tbuckley/cabot-search huggingface dataset:
Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation
Authors: Li Zhan, Joseph Sushil Rao, Nikhil Sethia, Michael Q. Slama, Zonghu Han, Diane Tobolt, Michael Etheridge, Quinn P. Peterson, Cari S. Dutcher, John C. Bischof, Erik B. Finger
Journal: Nature Medicine (2022)

Abstract Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provide high recovery, viability, function and scalability. Here, we achieve this goal in mouse, porcine, human and human stem cell (SC)-derived beta cell (SC-beta) islets by comprehensive optimization of cryoprotectant agent (CPA) composition, CPA loading and unloading conditions and methods for vitrification and rewarming (VR). Post-VR islet viability, relative to control, was 90.5% for mouse, 92.1% for SC-beta, 87.2% for porcine and 87.4% for human islets, and it remained unchanged for at least 9 months of cryogenic storage. VR islets had normal macroscopic, microscopic, and ultrastructural morphology. Mitochondrial membrane potential and adenosine triphosphate (ATP) levels were slightly reduced, but all other measures of cellular respiration, including oxygen consumption rate (OCR) to produce ATP, were unchanged. VR islets had normal glucose-stimulated insulin secretion (GSIS) function in vitro and in vivo. Porcine and SC-beta islets made insulin in xenotransplant models, and mouse islets tested in a marginal mass syngeneic transplant model cured diabetes in 92% of recipients within 24–48 h after transplant. Excellent glycemic control was seen for 150 days. Finally, our approach processed 2,500 islets with &gt;95% islets recovery at &gt;89% post-thaw viability and can readily be scaled up for higher throughput. These results suggest that cryopreservation can now be used to supply needed islets for improved transplantation outcomes that cure diabetes.
Developing a minimum data set for older adult care homes in the UK: exploring the concept and defining early core principles
Authors: Jennifer Kirsty Burton, Arne Timon Wolters, Ann-Marie Towers, Liz Jones, Julienne Meyer, Adam Lee Gordon, Lisa Irvine, Barbara Hanratty, Karen Spilsbury, Guy Peryer, Stacey Rand, Anne Killett, Gizdem Akdur, Stephen Allan, Priti Biswas, Claire Goodman
Journal: The Lancet Healthy Longevity (2022)
The RIG-I–NRF2 axis regulates the mesenchymal stromal niche for bone marrow transplantation
Authors: Qi Lou, Kaizheng Jiang, Quanhui Xu, Lisha Yuan, Siyu Xie, Yuan Pan, Jian Chen, Jun Wu, Jiang Zhu, Linjia Jiang, Meng Zhao
Journal: Blood (2022)
SAFE AND EFFECTIVE LESION CROSSING IN BALLOON PULMONARY ANGIOPLASTY: THERAPEUTIC WINDOW FOR A NOVEL DEVICE
Authors: Sidney Perkins, Miguel L. Funes, Daniel Cheah, David Gordon, Jonathan Haft, David Williams, Vallerie V. McLaughlin, Victor Moles, Prachi Agarwal, Thomas Cascino, Albert Shih, Vikas Aggarwal
Journal: Journal of the American College of Cardiology (2022)
ACUTE LIFE-THREATENING CARDIAC TAMPONADE WITH RIGHT HEART FAILURE DUE TO RUPTURE AND EXTRINSIC COMPRESSION OF A MATURE ANTERIOR MEDIASTINAL TERATOMA: IN 14-YEAR-OLD BOY
Authors: George De Santolo, Marianela Reinaga, Herman Rodríguez, Antonio Rios Fabra, Yoxsivell Limas, Lorelei Gorrin, Yoly Tarache, Luanne Milaidy Piamo, Pascual Carucci, Hildamari Atienza
Journal: Journal of the American College of Cardiology (2022)
Corrigendum to “Safety and efficacy of self-assembling bubble carriers stabilized with sodium dodecyl sulfate for oral delivery of therapeutic proteins” [Journal of Controlled Release, Volume 259, pp. 168–175, (2017), doi: 10.1016/j.jconrel.2016.12.018]
Authors: Po-Yen Lin, Er-Yuan Chuang, Yi-Hsuan Chiu, Hsin-Lung Chen, Kun-Ju Lin, Jyuhn-Huarng Juang, Ching-Hua Chiang, Fwu-Long Mi, Hsing-Wen Sung
Journal: Journal of Controlled Release (2022)
Endoscopic removal of a migrated esophageal covered self-expandable metal stent: the nylon loop pusher-assisted method
Authors: Yan Ou, Long Chen, Junxiu Li, Yan Ye, Zhiqian Chen, Lin Cai, Juan Liao
Journal: Endoscopy (2022)

