bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and tolerability of a single infusion of autologous ex vivo expanded regulatory T cells in adults with ulcerative colitis (ER-TREG 01): protocol of a phase 1, open-label, fast-track dose-escalation clinical trial
Authors: Voskens Caroline J , Stoica Diane , Roessner Susanne , Vitali Francesco , Zundler Sebastian , Rosenberg Marita , Wiesinger Manuel , Wunder Jutta , Siegmund Britta , Schuler-Thurner Beatrice , Schuler Gerold , Berking Carola , Atreya Raja , Neurath Markus F 
Published: December 2021

IntroductionAccumulating evidence suggests that the adoptive transfer of ex vivo expanded regulatory T cells (Treg) may overcome colitogenic immune responses in patients with inflammatory bowel diseases. The objective of the ER-TREG 01 trial is to assess safety and tolerability of a single infusion of autologous ex vivo expanded Treg in adults with ulcerative colitis.Methods and analysisThe study is designed as a single-arm, fast-track dose-escalation trial. The study will include 10 patients with ulcerative colitis. The study intervention consists of (1) a baseline visit; (2) a second visit that includes a leukapheresis to generate the investigational medicinal product, (3) a third visit to infuse the investigational medicinal product and (4) five subsequent follow-up visits within the next 26 weeks to assess safety and tolerability. Patients will intravenously receive a single dose of 0.5×106, 1×106, 2×106, 5×106 or 10×106autologous Treg/kg body weight. The primary objective is to define the maximum tolerable dose of a single infusion of autologous ex vivo expanded Treg. Secondary objectives include the evaluation of safety of one single infusion of autologous ex vivo expanded Treg, efficacy assessment and accompanying immunomonitoring to measure Treg function in the peripheral blood and intestinal mucosa.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany (number 417_19 Az). In addition, the study was approved by the Paul-Ehrlich Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany (number 3652/01). The study is funded by the German Research Foundation (DFG, KFO 257 project 08 and SFB/TransRegio 241 project C04). The trial will be conducted in compliance with this study protocol, the Declaration of Helsinki, Good Clinical Practice and Good Manufacturing Practice. The results will be published in peer-reviewed scientific journals and disseminated in scientific conferences and media.Trial registration numberNCT04691232.
Use of interrupted time-series analysis to characterise antibiotic prescription fills across pregnancy: a Norwegian nationwide cohort study
Authors: Trinh Nhung Thi Hong , Hjorth Sarah , Nordeng Hedvig Marie Egeland 
Published: December 2021

ObjectivesAntibiotics are the most frequently prescribed medications for pregnant and breastfeeding women. We applied interrupted time-series analysis (ITSA) to describe antibiotic prescription fills patterns in pregnant women and examined recurrent antibiotic fills in subsequent pregnancies.DesignsA population-based drug utilisation study.SettingNorwegian primary care.Participants653 058 pregnancies derived from Medical Birth Registry of Norway linked to the Norwegian Prescription Database (2006–2016).Main outcome measureProportion of pregnancies exposed to antibiotics aggregated by week in pregnancy time windows.Statistical analysesWe descriptively analysed antibiotic prescription fills patterns and components in pregnant women. The changes in antibiotic fills in pregnancy time windows were assessed using ITSA. Interruptions points at week 4 to week 7 into pregnancy and delivery were used. Factors associated with antibiotic fills during pregnancy were identified using generalised estimating equations for Poisson regression. Recurrent antibiotic use was estimated using proportion of women who filled antibiotic prescription in a subsequent pregnancy.ResultsAntibiotics were filled in 27.6% pregnancies. The ITSA detected an immediate decrease of 0.07 percentage points (95% CI −0.13 to –0.01) in the proportion of exposed pregnancies at 4 weeks after conception, mainly among women taking folic acid before pregnancy. This proportion increased shortly after delivery (immediate change=1.61 percentage points (95% CI 0.31 to 2.91)) then decreased gradually afterwards (change in slope=−0.19 percentage points, 95% CI −0.34 to –0.05)). The strongest factor associated with antibiotic fills during pregnancy was having recurrent urinary tract infections (adjusted OR=2.65, 95% CI 2.59 to 2.72). Women who had filled antibiotics during a pregnancy were up to three times more likely to fill antibiotics in the subsequent pregnancies.ConclusionsITSA highlighted important impact of pregnancy and delivery on antibiotic fillings. Having antibiotic fills in a pregnancy was associated with recurrent antibiotic fills in subsequent ones.
Cost-effectiveness of human papillomavirus vaccine in China: a systematic review of modelling studies
Authors: Shi Wenchuan , Cheng Xiaoli , Wang Haitao , Zang Xiao , Chen Tingting 
Published: December 2021

