tbuckley/cabot-search huggingface dataset:
Influenza vaccination, airways disease and the risk of COVID-19 related mortality
Authors: L. Morrison, L. Wiffen, P. Meredith, T. Brown, L. D'Cruz, A. Chauhan
Journal: Gut (2021)

Introduction UK public health policy emphasises the need for increased influenza vaccination during the COVID-19 pandemic  However, there are claims on social media that influenza vaccination increases risk of adverse outcomes in SARSCoV- 2 infection that may compromise uptake, especially in high risk groups such as those with airways disease  There is also emerging evidence that inhaled corticosteroids (ICS) may modify this risk  We therefore sought to urgently assess the risk of morbidity and mortality in individuals admitted with COVID-19, and whether this influenced by influenza vaccination, airways disease and ICS use  Method We examined data in patients admitted to a large acute hospital with microbiologically proven COVID-19 infection (positive PCR) between 23/01/2020 to 21/06/2020  Demographic and outcome data was extracted from discharge summaries, death certificates and electronic patient records  Multiple logistic regressions was performed using STATA version 12, and results for inpatient mortality expressed as odds ratios, and length of stay (morbidity) as coefficients with 95% CIs  Results 525 patients were hospitalised with COVID-19 of whom 451 had a vaccination record available and 64% had been vaccinated  22% had airways disease (10% asthma, 12% COPD) and 17 5% were on an inhaled corticosteroid  Increasing age (OR=1 04 [1 02, 1 05], p<0 001) and male gender (OR=2 26 [1 5, 3 4], p<0 001) were important predictors of inpatient mortality  Previous influenza vaccination (OR=0 99 [0 6, 1 6], p=0 98), the presence of airways disease (Asthma OR=0 74 [0 4, 1 5], p=0 41, COPD OR= 1 1 [0 6, 2 0], p=0 68), and ICS use (OR=0 84 [0 3, 2 1], p=0 71) did not increase risk of in-hospital mortality and were not associated with an increased length of stay, after adjusting for age and gender  Further sub-analysis including type of airways disease and dose of ICS did not change the risk  Conclusions Advancing age and male gender increased the risk of in-hospital mortality from COVID-19  Furthermore previous influenza vaccination and the presence of airways disease and/or the use of ICS did not impact morbidity or mortality  Whilst this requires replication using national data sets, it is reassuring data from a single centre that supports the current public health message
A novel full-human CD22-CAR T cell therapy with potent activity against CD22low B-ALL
Authors: Yue Tan, Haodong Cai, Chuo Li, Biping Deng, Weiliang Song, Zhuojun Ling, Guang Hu, Yongkun Yang, Panpan Niu, Guangrong Meng, Wei Cheng, Jinlong Xu, Jiajia Duan, Zelin Wang, Xinjian Yu, Xiaoming Feng, Jianfeng Zhou, Jing Pan
Journal: Blood Cancer Journal (2021)
Abstract 1318: Aging Inhibits The Apoptotic Resolution Of Inflammation Leading To An Exaggerated Neointimal Development In Response To Vascular Injury.