Covered self-expandable metal stents (SEMSs) can migrate, with an incidence of more than 30 % [1]. Various techniques for removal of migrated SEMSs have been reported [2] [3] [4]. However, the nylon loop pusher-assisted approach for removal of a distally migrated SEMS has not been reported previously.
Abstract OT1-16-01: A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer
Authors: Hyo S Han, Mary Disis, Robert Wesolowski, Carla Fisher, Shipra Gandhi, Nancy Chan, William Gwin, Keerthi Gogineni, Rosemarie Mick, Christina Sierra Rodriguez, Deanna Hogue, Hien Liu, Ricardo Costa, Brian Czerniecki
Journal: Cancer Research (2022)

Abstract Background: HER2-positive breast cancer patients are commonly treated with neoadjuvant therapy including HER2-targeted therapy. Patients who have residual invasive disease have less favorable outcomes with an increased risk of recurrent disease than patients with complete pathologic response (pCR). It has also been observed that these non-pCR patients have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting the anti-HER-2 CD4 Th1 response using vaccines will increase interferon gamma production which we have shown is a potent inducer of apoptosis and senescence in HER2-positive breast cancer. This study will be evaluating safety and immunogenicity of two vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: This is a multi-center, phase 2, randomized study to determine the safety and tolerability of HER2 vaccines (DC1 and WOKVAC), assess immunogenicity, and evaluate recurrence free survival. Patients with HER2-positive early breast cancer (stage I-III) are eligible if they have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant chemotherapy plus HER2 -targeted therapy. Patients are randomly assigned in a 1:1 ratio to receive 1 of 2 adjuvant HER2 vaccines, either DC1 or WOKVAC for 1 year. A permuted-block randomization scheme was used with stratification according to residual cancer burden (RCB) (1+2 vs 3). The primary end points are safety and immunogenicity (immune response rate measured by ELISPOT). Each treatment arm will be assessed separately. Any statistical comparison between arms is purely exploratory, as this study is neither designed nor powered for comparative hypotheses. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune markers. The enrollment began in 2018 and we plan to accrue the total of 110 patients. ClinicalTrials.gov Identifier: NCT03384914 Citation Format: Hyo S Han, Mary Disis, Robert Wesolowski, Carla Fisher, Shipra Gandhi, Nancy Chan, William Gwin, Keerthi Gogineni, Rosemarie Mick, Christina Sierra Rodriguez, Deanna Hogue, Hien Liu, Ricardo Costa, Brian Czerniecki. A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-16-01.
Comparing Human Milk Antibody Response After 4 Different Vaccines for COVID-19
Authors: Hannah G. Juncker, Sien J. Mulleners, Esmée R. M. Coenen, Johannes B. van Goudoever, Marit J. van Gils, Britt J. van Keulen
Journal: JAMA Pediatrics (2022)