ObjectivesChina suffers from high burdens of human papillomavirus (HPV) and cervical cancer, whereas the uptake of HPV vaccine remains low. The first Chinese domestic HPV vaccine was released in 2019. However, collective evidence on cost-effectiveness of HPV vaccination in China has yet to be established. We summarised evidence on the cost-effectiveness of HPV vaccine in China.DesignSystematic review and narrative synthesisData sourcesPubMed, EMBASE, China National Knowledge Infrastructure and Wanfang Data were searched through 2 January 2021Eligibility criteria for selecting studiesCost-effectiveness studies using a modelling approach focusing on HPV vaccination interventions in the setting of China were included for review.Data extraction and synthesisWe extracted information from the selected studies focusing on cost-effectiveness results of various vaccination programmes, key contextual and methodological factors influencing cost-effectiveness estimates and an assessment of study quality.ResultsA total of 14 studies were included for review. Considerable heterogeneity was found in terms of the methodologies used, HPV vaccination strategies evaluated and study quality. The reviewed studies generally supported the cost-effectiveness of HPV vaccine in China, although some reached alternative conclusions, particularly when assessed incremental to cervical cancer screening. Cost of vaccination was consistently identified as a key determinant for the cost-effectiveness of HPV vaccination programmes.ConclusionsImplementing HPV vaccination programmes should be complemented with expanded cervical cancer screening, while the release of lower-priced domestic vaccine offers more promising potential for initiating public HPV vaccination programmes. Findings of this study contributes important evidence for policies for cervical cancer prevention in China and methodological implications for future modelling efforts.
Intersectional effects of gender and ethnicity? A quantitative analysis of bonus pay gap data for Shelford Hospital consultants
Authors: Bajwah Sabrina , Oluyase Adejoke 
Published: December 2021

BackgroundMale hospital consultants earn 13% more than their female counterparts. The intersectional effects of ethnicity and gender are not known.ObjectiveTo describe and analyse the mean bonus pay gap in terms of gender and ethnicity for consultants across the Shelford Group.DesignCross-sectional study.SettingHospitals in the Shelford Group.ParticipantsShelford Group hospitals.Main outcome measuresMean bonus pay gap for male vs female and White vs Black, Asian, Minority Ethnic (BAME) consultants.ResultsSeven of the 10 Shelford Group hospitals provided data for financial year 2018/2019. The average mean bonus gender pay gap was in favour of male consultants (30%; range 12%–48%), and also favoured White consultants compared with BAME consultants (17%; range 7%–31%). The average mean bonus pay gap between White male and BAME male consultants was 20% (range 7%–34%) in favour of White male consultants, while that for White male and BAME female consultants was 46% (range 26%–60%) in favour of White male consultants.ConclusionsOur data show for the first time that there may be an intersectional effect of gender and ethnicity associated with mean bonus pay for consultants. Action is needed to address this imbalance.
Endovascular thrombectomy for acute ischemic stroke in patients with cancer: a propensity-matched analysis
Authors: Joshi Krishna C , Grewal Parneet , Beer-Furlan André , Vargas Alejandro , Osteraas Nicholas , Dafer Rima , Chen Michael 
Published: December 2021

