tbuckley/cabot-search huggingface dataset:
TCT-416 Clinical Impact of Tricuspid Regurgitation on Transcatheter Edge-to-Edge Mitral Valve Repair for Secondary Mitral Regurgitation: A Systematic Review and Meta-Analysis
Authors: Kalyan Chitturi, Bhaskar Bhardwaj, Ghulam Murtaza, Poorna Karuparthi, Nadeen Faza, Sachin Goel, Michael Reardon, Neal Kleiman, Kul Aggarwal
Journal: Journal of the American College of Cardiology (2021)
CARTITUDE-2: Efficacy and Safety of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T-Cell Therapy, in Patients with Multiple Myeloma and Early Relapse after Initial Therapy
Authors: Niels W.C.J. Van de Donk, Michel Delforge, Mounzer Agha, Adam D Cohen, Yael C Cohen, Jens Hillengass, Sebastien Anguille, Tessa Kerre, Wilfried Roeloffzen, Jordan M. Schecter, Kevin C. De Braganca, Helen Varsos, Liwei Wang, Martin Vogel, Enrique Zudaire, Christina Corsale, Muhammad Akram, Dong Geng, Tonia Nesheiwat, Lida Pacaud, Pieter Sonneveld, Sonja Zweegman
Journal: Blood (2021)
Regulation of SARS CoV-2 Host Factors in the Kidney and Heart in Rats with 5/6 Nephrectomy: Effects of Salt, ARB, Dipeptidyl Peptidase 4 Inhibitor, and SGLT-2 Blocker
Authors: Denis Delic, Yingquan Xiong, Shufei Zeng, Xin Chen, Chang Chu, Ahmed A. Hasan, Bernhard K. Krämer, Thomas Klein, Berthold Hocher
Journal: Journal of the American Society of Nephrology (2021)

Background: Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine subtype 2 (TMPRSS2) are important factors for SARSCoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-inhibitors may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods: We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham+normal diet (ND)+placebo (PBO);5/6Nx+ND+ PBO;5/6Nx+2% salt-diet (HSD)+PBO;5/6Nx+HSD+telmisartan;5/6Nx+HSD+linagliptin;5/6Nx+HSD+empagliflozin. Results: In the kidney the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) was not affected, whereas the cardiac level was significantly increased in 5/6 Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions: Overall, our study indicated that there is no upregulation regarding host factors potentially promoting SARS CoV-2 virus entry into host cells when the SGLT2 inhibitor empagliflozin, telmisartan and the DPP4 blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit
Authors: Xiaomeng Gao, Jieqiong You, Yanling Gong, Meng Yuan, Haiying Zhu, Liang Fang, Hong Zhu, Meidan Ying, Qiaojun He, Bo Yang, Ji Cao
Journal: Acta Pharmaceutica Sinica B (2021)

The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.
American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity
Authors: Julianna Desmarais, James T. Rosenbaum, Karen H. Costenbader, Ellen M. Ginzler, Nicole Fett, Susan Goodman, James O’Dell, Christian A. Pineau, Gabriela Schmajuk, Victoria P. Werth, Mark S. Link, Richard Kovacs
Journal: Arthritis & Rheumatology (2021)

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well‐established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)–prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID‐19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus‐based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long‐term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk–benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.
Kidney Transplant Patients with and Without COVID-19 Infection: Comparison of Baseline Characteristics and Outcomes
Authors: Omar K. Salameh, Muhammad Abdulbasit, Mujahed M. Dauleh, Ali M. Zebi, Gurwant Kaur, Nasrollah Ghahramani
Journal: Journal of the American Society of Nephrology (2021)

Salameh, Omar K.; Abdulbasit, Muhammad; Dauleh, Mujahed M.; Zebi, Ali M.; Kaur, Gurwant; Ghahramani, Nasrollah Author Information
hnRNPU in Sertoli cells cooperates with WT1 and is essential for testicular development by modulating transcriptional factors <i>Sox8/9</i>
Authors: Yujiao Wen, Xixiang Ma, Xiaoli Wang, Fengli Wang, Juan Dong, Yanqing Wu, Chunyu Lv, Kuan Liu, Yan Zhang, Zhibing Zhang, Shuiqiao Yuan
Journal: Theranostics (2021)

