3>Conclusions</h3> High OX-40 IHC expression in the tumor immune infiltrate is associated with favorable prognosis and increased levels of immune-related genes including IFN-gamma in patients with surgically resected stage I-III NSCLC. Its prognostic utility is independent of PD-L1 and other common markers of immune activation. High OX-40 expression potentially identifies a unique subgroup of NSCLC that may benefit from co-stimulation with OX-40 agonist antibodies and potentially enhance the efficacy of existing immune checkpoint therapies.
A Pharmacogenomic Landscape in Human Liver Cancers
Authors: Zhixin Qiu, Hong Li, Zhengtao Zhang, Zhenfeng Zhu, Sheng He, Xujun Wang, Pengcheng Wang, Jianjie Qin, Liping Zhuang, Wei Wang, Fubo Xie, Ying Gu, Keke Zou, Chao Li, Chun Li, Chenhua Wang, Jin Cen, Xiaotao Chen, Yajing Shu, Zhao Zhang, Lulu Sun, Lihua Min, Yong Fu, Xiaowu Huang, Hui Lv, He Zhou, Yuan Ji, Zhigang Zhang, Zhiqiang Meng, Xiaolei Shi, Haibin Zhang, Yixue Li, Lijian Hui
Journal: Cancer Cell (2019)
Molecular networks of FOXP family: dual biologic functions, interplay with other molecules and clinical implications in cancer progression
Authors: Ju-Ha Kim, Jisung Hwang, Ji Hoon Jung, Hyo-Jung Lee, Dae Young Lee, Sung-Hoon Kim
Journal: Molecular Cancer (2019)

Abstract Though Forkhead box P (FOXP) transcription factors comprising of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression, the underlying function of FOXP3 targeting CD4 + CD25+ regulatory T (Treg) cells and the dual roles of FOXP proteins as an oncogene or a tumor suppressor are unclear and controversial in cancers to date. Thus, the present review highlighted research history, dual roles of FOXP proteins as a tumor suppressor or an oncogene, their molecular networks with other proteins and noncoding RNAs, cellular immunotherapy targeting FOXP3, and clinical implications in cancer progression.
Abstract 3048: A Prospective Randomized Trial of Blood B-type Natriuretic Peptide Levels Informing Management after Elective Coronary Artery Bypass Grafting
Authors: Hamid Deliri, Elaine Davis, Casey S Hager, Christine A Welch, Firasat S Malik, Peter A McCullough, Galen S Wagner, William H Carter
Journal: Circulation (2007)

