tbuckley/cabot-search huggingface dataset:
TIMP1 Triggers Neutrophil Extracellular Trap Formation in Pancreatic Cancer
Authors: Benjamin Schoeps, Celina Eckfeld, Olga Prokopchuk, Jan Böttcher, Daniel Häußler, Katja Steiger, Ihsan Ekin Demir, Percy Knolle, Oliver Soehnlein, Dieter E. Jenne, Chris D. Hermann, Achim Krüger
Journal: Cancer Research (2021)

Abstract Tumor-derived protein tissue inhibitor of metalloproteinases-1 (TIMP1) correlates with poor prognosis in many cancers, including highly lethal pancreatic ductal adenocarcinoma (PDAC). The noncanonical signaling activity of TIMP1 is emerging as one basis for its contribution to cancer progression. However, TIMP1–triggered progression-related biological processes are largely unknown. Formation of neutrophil extracellular traps (NET) in the tumor microenvironment is known to drive progression of PDAC, but factors or molecular mechanisms initiating NET formation in PDAC remain elusive. In this study, gene-set enrichment analysis of a human PDAC proteome dataset revealed that TIMP1 protein expression most prominently correlates with neutrophil activation in patient-derived tumor tissues. TIMP1 directly triggered formation of NETs in primary human neutrophils, which was dependent on the interaction of TIMP1 with its receptor CD63 and subsequent ERK signaling. In genetically engineered PDAC-bearing mice, TIMP1 significantly contributed to NET formation in tumors, and abrogation of TIMP1 or NETs prolonged survival. In patient-derived PDAC tumors, NETs predominantly colocalized with areas of elevated TIMP1 expression. Furthermore, TIMP1 plasma levels correlated with DNA-bound myeloperoxidase, a NET marker, in the blood of patients with PDAC. A combination of plasma levels of TIMP1 and NETs with the clinically established marker CA19–9 allowed improved identification of prognostically distinct PDAC patient subgroups. These observations may have a broader impact, because elevated systemic levels of TIMP1 are associated with the progression of a wide range of neutrophil-involved inflammatory diseases. Significance: These findings highlight the prognostic relevance of TIMP1 and neutrophil extracellular traps in highly lethal pancreatic cancer, where a noncanonical TIMP1/CD63/ERK signaling axis induces NET formation.
Integrating Biomaterials and Genome Editing Approaches to Advance Biomedical Science
Authors: Amr A. Abdeen, Brian D. Cosgrove, Charles A. Gersbach, Krishanu Saha
Journal: Annual Review of Biomedical Engineering (2021)

The recent discovery and subsequent development of the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeat-CRISPR-associated protein 9) platform as a precise genome editing tool have transformed biomedicine. As these CRISPR-based tools have matured, multiple stages of the gene editing process and the bioengineering of human cells and tissues have advanced. Here, we highlight recent intersections in the development of biomaterials and genome editing technologies. These intersections include the delivery of macromolecules, where biomaterial platforms have been harnessed to enable nonviral delivery of genome engineering tools to cells and tissues in vivo. Further, engineering native-like biomaterial platforms for cell culture facilitates complex modeling of human development and disease when combined with genome engineering tools. Deeper integration of biomaterial platforms in these fields could play a significant role in enabling new breakthroughs in the application of gene editing for the treatment of human disease.
Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation
Authors: Felix Mahfoud, Raymond R. Townsend, David E. Kandzari, Kazuomi Kario, Roland E. Schmieder, Konstantinos Tsioufis, Stuart Pocock, Shukri David, Kiritkumar Patel, Anjani Rao, Antony Walton, Jason E. Bloom, Thomas Weber, Markus Suppan, Lucas Lauder, Sidney A. Cohen, Pamela McKenna, Martin Fahy, Michael Böhm, Michael A. Weber
Journal: Journal of the American College of Cardiology (2021)

