bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 seroprevalence among Vancouver public school staff in British Columbia, Canada: a cross-sectional study
Authors: Goldfarb David M , Mâsse Louise C , Watts Allison W , Hutchison Sarah M , Muttucomaroe Lauren , Bosman Else S , Barakauskas Vilte E , Choi Alexandra , Dhillon Nalin , Irvine Michael A , Reicherz Frederic , O’Reilly Collette , Sediqi Sadaf , Xu Rui Yang , Razzaghian Hamid R , Sadarangani Manish , Coombs Daniel , O’Brien Sheila F , Lavoie Pascal M 
Published: April 2022

ObjectivesFew studies reported COVID-19 cases in schools during the 2020/21 academic year in a setting of uninterrupted in-person schooling. The main objective was to determine the SARS-CoV-2 seroprevalence among school staff in Vancouver public schools.DesignCumulative incident COVID-19 cases among all students and school staff based on public health data, with an embedded cross-sectional serosurvey among a school staff sample that was compared to period, age, sex and geographical location-weighted data from blood donors.SettingVancouver School District (British Columbia, Canada) from kindergarten to grade 12.ParticipantsActive school staff enrolled from 3 February to 23 April 2021 with serology testing from 10 February to 15 May 2021.Main outcome measuresSARS-CoV-2 seroprevalence among school staff, based on spike (S)-based (unvaccinated staff) or N-based serology testing (vaccinated staff).ResultsPublic health data showed the cumulative incidence of COVID-19 among students attending in-person was 9.8 per 1000 students (n=47 280), and 13 per 1000 among school staff (n=7071). In a representative sample of 1689 school staff, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week (IQR: 5.0–25 hours). Although 21.5% (363/1686) of surveyed staff self-reported close contact with a COVID-19 case outside of their household (16.5% contacts were school-based), 5 cases likely acquired the infection at school based on viral testing. Sensitivity/Specificity-adjusted seroprevalence in 1556/1689 staff (92.1%) was 2.3% (95% CI: 1.6% to 3.2%), comparable to a sex, age, date and residency area-weighted seroprevalence of 2.6% (95% CI: 2.2% to 3.1%) among 5417 blood donors.ConclusionSeroprevalence among staff was comparable to a reference group of blood donors from the same community. These data show that in-person schooling could be safely maintained during the 2020/21 school year with mitigation measures, in a large school district in Vancouver, Canada.
Transmission of SARS-CoV-2 in educational settings in 2020: a review
Authors: Vardavas Constantine , Nikitara Katerina , Mathioudakis Alexander G , Hilton Boon Michele , Phalkey Revati , Leonardi-Bee Jo , Pharris Anastasia , Deogan Charlotte , Suk Jonathan E 
Published: April 2022

ObjectivesSchool closures have been used as a core non-pharmaceutical intervention (NPI) during the COVID-19 pandemic. This review aims at identifying SARS-CoV-2 transmission in educational settings during the first waves of the pandemic.MethodsThis literature review assessed studies published between December 2019 and 1 April 2021 in Medline and Embase, which included studies that assessed educational settings from approximately January 2020 to January 2021. The inclusion criteria were based on the PCC framework (P-Population, C-Concept, C-Context). The studyPopulationwas restricted to people 1–17 years old (excluding neonatal transmission), theConceptwas to assess child-to-child and child-to-adult transmission, while theContextwas to assess specifically educational setting transmission.ResultsFifteen studies met inclusion criteria, ranging from daycare centres to high schools and summer camps, while eight studies assessed the re-opening of schools in the 2020–2021 school year. In principle, although there is sufficient evidence that children can both be infected by and transmit SARS-CoV-2 in school settings, the SAR remain relatively low—when NPI measures are implemented in parallel. Moreover, although the evidence was limited, there was an indication that younger children may have a lower SAR than adolescents.ConclusionsTransmission in educational settings in 2020 was minimal—when NPI measures were implemented in parallel. However, with an upsurge of cases related to variants of concern, continuous surveillance and assessment of the evidence is warranted to ensure the maximum protection of the health of students and the educational workforce, while also minimising the numerous negative impacts that school closures may have on children.
Experiences of children with disabilities during the COVID-19 pandemic in Sweden: a qualitative interview study
Authors: Fäldt Anna Erica , Klint Filippa , Warner Georgina , Sarkadi Anna 
Published: April 2022

