tbuckley/cabot-search huggingface dataset:
Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome
Authors: Mirko Scarsi, Silvia Piantoni, Enrico Colombo, Paolo Airó, Donata Richini, Marco Miclini, Valeria Bertasi, Marta Bianchi, Damiano Bottone, Patrizia Civelli, Maria-Sofia Cotelli, Ezio Damiolini, Gloria Galbassini, Diego Gatta, Maria-Laura Ghirardelli, Roberto Magri, Paola Malamani, Monia Mendeni, Stefano Molinari, Andrea Morotti, Luisa Salada, Marinella Turla, Angiola Vender, Angela Tincani, Antonio Brucato, Franco Franceschini, Roberto Furloni, Laura Andreoli
Journal: Annals of the Rheumatic Diseases (2020)

The outbreak of COVID-19 posed the issue of urgently identifying treatment strategies. Colchicine was considered for this purpose based on well-recognised anti-inflammatory effects and potential antiviral properties. In the present study, colchicine was proposed to patients with COVID-19, and its effects compared with 'standard-of-care' (SoC).In the public hospital of Esine, northern Italy, 140 consecutive inpatients, with virologically and radiographically confirmed COVID-19 admitted in the period 5-19 March 2020, were treated with 'SoC' (hydroxychloroquine and/or intravenous dexamethasone; and/or lopinavir/ritonavir). They were compared with 122 consecutive inpatients, admitted between 19 March and 5 April 2020, treated with colchicine (1 mg/day) and SoC (antiviral drugs were stopped before colchicine, due to potential interaction).Patients treated with colchicine had a better survival rate as compared with SoC at 21 days of follow-up (84.2% (SE=3.3%) vs 63.6% (SE=4.1%), p=0.001). Cox proportional hazards regression survival analysis showed that a lower risk of death was independently associated with colchicine treatment (HR=0.151 (95% CI 0.062 to 0.368), p<0.0001), whereas older age, worse PaO2/FiO2, and higher serum levels of ferritin at entry were associated with a higher risk.This proof-of-concept study may support the rationale of use of colchicine for the treatment of COVID-19. Efficacy and safety must be determined in controlled clinical trials.
Inhibition of MAN2A1 Enhances the Immune Response to Anti–PD-L1 in Human Tumors
Authors: Sailing Shi, Shengqing Gu, Tong Han, Wubing Zhang, Lei Huang, Ziyi Li, Deng Pan, Jingxin Fu, Jun Ge, Myles Brown, Peng Zhang, Peng Jiang, Kai W. Wucherpfennig, X. Shirley Liu
Journal: Clinical Cancer Research (2020)

Immune checkpoint blockade has shown remarkable efficacy, but in only a minority of patients with cancer, suggesting the need to develop additional treatment strategies. Aberrant glycosylation in tumors, resulting from the dysregulated expression of key enzymes in glycan biosynthesis, modulates the immune response. However, the role of glycan biosynthesis enzymes in antitumor immunity is poorly understood. We aimed to study the immunomodulatory effects of these enzymes.We integrated transcriptional profiles of treatment-naïve human tumors and functional CRISPR screens to identify glycometabolism genes with immunomodulatory effects. We further validated our findings using in vitro coculture and in vivo syngeneic tumor growth assays.We identified MAN2A1, encoding an enzyme in N-glycan maturation, as a key immunomodulatory gene. Analyses of public immune checkpoint blockade trial data also suggested a synergy between MAN2A1 inhibition and anti-PD-L1 treatment. Loss of Man2a1 in cancer cells increased their sensitivity to T-cell-mediated killing. Man2a1 knockout enhanced response to anti-PD-L1 treatment and facilitated higher cytotoxic T-cell infiltration in tumors under anti-PD-L1 treatment. Furthermore, a pharmacologic inhibitor of MAN2A1, swainsonine, synergized with anti-PD-L1 in syngeneic melanoma and lung cancer models, whereas each treatment alone had little effect.Man2a1 loss renders cancer cells more susceptible to T-cell-mediated killing. Swainsonine synergizes with anti-PD-L1 in suppressing tumor growth. In light of the limited efficacy of anti-PD-L1 and failed phase II clinical trial on swainsonine, our study reveals a potential therapy combining the two to overcome tumor immune evasion.See related commentary by Bhat and Kabelitz, p. 5778.
Abstract #4583: CCL25 blockade inhibits anti-apoptotic signals in prostate cancer cells and enhances cytotoxic effects of etoposide
Authors: Praveen Sharma, Rajesh Singh, John Eaton, James Lillard, Kristian Novakovic, William Grizzle, Leland Chung, Shailesh Singh
Journal: Cancer Research (2009)

