tbuckley/cabot-search huggingface dataset:
Abstract 15590: Genetic Testing and Cardiac Magnetic Resonance Imaging Results Improve Precision Stratification in Dilated Cardiomyopathy
Authors: Ravi Amin, Richard Jones, Daniel Hammersley, sabiha gati, Zohya Khalique, Batool Almogheer, Dudley J Pennell, Antonis Pantazis, John Baksi, Sanjay K Prasad, Brian Halliday
Journal: Circulation (2020)

Introduction: Dilated cardiomyopathy (DCM) has a heterogenous aetiology. Precise disease stratification enabling personalised therapy may be key to improving management. Genetic testing and cardiac magnetic resonance (CMR) may help stratify the cause of DCM. Hypothesis: Adding genetic testing and CMR to routine tests will improve confidence and reproducibility in DCM stratification and, in turn, guide management. Methods: Case profiles for 60 consecutive patients with DCM were sent to 4 independent experts. Using routinely available clinical information, they were asked to determine the aetiology of the phenotype, based on the classification in the ESC Position Statement on DCM, and record their confidence (score 1-3) in the diagnosis. This was repeated after the addition of genetic testing and CMR results in a step-wise manner. Clinicians were also asked whether they would make changes to patient management. Results: Overall, 4 physicians reviewed 60 cases, giving 240 responses. Adding genetic testing and CMR resulted in changes to disease stratification ( Table 1 ). The most common change was from idiopathic to genetic DCM, following the identification of pathogenic or likely pathogenic variants in 13 cases. Confidence scores improved with the addition of genetic testing and CMR results (routine 1.69±0.53; routine &amp; genetic 1.93±0.61, p&lt;0.0005; routine, genetic &amp; CMR 2.26±0.69, p&lt;0.0005). Adding genetic testing and CMR led to changes in management, with family screening the most common. Where LMNA or DSP variants were identified (n=3, 5.0%), new recommendations for device therapy were made. Adding genetic and CMR data improved interobserver agreement in stratification (routine κ=0.40; routine &amp; genetic κ=0.66; routine, genetic &amp; CMR κ=0.68). Conclusion: Adding genetic testing and CMR to routine tests changed how DCM was stratified, improved confidence and interobserver variability in making this diagnosis, and subsequently, directed management.
Abstract 16357: Application of the H2FPEF-score in Pulmonary Arterial Hypertension: Insights From the Amsterdam UMC PAH-cohort
Authors: Azar Kianzad, Frances S De Man, Lucas R Celant, anton vonk noordegraaf, M M Handoko, Harm Bogaard
Journal: Circulation (2020)

Introduction: Newly diagnosed idiopathic pulmonary arterial hypertension (PAH) patients increasingly have features of patients with heart failure with preserved ejection fraction (HFpEF). These so-called “atypical” PAH patients can be identified using the H2FPEF-score (Reddy, Circulation 2018). This patient group is often excluded from clinical trials, and it is therefore unclear whether they respond similarly to PAH-specific medication. Aim: To assess baseline characteristics and treatment response of patients diagnosed with PAH stratified by the H2FPEF-score. Methods: A retrospective analysis of 253 treatment naïve PAH-patients who underwent diagnostic right heart catheterization at baseline. Groups were compared with ANOVA, post-hoc pairwise t-tests with Bonferroni correction and multivariate Cox proportional hazards analysis. Results: This cohort included 58 (23%) patients with a low (≤1), 159 (63%) patients with an intermediate (2-5) and 36 (14%) patients with a high (≥6) H2FPEF-score. Patients with a high H2FPEF-score were older and more often male, used more diuretics, had more comorbidities and had more often PAH with severely impaired diffusion capacity compared to patients with a low H2FPEF-score. In addition, patients with a high H2FPEF-score had a significantly lower cardiac index, mixed venous blood gas, oxygen saturation and 6-minute walk distance (6MWD) compared to patients with a low H2FPEF-score. A high H2FPEF-score was associated with worse survival despite correcting for confounders (HR 2.99, 95% CI 1.53-5.84, Fig.1 A). Despite potential survival bias, at 1-year follow-up 6MWD (Fig.1 B) significantly improved in patients with a low and intermediate H2FPEF-score, but did not change in patients with a high H2FPEF-score (interaction p-value&lt; 0.001). Conclusions: A high H2FPEF-score is associated with worse survival in PAH. Also, no improvement in 6MWD was observed in patients with a high H2FPEF-score only.
Abstract 14927: Effects of Low Intensity Resistance Exercise Under Kaatsu Condition on Skeletal Muscle Size and Its Safety inCardiovascular Surgery Patients
Authors: ogawa hironaga, IKUKO SHIBASAKI, Hirotsugu Fukuda, Shigeru Toyoda, Azusa Uematsu, Tomohiro YASUDA, Teruo Inoue, Toshiaki Nakajima
Journal: Circulation (2020)