BackgroundThe impact of the COVID-19 pandemic on people with disabilities has been described as a ‘triple jeopardy’. Not only have they experienced the negative social impacts of disease control measures, but access to required health services has been affected, and, not least, they are at increased risk of severe outcomes from COVID-19. This study aimed to determine how children with disabilities have experienced the pandemic in Sweden and its impact on their lives.MethodsSix children (5–13 years) were interviewed via video conferencing. An interview guide was adapted based on the children’s communicative abilities and included augmentative and alternative communication support. Reflective field notes were included in the analysis. The data were analysed using qualitative content analysis.ResultsTwo themes were identified: The child’s knowledge of Corona raises anxiety and fear; and Boring Corona makes the child even lonelier. The children had knowledge about and were worried about COVID-19, primarily about illness and death of their grandparents. The children longed for their grandparents and other social contacts at school, and life was described as boring and lonely. Many families lacked adequate tools to communicate with their children about the pandemic.ConclusionGiven adequate support, children with disabilities and communication difficulties can give insights to their unique life situations. The interviewed children reported significant impact on their life and school life. Children were worried about their grandparents based on their knowledge about the virus. The enthusiasm with which the children engaged in the interviews is testament to the need and right of all children, regardless of communicative competence, to voice their experiences
Characterization of the treatment-naive immune microenvironment in melanoma with BRAF mutation
Authors: Wang Minyu , Zadeh Soroor , Pizzolla Angela , Thia Kevin , Gyorki David E , McArthur Grant A , Scolyer Richard A , Long Georgina , Wilmott James S , Andrews Miles C , Au-Yeung George , Weppler Ali , Sandhu Shahneen , Trapani Joseph A , Davis Melissa J , Neeson Paul Joseph 
Published: April 2022

BackgroundPatients with BRAF-mutant and wild-type melanoma have different response rates to immune checkpoint blockade therapy. However, the reasons for this remain unknown. To address this issue, we investigated the precise immune composition resulting from BRAF mutation in treatment-naive melanoma to determine whether this may be a driver for different response to immunotherapy.MethodsIn this study, we characterized the treatment-naive immune context in patients with BRAF-mutant and BRAF wild-type (BRAF-wt) melanoma using data from single-cell RNA sequencing, bulk RNA sequencing, flow cytometry and immunohistochemistry (IHC).ResultsIn single-cell data, BRAF-mutant melanoma displayed a significantly reduced infiltration of CD8+ T cells and macrophages but also increased B cells, natural killer (NK) cells and NKT cells. We then validated this finding using bulk RNA-seq data from the skin cutaneous melanoma cohort in The Cancer Genome Atlas and deconvoluted the data using seven different algorithms. Interestingly, BRAF-mutant tumors had more CD4+ T cells than BRAF-wt samples in both primary and metastatic cohorts. In the metastatic cohort, BRAF-mutant melanoma demonstrated more B cells but less CD8+ T cell infiltration when compared with BRAF-wt samples. In addition, we further investigated the immune cell infiltrate using flow cytometry and multiplex IHC techniques. We confirmed that BRAF-mutant melanoma metastases were enriched for CD4+ T cells and B cells and had a co-existing decrease in CD8+ T cells. Furthermore, we then identified B cells were associated with a trend for improved survival (p=0.078) in the BRAF-mutant samples and Th2 cells were associated with prolonged survival in the BRAF-wt samples.ConclusionsIn conclusion, treatment-naive BRAF-mutant melanoma has a distinct immune context compared with BRAF-wt melanoma, with significantly decreased CD8+ T cells and increased B cells and CD4+ T cells in the tumor microenvironment. These findings indicate that further mechanistic studies are warranted to reveal how this difference in immune context leads to improved outcome to combination immune checkpoint blockade in BRAF-mutant melanoma.
Assessment of hyperprogression versus the natural course of disease development with nivolumab with or without ipilimumab versus placebo in phase III, randomized, controlled trials
Authors: Kang Yoon-Koo , Reck Martin , Nghiem Paul , Feng Yan , Plautz Gregory , Kim Hye Ryun , Owonikoko Taofeek K , Boku Narikazu , Chen Li-Tzong , Lei Ming , Chang Han , Lin Wen Hong , Roy Amit , Bello Akintunde , Sheng Jennifer 
Published: April 2022

