tbuckley/cabot-search huggingface dataset:
Abstract PO-003: Mitotic enrichment as an efficient radiosensitization strategy
Authors: Mark C. de Gooijer, Paul L.G. Slangen, Hilal Çolakoğlu, Ceren H. Çitirikkaya, Amal El Ouazani, Ronak Shah, Gerben R. Borst, Olaf van Tellingen
Journal: Clinical Cancer Research (2021)

Abstract Radiotherapy remains one of the most effective modalities for anticancer treatment. Boosting the efficacy of radiotherapy is therefore a logical avenue to improve patient survival. We have developed a radiosensitization strategy called ‘induction of mitotic enrichment’. It has long been known that the radiosensitivity of a cell depends to a large extent on the phase of the cell cycle and that especially mitotic cells are especially vulnerable. Enriching the tumor for mitotic cells by arresting them during division prior to each radiotherapy fraction should therefore render the tumor population more sensitive to irradiation. Ideally, induction of mitotic enrichment should be reversible and non-cytotoxic to prevent healthy tissue toxicity and be compatible with clinically applied fractionated radiotherapy regimens. We have now identified an orally available targeted tubulin polymerization inhibitor that can achieve repeated and reversible mitotic enrichment for up to 10 hours prior to radiotherapy, without causing cytotoxicity in vitro or healthy tissue toxicity in vivo. Most importantly, this tubulin inhibitor efficiently radiosensitizes a range of preclinical glioblastoma models in vitro and in vivo and significantly improves survival, but only in a mitotic enrichment setup when given several hours prior to radiotherapy to allow accumulation in mitosis. We have initiated development of mitotic enrichment for GBM, the most common primary malignant brain tumor. Their location and highly aggressive nature renders GBM among the most deadly and devastating of human malignancies. Despite extensive treatment involving surgery and adjuvant chemo-radiotherapy, prognosis is still dismal and novel treatment strategies are urgently needed. Of all available adjuvant therapies, radiotherapy contributes most to extending overall survival. Increasing the efficacy of existing radiotherapeutic regimens therefore offers a logical rationale to improve the survival of GBM patients. We are currently also expanding our preclinical development of mitotic enrichment as a radiosensitization strategy to other mitotic targets and different cancers for which radiotherapy is a mainstay treatment and have thus far achieved promising results in vitro. In parallel, we are preparing a phase 0 trial to demonstrate induction of mitotic enrichment in human GBM. Citation Format: Mark C. de Gooijer, Paul L.G. Slangen, Hilal Çolakoğlu, Ceren H. Çitirikkaya, Amal El Ouazani, Ronak Shah, Gerben R. Borst, Olaf van Tellingen. Mitotic enrichment as an efficient radiosensitization strategy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-003.
Myocardial Injury and Fibrosis From Acute Carbon Monoxide Poisoning
Authors: Dong-Hyuk Cho, Sung Min Ko, Jung-Woo Son, Eung Joo Park, Yong Sung Cha
Journal: JACC. Cardiovascular imaging (2021)

This study sought to evaluate the prevalence and patterns of late gadolinium enhancement (LGE) after carbon monoxide (CO) poisoning using cardiac magnetic resonance (CMR) imaging (CMRI) and transthoracic echocardiography (TTE).In acute CO poisoning, cardiac injury can predict mortality. However, it remains unclear why increased mortality and cardiovascular events occur despite normalization of CO-induced elevated troponin I (TnI) and cardiac dysfunction.Patients with acute CO poisoning with elevated TnI were evaluated. CMRI was performed within 7 days of CO exposure and after 4 to 5 months. Patients were divided into LGE (n = 72; 69.2%) and no-LGE (n = 32; 30.8%) groups.In the LGE group, 39.4%, 4.8%, and 25.0% of patients exhibited midwall, subendocardial, and right ventricular insertion point injury, respectively. Diffuse injury was observed in 22.1% of patients, and 67.6% of the 37 patients who underwent follow-up CMRI showed no interval change. On TTE, baseline left ventricular ejection fraction and global longitudinal strain were significantly deteriorated in the LGE group; serial TTE within 7 days indicated that only left ventricular global longitudinal strain remained significantly deteriorated. Three cases of mortality occurred in the LGE group during the 1-year follow-up.The LGE prevalence in patients with acute CO poisoning with elevated TnI levels, with no underlying cardiovascular diseases and eligible for CMRI, was 69.2%; this proportion primarily comprised patients with a midwall injury. Of the 37 patients who underwent follow-up CMRI, most chronic phase images showed no interval change. Myocardial fibrosis detected on CMR images was related to acute myocardial dysfunction and subacute deterioration of myocardial strain on TTE. (Cardiac Magnetic Resonance Image in Acute Carbon Monoxide Poisoning; NCT04419298).
Model-Based Estimation of Colorectal Cancer Screening and Outcomes During the COVID-19 Pandemic
Authors: Rachel B. Issaka, Preston Taylor, Anand Baxi, John M. Inadomi, Scott D. Ramsey, Joshua Roth
Journal: JAMA Network Open (2021)