Introduction: Surgery for cardiovascular disease is often accompanied by sarcopenia and physical frailty, and improvement of muscle mass, muscle strength, and ADL, is often difficult only with cardiac rehabilitation using aerobic exercise. The resistance training under moderately restricted muscle blood flow, named as KAATSU, induces muscle hypertrophy and strengthens muscle through low intensity exercise. However, it remains uninvestigated whether KAATSU resistance training using low intensity load (KAATSU-RE) increases muscle strength, and induces hypertrophy in patients early after cardiovascular surgery. Hypothesis: To investigate the effects of KAATSU-RE on skeletal muscle strength, hypertrophy and its safety in patients early after cardiovascular surgery. Methods: Nine patients early after cardiac surgery were included in this study (seven males, age 54 ± 18 years, BMI 23.0 ± 3.7 kg/m 2 , AVR 5 cases, MVP 3, Bentall operation 1). The patients performed leg extension exercise (20~30% 1RM) under KAATSU condition two times/week for three months. Training started after 200 m walking early after the operation. Skeletal muscle mass index (SMI) was evaluated using bioelectrical impedance analysis (BIA). The anterior mid-thigh thickness (MTH) was measured using B mode transverse ultrasound images. Physical functions (isometric knee extension peak torque, handgrip strength, and walking speed) were also measured at three points, i.e. baseline (before operation), ~7 days early after operation, and ~3 months after the training. Results: SMI and MTH decreased significantly from 7 ± 1.1, and 2.5 ± 0.4 cm preoperatively to 6.7 ± 1.0, and 2.2 ± 0.3 cm approximately 1 week after surgery. Approximately 3 months after the training, they increased significantly to 7.6 ± 0.8 and 3 ± 0.4 cm. During the rehabilitation period, hemodynamic deterioration and side effects including subcutaneous hemorrhage were not observed, and all the patients completely finished the study. Conclusions: These results suggest that KAATSU training safely increased muscle mass in patients in the early perioperative period of cardiovascular surgery. KAATSU training appears to be a promising and effective method for cardiac rehabilitation in patients with cardiovascular surgery.
Enhancing CAR T Cell Anti-Tumor Efficacy through Secreted Single Chain Variable Fragment (scFv) Immune Checkpoint Blockade
Authors: Sarwish Rafiq, Hollie J. Jackson, Oladapo Yeku, Terence J Purdon, Dayenne G. van Leeuwen, Kevin J. Curran, Ryan N Ahmed, Grace D Cullen, Su Yan, Pei Wang, Jingyi Xiang, Cheng Liu, Renier J. Brentjens
Journal: Blood (2017)
Abstract 17200: Improving the Early Detection of Cardiac Amyloidosis: Experience From a Large Urban Academic Center
Authors: Valery S Effoe, Melvin R Echols, Fengxia Yan, Temidayo Abe, Anekwe Onwuanyi
Journal: Circulation (2020)