BackgroundRetrospective studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving immune checkpoint inhibitors (ICIs). We compared the incidence of HPD during treatment with nivolumab±ipilimumab versus natural tumor progression with placebo in post hoc analyses of two randomized, double-blind clinical trials.MethodsATTRACTION-2 randomized patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) and progression on ≥2 prior regimens to nivolumab 3 mg/kg Q2W or placebo. CheckMate 451 randomized patients with extensive-disease small cell lung cancer (ED SCLC) and ongoing complete/partial response or stable disease after first-line chemotherapy to nivolumab 240 mg Q2W, nivolumab 1 mg/kg+ipilimumab 3 mg/kg Q3W for four doses then nivolumab 240 mg Q2W, or placebo. Patients receiving ≥1 dose of study drug and with tumor scans at baseline and the first on-treatment evaluation were included in the HPD analyses. HPD definitions were ≥20%, ≥50%, and ≥100% increase in target lesion sum of the longest diameters (SLD) at the first on-treatment assessment.ResultsIn the ATTRACTION-2 HPD-evaluable population, 243 patients received nivolumab and 115 placebo. Fewer patients receiving nivolumab versus placebo had increases in SLD ≥20% (33.7% vs 46.1%) and ≥50% (6.2% vs 11.3%); similar proportions had increases in SLD ≥100% (1.6% vs 1.7%). In the CheckMate 451 HPD-evaluable population, 177 patients received nivolumab, 179 nivolumab+ipilimumab, and 175 placebo. Fewer patients receiving nivolumab or nivolumab+ipilimumab versus placebo had increases in SLD ≥20% (27.1%, 27.4% vs 45.7%), ≥50% (10.2%, 11.2% vs 22.3%), and ≥100% (2.8%, 2.8% vs 6.3%).ConclusionsNivolumab±ipilimumab was not associated with an increased rate of progression versus placebo in patients with GC, GEJC, or ED SCLC, suggesting that previous reports of HPD may reflect the natural disease course in some patients rather than ICI-mediated progression.Trial registration numberNCT02538666;NCT02267343.
Subtyping of microsatellite stability colorectal cancer reveals guanylate binding protein 2 (GBP2) as a potential immunotherapeutic target
Authors: Wang Haizhou , Zhou Yabo , Zhang Yangyang , Fang Shilin , Zhang Meng , Li Haiou , Xu Fei , Liu Lan , Liu Jing , Zhao Qiu , Wang Fan 
Published: April 2022

BackgroundsProficient-mismatch-repair or microsatellite stability (pMMR/MSS) colorectal cancer (CRC) has limited efficacy for immune checkpoint blockade (ICB) therapy and its underlying mechanism remains unclear. Guanylate binding protein 2 (GBP2) is a member of the GTPase family and is crucial to host immunity against pathogens. However, the correlations between GBP2 and immunosurveillance and immunotherapy for pMMR/MSS CRC have not been reported.MethodsUnsupervised clustering was employed to classify immune class and non-immune class in 1424 pMMR/MSS patients from six independent public datasets. This binary classification was validated using immune cells or response related signatures. The correlation between GBP2 and immune microenvironment was explored using well-established biological algorithms, multiplex immunohistochemistry (mIHC), in vitro and in vivo experiments.ResultsWe classified 1424 pMMR/MSS CRC patients into two classes, ‘immune’ and ‘non-immune’, and GBP2 was identified as a gene of interest. We found that lower GBP2 expression was correlated with poor prognosis and metastasis. GBP2 expression was also upregulated in the immune class and highly associated with interferon-γ (IFN-γ) signaling pathway and CD8 +T cell infiltration using gene set enrichment analysis, gene ontology analysis, single-cell sequencing and mIHC. Moreover, reduced GBP2 expression inhibited the antigen processing and presentation machinery and CXCL10/11 expression in MSS CRC cells on IFN-γ stimulation. A Transwell assay revealed that deletion of GBP2 in murine MSS CRC cells reduced CD8 +T cell migration. Mechanistically, GBP2 promoted signal transducer and transcription activator 1 (STAT1) phosphorylation by competing with SHP1 for binding to STAT1 in MSS CRC cells. Finally, an unsupervised subclass mapping (SubMap) algorithm showed that pMMR/MSS patients with high GBP2 expression may correlate with a favorable response to anti-PD-1 therapy. We further confirmed that GBP2 knockout reduced CD8 +T cell infiltration and blunted the efficacy of PD-1 blockade in tumor-bearing mice.ConclusionsOur study reveals that pMMR/MSS CRC is immunogenically heterogeneous and that GBP2 is a promising target for combinatorial therapy with ICB.
OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
Authors: Cui ChuanLiang , Wang Xuan , Lian Bin , Ji Qing , Zhou Li , Chi Zhihong , Si Lu , Sheng Xinan , Kong Yan , Yu Jiayi , Li Siming , Mao Lili , Tang Bixia , Dai Jie , Yan Xieqiao , Bai Xue , Andtbacka Robert , Guo Jun 
Published: April 2022