<h3>Importance</h3> COVID-19 has decreased colorectal cancer screenings. <h3>Objective</h3> To estimate the degree to which expanding fecal immunochemical test–based colorectal cancer screening participation during the COVID-19 pandemic is associated with clinical outcomes. <h3>Design, Setting, and Participants</h3> A previously developed simulation model was adopted to estimate how much COVID-19 may have contributed to colorectal cancer outcomes. The model included the US population estimated to have completed colorectal cancer screening pre–COVID-19 according the American Cancer Society. The model was designed to estimate colorectal cancer outcomes between 2020 and 2023. This analysis was completed between July and December 2020. <h3>Exposures</h3> Adults screened for colorectal cancer and colorectal cancer cases detected by stage. <h3>Main Outcomes and Measures</h3> Estimates of colorectal cancer outcomes across 4 scenarios: (1) 9 months of 50% colorectal cancer screenings followed by 21 months of 75% colorectal cancer screenings; (2) 18 months of 50% screening followed by 12 months of 75% screening; (3) scenario 1 with increased use of fecal immunochemical tests; and (4) scenario 2 with increased use of fecal immunochemical tests. <h3>Results</h3> In our simulation model, COVID-19–related reductions in care utilization resulted in an estimated 1 176 942 to 2 014 164 fewer colorectal cancer screenings, 8346 to 12 894 fewer colorectal cancer diagnoses, and 6113 to 9301 fewer early-stage colorectal cancer diagnoses between 2020 and 2023. With an abbreviated period of reduced colorectal cancer screenings, increasing fecal immunochemical test use was associated with an estimated additional 588 844 colorectal cancer screenings and 2836 colorectal cancer diagnoses, of which 1953 (68.9%) were early stage. In the event of a prolonged period of reduced colorectal cancer screenings, increasing fecal immunochemical test use was associated with an estimated additional 655 825 colorectal cancer screenings and 2715 colorectal cancer diagnoses, of which 1944 (71.6%) were early stage. <h3>Conclusions and Relevance</h3> These results suggest that the increased use of fecal immunochemical tests during the COVID-19 pandemic was associated with increased colorectal cancer screening participation and more colorectal cancer diagnoses at earlier stages. If our estimates are borne out in real-world clinical practice, increasing fecal immunochemical test–based colorectal cancer screening participation during the COVID-19 pandemic could mitigate the consequences of reduced screening rates during the pandemic for colorectal cancer outcomes.
Harnessing amphiphilic polymeric micelles for diagnostic and therapeutic applications: Breakthroughs and bottlenecks
Authors: Jaskiran Kaur, Vijay Mishra, Sachin Kumar Singh, Monica Gulati, Bhupinder Kapoor, Dinesh Kumar Chellappan, Gaurav Gupta, Harish Dureja, Krishnan Anand, Kamal Dua, Gopal L. Khatik, Kuppusamy Gowthamarajan
Journal: Journal of Controlled Release (2021)
ZnO/CPAN Modified Contact Lens with Antibacterial and Harmful Light Reduction Capabilities
Authors: Zhenling Zhu, Liguo Jin, Fen Yu, Feifei Wang, Zhenzhen Weng, Jia Liu, Zhen Han, Xiaolei Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Compared with traditional glasses, the comfortable and convenient contact lens (CL) has seen an upsurge among the public. However, due to the lack of antibacterial properties of ordinary CLs, the risk of eye infection is greatly increased accordingly. On the other hand, ordinary CLs also cannot effectively reduce the short‐wavelength blue light emitted from electronic products, such as mobile phones and computers. Aiming at the above two problems, zinc oxide (ZnO)/cyclized polyacrylonitrile (CPAN) composites are developed for CL modification. After loading with ZnO/CPAN (ZC), the CL shows a broad‐spectrum antibacterial property. Further experiments also prove that it can block UVB, UVA, as well as blue light selectively, under the premise of ensuring hydrophilicity and certain transparency. Theoretically, this ZC‐decorated CL can fundamentally reduce the damage to the eyes from harmful light emitted by light‐emitting diodes and the secretion of pro‐inflammatory factors, which is thus a promising eye protection strategy for modern society.
A fetal wave of human type 3 effector γδ cells with restricted TCR diversity persists into adulthood
Authors: Likai Tan, Alina Suzann Fichtner, Elena Bruni, Ivan Odak, Inga Sandrock, Anja Bubke, Alina Borchers, Christian Schultze-Florey, Christian Koenecke, Reinhold Förster, Michael Jarek, Constantin von Kaisenberg, Ansgar Schulz, Xiaojing Chu, Bowen Zhang, Yang Li, Ulf Panzer, Christian F. Krebs, Sarina Ravens, Immo Prinz
Journal: Science Immunology (2021)

Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector γδ T cells. However, it is unclear whether this process occurs similarly in humans and whether it comprises a dedicated subset of innate-like type 3 effector γδ T cells. Here, we present a protocol for high-throughput sequencing of TRG and TRD pairs that comprise the clonal γδTCR. In combination with single-cell RNA sequencing, multiparameter flow cytometry, and TCR sequencing, we reveal a high heterogeneity of γδ T cells sorted from neonatal and adult blood that correlated with TCR usage. Immature γδ T cell clusters displayed mixed and diverse TCRs, but effector cell types segregated according to the expression of either highly expanded individual Vδ1+ TCRs or moderately expanded semi-invariant Vγ9Vδ2+ TCRs. The Vγ9Vδ2+ T cells shared expression of genes that mark innate-like T cells, including ZBTB16 (encoding PLZF), KLRB1, and KLRC1, but consisted of distinct clusters with unrelated Vγ9Vδ2+ TCR clones characterized either by TBX21, FCGR3A, and cytotoxicity-associated gene expression (type 1) or by CCR6, RORC, IL23R, and DPP4 expression (type 3). Effector γδ T cells with type 1 and type 3 innate T cell signatures were detected in a public dataset of early embryonic thymus organogenesis. Together, this study suggests that functionally distinct waves of human innate-like effector γδ T cells with semi-invariant Vγ9Vδ2+ TCR develop in the early fetal thymus and persist into adulthood.
Kinetic Analysis Suggests Evolution of Ribosome Specificity in Modern Elongation Factor-Tus from “Generalist” Ancestors
Authors: Arindam De Tarafder, Narayan Prasad Parajuli, Soneya Majumdar, Betül Kaçar, Suparna Sanyal
Journal: Molecular Biology and Evolution (2021)

It has been hypothesized that early enzymes are more promiscuous than their extant orthologs. Whether or not this hypothesis applies to the translation machinery, the oldest molecular machine of life, is not known. Efficient protein synthesis relies on a cascade of specific interactions between the ribosome and the translation factors. Here, using elongation factor-Tu (EF-Tu) as a model system, we have explored the evolution of ribosome specificity in translation factors. Employing presteady state fast kinetics using quench flow, we have quantitatively characterized the specificity of two sequence-reconstructed 1.3- to 3.3-Gy-old ancestral EF-Tus toward two unrelated bacterial ribosomes, mesophilic Escherichia coli and thermophilic Thermus thermophilus. Although the modern EF-Tus show clear preference for their respective ribosomes, the ancestral EF-Tus show similar specificity for diverse ribosomes. In addition, despite increase in the catalytic activity with temperature, the ribosome specificity of the thermophilic EF-Tus remains virtually unchanged. Our kinetic analysis thus suggests that EF-Tu proteins likely evolved from the catalytically promiscuous, "generalist" ancestors. Furthermore, compatibility of diverse ribosomes with the modern and ancestral EF-Tus suggests that the ribosomal core probably evolved before the diversification of the EF-Tus. This study thus provides important insights regarding the evolution of modern translation machinery.
David Charles Taylor
Authors: Ian M Goodyer
Journal: BMJ (2021)

David Charles Taylor was a world renowned psychiatrist who specialised in the connections between severe brain malfunctions and mental illnesses. Originally making his observations in adult patients, his research became increasingly focused on the neurologically vulnerable child. Supported by the eminent neuropathologist John Corsellis, he was the first to describe focal cortical dysplasia (Taylor type cortical dysplasia), a now known important cause of surgically treatable epilepsy. This was a notable discovery, and has had a longlasting impact on the field. Taylor was the first clinician scientist to investigate the behavioural effects of patients who had undergone epilepsy surgery and among the first to suggest a sex difference in how the brain develops. The latter is a topic of considerable interest in today’s field of cognitive neuroscience.

David Charles Taylor was the youngest of five children born to parents who managed newsagent and tobacconist shops in central London. David and his family lived over one of the shops which was situated between Buckingham Palace Gardens and Victoria Station. David was aged 6 when the second world war broke out and, along with his 10 year old brother, was evacuated to mid-Wales and became a Welsh speaking child. His parents and other siblings also evacuated to Wales in 1941, where they farmed. Although the family returned to London in 1944, David was sent back to Wales until the end of the war. In 1946, aged 13 years, he went to boarding school, Allhallows, …
Low immunogenicity to SARS-CoV-2 vaccination among liver transplant recipients
Authors: Liane Rabinowich, Ayelet Grupper, Roni Baruch, Merav Ben-Yehoyada, Tami Halperin, Dan Turner, Eugene Katchman, Sharon Levi, Inbal Houri, Nir Lubezky, Oren Shibolet, Helena Katchman
Journal: Journal of Hepatology (2021)

Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population.
Tests for tuberculosis infection: landscape analysis
Authors: Yohhei Hamada, Daniela Maria Cirillo, Alberto Matteelli, Adam Penn-Nicholson, Molebogeng X. Rangaka, Morten Ruhwald
Journal: European Respiratory Journal (2021)

Background Only the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube and T-SPOT.TB, are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than the TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed. Methods We reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally. Results We identified 20 tests for TB infection: 15 in vitro tests and five skin tests. 13 of the in vitro tests are whole-blood IGRAs and 14 use early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. 10 of the tests are based on assays other than an ELISA, such as a fluorescent lateral flow assay that requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared with the existing IGRAs. Four of the five skin tests use ESAT-6 and CFP-10 proteins, while the remaining test uses a new antigen that is specific to Mycobacterium tuberculosis complex. Conclusions New tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.
Abstract 16601: Sustained And Non Sustained Ventricular Tachycardia Are Important Predictors To Differentiate Arrhythmogenic Right Ventricular Cardiomyopathy With Fat And Fibrotic Invasion To Left Ventricular Myocardium Using Four-dimensional Cardiac Computed Tomography
Authors: Nobusada Funabashi, Yoshio Kobayashi
Journal: Circulation (2019)

Introduction: Arrhythmogenic Right Ventricular Cardiomyopathy (RV) cardiomyopathy (ARVC) is a genetic heart muscle disorder with an increased risk of critical ventricular arrhythmias and sometimes ...
MYOCARDIAL INVOLVEMENT IN COVID-19 - DATA FROM 102 CLINICAL AND FORENSIC AUTOPSIES IN ST PETERSBURG DURING THE FIRST WAVE OF SARS-COV2 PANDEMICS
Authors: Pyotr G. Platonov, Valery Vasilyev, Galina Startseva, Vadim Karev, Margarita Rybakova, Elena Romanova
Journal: Journal of the American College of Cardiology (2021)
Strategy for Designing a Cell Scaffold to Enable Wireless Electrical Stimulation for Enhanced Neuronal Differentiation of Stem Cells
Authors: Fang Han, Xun Ma, Yuanxin Zhai, Leisha Cui, Lingyan Yang, Zhanchi Zhu, Ying Hao, Guosheng Cheng
Journal: Advanced Healthcare Materials (2021)

