tbuckley/cabot-search huggingface dataset:
CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment
Authors: Rebecca A. Drummond, Muthulekha Swamydas, Vasileios Oikonomou, Bing Zhai, Ivy M. Dambuza, Brian C. Schaefer, Andrea C. Bohrer, Katrin D. Mayer-Barber, Sergio A. Lira, Yoichiro Iwakura, Scott G. Filler, Gordon D. Brown, Bernhard Hube, Julian R. Naglik, Tobias M. Hohl, Michail S. Lionakis
Journal: Nature Immunology (2019)
Relationship between exposure to air pollutants and development of systemic autoimmune rheumatic diseases: a nationwide population-based case–control study
Authors: Kuo-Tung Tang, Ben-Jei Tsuang, Kai-Chen Ku, Yi-Hsing Chen, Ching-Heng Lin, Der-Yuan Chen
Journal: Annals of the Rheumatic Diseases (2019)

Air pollutants are a heterogeneous mixture of gases and particles including particulate matter <2.5 µm in size (PM2.5), particulate matter <10 µm in size (PM10), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2) and ozone (O3). Air pollutants have proinflammatory effects and are therefore among the environmental factors contributing to the generation of inflammation and autoimmunity. However, there is scanty data supporting the correlation between air pollution and systemic autoimmune rheumatic diseases (SARDs), which mainly include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis and autoimmune myositis.

We investigated the relationship between air pollutants exposure and SARDs in a nationwide population-based case–control study. From the National Health Insurance Research Database, we identified Chinese adult incident cases afflicted with one of SARDs as well as age-matched and gender-matched controls in a 1:4 ratio from 1 January 2012 to 31 December 2013 (table 1). Long-term residential exposure to air pollutants was estimated based on the monitoring data from Environmental Protection Agency in 2011. …
Timing of treatment with concurrent chemoradiotherapy (CRT) and impact on progression free survival (PFS) in limited stage small cell lung cancer (LSSCLC)
Authors: L.M. McSorley, C.M. Goggin, N. Elhadi, P. O’Dea, J.S.Y. Sui, D.C. Kelly, C. Brady, D. O’Mahony
Journal: Annals of Oncology (2019)

Background: SCLC is an aggressive cancer subtype, with early metastatic spread and poor prognosis. We review Irish patient outcomes, outside of a clinical trial setting, to determine if patients who commenced radiotherapy (RT) within 30days of chemotherapy (CT) had a longer PFS. Methods: SCLC cases diagnosed between 2006-2016 were identified from a prospectively maintained lung cancer registry at a tertiary referral centre. Electronic patient records, paper charts, and pathology reports were reviewed to extract relevant data. In order to detect a statistical difference between the two groups with 95% confidence interval and a 5% margin of error, a sample size of 125 patients with SCLC was needed, and a sample size of 56 with LSSCLC. A two-sided t-test was used where data was normally distributed. A p value of < 0.05 was accepted. Kaplan-Meier analysis was used to assess progression free survival and a Mann-Whitney test to assess differences between groups. Results: 265 patients identified, 70 with LSSCLC, 44 had concurrent treatment. Median time to starting CT was 20 days (95%CI; 15.8-24.2days). The median time between diagnosis and CT was 28days, from CT to RT was 28.5 days. 21 patients started RT within 30 days of commencing CT; median time 19days. 19 patients started RT more than 30 days post CT; median time 67days. Median time from diagnosis to CT was 12days in this group. Median PFS where the time from day1 CT to day1 of RT was less than 30days was 12.1months. For patients where the treatment interval was greater than 30 days, median PFS was 10.6months. Using a non-parametric Mann-Whitney test to evaluate the median PFS produced a U value of 127, and a P-value of 0.41. Conclusions: This study reports real-world outcomes in patients with LSSCLC over a 10-year period. Although not reaching statistical significance there is a numerical difference in PFS favouring shorter time to combination CRT. We have also identified areas where there is room to improve our practice. Further attention will focus on strategies to reduce both the interval between histological diagnosis and commencing CT, and the interval between CT and RT in this setting. A study expansion is planned. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Basal cell carcinoma: Clinical practice assessment and educational gap analysis.
Authors: Tara Herrmann, Suman Pearce, Evan Rhodes, Pamela M. Peters
Journal: Journal of Clinical Oncology (2015)

