tbuckley/cabot-search huggingface dataset:
Expanding mechanistic insights into the pathogenesis of idiopathic CD4+ T cell lymphocytopenia
Authors: Jose S. Campos, Sarah E. Henrickson, Roshini S. Abraham
Journal: Journal of Clinical Investigation (2020)

Idiopathic CD4+ T cell lymphocytopenia (ICL) is a heterogeneous syndrome presenting with persistent CD4+ T cell lymphopenia of unknown origin, and opportunistic infections in some patients. The underlying pathogenesis and appropriate management remain understudied. In this issue of the JCI, Perez-Diez and Wong et al. assessed the prevalence of autoantibodies from the sera of 51 adult ICL patients (out of a cohort of 72). Some patients showed high levels of IgG and IgM autoantibodies against numerous autoantigens, and some autoantibodies were specific for lymphocytes. The researchers implicate these autoantibodies as a possible pathogenic mechanism responsible for the reduction in circulating CD4+ T cells. This study goes beyond defining a mechanism in a complex, poorly defined disease; it also brings a renewed focus on ICL that will likely result in improved diagnostic evaluation and treatment.
SAT0260 Effect of electrical stimulation on closed kinetic chain exercises
Authors: J Meray, F Göðüþ, G Kaymak Karataþ, N Güler
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To investigate the effectiveness of electrical stimulation on quadriceps and hamstring muscle performance in patients with patellofemoral pain. <h3>Methods</h3> Twenty-one patients participated in the 4-week exercise program and were randomly assigned to either closed kinetic chain exercises or closed kinetic chain exercises combined with electrical stimulation of bilateral quadriceps and hamstring muscles. Quadriceps and hamstring muscle peak torques were measured at baseline and at 4 weeks with an isokinetic dynamometer at 60°/sec and 180°/sec angular velocities. <h3>Results</h3> After the 4-week exercise program the mean torque values for quadriceps and hamstring at both angular velocities were higher in both groups. There was a significant difference in the left hamstring peak torque values at 60°/sec and 180°/sec angular velocities and in the left quadriceps peak torque at 180°/sec angular velocity in the electrical stimulation group (p &lt; 0.01). In the other group the peak torque differences in the left hamstring and quadriceps muscles at 60°/sec angular velocity and in the left hamstring muscle at 180°/sec angular velocity were statistically significant (p &lt; 0.05). <h3>Conclusion</h3> Although it seems that electrical stimulation does not provide an additional effect on muscle performance, it can be used with closed kinetic chain exercises to accelerate the rehabilitation program.
Abstract 2854: Multi-omic considerations: Exploring LBgard blood tubes for proteomic analysis
Authors: Jacob M. Vasquez, Joel Desharnais
Journal: Cancer Research (2020)

Abstract Expanding the number of -omic (genomic, proteomic, etc.) analyte classes, a single blood draw will serve to increase the scientific value of that sample by affording additional multi-variant analyses. The detection and monitoring of many chronic diseases and cancers requires multi-factorial/multi-analyte measurement. Specialized blood collection tubes (e.g., liquid biopsy tubes) are routinely used in the development of minimally invasive methods to monitor key cancer biomarkers in blood. The suitability of plasma isolated from liquid biopsy blood tubes for quantitative proteomics studies needs further exploration. Herein we performed proteomic analyses of whole blood collected and stored in LBgard Blood Tubes. In this study, matched blood samples from 3 healthy donors were collected in LBgard Blood Tubes and K3EDTA (EDTA) tubes, which is the standard blood collection tube used for plasma proteomic analyzes. Blood collected in LBgard Blood Tubes was stored for either 5 days or 7 days at ambient temperature. Following high-abundant plasma protein depletion, plasma proteins were analyzed in quantitative discovery proteomics by liquid chromatography tandem-mass spectrometry (TMT-LC-MS/MS). Over 800 unique proteins were identified by mass spectrometry in the plasma samples analyzed. Of those, &amp;gt;90% were found to be of similar abundance between EDTA Day 0 plasma samples and plasma isolated from whole blood collected in LBgard Blood Tubes. After storage of the LBgard Blood Tube samples for up to 7 days at ambient temperature, &amp;gt;85% of the proteins demonstrated similar abundance in both stored LBgard Blood samples and EDTA tube samples processed immediately after collection. Samples were also evaluated via ELISA to quantify the levels of proteins known to be cancer related. LBgard Blood Tubes prevented changes in the plasma concentrations of several protein biomarkers known to be sensitive to preanalytical variability in samples stored for 5 days at ambient temperature as compared to samples stored in EDTA tubes under the same conditions. Utilizing tandem-mass tag spectrometry and immunoassay methodologies, we have determined the compatibility of LBgard Blood Tube for determining proteomic profiles of blood samples. Additionally, blood collected in LBgard Blood Tubes was shown to have consistent concentrations of protein after storing the collected blood sample for several days, with enhanced protein detection as compared to EDTA tubes. Citation Format: Jacob M. Vasquez, Joel Desharnais. Multi-omic considerations: Exploring LBgard blood tubes for proteomic analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2854.
A 300 IR sublingual tablet is an effective, safe treatment for house dust mite–induced allergic rhinitis: An international, double-blind, placebo-controlled, randomized phase III clinical trial
Authors: Pascal Demoly, Jonathan Corren, Peter Creticos, Frédéric De Blay, Philippe Gevaert, Peter Hellings, Krzysztof Kowal, Martine Le Gall, Natalia Nenasheva, Giovanni Passalacqua, Oliver Pfaar, Miguel Tortajada-Girbés, Carmen Vidal, Margitta Worm, Thomas B. Casale
Journal: Journal of Allergy and Clinical Immunology (2020)
More Evidence for SGLT2 Inhibitors in Heart Failure
Authors: John A. Jarcho
Journal: New England Journal of Medicine (2020)

