tbuckley/cabot-search huggingface dataset:
T cell mediated hypersensitivity to previously tolerated iodinated contrast media precipitated by introduction of atezolizumab
Authors: Sean Hammond, Anna Olsson-Brown, Joshua Gardner, Paul Thomson, Serat-E Ali, Carol Jolly, Dan Carr, Lorenzo Ressel, Munir Pirmohamed, Dean Naisbitt
Journal: Journal for ImmunoTherapy of Cancer (2021)

Many adverse reactions associated with immune checkpoint inhibitor (ICI) treatments are immunologically driven and may necessitate discontinuation of the ICI. Herein, we present a patient who had been administered the radio contrast media amidotrizoate multiple times without issue but who then developed a Stevens-Johnson syndrome reaction after coadministration of atezolizumab. Causality was confirmed by a positive re-challenge with amidotrizoate and laboratory investigations that implicated T cells. Importantly, the introduction of atezolizumab appears to have altered the immunologic response to amidotrizoate in terms of the tolerance–elicitation continuum. Proof of concept studies demonstrated enhancement of recall responses to a surrogate antigen panel following in-vitro (healthy donors) and in-vivo (ICI patients) administrations of ICIs. Our findings highlight the importance of considering all concomitant medications in patients on ICIs who develop immune-mediated adverse reactions. In the event of some immune-related adverse reactions, it may be critical to identify the culprit antigen-forming entity that the ICIs have altered the perception of rather than simply attribute causality to the ICI itself in order to optimize both patient safety and treatment of malignancies.
Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses
Authors: Rosanne C. van Deuren, Peer Arts, Giulio Cavalli, Martin Jaeger, Marloes Steehouwer, Maartje van de Vorst, Christian Gilissen, Leo A. B. Joosten, Charles A. Dinarello, Musa M. Mhlanga, Vinod Kumar, Mihai G. Netea, Frank L. van de Veerdonk, Alexander Hoischen
Journal: Genome Medicine (2021)

Abstract Background The interleukin (IL)-1 pathway is primarily associated with innate immunological defense and plays a major role in the induction and regulation of inflammation. Both common and rare genetic variation in this pathway underlies various inflammation-mediated diseases, but the role of rare variants relative to common variants in immune response variability in healthy individuals remains unclear. Methods We performed molecular inversion probe sequencing on 48 IL-1 pathway-related genes in 463 healthy individuals from the Human Functional Genomics Project. We functionally grouped common and rare variants, over gene, subpathway, and inflammatory levels and performed the Sequence Kernel Association Test to test for association with in vitro stimulation-induced cytokine responses; specifically, IL-1β and IL-6 cytokine measurements upon stimulations that represent an array of microbial infections: lipopolysaccharide (LPS), phytohaemagglutinin (PHA), Candida albicans ( C. albicans ), and Staphylococcus aureus ( S. aureus ). Results We identified a burden of NCF4 rare variants with PHA-induced IL-6 cytokine and showed that the respective carriers are in the 1% lowest IL-6 producers. Collapsing rare variants in IL-1 subpathway genes produces a bidirectional association with LPS-induced IL-1β cytokine levels, which is reflected by a significant Spearman correlation. On the inflammatory level, we identified a burden of rare variants in genes encoding for proteins with an anti-inflammatory function with S. aureus -induced IL-6 cytokine. In contrast to these rare variant findings which were based on different types of stimuli, common variant associations were exclusively identified with C. albicans -induced cytokine over various levels of grouping, from the gene, to subpathway, to inflammatory level. Conclusions In conclusion, this study shows that functionally grouping common and rare genetic variants enables the elucidation IL-1-mediated biological mechanisms, specifically, for IL-1β and IL-6 cytokine responses induced by various stimuli. The framework used in this study may allow for the analysis of rare and common genetic variants in a wider variety of (non-immune) complex phenotypes and therefore has the potential to contribute to better understanding of unresolved, complex traits and diseases.
Occurrence of severe COVID-19 in vaccinated transplant patients
Authors: Sophie Caillard, Nathalie Chavarot, Dominique Bertrand, Nassim Kamar, Olivier Thaunat, Valerie Moal, Christophe Masset, Marc Hazzan, Philippe Gatault, Antoine Sicard, Jonathan M. Chemouny, Jean Philippe Rerolle, Charlotte Colosio, Hélène Francois, Jamal Bamoulid, Nicolas Bouvier, Agnès Duveau, Dany Anglicheau, Gilles Blancho
Journal: Kidney International (2021)
Impairment of human terminal erythroid differentiation by histone deacetylase 5 deficiency
Authors: Yaomei Wang, Wei Li, Vincent P. Schulz, Huizhi Zhao, Xiaoli Qu, Qian Qi, Yong Cheng, Xinhua Guo, Shijie Zhang, Xin Wei, Donghao Liu, Karina Yazdanbakhsh, Christopher D. Hillyer, Narla Mohandas, Lixiang Chen, Patrick G. Gallagher, Xiuli An
Journal: Blood (2021)
Metagenomic analysis of the conjunctival bacterial and fungal microbiome in vernal keratoconjunctivitis
Authors: Andrea Leonardi, Rocco Luigi Modugno, Fabiano Cavarzeran, Umberto Rosani
Journal: Allergy (2021)