Background: Measuring B-type natriuretic peptide (BNP) levels is valuable in diagnosis, risk stratification, and management of patients with congestive heart failure. Hypothesis: Knowledge of peri-operative levels of BNP by physicians in patients undergoing elective coronary artery bypass grafting (CABG) influences care processes and clinical outcomes. Methods: Patients undergoing CABG between the ages of 18 –79, with left ventricular ejection fraction (LVEF) ≥ 40%, serum creatinine ≤ 2.0 mg/dl, and without a history of myocardial infarction within six months or a history of atrial fibrillation (AF) at any time were eligible for this prospective randomized trial. Of 150 patients recruited, 75 were randomized to BNP-informed group with levels obtained immediately before surgery, 12, and 72 hours post-operatively. The remaining 75 patients were in a control group and had no routine BNP measurements. Cardiovascular surgeons and cardiologists were presented the BNP results and encouraged to integrate them into clinical decision making. Clinical outcomes were pre-specified as initial hours of post-operative ventilation, re-intubation, weight change from baseline, creatinine change from baseline, occurrence of post-operative AF, post-operative hospital length-of-stay, in-hospital mortality, and re-admission during the first 30 days after discharge. Results: Both groups were similar in age, BMI, LVEF, pump time, use of intra-aortic balloon pump or inotropes, and prophylactic beta-clocker or amiodarone. The mean BNP values were 63.7±91.4, 131.3±103.4, 315.6±238.4 pg/ml at baseline, 12 and 72 hours after CABG. The rates of post-operative AF were 5/75 (6.7%) and 15/75 (20.0%), in the BNP-informed and control groups, respectively, p=0.02. The median surgery-to-discharge length-of-stays were 5.8±1.8 days and 6.6± 2.5 days respectively, in the BNP-informed and control groups, p = 0.04. There was no difference between the groups in regards to other pre-specified outcomes. Conclusion: Provision of peri-operative BNP values to cardiothoracic surgeons and cardiologists caring for patients after CABG reduces the occurrence of post-operative AF, and shortens the post-operative length-of-stay.
OP0100 Infectious complications in systemic lupus erythematosus
Authors: JJ Rovensky, F Mateicka
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In the last decades long time survival of patients with systemic diseases of connective tissue improved dramatically, not only due to new therapeutic methods but also thanks to prompt diagnostics of infections and their effective treatment. In spite of this, infection complications constitute a considerable determinant of mortality in patients with systemic lupus erythematosus (SLE). In these patients, morbidity by bacterial, viral and fungal diseases is higher compared to patients suffering from other rheumatic diseases. There are many reasons why it is so, the most important include variability of infection agents virulence factors, immunopathogenic features of diseases (dysbalance of T-lymphocytes populations, cytokine dysbalance), activity of disease, factors related to it and also the therapy (corticosteroids and immunosuppressants). <h3>Objectives</h3> Authors present detailed results of longitudinal retrospective analysis of morbidity and mortality caused by infections summarised from studies published up to now in the world literature as well as clinical analysis of infectious complications in a group of SLE patients treated in Research Institute of Rheumatic Diseases. <h3>Methods</h3> A group of 135 patients with SLE diagnosed according ARA criteria was studied for infections induced by community acquired pathogens and opportune microorganisms. Clinical and laboratory predictors of infection development in these patients were assessed as well. <h3>Results</h3> Actual morbidity for infection was 36,3% and mortality in connexion to the infection was 1,5%. From the community acquired pathogens the most frequent were infections caused by enterobacteria and Staphylococcus aureus. Fungal infections caused by Candida spp. were predominant in the group of opportune infections. Regarding anatomical site of infection the most frequent were infections of lower respiratory tract and urogenital system. Significant correlation between past infection, activity of the disease (evaluated by ECLAM and SLEDAI indices), proteinuria, leucopenia and high corticoids dosage were revealed. In multiple regression model only activity of the disease as a risk factor for development of infection in patients with SLE was designated. <h3>Conclusion</h3> For effective control and prevention of infectious complications in systemic diseases of connective tissues, changing pathogenicity time trends and resistance to anti-infectious therapy (antibiotics, antifungal and antiviral agents) have to be considered.
PML Plays a Key Role in Severe Congenital Neutropenia with Mutant ELANE Causing Neutrophil Elastase Protein Misfolding
Authors: Patricia Olofsen, Paulette van Strien, Onno Roovers, Hans De Looper, Remco Hoogenboezem, Dennis Bosch, Mehrnaz Ghazvini, Eric Bindels, Emma De Pater, Ivo Touw
Journal: Blood (2019)
An intrinsic role of IL-33 in Treg cell–mediated tumor immunoevasion
Authors: Aikaterini Hatzioannou, Aggelos Banos, Theodore Sakelaropoulos, Constantinos Fedonidis, Maria-Sophia Vidali, Maren Köhne, Kristian Händler, Louis Boon, Ana Henriques, Vasiliki Koliaraki, Panagiotis Georgiadis, Jerome Zoidakis, Aikaterini Termentzi, Marc Beyer, Triantafyllos Chavakis, Dimitrios Boumpas, Aristotelis Tsirigos, Panayotis Verginis
Journal: Nature Immunology (2019)
Severity Classification for Sickle Cell Disease: A RAND/UCLA Modified Delphi Panel
Authors: Nirmish Shah, David Beenhouwer, Michael S Broder, Lanetta Bronte-Hall, Laura De Castro, Sarah N Gibbs, Victor R Gordeuk, Julie Kanter, Elizabeth S Klings, Thokozeni Lipato, Deepa Manwani, Brigid Scullin, Irina Yermilov, Wally R Smith
Journal: Blood (2019)
Eight novel variants in the <i>SLC34A2</i> gene in pulmonary alveolar microlithiasis
Authors: Åsa Lina M. Jönsson, Elisabeth Bendstrup, Susie Mogensen, Elizabeth J. Kopras, Francis X. McCormack, Ilaria Campo, Francesca Mariani, Amparo Escribano-Montaner, Are M. Holm, Maria del Mar Martinez-Colls, Guillem Pintos-Morell, Camille Taillé, Bruno Crestani, Ole Hilberg, Jane Hvarregaard Christensen, Ulf Simonsen
Journal: European Respiratory Journal (2019)

