tbuckley/cabot-search huggingface dataset:
Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy
Authors: M. J. Mansilla, S. Presas-Rodríguez, A. Teniente-Serra, I. González-Larreategui, B. Quirant-Sánchez, F. Fondelli, N. Djedovic, D. Iwaszkiewicz-Grześ, K. Chwojnicki, Đ. Miljković, P. Trzonkowski, C. Ramo-Tello, E. M. Martínez-Cáceres
Journal: Cellular and Molecular Immunology (2021)

Abstract Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatments as well as different cell-based therapies that have been proposed to restore homeostasis in MS patients (tolerogenic dendritic cells, regulatory T cells, mesenchymal stem cells, and vaccination with T cells). Data collected from preclinical studies performed in the experimental autoimmune encephalomyelitis (EAE) model of MS in animals, in vitro cultures of cells from MS patients and the initial results of phase I/II clinical trials are analyzed to better understand which parameters are relevant for obtaining an efficient cell-based therapy for MS.
Reply to K. Yokoyama et al
Authors: Christopher W. Noel, Rinku Sutradhar, Haoyu Zhao, Victoria Delibasic, David Forner, Jonathan C. Irish, John Kim, Zain Husain, Alyson Mahar, Irene Karam, Danny J. Enepekides, Kelvin K. W. Chan, Simron Singh, Julie Hallet, Natalie G. Coburn, Antoine Eskander
Journal: Journal of Clinical Oncology (2021)
Translating complexity and heterogeneity of pancreatic tumor: 3D in vitro to in vivo models
Authors: Marcel A. Heinrich, Ahmed M.R.H. Mostafa, Jennifer P. Morton, Lukas J.A.C. Hawinkels, Jai Prakash
Journal: Advanced Drug Delivery Reviews (2021)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive type of cancer with an overall survival rate of less than 7–8%, emphasizing the need for novel effective therapeutics against PDAC. However only a fraction of therapeutics which seemed promising in the laboratory environment will eventually reach the clinic. One of the main reasons behind this low success rate is the complex tumor microenvironment (TME) of PDAC, a highly fibrotic and dense stroma surrounding tumor cells, which supports tumor progression as well as increases the resistance against the treatment. In particular, the growing understanding of the PDAC TME points out a different challenge in the development of efficient therapeutics – a lack of biologically relevant in vitro and in vivo models that resemble the complexity and heterogeneity of PDAC observed in patients. The purpose and scope of this review is to provide an overview of the recent developments in different in vitro and in vivo models, which aim to recapitulate the complexity of PDAC in a laboratory environment, as well to describe how 3D in vitro models can be integrated into drug development pipelines that are already including sophisticated in vivo models. Hereby a special focus will be given on the complexity of in vivo models and the challenges in vitro models face to reach the same levels of complexity in a controllable manner. First, a brief introduction of novel developments in two dimensional (2D) models and ex vivo models is provided. Next, recent developments in three dimensional (3D) in vitro models are described ranging from spheroids, organoids, scaffold models, bioprinted models to organ-on-chip models including a discussion on advantages and limitations for each model. Furthermore, we will provide a detailed overview on the current PDAC in vivo models including chemically-induced models, syngeneic and xenogeneic models, highlighting hetero- and orthotopic, patient-derived tissues (PDX) models, and genetically engineered mouse models. Finally, we will provide a discussion on overall limitations of both, in vitro and in vivo models, and discuss necessary steps to overcome these limitations to reach an efficient drug development pipeline, as well as discuss possibilities to include novel in silico models in the process.
PREVALENCE AND PROGNOSTIC IMPACT OF HIGH BLEEDING RISK STATUS IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION FOR LEFT MAIN CORONARY ARTERY DISEASE
Authors: Mauro Chiarito, Anastasios Roumeliotis, Davide Cao, David Power, samantha sartori, Zhongjie Zhang, Adam Reisman, Tafadzwa Mtisi, Matteo Nardin, Johny Nicolas, Hanbo Qiu, Ali Turfah, Gennaro Giustino, Ridhima Goel, Rishi Chandiramani, Giulio Stefanini, Prakash Krishnan, Nitin Barman, Joseph Sweeny, Usman Baber, Roxana Mehran, George Dangas, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2021)
Alternative splicing during mammalian organ development
Authors: Pavel V. Mazin, Philipp Khaitovich, Margarida Cardoso-Moreira, Henrik Kaessmann
Journal: Nature Genetics (2021)

Abstract Alternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.
Tissue-resident macrophages mediate neutrophil recruitment and kidney injury in shiga toxin-induced hemolytic uremic syndrome
Authors: Julia K. Lill, Stephanie Thiebes, Judith-Mira Pohl, Jenny Bottek, Nirojah Subramaniam, Robin Christ, Camille Soun, Faikah Gueler, Denise Zwanziger, Franziska Hoffmann, Ferdinand von Eggeling, Thilo Bracht, Barbara Sitek, Michael J. Hickey, Oliver Hofnagel, Daniel R. Engel
Journal: Kidney International (2021)
BODY FAT DISTRIBUTION AND REDUCED CORONARY ENDOTHELIAL FUNCTION IN PEOPLE LIVING WITH HIV
Authors: Erin Goerlich, Michael Schar, Shashwatee Bagchi, Patricia Barditch-Crovo, Gabriele Bonanno, Yohannes Afework, Valerie Streeb, Gary Gerstenblith, Robert Weiss, Allison Hays
Journal: Journal of the American College of Cardiology (2021)
Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals
Authors: Vibhu Parcha, Nirav Patel, Orlando M Gutierrez, Peng Li, Karen L Gamble, Kiran Musunuru, Kenneth B Margulies, Thomas P Cappola, Thomas J Wang, Garima Arora, Pankaj Arora
Journal: Journal of the American College of Cardiology (2021)
Diagnosis and Management of Stable Angina
Authors: Parag H. Joshi, James A. de Lemos
Journal: JAMA (2021)

<h3>Importance</h3> Nearly 10 million US adults experience stable angina, which occurs when myocardial oxygen supply does not meet demand, resulting in myocardial ischemia. Stable angina is associated with an average annual risk of 3% to 4% for myocardial infarction or death. Diagnostic tests and medical therapies for stable angina have evolved over the last decade with a better understanding of the optimal use of coronary revascularization. <h3>Observations</h3> Coronary computed tomographic angiography is a first-line diagnostic test in the evaluation of patients with stable angina due to higher sensitivity and comparable specificity compared with imaging-based stress testing. Moreover, coronary computed tomographic angiography allows detection of nonobstructive atherosclerosis that would not be identified with other noninvasive imaging modalities, improving risk assessment and potentially triggering more appropriate allocation of preventive therapies. Novel therapies treating lipids (proprotein convertase subtilisin/kexin type 9 inhibitors, ezetimibe, and icosapent ethyl) and type 2 diabetes (sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists) have improved cardiovascular outcomes in patients with stable ischemic heart disease when added to usual care. Randomized clinical trials showed no improvement in the rates of mortality or myocardial infarction with revascularization (largely by percutaneous coronary intervention) compared with optimal medical therapy alone, even in the setting of moderate to severe ischemia. In contrast, revascularization provides a meaningful benefit on angina and quality of life compared with antianginal therapies. Measures of the effect of angina on a patient's quality of life should be integrated into the clinic encounter to assist with the decision to proceed with revascularization. <h3>Conclusions and Relevance</h3> For patients with stable angina, emphasis should be placed on optimizing lifestyle factors and preventive medications such as lipid-lowering and antiplatelet agents to reduce the risk for cardiovascular events and death. Antianginal medications, such as β-blockers, nitrates, or calcium channel blockers, should be initiated to improve angina symptoms. Revascularization with percutaneous coronary intervention should be reserved for patients in whom angina symptoms negatively influence quality of life, generally after a trial of antianginal medical therapy. Shared decision-making with an informed patient is important for effective treatment of stable angina.
SHOCKWAVE INTRAVASCULAR LITHOTRIPSY FOR CALCIFIED CORONARY LESIONS: A TWO YEAR RETROSPECTIVE SINGLE CENTRE REVIEW
Authors: Hani Muradagha, Kevin Millar, Bing Wei Thaddeus Soh, Padraig O Drisceoil, Rory Gallen, Majid Al Maini, Khalid Ahmed, Samer Arnous, Thomas Kiernan
Journal: Journal of the American College of Cardiology (2021)
OUTCOMES OF TRANSCATHETER VS. SURGICAL AORTIC VALVE REPLACEMENT IN OCTOGENARIANS WITH HEART FAILURE
Authors: Yasar Sattar, Bachar Ahmad, Junaid Arshad, Uneza Khawaja, Abdul-Rahman M. Suleiman, Zaher Hakim, Omar E. Ali, Delair Gardi, Ghaith Alhatemi, Fahed Darmoch, Waqas Ullah, Anoosha Mehmood, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2021)
Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours: a multicentre, open-label, randomised controlled trial
Authors: Min Wang, Dewei Li, Rufu Chen, Xiaobing Huang, Jing Li, Yahui Liu, Jianhua Liu, Wei Cheng, Xuemin Chen, Wenxing Zhao, Jingdong Li, Zhijian Tan, Heguang Huang, Deyu Li, Feng Zhu, Tingting Qin, Jingdong Ma, Guangsheng Yu, Baoyong Zhou, Shangyou Zheng, Yichen Tang, Wei Han, Lingyu Meng, Jianji Ke, Feng Feng, Botao Chen, Xinmin Yin, Weibo Chen, Hongqin Ma, Jian Xu, Yifeng Liu, Ronggui Lin, Yadong Dong, Yahong Yu, Jun Liu, Hang Zhang, Renyi Qin
Journal: The Lancet. Gastroenterology & hepatology (2021)
Is PTSD overdiagnosed?
Authors: John Tully, Dinesh Bhugra, Stephanie J Lewis, Gerard Drennan, Sarah Markham
Journal: BMJ (2021)

Some of the burgeoning rates of PTSD diagnosis are attributable to broadened disease definitions, say <b>John Tully</b> and <b>Dinesh Bhugra</b>. But <b>Stephanie J Lewis</b>, <b>Gerard Drennan</b>, and <b>Sarah Markham</b> argue that underdiagnosis, not overdiagnosis, may be the greater problem
DEP-induced ZEB2 promotes nasal polyp formation via epithelial-to-mesenchymal transition
Authors: Mingyu Lee, Suha Lim, Yi Sook Kim, Roza Khalmuratova, Seung-Hyun Shin, Iljin Kim, Hyun-Jik Kim, Dong-Young Kim, Chae-Seo Rhee, Jong-Wan Park, Hyun-Woo Shin
Journal: Journal of Allergy and Clinical Immunology (2021)
Sitosterolemia: A Rare Case with Broad Implications
Authors: Zed Seedat
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Sitosterolemia is an ultra-rare autosomal recessive dyslipidemia characterized by mutations in genes encoding the ATP-binding cassette (ABC) G5/8 transporters. We describe the case of a 20-month-old female presenting with xanthomas and serum low density lipoprotein cholesterol of 657 mg/dL. Diagnostic workup revealed a previously undescribed sitosterolemia-causing mutation. After elimination of dietary sterols and initiation of ezetimibe therapy, the patient’s xanthomas resolved, and serum low density lipoprotein cholesterol was reduced to 104 mg/dL. Importantly, pathologically elevated serum phytosterols were found in each of the proband’s heterozygous parents. Elevated phytosterols, an established cause of atherosclerosis, are typically unrevealed by standard lipid testing. As heterozygous mutations for ABCG5/8 are relatively common, this has implications for a broader population than the ultra-rare sitosterolemia cohort. Thus, insights gleaned from this case highlight underappreciated matters in the prevention of atherosclerotic disease in both heterozygous and homozygous carriers alike.
The Key Role of Nonpharmacologic Management of Cachexia in Persons With Advanced Illness
Authors: Aamna Kabani, Sydney M. Dy, Arjun Gupta
Journal: JAMA Internal Medicine (2021)

This Teachable Moment considers the psychological distress that anorexia and/or cachexia leads to in caregivers and patients with advanced illness, and how clinicians can help without using pharmacologic management.
Perspectives on metals-based radioimmunotherapy (RIT): moving forward
Authors: Jordan M White, Freddy E Escorcia, Nerissa T Viola
Journal: Theranostics (2021)

Radioimmunotherapy (RIT) is FDA-approved for the clinical management of liquid malignancies, however, its use for solid malignancies remains a challenge. The putative benefit of RIT lies in selective targeting of antigens expressed on the tumor surface using monoclonal antibodies, to systemically deliver cytotoxic radionuclides. The past several decades yielded dramatic improvements in the quality, quantity, recent commercial availability of alpha-, beta- and Auger Electron-emitting therapeutic radiometals. Investigators have created new or improved existing bifunctional chelators. These bifunctional chelators bind radiometals and can be coupled to antigen-specific antibodies. In this review, we discuss approaches to develop radiometal-based RITs, including the selection of radiometals, chelators and antibody platforms (i.e. full-length, F(ab')
PROGNOSTIC IMPLICATION OF PRE-CANNULATION CARDIAC ARREST IN PATIENTS UNDERGOING EXTRACORPOREAL MEMBRANE OXYGENATION FOR THE MANAGEMENT OF CARDIOGENIC SHOCK
Authors: Hoyle Lee Whiteside, Dustin Hillerson, Riley Coots, Ahmed Abdel-Latif, Vedant Gupta
Journal: Journal of the American College of Cardiology (2021)
National Estimates of CKD Prevalence and Potential Impact of Estimating Glomerular Filtration Rate Without Race
Authors: Vishal Duggal, I-chun Thomas, Maria E. Montez-Rath, Glenn M. Chertow, Manjula Kurella Tamura
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement The adjustment for Black race in equations to estimate GFR is controversial. We found that the prevalence of CKD among US Black adults would double if race adjustment were removed. The change could affect up to 40% of Black adults using common medications for which dose adjustments are recommended on the basis of kidney function. Accuracy of a prognostic model for kidney failure remained high without race adjustment, and was improved at higher levels of predicted risk. This study suggests that estimating GFR without race adjustment could lead to sizable changes in clinical care and population health strategies for Black adults. Background The implications of removing the adjustment for Black race in equations to eGFR on the prevalence of CKD and management strategies are incompletely understood. Methods We estimated changes in CKD prevalence and the potential effect on therapeutic drug prescriptions and prediction of kidney failure if race adjustment were removed from the CKD-EPI GFR estimating equation. We used cross-sectional and longitudinal data from adults aged ≥18 years in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2016, and the Veterans Affairs (VA) Health Care System in 2015. In the VA cohort, we assessed use of common medications that require dose adjustment on the basis of kidney function, and compared the prognostic accuracy of the Kidney Failure Risk Equation with versus without race adjustment of eGFR. Results The prevalence of CKD among Black adults increased from 5.2% to 10.6% in NHANES, and from 12.4% to 21.6% in the VA cohort after eliminating race adjustment. Among Black veterans, 41.0% of gabapentin users, 33.5% of ciprofloxacin users, 24.0% of metformin users, 6.9% of atenolol users, 6.6% of rosuvastatin users, and 5.8% of tramadol users were reclassified to a lower eGFR for which dose adjustment or discontinuation is recommended. Without race adjustment of eGFR, discrimination of the Kidney Failure Risk Equation among Black adults remained high and calibration was marginally improved overall, with better calibration at higher levels of predicted risk. Conclusions Removal of race adjustment from CKD-EPI eGFR would double the estimated prevalence of CKD among Black adults in the United States. Such a change is likely to affect a sizeable number of drug-dosing decisions. It may also improve the accuracy of kidney failure risk prediction among higher-risk Black adults.
NON-VITAMIN K ANTAGONISTS SHOULD BE PREFERRED OVER WARFARIN IN PATIENTS WITH ATRIAL FIBRILLATION AND BIOPROSTHETIC VALVES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rhanderson Cardoso, Caique M.P. Ternes, Leonardo Knijnik, Amanda Fernandes, Victoria N. Fernandez, Gustavo B. Justino, Andre d’Avila, Renato Lopes
Journal: Journal of the American College of Cardiology (2021)
SUCCESSFUL CONTINUATION OF PREGNANCY AND DELIVERY IN A PATIENT WITH COVID-19 COMPLICATED BY MULTISYSTEM INFLAMMATORY SYNDROME (MIS) AND CARDIOGENIC SHOCK
Authors: Linle Hou, Byung Joon Park, Avneet Singh, Sirish Vullaganti, Brian Lima, Gerin Stevens, Rajiv Jauhar, Evelina Grayver
Journal: Journal of the American College of Cardiology (2021)
Rapid and simple single-chamber nucleic acid detection system prepared through nature-inspired surface engineering
Authors: Jihyo Park, Sangwon Woo, Jiyeon Kim, Hakho Lee, Yeong-Eun Yoo, Seonki Hong
Journal: Theranostics (2021)