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Covid-19: Public debate is needed to decide how UK will live with SARS-CoV-2, says ethics collaborative
Authors: Elisabeth Mahase
Journal: BMJ (2021)

As the UK eases its covid-19 restrictions, and the initial two-dose vaccination rollout nears its end, more radical forms of public engagement will be essential when resolving the difficult questions about how the country will live with SARS-CoV-2, the UK Pandemic Ethics Accelerator collaborative has said.As part of the collaborative, researchers from the universities of Oxford, Bristol, Edinburgh, and University College London considered some of the challenging ethical questions that the pandemic has raised. 1 UK Pandemic Ethics Accelerator.Living and dying with covid-19-an ethical perspective is vital [press release].
Ambient PM<sub>2.5</sub>exposure and hospital cost and length of hospital stay for respiratory diseases in 11 cities in Shanxi Province, China
Authors: Dawei Cao, Dongyan Li, Yinglin Wu, Zhengmin (Min) Qian, Yi Liu, Qiyong Liu, Jimin Sun, Yuming Guo, Shiyu Zhang, Guangyuan Jiao, Xiaoran Yang, Chongjian Wang, Stephen Edward McMillin, Xinri Zhang, Hualiang Lin
Journal: Thorax (2021)

Background Few studies have examined the effects of ambient particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM 2.5 ) on hospital cost and length of hospital stay for respiratory diseases in China. Methods We estimated ambient air pollution exposure for respiratory cases through inverse distance-weighted averages of air monitoring stations based on their residential address and averaged at the city level. We used generalised additive models to quantify city-specific associations in 11 cities in Shanxi and a meta-analysis to estimate the overall effects. We further estimated respiratory burden attributable to PM 2.5 using the standards of WHO (25 µg/m 3 ) and China (75 µg/m 3 ) as reference. Results Each 10 µg/m 3 increase in lag 03 PM 2.5 corresponded to 0.53% (95% CI: 0.33% to 0.73%) increase in respiratory hospitalisation, an increment of 3.75 thousand RMB (95% CI: 1.84 to 5.670) in hospital cost and 4.13 days (95% CI: 2.51 to 5.75) in length of hospital stay. About 9.7 thousand respiratory hospitalisations, 132 million RMB in hospital cost and 145 thousand days of hospital stay could be attributable to PM 2.5 exposures using WHO’s guideline as reference. We estimated that 193 RMB (95% CI: 95 to 292) in hospital cost and 0.21 days (95% CI: 0.13 to 0.30) in hospital stay could be potentially avoidable for an average respiratory case. Conclusion Significant respiratory burden could be attributable to PM 2.5 exposures in Shanxi Province, China. The results need to be factored into impact assessment of air pollution policies to provide a more complete indication of the burden addressed by the policies.
From Assessment to Implementation and Beyond in Cancer and Aging Research
Authors: Stuart M. Lichtman, Harvey J. Cohen, Hyman Muss, William P. Tew, Beatriz Korc-Grodzicki
Journal: Journal of Clinical Oncology (2021)