Authors: Roberto I Vazquez-Padron, Yuntao Wei, Dania Mateo, Sen Li, Sashi Salgar, Si M Pham
Journal: Circulation (2007)

Objective : This study aims to determine the mechanisms by which aging prolongs inflammation in response to vascular injury, and exaggerate neointimal formation. Methods and Results : Using balloon injury model in rat iliac arteries, we found that aging rats (22 month-old) developed thicker neointima at 4 weeks after injury than their younger counter parts (4 month-old) (I/M: 0.8 ± 0.2 vs. 0.54 ± 0.15, p&lt;0.008). We also found that injured arteries in aging animals accumulated more alpha-actin positive VSMC in the neointima than those from the young ones (500 ± 100 vs. 320 ± 120 cell/mm 2 ). Although similar number of macrophages (CD68+; detected by immunohistochemistry; IHC) appeared in the adventitia 24 h after injury in both groups, these cells disappeared in the young arteries after 3 days, while remained in the media and neointima of aging arteries until 30 days after injury. Macrophages in aging arteries were CD163 negative and IL-6 and IL-18 positive, indicating they are of pro-inflammatory phenotype. There were no differences in the number of vascular T cells and dendritic cells between groups. Vascular apoptotic cells were determined by ISOL combined with IHC either for VSMC or macrophages. Aging arteries had fewer apoptotic VSMC or macrophages (0.2% ± 0.05) at any time after vascular injury when compared with the younger ones which had abundant vascular apoptotic cells in the media and neointima at 7 days after surgery (2.7% ± 0.45). Finally, the vascular cytokines production was assessed after balloon injury using the LincoPlex system. At three days after injury aging arteries contained three folds or higher levels of IL18, IL-6, Gro KC, and Leptin than the young ones. These pro-inflammatory cytokines stayed elevated in the aging vessels for most of the arterial remodeling process. In contrast, when compared with aging arteries, young arteries produced three times or higher levels of anti-inflammatory cytokines IL-10, IL-17, IL13 and IL-9 at seven days after injury. Conclusions : Our data suggests that aging inhibits the apoptotic resolution of the vascular inflammatory response to injury, leading to exaggerated neointimal formation.
Optimization of therapeutic antibodies by predicting antigen specificity from antibody sequence via deep learning
Authors: Derek M. Mason, Simon Friedensohn, Cédric R. Weber, Christian Jordi, Bastian Wagner, Simon M. Meng, Roy A. Ehling, Lucia Bonati, Jan Dahinden, Pablo Gainza, Bruno E. Correia, Sai T. Reddy
Journal: Nature Biomedical Engineering (2021)
Post-acute COVID-19 outcomes in children with mild and asymptomatic disease
Authors: Daniela Say, Nigel Crawford, Sarah McNab, Danielle Wurzel, Andrew Steer, Shidan Tosif
Journal: The Lancet Child & Adolescent Health (2021)

Post-acute COVID-19 outcomes in children with mild and asymptomatic diseaseData on the clinical outcomes of children with COVID-19 are scarce, particularly in those with asymptomatic and mild disease. 1,2tudies involving adults suggest that long-term multisystem sequelae and complications can occur, even with mild COVID-19. 3We aimed to describe medium-term clinical outcomes 3-6 months after diagnosis in children with COVID-19 presenting to a tertiary paediatric hospital.We followed children (aged ≤18 years) at a dedicated COVID-19 follow-up clinic at the Royal Children's Hospital (RCH) in Melbourne, Australia, between March 21, 2020 and March 17, 2021.Children who tested positive for SARS-CoV-2 at the RCH or externally between March 21 and Oct 28, 2020, were referred to this clinic.A standardised clinic proforma was used to collect information on acute COVID-19 symptoms, transmission risk factors, medical history, and post-acute COVID-19 symptoms (eg, dyspnoea, fatigue, rash, or abdominal pain; appendix pp 1-2).Acute disease severity was classified according to WHO criteria. 4Data were extracted from the RCH electronic medical record.This study was approved by the RCH Human Research and Ethics Committee (HREC QA/63103/ RCHM-2020).A total of 171 children from 137 house holds attended the clinic (appen dix p 3).Most cases of COVID-19 (136 [80%] of 171 children) were identified between July and August, 2020, corresponding with the epidemio logical peak in Melbourne during this period. 5 There have been 3285 reported cases of COVID-19 in children and adolescents (aged 0-19 years) in Victoria to date (March 17, 2021). 5 Our cohort comprised of 171 children (median age 3 years [IQR 1-8]): 90 (53%) boys and 81 (47%) girls.Most children had mild disease (100 [58%]) or were asymptomatic (61 [36%]), and nine (5%) children had moderate disease.The few hospital admissions (14 [8%] children) were generally brief and were for observation or fluid rehydration.One (1%) child with complex congenital heart disease had severe COVID-19 pneumonitis with acute respiratory failure (appendix p 3).Two (1%) children had postacute COVID-19 inflammatory conditions temporally associated with SARS-CoV-2: a 7-year-old child with paediatric multisystem inflammatory syndrome who required intensive care management, and an 11-month-old child with Kawasaki disease.Follow-up data at 3-6 months were available for 151 (88%) of 171 children, of whom 54 (36%) were asymptomatic and 97 (64%) were symptomatic (ie, with mild, moderate, or severe disease) withWe declare no competing interests.DS, ST, and NC designed the study.DS and ST extracted and analysed the data.