Background Pulmonary alveolar microlithiasis (PAM) is caused by genetic variants in the SLC34A2 gene, which encodes the sodium-dependent phosphate transport protein 2B (NaPi-2b). PAM is characterised by deposition of calcium phosphate concretions (microliths) in the alveoli leading to pulmonary dysfunction. The variant spectrum of SLC34A2 has not been well investigated and it is not yet known whether a genotype–phenotype correlation exists. Methods We collected DNA from 14 patients with PAM and four relatives, and analysed the coding regions of SLC34A2 by direct DNA sequencing. To determine the phenotype characteristics, clinical data were collected and a severity score was created for each variant, based on type and localisation within the protein. Results We identified eight novel allelic variants of SLC34A2 in 14 patients with PAM. Four of these were nonsense variants, three were missense and one was a splice site variant. One patient was heterozygous for two different variants and all other patients were homozygous. Four patients were asymptomatic and 10 patients were symptomatic. The severity of the disease was associated with the variant severity. Conclusions Our findings support a significant role for SLC34A2 in PAM and expand the variant spectrum of the disease. Thus, SLC34A2 variants were detected in all patients and eight novel allelic variants were discovered. An association between disease severity and the severity of the variants was found; however, this needs to be investigated in larger patient populations.
Case 38-2019: A 20-Year-Old Man with Dyspnea and Abnormalities on Chest Imaging
Authors: Robert W. Hallowell, Michael B. Feldman, Brent P. Little, Rebecca S. Karp Leaf, Lida P. Hariri
Journal: New England Journal of Medicine (2019)

A 20-year-old man with a history of electronic-cigarette use presented to the hospital because of a history of dyspnea, intermittent fever, joint stiffness, and nasal congestion. Chest imaging showed ground-glass nodular opacities that were most prominent in the lower lungs. A diagnostic procedure was performed.
THE ETIOLOGY OF TRACHOMA
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1928)

In Supplement No. 2, issued with the August, 1928, number of The Journal of Experimental Medicine, in the caption at the top of page 1, for July read August; for Vol. xlviii, No. 1, read Vol. xlviii, No. 2. The attached slip may be pasted over the present caption.
Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension
Authors: Panagiota Xanthouli, Suzana Jordan, Nicklas Milde, Alberto Marra, Norbert Blank, Benjamin Egenlauf, Matthias Gorenflo, Satenik Harutyunova, Hanns-Martin Lorenz, Christian Nagel, Vivienne Theobald, Mona Lichtblau, Charlotte Berlier, Silvia Ulrich, Ekkehard Grünig, Nicola Benjamin, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2019)

Background In this study, we investigated the impact of the new haemodynamic definition of pulmonary arterial hypertension (PAH) as proposed by the 6th PH World Symposium on phenotypes and survival in patients with systemic sclerosis (SSc). Methods In SSc patients who were prospectively and consecutively screened for PAH including right heart catheterisation in Heidelberg or Zurich, haemodynamic and clinical variables have been reassessed according to the new PAH definition. Patients have been followed for 3.7±3.7 (median 3.4) years; Kaplan-Meier survival analysis was performed. Patients with significant lung or left heart disease were excluded from comparative analyses. Results The final dataset included 284 SSc patients, 146 patients (49.2%) had mean pulmonary arterial pressure (mPAP) ≤20 mm Hg, 19.3% had mPAP 21–24 mm Hg and 29.4% had mPAP ≥25 mm Hg. In the group of mildly elevated mPAP, only four patients (1.4% of the whole SSc cohort) had pulmonary vascular resistance (PVR) values ≥3 Wood Units (WU) and could be reclassified as manifest SSc-APAH. Twenty-eight (9.8%) patients with mPAP of 21–24 mm Hg and PVR ≥2 WU already presented with early pulmonary vascular disease with decreased 6 min walking distance (6MWD) (p&lt;0.001), TAPSE (p=0.004) and pulmonary arterial compliance (p&lt;0.001). A PVR ≥2 WU was associated with reduced long-term survival (p=0.002). PVR and 6MWD were independent prognostic predictors in multivariate analysis. Conclusion The data of this study show that a PVR threshold ≥3 WU is too high to enable an early diagnosis of PAH. A PVR threshold ≥2 WU was already associated with pulmonary vascular disease, significantly reduced survival and would be more appropriate in SSc patients with mild PAH.
Esketamine is approved in Europe for treating resistant major depressive disorder
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Esketamine nasal spray—sold under the name Spravato—has been approved by the European Commission (EC) in combination with a selective serotonin reuptake inhibitor or serotonin and norepinephrine reuptake inhibitor, for adults living with treatment resistant major depressive disorder.1

