bluuebunny/crossref_metadata_2025_split huggingface dataset:
The incidence of COVID-19-related hospitalisation in migrants in the UK: Findings from the Virus Watch prospective community cohort study
Authors: Fong Wing Lam Erica , Nguyen Vincent G , Burns Rachel , Boukari Yamina , Beale Sarah , Braithwaite Isobel , Byrne Thomas E , Geismar Cyril , Fragaszy Ellen , Hoskins Susan , Kovar Jana , Navaratnam Annalan MD , Oskrochi Youssof , Patel Parth , Tweed Sam , Yavlinsky Alexei , Hayward Andrew C , Aldridge Robert W 
Published: January 2023

AbstractBackgroundMigrants in the UK may be at higher risk of SARS-CoV-2 exposure; however, little is known about their risk of COVID-19-related hospitalisation during waves 1-3 of the pandemic.MethodsWe analysed secondary care data linked to Virus Watch study data for adults and estimated COVID-19-related hospitalisation incidence rates by migration status. To estimate the total effect of migration status on COVID-19 hospitalisation rates, we ran fixed-effect Poisson regression for wave 1 (01/03/2020-31/08/2020; wildtype), and fixed-effect negative binomial regressions for waves 2 (01/09/2020-31/05/2021; Alpha) and 3 (01/06/2020-31/11/2021; Delta). Results of all models were then meta-analysed.ResultsOf 30,276 adults in the analyses, 26,492 (87.5%) were UK-born and 3,784 (12.5%) were migrants. COVID-19-related hospitalisation incidence rates for UK-born and migrant individuals across waves 1-3 were 2.7 [95% CI 2.2-3.2], and 4.6 [3.1-6.7] per 1,000 person-years, respectively. Pooled incidence rate ratios across waves suggested increased rate of COVID-19-related hospitalisation in migrants compared to UK-born individuals in unadjusted 1.68 [1.08-2.60] and adjusted analyses 1.35 [0.71-2.60].ConclusionOur findings suggest migration populations in the UK have excess risk of COVID-19-related hospitalisations and underscore the need for more equitable interventions particularly aimed at COVID-19 vaccination uptake among migrants.
Who Gets Long COVID and Suffers its Mental Health and Socioeconomic Consequences in the United States? Preliminary Findings from a Large Nationwide Study
Authors: Kim Daniel 
Published: January 2023

ABSTRACTAs the number of confirmed COVID-19 cases now exceeds 100 million cases in the United States and continues to climb, concerns have been increasingly raised over the future public health and economic burden of long COVID including disability and concomitant declines in labor force participation. Only a handful of US population-based studies have explored sociodemographic and socioeconomic characteristics that put people at risk of long COVID or have investigated its mental health and socioeconomic sequelae. Herein, I report findings from the largest multivariable analysis to date using US nationally-representative data on 153,543 adults including 19,985 adults with long COVID to explore key predictors and sequelae of long COVID. An estimated 14.0% of adults aged 18-84 y (35.11 million adults) and 15.5% of working-aged adults aged 18-64 y (30.65 million adults) had developed long COVID by November 2022. Several sociodemographic and socioeconomic factors predicted long COVID including lower household income, being aged 30-49 y, Hispanic, female, gay/lesbian or bisexual, and divorced/separated. Even after accounting for such factors, having long COVID was linked to higher risks of recent unemployment, financial hardship, and anxiety and depressive symptomatology, with evidence of dose-response relationships. Overall, an estimated 27.7 million US adults aged 18-84 y and 24.2 million working-aged adults with long COVID who had been or may still be at risk of adverse socioeconomic and mental health outcomes. Lost work was further calculated to be the equivalent of 3 million workers annually, and the estimated annual lost earnings due to long COVID among working-aged adults totaled $175 billion. These preliminary findings highlight the substantial public health and economic implications of long COVID among Americans and should prompt further inquiry and intervention.
Down-regulation ofMALAT1is a hallmark of tissue and peripheral proliferative T cells in COVID-19
Authors: Dey Shoumit , Ashwin Helen , Milross Luke , Hunter Bethany , Majo Joaquim , Filby Andrew J , Fisher Andrew J , Kaye Paul M. , Lagos Dimitris 
Published: January 2023