Background: Sertoli cells are essential regulators of testicular fate in the differentiating gonad; however, its role and underlying molecular mechanism of regulating testicular development in prepubertal testes are poorly understood. Although several critical regulatory factors of Sertoli cell development and function have been identified, identifying extrinsic factors that regulate gonocyte proliferation and migration processes during neonatal testis development remains largely unknown. Methods: We used the Sertoli cell-specific conditional knockout strategy (Cre/Loxp) in mice and molecular biological analyses (Luciferase assay, ChIP-qPCR, RNA-Seq, etc.) in vitro and in vivo to study the physiological roles of hnRNPU in Sertoli cells on regulating testicular development in prepubertal testes. Results: We identified a co-transcription factor, hnRNPU, which is highly expressed in mouse and human Sertoli cells and required for neonatal Sertoli cell and pre-pubertal testicular development. Conditional knockout of hnRNPU in murine Sertoli cells leads to severe testicular atrophy and male sterility, characterized by rapid depletion of both Sertoli cells and germ cells and failure of spermatogonia proliferation and migration during pre-pubertal testicular development. At molecular levels, we found that hnRNPU interacts with two Sertoli cell markers WT1 and SOX9, and enhances the expression of two transcriptional factors, Sox8 and Sox9, in Sertoli cells by directly binding to their promoter regions. Further RNA-Seq and bioinformatics analyses revealed the transcriptome-wide of key genes essential for Sertoli cell and germ cell fate control, such as biological adhesion, proliferation and migration, were deregulated in Sertoli cell-specific hnRNPU mutant testes. Conclusion: Our findings demonstrate an essential role of hnRNPU in Sertoli cells for prepubertal testicular development and testis microenvironment maintenance and define a new insight for our understanding of male infertility therapy.
USPSTF Approach to Addressing Sex and Gender When Making Recommendations for Clinical Preventive Services
Authors: Aaron B. Caughey, Alex H. Krist, Tracy A. Wolff, Michael J. Barry, Jillian T. Henderson, Douglas K. Owens, Karina W. Davidson, Melissa A. Simon, Carol M. Mangione
Journal: JAMA (2021)

Clinical preventive service recommendations from the US Preventive Services Task Force (USPSTF) are based on transparent, systematic, and rigorous methods that consider the certainty of the evidence and magnitude of net benefit. These guidelines aim to address the needs of diverse populations. Biological sex and gender identity are sources of diversity that are not often considered in studies of clinical preventive services that inform the recommendations, resulting in challenges when evaluating the evidence and communicating recommendations for persons in specific gender identification categories (man/woman/gender nonbinary/gender nonconforming/transgender). To advance its methods, the USPSTF reviewed its past recommendations that included the use of sex and gender terms, reviewed the approaches of other guideline-making bodies, and pilot tested strategies to address sex and gender diversity. Based on the findings, the USPSTF intends to use an inclusive approach to identify issues related to sex and gender at the start of the guideline development process; assess the applicability, variability, and quality of evidence as a function of sex and gender; ensure clarity in the use of language regarding sex and gender; and identify evidence gaps related to sex and gender. Evidence reviews will identify the limitations of applying findings to diverse groups from underlying studies that used unclear terminology regarding sex and gender. The USPSTF will use gender-neutral language when appropriate to communicate that recommendations are inclusive of people of any gender and will clearly state when recommendations apply to individuals with specific anatomy associated with biological sex (male/female) or to specific categories of gender identity. The USPSTF recognizes limited evidence to inform the preventive care of populations based on gender identity.
Drug exposure and susceptibility of second-line drugs correlate with treatment response in patients with multidrug-resistant tuberculosis: a multicentre prospective cohort study in China
Authors: Xubin Zheng, Lina Davies Forsman, Ziwei Bao, Yan Xie, Zhu Ning, Thomas Schön, Judith Bruchfeld, Biao Xu, Jan-Willem Alffenaar, Yi Hu
Journal: European Respiratory Journal (2021)

Background Understanding the impact of drug exposure and susceptibility on treatment response of multidrug-resistant tuberculosis (MDR-TB) will help to optimise treatment. This study aimed to investigate the association between drug exposure, susceptibility and response to MDR-TB treatment. Methods Drug exposure and susceptibility for second-line drugs were measured for patients with MDR-TB. Multivariate analysis was applied to investigate the impact of drug exposure and susceptibility on sputum culture conversion and treatment outcome. Probability of target attainment was evaluated. Random Forest and CART (Classification and Regression Tree) analysis was used to identify key predictors and their clinical targets among patients on World Health Organization-recommended regimens. Results Drug exposure and corresponding susceptibility were available for 197 patients with MDR-TB. The probability of target attainment was highly variable, ranging from 0% for ethambutol to 97% for linezolid, while patients with fluoroquinolones above targets had a higher probability of 2-month culture conversion (56.3% versus 28.6%; adjusted OR 2.91, 95% CI 1.42–5.94) and favourable outcome (88.8% versus 68.8%; adjusted OR 2.89, 95% CI 1.16–7.17). Higher exposure values of fluoroquinolones, linezolid and pyrazinamide were associated with earlier sputum culture conversion. CART analysis selected moxifloxacin area under the drug concentration–time curve/minimum inhibitory concentration (AUC 0–24h /MIC) of 231 and linezolid AUC 0–24h /MIC of 287 as best predictors for 6-month culture conversion in patients receiving identical Group A-based regimens. These associations were confirmed in multivariate analysis. Conclusions Our findings indicate that target attainment of TB drugs is associated with response to treatment. The CART-derived thresholds may serve as targets for early dose adjustment in a future randomised controlled study to improve MDR-TB treatment outcome.
TCT-308 Cardiogenic Shock–Associated Cardiorenal Syndrome Improves With the Use of Left Atrial Venous Arterial Extracorporeal Membrane Oxygenation (LAVA-ECMO)
Authors: Marvin Eng, Waleed Al-Darzi, Pedro Villablanca, Tiberi Frisoli, Pedro Engel Gonzalez, Michael Chiang, Mir Basir, Jennifer Cowger, Khaldoon Alaswad, Anand Prasad, William O'Neill
Journal: Journal of the American College of Cardiology (2021)
TCT-318 Sex Differences in Outcomes and Readmissions After Left Atrial Appendage Occlusion
Authors: Aaqib Malik, Jayakumar Sreenivasan, Syed Zaid, Wilbert Aronow, Alexandros Briasoulis, Syed Haidry, Gilbert Tang, Ryan Kaple, Hasan Ahmad
Journal: Journal of the American College of Cardiology (2021)
High-Normal Protein Intake Is Not Associated With Faster Renal Function Deterioration in Patients With Type 2 Diabetes: A Prospective Analysis in the DIALECT Cohort
Authors: Milou M. Oosterwijk, Dion Groothof, Gerjan Navis, Stephan J.L. Bakker, Gozewijn D. Laverman
Journal: Diabetes Care (2021)

To study the prospective association between dietary protein intake and renal function deterioration in patients with type 2 diabetes (T2D).Prospective analyses were performed in data of 382 patients of the Diabetes and Lifestyle Cohort Twente (DIALECT) study. Dietary protein intake was determined by the Maroni equation from 24-h urinary urea excretion. Renal function deterioration was defined as need for renal replacement therapy or a persistent increase of ≥50% in serum creatinine. Cox proportional hazards models were used to calculate hazard ratios (HRs) for the association between dietary protein intake and renal function deterioration. Threshold levels represent the dietary protein intake at which there was a significantly increased and reduced hazard of renal function deterioration.Renal function deterioration occurred in 53 patients (14%), with a median follow-up duration of 6 (interquartile range 5-9) years. Mean dietary protein intake was 91 ± 27 g/day (1.22 ± 0.33 g/kg ideal body weight/day). Dietary protein intake was inversely associated with renal function deterioration (HR 0.62 [95% CI 0.44-0.90]). Patients with an intake <92 g/day had an increased hazard for renal function deterioration (HR 1.44 [95% CI 1.00-2.06]), while patients with an intake >163 g/day had a decreased hazard for renal function deterioration (HR 0.42 [95% CI 0.18-1.00]). Regarding dietary protein intake per kilogram body weight, patients with an intake <1.08 g/kg/day had an increased hazard for renal function deterioration (HR 1.63 [95% CI 1.00-2.65]).In patients with T2D, unrestricted dietary protein intake was not associated with an increased hazard of renal function deterioration. Therefore, substituting carbohydrates with dietary protein is not contraindicated as a part of T2D management, although it may have a positive effect on body weight while minimizing loss of muscle mass.
SARS-CoV-2 vaccine uptake in a multi-ethnic UK healthcare workforce: A cross-sectional study
Authors: Christopher A. Martin, Colette Marshall, Prashanth Patel, Charles Goss, David R. Jenkins, Claire Ellwood, Linda Barton, Arthur Price, Nigel J. Brunskill, Kamlesh Khunti, Manish Pareek
Journal: PLoS Medicine (2021)