Arterial Thromboembolism in Cancer Patients
Authors: Frits I. Mulder, Erzsébet Horváth–Puhó, Nick van Es, Lars Pedersen, Harry R. Büller, Hans Erik Bøtker, Henrik T. Sørensen
Journal: JACC CardioOncology (2021)

The relation between cancer and arterial thromboembolism (ATE) remains unclear.The purpose of this study was to evaluate ATE risk in cancer patients.Danish registries were used to identify all cancer patients between 1997 and 2017, each matched to three cancer-free comparator individuals. ATE was defined as the composite of myocardial infarction, ischemic/unspecified stroke, and peripheral arterial occlusion. A competing risk approach was used to compute cumulative incidences and subdistribution hazard ratios (SHRs). Cause-specific hazard ratios (HRs) were calculated using Cox regression. Among cancer patients, mortality risk was estimated in Cox regression analysis by treating ATE as a time-varying exposure. Patients were followed for 12 months.The study included 458,462 cancer patients and 1,375,386 comparator individuals. In the 6-month period following cancer diagnosis/index date, the cumulative incidence for ATE was 1.50% (95% confidence interval [CI]: 1.47% to 1.54%) in cancer patients and 0.76% (95% CI: 0.75% to 0.77%) in comparator individuals (HR: 2.36; 95% CI: 2.28 to 2.44). Among cancer patients age <65 years, 65 to 75 years, and >75 years, this was 0.79% (95% CI: 0.74% to 0.83%), 1.61% (95% CI: 1.55% to 1.67%), and 2.30% (95% CI: 2.22% to 2.38%), respectively. Other predictors for ATE among cancer patients were prior ATE (SHR: 2.96; 95% CI: 2.77 to 3.17), distant metastasis (adjusted SHR: 1.21; 95% CI: 1.12 to 1.30), and chemotherapy (SHR: 1.47; 95% CI: 1.33 to 1.61). Among cancer patients, ATE was associated with an increased risk of mortality (HR: 3.28; 95% CI: 3.18 to 3.38).Cancer patients are at increased risk of ATE. Clinicians should be aware of this risk, which is associated with mortality.