AbstractT cells play key protective but also pathogenic roles in COVID-19. We studied expression of long non-coding RNAs (lncRNAs) in COVID-19 T cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNAMALAT1was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highestMALAT1expression, amongst CD4+ and CD8+ T cells populations, respectively. We then identified gene signatures that covaried withMALAT1in single T cells. A significantly higher number of transcripts correlated negatively withMALAT1than those that correlated. Enriched functional annotations of theMALAT1-anti-correlating gene signature included processes associated with T cell activation such as cell division, oxidative phosphorylation and response to cytokine. TheMALAT1anti-correlating gene signature shared by both CD4+ and CD8+ T cells marked dividing T cells in both lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated thatMALAT1suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results revealMALAT1suppression and its associated gene signature are a hallmark of human proliferating T cells.
Wastewater and seroprevalence for pandemic preparedness: variant analysis, vaccination effect, and hospitalization forecasting for SARS-CoV-2, in Jefferson County, Kentucky
Authors: Holm Rochelle H. , Rempala Grzegorz A. , Choi Boseung , Brick J. Michael , Amraotkar Alok R. , Keith Rachel J. , Rouchka Eric C. , Chariker Julia H. , Palmer Kenneth E. , Smith Ted , Bhatnagar Aruni 
Published: January 2023

AbstractDespite wide scale assessments, it remains unclear how large-scale SARS-CoV-2 vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021–August 2021 in Jefferson County, Kentucky (USA). Our susceptible (S), vaccinated (V), variant-specific infected (I1andI2), recovered (R), and seropositive (T) model (SVI2RT) tracked prevalence longitudinally. This was related to wastewater concentration. The 64% county vaccination rate translated into about 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence was a 24-fold increase of infection counts, which corresponded to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration had the strongest correlation (r = 0.95) at 1 week lag. Our study underscores the importance of continued environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.
OmiCrisp: A CRISPR SARS-CoV-2 test with Omicron detection
Authors: Sharma Suruchi , Prakash Manasa Bagur , Gupta Nimisha , Gupta Vaijayanti , Chandru Vijay 
Published: January 2023

AbstractWe have developed a CRISPR based assay that can detect the presence of SARS-CoV-2 in RNA extracted from human samples and also predict if it is an Omicron or non-Omicron variant of the virus. This is a nucleic acid amplification-based test (NAAT). The amplification and detection are carried out in two independent steps in this assay. Amplification is done using a standard one-step RT-PCR method. The detection is done using a method that utilizes the trans-cleavage activity of the Cas12a enzyme. We have evaluated the performance of OmiCrisp in more than 80 clinical samples and observed an agreement of 100% with the sequencing results, in labeling SARS-CoV-2 positive samples as Omicron or non-Omicron. OmiCrisp -like platform can be developed quickly and can potentially complement sequencing for quick and rapid tracking of the transmission of new pathogen variants.
Impact of the COVID-19 pandemic on food safety inspection outcomes in Toronto, Canada: a Bayesian interrupted time series analysis
Authors: Young Ian , Desta Binyam Negussie , Sekercioglu Fatih 
Published: January 2023

SummaryThe coronavirus disease (COVID-19) pandemic resulted in major disruptions to the food service industry and regulatory food inspections. The objective of this study was to conduct an interrupted time series analysis to investigate the impact of the COVID-19 pandemic on food safety inspection trends in Toronto, Canada. Inspection data for restaurants and take-out establishments were obtained from 2017 to 2022 and ordered as a weekly time series. Bayesian segmented regression was conducted to evaluate the impact of the pandemic on weekly infraction and inspection pass rates. On average, a 0.31-point lower weekly infraction rate (95% credible interval [CI]: 0.23, 0.40) and a 2.0% higher probability of passing inspections (95% CI: 1.1%, 3.0%) were predicted in the pandemic period compared to pre-pandemic. Models predicted lower infraction rates and higher pass rates immediately following the pandemic that were regressing back toward pre-pandemic levels in 2022. Seasonal effects were also identified, with infraction rates highest in April and pass rates lowest in August. The COVID-19 pandemic resulted in an initial positive effect on food safety outcomes in restaurants and take-out food establishments in Toronto, but this effect appears to be temporary. Additional research is needed on seasonal and long-term inspection trends post-pandemic.
Development ofEncarsia tabacivora(Viggiani) (Hymenoptera: Aphelinidae) in nymphs ofBemisia tabaci(Gennadius) MEAN 1 (Hemiptera: Aleyrodidae)
Authors: Gamarra Heidy , Sporleder Marc , Supanta Luz , Rodríguez Alexander , Kroschel Jürgen , Kreuze Jan 
Published: January 2023