Article Tools REVIEW ARTICLES Caring for Older Adults With Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.21.00317 Journal of Clinical Oncology - published online before print May 27, 2021 PMID: 34043443 From Assessment to Implementation and Beyond in Cancer and Aging Research Stuart M. Lichtman , MD1xStuart M. LichtmanSearch for articles by this author; Harvey J. Cohen, MD2xHarvey J. CohenSearch for articles by this author; Hyman Muss , MD3xHyman MussSearch for articles by this author; William P. Tew , MD1xWilliam P. TewSearch for articles by this author; and Beatriz Korc-Grodzicki , MD, PhD1xBeatriz Korc-GrodzickiSearch for articles by this author Show More 1Memorial Sloan Kettering Cancer Center, New York, NY2Duke University Medical Center, Durham, NC3Department of Medicine and UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC https://doi.org/10.1200/JCO.21.00317 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologyCONTEXTKey ObjectiveTo discuss the development of geriatric oncology over the past 40 years including important contributions of various investigators and organizations.Knowledge GeneratedWe studied the importance of an oncology-specific geriatric assessment for clinical practice and research and the need for interdisciplinary involvement.RelevanceNeed to incorporate geriatric assessment principles into routine practice and to use these methods for clinical trials to develop data to improve patient treatment outcomes.AUTHOR CONTRIBUTIONSConception and design: All authorsProvision of study materials or patients: Stuart M. LichtmanCollection and assembly of data: Stuart M. Lichtman, Beatrice Korc-GrodzickiData analysis and interpretation: Stuart M. Lichtman, Hyman Muss, Beatrice Korc-GrodzickiManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFrom Assessment to Implementation and Beyond in Cancer and Aging ResearchThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Stuart LichtmanConsulting or Advisory Role: Remedy One, Magellan Health.No other potential conflicts of interest were reported.
Diagnostic and Therapeutic Delays in Patients With Hepatocellular Carcinoma
Authors: Ashwin Rao, Nicole E. Rich, Jorge A. Marrero, Adam C. Yopp, Amit G. Singal
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Delays in diagnosis and treatment have been reported for many cancers, with resultant stage migration and worse survival; however, few data exist in patients with hepatocellular carcinoma (HCC). These data are of particular importance in light of the COVID-19 pandemic, which has caused disruptions in healthcare processes and may continue to impact cancer care for the foreseeable future. The aim of our study was to characterize the prevalence and clinical significance of diagnostic and treatment delays in patients with HCC. Methods: We performed a retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and July 2017 at 2 US health systems. Diagnostic and treatment delays were defined as &gt;90 days between presentation and HCC diagnosis and between diagnosis and treatment, respectively. We used multivariable logistic regression to identify factors associated with diagnostic and treatment delays and Cox proportional hazard models to identify correlates of overall survival. Results: Of 925 patients with HCC, 39.0% were diagnosed via screening, 33.1% incidentally, and 27.9% symptomatically. Median time from presentation to diagnosis was 37 days (interquartile range, 18–94 days), with 120 patients (13.0%) experiencing diagnostic delays. Median time from HCC diagnosis to treatment was 46 days (interquartile range, 29–74 days), with 17.2% of patients experiencing treatment delays. Most (72.5%) diagnostic delays were related to provider-level factors (eg, monitoring indeterminate nodules), whereas nearly half (46.2%) of treatment delays were related to patient-related factors (eg, missed appointments). In multivariable analyses, treatment delays were not associated with increased mortality (hazard ratio, 0.90; 95% CI, 0.60–1.35); these results were consistent across subgroup analyses by Barcelona Clinic Liver Cancer stage and treatment modality. Conclusions: Diagnostic and therapeutic delays exceeding 3 months are common in patients with HCC; however, observed treatment delays do not seem to significantly impact overall survival.
POS0711 SUICIDAL BEHAVIOUR IN SLE PATIENTS: A SYSTEMATIC LITERATURE REVIEW
Authors: A. Kyriakou, A. Chatzittofis, K. Parperis
Journal: Annals of the Rheumatic Diseases (2021)