Abstract Electrical stimulation (ES) offers significant advantages in modulating the behavior of stem cells on conductive scaffolds for neural tissue engineering. However, it is necessary to realize wireless ES to avoid the use of external wires in tissues. Thus, herein, a strategy is reported to develop a stem cell scaffold that allows wireless ES. A conductive annular graphene substrate is designed and grown by chemical vapor deposition; this substrate is used as a secondary coil to achieve wireless ES via electromagnetic induction in the presence of a primary coil. The substrate shows excellent biocompatibility for the culture of neural stem cells (NSCs). The results indicate that the applied wireless ES enhances neuronal differentiation, facilitates the formation of neurites, and does not substantially affect the viability and stemness maintenance of NSCs. Collectively, this system provides a strategy for achieving synergy between wireless ES and conductive scaffolds for neural regenerative medicine, which can be further utilized for the regeneration of other tissues.
Association of Gestational Opioid Exposure and Risk of Major and Minor Congenital Malformations
Authors: Xuerong Wen, Nicholas Belviso, Emily Murray, Adam K. Lewkowitz, Kristina E. Ward, Kimford J. Meador
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The rapid increase of opioid-related overdoses and deaths has become a public health concern in the US. Use of prescription opioids in pregnant women has increased; results from teratogenicity studies remain controversial. <h3>Objective</h3> To evaluate the association between maternal prescription opioid use (excluding opioid use disorders) during pregnancy and the incidence of congenital malformations. <h3>Design, Setting, and Participants</h3> This retrospective population-based cohort study evaluated linked Rhode Island Medicaid claims and vital statistics data of live births from January 1, 2008, to December 31, 2016. Data analysis was conducted from May 1, 2019, to May 31, 2020. Women who had a live birth during the study period, but no cancer or opioid use disorder, were followed up from 3 months before pregnancy to the end of pregnancy. <h3>Exposures</h3> Data on the mother's prescription opioid exposure were obtained through pharmacy claims and exposure was defined as dispensing of at least 1 prescription opioid during the first, second, or third trimester. <h3>Main Outcomes and Measures</h3> The primary outcome was overall major or minor congenital malformations, defined as 1 or more major or minor congenital malformation. Secondary outcomes were defined as 10 specific categories of congenital malformations classified by organ systems using<i>International Classification of Diseases</i>diagnosis codes. <h3>Results</h3> Of 12 424 included pregnancies, 891 mothers (7.2%) received prescription opioids during pregnancy and 3153 infants (25.4%) were diagnosed with major or minor congenital malformations. Comparing prescription opioid exposure vs nonexposure, no excess risk was observed for major birth defects in infants with opioid exposure in trimester 1 (adjusted relative risk [aRR], 1.40; 95% CI, 0.84-2.34), and higher risks were found for overall minor birth defects in trimester 3 (aRR, 1.26; 95% CI, 1.04-1.53) and minor birth defects in the musculoskeletal system in trimester 2 (aRR, 1.50; 95% CI, 1.10-2.03) and trimester 3 (aRR, 1.65; 95% CI, 1.23-2.22). Significant dose responses in selected minor malformations and effects of specific opioids were also identified. Hydrocodone in trimester 2 (aRR, 3.01; 95% CI, 1.80-5.03) and oxycodone in trimester 3 (aRR, 2.43; 95% CI, 1.37-4.02) were associated with plagiocephaly, polydactyly, and other specified congenital deformities of the hip. <h3>Conclusions and Relevance</h3> The findings of this study suggest a higher risk of minor congenital malformations associated with use of prenatal prescription opioids in trimester 3, which seems to be dose-dependent. Further investigation is needed to establish causality and explore the physiologic plausibility of the association.
Sex-Specific Computed Tomography Coronary Plaque Characterization and Risk of Myocardial Infarction
Authors: Michelle C. Williams, Jacek Kwiecinski, Mhairi Doris, Priscilla McElhinney, Michelle S. D’Souza, Sebastien Cadet, Philip D. Adamson, Alastair J. Moss, Shirjel Alam, Amanda Hunter, Anoop S.V. Shah, Nicholas L. Mills, Tania Pawade, Chengjia Wang, Jonathan R. Weir-McCall, Michael Bonnici-Mallia, Christopher Murrills, Giles Roditi, Edwin J.R. van Beek, Leslee J. Shaw, Edward D. Nicol, Daniel S. Berman, Piotr J. Slomka, David E. Newby, Marc R. Dweck, Damini Dey
Journal: JACC. Cardiovascular imaging (2021)
Sixty seconds on . . . dog bites
Authors: Abi Rimmer
Journal: BMJ (2021)

Good question. Arguably you could say it was Prime Minister Boris Johnson when he announced a national lockdown in England in March 2020. While there are no official figures, data from the pet food industry show that in 20191 25% of UK households owned a dog, compared with 33%2 in 2021, with the number of dogs rising from nine million to 12.5 million.

Not necessarily. However, Simon Minford, advanced paediatric nurse practitioner at Alder Hey Children’s Hospital in Liverpool, says that around six …
Defining the lineage of thermogenic perivascular adipose tissue
Authors: Anthony R. Angueira, Alexander P. Sakers, Corey D. Holman, Lan Cheng, Michelangella N. Arbocco, Farnaz Shamsi, Matthew D. Lynes, Rojesh Shrestha, Chihiro Okada, Kirill Batmanov, Katalin Susztak, Yu-Hua Tseng, Lucy Liaw, Patrick Seale
Journal: Nature Metabolism (2021)