Association of Sleepwalking and REM Sleep Behavior Disorder With Parkinson Disease in Men
Authors: Xinyuan Zhang, Samantha A. Molsberry, Milena Pavlova, Michael A. Schwarzschild, Alberto Ascherio, Xiang Gao
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Previous studies conducted among patients with Parkinson disease (PD) reported that parasomnias other than rapid eye movement (REM) sleep behavior disorder (RBD), particularly sleepwalking (SW), are associated with PD severity. However, it remains unclear whether the presence of SW is associated with altered odds of having PD in a population-based study. <h3>Objective</h3> To evaluate whether probable SW, either alone or co-occurring with probable RBD, is associated with higher odds of PD in men. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 25 694 men from the Health Professionals Follow-up Study, a population-based cohort of male health professionals in the US with information on probable SW and probable RBD. Data collection took place between January 2012 and June 2018, and data analysis took place from July 2020 to October 2020. <h3>Exposures</h3> Probable SW and probable RBD were measured by questions adapted from the Mayo Sleep Questionnaire in 2012. <h3>Main Outcomes and Measures</h3> PD, confirmed after review of medical records by a movement disorder specialist. <h3>Results</h3> Of the 25 694 studied men (mean [SD] age, 75.6 [7.4] years), 223 (0.9%) had probable SW, 2720 (10.6%) had probable RBD, and 257 (1.0%) had PD. After adjusting for potential confounders (eg, age, smoking, caffeine intake, chronic disease status, and other sleep disorders), compared with individuals without probable SW and probable RBD, participants with probable SW, probable RBD, and both probable SW and probable RBD had higher odds of PD, (probable SW: odds ratio [OR], 4.80; 95% CI, 1.61-14.26; probable RBD: OR, 6.36; 95% CI, 4.83-8.37; both probable SW and probable RBD: OR, 8.44; 95% CI, 3.90-18.27). <h3>Conclusions and Relevance</h3> In this cross-sectional study of a male population, probable sleep parasomnias, including both SW and RBD, were associated with higher odds of having PD. PD-related neurodegeneration may impair arousal regulation during sleep.
Abstract 16407: Plasma Omega-3 Fatty Acids Predict Cardiovascular Events Stratified by Coronary Artery Calcium
Authors: Abdulhamied Alfaddagh, Karan Kapoor, Zeina Dardari, Deepak L Bhatt, Matthew J Budoff, Khurram Nasir, Michael Miller, Francine K Welty, Michael D Miedema, Michael D Shapiro, Roger S Blumenthal, Michael J Blaha
Journal: Circulation (2020)

Background: In REDUCE-IT, high-dose eicosapentaenoic acid (EPA) was beneficial in high-risk patients without clinical CVD independent of triglyceride levels. Whether the benefit of higher plasma EPA extends to those without subclinical CVD is unclear. Hypothesis: In those without clinical CVD, plasma omega-3 fatty acid (O3FA) levels predict long-term CVD events, and subclinical CVD measured by coronary artery calcium (CAC) modifies the effect such that individuals with the highest CAC attain the greatest benefit from higher O3FA. Methods: We examined 6568 MESA participants with plasma EPA and docosahexaenoic acid (DHA) levels measured at baseline and classified them by tertiles of EPA and DHA and by CAC category (0, 1-99, ≥100). Our outcome was time to CVD event (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Cox regression models were used to assess the associations between log-transformed EPA and DHA and CVD events adjusted for demographic factors, CVD risk factors, and medication use. Results: Mean age was 62.1±10.2 and 52.9% were females. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.93; P = 0.002) and log(DHA) (aHR = 0.80; 95% CI, 0.66-0.96; P = 0.019) were independently associated with fewer CVD events. The difference in absolute CVD event rates between the lowest and highest EPA tertile increased at higher CAC levels (Figure). The adjusted HR for highest compared to lowest EPA tertile within CAC 0 was 1.02 (95% CI, 0.72-1.45), CAC 1-99 was 0.71 (95% CI, 0.51-0.98), and CAC≥100 was 0.66 (95% CI, 0.52-0.83). A similar association was seen in tertiles of DHA by CAC category. These findings were consistent by sex and race category and after adjusting for O3FA supplement use. Conclusion: In an ethnically diverse population free of clinical CVD at baseline, higher plasma O3FA levels were associated with fewer CVD events. The absolute reduction in CVD events with higher O3FA levels was more apparent at higher CAC scores.