Introduction: Cardiac amyloidosis (CA) is associated with a poor prognosis and the condition is often overlooked or the diagnosis is delayed by an average of 2 years. With the availability of treatment, identifying patients early in the course of the disease could significantly improve outcomes associated with CA. We describe the characteristics of patients with suspected CA and factors associated with obtaining a 99m Technetium-pyrophosphate ( 99m Tc-PYP) scan. Methods: We systematically reviewed and abstracted data from electronic medical records of 199 patients at the Grady Memorial Hospital in Atlanta, Georgia, between January 2018 to October 2019. Eligible patients had an echocardiographic left ventricular posterior wall (LVPWd) or interventricular septal wall (IVSd) thickness in diastole ≥ 1.4 cm and no evidence of aortic stenosis. Descriptive analyses were performed using SAS 9.4. Results: Mean age of sample was 65 ± 13 years (96% blacks, 40% women). Over 72% had health insurance, 87% had an LV ejection fraction &gt; 50%, 52% had a diagnosis of heart failure (HF), and 31% had associated peripheral neuropathy. Fifty-nine (30%) patients had a 99m Tc-PYP scan, 10 had a cardiac MRI and only 1 had an endomyocardial biopsy. Of the 4 patients with confirmed CA, mean age was 79 ± 5 years, mean IVSd was 1.7 ± 02 cm and mean LV mass index was 184 ± 33. All 4 patients were black males, had a 99m Tc-PYP scan and 3/4 had health insurance. Table 1 compares characteristics of patients who received a 99m Tc-PYP scan with those who did not. Overall, age, sex, health insurance status, presence of HF and LVH were not associated with the odds of obtaining a 99m Tc-PYP scan. Conclusion: These preliminary results appear to demonstrate variability in diagnostic testing for CA among patients with similar demographic and bioclinical profiles. Understanding the reasons for these differences may be key in improving early testing and diagnosis of CA among our patient population.
Adaptable hydrogel with reversible linkages for regenerative medicine: Dynamic mechanical microenvironment for cells
Authors: Zongrui Tong, Lulu Jin, Joaquim Miguel Oliveira, Rui L. Reis, Qi Zhong, Zhengwei Mao, Changyou Gao
Journal: Bioactive Materials (2020)

Hydrogels are three-dimensional platforms that serve as substitutes for native extracellular matrix. These materials are starting to play important roles in regenerative medicine because of their similarities to native matrix in water content and flexibility. It would be very advantagoues for researchers to be able to regulate cell behavior and fate with specific hydrogels that have tunable mechanical properties as biophysical cues. Recent developments in dynamic chemistry have yielded designs of adaptable hydrogels that mimic dynamic nature of extracellular matrix. The current review provides a comprehensive overview for adaptable hydrogel in regenerative medicine as follows. First, we outline strategies to design adaptable hydrogel network with reversible linkages according to previous findings in supramolecular chemistry and dynamic covalent chemistry. Next, we describe the mechanism of dynamic mechanical microenvironment influence cell behaviors and fate, including how stress relaxation influences on cell behavior and how mechanosignals regulate matrix remodeling. Finally, we highlight techniques such as bioprinting which utilize adaptable hydrogel in regenerative medicine. We conclude by discussing the limitations and challenges for adaptable hydrogel, and we present perspectives for future studies.
Abstract 14181: Impact of Prehospital Mobile Cloud Electrocardiogram Transmission System to Reduce Door to Balloon Time and Onset to Recanalization Time in ST-elevation Myocardial Infarction
Authors: Motoko Kametani, Takashi Unoki, Daisuke Takagi, Yudai Tamura, Tomoko Nakayama, Yutaka Konami, Hiroto Suzuyama, Masayuki Inoue, Tetsuo Yufu, Kazuhisa Kodama, Eiji Taguchi, Tadashi Sawamura, Junichi Maehara, KOICHI NAKAO, Tomohiro Sakamoto
Journal: Circulation (2020)