e20111 Background: Basal cell carcinoma (BCC) is one of the most common malignant tumors of the skin in humans. Mortality from BCC is low, but the disease causes considerable morbidity, places a large burden on healthcare resources, and can have a substantial negative effect on a patient’s quality of life. A study was conducted to identify knowledge and clinical practice gaps among dermatologists and oncologists involved in BCC management. Methods: A clinical practice assessments (CPA) survey was developed based on current evidence-based consensus guidelines and best practices in the treatment of patients with BCC. The assessment design included both knowledge- and case -based, multiple-choice questions made available online to clinicians with neither monetary compensation nor charge. Confidentiality of survey respondents was maintained and responses were de-identified and aggregated prior to analyses. The survey launched on June 25, 2012 and participant responses were collected over the following 30 days. Results: In total, 175 physicians responded to the survey. Oncologists who participated in the CPA saw an average of 8 patients with BCC per week, with 74% seeing 1-10 patients with BCC per week.. A majority (58%) of oncologists did not appropriately select Mohs surgery for a patient with a 2.5 cm superficial BCC lesion on her back and 39% failed to recognize that a BCC ≥ 6 mm in the mask areas of the face would indicate a high risk of recurrence. Moreover only 21% of oncologists said that they were confident in managing patients on oral medications that require frequent monitoring and follow-up. In addition, significant gaps were identified in BCC pathogenesis, etiologic factors, risk stratification, and evidence-based management of metastatic BCC. Barriers to appropriate management cited most frequently by respondents included lack of familiarity regarding existing treatment guidelines as well as delayed patient presentation. Conclusions: This assessment of clinical practices identified gaps in risk stratification and management of BCC among oncologists.
Abstract 335: Inhibition of Histone Deacetylases Post Myocardial Infarction, Upregulates Wisp-1, a Novel Regulator of Cardiac Angiogenesis
Authors: Lillianne Wright, Daniel Herr, Symone Brown, Harinath Kasiganesan, Donald Menick
Journal: Circulation Research (2017)

Introduction: Re-establishing vasculature after a myocardial infarction (MI) may spare cardiomyocytes from death due to lack of sufficient oxygen. WISP-1 -a secreted matricellular protein that regulates angiogenesis in certain cancers- promotes cell survival in isolated cardiomyocytes in vitro . However, the potential role WISP-1 plays post-MI, has not been evaluated. Histone deacetylase inhibition (HDACi) attenuate adverse effects of an MI in small animal models but it is unclear which genes and or targets contribute to this benefit. Our preliminary data shows that Wisp-1 is upregulated 15-fold in response to MI injury compared to sham-operated mice, but is upregulated 45-fold in mice that are subjected to an MI injury and treated with the HDAC inhibitor, Vorinostat. Therefore, we hypothesized that HDACi mediated upregulation of Wisp-1 contributes to beneficial angiogenesis, post-MI . Methods: To test this, we subjected 10-12 week old male mice to ligation of the L.A.D. coronary artery or a sham operation. Mice were injected daily with either DMSO/vehicle, or Vorinostat. Seven days post-MI, mice were euthanized and their heart tissue was assessed for the expression of Wisp-1 and microvasculature. We also assessed the impact of recombinant WISP-1, and respective lentiviral mediated upregulation and shRNA mediated suppression of WISP-1 expression on human coronary artery endothelial cells (HCAECs). Results: In vivo , HDACi mediated upregulation and expression of Wisp-1 /Wisp-1 is observed at the border zone of infarction and its expression is proximal to microvasculature. Recombinant WISP-1 protein promotes expression of pro-angiogenic genes and phenotypic characteristics in HCAECs. Lastly, lentiviral activation and shRNA-targeted suppression of endogenous WISP-1 respectively enhances and reduces endothelial cell network branching in vitro . Conclusion: Therapeutic interventions after a heart attack impact the extent of infarct injury, cell survival and overall prognosis. Our studies shown here identify a novel pro-angiogenic target, Wisp-1, that may be useful in post-MI treatment modalities.
A translational study to investigate the role of carbohydrate sulfotransferase 15 for pancreatic cancer biology from in vitro to first-in-human clinical research.
Authors: Makoto Nishimura, Naohisa Yahagi, Takao Itoi, Yasutoshi Ochiai, Yoko Matsuda
Journal: Journal of Clinical Oncology (2015)