Background: Previous studies have demonstrated that SLE patients have a higher risk of suicidal behaviour, including suicidal ideation, attempt and complete suicide (1,2). Data describing the SLE patients’ clinical characteristics and risk factors of suicidal behaviour are lacking. Objectives: To determine the magnitude of suicidal behaviour among SLE patients and to examine predictors associated with suicidal behaviour. Methods: According to the PRISMA guidelines, we conducted a systematic literature review of the online databases, PubMed/Medline, EMBASE, and Web of Science, from inception to December 2020 (Figure 1). Full-text original articles that examined the relationship between SLE patients with suicidal behaviour were eligible for our review. Two reviewers independently review articles to assess eligibility using the Newcastle-Ottawa Scale and the Joanna Briggs Institute tools. Systematic reviews, metanalysis, narrative review, case reports, case series, including less than 10 patients and conference abstracts, were excluded. Results: Of the 64 articles identified, 22 were relevant to the study question; cross-sectional (n=8) and prospective cohorts (n=6) were the most frequently retrieved studies. Among the 27106 SLE patients with SLE, 802 had suicidal behaviour (2.9%), and of those, 87.9% were female. Suicide attempt occurred in 573/802 (71.4%) and complete suicide in 18/802 (2,3%). Major depressive disorder (MDD) was the most frequently reported coexisting psychiatric condition associated with suicidal behavior, followed by psychosis and social phobia. Several clinical manifestations were linked to suicidal behaviour, particularly neuropsychiatric lupus, mucocutaneous, renal involvement and serositis. Further, high scores in disease activity and damage indices were associated with suicidal behaviour. Conclusion: Suicidal behavior in SLE patients was associated with MDD, NPSLE, active disease and damage. Awareness of these findings can guide clinicians to recognize suicide behavior promptly and prevent suicide attempts. References: [1]Hajduk A, Nowicka-Sauer K, Smoleńska Ż, Czuszyńska Z, Zdrojewski Z. Prevalence and correlates of suicidal thoughts in patients with neuropsychiatric lupus. Lupus. 2016 Feb;25(2):185-92. doi: 10.1177/0961203315603136. [2]Buji RI, Abdul Murad NA, Chan LF, Maniam T, Mohd Shahrir MS, Rozita M, Shamsul AS, Mohamad Hussain R, Abdullah N, Jamal R, Nik Jaafar NR. Suicidal ideation in systemic lupus erythematosus: NR2A gene polymorphism, clinical and psychosocial factors. Lupus. 2018 Apr;27(5):744-752. doi: 10.1177/0961203317742711. Figure 1. A PRISMA chart describing the inclusion/exclusion process Disclosure of Interests: None declared
Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19
Authors: Jacqui Venturas, Jarrod Zamparini, Erica Shaddock, Sarah Stacey, Lyle Murray, Guy A Richards, Ismail Kalla, Adam Mahomed, Farzahna Mohamed, Mervyn Mer, Innocent Maposa, Charles Feldman
Journal: Journal of Infection (2021)

South Africa has the highest prevalence of HIV in the world and to date has recorded the highest number of cases of COVID-19 in Africa. There is uncertainty as to what the significance of this dual infection is, and whether people living with HIV (PLWH) have worse outcomes compared to HIV-negative patients with COVID-19. This study compared the outcomes of COVID-19 in a group of HIV-positive and HIV-negative patients admitted to a tertiary referral centre in Johannesburg, South Africa.
Clinical Approach to Cardiovascular Toxicity of Oral Antineoplastic Agents
Authors: Vijay U. Rao, David J. Reeves, Atul R. Chugh, Rupal O’Quinn, Michael G. Fradley, Meghana Raghavendra, Susan Dent, Ana Barac, Daniel Lenihan
Journal: Journal of the American College of Cardiology (2021)