Prostate cancer (PCa) remains the second leading cause of cancer-related deaths among men in the US. Chemotherapy is often the last option for treating hormone refractory PCa. This results in an initial response, but is nearly always followed by relapse due to chemoresistance and the indolent nature of PCa cells that have a relatively low rate of apoptosis. Therefore, better efficacy of chemotherapeutics can be achieved by combining additional agents, which can block the mechanisms responsible for this low apoptosis rate. We have previously shown functional expression of CCR9 by PCa cells. T cells primarily express CCR9 and signaling mediated by CCR9-CCL25 interactions not only induces T cell chemotaxis but the activation of anti-apoptotic pathways for T cell survival. Therefore, this study investigates CCR9-mediated anti-apoptotic signals in PCa cells in vitro and the therapeutic application of CCR9 blockade in combination with chemotherapeutic agents in vivo. PCa cell lines (PC3 and LNCaP) were treated with or without CCL25, anti-CCR9 antibody, and/or etoposide. The change in apoptosis was quantified by ImageStream analysis and CCR9-mediated activation of anti-apoptotic kinases were characterized by immunoblots. Tumor xenograft models were used to determine the in vivo efficacy of anti-CCR9 antibody or etoposide alone, or the combination of both. Tumor response to therapies was quantified by luciferase-based in vivo imaging. In the present study, we demonstrate that the interaction of CCR9 with its natural ligand (CCL25) increased the activity of anti-apoptotic proteins (i.e., PI3K, ERK1/2, AKT, and GSK-3\#946;) to promote PCa cell survival. Inhibition of CCL25-CCR9 interactions using antibody blockade enhanced the in vitro and in vivo efficacy of etoposide. These results suggest that targeting the CCL25-CCR9 axis can enhance the cytotoxic effect of etoposide. [This work was supported in part by DoD-W81XWH-06-1-0521]  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4583.
Abstract 12737: Quality of Life Outcomes After Catheter Ablation Among Patients With Atrial Fibrillation in the Real World Practice
Authors: Nobuhiro Ikemura, Takehiro Kimura, Ikuko Ueda, Hiroshi Miyama, Taishi Fujisawa, Yoshinori Katsumata, Keiichi Fukuda, Seiji Takatsuki, Shun Kohsaka
Journal: Circulation (2019)

Introduction: Catheter ablation (CA) is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on quality of life (QOL) in ...
Training of Male and Female Surgical Residents
Authors: Jessica G. Y. Luc, Mara B. Antonoff
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
A committed tissue-resident memory T cell precursor within the circulating CD8+ effector T cell pool
Authors: Lianne Kok, Feline E. Dijkgraaf, Jos Urbanus, Kaspar Bresser, David W. Vredevoogd, Rebeca F. Cardoso, Leïla Perié, Joost B. Beltman, Ton N. Schumacher
Journal: The Journal of Experimental Medicine (2020)