BackgroundMelanoma in people of Asian descent presents primarily in non-sun-exposed areas, such as acral and mucosal melanoma. Compared with the predominant sun-exposed area melanomas in Caucasians, acral and mucosal melanomas do not respond as well to immunotherapy and are associated with a worse prognosis. Hence, there is an urgent need for improved treatment for melanoma in Asians. This phase Ib trial evaluated the safety and efficacy of the modified herpes simplex virus-1 oncolytic virus OrienX010 in Chinese patients with unresectable stage IIIC–IV melanoma.MethodsPatients were treated in two different cohorts. In cohort 08 (n=12), patients received up to 5 mL of 8×107pfu/mL OrienX010 intratumoral injections every 2 weeks until disease progression and responses were evaluated every 6 weeks. In cohort 09 (n=14), patients received up to 10 mL of 8×107pfu/mL OrienX010 intratumoral injections and responses were evaluated every 8 weeks.ResultsBetween June 2014 and May 2017, 26 patients were enrolled, including 18 (69.2%) patients with acral melanoma. Fever and injection site reaction were the most frequent adverse events. Only one patient experienced a grade ≥3 adverse event and no dose-limiting toxicities were observed. The objective response rate was 19.2% and the disease control rate was 53.8%. The median duration of response was 6.0 months. Antitumor effects were observed in 54.6% of injected lesions and 48.8% of non-injected lesions, including one (16.7%) of six evaluable distant lung metastases. The median progression-free survival was 2.9 months and overall survival was 19.2 months. Compared with patients treated in cohort 08, patients treated in cohort 09 had an improved objective response rate (28.6% vs 8.3%) and a median progression-free survival of 3.0 months vs 2.8 months.ConclusionsOrienX010 oncolytic virotherapy has a tolerable safety profile with antitumor effects in both injected and non-injected metastases and warrants further evaluation in patients with melanoma. Based on these results, the higher cohort 09 dose (up to 10 mL of 8×107pfu/mL every 2 weeks) was selected as the recommended phase II dose for ongoing trials.Trial registration numberCTR20140631 (cohort 08), CTR20150881 (cohort 09).
Association of adverse childhood experiences with the development of multiple sclerosis
Authors: Eid Karine , Torkildsen Øivind , Aarseth Jan , Aalstad Mari , Bhan Alok , Celius Elisabeth G , Cortese Marianna , Daltveit Anne Kjersti , Holmøy Trygve , Myhr Kjell-Morten , Riise Trond , Schüler Stephan , Torkildsen Cecilie F , Wergeland Stig , Gilhus Nils Erik , Bjørk Marte-Helene 
Published: April 2022

ObjectiveTo study whether exposure to childhood emotional, sexual or physical abuse is associated with subsequent multiple sclerosis (MS) development.MethodsA nationwide, prospective cohort study based on participants in the Norwegian Mother, Father and Child cohort study. Enrolment took place 1999–2008, with follow-up until 31 December 2018. Childhood abuse before age 18 years was obtained from self-completed questionnaires. We identified MS diagnoses through data-linkage with national health registries and hospital records. The Cox model was used to estimate HRs for MS with 95% CIs, adjusting for confounders and mediators.ResultsIn this prospective cohort study, 14 477 women were exposed to childhood abuse and 63 520 were unexposed. 300 women developed MS during the follow-up period. 71 of these (24%) reported a history of childhood abuse, compared with 14 406 of 77 697 (19%) women that did not develop MS. Sexual abuse (HR 1.65, 95% CI 1.13 to 2.39) and emotional abuse (HR 1.40, 95% CI 1.03 to 1.90) in childhood were both associated with an increased risk of developing MS. The HR of MS after exposure to physical abuse was 1.31 (95% CI 0.83 to 2.06). The risk of MS was further increased if exposed to two (HR 1.66, 95% CI 1.04 to 2.67) or all three abuse categories (HR 1.93, 95% CI 1.02 to 3.67).InterpretationChildhood sexual and emotional abuse were associated with an increased risk of developing MS. The risk was higher when exposed to several abuse categories, indicating a dose–response relationship. Further studies are needed to identify underlying mechanisms.
Validity of the EULAR recommendations on the use of ultrasound in the diagnosis of giant cell arteritis
Authors: Fernández-Fernández Elisa , Monjo Irene , Peiteado Diana , Balsa Alejandro , De Miguel Eugenio 
Published: April 2022