AbstractEncarsia tabacivoraViggiani 1985 (Hymenoptera: Aphelinidae), is an endoparasitoid of whiteflies, includingBemisia tabaci(Gennadius) MEAN 1 (Hemiptera: Aleyrodidae), reported from southern USA, Caribbean, and Brazil. In field surveys, the natural occurrence ofE. tabacivorawas confirmed in the Cañete valley of Peru. Its biology and development was studied under laboratory conditions at 20°C and 70-75% RH. The results showed that fertilized females lay their eggs inside nymphs of the 3rdand early 4thinstar ofB. tabaciMEAN 1. The stages of development are egg, three larval instars, prepupa and pupa. Development from egg to adult lasted 19.3 (SE±0.17) days for females. No males were produced, which indicates thatE. tabacivoraexhibits thelytokous parthenogenesis. Parasitized host nymphs exhibited multiple oviposition punctures and several L1-instar wasps were observed in individual host nymphs, indicating superparasitism. However, from the L2-instar onwards only one individual developed to adult stage.E. tabacivoramight be a prospective biological control agent forB. tabaciin sweet potato also for minimizing the spread of whitefly-induced plant viruses in Peru and other regions of the world. The knowledge gained might be helpful in establishing mass rearing protocols ofE. tabacivorafor inoculative releases.
A multicolor suite for deciphering population coding in calcium and cAMPin vivo
Authors: Yokoyama Tatsushi , Manita Satoshi , Uwamori Hiroyuki , Tajiri Mio , Imayoshi Itaru , Yagishita Sho , Murayama Masanori , Kitamura Kazuo , Sakamoto Masayuki 
Published: January 2023

SUMMARYcAMP is a pivotal second messenger regulated by various upstream pathways including Ca2+and G protein-coupled receptors (GPCRs). To decipherin vivocAMP dynamics, we rationally designed cAMPinG1, an ultrasensitive genetically encoded green cAMP indicator that outperformed its predecessors in both dynamic range and cAMP affinity. Two-photon cAMPinG1 imaging detected cAMP transients in the somata and dendritic spines of neurons in the mouse visual cortex on the order of tens of seconds. In addition, multicolor imaging with a highly sensitive new red Ca2+indicator RCaMP3 allowed simultaneous measurement of population patterns in Ca2+and cAMP in hundreds of neurons. We identified Ca2+-induced cAMP responses that represented specific information, such as direction selectivity in vision and locomotion, as well as GPCR-induced cAMP responses. Overall, our multicolor suite revealed that information encoded in Ca2+and GPCRs signaling is integrated and stored as cAMP transients for longer periodsin vivo.HighlightsDeveloping an ultrasensitive cAMP indicator, cAMPinG1, for visualizing cAMP transients in somata and dendritic spinesin vivo.Developing a highly sensitive red Ca2+indicator, RCaMP3, for visualizing Ca2+transients in large neuronal population.Dual-color Ca2+and cAMP imaging for dissecting Ca2+-induced and GPCR-induced cAMP responses.Single-cell, single-timepoint cAMP imaging for GRCR biology and drug screening.
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting
Authors: Jun Lee Eric Hee , Cullen Cody , Murad John P. , Gumber Diana , Park Anthony K. , Yang Jason , Stern Lawrence A. , Adkins Lauren N. , Dhapola Gaurav , Gittins Brenna , Chung-Chang Wen , Martinez Catalina , Woo Yanghee , Cristea Mihaela , Rodriguez-Rodriguez Lorna , Ishihara Jun , Lee John K. , Forman Stephen J. , Wang Leo D. , Priceman Saul J. 
Published: January 2023

AbstractChimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies, which are being harnessed to improve solid tumor CAR T cell therapies. Here, we describe fully optimized CAR T cells targeting tumor-associated glycoprotein-72 (TAG72) for the treatment of solid tumors, identifying the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFNγ secretion. These findings have culminated into a phase 1 trial evaluating safety, feasibility, and bioactivity of TAG72-CAR T cells for the treatment of patients with advanced ovarian cancer (NCT05225363). Preclinically, we found that CAR T cell-mediated IFNγ production facilitated by IL-12 signaling was required for tumor cell killing, which was recapitulated by expressing an optimized membrane-bound IL-12 (mbIL12) molecule on CAR T cells. Critically, mbIL12 cell surface expression and downstream signaling was induced and sustained only following CAR T cell activation. CAR T cells with mbIL12 demonstrated improved antigen-dependent T cell proliferation and potent cytotoxicity in recursive tumor cell killing assaysin vitroand showed robustin vivoanti-tumor efficacy in human xenograft models of ovarian cancer peritoneal metastasis. Further, locoregional administration of TAG72-CAR T cells with antigen-dependent IL-12 signaling promoted durable anti-tumor responses against both regional and systemic disease in mice and was associated with improved systemic T cell persistence. Our study features a clinically-applicable strategy to improve the overall efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting both regional and systemic disease.
Gene Expression Changes in Cultured Reactive Rat Astrocyte Models and Comparison to Device-Associated Effects in the Brain
Authors: Riggins Ti’Air E. , Whitsitt Quentin A. , Saxena Akash , Hunter Emani , Hunt Bradley , Thompson Cort H. , Moore Michael G. , Purcell Erin K. 
Published: January 2023

AbstractImplanted microelectrode arrays hold immense therapeutic potential for many neurodegenerative diseases. However, a foreign body response limits long-term device performance. Recent literature supports the role of astrocytes in the response to damage to the central nervous system (CNS) and suggests that reactive astrocytes exist on a spectrum of phenotypes, from beneficial to neurotoxic. The goal of our study was to gain insight into the subtypes of reactive astrocytes responding to electrodes implanted in the brain. In this study, we tested the transcriptomic profile of two reactive astrocyte culture models (cytokine cocktail or lipopolysaccharide, LPS) utilizing RNA sequencing, which we then compared to differential gene expression surrounding devices inserted into rat motor cortex via spatial transcriptomics. We interpreted changes in the genetic expression of the culture models to that of 24 hour, 1 week and 6 week rat tissue samples at multiple distances radiating from the injury site. We found overlapping expression of up to ∼250 genes betweenin vitromodels andin vivoeffects, depending on duration of implantation. Cytokine-induced cells shared more genes in common with chronically implanted tissue (≥1 week) in comparison to LPS-exposed cells. We revealed localized expression of a subset of these intersecting genes (e.g.,Serping1, Chi3l1, and Cyp7b1)in regions of device-encapsulating, glial fibrillary acidic protein (GFAP)-expressing astrocytes identified with immunohistochemistry. We applied a factorization approach to assess the strength of the relationship between reactivity markers and the spatial distribution of GFAP-expressing astrocytesin vivo. We also provide lists of hundreds of differentially expressed genes between reactive culture models and untreated controls, and we observed 311 shared genes between the cytokine induced model and the LPS-reaction induced control model. Our results show that comparisons of reactive astrocyte culture models with spatial transcriptomics data can reveal new biomarkers of the foreign body response to implantable neurotechnology. These comparisons also provide a strategy to assess the development ofin vitromodels of the tissue response to implanted electrodes.
Identification of common sequence motifs shared exclusively among selectively packed exosomal pathogenic microRNAs during rickettsial infections
Authors: Bei Jiani , Qiu Yuan , Cockrell Diane , Chang Qing , Husseinzadeh Sorosh , Zhou Changcheng , Gaitas Angelo , Fang Xiang , Jin Yang , Khanipov Kamil , Saito Tais B. , Gong Bin 
Published: January 2023