An increasing body of evidence emphasizes the role of tissue-resident memory T cells (TRM) in the defense against recurring pathogens and malignant neoplasms. However, little is known with regard to the origin of these cells and their kinship to other CD8+ T cell compartments. To address this issue, we followed the antigen-specific progeny of individual naive CD8+ T cells to the T effector (TEFF), T circulating memory (TCIRCM), and TRM pools by lineage-tracing and single-cell transcriptome analysis. We demonstrate that a subset of T cell clones possesses a heightened capacity to form TRM, and that enriched expression of TRM–fate-associated genes is already apparent in the circulating TEFF offspring of such clones. In addition, we demonstrate that the capacity to generate TRM is permanently imprinted at the clonal level, before skin entry. Collectively, these data provide compelling evidence for early stage TRM fate decisions and the existence of committed TRM precursor cells in the circulatory TEFF compartment.
Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity
Authors: Henrique Lemos, Rong Ou, Caroline McCardle, Yijun Lin, Jessica Calver, Jack Minett, Ahmed Chadli, Lei Huang, Andrew L Mellor
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Activating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mice bearing LLC tumors. Methods Mice bearing established LLC tumors were treated with synthetic cyclic diadenyl monophosphate (CDA) to activate STING. Mice were monitored to assess LLC tumor growth, survival and protective antitumor immunity. Transcriptional and metabolic analyses were used to identify pathways responsive to CDA, and mice were co-treated with CDA and drugs that disrupt these pathways. Results CDA slowed LLC tumor growth but most CDA-treated mice (77%) succumbed to tumor growth. No evidence of tumor relapse was found in surviving CDA-treated mice at experimental end points but mice were not immune to LLC challenge. CDA induced rapid increase in immune regulatory pathways involving programmed death-1 (PD-1), indoleamine 2,3 dioxygenase (IDO) and cyclooxygenase-2 (COX2) in the TME. PD-1 blockade enhanced antitumor responses to CDA and increased mouse survival but mice did not eliminate primary tumor burdens. Two IDO inhibitor drugs had little or no beneficial effects on antitumor responses to CDA. A third IDO inhibitor drug synergized with CDA to enhance tumor control and survival but mice did not eliminate primary tumor burdens. In contrast, co-treatments with CDA and the COX2-selective inhibitor celecoxib controlled tumor growth, leading to uniform survival without relapse, and mice acquired resistance to LLC re-challenge and growth of distal tumors not exposed directly to CDA. Thus, mice co-treated with CDA and celecoxib acquired stable and systemic antitumor immunity. Conclusions STING activation incites potent antitumor responses and boosts local immune regulation to attenuate antitumor responses. Blocking STING-responsive regulatory pathways synergizes with CDA to enhance antitumor responses, particularly COX2 inhibition. Thus, therapy-induced resistance to STING may necessitate co-treatments to disrupt regulatory pathways responsive to STING in patients with cancer.
Squamous Cell Carcinoma of Thymus Presenting as Constrictive Pericarditis Diagnosed With 18F-FDG PET/CT
Authors: Vankadari Kousik, Milap Milap, Rajesh Bollam, Rama Krishna Prasad, Gopi Krishna
Journal: Clinical Nuclear Medicine (2020)

Abstract Constrictive pericarditis refers to focal or global thickening of pericardium causing impedance to diastolic filling and increased systemic venous pressure. We discuss a case of thymic carcinoma presenting as constrictive pericarditis. A 70-year-old man experiencing shortness of breath underwent Doppler echocardiography for further evaluation. Echocardiography was suggestive of thickened nodular pericardium with minimal pericardial effusion, and Doppler features were suggestive of constrictive pericarditis. 18 F-FDG PET/CT done to exclude malignancy reveals locally advanced thymic carcinoma spreading along the pericardial sheath with metabolically active rib metastases.
The small molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical- and JNK-dependent mechanism
Authors: Xin-Yan Pei, Yun Dai, Steven Grant
Journal: Cancer Research (2004)