Background: Guidelines strongly recommend patients with ST-elevation myocardial infarction (STEMI) receive timely mechanical reperfusion, defined as door-to-balloon time (DTBT) ≤90 minutes. Objective: To evaluate the impact of the prehospital mobile cloud ECG transmission system (C-ECG) on DTBT and mortality in patients with STEMI. Methods: On June 2018, eight mobile C-ECG systems (SCUNA®, MEHERGEN GROUP) were implemented into the Uki and Kamimashiki fire departments in Kumamoto, Japan. Within two years, 428 ECGs of patients complaining of chest pain, difficulty in breathing and any other symptom that the emergency staff deemed necessary were transmitted to our hospital. 119 patients were diagnosed with ACS, 93 received emergency CAG and 69 were diagnosed with STEMI. After excluding eight patients with onset to arrival over 24 hours, a total of 137 consecutive STEMI patients received emergency PCI during the study period. Among them, 68 received PCI during the pre-C-ECG period (Pre: from June 2016 to May 2018), whereas 69 were received during the post-C-ECG period (Post: June 2018 to May 2020). We compared the DTBT, Onset to Recanalization time (OTRT), and in-hospital mortality between the two periods. Results: There was no significant difference in age, gender, Killip classification, and number of diseased coronary lesion between the two periods. The door to Cath-Lab time (DTCT) and DTBT were significantly shorter in the post-C-ECG period compared to the pre-C-ECG period (Pre: 34 min [IQR; 23-44] vs. Post: 24 min [IQR; 18-38]; P=0.01, Pre: 66 min [IQR; 48-80] vs. Post: 49 min [IQR; 42-71]; P=0.02, respectively). Furthermore, OTRT was also significantly shorter in the post-C-ECG period compared to the pre-C-ECG period (Pre: 190 min [IQR; 137-343] vs. Post: 153 min [IQR; 110-247]; P=0.02). However, peak-CPK and in-hospital mortality were not significantly different between the two periods (Pre: 2254 IU/L [IQR; 1153-4257] vs. Post: 1985 IU/L [IQR; 740-4021]; P=0.2, Pre: 5.9% vs. Post: 4.4%; P=0.7, respectively). Conclusion: Prehospital mobile cloud ECG transmission system reduced not only the DTBT but also OTRT.
Abstract IA-19: Dissecting the immune complexity of pancreatic cancer survivors through team science
Authors: Vinod P. Balachandran
Journal: Cancer Research (2020)

Abstract The advent of next-generation genomic sequencing has heralded unprecedented insight into the complexity of the interactions between the immune system and cancer. These tools to capture the genomes, exomes, and transcriptomes of cells in cancers has revealed the diversity of cancer antigens, the T cells and receptors that recognize them, and the supporting cells and states that regulate these associations. What is evident from these efforts is not only the high-dimensionality of the cancer space, but also the need for specialized analytical skills and cross-disciplinary expertise outside of the traditional biological sciences to integrate these vast data. Pancreatic cancer survivors represent a unique cohort of immunologic outliers to apply these tools to glean greater insight into rules governing immune recognition of cancer. In this talk, I will discuss our efforts to use a team of investigators spanning medical, computational, physical, and biological sciences to identify the immunogenicity, and evolution of cancer neoantigens in these unique patients, and how this antigen recognition is regulated by other novel cells in the environment. Citation Format: Vinod P. Balachandran. Dissecting the immune complexity of pancreatic cancer survivors through team science [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-19.
Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition
Authors: Allison J. Greaney, Tyler N. Starr, Pavlo Gilchuk, Seth J. Zost, Elad Binshtein, Andrea N. Loes, Sarah K. Hilton, John Huddleston, Rachel Eguia, Katharine H.D. Crawford, Adam S. Dingens, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Paul W. Rothlauf, Zhuoming Liu, Sean P.J. Whelan, Robert H. Carnahan, James E. Crowe, Jesse D. Bloom
Journal: Cell Host & Microbe (2020)

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails—including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
Investigating the stress corrosion cracking of a biodegradable Zn-0.8 wt%Li alloy in simulated body fluid
Authors: Guan-Nan Li, Su-Ming Zhu, Jian-Feng Nie, Yufeng Zheng, Zhili Sun
Journal: Bioactive Materials (2020)

Stress corrosion cracking (SCC) may lead to brittle, unexpected failure of medical devices. However, available researches are limited to Mg-based biodegradable metals (BM) and pure Zn. The stress corrosion behaviors of newly-developed Zn alloys remain unclear. In the present work, we conducted slow strain rate testing (SSRT) and constant-load immersion test on a promising Zn-0.8 wt%Li alloy in order to investigate its SCC susceptibility and examine its feasibility as BM with pure Zn as control group. We observed that Zn-0.8 wt%Li alloy exhibited low SCC susceptibility. This was attributed to variations in microstructure and deformation mechanism after alloying with Li. In addition, both pure Zn and Zn-0.8 wt%Li alloy did not fracture over a period of 28 days during constant-load immersion test. The magnitude of applied stress was close to physiological condition and thus, we proved the feasibility of both materials as BM.
In type 2 diabetes, GLP-1 RA plus SGLT2 inhibitor vs. either drug alone reduces HbA<sub>1c</sub> and SBP and may reduce body weight
Authors: Michael Tanner
Journal: Annals of Internal Medicine (2020)

