bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 infections and attitudes towards COVID-19 vaccines among healthcare workers in the New York Metropolitan area, USA
Authors: Agaku Israel T , Dimaggio Alisa , Fishelov Avigal , Brathwaite Alianne , Ahmed Saief , Malinowski Michelle , Long Theodore 
Published: July 2022

ObjectiveBecause of their increased interaction with patients, healthcare workers (HCWs) face greater vulnerability to COVID-19 exposure than the general population. We examined prevalence and correlates of ever COVID-19 diagnosis and vaccine uncertainty among HCWs.DesignCross-sectional data from the Household Pulse Survey (HPS) conducted during July to October 2021.SettingHPS is designed to yield representative estimates of the US population aged ≥18 years nationally, by state and across selected metropolitan areas.ParticipantsOur primary analytical sample was adult HCWs in the New York Metropolitan area (n=555), with HCWs defined as individuals who reported working in a ‘Hospital’; ‘Nursing and residential healthcare facility’; ‘Pharmacy’ or ‘Ambulatory healthcare setting’. In the entire national sample, n=25 909 HCWs completed the survey. Descriptive analyses were performed with HCW data from the New York Metropolitan area, the original epicentre of the pandemic. Multivariable logistic regression analyses were performed on pooled national HCW data to explore how HCW COVID-19-related experiences, perceptions and behaviours varied as a function of broader geographic, clinical and sociodemographic characteristics.ResultsOf HCWs surveyed in the New York Metropolitan area, 92.3% reported being fully vaccinated, and 20.9% had ever been diagnosed of COVID-19. Of the subset of HCWs in the New York Metropolitan area not yet fully vaccinated, 41.8% were vaccine unsure, 4.5% planned to get vaccinated for the first time soon, 1.6% had got their first dose but were not planning to receive the remaining dose, while 52.1% had got their first dose and planned to receive the remaining dose. Within pooled multivariable analysis of the national HCW sample, personnel in nursing/residential facilities were less likely to be fully vaccinated (adjusted OR, AOR 0.79, 95% CI 0.63 to 0.98) and more likely to report ever COVID-19 diagnosis (AOR 1.35, 95% CI 1.13 to 1.62), than those working in hospitals. Of HCWs not yet vaccinated nationally, vaccine-unsure individuals were more likely to be White and work in pharmacies, whereas vaccine-accepting individuals were more likely to be employed by non-profit organisations and work in ambulatory care facilities. Virtually no HCW was outrightly vaccine-averse, only unsure.ConclusionsDifferences in vaccination coverage existed by individual HCW characteristics and healthcare operational settings. Targeted efforts are needed to increase vaccination coverage.
Nationwide gastric cancer prevention in China, 2021–2035: a decision analysis on effect, affordability and cost-effectiveness optimisation
Authors: Wang Zixing , Han Wei , Xue Fang , Zhao Yujie , Wu Peng , Chen Yali , Yang Cuihong , Gu Wentao , Jiang Jingmei 
Published: July 2022

ObjectiveTo project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness.DesignUsing a cohort of Chinese men and women born during 1951–1980, we assumed that different prevention strategies were conducted, including eradication ofHelicobacter pylori(Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021–2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention.ResultsDuring 2021–2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%–35.5% and 6.9%–44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%–49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening,ConclusionOur findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.
Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic
Authors: Kennedy Nicholas A , Janjua Malik , Chanchlani Neil , Lin Simeng , Bewshea Claire , Nice Rachel , McDonald Timothy J , Auckland Cressida , Harries Lorna W , Davies Merlin , Michell Stephen , Kok Klaartje B , Lamb Christopher A , Smith Philip J , Hart Ailsa L , Pollok Richard CG , Lees Charlie W , Boyton Rosemary J , Altmann Daniel M , Sebastian Shaji , Powell Nicholas , Goodhand James R , Ahmad Tariq 
Published: July 2022

ObjectiveAntitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD.DesignThird dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study.ResultsGeometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and was predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups.ConclusionsFollowing a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant.Trial registration numberISRCTN45176516.
Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery
Authors: Kwak Soongu , Lee Seung-Ah , Lim Jaehyun , Yang Seokhun , Choi Hong-Mi , Hwang In-Chang , Lee Sahmin , Yoon Yeonyee Elizabeth , Park Jun-Bean , Kim Hyung-Kwan , Kim Yong-Jin , Song Jong-Min , Cho Goo-Yeong , Kim Kyung-Hwan , Kang Duk-Hyun , Kim Dae-Hee , Lee Seung-Pyo 
Published: July 2022

ObjectivesPatients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery.MethodsThe retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery.ResultsDuring follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1–3) and two older groups (group 4–5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1–5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; p<0.001). Phenogroups had similar predictive performance compared with the Mitral Regurgitation International Database score in patients with degenerative MR (3-year C-index, 0.763 vs 0.750, p=0.602). These findings were reproduced in the validation cohort.ConclusionFive phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.
Completeness and representativeness of small area socioeconomic data linked with the UK Clinical Practice Research Datalink (CPRD)
Authors: Mahadevan Preveina , Harley Mia , Fordyce Stuart , Hodgson Susan , Ghosh Rebecca , Myles Puja , Booth Helen , Axson Eleanor 
Published: July 2022

BackgroundThe Clinical Practice Research Datalink (CPRD) holds primary care electronic healthcare records for 25% of the UK population. CPRD data can be linked via practice postcode in the UK, and additionally via patient postcode in England, to area-level socioeconomic status (SES) data including the Index of Multiple Deprivation (IMD), the Carstairs Index and the Townsend Deprivation Index; as well as rural–urban classification (RUC). This study aims to describe the completeness and representativeness of CPRD-linked SES and RUC data.MethodsPatients currently registered at general practices contributing data to the May 2021 snapshots of CPRD GOLD (n=445 587) and CPRD Aurum (n=13 278 825) were used to assess the completeness and representativeness of CPRD-linked SES and RUC data against the UK general population.ResultsAll currently registered patients had complete SES and RUC data at practice level across the UK. Most English patients in CPRD GOLD (78%), CPRD Aurum (94%) and combined (93%) had SES and RUC data at patient level. Patient-level SES data in CPRD for England were comparable to England’s general population (average IMD decile in CPRD 5.52±0.00 vs 5.50±0.02). CPRD UK practices were on average in more deprived areas than the UK general population (6.06±0.07 vs 5.50±0.02). A slightly higher proportion of CPRD patients and practices were from urban areas (85%) as compared with the UK general population (82%).ConclusionCompleteness of CPRD-linked SES and RUC data is high. The CPRD populations were broadly representative of the general populations in the UK in terms of SES and RUC.
Reshaping the tumor microenvironment with oncolytic viruses, positive regulation of the immune synapse, and blockade of the immunosuppressive oncometabolic circuitry
Authors: Nguyen Teresa T , Shin Dong Ho , Sohoni Sagar , Singh Sanjay K , Rivera-Molina Yisel , Jiang Hong , Fan Xuejun , Gumin Joy , Lang Frederick F , Alvarez-Breckenridge Christopher , Godoy-Vitorino Filipa , Zhu Lisha , Zheng W Jim , Zhai Lijie , Ladomersky Erik , Lauing Kristen L , Alonso Marta M , Wainwright Derek A , Gomez-Manzano Candelaria , Fueyo Juan 
Published: July 2022

BackgroundOncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.MethodsWe used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography–mass spectrometry. Aryl hydrocarbon receptor (AhR) activation was analyzed by examination of promoter activity. Therapeutic efficacy was assessed by tumor histopathology and survival in syngeneic murine models of gliomas, including Indoleamine 2,3-dioxygenase (IDO)-/- mice. Flow cytometry was used for immunophenotyping and quantification of cell populations. Immune activation was examined in co-cultures of immune and cancer cells. T-cell depletion was used to identify the role played by specific cell populations. Rechallenge experiments were performed to identify the development of anti-tumor memory.ResultsBulk RNA-seq analyses showed the activation of the immunosuppressive IDO-kynurenine-AhR circuitry in response to Delta-24-RGDOX infection of tumors. To overcome the effect of this pivotal pathway, we combined Delta-24-RGDOX with clinically relevant IDO inhibitors. The combination therapy increased the frequency of CD8+T cells and decreased the rate of myeloid-derived suppressor cell and immunosupressive Treg tumor populations in animal models of solid tumors. Functional studies demonstrated that IDO-blockade-dependent activation of immune cells against tumor antigens could be reversed by the oncometabolite kynurenine. The concurrent targeting of the effectors and suppressors of the tumor immune landscape significantly prolonged the survival in animal models of orthotopic gliomas.ConclusionsOur data identified for the first time thein vivorole of IDO-dependent immunosuppressive pathways in the resistance of solid tumors to oncolytic adenoviruses. Specifically, the IDO-Kyn-AhR activity was responsible for the resurface of local immunosuppression and resistance to therapy, which was ablated through IDO inhibition. Our data indicate that combined molecular and immune therapy may improve outcomes in human gliomas and other cancers treated with virotherapy.
Genotype–phenotype correlations in valosin-containing protein disease: a retrospective muticentre study
Authors: Schiava Marianela , Ikenaga Chiseko , Villar-Quiles Rocío Nur , Caballero-Ávila Marta , Topf Ana , Nishino Ichizo , Kimonis Virginia , Udd Bjarne , Schoser Benedikt , Zanoteli Edmar , Souza Paulo Victor Sgobbi , Tasca Giorgio , Lloyd Thomas , Lopez-de Munain Adolfo , Paradas Carmen , Pegoraro Elena , Nadaj-Pakleza Aleksandra , De Bleecker Jan , Badrising Umesh , Alonso-Jiménez Alicia , Kostera-Pruszczyk Anna , Miralles Francesc , Shin Jin-Hong , Bevilacqua Jorge Alfredo , Olivé Montse , Vorgerd Matthias , Kley Rudi , Brady Stefen , Williams Timothy , Domínguez-González Cristina , Papadimas George K , Warman-Chardon Jodi , Claeys Kristl G , de Visser Marianne , Muelas Nuria , LaForet Pascal , Malfatti Edoardo , Alfano Lindsay N , Nair Sruthi S , Manousakis Georgios , Kushlaf Hani A , Harms Matthew B , Nance Christopher , Ramos-Fransi Alba , Rodolico Carmelo , Hewamadduma Channa , Cetin Hakan , García-García Jorge , Pál Endre , Farrugia Maria Elena , Lamont Phillipa J , Quinn Colin , Nedkova-Hristova Velina , Peric Stojan , Luo Sushan , Oldfors Anders , Taylor Kate , Ralston Stuart , Stojkovic Tanya , Weihl Conrad , Diaz-Manera Jordi 
Published: July 2022

BackgroundValosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget’s disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype–phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype–phenotype correlations.MethodsDescriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene.ResultsTwo hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8±9.6 years and mean age of onset 45.6±9.3 years. Mean diagnostic delay was 7.7±6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8±7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC <70% and being a full-time wheelchair user were associated with death.ConclusionThis study expands the knowledge on the phenotypic presentation, natural history, genotype–phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.
Systematic evaluation of genetic mutations in ALS: a population-based study
Authors: Grassano Maurizio , Calvo Andrea , Moglia Cristina , Sbaiz Luca , Brunetti Maura , Barberis Marco , Casale Federico , Manera Umberto , Vasta Rosario , Canosa Antonio , D’Alfonso Sandra , Corrado Lucia , Mazzini Letizia , Dalgard Clifton , Karra Ramita , Chia Ruth , Traynor Bryan , Chiò Adriano 
Published: July 2022

