tbuckley/cabot-search huggingface dataset:
Prevalence and Characteristics of Persistent Clonal T Cell Large Granular Lymphocyte Expansions in Rheumatoid Arthritis
Authors: Eva C. Schwaneck, Regina Renner, Lara Junker, Hermann Einsele, Ottar Gadeholt, Eva Geissinger, Stefan Kleinert, Michael Gernert, Hans‐Peter Tony, Marc Schmalzing
Journal: Arthritis & Rheumatology (2018)

Up to one-third of patients with T cell large granular lymphocyte (T-LGL) leukemia display symptoms of rheumatoid arthritis (RA). In Crohn's disease and psoriasis, treatment with tumor necrosis factor (TNF) inhibitors is associated with hepatosplenic γδ T cell lymphoma and with clonal expansion of γδ T cells, respectively. This study was undertaken to determine the prevalence of clonal T-LGL cells in patients with RA and define risk factors for this rare hematologic malignancy.A total of 529 RA patients were recruited between November 2013 and August 2015. Eight-color flow cytometry (fluorescence-activated cell sorting [FACS]) was performed to screen for aberrant T cell populations of LGLs. Molecular analysis of the T cell receptor was used to confirm the diagnosis in patients with suggestive FACS findings. Electronic patient files were used to determine risk factors. Patients with clonal populations were monitored prospectively for up to 4 years.The median patient age was 61 years, and 74% were female. The median duration of RA was 12 years. The median Disease Activity Score in 28 joints was 2.8, and 69.9% of patients had ever been treated with biologic disease-modifying antirheumatic drugs. We identified clonal T-LGL expansions in 19 patients, equaling a prevalence of 3.6%. The T-LGL cell clone was constant over time in most patients and was significantly associated with the duration of the exposure to TNF-blocking agents (P = 0.01). No other risk factors could be detected.RA patients with long-term exposure to TNF-blocking agents were at a greater risk of developing clonal expansions of LGLs. This finding may prompt clinicians to refrain from using these substances in RA patients with known T cell aberrations.
Abstract 2289: Precision-weighted RNA-seq analyses of molecular abundance (RoMA) for detecting differential gene expression
Authors: Guoshuai Cai, Jennifer M. Franks, Michael L. Whitfield
Journal: Cancer Research (2018)

Abstract In this study, we propose a novel method, RoMA, to accurately detect differential expression and unlock the integration with numerous upstream and downstream analyses on mRNA abundance in RNA-seq studies. Various methods have been proposed, each with its own limitations. Some naive normal-based tests have low testing power with the invalid normal distribution assumptions for RNA-seq read counts, whereas count-based methods lack a biologically meaningful interpretation and have limited capability for integration with other analysis packages for mRNA abundance. RoMA incorporates information from both mRNA abundance and raw counts by modeling RPKM (reads per kilobase per million), which represents the relative abundance of mRNA transcripts, and borrowing mean-variance dependency from CPM (counts per million) as a precision weight accounting for the variability in sequencing depth. Studies on simulated data and two real datasets showed that RoMA provides an accurate quantification of mRNA abundance and a value adjustment-tolerant DE analysis with high AUC, low FDR and a desirable type I error rate. This study provides a valid strategy for mRNA abundance modeling and data analysis integration for RNA-seq studies, which will greatly facilitate the identification and interpretation of DE genes. The methods is implemented in a user-friendly R package (RoMA). Citation Format: Guoshuai Cai, Jennifer M. Franks, Michael L. Whitfield. Precision-weighted RNA-seq analyses of molecular abundance (RoMA) for detecting differential gene expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2289.
Making Neighborhood-Disadvantage Metrics Accessible — The Neighborhood Atlas
Authors: Amy J.H. Kind, William R. Buckingham
Journal: New England Journal of Medicine (2018)

Interview with Dr. Amy Kind on a new tool for incorporating data on neighborhood disadvantage into research, policy, and health interventions. (15:45)Download Better understanding of variations in neighborhood disadvantage could lead to improved insight into the sociobiologic mechanisms that underlie health disparities, which could, in turn, facilitate the development of improved therapeutics and interventions.
Primary Care and the Opioid-Overdose Crisis — Buprenorphine Myths and Realities
Authors: Sarah E. Wakeman, Michael L. Barnett
Journal: New England Journal of Medicine (2018)

Buprenorphine Myths and Realities A realistic solution for reaching the millions of Americans with opioid use disorder is to mobilize the primary care physician workforce to offer office-based addiction treatment with buprenorphine. But stigma and myths inhibit acceptance of this approach.
Abstract 2125: Cancer-associated fibroblasts-stimulated IL-11 promotes metastasis of gastric cancer cells mediated by upregulation of MUC1
Authors: Xiaoxun Wang, Xiaofang Che, Ming Bai, Yibo Fan, Yunpeng Liu, xiujuan qu
Journal: Cancer Research (2018)

Abstract Background: Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma and regulators of tumor progression. However, the molecular mechanism by which CAFs promote gastric cancer progression should be further explored. Methods: Mouse model was used to certify that CAFs could promote peritoneal metastasis of gastric cancer cells. The expression of interleukin-11 (IL-11) was analyzed in two gastric cancer cell lines by real-time RT-PCR and ELISA. The role of IL-11 in gastric cancer cell migration and invasion explored by Transwell. Western blotting was conducted to detect the activation of STAT3 and ERK signaling pathway. Results: In our study, we reveal that when CAFs co-cultured with gastric cancer cells secreted significant amounts of IL-11. CAFs promote the ability of migration and invasion through the production of IL-11 by stimulating JAK/STAT3 and MAPK/ERK pathways to upregulate MUC1 in gastric cancer cells. On the other hand, when IL-11 was deprived using a neutralizing antibody or inhibition of JAK/STAT3 and MAPK/ERK pathways with specific inhibitors, Stattic and PD-98059, markedly attenuated these CAFs-induced phenotypes in gastric cancer cells. Conclusions: Taken together, these results revealed that CAFs play a significant role in the gastric cancer progression in the tumor microenvironment through IL-11-STAT3/ERK signaling by upregulating MUC1. Also, IL-11 targeted therapy can achieve an effective treatment against gastric cancer indirectly by exerting their action on stromal fibroblasts. Citation Format: Xiaoxun Wang, Xiaofang Che, Ming Bai, Yibo Fan, Yunpeng Liu, xiujuan qu. Cancer-associated fibroblasts-stimulated IL-11 promotes metastasis of gastric cancer cells mediated by upregulation of MUC1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2125.
Abstract 15548: Comparing the Prediction of Heart Failure Symptoms Using a Clinical Score Assessing Risk of Atrial Fibrillation (CHARGE-AF) to Traditional Heart Failure Risk Scores
Authors: Satish Ramkumar, Hong Yang, Ying Wang, Mark Nolan, Kazuaki Negishi, Thomas H Marwick
Journal: Circulation (2016)

Introduction:  The CHARGE-AF score gives a 5 year risk of developing atrial fibrillation (AF). Heart failure (HF) shares similar risk factors to AF. The CHARGE-AF score shares similar characteristics to the ARIC HF score.   Hypothesis:  The CHARGE-AF score is similar to the ARIC score in prediction of HF symptoms.   Methods:  A community based study of participants’ ≥ 65 years were recruited if they had presence of risk factors for HF (hypertension (HTN), diabetes mellitus (DM), obesity etc). HF risk was assessed using the CHARGE-AF and ARIC. Baseline ECG and echocardiography was performed in all participants and functional outcome was assessed using the six minute walk test (SMWT). HF symptoms were assessed at follow up using the Framingham criteria. Receiver operator characteristic (ROC) curves were generated to compare both scores using the Hanley and McNeil method.   Results:  Total of 503 patients (age 70.8±4.7 yrs, male 48% with follow up 12 months±3). The median CHARGE-AF and ARIC scores were 7.5% (3.8–11.3%) and 5.9% (2.6–9.3%). During follow up, 55 patients developed HF symptoms. Patients with new onset HF were older with higher rates of DM (p=0.041), HTN (p=0.036) and previous ischaemic heart disease (p=0.003). New onset HF was associated with impaired global longitudinal (p   Conclusion:  The CHARGE-AF score is a useful clinical tool in predicting HF symptoms in patients and appears to be as predictive as the ARIC score. In the community setting it is useful in assessing both AF and HF risk.
Abstract 18122: Cardiac Rehabilitation in Subjects With Peripheral Arterial Disease: A Higher Risk Patient Population Who Benefit From Attendance
Authors: Billie-Jean Martin, Andrea Devrome, Trina Hauer, Leslie Austford, Ross Arena, James A Stone, Sandeep Aggarwal
Journal: Circulation (2016)

Introduction:  Peripheral vascular disease (PAD) is a common co-morbidity in subjects with coronary artery disease referred for cardiac rehabilitation (CR).   Hypothesis:  Subjects with PAD derive benefit from CR, but are less likely to attend.   Methods:  This study included all subjects who were referred to a 12-week, exercise based CR program in Calgary, Canada between 1996 and 2013. Baseline patient characteristics including age, sex, and clinical characteristics were compared between those who completed CR and did not. Rates of attendance and completion were compared by PAD, as was change in exercise capacity measured by exercise testing over the course of CR for all those who completed the program. Unadjusted and adjusted (for all available clinical covariates) Cox proportional hazard models were constructed to assess the association between CR completion and mortality. Models were stratified by PAD diagnosis.   Results:  A total of 15927 subjects were referred to CR; of those, only 894 (5.6%) had a formal diagnosis of PAD. Subjects with PAD were less likely to complete CR (44.4 vs 55.6% for non-PAD, p   Conclusions:  Subjects with coexisting PAD in a CR program have a higher mortality and thus are a higher risk CR group. They derive significant mortality reduction from attending CR even though they have less improvement in their exercise capacity. They are, however, less likely to attend and more likely to drop out. Removing barriers to CR attendance and completion is important for those suffering from PAD.
Abstract 17880: Dynamic Changes in Cardiac Mechanics in AL Amyloidosis and Its Relationship to Immunologic Response to Chemotherapy
Authors: Mirela Tuzovic, Yukari Kobayashi, Matthew Wheeler, Michaela Liedtke, Francois Haddad, Ronald Witteles
Journal: Circulation (2016)

Background:  Cardiac involvement is common in patients with Light Chain (AL) Amyloidosis and portends a poor prognosis. Little is known about the changes in cardiac mechanics following chemotherapy.   Hypothesis:  We assessed the hypothesis that immunologic response to chemotherapy is associated with improvement in cardiac mechanics.   Methods:  We identified 41 consecutive patients from the Stanford AL Amyloidosis database who had Echocardiograms and free light chain (FLC) values before and after chemotherapy. Echocardiographic assessment included global longitudinal strain (GLS), LV diastolic function metrics, and left atrial (LA) stiffness. Forty age and sex-matched controls were included. Immunologic response to chemotherapy was defined as ≥50% reduction in the difference between the involved and uninvolved FLC. Structural and functional improvement was defined as >10% improvement in cardiac parameters based on the inter-reader variability in our laboratory.   Results:  The mean age was 66.9 ± 8.4 years and 66% were male. Compared to controls, atrial and ventricular mechanics were significantly impaired in patients with cardiac amyloidosis. Higher Mayo stage was associated with worse GLS, E/e’ and LA stiffness. The average time to post-chemotherapy Echocardiogram was 9.2 ± 3.6 months. There was no significant change in myocardial remodeling and functional parameters following chemotherapy in the cohort overall, however individual responses showed considerable variability. Immunologic response was seen in 30 (73%) of patients. Improvement in E/e’ and LA stiffness was associated with immunologic response to chemotherapy (p = 0.028, p = 0.006 respectively) while there was a trend for GLS (p = 0.056).   Conclusion:  Improvement in diastolic parameters and LA stiffness are associated with immunologic response. Further studies with longer follow-up intervals are needed to explore the full range of atrial and ventricular remodeling following chemotherapy.
Abstract 5047: Exosomes derived from HIV-1-infected T cells activate ERK 1/2 through EGFR and TLR3 in cancer cells
Authors: Zhimin Feng, Lechuang Chen, Hong Yue, Bingcheng Wang, Ge Jin
Journal: Cancer Research (2018)