Mantsiou C, Karagiannis T, Kakotrichi P, et al. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors as combination therapy for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2020;22:1857-68. 32476254.
Cryo-EM Structures of SARS-CoV-2 Spike without and with ACE2 Reveal a pH-Dependent Switch to Mediate Endosomal Positioning of Receptor-Binding Domains
Authors: Tongqing Zhou, Yaroslav Tsybovsky, Jason Gorman, Micah Rapp, Gabriele Cerutti, Gwo-Yu Chuang, Phinikoula S. Katsamba, Jared M. Sampson, Arne Schön, Jude Bimela, Jeffrey C. Boyington, Alexandra Nazzari, Adam S. Olia, Wei Shi, Mallika Sastry, Tyler Stephens, Jonathan Stuckey, I-Ting Teng, Pengfei Wang, Shuishu Wang, Baoshan Zhang, Richard A. Friesner, David D. Ho, John R. Mascola, Lawrence Shapiro, Peter D. Kwong
Journal: Cell Host & Microbe (2020)
Abstract PO-037: The conversion of induced pluripotent stem cells into cancer stem cells under pancreatic cancer microenvironment is inhibiting by lapatinib
Authors: Ghmkin Hassan, Masaharu Seno
Journal: Cancer Research (2020)

Abstract Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms that regulating CSCs are still under investigation. Our lab has established a novel method to produce CSCs from induced pluripotent stem cells (iPSCs) under cancer microenvironment using conditioned medium (CM) from cancer cell lines. By treatment iPSCs with CM, cells gain CSC characteristics. Here, we analyzed transcriptome from CSCs, which converted from iPSCs using CM from pancreatic ductal adenocarcinoma cells, and differentially expressed genes were identified. Pathway enrichment was analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG). Comparing iPSCs with CSCs converted from iPSCS showed elevated expression of genes related to ERBB2, ERBB3 and PI3K, while KEGG pathways revealed enrich of pathways known to be involved in cancer including ERBB2/ERBB3 signal pathway by conversion of iPSCs to CSCs. Inhibition of ERBB2 by lapatinib induced cell proliferation arrest and losing of tumorgenicity of converted cells. This study shows a potential involvement of ERBB2/ERBB3 pathway in CSCs generation and could lead to potentially new options for cancer treatment and prevention. Citation Format: Ghmkin Hassan, Masaharu Seno. The conversion of induced pluripotent stem cells into cancer stem cells under pancreatic cancer microenvironment is inhibiting by lapatinib [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-037.
Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome
Authors: Robert W. Davies, Ania M. Fiksinski, Elemi J. Breetvelt, Nigel M. Williams, Stephen R. Hooper, Thomas Monfeuga, Anne S. Bassett, Michael J. Owen, Raquel E. Gur, Bernice E. Morrow, Donna M. McDonald-McGinn, Ann Swillen, Eva W. C. Chow, Marianne van den Bree, Beverly S. Emanuel, Joris R. Vermeesch, Therese van Amelsvoort, Celso Arango, Marco Armando, Linda E. Campbell, Joseph F. Cubells, Stephan Eliez, Sixto Garcia-Minaur, Doron Gothelf, Wendy R. Kates, Kieran C. Murphy, Clodagh M. Murphy, Declan G. Murphy, Nicole Philip, Gabriela M. Repetto, Vandana Shashi, Tony J. Simon, Damiàn Heine Suñer, Stefano Vicari, Stephen W. Scherer, Carrie E. Bearden, Jacob A. S. Vorstman
Journal: Nature Medicine (2020)
Navigating the crowd: visualizing coordination between genome dynamics, structure, and transcription
Authors: Haitham A. Shaban, Roman Barth, Kerstin Bystricky
Journal: Genome biology (2020)

Abstract The eukaryotic genome is hierarchically structured yet highly dynamic. Regulating transcription in this environment demands a high level of coordination to permit many proteins to interact with chromatin fiber at appropriate sites in a timely manner. We describe how recent advances in quantitative imaging techniques overcome caveats of sequencing-based methods (Hi-C and related) by enabling direct visualization of transcription factors and chromatin at high resolution, from single genes to the whole nucleus. We discuss the contribution of fluorescence imaging to deciphering the principles underlying this coordination within the crowded nuclear space in living cells and discuss challenges ahead.