Abstract IA-020: Optimizing stem cell niche for post-irradiation regeneration
Authors: Rob P. Coppes
Journal: Clinical Cancer Research (2021)

Abstract Radiotherapy involves unavoidable co-irradiation of the normal tissue, often resulting in side effects that limit the dose to the tumor and/or reduce quality of life of cancer survivors. The response of normal tissues to irradiation is mainly determined by the survival and regenerative potential of the tissue stem cells, and modulated by inflammatory processes, vasculature damage, altered neuronal innervation and fibrosis. Indeed, transplantation of tissue specific stem cells has been shown to restores tissue homeostasis and prevent late radiation effects. However, the radiation-induced senescence, fibrosis, and chronic inflammation may chance the stem cell niche engender an unfavorable environment for the regenerative potential of the tissue’s stem cells. Here changes in the salivary gland stem cell niche will be discussed using irradiated murine submandibular salivary gland tissue and derived organoids. Recently, we have developed methods to culture murine and patient specific tissue resembling salivary gland organoids (SGO). SGO contain all the glandular lineages, are able to extensively self-renew and up on transplantation rescue salivary gland function, allowing the study of radiation responses. The role of stemness factors, senescence and inflammatory processes in stem cell self-renewal and differentiation and post-irradiation regeneration will be discussed. Using SGO formation efficiency (OFE) as a measure of regenerative potential it is shown that stem cell potency after in vivo irradiation, is time dependent reduced. Interestingly, the conditioned medium of irradiated SGO reduced the OFE of unirradiated SGO. The potential role of radiation-induced senescence-associated secretory phenotype, hippo-signaling and inflammation through activation of cytosolic DNA sensing pathways on stem cells function will be addressed. Radiation-induced environmental changes in the stem cells niche have a severe impact on stem cell function. Modulation of these effect may enhance regenerative potential of surviving stem cells and improve engraftment and regeneration after stem cell transplantation. Supported by the Dutch Cancer Society (KWF, grant No. 10650 and 12092) and The Netherlands Organisation for Health Research and Development (ZonMw, Grant nrs. 11.600.1023 and 40-43600-98-14003). Citation Format: Rob P. Coppes. Optimizing stem cell niche for post-irradiation regeneration [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 IA-020.
Estimated life expectancy gains with antiretroviral therapy among adults with HIV in Latin America and the Caribbean: a multisite retrospective cohort study
Authors: Casey L Smiley, Peter F Rebeiro, Carina Cesar, Pablo F Belaunzaran-Zamudio, Brenda Crabtree-Ramirez, Denis Padgett, Eduardo Gotuzzo, Claudia P Cortes, Jean Pape, Valdiléa G Veloso, Catherine C McGowan, Jessica L Castilho
Journal: The Lancet HIV (2021)
Brain proteome-wide association study implicates novel proteins in depression pathogenesis
Authors: Thomas S. Wingo, Yue Liu, Ekaterina S. Gerasimov, Jake Gockley, Benjamin A. Logsdon, Duc M. Duong, Eric B. Dammer, Adriana Lori, Paul J. Kim, Kerry J. Ressler, Thomas G. Beach, Eric M. Reiman, Michael P. Epstein, Philip L. De Jager, James J. Lah, David A. Bennett, Nicholas T. Seyfried, Allan I. Levey, Aliza P. Wingo
Journal: Nature Neuroscience (2021)
Abstract IA-005: Base excision repair and cancer
Authors: Joann B. Sweasy
Journal: Clinical Cancer Research (2021)

Abstract The Base Excision Repair (BER) machinery has evolved to process DNA bases damaged by reactive oxygen and nitrogen species as well as base lesions induced by alkylating agents. Deficient repair of damaged bases results in mutagenesis and genomic instability, whereas efficient repair of alkylating agents used to treat tumors leads to drug resistance. Human genome sequencing studies show that there are hundreds of germline variants in BER genes that are likely to encode proteins with altered function. This presentation will focus on the mechanistic insights gained from our characterization of some of these germline BER variants. We have discovered that variants in DNA glycosylase and DNA polymerase genes induce genomic instability and cellular transformation when expressed in non-transformed cells. These phenotypes result from defective or aberrant enzymatic function. Our results suggest that germline variants of BER genes likely increase risk for cancer and other diseases. Citation Format: Joann B. Sweasy. Base excision repair and cancer [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 IA-005.