The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP. The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN. Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models. Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (−0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (−1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN. Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)
Modulating innate immune activation states impacts the efficacy of specific Aβ immunotherapy
Authors: Yona Levites, Cory Funk, Xue Wang, Paramita Chakrabarty, Karen N. McFarland, Baxter Bramblett, Veronica O’Neal, Xufei Liu, Thomas Ladd, Max Robinson, Mariet Allen, Minerva M. Carrasquillo, Dennis Dickson, Pedro Cruz, Danny Ryu, Hong-Dong Li, Nathan D. Price, NIlüfer Ertekin-Taner, Todd E. Golde
Journal: Molecular Neurodegeneration (2021)

Abstract Introduction Passive immunotherapies targeting Aβ continue to be evaluated as Alzheimer’s disease (AD) therapeutics, but there remains debate over the mechanisms by which these immunotherapies work. Besides the amount of preexisting Aβ deposition and the type of deposit (compact or diffuse), there is little data concerning what factors, independent of those intrinsic to the antibody, might influence efficacy. Here we (i) explored how constitutive priming of the underlying innate activation states by Il10 and Il6 might influence passive Aβ immunotherapy and (ii) evaluated transcriptomic data generated in the AMP-AD initiative to inform how these two cytokines and their receptors’ mRNA levels are altered in human AD and an APP mouse model. Methods rAAV2/1 encoding EGFP, Il6 or Il10 were delivered by somatic brain transgenesis to neonatal (P0) TgCRND8 APP mice. Then, at 2 months of age, the mice were treated bi-weekly with a high-affinity anti-Aβ1–16 mAb5 monoclonal antibody or control mouse IgG until 6 months of age. rAAV mediated transgene expression, amyloid accumulation, Aβ levels and gliosis were assessed. Extensive transcriptomic data was used to evaluate the mRNA expression levels of IL10 and IL6 and their receptors in the postmortem human AD temporal cortex and in the brains of TgCRND8 mice, the later at multiple ages. Results Priming TgCRND8 mice with Il10 increases Aβ loads and blocks efficacy of subsequent mAb5 passive immunotherapy, whereas priming with Il6 priming reduces Aβ loads by itself and subsequent Aβ immunotherapy shows only a slightly additive effect. Transcriptomic data shows that (i) there are significant increases in the mRNA levels of Il6 and Il10 receptors in the TgCRND8 mouse model and temporal cortex of humans with AD and (ii) there is a great deal of variance in individual mouse brain and the human temporal cortex of these interleukins and their receptors. Conclusions The underlying immune activation state can markedly affect the efficacy of passive Aβ immunotherapy. These results have important implications for ongoing human AD immunotherapy trials, as they indicate that underlying immune activation states within the brain, which may be highly variable, may influence the ability for passive immunotherapy to alter Aβ deposition.
A New Sensitive and Fast Molecular Analysis Method for the Identification of 30 Different Markers in Acute Myeloid and Lymphoid Leukemias at Diagnosis Time
Authors: Emilia Giugliano, Roberta Lorenzatti, Enrico Marco Gottardi, Chiara Sammartino, Roberta Toja, Francesca Crasto, Alessandro Volpengo, Cristina Fantino, Filomena Daraio, Anna Serra, Francesca Carnuccio, Giuseppe Saglio, Angelo Guerrasio
Journal: Blood (2017)
CRITERIA FOR PREDICTING LOWER RISK OF ADVERSE EVENTS AMONG PATIENTS RECEIVING PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Ayman Elbadawi, Bao Nguyen, Suartcha Prueksaritanond, Khaled Ziada, Syed Gilani
Journal: Journal of the American College of Cardiology (2021)
THE EFFECT OF DIABETES MELLITUS, PREDIABETES AND GLYCEMIA ON LEFT VENTRICULAR ASSIST DEVICE-MEDIATED CARDIAC RECOVERY
Authors: Christos P. Kyriakopoulos, Iosif Taleb, Chris Chaudhary, Elizabeth L. Stauder, Monte Scott, Tyler J. Richins, Elizabeth Dranow, Michael Yaoyao Yin, Sutip Navankasattusas, Rami Alharethi, Bruce Reid, Line Kemeyou, Kevin Shah, Matthew Goodwin, Craig Selzman, Stavros Drakos
Journal: Journal of the American College of Cardiology (2021)
INCIDENCE OF ACTIONABLE EVENTS ON IMPLANTABLE CARDIAC MONITORS: A PROSPECTIVE STUDY COMPARING REVEAL LINQTM OR CONFIRM RXTMIMPLANTABLE CARDIAC MONITORS
Authors: Sandeep Banga, Zulfiqar Qutrio Baloch, Abbas Ali, Abdullah Al-abcha, John Ip
Journal: Journal of the American College of Cardiology (2021)
ABO 불일치 간이식 후 발생한 Passenger Lymphocyte Syndrome 1예
Authors: 박동균(Dong Kyun Park), 김선숙(Sun Suk Kim), 박현철(Hyun Chul Park), 최덕주(Duck Joo Choi), 강동훈(Dong Hoon Kang), 김유경(You Kyoung Kim), 박종재(Jong Jae Park), 이정남(Joung Nam Lee), 서일해(Ill Hae Seo), 김주현(Ju Hyun Kim)
Journal: Clinical and Molecular Hepatology (1999)
In men who are overweight or obese, adding testosterone therapy reduced glucose intolerance/T2DM
Authors: Tomás P. Griffin, Sean F. Dinneen
Journal: Annals of Internal Medicine (2021)