John Jarcho comments on the findings of the EMPEROR-Reduced trial, which assesses the potential benefit of empagliflozin in patients with heart failure and a reduced EF. He notes that the findings substantially strengthen the rationale for the use of SGLT2 inhibitors in such patients.
FRI0221 Primary and secondary sjÖgren’s syndrome – respiratory involvement
Authors: A Carvalheira, P Ferreira, J Figueirinhas, L Ferreira, J Vaz Patto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Pulmonary disease is reported in both primary and secondary Sjögren's syndrome. <h3>Objectives</h3> In order to study the respiratory involvement we evaluated 52 patients with Sjögren's syndrome. <h3>Methods</h3> Fourty seven patients were female (90.4%) and five were male (9.6%). The mean age was 53 years (range 26–80). The median duration of the disease was 11 years. Twenty four patients (46%) had criteria (European criteria) for primary Sjögren's syndrome (A Group) and 28 patients (54%) for secondary Sjögren's syndrome (B Group). Rheumatoid arthritis was present in 20/28 (71%) with secondary Sjögren's syndrome (B Group). We used clinical, radiological and functional criteria for the assessment of respiratory involvement. <h3>Results</h3> A total of 21/52 patients (40%) reported symptoms, 9 from A Group (17%) and 12 from B Group (23%). Chest radiographs had evidence of abnormality in 21/52 patients (40%), 11 from A Group (21%) and 10 from B Group (19%). Lung function impairment was seen in 15/52 patients (29%), 6 from A Group (12%) and 9 from B Group (17%). <h3>Conclusion</h3> This study provides evidence that lung involvement is an important manifestation of Sjögren's syndrome in primary as in secondary disease.
Patient-Tailored Mouse Genome Editing Recapitulates Hematopoietic and Systemic Manifestations of Barth Syndrome
Authors: Donna Edwards, Elizabeth Sierra Potchanant, Xinxin Huang, Zejin Sun, Maegan Capitano, Caroline Miller, Ying He, Hal E. Broxmeyer, Grzegorz Nalepa
Journal: Blood (2017)
Abstract 2667: CaMKK2 knockout in mice challenged by orthotopic GBM leads to upregulation of MHC II on TAMs and an increase in accumulation of CD4+ TILs
Authors: Molly A. Chakraborty, William H. Tomaszewski, Jessica Waibl Polania, Lauren S. Riley, Luigi Racioppi, Luis A. Sanchez-Perez, John H. Sampson
Journal: Cancer Research (2020)