Abstract Exosomes secreted from HIV-1-infected T cells play important roles in coordinating the immune responses and disease processes in HIV-infected people who are treated with antiretroviral therapy. We hypothesize that exosomes from HIV-infected T cells can promote growth and progression of non-AIDS-defining cancer cells. Activation of the MAPK ERK 1/2 is important for cancer cell survival, proliferation and invasion. We investigated the ability of exosomes from HIV-1-infected T cells to activate ERK 1/2 in head neck squamous cell carcinoma (HNSCC) and lung cancer cells for cancer cell proliferation and progression. Exosomes were isolated from Jurkat and J1.1, a latently HIV-1-infected Jurkat cells, using differential ultracentrifugation and quantified by acetylcholinesterase (AchE) activity. HNSCC cell line HSC3 and lung cancer cell lines NCI-H1299 and NCI-H1437 cells were treated with exosomes. To test the involvement of EGFR and TLR3 in ERK 1/2 activation by exosomes, EGFR neutralizing antibody Cetuximab or the TLR3/dsRNA inhibitor complex was added to cancer cells 30 min prior to adding exosomes. To test the entry of exosomes into cells, HEK293 cells were transiently transfected with EGFR-GFP, and seeded into glass bottom 35 mm dishes, time lapse Z-stacking imaging was performed and deconvolution was used to remove out of focus signals. By using Western blotting, we found that exosomes from J1.1 cells (HIV-1-infected), but not those from HIV-negative Jurkat cells, constantly induced ERK 1/2 phosphorylation in HNSCC and lung cancer cells. Cetuximab dramatically decreased ERK activation by exosomes from J1.1 cells, suggesting an EGFR-dependent ERK activation. While EGF induced a whole series of EGFR phosphorylation, exosomes from J1.1 cells failed to do so, suggesting that exosomes from J1.1 cells trigger ERK activation through a non-canonical EGFR pathway. Furthermore, ERK activation was significantly reduced in TLR3/dsRNA inhibitor pretreated cancer cells in response to exosomes from J1.1 cells, indicating exosomes triggered ERK activation is also TLR3 dependent. Time lapse imaging showed that exosomes quickly entered into cells within two minutes; however, Cetuximab greatly delayed exosome entry. To conclude, we found that exosomes from HIV-infected T cells can induce ERK activation in HNSCC and lung cancer cells through interaction with EGFR and TLR3. Citation Format: Zhimin Feng, Lechuang Chen, Hong Yue, Bingcheng Wang, Ge Jin. Exosomes derived from HIV-1-infected T cells activate ERK 1/2 through EGFR and TLR3 in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5047.
Prospective comparative study of endoscopic submucosal dissection and gastrectomy for early neoplastic lesions including patients’ perspectives
Authors: Diogo Libânio, Vânia Braga, Sílvia Ferraz, Rui Castro, Jorge Lage, Inês Pita, Cátia Ribeiro, Joaquim Abreu De Sousa, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes
Journal: Endoscopy (2018)

Abstract Background There are no prospective studies comparing endoscopic submucosal dissection (ESD) and gastrectomy, especially evaluating patient-reported outcomes. Our aim was to compare the safety and impact on quality of life (QoL) of ESD and gastrectomy in patients with early gastric neoplasia. Methods This prospective study included consecutive patients presenting with early gastric neoplasia in a tertiary center from January 2015 to August 2016. Data collection included curative resection, adverse events (AEs), and patient-reported outcomes (questionnaires: EORTC QLQ-C30, EORTC STO-22, EQ-5D-5 L, and Assessment of Survivor Concerns) before and after interventions (after 1 month, 3 – 6 months, and 1 year). Results 254 patients with early lesions were included: 153 managed by ESD and 101 by gastrectomy, the former being significantly older and with less advanced lesions. Mean procedural time and length of stay were significantly higher in the surgery group (164 vs. 72 minutes and 16.3 vs. 3.5 days; P &lt; 0.001). Complete resection was higher in the surgical group (99 % vs. 90 %; P = 0.02); ESD was curative in 79 % of patients. Severe AEs and surgical re-intervention were significantly more frequent in the gastrectomy group (21.8 % vs. 7.8 % and 11 % vs. 1 %, respectively). Endoscopic treatment was associated with a positive impact on global health-related QoL at 1 year (net difference + 9.9; P = 0.006), role function and symptom scales (fatigue, pain, appetite, eating restrictions, dysphagia, and body image). Concerns about recurrence did not differ between the groups. Conclusions In patients with early gastric neoplasia, ESD is safer and is associated with a positive impact on health-related QoL when compared with gastrectomy, without increasing fear of recurrence and new lesions.
Endoscopic ultrasound-guided angiotherapy in refractory gastrointestinal bleeding from large isolated gastric varices: a same-session combined approach
Authors: Ilaria Tarantino, Roberto Miraglia, Michele Amata, Dario Ligresti, Fabio Cipolletta, Luigi Maruzzelli, Mario Traina
Journal: Endoscopy (2018)