Engineering Selectively Targeting Antimicrobial Peptides
Authors: Ming Lei, Arul Jayaraman, James A. Van Deventer, Kyongbum Lee
Journal: Annual Review of Biomedical Engineering (2021)

The rise of antibiotic-resistant strains of bacterial pathogens has necessitated the development of new therapeutics. Antimicrobial peptides (AMPs) are a class of compounds with potentially attractive therapeutic properties, including the ability to target specific groups of bacteria. In nature, AMPs exhibit remarkable structural and functional diversity, which may be further enhanced through genetic engineering, high-throughput screening, and chemical modification strategies. In this review, we discuss the molecular mechanisms underlying AMP selectivity and highlight recent computational and experimental efforts to design selectively targeting AMPs. While there has been an extensive effort to find broadly active and highly potent AMPs, it remains challenging to design targeting peptides to discriminate between different bacteria on the basis of physicochemical properties. We also review approaches for measuring AMP activity, point out the challenges faced in assaying for selectivity, and discuss the potential for increasing AMP diversity through chemical modifications.
Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma
Authors: Jiayi Zhou, Xiaojuan Pei, Yingui Yang, Zhu Wang, Weijie Gao, Ran Ye, Xiantong Zhang, Jiangang Liu, Zhuohao Liu, Xinzhi Yang, Jingli Tao, Chunshan Gu, Wei Hu, Franky Lueng Chan, Xin Li, Jie Mao, Dinglan Wu
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background High-grade gliomas are rapidly progressing tumors of the central nervous system, and are associated with poor prognosis and highly immunosuppressive microenvironments. Meanwhile, a better understanding of PD-L1, a major prognostic biomarker for checkpoint immune therapy, regulation may provide insights for developing novel immunotherapeutic strategies for treating gliomas. In the present study, we elucidate the functional significance of the orphan nuclear receptor TLX in human glioma, and its functional role in immune suppression through regulation of PD-L1/PD-1 axis. Methods TLX and PD-L1 expression patterns, and their association with clinicopathological parameters and immune phenotypes of glioma were analysed using CIBERSORT algorithm and single-sample gene-set enrichment analysis from The Cancer Genome Atlas (n=695) and Chinese Glioma Genome Atlas (n=1018) databases. Protein expression and cellular localization of TLX, PD-L1, and PD-1, as well as the prevalence of cytotoxic tumor-infiltrating lymphocytes (TILs), and tumor-associated macrophages (TAMs), in the glioma immune microenvironment were analyzed via tissue microarray by immunohistochemistry and multiplex immunofluorescence. Glioma allografts and xenografts with TLX manipulation (knockdown/knockout or reverse agonist) were inoculated subcutaneously, or orthotopically into the brains of immunodeficient and immunocompetent mice to assess tumor growth by imaging, and the immune microenvironment by flow cytometry. PD-L1 transcriptional regulation by TLX was analyzed by chromatin immunoprecipitation and luciferase reporter assays. Results TLX and PD-L1 expression was positively associated with macrophage-mediated immunosuppressive phenotypes in gliomas. TLX showed significant upregulation and positive correlation with PD-L1. Meanwhile, suppression of TLX significantly inhibited in vivo growth of glioma allografts and xenografts (p&lt;0.05), rescued the antitumoral immune response, significantly decreased the PD-L1 + , and glioma-associated macrophage population, and increased cytotoxic lymphocyte infiltration (p&lt;0.05). Mechanistically, TLX binds directly to CD274 (PD-L1) gene promoter and activates CD274 transcription. Conclusions TLX contributes to glioma malignancy and immunosuppression through transcriptional activation of PD-L1 ligands that bind to PD-1 expressed on both TILs and TAMs. Thus, targeting the druggable TLX may have potential therapeutic significance in glioma immune therapy.