Abstract Glioblastoma (GBM) is the most lethal primary brain tumor in adults, with the median survival time for GBM patients being only about 15 months. Although immunotherapy treatments have been successful in more immunogenic tumors, it has shown very limited success in GBM. This could be because it is difficult for T cells to infiltrate the tumor, and the tumors have a very immunosuppressive tumor microenvironment (TME) that can often consist of up to about 30 percent tumor associated macrophages (TAMs) by mass. Thus, two ways of possibly improving immunotherapy treatments on GBMs would be to increase the number of tumor infiltrating lymphocytes (TILs) present, and to target tumor-supportive cells such as TAMs. Calmodulin Dependent Protein Kinase Kinase 2 (CaMKK2) is a gene that has been shown to be highly expressed in myeloid cells and is known to alter their phenotype. Recent studies in breast cancer have shown that myeloid cells adopt a more immunostimulatory phenotype in murine knockout CaMKK2 models. However, it is not well understood how CaMKK2 causes this immunosuppressive effect and warrants further exploration. The data from our experiments help to answer this question. High-dimensional flow cytometry with 15 parameters was used in order to determine the identities of immune cells found in the tumor of wildtype and CaMKK2-/- mice. The results of our experiments show that there appear to be more CD4+ TILs present in the TME of knockout mice and that there is an increase in MHC II expression on TAMs found in knockout mice. Since CD4+ TILs recognize peptides presented on MHC II molecules, and there is an increase in the number of CD4+ TILs and expression of MHC II on TAMs in knockout mice, we hypothesize that a stronger immune response could be instigated against the tumor. Therefore, it can be concluded that a possible reason that knocking out CaMKK2 leads to a less immunosupressive TME is because MHC II expression on TAMs is upregulated, and the number of CD4+ TILs in the TME is increased. Whether or not the increase in MHC II expression causes the increase in the number CD4+ TILs requires further exploration. This makes CaMKK2 a promising therapeutic target to treat tumors with immunosuppressive TMEs such as GBM. Citation Format: Molly A. Chakraborty, William H. Tomaszewski, Jessica Waibl Polania, Lauren S. Riley, Luigi Racioppi, Luis A. Sanchez-Perez, John H. Sampson. CaMKK2 knockout in mice challenged by orthotopic GBM leads to upregulation of MHC II on TAMs and an increase in accumulation of CD4+ TILs [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2667.
Abstract B02: miR-181a initiates and perpetuates oncogenic transformation through the regulation of innate immune signaling
Authors: Matthew Knarr, Lily J. Kwiatkowski, Michele Dziubinski, Jessica McAnulty, Stephanie Skala, Stefanie Avril, Ronny Drapkin, Analisa DiFeo
Journal: Clinical Cancer Research (2020)

Abstract Genomic instability predisposes cells to malignant transformation; however, the molecular mechanisms that allow for the propagation of cells with a high degree of genomic instability remain unclear. Here we report that miR-181a is able to transform fallopian tube secretory epithelial cells—the precursor cell type for the majority of high-grade serous ovarian cancers—through the inhibition of RB1 and simultaneously drives a cell-protective inhibition of the stimulator-of-interferon-genes (STING) in order to maintain a microenvironment conducive to the propagation of cells with a high-degree of genomic instability. We found that miR-181a inhibition of RB1 leads to profound nuclear defects, genomic instability, and nuclear rupture resulting in a persistence of genomic material in the cytoplasm. While normally, this persistence of genomic material in the cytoplasm induces interferon response through STING to drive cell death, miR-181a directly downregulates STING and prevents apoptosis. The most common mechanism by which oncogenic miRNAs promote tumorigenesis is through the direct inhibition of tumor suppressor genes; however, our studies highlight a new mechanism of oncomiR transformation through the combination of tumor suppressor gene inhibition and abrogation of immune surveillance that initiates and propagates tumor cell survival. Importantly, we found that miR-181a induction in human ovarian tumors is tightly associated with decreased IFNg response and downregulation of lymphocyte infiltration and leukocyte fraction. To date, DNA oncoviruses are the only known inhibitors of STING that allow for cellular transformation; thus, our findings are the first to identify a genetic factor, miR-181a, that can downregulate STING expression and impair signaling in cancer cells, creating a survival advantage. Our studies support the notion that the induction of STING-mediated signaling in cancer cells could lead directly to cancer cell death; however, these effects are abrogated by miR-181a. Given the recent interest in the development of STING agonists as a strategy to harness the immune system to treat cancer, this study introduces a novel patient-selective biomarker as well as potent therapeutic target for development of the most effective combination treatments. Citation Format: Matthew Knarr, Lily J. Kwiatkowski, Michele Dziubinski, Jessica McAnulty, Stephanie Skala, Stefanie Avril, Ronny Drapkin, Analisa DiFeo. miR-181a initiates and perpetuates oncogenic transformation through the regulation of innate immune signaling [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B02.
Abstract 2634: Oral bacteria effects on oral cancer initiation and progression
Authors: Stefan Kovac, Tiara S. Napier, Jessica Scoffield, Hope M. Amm
Journal: Cancer Research (2020)

Abstract Oral squamous cell carcinoma (OSCC) is the most common site of head and neck squamous cell carcinoma. It is estimated to be diagnosed in 50,000 patients this year with an overall 5-year survival rate of 64%. The tumor microenvironment has been shown to play a role in the progression of many human cancers, including OSCC. Given the complexity of the oral microbiome, we hypothesize that OSCC and oral bacteria interact to affect the tumorigenic properties of OSCC. Methods: OSCC cells were cultured in the presence of oral pathogenic (Aggregatibacter actinomycetemcomitans (Aa), Enterococcus faecalis (Ef), Fusobacterium nucleatum (Fn)) and non-pathogenic (Streptococcus parasanguinis (Sp)) bacteria. Human oral keratinocytes (HOK) and OSCC cells were treated with oral bacteria and assessed for changes in cell proliferation and gene expression. Results: HOK treated with Ef demonstrated significantly increased proliferation and increased expression of HES1, MMP11, and CDKN1A(p21). Of the five OSCC cell lines, Ef increased proliferation in the two cell lines that were human papilloma virus positive (HPV+) (2A3, SCC152) and in one of three cell lines that were HPV negative (HPV-, Cal27). Ef increased the expression of HES1, MMP2, CDKN1A, and GLI1 in SCC152 cell and HES1, MMP11, and CDKN1A in 2A3 cells. Ef also increased the invasion of SCC152 cells in a transwell experiment. In HPV- Cal27 cells, Ef increased MMP2 and GLI1 expression. Aa also increased proliferation in 2A3 HPV+ cells. Fn did not increase proliferation of OSCC cells, but it did increase the expression of HES1, CDKN1A, and GLI1 in SCC152 HPV+ cells. Conclusions: Oral bacteria have direct interactions with human oral keratinocytes and cancer cells. In particular, Ef may be involved in both the initiation and progression stages of oral cancer. Citation Format: Stefan Kovac, Tiara S. Napier, Jessica Scoffield, Hope M. Amm. Oral bacteria effects on oral cancer initiation and progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2634.
CXCR3 and Cognate Ligands are Associated with Immune Cell Alteration and Aggressiveness of Pancreatic Ductal Adenocarcinoma
Authors: Andrew Cannon, Christopher M. Thompson, H. Carlo Maurer, Pranita Atri, Rakesh Bhatia, Sean West, Dario Ghersi, Kenneth P. Olive, Sushil Kumar, Surinder K. Batra
Journal: Clinical Cancer Research (2020)

The cytokine milieu in pancreatic ductal adenocarcinoma (PDAC) promotes tumor progression and immune suppression, contributing to the dismal prognosis of patients with PDAC. The roles of many of these cytokines, however, have not been thoroughly investigated in PDAC.PDAC microarray and The Cancer Genome Atlas datasets were analyzed to identify cytokines and cognate receptors overexpressed in PDAC and associated with survival. Pathway and CIBERSORT analyses were used to elucidate potential mechanisms of altered patient survival. Comparative analysis of cytokine expression in KPC (K-rasG12D; TP53R172H; Pdx-1cre) and KC (K-rasG12D; Pdx-1cre) PDAC models and multicolor immunofluorescence (IF) staining of human PDAC-resected samples were used to validate these findings.CXCL9 and CXCL10 were among the most highly overexpressed cytokines by bioinformatics analyses, while their receptor, CXCR3, was significantly overexpressed by IHC analysis. Higher CXCR3 ligand expression was associated with shorter overall survival, while high CXCR3 expression was associated with better survival. The CXCR3 ligands, CXCL4, 9, and 10, were overexpressed in KPC compared with KC mice. Pathway analysis of CXCR3- and CXCR3 ligand-associated genes showed that CXCR3 is a marker of antitumor immunity, while its ligands may promote immunosuppression. CIBERSORT and IF studies of PDAC tissues demonstrated that high CXCR3 expression was associated with increased CD8+ T-cell and naïve B-cell signatures and loss of plasma cell signatures. CXCR3 ligand expression was associated with increased CD8+ T-cell signatures and loss of natural killer-cell signatures.CXCR3 ligands are overexpressed in PDAC and are associated with poor survival likely related to alterations in tumor immune infiltrate/activity.
Daratumumab Activity Is Agnostic to Fc Gamma Receptor 3A (FcγR3A) 158 Genotype in Patients with Primary Refractory or Relapsed Systemic AL Amyloidosis
Authors: Lisa Xingguang Lee, Katelynn Ho, Ping Zhou, Cindy Varga, Teresa Fogaren, Denis Toskic, Adin Kugelmass, Raymond Comenzo
Journal: Blood (2017)
Caring for patients with COPD and COVID-19: a viewpoint to spark discussion
Authors: Sami O Simons, John R Hurst, Marc Miravitlles, Frits M E Franssen, Daisy J A Janssen, Alberto Papi, Marieke L Duiverman, Huib A M Kerstjens
Journal: Thorax (2020)