Source Citation Wittert G, Bracken K, Robledo KP, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9:32-45. 33338415
METABOLOMICS REVEALS PERTURBATIONS IN ARGININE-NO METABOLISM, PURINE BIOSYNTHESIS AND CELLULAR ENERGY CHARGE IN PATIENTS WITH CORONARY HEART DISEASE
Authors: Ehsan Ullah, Ayman El-Menyar, Khalid Kunji, Reem Elsousy, Haira Rizan Binti Mokhtar, Nada Ali Al-Tamimi, Maryam Ali Yousef Al-Nesf, Alka Beotra, Mohammed Al-Maadheed, Vidya Mohamed-Ali, Mohamad Saad, Jassim Al Suwaidi
Journal: Journal of the American College of Cardiology (2021)
MAYO MODEL FOR PREDICTING ACUTE CARDIOVASCULAR AND CEREBROVASCULAR EVENTS AFTER CHEST RADIOTHERAPY IN PATIENTS WITH BREAST OR LUNG CANCER
Authors: Anan Abu Rmilah, Adham Alkurashi, Ikram-Ul Haq, Nandan Anavekar, Hayan Jouni, Grace Lin, Nadia Laack, Joerg Herrmann
Journal: Journal of the American College of Cardiology (2021)
KRAS Secondary Mutations That Confer Acquired Resistance to KRAS G12C Inhibitors, Sotorasib and Adagrasib, and Overcoming Strategies: Insights From In Vitro Experiments
Authors: Takamasa Koga, Kenichi Suda, Toshio Fujino, Shuta Ohara, Akira Hamada, Masaya Nishino, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Takeo Arita, Michael Gmachl, Marco H. Hofmann, Junichi Soh, Tetsuya Mitsudomi
Journal: Journal of Thoracic Oncology (2021)
Violence, Place, and Strengthened Space: A Review of Immigration Stress, Violence Exposure, and Intervention for Immigrant Latinx Youth and Families
Authors: Sarah A. Jolie, Ogechi Cynthia Onyeka, Stephanie Torres, Cara DiClemente, Maryse Richards, Catherine DeCarlo Santiago
Journal: Annual Review of Clinical Psychology (2021)

Latinx immigrant families are greatly impacted by US policies and practices that limit immigrant families' and children's rights. This article reviews the effects of such policies and the growing literature examining migration experiences. Latinx immigrant youth and parents may encounter multiple stressors across the stages of migration, including physical and structural violence, fear, poverty, and discrimination, which contribute to higher rates of mental health problems in this population. Despite significant trauma exposure, immigrants demonstrate incredible resilience within themselves, their families, and their communities and through movements and policies aimed at protecting their rights. Numerous culturally relevant universal, targeted, and intensive interventions were developed to magnify these protective factors to promote healing, advance immigration reform, and provide trauma-informed training and psychoeducation. Psychologistsplay a crucial role in implementing, evaluating, and advocating for accessible and collaborative approaches to care so that Latinx immigrant families have the resources to combat the harmful sequelae of immigration stress.
Prdm16 Supports Arterial Flow Recovery by Maintaining Endothelial Function
Authors: Sander Craps, Jore Van Wauwe, Sofie De Moudt, Dorien De Munck, Arthur J.A. Leloup, Bram Boeckx, Tim Vervliet, Wouter Dheedene, Nathan Criem, Carla Geeroms, Elizabeth A.V. Jones, An Zwijsen, Diether Lambrechts, Paul Fransen, Manu Beerens, Aernout Luttun
Journal: Circulation Research (2021)

[Figure: see text].
Detection of autoreactive CD4+ T cells by MHC class II multimers in HLA-linked human autoimmune diseases
Authors: Karolin Wieber, Christine L. Zimmer, Michael Hertl
Journal: Journal of Clinical Investigation (2021)

Recognition of self-peptides in association with distinct HLA class II alleles by autoreactive CD4+ T cells is central for loss of immunological tolerance leading to autoimmune disease. However, identifying immunodominant self-peptides and characterizing autoreactive T cells is challenging. In this issue of the JCI, Falta et al. identify a disease-associated complementarity-determining region 3β motif specific for beryllium-modified C-C motif ligand 4 (CCL4) and CCL3 self-peptides in patients with chronic beryllium disease (CBD), a granulomatous lung disorder with a known HLA class II allelic association. Detection of these antigen-specific CD4+ T cells by beryllium-pulsed HLA-DP2 tetramers presenting CCL4/CCL3 confirms these autoantigens in humans and mice and enables monitoring in the progress of disease. Detection of autoreactive CD4+ T cells by peptide-MHC class II multimers allows for the detailed characterization of disease-promoting T cells. This knowledge has profound implications for the monitoring and development of targeted therapies in human autoimmune disorders.
Keith Glennie-Smith
Authors: Janet Oliver
Journal: BMJ (2021)

Keith Glennie-Smith qualified at St Thomas’ Hospital Medical School in 1951. The following year he was posted to Korea as part of the Royal Army Medical Corps. On return to the UK, Keith gained his fellowship in the Faculty of Anaesthetists in 1960 and, in 1963, was offered the position of consultant anaesthetist at Poole General Hospital, …
Novel cell sources for bone regeneration
Authors: Chenshuang Li, Zane Mills, Zhong Zheng
Journal: MedComm (2021)

Abstract A plethora of both acute and chronic conditions, including traumatic, degenerative, malignant, or congenital disorders, commonly induce bone disorders often associated with severe persisting pain and limited mobility. Over 1 million surgical procedures involving bone excision, bone grafting, and fracture repair are performed each year in the U.S. alone, resulting in immense levels of public health challenges and corresponding financial burdens. Unfortunately, the innate self‐healing capacity of bone is often inadequate for larger defects over a critical size. Moreover, as direct transplantation of committed osteoblasts is hindered by deficient cell availability, limited cell spreading, and poor survivability, an urgent need for novel cell sources for bone regeneration is concurrent. Thanks to the development in stem cell biology and cell reprogramming technology, many multipotent and pluripotent cells that manifest promising osteogenic potential are considered the regenerative remedy for bone defects. Considering these cells' investigation is still in its relative infancy, each of them offers their own particular challenges that must be conquered before the large‐scale clinical application.
Metabolon: a novel cellular structure that regulates specific metabolic pathways
Authors: Tian Tian, Jun Fan, Shannon Elisabeth Elf
Journal: Cancer Communications (2021)