539  Multiple myeloma represents a generally incurable plasma cell disorder that arises from the dysregulated growth and survival of differentiated plasma cells. Recently, preclinical evidence has been accumulating that multiple myeloma cells are highly sensitive to the CDK inhibitor flavopiridol, leading to Phase II trials of flavopiridol in myeloma and related malignancies. Because flavopiridol induces apoptosis through the mitochondrial dysfunction, the notion that blockade of Bcl-2, which is present at relatively high levels in myeloma cells, might amplify this process appears plausible. To address this issue, interactions between the flavopiridol and the small molecule Bcl-2 antagonist HA14-1 were examined in human multiple myeloma cells. Whereas individual treatment of U266 myeloma cells with 10 μM HA14-1 or 100 nM flavopiridol had little effect, exposure to flavopiridol (6 hr) followed by HA14-1 (18 hr) resulted in a striking increase in apoptosis, accompanied by mitochondrial damage (cytochrome c and Smac/DIABLO release; loss of ΔΨm), activation of caspases-9, -8, and –3, as well as diminished clonogenic survival. Similar findings were noted in other myeloma cell lines (e.g., MM.1S) as well as those resistant to dexamethasone (MM.1R). Combined exposure to flavopiridol and HA14-1 triggered a marked increase in ROS generation; moreover, the anti-oxidant L-N-acetylcysteine attenuated this event and apoptosis. The lethality of flavopiridol/HA14-1 was associated with down-regulation of Mcl-1, Bcl-xL, Bid cleavage, mitochondrial translocation of Bax, and diminished association of Bcl-2 with Bax and Bak. Flavopiridol/HA14-1-treated cells also exhibited a marked activation of JNK, a modest activation of p38 MAPK, and down-regulation of cyclin D1. Finally, in contrast to dexamethasone, flavopiridol/HA14-1-induced lethality was unaffected by exogenous IL-6. Together, these findings indicate that flavopiridol and HA14-1 cooperate to trigger oxidant injury, mitochondrial dysfunction, caspase activation, and apoptosis in human multiple myeloma cells, and suggest that this approach may warrant further evaluation as an anti-myeloma strategy.
Abstract 10962: 3d Net Mold System Derived Myocardial Block: Initial Feasibility and Effect of in situ Regeneration
Authors: Takeyoshi Ota, Keigo Kawaji, Austeja Staneviciute, Marcella K Vaicik, Andrew Beaser, Roderick Tung, Hiroshi Matsushita, Narutoshi Hibino
Journal: Circulation (2019)

Objective: A novel 3D Net Mold System enables us to create a myocardial block as a scaffold-free structure. We examined the feasibility and the in-situ regenerative effect of the myocardial block. ...
Multifunctional biomimetic hydrogel systems to boost the immunomodulatory potential of mesenchymal stromal cells
Authors: Ainhoa Gonzalez-Pujana, Kyle H. Vining, David K.Y. Zhang, Edorta Santos-Vizcaino, Manoli Igartua, Rosa Maria Hernandez, David J. Mooney
Journal: Biomaterials (2020)
Heart failure with preserved ejection fraction: insights into diagnosis and pathophysiology
Authors: Sherif F Nagueh
Journal: Cardiovascular Research (2020)

Heart failure with preserved ejection fraction (HFpEF) accounts for at least half the cases of heart failure, currently diagnosed. There are several cardiac and non-cardiac manifestations of the syndrome. Structure and function abnormalities can include all four cardiac chambers. The left ventricle has abnormal systolic and diastolic functions which can be examined by invasive and non-invasive measurements. In addition, the left atrium enlarges with abnormal left atrial function, pulmonary hypertension occurs, and the right ventricle can develop hypertrophy, enlargement, and systolic dysfunction. There are a paucity of data on calcium handling in HFpEF patients. Growing literature supports the presence of abnormalities in titin and its phosphorylation, and increased interstitial fibrosis contributing to increased chamber stiffness. A systemic inflammatory state causing reduced myocardial cyclic guanosine monophosphate along with defects in the unfolded protein response have been recently reported. Diagnosis relies on signs and symptoms of heart failure, preserved ejection fraction, and detection of diastolic function abnormalities based on echocardiographic findings and abnormally elevated natriuretic peptide levels or invasive measurements of wedge pressure at rest or with exercise. There are currently two diagnostic algorithms: H2FPEF, and HFA-PEFF with limited data comparing their performance head to head in the same patient population. Despite the growing understanding of the syndrome's pathophysiology, there have been little success in developing specific treatment for patients with HFpEF.
Trends in HIV Preexposure Prophylaxis Prescribing in the United States, 2012-2018
Authors: Hyun Jin Song, Patrick Squires, Debbie Wilson, Wei-Hsuan Lo-Ciganic, Robert L. Cook, Haesuk Park
Journal: JAMA (2020)