Comparing Human Milk Antibody Response After 4 Different Vaccines for COVID-19COVID-19 usually has a mild course in children; however, newborns and infants are more susceptible to severe disease. 1 Human milk is suggested to play an important role to protect against infections, mostly owing to disease-specific antibodies. 2 Antibodies against SARS-CoV-2 are present in the human milk of previously infected women, 3 as well as following vaccination with a SARS-CoV-2 vaccine, 4 and are capable of neutralizing the virus.Because maternal vaccination during lactation may protect not only the mother but also her breastfed infant, knowledge of its effect is important to guide health care workers and lactating women in decision-making regarding SARS-CoV-2 vaccination.Therefore, this study aims to compare the antibody response in human milk after vaccination with mRNA-based and vector-based vaccines.Methods | A total of 4 vaccines are available in the Netherlands: 2 mRNA-based vaccines (BNT162b2 developed by Pfizer-BioNTech and mRNA-1273 developed by Moderna) and 2 vector-based vaccines (AZD1222 developed by Oxford/ AstraZeneca and Ad26.COV2.S developed by Johnson & Johnson/Janssen).Lactating women who received full vaccination with 1 of these vaccines were eligible to participate in this prospective longitudinal study.Each participant collected 17 human milk samples over a period of 100 days.
Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non–small cell lung cancer
Authors: Erik Wennerberg, Sumit Mukherjee, Sheila Spada, Clarey Hung, Christopher J. Agrusa, Chuang Chen, Amanda Valeta-Magara, Nils-Petter Rudqvist, Samantha J. Van Nest, Mohamed K. Kamel, Abu Nasar, Navneet Narula, Vivek Mittal, Geoffrey J. Markowitz, Xi Kathy Zhou, Prasad S. Adusumilli, Alain C. Borczuk, Thomas E. White, Abdul G. Khan, Paul J. Balderes, Ivo C. Lorenz, Nasser Altorki, Sandra Demaria, Timothy E. McGraw, Brendon M. Stiles
Journal: Science Translational Medicine (2022)

Most patients with non–small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)–induced cell death (NICD) of P2X7 receptor (P2X7R)–expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono–adenosine 5′-diphosphate (ADP)–ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R + CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R + CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon blockade of the NAD + -degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell–dependent manner. This was associated with increased infiltration of activated P2X7R + CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies.
36P A point mutation replacing cysteine with arginine at position 382 (C382R) in the transmembrane domain of FGFR2 leads to response to FGF2-inhibitor pemigatinib in chemo-refractory intrahepatic cholangiocarcinoma
Authors: L.C. Hempel, C. Lapa, A. Gaumann, J. Veloso de Oliveira, J. Scheiber, P. Philipp, C. Oyarzun, S. Wesarg, S. Robert, D. Hempel
Journal: Annals of Oncology (2022)
SUCCESSFUL USE OF MITRACLIP FOR TREATMENT OF ACUTE MITRAL REGURGITATION DUE TO PAPILLARY MUSCLE RUPTURE: A CASE REPORT
Authors: Antonio Lewis, Alejandro Sanchez, Shruti Shettigar, Dave Heeransh, Manojna Nimmagadda, Jose Sleiman, Eduardo Javier Perez, Emad Hakemi, Craig R. Asher
Journal: Journal of the American College of Cardiology (2022)
OUTCOMES OF TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH CONCOMITANT MITRAL ANNULAR CALCIFICATION
Authors: Hassan Mehmood Lak, Sanchit Chawla, Beni Verma, Taha Ahmed, Rama Dilip Gajulapalli, Ankit Agrawal, Sachin Kumar, Bindesh Ghimire, Feras Alkhalaileh, Mohamed M. Gad, Shashank Shekhar, Raunak M. Nair, Grant W. Reed, Gosta Pettersson, James Yun, Rishi Puri, Shinya Unai, Amar Krishnaswamy, Serge C. Harb, Samir R. Kapadia
Journal: Journal of the American College of Cardiology (2022)
Vascularized Lung Cancer Model for Evaluating the Promoted Transport of Anticancer Drugs and Immune Cells in an Engineered Tumor Microenvironment
Authors: Dasom Kim, Kyeong Seob Hwang, Eun U Seo, Suyeong Seo, Byung Chul Lee, Nakwon Choi, Jonghoon Choi, Hong Nam Kim
Journal: Advanced Healthcare Materials (2022)

The tumor microenvironment (TME) is the environment around the tumor, including blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix (ECM). Owing to its component interactions, the TME influences tumor growth and drug delivery in a highly complex manner. Although several vascularized cancer models are developed to mimic the TME in vitro, these models cannot comprehensively reflect blood vessel-tumor spheroid interactions. Here, a method for inducing controlled tumor angiogenesis by engineering the microenvironment is presented. The interstitial flow direction regulates the direction of capillary sprouting, showing that angiogenesis occurs in the opposite direction of flow, while the existence of lung fibroblasts affects the continuity and lumen formation of sprouted capillaries. The vascularized tumor model shows enhanced delivery of anticancer drugs and immune cells to the tumor spheroids because of the perfusable vascular networks. The possibility of capillary embolism using anticancer drug-conjugated liquid metal nanoparticles is investigated using the vascularized tumor model. This vascularized tumor platform can aid in the development of effective anticancer drugs and cancer immunotherapy.
<i>ZEB2</i> Shapes the Epigenetic Landscape of Atherosclerosis
Authors: Paul Cheng, Robert C. Wirka, Lee Shoa Clarke, Quanyi Zhao, Ramendra Kundu, Trieu Nguyen, Surag Nair, Disha Sharma, Hyun-jung Kim, Huitong Shi, Themistocles Assimes, Juyong Brian Kim, Anshul Kundaje, Thomas Quertermous
Journal: Circulation (2022)

Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci.
VARIATION IN SURVIVAL AFTER CARDIOPULMONARY ARREST IN CARDIAC CATHETERIZATION LABORATORIES IN THE UNITED STATES: INSIGHTS FROM GWTG - RESUSCITATION
Authors: Avnish Tripathi, Paul S. Chan, Mazen S. Albagdadi, Mohammad Saud Khan, Varunsiri Atti, Arti Saraswat, Glenn A. Hirsch, Sammy Elmariah, Douglas E. Drachman, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2022)
Ultrathin, elastic, and self-adhesive nanofiber bio-tape: An intraoperative drug-loading module for ureteral stents with localized and controlled drug delivery properties for customized therapy
Authors: Liheng Gao, Mingxi Xu, Wenshuo Zhao, Ting Zou, Fujun Wang, Jun Da, Yiwei Wang, Lu Wang
Journal: Bioactive Materials (2022)

During the postoperative management of urinary diseases, oral or intravenous administration of drugs and implanting ureteral stents are usually required, making localized drug delivery by ureteral stent a precise and effective medication strategy. In the traditional drug loading method, the drug was premixed in the implants in production lines and the versatility of drugs was restricted. However, the complex situation in the urinary system fails the possibility of finding a "one fits all" medication plan, and the intraoperative drug-loading of implants is highly desired to support customized therapy. Here, we designed an ultrathin (8 μm), elastic, and self-adhesive nanofiber bio-tape (NFBT) that can easily encapsulate drugs on the stent surface for controllable localized drug delivery. The NFBT exhibited high binding strength to a ureteral stent, a sustained release over 7 d in PBS for hydrophilic drug, and a zero-order release curve over 28 days for the hydrophobic drug nitrofurantoin (NFT). Further in vivo experiments using a porcine ureteral tract infection model demonstrated that NFBT loaded with NFT could significantly reduce the bacterial concentration in urine. The total amount of NFT delivered by the NFBT was about 2.68 wt% of the recommended dose for the systemic administration.
Abstract P5-17-10: Anti-progranulin (GP88) antibody AG01 inhibitory effect on the growth of triple negative breast cancer cells
Authors: Ginette Serrero, Rupa Guha, Jianping Dong, Binbin Yue
Journal: Cancer Research (2022)

Abstract Background: Triple negative breast cancer (TNBC) is characterized by invasiveness and short survival. Identifying novel TNBC targeted therapies to potentiate standard of care (SOC) therapy, is an unmet need. Progranulin (PGRN/GP88) is a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC). PGRN/GP88 tissue expression is an independent prognostic factor of recurrence while elevated serum PGRN/GP88 level is associated with poor outcomes such as progression of disease and shortened survival. Since PGRN/GP88 expression is elevated in 30% TNBC, we investigated the effect of inhibiting PGRN/GP88 effect on the proliferation and tumor growth of triple negative breast cancer cells. Methods: For this purpose, we have developed a neutralizing anti-human PGRN/GP88 monoclonal antibody AG01 and examined its effect on the proliferation, migration, signaling pathway activation and biomarker expression of two TNBC cell lines MDA-MB-231 and HS578-T expressing PGRN/GP88, both in vitro and in vivo. Results: The inhibition of PGRN/GP88 action by AG01 treatment reduced proliferation and migration in a dose-and time-dependent fashion in MDA-MB-231 and HS578-T cells. Western blot analysis showed decreased expression of phosphorylated protein kinases p-Src, p-AKT and p-ERK involved in proliferation and survival upon AG01 treatment for both cell lines. Transwell assay showed that AG01 treatment inhibited migration and invasion in a dose-dependent fashion. Microarray analysis of several oncoproteins in cells treated with AG01 or control antibody demonstrated the inhibition of the expression of several markers of migration and angiogenesis. In vivo xenograft studies with MDA-MB-231 cells injected in athymic nude mice showed that AG01 treatment inhibited tumor growth as well as Ki67 expression, mitotic index and microvessel counts when compared to antibody control treated mice. In vivo dose response of AG01 in MDA-MB-231 tumor bearing mice will be provided. Conclusion: TNBC is a disease with poor prognosis in need of novel targeted therapeutic solutions. PGRN/GP88 represents a therapeutic target for TNBC with two companion diagnostics (tissue test and ELISA to measure GP88 circulating levels). Blocking PGRN/GP88 with AG01 antibody treatment will provide novel targeted therapeutic option for TNBC which could address the issue of toxicity, and unresponsiveness associated with SOC. This work is supported by a grant CA 224718 from the National Cancer Institute to GS. Citation Format: Ginette Serrero, Rupa Guha, Jianping Dong, Binbin Yue. Anti-progranulin (GP88) antibody AG01 inhibitory effect on the growth of triple negative breast cancer cells [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-17-10.
ACETYLCHOLINESTERASE INHIBITION AS A NEW THERAPEUTIC TARGET AGAINST TRASTUZUMAB-INDUCED CARDIOTOXICITY VIA ATTENUATING CARDIAC MITOCHONDRIAL OXIDATIVE STRESS AND INFLAMMATION IN RATS
Authors: Thawatchai Khuanjing, Benjamin Ongnok, Nanthip Prathumsap, Apiwan Arinno, Chayodom Maneechote, Titikorn Chunchai, Busarin Arunsak, Siriporn Chattipakorn, Nipon Chattipakorn
Journal: Journal of the American College of Cardiology (2022)
GLP-1RAs for Ischemic Stroke Prevention in Patients With Type 2 Diabetes Without Established Atherosclerotic Cardiovascular Disease
Authors: Yi-Sun Yang, Hsin-Hung Chen, Chien-Ning Huang, Chung Y. Hsu, Kai-Chieh Hu, Chia-Hung Kao
Journal: Diabetes Care (2022)

OBJECTIVE We assessed the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on ischemic stroke prevention in the Asian population with type 2 diabetes (T2D) without established cardiovascular disease. RESEARCH DESIGN AND METHODS This retrospective cohort study examined data obtained from the Taiwan National Health Insurance Research Database for the period from 1998 to 2018. The follow-up ended upon the occurrence of hospitalization for ischemic stroke. The median follow-up period was 3 years. The effect of GLP-1RA exposure time on the development of hospitalization for ischemic stroke was assessed. RESULTS The GLP-1RA and non–GLP-1RA user groups both included 6,534 patients. Approximately 53% of the patients were women, and the mean age was 49 ± 12 years. The overall risk of ischemic stroke hospitalization for GLP-1RA users was not significantly lower than that for GLP-1RA nonusers (adjusted hazard ratio [HR] 0.69 [95% CI 0.47–1.00]; P = 0.0506), but GLP-1RA users with a &amp;gt;251-day supply during the study period had a significantly lower risk of ischemic stroke hospitalization than GLP-1RA nonusers (adjusted HR 0.28 [95% CI 0.11–0.71]). Higher cumulative dose of GLP-1 RAs (&amp;gt;1,784 mg) was associated with significantly lower risk of ischemic stroke hospitalization. The subgroup analyses defined by various baseline features did not reveal significant differences in the observed effect of GLP-1RAs. CONCLUSIONS Longer use and higher dose of GLP-1 RAs were associated with a decreased risk of hospitalization for ischemic stroke among Asian patients with T2D who did not have established atherosclerotic cardiovascular diseases, but who did have dyslipidemia or hypertension.
ACUTE CORONARY SYNDROME IN A PATIENT WITH BEHCET’S DISEASE AFTER MODIFIED BENTALL PROCEDURE
Authors: Chayapol Limtrakul, Chayakorn Udomchanya, Wiwun Tungsubutra, Vithaya Chaithiraphan, Decho Jakrapanichakul
Journal: Journal of the American College of Cardiology (2022)