A 36-year-old Asian man with severe portal hypertension due to hepatitis B virus-related cirrhosis had been previously treated for acute gastrointestinal bleeding from a large isolated gastric varix (IGV-1) by injection of endoscopic cyanoacrylate glue at a local hospital ([Fig. 1]). Following an episode of massive recurrent hematemesis, the patient was hemodynamically stabilized and referred to our institute. Radiological evaluation revealed the presence of numerous collaterals in the gastric fundus with a large-caliber splenorenal shunt.
Discriminating a common somatic ASXL1 mutation (c.1934dup; p.G646Wfs*12) from artifact in myeloid malignancies using NGS
Authors: Michael O. Alberti, Sridhar Nonavinkere Srivatsan, Jin Shao, Samantha N. McNulty, Gue Su Chang, Christopher A. Miller, Jennifer B. Dunlap, Fei Yang, Richard D. Press, Qingsong Gao, Li Ding, Jonathan W. Heusel, Eric J. Duncavage, Matthew J. Walter
Journal: Leukemia (2018)
F(ab′) <sub>2</sub> Fragments to Overcome Daratumumab Interference in Transfusion Tests
Authors: Kathleen Selleng, Patrycja D Gebicka, Thomas Thiele
Journal: New England Journal of Medicine (2018)

False Positive Coombs’ Tests and Daratumumab Daratumumab is an effective agent in multiple myeloma. Its binding of CD38 on red cells causes false positive results on Coombs’ blood-compatibility tes...
Diagnosis of invasive aspergillosis in hematological malignancy patients: Performance of cytokines, Asp LFD, and Aspergillus PCR in same day blood and bronchoalveolar lavage samples
Authors: Sven Heldt, Juergen Prattes, Susanne Eigl, Birgit Spiess, Holger Flick, Jasmin Rabensteiner, Gemma Johnson, Florian Prüller, Albert Wölfler, Tobias Niedrist, Tobias Boch, Peter Neumeister, Heimo Strohmaier, Robert Krause, Dieter Buchheidt, Martin Hoenigl
Journal: Journal of Infection (2018)
Abstract 2305: Targeting 6-phosphofructo-2-kinase to increase the efficacy of ER and CDK4/6 inhibitors against breast cancer
Authors: Yoannis Imbert-Fernandez, Lilibeth Lanceta, Sucheta Telang, Jason Chesney
Journal: Cancer Research (2018)

Abstract We demonstrated that estradiol stimulates the expression and activity of an enzyme, 6-phosphofructo-2-kinase (PFKFB3), that regulates glucose metabolism via allosteric stimulation of 6-phosphofructo-1-kinase. PFKFB3 expression is increased in breast cancer cells that have metastasized to lymph nodes and the combination of the anti-estrogen, fulvestrant, with a PFKFB3 inhibitor, PFK158, synergistically increases apoptosis in ER+ breast cancer cells in vitro and in vivo. Given that estradiol simultaneously increases the expression of both the regulatory subunit of CDK4/6, cyclin D1, and PFKFB3, we postulated that the combination of palbociclib with PFK158 would yield synergy against breast cancer cells. In new preliminary studies, co-treatment with palbociclib and PFK158 resulted in a marked decrease in cell proliferation in two ER+ breast cancer cell lines that was accompanied by a synergistic decrease in phospho-Retinoblastoma (Rb). Importantly, exposure of ER+ breast cancer cells to palbociclib and PFK158 causes an increase in cell cycle arrest and apoptotic cell death in vitro. Notably, this combination has no effect on cell cycle arrest or apoptosis in normal mammary cells suggesting that this therapeutic strategy may be well tolerated and selective for breast cancer. Citation Format: Yoannis Imbert-Fernandez, Lilibeth Lanceta, Sucheta Telang, Jason Chesney. Targeting 6-phosphofructo-2-kinase to increase the efficacy of ER and CDK4/6 inhibitors against breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2305.
Meningitis: UK adults face diagnosis delays and inappropriate treatment, study finds
Authors: Susan Mayor
Journal: BMJ (2018)

Adults with meningitis admitted to hospitals in England experience substantial delays in diagnostic testing and receive inappropriate treatment, both of which are associated with longer hospital stays, an observational study has reported.1

The prospective observational cohort study enrolled 1126 patients aged over 16 admitted with clinically suspected meningitis to 42 hospitals around England from September 2011 to September 2014. It included all 24 acute hospitals in the northwest region.

The results, reported in the Lancet Infectious Diseases ,1 showed that nearly two thirds of the patients …