This manuscript of research highlight focused on one paper recently published in Nature Metabolism entitled "Mitochondrial Long Non-coding RNA GAS5 Tunes TCA Metabolism in Response to Nutrient Stress" from Lin Aifu's group in Zhejiang University. In this manuscript, we discussed the novel findings in Lin's paper and concluded that the metabolon is emerging as a novel cellular structure that regulates specific metabolic pathways.
SEX DIFFERENCES IN SYMPTOM REPORTING AMONGST ATRIAL FIBRILLATION ABLATION PATIENTS: A SUB-STUDY OF THE ADENOSINE FOLLOWING PULMONARY VEIN ISOLATION TO TARGET DORMANT CONDUCTION ELIMINATION (ADVICE) TRIAL
Authors: Laura D'Aronco, Michelle Samuel, Paul Khairy, Jason Andrade, Paul Novak, Atul Verma, George Veenhuyzen, Lena Rivard, Peter G. Guerra, Marc Dubuc, Bernard Thibault, Katia Dyrda, Rafik Tadros, Julia Cadrin-Tourigny, Martin Aguilar, Alexandre Raymond-Paquin, Mario Talajic, Sylvie Levesque, Denis Roy, Jean Claude Tardif, Stanley Nattel, Laurent Macle
Journal: Journal of the American College of Cardiology (2021)
The abscopal effect: a sense of DNA damage is in the air
Authors: Timothy P. Lippert, Roger A. Greenberg
Journal: Journal of Clinical Investigation (2021)

Tumor metastasis is a singularly important determinant of survival in most cancers. Historically, radiation therapy (RT) directed at a primary tumor mass was associated infrequently with remission of metastasis outside the field of irradiation. This away-from-target or "abscopal effect" received fringe attention because of its rarity. With the advent of immunotherapy, there are now increasing reports of abscopal effects upon RT in combination with immune checkpoint inhibition. This sparked investigation into underlying mechanisms and clinical trials aimed at enhancement of this effect. While these studies clearly attribute the abscopal effect to an antitumor immune response, the initial molecular triggers for its onset and specificity remain enigmatic. Here, we propose that DNA damage-induced inflammation coupled with neoantigen generation is essential during this intriguing phenomenon of systemic tumor regression and discuss the implications of this model for treatment aimed at triggering the abscopal effect in metastatic cancer.
Health Information Privacy, Protection, and Use in the Expanding Digital Health Ecosystem: A Position Paper of the American College of Physicians
Authors: Brooke Rockwern, Dejaih Johnson, Lois Snyder Sulmasy
Journal: Annals of Internal Medicine (2021)

Technologic advancements and the evolving digital health landscape have offered innovative solutions to several of our health care system's issues as well as increased the number of digital interactions and type of personal health information that is generated and collected, both within and outside of traditional health care. This American College of Physicians' position paper discusses the state of privacy legislation and regulations, highlights existing gaps in health information privacy protections, and outlines policy principles and recommendations for the development of health information privacy and security protections that are comprehensive, transparent, understandable, adaptable, and enforceable. The principles and recommendations aim to improve on the privacy framework in which physicians have practiced for decades and expand similar privacy guardrails to entities not currently governed by privacy laws and regulations. The expanded privacy framework should protect personal health information from unauthorized, discriminatory, deceptive, or harmful uses and align with the principles of medical ethics, respect individual rights, and support the culture of trust necessary to maintain and improve care delivery.
SAFETY AND EFFICACY OF SAME-DAY ELECTIVE CORONARY ANGIOGRAPHY AND SYNCHRONIZED CARDIOVERSION IN PATIENTS WITH ATRIAL FIBRILLATION WITH UNINTERRUPTED ANTICOAGULATION
Authors: Rory Gallen, Sacchin Arockiam, Marianna Kalaszi, Myles McKittrick, Hani Muradagha, Terence Hennessy, Padraig O'Drisceoil, Samer Arnous, Thomas Kiernan
Journal: Journal of the American College of Cardiology (2021)
IMPLEMENTATION OF A STANDARDIZED NEONATAL CARDIAC SURGERY PROTOCOL IMPROVES POSTOPERATIVE OUTCOMES
Authors: Nischal Gautam, Ahmed Deniwar, Richard Hubbard, Olga Pawelek, Evelyn Griffin, Kayla Edmonds, Rebecca Sam, Eric Rydalch, Jon Meliones, Jorge Salazar
Journal: Journal of the American College of Cardiology (2021)
COVID-19 transmission in Hong Kong despite universal masking
Authors: Mario Martín-Sánchez, Wey Wen Lim, Amy Yeung, Dillon C. Adam, Sheikh Taslim Ali, Eric H.Y. Lau, Peng Wu, Kwok-Yung Yuen, Gabriel M. Leung, Benjamin J. Cowling
Journal: Journal of Infection (2021)