AbstractWe previously reported that microRNA (miR)23a and miR30b are selectively sorted into rickettsia-infected, endothelial cell-derived exosomes (R-ECExos). Yet, the mechanism remains unknown. The number of cases of spotted fever rickettsioses has been increasing in recent years, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues. Therefore, the aim of the present study is to continue to dissect the molecular mechanism underlyingR-ECExos-induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Rickettsiae are transmitted to human hosts by the bite of an infected tick into the skin. In the present study we demonstrate that treatment withR-ECExos, which were derived from spotted fever groupR parkeriinfected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE-cadherin and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA-dependent manner. Similarly, we did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy-relevant miR23a-27a-24 cluster and miR30b are selectively enriched inR-ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively-enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a single, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy-relevant miR23a-27a-24 and miR30b, and subsequently results in their selective enrichments inR-ECExos.
Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations inTP53, KMTgenes andPDGFBfusions
Authors: Das Sunetra , Idate Rupa , Lana Susan E. , Regan Daniel P. , Duval Dawn L. 
Published: January 2023

AbstractCanine soft tissue sarcomas (STS) are a heterogenous group of malignant tumors arising from mesenchymal cells of soft tissues. This simplified collective of tumors most commonly arise from subcutaneous tissues, are treated similar clinically, and conventionally exclude other sarcomas with more definitive anatomical, histological, or biological features. Histologically, canine STS sub-types are difficult to discern at the light microscopic level due to their overlapping features. Thus, genomic, and transcriptomic profiling of canine STS may prove valuable in differentiating the diverse sub-types of mesenchymal neoplasms within this group. To this purpose we sought to characterize the transcript expression and genomic mutation profiles of canine STS. To delineate transcriptomic sub-types, hierarchical clustering was used to identify 4 groups with district expression profiles. Using the RNAseq data, we identified three samples carrying driver fusions of platelet derived growth factor B (PDGFB) and collagen genes. Sensitivity to imatinib was evaluated in a canine STS cell line also bearing aPDGFBfusion. Using whole exome sequencing, recurrent driver variants were identified in the cancer genesKMT2D(21% of the samples) andTP53(21%) along with copy number losses of RB1 and CDKN2A. Gene amplifications and resulting transcript increases were identified in genes on chromosomes 13, 14, and 36. A subset of STS was identified with high T-cell infiltration. This multi-omics approach has defined canine STS sub-types at a molecular level for comparison to their human counterparts, to improve diagnosis, and may provide additional targets for therapy.
A hierarchical pathway for assembly of the distal appendages that organize primary cilia
Authors: Kanie Tomoharu , Love Julia F. , Fisher Saxton D. , Gustavsson Anna-Karin , Jackson Peter K. 
Published: January 2023

SummaryDistal appendages are nine-fold symmetric blade-like structures attached to the distal end of the mother centriole. These structures are critical for formation of the primary cilium, by regulating at least four critical steps: ciliary vesicle recruitment, recruitment and initiation of intraflagellar transport (IFT), and removal of CP110. While specific proteins that localize to the distal appendages have been identified, how exactly each protein functions to achieve the multiple roles of the distal appendages is poorly understood. Here we comprehensively analyze known and newly discovered distal appendage proteins (CEP83, SCLT1, CEP164, TTBK2, FBF1, CEP89, KIZ, ANKRD26, PIDD1, LRRC45, NCS1, C3ORF14) for their precise localization, order of recruitment, and their roles in each step of cilia formation. Using CRISPR-Cas9 knockouts, we show that the order of the recruitment of the distal appendage proteins is highly interconnected and a more complex hierarchy. Our analysis highlights two protein modules, CEP83-SCLT1 and CEP164-TTBK2, as critical for structural assembly of distal appendages. Functional assay revealed that CEP89 selectively functions in RAB34+ciliary vesicle recruitment, while deletion of the integral components, CEP83-SCLT1-CEP164-TTBK2, severely compromised all four steps of cilium formation. Collectively, our analyses provide a more comprehensive view of the organization and the function of the distal appendage, paving the way for molecular understanding of ciliary assembly.