The spray, sold by Janssen (the pharmaceutical branch of Johnson and Johnson), will be made available for patients with the disorder if they have not responded to at least two different treatments with antidepressants.

The approval comes despite criticism over the limited evidence base.

Before the drug can be marketed in the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) has to review whether any additional safety requirements need to be implemented. The National Institute for Health and …
Hidradenitis suppurativa encounters in a national electronic health record database notable for low dermatology utilization, infrequent biologic prescriptions, and frequent opiate prescriptions
Authors: Mackenzie R. Wehner, Robert Micheletti, Megan H. Noe, Eleni Linos, David J. Margolis, Haley B. Naik
Journal: Journal of the American Academy of Dermatology (2019)
HIV infection predominantly affecting children in Sindh, Pakistan, 2019: a cross-sectional study of an outbreak
Authors: Fatima Mir, Faisal Mahmood, Amna Rehana Siddiqui, Shehla Baqi, Syed Hani Abidi, Abdul Momin Kazi, Apsara Ali Nathwani, Amerta Ladhani, Farah Naz Qamar, Sajid Bashir Soofi, Sikander Ali Memon, Jamila Soomro, Saqib Ali Shaikh, Victoria Simms, Palwasha Khan, Rashida Abbas Ferrand
Journal: The Lancet Infectious Diseases (2019)
Abstract PR12: The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice
Authors: Dannielle Engle, Herve Tiriac, Keith Rivera, Arnaud Pommier, Sean Whalen, Tobiloba Oni, Brinda Alagesan, Eun Lee, Melissa Yao, Matthew Lucito, Benjamin Spielman, Kenneth Yu, Robert Grutzmann, Daniela Aust, Phyllis Gimotty, Katherine Pollard, Ralph Hruban, Michael Goggins, Christian Pilarsky, Young Park, Darryl Pappin, Michael A. Hollingsworth, David Tuveson
Journal: Cancer Research (2019)

Abstract Glycosylation alterations are indicative of tissue inflammation and neoplasia, but whether these alterations contribute to disease pathogenesis is largely unknown. To study the role of glycan changes in pancreatic disease, we inducibly expressed human fucosyltransferase 3 and b1,3-galactosyltransferase 5 in mice, reconstituting the glycan sialyl-Lewis a, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricellular protein fibulin-3 increased its interaction with EGFR, and blockade of fibulin-3, EGFR, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9–mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the KrasG12D oncogene to produce aggressive pancreatic cancer. These findings implicate CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominate CA19-9 as a therapeutic target. This abstract is also being presented as Poster C16. Citation Format: Dannielle Engle, Herve Tiriac, Keith Rivera, Arnaud Pommier, Sean Whalen, Tobiloba Oni, Brinda Alagesan, Eun Lee, Melissa Yao, Matthew Lucito, Benjamin Spielman, Kenneth Yu, Robert Grutzmann, Daniela Aust, Phyllis Gimotty, Katherine Pollard, Ralph Hruban, Michael Goggins, Christian Pilarsky, Young Park, Darryl Pappin, Michael A. Hollingsworth, David Tuveson. The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr PR12.
Association of Media Screen Time Use With Depression in Adolescents
Authors: Jhia Jiat Teh, Wenyi Cai, Nicole Ellen James
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal