tbuckley/cabot-search huggingface dataset:
Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome
Authors: Gregory G. Schwartz, Philippe Gabriel Steg, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, Yong-Un Kim, J. Wouter Jukema, Robert Pordy, Matthew T. Roe, Harvey D. White, Deepak L. Bhatt
Journal: Circulation (2020)

Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C.This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18 924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-Ccorrected) for cholesterol content in lipoprotein(a).At baseline, median lipoprotein(a) and LDL-Ccorrected were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (Ptrend=0.0021), and tended to associate with baseline quartile of LDL-Ccorrected (Ptrend=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (Ptrend=0.06), but not LDL-Ccorrected (Ptrend=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54-0.89]; P=0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44-1.01]; P=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (Ptrend=0.03), but not LDL-Ccorrected (Ptrend=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-Ccorrected, was associated with the risk of VTE and the composite of VTE and PAD events.In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.
Abstract P4-14-09: Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis
Authors: Ramy Saleh, Michelle B Nadler, Alexandra Desnoyers, Rouhi Fazelzad, Eitan Amir
Journal: Cancer Research (2020)

Abstract Background: The addition of platinum agents to anthracycline and taxane-based chemotherapy in early-stage triple negative breast cancer (TNBC) patients improves pathological complete response (pCR). Long-term outcomes, such as disease-free survival (DFS) and overall survival (OS), have not been well-established. Methods: A systematic literature review identified studies using platinum-based treatment in TNBC patients in the neoadjuvant or adjuvant setting with reportable long-term outcomes. Hazard ratios (HR) from collected data were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on treatment setting (neoadjuvant vs. adjuvant) and study design (retrospective vs. randomized controlled trials). When available, odds ratios (OR) for commonly reported safety and tolerability measures such as treatment-related death, treatment discontinuation without progression, dose reduction, neuropathy, renal impairment and hematological toxicity were calculated. Results: Seven studies comprising 1699 patients met the inclusion criteria. Median follow up was 54.5 months. All studies reported DFS and 4 studies reported OS. DFS was significantly better in platinum-based treatment (HR 0.71, 95% confidence interval (CI) 0.53-0.96; P = 0.03). However, OS was no different with a higher number of events in the platinum-based treatment arm (HR 1.17, 95% CI 0.81-1.69; P = 0.42). There was no significant difference between treatment settings (p = 0.74) or between study designs (p = 0.74), although a higher HR for OS was observed for studies in the adjuvant (HR 1.34, 95% CI 0.54-3.35) compared to neoadjuvant setting (HR 1.14, 95% CI 0.76-1.70). The reporting of toxicity was suboptimal with most studies not reporting safety and tolerability metrics clearly. Platinum-based treatment was associated with more neutropenia and thrombocytopenia and treatment discontinuation, however, the magnitude of this effect could not be estimated accurately. Conclusions: Platinum-based treatment improves DFS but has no effect on OS and increases toxicity. The discordant effect of platinum-based treatment on DFS and OS suggest the potential development of platinum resistance and worse outcomes after recurrence. The higher magnitude of discordance in adjuvant compared to neoadjuvant studies suggests an effect of platinum-based therapy on loco-regional control prior to surgery rather than prevention of distant metastatic disease. Platinum-based chemotherapy cannot be recommended in unselected patients with TNBC. Citation Format: Ramy Saleh, Michelle B Nadler, Alexandra Desnoyers, Rouhi Fazelzad, Eitan Amir. Platinum-based chemotherapy in early-stage triple negative breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-14-09.
Follicular regulatory helper T cells control the response of regulatory B cells to a high-cholesterol diet
Authors: Fabienne Burger, Kapka Miteva, Daniela Baptista, Aline Roth, Rodrigo A Fraga-Silva, Catherine Martel, Nikolaos Stergiopulos, François Mach, Karim J Brandt
Journal: Cardiovascular Research (2020)

B cell functions in the process of atherogenesis have been investigated but several aspects remain to be clarified.
An Invited Commentary on “Comparison of the safety and efficacy of single-stage endoscopic retrograde cholangiopancreatography plus laparoscopic cholecystectomy versus two-stage ERCP followed by laparoscopic cholecystectomy six-to-eight weeks later: A randomized controlled trial” (Int J Surg. 2020;76:37-44)
Authors: Damiano Caputo, Alessandro Coppola
Journal: International Journal of Surgery (2020)
Abstract 15839: Relation Between HbA1c Level and Effectiveness of SGLT2 Inhibitors in Diabetic Patients With Acute Decompensated Heart Failure
Authors: Masaki Nakagaito, Shuji Joho, Ryuichi Ushijima, Makiko Nakamura, Tadakazu Hirai, Koichiro Kinugawa
Journal: Circulation (2018)

Introduction: The EMPA-REG outcome and CANVAS program revealed that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced heart failure (HF) hospitalization in type 2 diabetic mellitus (T2DM) ...
Letter to the Editor: Does Augmenter of Liver Regeneration Deficiency Pave the Way for Nonalcoholic Steatohepatitis Progression?
Authors: Thomas S. Weiss, Michael Melter, Rania Dayoub
Journal: Hepatology (2020)

To the Editor: We read with interest the recent article by Kumar et al.(1) on the impact of augmenter of liver regeneration (ALR) deficiency on nonalcoholic fatty liver disease (NAFLD) progression from steatosis to nonalcoholic steatohepatitis (NASH). By using hepatocyte-specific ALR knockout/knockdown high-fat/high-carbohydrate mouse models, they demonstrated an involvement of ALR in lipid metabolism, oxidative stress, and inflammatory response leading to fibrosis. However, ALR is expressed in three isoforms (15, 21, 23 kDa),(2) and their specific roles in this "loss-of-function" strategy is not addressed. In earlier publications, using an overexpression approach ("gain-of-function") of the mainly mitochondrial 23-kDa ALR, a reduction in hepatic fibrosis and ischemia reperfusion injury (IRI) in steatotic livers was shown.(2) Expression of cytosolic 15-kDa ALR reduced severity of liver injury in a methionine-choline–deficient NASH mouse model.(2) Furthermore, it was shown that cytosolic 15-kDa ALR, different from exogenously applied 15-kDa ALR, diminished triacylglycerol levels and lipoapotosis in vitro by attenuating endoplasmatic stress, increasing lipolytic and decreasing lipogenic gene expression.(3) Additionally, treatment with exogenous ALR reduced hepatic IRI in mice by reducing neutrophil infiltration through less hepatocytic chemokine expression.(4) More detailed knowledge of the function of individual ALR isoforms is necessary for future therapeutic interventions. Kumar et al. found decreased ALR levels in human NASH patients (tissue and serum) and pointed to a lack of information about ALR regulation. This was addressed earlier, demonstrating reduced hepatic ALR mRNA levels in patients with steatosis and even more with NASH.(2, 3) ALR is regulated, among others, by forkhead box A2 (FOXA2; hepatocyte nuclear factor 3β), which translocates from the nucleus to the cytosol upon treatment with free fatty acids, and whose expression correlates with ALR expression in NAFLD patients.(3) Nuclear factor erythroid 2–related factor 2 (Nrf2), another ALR-regulating transcription factor,(2) was shown to attenuate liver steatosis and therefore it is likely that FOXA2 and Nrf2 diminished endogenous ALR levels in hepatic steatosis/NASH. However, the conclusion that ALR deficiency may be a major determinant of accelerated progression of NASH to end-stage liver disease, that is, cirrhosis, is not supported by enhanced ALR levels in patients with cirrhosis(2) or by clinical characterization of patients with mutations in the growth factor erv1-like (GFER) gene (encoding for ALR) showing almost no distinctive feature regarding hepatic function(2) and therefore should to be taken with caution.
Liver transplantation in patients with incidental hepatocellular carcinoma/cholangiocarcinoma and intrahepatic cholangiocarcinoma: A single-center experience
Authors: Ender Anilir, Tolga Sahin, Birkan Bozkurt, Pinar Yazici, Gulen Dogusoy, Sadik Server, Yildiray Yuzer, Yaman Tokat
Journal: International Journal of Surgery (2020)
Abstract 14374: Performance of ACC/AHA Cardiovascular Disease Risk Equations in Indigenous Australians With and Without Diabetes: The CRISP Study Collaboration
Authors: Elizabeth L Barr, Federica Barzi, Athira Rohit, Joan Cunningham, Shawn Tatipata, Robyn McDermott, Wendy E Hoy, Zhiqiang Wang, Pamela Bradshaw, Lyn Dimer, Peter Thompson, Julie Brimblecombe, Kerin O’Dea, Christine Connors, Steven Guthridge, Alex D Brown, Alan Cass, Jonathan E Shaw, Louise J Maple-Brown
Journal: Circulation (2018)

Introduction: Atherosclerotic cardiovascular disease (ASCVD) remains a major public health issue for many Indigenous populations, including Indigenous Australians because of earlier onset diabetes ...
Methods in predictive techniques for mental health status on social media: a critical review
Authors: Stevie Chancellor, Munmun De Choudhury
Journal: npj Digital Medicine (2020)

Social media is now being used to model mental well-being, and for understanding health outcomes. Computer scientists are now using quantitative techniques to predict the presence of specific mental disorders and symptomatology, such as depression, suicidality, and anxiety. This research promises great benefits to monitoring efforts, diagnostics, and intervention design for these mental health statuses. Yet, there is no standardized process for evaluating the validity of this research and the methods adopted in the design of these studies. We conduct a systematic literature review of the state-of-the-art in predicting mental health status using social media data, focusing on characteristics of the study design, methods, and research design. We find 75 studies in this area published between 2013 and 2018. Our results outline the methods of data annotation for mental health status, data collection and quality management, pre-processing and feature selection, and model selection and verification. Despite growing interest in this field, we identify concerning trends around construct validity, and a lack of reflection in the methods used to operationalize and identify mental health status. We provide some recommendations to address these challenges, including a list of proposed reporting standards for publications and collaboration opportunities in this interdisciplinary space.
Abstract P3-03-11: Notch inhibition promotes triple negative breast cancer growth
Authors: Pothana Saikumar, Prajjal K Singha, Manjeri A Venkatachalam
Journal: Cancer Research (2020)

Abstract Notch1 and Transforming Growth Factor-beta (TGF-β) signaling pathways in cancer have a paradoxical roles as they were shown to have both tumor suppressive and tumor promoting activities. The interaction between these two signaling pathways in cancer progression was addressed in a systematic way. In these studies, we utilized primary human mammary epithelial cells (HMEC) and various triple negative breast cancer (TNBC) cells and examined the molecular cross-talk between TGF-β and Notch signaling pathways using biochemical, molecular and cell biology techniques. First, we noticed lower expression of Notch1 in most of the TNBC cells compared to normal cells. Second, most of these TNBC cells overexpressed TMEPAI (transmembrane prostate androgen induced) protein, which was shown to switch TGF-β from a tumor suppressor to a tumor promoter role in breast cancer. Surprisingly, treatment of TNBC cells with Notch inhibitors increased their growth rate both in the absence or presence of TGF-β. Moreover, Notch inhibition relieved the growth suppression by TGF-β in normal cells. Both normal and TNBC cells showed increased growth in the presence of Notch inhibitors with decreased TGF-β signaling activity. Normal cells that express very low levels of TMEPAI both at mRNA and protein levels, overexpressed TMEPAI protein in the presence of various Notch inhibitors, suggesting that Notch negatively regulates TMEPAI expression. Correspondingly, knockdown of TMEPAI in TNBC cell lines showed increased expression of Notch1 and Jagged 1 suggesting a negative regulation of Notch1 by TMEPAI. Consistent with these observations, TMEPAI, a known binding partner of E3 ligases, causes increased turnover of Notch1 protein. In fact, over expression of active Notch1 in MDA-MB-231 cells inhibited tumor cell growth both in vitro and in vivo. Our results clearly suggest that a crosstalk exists between TGF-β and Notch1 signaling through TMEPAI. Therefore, our studies clearly indicate that use of Notch inhibitors is contraindicated in triple negative breast cancer patients. Citation Format: Pothana Saikumar, Prajjal K Singha, Manjeri A Venkatachalam. Notch inhibition promotes triple negative breast cancer growth [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-11.
Consumption of the Fish Oil High-Fat Diet Uncouples Obesity and Mammary Tumor Growth through Induction of Reactive Oxygen Species in Protumor Macrophages
Authors: Lianliang Liu, Rong Jin, Jiaqing Hao, Jun Zeng, Di Yin, Yanmei Yi, Mingming Zhu, Anita Mandal, Yuan Hua, Chin K. Ng, Nejat K. Egilmez, Edward R. Sauter, Bing Li
Journal: Cancer Research (2020)

Abstract Obesity is associated with increased risk of many types of cancer and can be induced by various high-fat diets (HFD) from different fat sources. It remains unknown whether fatty acid composition in different HFD influences obesity-associated tumor development. Here we report that consumption of either a cocoa butter or fish oil HFD induced similar obesity in mouse models. While obesity induced by the cocoa butter HFD was associated with accelerated mammary tumor growth, consumption of the fish oil HFD uncoupled obesity from increased mammary tumor growth and exhibited a decrease in protumor macrophages. Compared with fatty acid (FA) components in both HFDs, n-3 FA rich in the fish oil HFD induced significant production of reactive oxygen species (ROS) and macrophage death. Moreover, A-FABP expression in the protumor macrophages facilitated intracellular transportation of n-3 FA and oxidation of mitochondrial FA. A-FABP deficiency diminished n-3 FA–mediated ROS production and macrophage death in vitro and in vivo. Together, our results demonstrate a novel mechanism by which n-3 FA induce ROS-mediated protumor macrophage death in an A-FABP–dependent manner. Significance: This study provides mechanistic insight into dietary supplementation with fish oil for breast cancer prevention and advances a new concept that not all HFDs leading to obesity are tumorigenic.
CSC Expert Consensus on Principles of Clinical Management of Patients With Severe Emergent Cardiovascular Diseases During the COVID-19 Epidemic
Authors: Yaling Han, Hesong Zeng, Hong Jiang, Yuejin Yang, Zuyi Yuan, Xiang Cheng, Zhicheng Jing, Bin Liu, Jiyan Chen, Shaoping Nie, Jianhua Zhu, Fei Li, Changsheng Ma
Journal: Circulation (2020)

In response to the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, the Chinese Society of Cardiology (CSC) issued this consensus statement after consulting with 125 medical experts in the fields of cardiovascular disease and infectious disease. The over-arching principles laid out here are the following: 1) Consider the prevention and control of COVID-19 transmission as the highest priority, including self-protection of medical staff; 2) Patient risk assessment of both infection and cardiovascular issues. Where appropriate, preferential use of conservative medical therapeutic approaches to minimize disease spread; 3) At all times, medical practices and interventional procedures should be conducted in accordance with the directives of the infection control department of local hospitals and local health commissions.
Abstract 316: Missing Data and the SOFA Score in Cardiac Arrest Research: A Scoping Review
Authors: Anne V Grossestreuer, Tuyen Yankama, Ari Moskowitz, Long H Ngo, Michael Donnino
Journal: Circulation (2019)

Introduction: The Sequential Organ Failure Assessment (SOFA) score is often used as an outcome or exposure in cardiac arrest studies. SOFA requires lab values and vital signs at certain time points which often results in missing data. How this missing data is handled is unknown. Methods: We performed a scoping review of PubMed, EMBASE, and Web of Science. English language peer-reviewed manuscripts were included. Titles/abstracts were screened by two independent reviewers to assess if they met inclusion criteria. Studies that met inclusion criteria were retrieved in full; those that did not were excluded. Disagreements between reviewers were resolved by a third reviewer. Results: The initial search provided 408 abstracts, 142 underwent full-text review (kappa: 0.91), and 66 were included (5 randomized controlled trials, 26 prospective and 25 retrospective studies). The studies had a median of 151 (IQR: 55, 278) subjects. SOFA was used as an outcome in 36 (55%) and a primary outcome in 10 (15%). Only 27 (41%) studies reported a method to handle missing SOFA data. The most common method was to exclude subjects with missing data (81%). Other methods were use of maximum SOFA while subjects were alive (11%), modified SOFA after excluding subjects who died prior to the timepoint (11%), and earlier and later SOFA to impute values (4%). When SOFA was the primary outcome, 4 (40%) reported a method; 3 (75%) excluded subjects and one (25%) used modified SOFA. Two studies conducted sensitivity analyses to test assumptions used to handle missing SOFA (one imputed values for death/discharge, one adjusted for mortality difference prior to SOFA measurement). Only 9 studies (14%) mentioned quantity of missing SOFA, ranging from 0-76% (median: 10% [IQR: 6%, 42%]). In the 50 studies using SOFA at time points after baseline, only 11 (22%) mentioned mortality prior to SOFA measurement; when mentioned, it ranged from 3%-76% with a median of 12% (IQR: 6%-35%). Conclusion: Missing data for SOFA scores used in cardiac arrest studies is pervasive yet often not acknowledged and/or handled with described or consistent methods. These findings illustrate that studies using SOFA may exhibit substantial bias and results could be misinterpreted, particularly if patients with missing data are excluded.
SIRT7: an influence factor in healthy aging and the development of age-dependent myeloid stem-cell disorders
Authors: Alexander Kaiser, Martin Schmidt, Otmar Huber, Jochen J. Frietsch, Sebastian Scholl, Florian H. Heidel, Andreas Hochhaus, Jörg P. Müller, Thomas Ernst
Journal: Leukemia (2020)

Abstract Molecular alterations within the hematopoietic system influence cellular longevity and development of age-related myeloid stem-cell disorders like acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). A reduced SIRT7-expression in aged murine hematopoietic stem cells (HSC) resulted in reduced longevity and increased proliferation. In this study we investigated age-related changes of SIRT7-expression in healthy humans and relevant pathomechanisms in AML and CML. SIRT7-expression in leukocytes of healthy people decreased in an age-dependent manner. Low SIRT7 mRNA levels were also detected in AML and CML patients. With positive treatment response, SIRT7-expression increased, but showed reduction when patients progressed or relapsed. Pharmacologic inhibition of driver mutations in AML (FLT3-ITD) or CML (BCR-ABL) also restored SIRT7 levels in cell lines and patient samples. Furthermore, SIRT7-expression increased with time during PMA-mediated monocyte differentiation of THP-1 cells. SIRT7-overexpression in THP-1 cells resulted in increased expression of differentiation markers. BCR-ABL, FLT3-ITD, and differentiation-associated SIRT7-expression in general were positively regulated by C/EBPα, -β, and -ε binding to two different C/EBP-binding sites within the SIRT7 promoter. SIRT7 is important in human hematopoietic cell aging and longevity. It might act as tumor suppressor and could potentially serve as general biomarker for monitoring treatment response in myeloid stem-cell disorders.
Ticagrelor With or Without Aspirin in High-Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention
Authors: Dominick J. Angiolillo, Usman Baber, Samantha Sartori, Carlo Briguori, George Dangas, David J. Cohen, Shamir R. Mehta, C. Michael Gibson, Rishi Chandiramani, Kurt Huber, Ran Kornowski, Giora Weisz, Vijay Kunadian, Keith G. Oldroyd, Han Ya-Ling, Upendra Kaul, Bernhard Witzenbichler, Dariusz Dudek, Gennaro Sardella, Javier Escaned, Samin Sharma, Richard A. Shlofmitz, Timothy Collier, Stuart Pocock, Roxana Mehran
Journal: Journal of the American College of Cardiology (2020)