Healthcare workers (HCWs) and ethnic minority groups are at increased risk of COVID-19 infection and adverse outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is now available for frontline UK HCWs; however, demographic/occupational associations with vaccine uptake in this cohort are unknown. We sought to establish these associations in a large UK hospital workforce.We conducted cross-sectional surveillance examining vaccine uptake amongst all staff at University Hospitals of Leicester NHS Trust. We examined proportions of vaccinated staff stratified by demographic factors, occupation, and previous COVID-19 test results (serology/PCR) and used logistic regression to identify predictors of vaccination status after adjustment for confounders. We included 19,044 HCWs; 12,278 (64.5%) had received SARS-CoV-2 vaccination. Compared to White HCWs (70.9% vaccinated), a significantly smaller proportion of ethnic minority HCWs were vaccinated (South Asian, 58.5%; Black, 36.8%; p < 0.001 for both). After adjustment for age, sex, ethnicity, deprivation, occupation, SARS-CoV-2 serology/PCR results, and COVID-19-related work absences, factors found to be negatively associated with vaccine uptake were younger age, female sex, increased deprivation, pregnancy, and belonging to any non-White ethnic group (Black: adjusted odds ratio [aOR] 0.30, 95% CI 0.26-0.34, p < 0.001; South Asian: aOR 0.67, 95% CI 0.62-0.72, p < 0.001). Those who had previously had confirmed COVID-19 (by PCR) were less likely to be vaccinated than those who had tested negative. Limitations include data being from a single centre, lack of data on staff vaccinated outside the hospital system, and that staff may have taken up vaccination following data extraction.Ethnic minority HCWs and those from more deprived areas as well as younger staff and female staff are less likely to take up SARS-CoV-2 vaccination. These findings have major implications for the delivery of SARS-CoV-2 vaccination programmes, in HCWs and the wider population, and should inform the national vaccination programme to prevent the disparities of the pandemic from widening.
RNA and Protein Delivery by Cell‐Secreted and Bioengineered Extracellular Vesicles
Authors: Bryan Z. Wang, Lori J. Luo, Gordana Vunjak‐Novakovic
Journal: Advanced Healthcare Materials (2021)

Extracellular vesicles (EVs) are carriers of biological signals through export and delivery of RNAs and proteins. Of increasing interest is the use of EVs as a platform for delivery of biomolecules. Preclinical studies have effectively used EVs to treat a number of diseases. Uniquely, endogenous machinery within cells can be manipulated in order to produce desirable loading of cargo within secreted EVs. In order to inform the development of such approaches, an understanding of the cellular mechanisms by which cargo is sorted to EVs is required. Here, the current knowledge of cargo sorting within EVs is reviewed. Here is given an overview of recent bioengineering approaches that leverage these advances. Methods of externally manipulating EV cargo are also discussed. Finally, a perspective on the current challenges of EVs as a drug delivery platform is offered. It is proposed that standardized bioengineering methods for therapeutic EV preparation will be required to create a well-defined clinical product.
TCT-130 Initial Results From the VECTOR-HF Trial—A System for Remote Left Atrial Pressure Monitoring for Patients With Heart Failure
Authors: Leor Perl, David Meerkin, Domenico D’Amario, Binyamin Ben Avraham, Tal Hasin, Hüseyin Ince, Sebastian Feickert, Ulrich Schaefer, Horst Sievert, Francisco Leyva, Zachary Whinnett, Carlo Di Mario, Michael Jonas, Oren Caspi, Oran Koren, William Abraham, Ran Kornowski, Filippo Crea
Journal: Journal of the American College of Cardiology (2021)
What it takes to become an orthopaedic surgeon: A comparison of orthopaedic surgical training programmes in 10 countries focusing on structure and fellowship requirements
Authors: Johanna Ludwig, Rune Bruhn Jakobsen, Yann Philippe Charles, Julia Seifert, Ian Incoll, Melissa Lillian Wood, Deovrat Parmar, Richard Canter
Journal: International Journal of Surgery (2021)
TCT-413 Outcomes of Adults With Severe Aortic Stenosis Undergoing Elective Versus Urgent or Emergent Transcatheter Aortic Valve Replacement Within an Integrated Health Care Delivery System
Authors: Justin Slade, Andrew Ambrosy, Thomas Leong, Sue Sung, Ivy Ku, Edward McNulty, Andrew Rassi, Alan Go, Jacob Mishell
Journal: Journal of the American College of Cardiology (2021)
제 7 차 춘계학술대회 초록집 : 구연 ; 간경변에서 발생한 흉막유출의 임상적 분석 - 간성 수흉 및 특발성 세균성 농흉을 중심으로 -
Authors: 신현덕, 송일한, 기명주, 허재형, 남승우, 김정원, 임창영, 노임환
Journal: Clinical and Molecular Hepatology (2001)
TCT-153 Circumferential Tricuspid Annuloplasty With the New-Generation Cardiac Implants Percutaneous Ring Annuloplasty System in a Beating Human Cadaver Heart Biosimulator
Authors: Yanping Cheng, Andreas Hueske, Nimrod Meller, Torsten Vahl, Juan Granada, Grzegorz Kaluza, Genghua Yi
Journal: Journal of the American College of Cardiology (2021)
Synergistic photothermal cancer immunotherapy by Cas9 ribonucleoprotein-based copper sulfide nanotherapeutic platform targeting PTPN2
Authors: Tao Yan, Kaiyong Yang, Chao Chen, Zhiruo Zhou, Peiliang Shen, Yuanyuan Jia, Yu Xue, Zhenyu Zhang, Xu Shen, Xin Han
Journal: Biomaterials (2021)