Coronavirus SARS-CoV-2 is currently causing a pandemic of COVID-19, with more than 3 million confirmed cases around the globe identified as of June 2020. During these extraordinary times, caring for patients with COVID-19 and underlying COPD poses particular challenges. Certain treatments relevant to treating patients with COPD, such as nebulised bronchodilators and non-invasive ventilation (NIV), are thought to carry an increased risk of viral spread via aerosols. Uncertainties on whether to use systemic steroids have entered the minds of intensive care and respiratory communities. Moreover, questions regarding which life-sustaining treatments to start, when to start them and even whether to start them are faced by clinicians on a daily basis. Treating COPD effectively in the context of COVID-19 is important since patients with COPD are at an increased risk of poor outcomes. Here, we summarise current viewpoints from four European countries on how to care for patients with COPD and COVID-19.

We will address the following specific questions:

1.  Are patients with COPD at an increased risk of COVID-19?

2.  Should COVID-19 be considered a COPD exacerbation?

3.  What is the optimal medical treatment for a patient with COPD and COVID-19?

4.  Which ventilatory support should be provided to patients with COPD and COVID-19?

5.  What other supportive treatments should be offered to patients with COPD and COVID-19?

6.  How should end-of-life care be delivered in patients with COPD during the COVID-19 pandemic?

### Are patients with COPD at an increased risk for COVID-19?

Since patients with COPD are vulnerable to viral respiratory tract infections, and COPD is generally a disease of the elderly, many had expected that patients with COPD would have a considerably increased risk of acquiring COVID-19. Studies so far, however, indicated only around 2% of patients admitted to hospital with COVID-19 infection in China had underlying COPD,1 2 while the prevalence of COPD in China ranges from 5% to 13%.3 Indeed, …
SAT0123 The efficacy of rofecoxib in the treatment of inflammatory arthropathies
Authors: MS Capraru, E Ilie
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The research aimed the development of a prospective investigation on the efficacy of the rofecoxib treatment in inflammatory arthropathies patients. Our previous expertize enabled us to suspect that there might be some consistent effects of the rofecoxib of the inflammatory disease class. <h3>Objectives</h3> Consequently the main objective of our research was to point out the influences of rofecoxib as an alternative treatment in the inflammatory disease class. <h3>Methods</h3> Basically, the method consists of taking measurements and surveying the effects of the rofecoxib treatment on patients during a two week time interval. The study involved a 55 patients target group with the following structure: acute gout present at 15 of them, 19 patients had seronegative spondylarthropathies, 7 suffering of psoriatic arthritis, 10 of them presenting rheumatoid arthritis and 2 patients diagnosticated as systemic sclerosis associated arthritis. The survey assumed the pain score measurement in terms of an analogical pain scale from 0 (no pain) to 10 (very severe pain). The measurements were taken at 48 h, 72 h, 7 days and 14 days following the initial moment when the therapy with rofecoxib started. <h3>Results</h3> Our results can be summarised as follows: very high efficacy in acute gout (50 mg in the first day, then 25 mg/day) together with significant decrease of the 48 h pain score. Also, good efficacy can be reported in case of seronegative spondylarthropathies, psoriatic arthritis and systemic sclerosis associated arthritis (25 mg/day 7 days, followed by 12.5 mg/day) but for patients suffering of rheumatoid arthritis the efficacy can be considered as being almost satisfactory (25 mg/day). However, the investigation of the chronic arthropathies patients continued for about two more months, and no digestive, hepatic or renal adverse reactions were reported while the whole therapeutic benefit was preserved. <h3>Conclusion</h3> We can conclude on this basis that the results confirmed most of our expectations but the experiment allowed us to refine our a priori hypothesis.