BackgroundA genetic diagnosis in Amyotrophic Lateral Sclerosis (ALS) can inform genetic counselling, prognosis and, in the light of incoming gene-targeted therapy, management. However, conventional genetic testing strategies are often costly and time-consuming.ObjectiveTo evaluate the diagnostic yield and advantages of whole-genome sequencing (WGS) as a standard diagnostic genetic test for ALS.MethodsIn this population-based cohort study, 1043 ALS patients from the Piemonte and Valle d’Aosta Register for ALS and 755 healthy individuals were screened by WGS for variants in 42 ALS-related genes and for repeated-expansions in C9orf72 and ATXN2.ResultsA total of 279 ALS cases (26.9%) received a genetic diagnosis, namely 75.2% of patients with a family history of ALS and 21.5% of sporadic cases. The mutation rate among early-onset ALS patients was 43.9%, compared with 19.7% of late-onset patients. An additional 14.6% of the cohort carried a genetic factor that worsen prognosis.ConclusionsOur results suggest that, because of its high diagnostic yield and increasingly competitive costs, along with the possibility of retrospectively reassessing newly described genes, WGS should be considered as standard genetic testing for all ALS patients. Additionally, our results provide a detailed picture of the genetic basis of ALS in the general population.
Poor sleep and multiple sclerosis: associations with symptoms of multiple sclerosis and quality of life
Authors: Laslett Laura L , Honan Cynthia , Turner Jason A , Dagnew Baye , Campbell Julie A , Gill Tiffany K , Appleton Sarah , Blizzard Leigh , Taylor Bruce V , van der Mei Ingrid 
Published: July 2022

BackgroundSleep difficulties are common in people with multiple sclerosis (MS), but whether associations between poor sleep quality and quality of life are independent of MS symptoms, obesity and other MS-related factors remains unclear.MethodsCross-sectional analyses of data from the Australian MS Longitudinal Study (n=1717). Sleep was assessed using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and International Restless Legs Syndrome Study Group Rating Scale; health-related quality of life using the Assessment of Quality-of-Life 8-D.ResultsPoor sleep quality was common (67%), and more common than in community samples. Sleep measures clustered independently within MS symptoms. The clusters ‘fatigue and cognitive’, ‘feelings of anxiety and depression’, ‘pain and sensory’, were independently associated with poor sleep quality. Quality-of-Life utility scores were a clinically meaningful 0.19 units lower in those with poor sleep. Sleep quality, daytime sleepiness and restless leg syndrome were associated with reduced quality of life, independent of MS-related symptoms and body mass index.ConclusionPoor sleep quality is common in MS and was strongly associated with worse health-related quality of life, independent of other MS symptoms and did not cluster with other common MS symptoms. Improving sleep quality may substantially improve quality of life in people with MS.
Immunogenicity of the third and fourth BNT162b2 mRNA COVID-19 boosters and factors associated with immune response in patients with SLE and rheumatoid arthritis
Authors: Assawasaksakul Theerada , Sathitratanacheewin Seelwan , Vichaiwattana Preeyaporn , Wanlapakorn Nasamon , Poovorawan Yong , Avihingsanon Yingyos , Assawasaksakul Nawaporn , Kittanamongkolchai Wonngarm 
Published: July 2022

ObjectivesTo evaluate the safety and immunogenicity of third and fourth BNT162b2 boosters in patients with SLE and rheumatoid arthritis (RA).MethodsPatients with SLE and RA aged 18–65 years who completed a series of inactivated, adenoviral vector, or heterogenous adenoviral vector/mRNA vaccines for at least 28 days were enrolled. Immunogenicity assessment was done before and day 15 after each booster vaccination. The third BNT162b2 booster was administered on day 1. Patients with suboptimal humoral response to the third booster dose (antireceptor-binding domain (RBD) IgG on day 15 <2360 BAU/mL) were given a fourth BNT162b2 booster on day 22.ResultsSeventy-one patients with SLE and 29 patients with RA were enrolled. The third booster raised anti-RBD IgG by 15-fold, and patients with positive neutralising activity against the Omicron variant increased from 0% to 42%. Patients with positive cellular immune response also increased from 55% to 94%. High immunosuppressive load and initial inactivated vaccine were associated with lower anti-RBD IgG titre. Fifty-four patients had suboptimal humoral responses to the third booster and 28 received a fourth booster dose. Although anti-RBD IgG increased further by sevenfold, no significant change in neutralising activity against the Omicron variant was observed. There were two severe SLE flares that occurred shortly after the fourth booster dose.ConclusionsThe third BNT162b2 booster significantly improved humoral and cellular immunogenicity in patients with SLE and RA. The benefit of a short-interval fourth booster in patients with suboptimal humoral response was unclear.Trial registration numberTCTR20211220004.