tbuckley/cabot-search huggingface dataset:
Sectm1a deficiency aggravates inflammation-triggered cardiac dysfunction through disruption of LXRα signalling in macrophages
Authors: Yutian Li, Shan Deng, Xiaohong Wang, Wei Huang, Jing Chen, Nathan Robbins, Xingjiang Mu, Kobina Essandoh, Tianqing Peng, Anil G Jegga, Jack Rubinstein, David E Adams, Yigang Wang, Jiangtong Peng, Guo-Chang Fan
Journal: Cardiovascular Research (2020)

Cardiac dysfunction is a prevalent comorbidity of disrupted inflammatory homeostasis observed in conditions such as sepsis (acute) or obesity (chronic). Secreted and transmembrane protein 1a (Sectm1a) has previously been implicated to regulate inflammatory responses, yet its role in inflammation-associated cardiac dysfunction is virtually unknown.
LIPID-LOWERING THERAPY PATTERNS AND LOW-DENSITY LIPOPROTEIN-CHOLESTEROL MANAGEMENT AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN ALBERTA, CANADA
Authors: Tayler Scory, Guanmin Chen, Megan S. Farris, Yu-Hsuan Shih, Lionel Pinto, Tara Cowling
Journal: Journal of the American College of Cardiology (2020)
Prediction of dementia risk in low-income and middle-income countries (the 10/66 Study): an independent external validation of existing models
Authors: Blossom C M Stephan, Eduwin Pakpahan, Mario Siervo, Silvan Licher, Graciela Muniz-Terrera, Devi Mohan, Daisy Acosta, Guillermina Rodriguez Pichardo, Ana Luisa Sosa, Isaac Acosta, Juan J Llibre-Rodriguez, Martin Prince, Louise Robinson, Matthew Prina
Journal: The Lancet Global Health (2020)

To date, dementia prediction models have been exclusively developed and tested in high-income countries (HICs). However, most people with dementia live in low-income and middle-income countries (LMICs), where dementia risk prediction research is almost non-existent and the ability of current models to predict dementia is unknown. This study investigated whether dementia prediction models developed in HICs are applicable to LMICs.
DEVELOPMENT OF A TOOL FOR EASY IDENTIFICATION OF STUDENTS AT HIGH RISK OF RHEUMATIC HEART DISEASE IN DHADING DISTRICT OF NEPAL
Authors: Madhab Ray, Ranga Raj Dhungana, Bipasha Ray, Rishi Shah, Haroon Zubair, Meghna Ray, Paushaly Sau, Santanu Guha, Robert Joel Goldberg, Harry P. Selker, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2020)
ASSESSMENT FOR DYNAMIC EFFECTS OF CISPLATIN-BASED CANCER CHEMOTHERAPY ON COAGULATION AND FIBRINOLYTIC SYSTEM
Authors: Wataru Shioyama, Toru Oka, Risa Kamada, Tatsuya Nishikawa, Makiko Oboshi, Taku Yasui, Masashi Fujita
Journal: Journal of the American College of Cardiology (2020)
BASELINE CARDIOVASCULAR RISK FOR PATIENTS WITH RECENT MYOCARDIAL INFARCTION PRESCRIBED A PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 INHIBITOR
Authors: Seth J. Baum, Pin Xiang, Belinda Schludi, Mohdhar Habib, Xin Wang, Sasikiran Nunna, Rolin L. Wade, Pallavi Rane, Chi-Chang Chen
Journal: Journal of the American College of Cardiology (2020)
Burnout in the Irish oncology community: Results of a single-institution study.
Authors: Lillian Smyth, Aonghus Lavelle, Reem Salman, James Lucey, John McCaffrey, Michael A. Maher, David James Gallagher
Journal: Journal of Clinical Oncology (2012)

e19601 Background: Several European studies suggest that healthcare professionals working in oncology display higher levels of professional burnout than their colleagues from non-oncology units. We aimed to identify the level of burnout of professionals working in cancer care at a single institution in Dublin, Ireland. Methods: 143 oncology staff members were emailed a 3 section questionaire. We employed the Maslach Burnout Inventory, a validated, burnout-specific instrument, incorporating a three-dimensional assessment of the syndrome through its subscales: emotional exhaustion (EE), depersonalization (DP) and personal achievment (PA). Sociodemographic, protective and predisposing variables were identified in tandem, while the final section afforded respondents an opportunity to speculate on workplace stressors and their potential remediation. The primary endpoint was overall high burnout. Secondary endpoints were mean scores for each individual category. Wilcoxon rank sum and Kruskal-Wallis tests were performed on SPSS version 18. Results: The overall response rate was 41.3% (59/143) (see table). Three respondents (5.1%) reported high levels of burnout in all 3 categories. In subcategory analysis, men had significantly higher mean DP scores [9, SD: 6.03] than women [5.3,SD: 4.46](p &lt; .05) and residents had significantly higher DP scores [8.11,SD: 4.46] than attendings [4.14,SD: 3.2]( p &lt; .05). Regression analysis, found that being male was a significant predictor for high levels of depersonalization but found no predictor for EE or PA. Conclusions: We identified low levels of burnout among Irish cancer care professional. Protective factors such as age &lt;35yrs (66%), religion (68%), hobbies (86%),working &lt;50 hours (66%) and being in a relationship (74%) were at high levels, which may have biased our results. A national expansion and comparison with international figures is planned and will be presented at ASCO. [Table: see text]
UNUSUAL SURVIVAL IN A PATIENT WITH MRSA PERICARDITIS WITH RAPIDLY PROGRESSIVE PERICARDIAL EFFUSION AND ABSCESS TREATED MEDICALLY IN COMBINATION WITH PERCUTANEOUS INTERVENTION
Authors: Mateen Saffarian, Peter Zihao Xu, Anilkumar Mehra, Enrique Ostrzega
Journal: Journal of the American College of Cardiology (2020)
Gefitinib in advanced unresectable hepatocellular carcinoma: Results from the Eastern Cooperative Oncology Group’s Study E1203
Authors: P. J. O’Dwyer, B. J. Giantonio, D. E. Levy, J. S. Kauh, D. B. Fitzgerald, A. B. Benson
Journal: Journal of Clinical Oncology (2006)

4143 Background: Worldwide, hepatocellular carcinoma (HCC) is the most common cause of cancer death. Chemotherapy yields no survival benefit, and median survival is &lt; 6 months. Up to 47% of HCCs express the epidermal growth factor receptor (EGFR), which predicts survival. Also, EGFR signaling activates c-Met, the hepatocyte growth factor receptor. Gefitinib is an oral selective EGFR inhibitor that has shown growth inhibition of HCC cell lines. Methods: E1203 was a single arm phase II study of gefitinib in advanced HCC. Eligibility requirements: unresectable measurable (by RECIST) HCC (diagnosed by histology or alpha-fetoprotein criteria); PS ≤ 2; total bilirubin ≤ 2× ULN; SGOT ≤ 5× ULN; INR ≤ 2.3; albumin ≥ 2.8 g/dl; Child Pugh Class &lt; C; no prior systemic therapy. Gefitinib 250 mg taken daily. 1 cycle = 3 weeks. Tumor assessments done every 6 weeks. Objectives: 4.5 month PFS of 63%, OS, RR, toxicity. A two-stage design was used. Results: Thirty-one patients were accrued to the first stage. Median follow-up is 13.2 months. Med age = 64.8 yrs (46–86). M:F 87%:10%. PS 0/1/2: 39%/42%/16%. Med PFS = 2.8 months (95%CI: 1.5, 3.9). Med OS = 6.5 months (95% CI: 4.4, 8.9). Response #s (CR/PR/SD): 0/1/7. Selected grade 3 adverse events: neutropenia ×2; rash ×2; diarrhea ×1. There was only 1 grade 4 AE (neutropenia). The criterion for second-stage accrual was not met. Conclusion: Gefitinib as a single agent is not active in advanced HCC. No significant financial relationships to disclose.
RENIN ANGIOTENSIN-ALDOSTERONE (RAAS) BLOCKADE FOR SECONDARY PREVENTION OF NON-VALVULAR ATRIAL FIBRILLATION: A META-ANALYSIS
Authors: Satyanarayana Vaidya, Dushyant Singh Dahiya, Varakantham Monica, Santhosh Reddy Devarapally
Journal: Journal of the American College of Cardiology (2020)
Endonuclease FEN1 Coregulates ERα Activity and Provides a Novel Drug Interface in Tamoxifen-Resistant Breast Cancer
Authors: Koen D. Flach, Manikandan Periyasamy, Ajit Jadhav, Dorjbal Dorjsuren, Joseph C. Siefert, Theresa E. Hickey, Mark Opdam, Hetal Patel, Sander Canisius, David M. Wilson, Maria Donaldson Collier, Stefan Prekovic, Marja Nieuwland, Roelof J.C. Kluin, Alexey V. Zakharov, Jelle Wesseling, Lodewyk F.A. Wessels, Sabine C. Linn, Wayne D. Tilley, Anton Simeonov, Simak Ali, Wilbert Zwart
Journal: Cancer Research (2020)

Abstract Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. In this study, we refined a previously identified 111-gene outcome prediction-classifier, revealing FEN1 as the strongest determining factor in ERα-positive patient prognostication. FEN1 levels were predictive of outcome in tamoxifen-treated patients, and FEN1 played a causal role in ERα-driven cell growth. FEN1 impacted the transcriptional activity of ERα by facilitating coactivator recruitment to the ERα transcriptional complex. FEN1 blockade induced proteasome-mediated degradation of activated ERα, resulting in loss of ERα-driven gene expression and eradicated tumor cell proliferation. Finally, a high-throughput 465,195 compound screen identified a novel FEN1 inhibitor, which effectively blocked ERα function and inhibited proliferation of tamoxifen-resistant cell lines as well as ex vivo–cultured ERα-positive breast tumors. Collectively, these results provide therapeutic proof of principle for FEN1 blockade in tamoxifen-resistant breast cancer. Significance: These findings show that pharmacologic inhibition of FEN1, which is predictive of outcome in tamoxifen-treated patients, effectively blocks ERα function and inhibits proliferation of tamoxifen-resistant tumor cells.
Catumaxomab: Pharmacodynamic and pharmacokinetic data from phase IIIb CASIMAS study in patients with malignant ascites.
Authors: Per Rosenberg, Alexander Serg Dudnitchenko, Vladimir Bondar, Christoph Salat, Hanne Havsteen, Carsten Bokemeyer, Dominique Berton-Rigaud, Xavier Durando, Ignace B. Vergote, Pauline Wimberger, Florian Lordick, Horst Lindhofer, Holger Martinius, Jalid Sehouli
Journal: Journal of Clinical Oncology (2012)