e22201 Background: Chondroitin sulfate E (CS-E) is known to promote tumor invasion by cleaving CD44 on pancreatic cancer cells. The biosynthesis of CS-E is mediated by specific enzyme carbohydrate sulfotransferase 15 (CHST15) that is reported to correlate with poor prognosis in several types of cancer. However, the effect of CHST15 blockade in pancreatic cancer has not been investigated. Methods: We synthesized CHST15 dsRNA that selectively inhibits CHST15 genes and tested the effects of CHST15 dsRNA on tumor biology in vitro and in vivo. To translate nonclinical results into clinical practice, we conducted an open-labeled, investigator initiated trial (IIT) through EUS-guided intratumoral injection in patients with unresectable pancreatic cancer to assess the safety in one month-observation as a primary outcome. Results: CHST15 dsRNA inhibited the expression of CHST15 mRNA on PANC-1 cells in vitro, which was associated with reduced secretion of soluble CD44 variant. Intratumoral injection with CHST15 dsRNA inhibited tumor growth and induced necrosis in PANC-1 xenograft model in mice. In IIT, 4 pancreatic cancer patients with a median age of 76.5 years (male: female = 2:2) were completed for one month-observation and approved by monitoring committee. A total of 16 ml of CHST15 dsRNA (250nM) was injected into the tumor under EUS guidance without drug-related adverse events. Mean tumor size changed from 32.2 mm to 30 mm in diameter. In exploratory measures, reduction of CHST15 protein and partial necrosis were detectable in biopsy specimens. Reduction in serum CD44 variant and CA19-9 were also detectable, suggesting the effectiveness of dsRNA injection. Conclusions: This is the first translational document showing the potential of CHST15 as a new therapeutic target for pancreatic cancer at least through mechanism regulating the secretion of soluble CD44 variant. High safety and feasibility were demonstrated, which will contribute to further clinical trials investigating CHST15 dsRNA. Clinical trial information: UMIN000014178.
<i>BIM</i> deletion polymorphism is not associated with BIM RNA expression or BIM immunohistochemistry intensity in epidermal growth factor receptor mutationpositive nonsmall cell lung cancer.
Authors: Kazutoshi Isobe, Yoshinobu Hata, Naobumi Tochigi, Atsushi Kakimoto, Tetsuo Mikami, Kyohei Kaburaki, Takashi Makino, Hahjime Otsuka, Go Sano, Keishi Sugino, Susumu Sakamoto, Yujiro Takai, Kazutoshi Shibuya, Akira Iyoda, Sakae Homma
Journal: Journal of Clinical Oncology (2015)

e22045 Background: BCL2-like 11 (BIM) deletion polymorphism was reported to be an independent prognostic factor for shorter progression-free survival (PFS) in patients treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). We examined the association of BIM polymorphism with BIM RNA isoform and BIM immunohistochemistry staining intensity in patients with EGFR-positive non–small cell lung cancer (NSCLC). Methods: Thirty-three EGFR-positive NSCLC patients treated with gefitinib between January 2008 and January 2014 were enrolled. BIM deletion polymorphism and BIM RNA-isoform (EL, L, S, γ) were determined by PCR, and BIM expression was classified as high or low by staining intensity in formalin-fixed paraffin-embedded slides of surgical specimens. We retrospectively analyzed clinical characteristics, response rate to gefitinib, and outcome. Results: BIM deletion polymorphism was present in 6 of 33 patients (18.1%). The frequency of BIM RNA isoform containing BH-3 domain (EL, L, S), which is required for BIM apoptotic function, did not differ between patients with and without BIM deletion polymorphism (83.3% vs. 70.3%, respectively). BIM staining intensity did not differ between patients with and without BIM deletion polymorphism. BIM staining intensity was correlated with the frequency of BIM RNA isoform containing BH-3 domain (EL, L, S). Median PFS was shorter for patients with BIM deletion polymorphism than for those without this polymorphism (206 days vs. 678 days, respectively; p < 0.001), but response rate to gefitinib did not differ (66.7% vs. 51.6%, p = 0.49). Although the response rate to gefitinib was higher for patients with high BIM expression than for those with low BIM expression (80% vs. 31.3%, respectively; p < 0.001), median PFS did not differ (493 days vs. 584 days, p = 0.51). Conclusions: BIM deletion polymorphism was not associated with the frequency of BIM RNA isoform containing BH-3 domain or BIM staining intensity. Median PFS was shorter for patients with BIM deletion polymorphism, and the response rate to gefitinib was higher for patients with high BIM expression.
Patient-reported outcomes of a nurse practitioner-led intervention to enhance chemotherapy symptom management.
Authors: Lara Traeger, Theresa Margaret McDonnell, Caitlin McCarty, Joseph A. Greer, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2015)