years), more likely to be male, and had lower rates of hypertension, congestive heart failure, pulmonary disease, and chronic obstructive pulmonary disease than white or black patients (P < .001for each pairwise comparison) (Table ).Discussion | More than 40% of Latinos in the Baltimore-Washington, DC metropolitan region who were tested for SARS-CoV-2 were positive, a much higher proportion than for any other racial/ethnic group.While SARS-CoV-2 testing inclusion criteria were standardized, differential access to testing may have contributed to higher rates of positivity; Latino patients have historically demonstrated lower rates of insurance and health care utilization. 3 However, an alternative explanation may be higher disease prevalence, with the spread of infection among Latinos driven by decreased opportunity for social distancing in the setting of dense housing and continued work engagement due to essential worker status and economic necessity. 1,4,5 This study was limited to patients visiting JHHS, excluding those tested for SARS-CoV-2 elsewhere in the region.In addition, this study cannot determine whether differences in Latino patient SARS-CoV-2 positivity represent a higher disease prevalence, differences in access to health care (eg, reluctance in seeking care), or both.
Audio Interview: New SARS-CoV-2 Vaccine Results, with Peter Piot
Authors: Eric J. Rubin, Lindsey R. Baden, Peter Piot, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

New SARS-CoV-2 Vaccine Results, with Peter Piot In this audio interview conducted on July 29, 2020, the editors are joined by Peter Piot, who talks about his own experience with Covid-19, as well a...
THU0061 Ribosomal p protein antibodies
Authors: SM Ivanova, GG Karpova, NV Bogachiova, TA Riazantctva, AI Speranskey
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Circulating autoantibodies are one of the main characteristic of autoimmune disease as systemic lupus erythematosus (SLE). The associations between anti-DNA antibodies and renal disease, anti-Ro with cutaneous manifestations and congenital heart block are well established. The human ribosomal P proteins (RPP) designated PO (38 kd), P1 (19 kd), and P2 (17 kd), the clinical significance of these antibodies is disputed, but some data suggest an association with aggressive disease, nephritis, central nervous system (CNS) abnormalities. <h3>Objectives</h3> The aim of the present study was to determine the possible clinical and immunological associations of anti-RPP antobodies in SLE. <h3>Methods</h3> Serum samples from 68 patients with SLE who satisfied the American Rheumatism Association revised criteria for SLE entered the study. Anti-RPP activity was determined by ELISA (TRINITY BIOTECH RIBOSOMAL P 1gG, A, M), the specifity was confirmed by Western blotting (Wb). Antinuclear factor (ANF) was detected by indirect immunofluorescence, anti-DNA -by ELISA, anti-Ro, La, RNP, Sm antibodies -by double immunodiffusion, CRP, C3, C4-by radial immunodiffusion. <h3>Results</h3> Anti-RPP antibodies were demonstrated by ELISA in sera of 13 patients (19%). 17 sera were investigated by Wb, 6 of them were positive by both ELISA and Wb, another 11 were negative as in ELISA, as in Wb. Anti-P reactivity was against 38 kd (P0), 19 kd (P1) and 17 kd (P2) in one sera; 38 kd and 17 kd (PO, P 2) in 4 sera; and 38 kd (PO) also in one sera. SLEDAI score was 13,6+ 8,65 in seropositive group, and 16,7+25,82 in seronegative. The frequency of nephritis, CNS involvement was significantly higher in RPP-positive patients-38,5% (5/13) and 38,5% (5/13) against 7,3% (4/55) and 18%(10/55). In the group of 15 SLE patients with CNS involvement 5 (33%) had increased anti-RPP antibody levels. The highest levels of anti-RPP had 3 patients with agressive disease, all of them had nephritis, one also psychosis-convulsions, and one-hemolytic anaemia. <h3>Conclusion</h3> In conclusion, we suggest that anti-RPP antibodies may be a good serological marker for not only SLE, but for aggressive duration of disease, including damaging of kidney and brain. (abstract for oral presentation).
Abstract IA28: Tumor uniformity
Authors: Sam Behjati
Journal: Cancer Research (2020)

Abstract Intra- and intertumor heterogeneity has emerged as a near-universal feature of human cancer. The definition of heterogeneity has advanced our understanding of various biologic and clinical challenges. At the same time, however, it distracts from unifying features of tumor that may lend themselves as universal targets. Here, I outline some observations from single-cell RNA sequencing experiments of childhood and adult cancers that indicate that transcriptional cellular identity transcends intra- and intertumor heterogeneity. Accordingly, the cellular transcriptome may in some cases represent a tumor-overarching target. Citation Format: Sam Behjati. Tumor uniformity [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA28.