e13108^ Background: Catumaxomab (anti-EpCAM x anti-CD3) is approved in the EU for the i.p. locoregional treatment of malignant ascites (MA). The peritoneal cavity invaded by epithelial tumor cells provides an environment for tumor-specific, EpCAM-targeted catumaxomab immunotherapy. In order to monitor the local and systemic pharmacodynamic/ pharmacokinetic (PD/PK) profile of catumaxomab, plasma and ascites samples from patients in the CASIMAS study were investigated. Methods: Plasma and ascites samples were collected in patients prior, during and after catumaxomab i.p. infusions. Samples were analysed for a) Selected cytokines (IL-2, -4, -6, -8, -10, and -12, IFN-gamma, TNF-alpha, and GM-CSF) in 20 patients, b) catumaxomab drug levels in 31 patients (14 patients with MA who received all 4 infusions of 10, 20, 50, and 150 µg were evaluable for systemic PK analysis), c) number of EpCAM+ tumor cells in ascites in 11 patients. Results: Drug levels were highest in ascites fluid ranging from 0 to 219.4 ng/mL at day 10 (n=31/31 patients). Low systemic plasma levels were detected in 7/14 patients (median cmax: 623 pg/mL). In 7/14 subjects no catumaxomab was detected systemically. Furthermore, cytokine concentrations in ascites were higher compared to plasma. Mainly IL-6, -8 &amp; -10 and IFN-gamma were detected; in few cases TNF-alpha and IL-2. Whereas IL-4, -12, and GM-CSF were not detected at all. Anti-tumor activity was proven by i.p. tumor cell elimination. Tumor cell count in ascites dropped markedly below baseline. In the majority (7/11) of patients no EpCAM+ tumor cells were detectable after therapy. Before therapy, in 165/166 evaluable patient samples EpCAM+ tumor cells were detected in the ascites fluid. Conclusions: Catumaxomab represents a locoregional immunological i.p. treatment eliminating tumor cells in the peritoneal cavity and thereby effectively controlling MA. Catumaxomab primarily remains in the peritoneal cavity with low systemic exposure. In line with this, cytokines are mainly released locally, at the site of action. These PD/PK results confirm the results obtained in the pivotal phase II/III study.
Outpatient letters to patients: many doctors and patients are non-native speakers
Authors: Stephen J Nickless
Journal: BMJ (2020)

I agree that clinicians should write directly to patients and “copy in” other professionals involved in their care.1 This will be challenging for UK trained, native speakers of advanced English, and even more challenging for our many NHS colleagues who trained elsewhere and have English as a second language. Moreover, many of these letters will be …
Altered Repertoire Diversity and Disease‐Associated Clonal Expansions Revealed by T Cell Receptor Immunosequencing in Ankylosing Spondylitis Patients
Authors: Aimee L. Hanson, Hendrik J. Nel, Linda Bradbury, Julie Phipps, Ranjeny Thomas, Kim‐Anh Lê Cao, Tony J. Kenna, Matthew A. Brown
Journal: Arthritis & Rheumatology (2020)

Objective Ankylosing spondylitis ( AS ) is a common spondyloarthropathy primarily affecting the axial skeleton and strongly associated with HLA –B*27 carriage. Genetic evidence implicates both autoinflammatory processes and autoimmunity against an HLA –B*27 –restricted autoantigen in immunopathology. In addition to articular symptoms, up to 70% of AS patients present with concurrent bowel inflammation, suggesting that adverse interactions between a genetically primed host immune system and the gut microbiome contribute to the disease. Accordingly, this study aimed to characterize adaptive immune responses to antigenic stimuli in AS . Methods The peripheral CD 4 and CD 8 T cell receptor ( TCR ) repertoire was profiled in AS patients (n = 47) and HLA –B*27 –matched healthy controls (n = 38). Repertoire diversity was estimated using the Normalized Shannon Diversity Entropy ( NSDE ) index, and univariate and multivariate statistical analyses were performed to characterize AS ‐associated clonal signatures. Furthermore, T cell proliferation and cytokine production in response to immunogenic antigen exposure were investigated in vitro in peripheral blood mononuclear cells from AS patients (n = 19) and HLA –B*27 –matched healthy controls (n = 14). Results Based on the NSDE measure of sample diversity across CD 4 and CD 8 T cell repertoires, AS patients showed increased TCR diversity compared to healthy controls (for CD 4 T cells, P = 7.8 × 10 −6 ; for CD 8 T cells, P = 9.3 × 10 −4 ), which was attributed to a significant reduction in the magnitude of peripheral T cell expansions globally. Upon in vitro stimulation, fewer T cells from AS patients than from healthy controls expressed interferon‐γ (for CD 8 T cells, P = 0.03) and tumor necrosis factor (for CD 4 T cells, P = 0.01; for CD 8 T cells, P = 0.002). In addition, the CD 8 TCR signature was altered in HLA –B*27 + AS patients compared to healthy controls, with significantly expanded Epstein‐Barr virus–specific clonotypes ( P = 0.03) and cytomegalovirus‐specific clonotypes ( P = 0.02). HLA–B*27 + AS patients also showed an increased incidence of “public” CD8 TCRs, representing identical clonotypes emerging in response to common antigen encounters, including homologous clonotypes matching those previously isolated from individuals with bacterial‐induced reactive arthritis. Conclusion The dynamics of peripheral T cell responses in AS patients are altered, suggesting that differential antigen exposure and disrupted adaptive immunity are underlying features of the disease.
ADXS11-011 immunotherapy: Preliminary safety data from two P2 studies in women with CIN 2/3 and with recurrent/refractory cervical cancer.
Authors: Robert G. Petit, Keith A. Aqua, Partha Basu
Journal: Journal of Clinical Oncology (2012)