ObjectivesThe European Alliance of Associations for Rheumatology (EULAR) recommendations for the use of imaging in large vessel vasculitis establish that an imaging test supported by clinical pretest probability (PTP) is sufficient for the diagnosis of giant cell arteritis (GCA). Our objective was to determine the validity of the EULAR recommendations on the use of Colour duplex ultrasound (CDUS) in GCA after calculating the PTP.MethodsWe collected data of all patients referred to our fast-track clinic between 2016 and 2020. The Southend pretest probability score (SPTPS) was calculated and classified as low (LR), intermediate and high risk (HR) according to the values obtained by its authors, <9, 9–12 and >12, respectively. All patients underwent a CDUS of the temporal arteries with their common, parietal and frontal branches, and the most also axillary (86.5%), and subclavian and carotid arteries. The gold-standard diagnosis was made according to the physician’s criteria after at least 9 months of follow-up.ResultsOf the 297 referred patients, 97 (32.7%) were diagnosed with GCA. The SPTPS area under the ROC curve was 0.787. The LR category included 105 patients (35.4%), of which 10 (9.5%) had GCA and 1 had a CDUS false negative result. The HR category included 67 patients (22.5%), 47 with GCA, and in 1 case the CDUS result was a false positive.ConclusionCombining the results of a PTP score, such as SPTPS, and the CDUS allows for an accurate diagnosis of GCA, as established by the EULAR group, with less than 2% misclassification of diagnosis.
Localization of the fungal symbiont (Chaetothyriales) inIpomoea carnea
Authors: Pistán María E. , Gutiérrez Susana A. , Schnittger Leonhard , Gardner Dale R. , Cholich Luciana A. , Gonzalez Ana M. 
Published: April 2022

Plants belonging to the genera Astragalus, Oxytropis, Ipomoea, Sida, and Swainsona often contain the toxin swainsonine (SW), which causes a neurological disorder in livestock. It has been demonstrated that SW is produced by a symbiont fungus associated with these plants. In I. carnea, the fungus belongs to the ascomycetes of the order Chaetothyriales and grows ectopically on the adaxial surface of leaves. In this study, the presence of the symbiont fungus in different organs of I. carnea was investigated using imaging techniques to understand the process of endophyte transmission. In I. carnea plants with whitish mycelia on the leaf surface, SW could be detected in seeds. Inside the seeds, the mycelium was located on the surface of the cotyledons and on the inner side of the seed coat. We corroborated that the presence of this fungus is a prerequisite for the presence of SW in I. carnea. The demonstration of the localization of the fungus within the seed strongly suggested that this endophyte is vertically transmitted. Our observations verified that the SW-producing fungus in I. carnea is an endosymbiont with epibiotic behavior.
Channel, dune and sand sheet architectures of a strait-adjacent delta, Rifian Corridor, Morocco
Authors: Beelen Daan , Wood Lesli Joy , Zaghloul Mohamed Najib , Cardona Sebastian , Arts Michiel 
Published: April 2022

Abstract
Sea straits are elongated zones where geographical constriction can amplify marine currents. Sediment deposits that formed in sea straits are relatively well studied and robust models of tidal strait depositional systems have been developed. However, models of strait-adjacent systems remain uncommon. In this study, we present such a model which is based on detailed outcrop descriptions of Miocene deposits that formed adjacent to the Rifian Corridor, an ancient sea strait that existed in what is now northern Morocco. The kilometre-scale outcrops at the Ben Allou locality (30 km north of Fez, Morocco) contain a succession of claystones, siltstones and sandstones that formed under a sea strait-adjacent process regime characterized by marine current constriction, tidal amplification and reduced wave activity. Detailed descriptions of the sandstone's sedimentary architectures reflect a development from mud drape-bearing sand sheets in the proximal regions of the system to stacked cross-strata and channel forms nearer to the basin depocentre. In the deep, distal reaches of this system, sediment grain sizes are generally fine (silt and clay) and are sparsely interbedded with sandy turbidites. These results confirm existing models which show that proximal strait-adjacent deposits tend to be tide dominated, and wave and fluvial influence can be overprinted by tidal processes. Some insights into the formation of tidal dunes are discussed. For example, it is shown that compound tidal dunes may not be preserved differently than simple tidal dunes, which is relevant for predicting sedimentary architectures and fluid flow properties of ancient tide-dominated successions.