Precision medicine has ushered in a new era of targeted treatments for numerous malignancies, leading to improvements in overall survival. Unlike traditional chemotherapy, many molecular targeted antineoplastic agents are available in oral formulation, leading to enhanced patient convenience and a perception of reduced risk of adverse effects. Although oral antineoplastic agents are generally well-tolerated, cardiovascular toxicities are being reported with increasing frequency in part due to U.S. Food and Drug Administration and manufacturer recommended cardiac monitoring. Monitoring strategies have focused on left ventricular dysfunction, hypertension, and QT prolongation/arrhythmias. Given the rapid pace of development and availability of new oral antineoplastic agents, the purpose of this review is to provide clinicians with an up-to-date practical approach to monitoring and management of cardiovascular toxicities with the aim of improving overall outcomes for patients with cancer.
Human kidney stones: a natural record of universal biomineralization
Authors: Mayandi Sivaguru, Jessica J. Saw, Elena M. Wilson, John C. Lieske, Amy E. Krambeck, James C. Williams, Michael F. Romero, Kyle W. Fouke, Matthew W. Curtis, Jamie L. Kear-Scott, Nicholas Chia, Bruce W. Fouke
Journal: Nature Reviews Urology (2021)
Embryonic macrophages function during early life to determine invariant natural killer T cell levels at barrier surfaces
Authors: Thomas Gensollen, Xi Lin, Ting Zhang, Michal Pyzik, Peter See, Jonathan N. Glickman, Florent Ginhoux, Matthew Waldor, Marko Salmi, Pia Rantakari, Richard S. Blumberg
Journal: Nature Immunology (2021)
On the Origin of Frameshift-Robustness of the Standard Genetic Code
Authors: Haiqing Xu, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2021)

Abstract The standard genetic code (SGC) has been extensively analyzed for the biological ramifications of its nonrandom structure. For instance, mismatch errors due to point mutation or mistranslation have an overall smaller effect on the amino acid polar requirement under the SGC than under random genetic codes (RGCs). A similar observation was recently made for frameshift errors, prompting the assertion that the SGC has been shaped by natural selection for frameshift-robustness—conservation of certain amino acid properties upon a frameshift mutation or translational frameshift. However, frameshift-robustness confers no benefit because frameshifts usually create premature stop codons that cause nonsense-mediated mRNA decay or production of nonfunctional truncated proteins. We here propose that the frameshift-robustness of the SGC is a byproduct of its mismatch-robustness. Of 564 amino acid properties considered, the SGC exhibits mismatch-robustness in 93–133 properties and frameshift-robustness in 55 properties, respectively, and that the latter is largely a subset of the former. For each of the 564 real and 564 randomly constructed fake properties of amino acids, there is a positive correlation between mismatch-robustness and frameshift-robustness across one million RGCs; this correlation arises because most amino acid changes resulting from a frameshift are also achievable by a mismatch error. Importantly, the SGC does not show significantly higher frameshift-robustness in any of the 55 properties than RGCs of comparable mismatch-robustness. These findings support that the frameshift-robustness of the SGC need not originate through direct selection and can instead be a site effect of its mismatch-robustness.
Why Did the Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC Not Reveal a Difference?
Authors: José S.A. Belderbos, Dirk K.M. De Ruysscher, Katrien De Jaeger, Friederike Koppe, Maarten L.F. Lambrecht, Yolande Lievens, Edith M.T. Dieleman, Jaap P.M. Jaspers, Jan P. Van Meerbeeck, Fred Ubbels, Magriet Kwint, Marianne Kuenen, Sabine Deprez, Michiel B. De Ruiter, Willem Boogerd, Karolina Sikorska, Harm Van Tinteren, Sanne B. Schagen
Journal: Journal of Thoracic Oncology (2021)
SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021
Authors: Anna Loenenbach, Inessa Markus, Ann-Sophie Lehfeld, Matthias an der Heiden, Walter Haas, Maya Kiegele, André Ponzi, Barbara Unger-Goldinger, Cornelius Weidenauer, Helen Schlosser, Alexander Beile, Udo Buchholz
Journal: Eurosurveillance (2021)

We investigated three SARS-CoV-2 variant B.1.1.7 childcare centre and related household outbreaks. Despite group cohorting, cases occurred in almost all groups, i.e. also among persons without close contact. Children's secondary attack rates (SAR) were similar to adults (childcare centres: 23% vs 30%; p = 0.15; households: 32% vs 39%; p = 0.27); child- and adult-induced household outbreaks also led to similar SAR. With the advent of B.1.1.7, susceptibility and infectiousness of children and adults seem to converge. Public health measures should be revisited accordingly.
細静脈ではなく細動脈における血管内皮以外の一酸化窒素供給源:生体内でのジアミノフルオレセイン・マイクロ・フルオログラフィーによって明らかにされる他の供給源
Authors: Kashiwagi S, Kajimura M, Yoshimura Y, Suematsu M
Journal: Circulation Research (2002)