e15546 Background: ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete a HPV-16-E7 fusion protein targeting HPV transformed cells. The Lm vector serves as its own adjuvant and infects APC where it naturally cross presents, stimulating both MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumors. Here we describe the preliminary survival data associated with ADXS11-001 administration in Lm-LLO-E7-015, a randomized phase II study being conducted in India in 110 patients with recurrent/refractory cervical cancer who have been treated previously with chemotherapy, radiotherapy or both. Methods: Patients are randomized to either 3 doses of ADXS11-001 at 1 x 10 9 CFU or 4 doses of ADXS11-001 at 1 x 10 9 CFU with cisplatin chemotherapy. Naprosyn and oral promethazine are given as premedications and a course of ampicillin is given 72h after infusion thereby clearing any residual vector. Patients receive CT scans at baseline and Days 84, 184, 273, 365 and 545. The primary endpoint is 12 month survival. Results: As of January 26, 2012, 88 patients have received 200 doses of ADXS11-001; with the percentage of patients alive at 6 months at 62% (34/55); at 9 months at 41% (15/37) and at 12 months at 40% (6/15). Tumor responses have been observed in both treatment arms with 3 complete responses (elimination of tumor burden) and 4 partial responses (≥30% reduction in tumor burden) by RECIST. One serious (Gr3) adverse event and 77 mild-moderate (Gr 1-2) adverse events possibly related to study treatment have been reported in 35% (31/88) of patients. The non-serious adverse events consisted predominately of transient, non-cumulative flu-like symptoms associated with infusion that responded to symptomatic treatment, or resolved on their own within hours of treatment. Conclusions: This immunotherapy can be safely administered to patients with advanced cancer alone and in combination with chemotherapy. ADXS11-001 is well tolerated and presents a predictable and manageable safety profile. Early signs of clinical benefit merit further investigation. Updated findings will be presented at the meeting.
Inositols in Polycystic Ovary Syndrome: An Overview on the Advances
Authors: Fabio Facchinetti, Vittorio Unfer, Didier Dewailly, Zdravko A. Kamenov, Evanthia Diamanti-Kandarakis, Antonio Simone Laganà, John E. Nestler, Christophe O. Soulage
Journal: Trends in Endocrinology and Metabolism (2020)
Avoiding immortal time bias in observational studies
Authors: Adam J.N. Raymakers, Mohsen Sadatsafavi, Don D. Sin, J. Mark FitzGerald, Carlo A. Marra, Larry D. Lynd
Journal: European Respiratory Journal (2020)