e20732 Background: Chemotherapy side effects are highly prevalent and commonly lead to urgent care needs. We evaluated a symptom management intervention for patients initiating chemotherapy for non-metastatic disease. The intervention was integrated into oncology clinics. Disease-specific nurse practitioners (NPs) called patients at set intervals during the first two chemotherapy cycles to assess/triage symptoms. We aimed to improve symptom burden through facilitating patient-NP collaboration. Methods: For this RCT (n = 60 intervention, 60 control), patients were age ≥ 18 and scheduled to receive chemotherapy for non-metastatic lung (LC), colorectal (CRC) or breast cancer (BRC) at the Massachusetts General Hospital. Participants completed self-report measures at the 1st chemotherapy infusion and then were randomly assigned (1:1, stratified by tumor type) to standard oncology care + NP calls, or standard oncology care alone. Participants completed follow-up measures at the 2nd and 3rd infusions. We analyzed group differences in symptoms based on intent to treat (Memorial Symptom Assessment-Short Form [MSAS] items; 2-sided p< .05). Secondary outcome was satisfaction with care (Family Caregiver Satisfaction-patient scale [FAMCARE]). Results: We reached target enrollment (consecutive enrollment rate = 83.9%). Study completion rate was 97.5%. Participants (70.8% age ≤ 65 years; 73.3% female) had LC (25%), CRC (25%) or BRC (50%). At 1st infusion, patients most commonly reported lack of energy (35.8%) and constipation (20.8%). By 3rd infusion, patients most commonly reported lack of energy (74.4%), nausea (34.2%) and constipation (29.3%). General linear modeling indicated that total symptom burden and satisfaction with care increased over time (MSAS: F= 55.5, p< .001; FAMCARE: F= 4.4, p= .02) but the changes did not differ by randomized group (MSAS: F= .20, p= .82; FAMCARE: F= 2.1, p= .13). Conclusions: The intervention did not reduce symptom burden over standard care. Early frequency of treatable symptoms highlights the potential value of early intervention and importance of continuing to examine strategies to improve symptom management during chemotherapy for non-metastatic disease. Clinical trial information: NCT01944137.
Anatomic Relationship of the Complex Tricuspid Valve, Right Ventricle, and Pulmonary Vasculature
Authors: Rebecca T. Hahn, Aaron B. Waxman, Paolo Denti, Tammo Delhaas
Journal: JAMA Cardiology (2019)

Severe functional or secondary tricuspid regurgitation (TR) is associated with poor long-term outcomes in natural history studies as well as specific disease states. An understanding of the physiologic causes of the TR is lacking precluding a systematic approach to treatment.The complex anatomic relationship between the tricuspid valve apparatus and structure of the right side of the heart lends insight into the functional changes seen with secondary TR. The association of these changes with changes in pulmonary vascular hemodynamics can lead to a cascade of events that result in disease progression.Appreciating the role of pulmonary vascular hemodynamics on right ventricular and tricuspid valve morphology and function improves our understanding of the pathophysiology of secondary TR. The limitations of current therapeutic approaches for secondary TR have stimulated interest in improving outcomes with this morbid disease. Changes in timing or approach to intervention require a more comprehensive understanding of the pathophysiology.
THU-407-Implementation of a hepatitis C testing and linkage to care program in the Philadelphia jail system
Authors: Lora Magaldi, Ebonee Allen, Jolie Anderson, Carla Coleman, Jalina Evans, Bruce Herdman, Jay Kostman, Ta-Wanda Preston, Alexandra Ripkin, Ricardo Rivera, Nabori Rosario, Stacey Trooskin
Journal: Journal of Hepatology (2019)
THU-006-Aberrant DNA methylation in bile accurately detects cholangiocarcinoma in patients with primary sclerosing cholangitis
Authors: Hege Marie Vedeld, Trine Folseraas, Kim Andresen, Heidi D. Pharo, Tom H. Karlsen, Marit Mæhle Grimsrud, Vemund Paulsen, Marine Jeanmougin, Lars Aabakken, Kirsten M. Boberg, Guro E. Lind
Journal: Journal of Hepatology (2019)
Elevated blood pressure (BP) and adverse events (AEs) of hypertension (HTN) in ponatinib (PON) leukemia trials.
Authors: Hanna Jean Khoury, Michele Baccarani, Francois Guilhot, Andreas Hochhaus, Timothy P. Hughes, Jeffrey Howard Lipton, Stephanie Lustgarten, Kumiko Yanase, Maureen G Conlan, Jorge E. Cortes, Michael W.N. Deininger, Hagop M. Kantarjian, Neil P. Shah, Moshe Talpaz, Michael J. Mauro
Journal: Journal of Clinical Oncology (2015)