Background: Nucleic acid (NA)-based diagnostics enable a rapid response to various diseases, but current techniques often require multiple labor-intensive steps, which is a major obstacle to successful translation to a clinical setting. Methods: We report on a surface-engineered single-chamber device for NA extraction and in situ amplification without sample transfer. Our system has two reaction sites: a NA extraction chamber whose surface is patterned with micropillars and a reaction chamber filled with reagents for in situ polymerase-based NA amplification. These two sites are integrated in a single microfluidic device; we applied plastic injection molding for cost-effective, mass-production of the designed device. The micropillars were chemically activated via a nature-inspired silica coating to possess a specific affinity to NA. Results: As a proof-of-concept, a colorimetric pH indicator was coupled to the on-chip analysis of NA for the rapid and convenient detection of pathogens. The NA enrichment efficiency was dependent on the lysate incubation time, as diffusion controls the NA contact with the engineered surface. We could detect down to 1×103 CFU by the naked eye within one hour of the total assay time. Conclusion: We anticipate that the surface engineering technique for NA enrichment could be easily integrated as a part of various types of microfluidic chips for rapid and convenient nucleic acid-based diagnostics.
Hospice Tax Status and Ownership Matters for Patients and Families
Authors: Melissa D. Aldridge
Journal: JAMA Internal Medicine (2021)

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DEEP LEARNING FROM NON-INVASIVE RADIAL ARTERY BLOOD PRESSURE WAVEFORM PREDICTS CARDIOVASCULAR DISEASE EVENTS IN A MULTI-ETHNIC STUDY COHORT: THE MESA STUDY
Authors: Anthony Prisco, Alex Deakyne, Weston Upchurch, Suraj Kapa, David Jacobs, Paul Iaizzo, Daniel Duprez
Journal: Journal of the American College of Cardiology (2021)
Multi-omics comparisons of different forms of centronuclear myopathies and the effects of several therapeutic strategies
Authors: Sarah Djeddi, David Reiss, Alexia Menuet, Sébastien Freismuth, Juliana de Carvalho Neves, Sarah Djerroud, Xènia Massana-Muñoz, Anne-Sophie Sosson, Christine Kretz, Wolfgang Raffelsberger, Céline Keime, Olivier M. Dorchies, Julie Thompson, Jocelyn Laporte
Journal: Molecular Therapy (2021)

Omics analyses are powerful methods to obtain an integrated view of complex biological processes, disease progression, or therapy efficiency. However, few studies have compared different disease forms and different therapy strategies to define the common molecular signatures representing the most significant implicated pathways. In this study, we used RNA sequencing and mass spectrometry to profile the transcriptomes and proteomes of mouse models for three forms of centronuclear myopathies (CNMs), untreated or treated with either a drug (tamoxifen), antisense oligonucleotides reducing the level of dynamin 2 (DNM2), or following modulation of DNM2 or amphiphysin 2 (BIN1) through genetic crosses. Unsupervised analysis and differential gene and protein expression were performed to retrieve CNM molecular signatures. Longitudinal studies before, at, and after disease onset highlighted potential disease causes and consequences. Main pathways in the common CNM disease signature include muscle contraction, regeneration and inflammation. The common therapy signature revealed novel potential therapeutic targets, including the calcium regulator sarcolipin. We identified several novel biomarkers validated in muscle and/or plasma through RNA quantification, western blotting, and enzyme-linked immunosorbent assay (ELISA) assays, including ANXA2 and IGFBP2. This study validates the concept of using multi-omics approaches to identify molecular signatures common to different disease forms and therapeutic strategies.
CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP) IN WILD-TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS
Authors: Sarah Godfrey, Hannah Rosenblum, Jianhua Zhao, Megan Hawley, Harpreet Gill, Robert Daber, Sam Harris, Sergio Teruya, Stephen Helmke, Daniel Judge, Marc Grodman, Mathew Maurer, Jan Griffin
Journal: Journal of the American College of Cardiology (2021)