<b>Immortal time bias is common in observational studies; however, in the analysis conducted by Raymakers and colleagues appropriate measures were taken to avoid this bias</b>http://bit.ly/36042OV
Clinical characterics of mixed neuroendocrine cancer of lung: Retrospective analysis of 20 cases from 2,501 lung cancer.
Authors: Dong-Hai Li, Lin Zhou, Zhenyu Ding
Journal: Journal of Clinical Oncology (2013)

e19055 Background: The mixed neuroendocirne cancer of the lung consists endocrine cancer and other pathological types of cancer, and is generally overlooked in daily practice. The current study to explore the clinical characteristics of mixed neuroendocirne cancer of the lung. Methods: Totally 2,501 cases with primary lung cancer were retrieved from the archive of the Cancer Center, West China Medical School. And the relevant medical records including diagnosis, histology, therapy, and outcome were collected. Results: Among the 2, 501 cases, 20 were found to have mixed neuroendocrine cancer with morbidity rate 0.01% (19 male, 1 female). The median age was 60 years. The surgery (13 cases, 65%) and chemotherapy (19 cases, 95%) were the mainstay of therapy. 2 cases (10%) received thoracic radiation, and 3 cases (15%) received whole brain radiation. Chemotherapy regimens included etoposide-based doublets (A) or the third-generation agent-based (B) regimens. The long-term follow-up data were available for 18 cases (90%) with the median follow-up duration of 20.5 months. The overall survival of the stage IV patients was 18.2 months, while that of the stage I-III was not reached (P=0.325). The chemotherapy regimens (A or B) did not exert impact on survival (P=0.535). Patients received operation (11 cases) had less mortality compared with those without operation (7 cases) (P&lt;0.001). Conclusions: The mixed neuroendocrine cancer of lung is a rare disease. Male takes a predominant part. Stage and histology are important for the prognosis. The chemotherapy seems to have less impact on the prognosis, but the surgery is critical for the long survival.
Diurnal proteomics and biomarker discovery in indolent versus aggressive chronic lymphocytic leukemia patients.
Authors: Georg A. Bjarnason, David Spaner, Suzanne Ackloo, Jieran Li, Pei Hong Zhu, Paulo S Nuin, Joseph Geraci, Moyez Dharsee, Tami Martino, Cathy Wang, Kenneth R. Evans
Journal: Journal of Clinical Oncology (2012)

10622 Background: In rodents, 10-20% of the genome has a 24-hour (h) rhythm in RNA expression. A molecular clock consisting of transcription / translation feedback loops of clock-genes controls this rhythmicity. In a microarray study (Affymetrix HG_U133_Plus2 chip) on RNA extracted from CLL cells sampled every 4 hours over 24 hours (6 samples) from 3 male (M) and 6 female (F) patients (pts) with chronic lymphocytic leukemia (CLL) we found 15,094 and 13,415 rhythmic transcripts (Cosinor analysis) in M and F respectively, only 6,629 of which were common to both M and F. We hypothesized that these gender differences in rhythmic RNA expression might have clinical implication for biomarker discovery with some important biomarkers only found at a certain times of day and with gender differences. Methods: Sampling was performed again at 6 time points in M and F CLL patients with indolent CLL (10pts, 5 M, 5F) and aggressive CLL (10 pts, 5M, 5F). An 8-plex iTRAQ kit was employed for mass spectrometry (MS) based relative quantification. Each iTRAQ block comprised all time-points for a single patient including a universal control. Results: At least 300 proteins were identified at a 95% confidence level in each iTRAQ experiment. Of these, 74 proteins displayed significant change between aggressive and indolent pts in 24-hour average or single time point normalized expression based on a non-parametric U-test (p&lt;0.05). The JTK_CYCLE algorithm was used to detect 24-hour rhythmic patterns in the proteomic datasets. Significant rhythmic expression was found for 44 proteins (p&lt;0.10) identified by iTRAQ. Data for each time point were independently analyzed using an in-house Butterfly clustering algorithm based on discrete dynamical systems. The 4 PM time point was found to be optimal for stratifying aggressive and indolent disease. Cellular pathways with significant association to differentially expressed proteins included PPAR signaling, fatty acid metabolism, and granzyme-A signaling. Confirmation by selected reaction monitoring (SRM) MS is ongoing. Conclusions: Rhythmic protein expression may have clinical implications for biomarker discovery.