7049 Background: PON is a potent, multitargeted tyrosine kinase inhibitor with proven efficacy in resistant Ph+ leukemia. This analysis reports elevated BP and AEs of HTN in PON leukemia trials. Methods: PON safety and efficacy were evaluated in patients (pts) with relapsed/refractory hematologic malignancies in the ongoing phase (ph) 1 trial, in heavily pretreated CML/Ph+ ALL pts in the ongoing PACE (ph 2) trial, and in newly diagnosed CP-CML pts in the terminated EPIC (ph 3) trial vs imatinib (IM). Ph 1 and EPIC, but not PACE, excluded pts with uncontrolled HTN (untreated systolic/diastolic >150/>100 mm Hg in ph 1, > 140/> 90 mm Hg in EPIC). Elevated BP was defined by single highest measurement (systolic/diastolic): grade (G) 1/pre-HTN 120–139/80–89, G2 140–159/90–99, G3 ≥ 160/≥ 100 mm Hg. HTN AEs were reported by investigators. Results: Elevated BP was frequent at trial entry; G1/G2–3 rates: 44%/42% in ph 1; 37%/47% in PACE; 51%/19% PON vs 52%/12% IM in EPIC. Any increase in BP grade from baseline was also frequent: 74% in ph 1; 68% in PACE; 68% PON vs 51% IM in EPIC. In PACE, estimated systolic/diastolic BP increases over time were low: 2.3/0.7 mm Hg/year. HTN AEs were reported in 38%, 28%, 18%, and 2% of ph 1, PACE, EPIC-PON, and EPIC-IM pts, respectively. Hypertensive crisis was reported in 2 PACE and 2 EPIC-PON pts. HTN AEs did not lead to discontinuation or death. Few pts had dose modifications for HTN AEs (0% ph1; 5% PACE; 3% EPIC-PON; 0% EPIC-IM). A retrospective multivariate analysis of pooled pts showed HTN AEs were significantly associated with PON dose intensity. Conclusions: Increase in BP was frequently observed in PON trials, including in pts on IM. Rates of HTN AEs were relatively lower and seen primarily with PON. While associated with PON dose intensity, HTN AEs rarely led to change in therapy. Given BP variability, AE reporting may be a more reliable indicator of clinically meaningful HTN. Clinical trial information: NCT00660920; NCT01207440; NCT01650805. Baseline* n Any Increase in BP Grade* on Study, % Pts G1 G2 G3 Ph 1 N = 81 Normal 11 18 45 27 G1 36 — 47 39 G2 27 — — 70 G3 7 — — — PACE N = 449 Normal 70 34 31 23 G1 167 — 53 35 G2 157 — — 62 G3 55 — — — EPIC-PON N = 154 Normal 46 57 22 7 G1 78 — 51 14 G2 30 — — 50 G3 0 — — — EPIC-IM N = 152 Normal 54 65 13 2 G1 79 — 35 5 G2 12 — — 17 G3 6 — — — Missing 1 — — — *Single measurement; Normal: <120/<80 mm Hg
Epigenetics in Human Obesity and Type 2 Diabetes
Authors: Charlotte Ling, Tina Rönn
Journal: Cell Metabolism (2019)

Epigenetic mechanisms control gene activity and the development of an organism. The epigenome includes DNA methylation, histone modifications, and RNA-mediated processes, and disruption of this balance may cause several pathologies and contribute to obesity and type 2 diabetes (T2D). This Review summarizes epigenetic signatures obtained from human tissues of relevance for metabolism-i.e., adipose tissue, skeletal muscle, pancreatic islets, liver, and blood-in relation to obesity and T2D. Although this research field is still young, these comprehensive data support not only a role for epigenetics in disease development, but also epigenetic alterations as a response to disease. Genetic predisposition, as well as aging, contribute to epigenetic variability, and several environmental factors, including exercise and diet, further interact with the human epigenome. The reversible nature of epigenetic modifications holds promise for future therapeutic strategies in obesity and T2D.
FRI-500-Sorafenib for recurrent hepatocellular carcinoma after liver transplantation: Intrinsic resistance or not?
Authors: Francesco Tovoli, Vito Sansone, Giovan Giuseppe Di Costanzo, Giulia Magini, Rodolfo Sacco, Tiziana Pressiani, Franco Trevisani, Raffaella Tortora, Laura Bucci, Maria Grazia Lucà, Luigi Bolondi
Journal: Journal of Hepatology (2019)