BackgroundThere is a paucity of data and a belief that endovascular thrombectomy (EVT) has low efficacy for acute ischemic stroke (AIS) in patients with cancer. We aimed to critically compare the clinical outcomes of EVT for AIS in patients with and without cancer.MethodsRecords of all patients undergoing EVT for AIS between January 2015 and 2020 were screened for cancer at the time of EVT. Active cancer was defined as patients who were diagnosed with cancer and were undergoing or refused treatment for that cancer. Baseline modified Rankin Scale (mRS), age and sex were used in a 1:5 propensity score matching ratio. After matching we evaluated for any change in the National Institutes of Health Stroke Scale (NIHSS) from baseline to discharge, hemorrhagic transformation (HT), and 90-day mRS and mortality.ResultsThere were 19 patients with cancer and 95 matched controls. The mean±SD age was 70.89±11.16 years, and 17 (89.47%) were female. The baseline NIHSS was 22±7.5 and baseline mRS was 1 (IQR 1). There was no significant difference in change in baseline to discharge NIHSS, 90-day mRS or mortality; 90-day mRS 0–2 was 45.2% in the non-cancer group versus 46.7% in cancer group (p=0.54). HT was significantly higher in patients with cancer (57.89% vs 6.49%, p<0.001).ConclusionsIn propensity matched analysis of patients undergoing EVT for AIS with and without cancer, 90-day functional outcomes and mortality were similar. However, there was a significantly higher rate of HT in cancer patients.
Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease
Authors: Shi Mengmeng , Leng Xinyi , Li Ying , Chen Zihan , Cao Ye , Chung Tiffany , Ip Bonaventure YM , Ip Vincent HL , Soo Yannie OY , Fan Florence SY , Ma Sze Ho , Ma Karen , Chan Anne Y Y , Au Lisa WC , Leung Howan , Lau Alexander Y , Mok Vincent CT , Choy Kwong Wai , Dong Zirui , Leung Thomas W 
Published: December 2021

ObjectivesThe predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.MethodsUnrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis.ResultsAmong 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.ConclusionsOur GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.
Impact of e-liquid warning labels on young adults’ perception of e-cigarettes and intention to use them: an experimental online study
Authors: Gantiva Carlos , Angel-Sanint Luna , Velasco-Vivas Ana 
Published: December 2021

IntroductionFlavoured e-liquids are especially appealing to young adults. The objective of the present study was to evaluate the effects of text warning labels (WLs) on e-liquid vials used in flavoured electronic cigarettes (e-cigarettes) on e-cigarette non-users’ perceptions of harm, addictiveness, emotional valence, interest in trying e-cigarettes and visual attention.MethodsYoung adults aged 18–25 years (n=313) who were non-e-cigarette users were recruited online and randomised to view images of one of two e-liquid vial conditions (with text WL or without text WL). Each participant was exposed to four images of e-liquid vials. After observing each image, participants reported interest in trying e-cigarettes, emotional valence, perceived harm and addictiveness. Additionally, participants completed an assessment of self-reported visual attention with a priori regions of interest (e-liquid branding and text WL).ResultsSeparate two-way Analysis of Variance(ANOVA) that examined the main effects of sex and warning were used for each measure. Text WL on e-liquid vials decreased young adults’ intention to use e-cigarettes (especially in men), increased harm perception and decreased appeal to the product. However, they did not influence the perceived addictiveness of e-cigarettes and rarely grabbed attention. Men perceived e-cigarettes as less harmful and less addictive.ConclusionsThe results suggest that text WLs on e-liquid vials are moderately effective in preventing e-cigarette use in young adults. However, they capture less attention than the rest of the vial and fail to increase the perception of addictiveness. It is suggested to explore other types of design to increase the effectiveness of WLs.
Higher spin glueballs from functional methods
Authors: Huber Markus Q. , Fischer Christian S. , Sanchis-Alepuz Hèlios 
Published: December 2021

AbstractWe calculate the glueball spectrum for spin up to $$J=$$

J
=

4 and positive charge parity in pure Yang–Mills theory. We construct the full bases for $$J=$$

J
=

0, 1, 2, 3, 4 and discuss the relation to gauge invariant operators. Using a fully self-contained truncation of Dyson–Schwinger equations as input, we obtain ground states and first and second excited states from extrapolations of the eigenvalue curves. Where available, we find good quantitative agreement with lattice results
Dark effects in $$\tilde{f}(R,P)$$ gravity
Authors: Marciu Mihai 
Published: December 2021

AbstractIn the present paper a new cosmological model is proposed by extending the Einstein–Hilbert Lagrangian with a generic functional $$\tilde{f}(R,P)$$

f
~

(
R
,
P
)

, which depends on the scalar curvature R and a term P which encodes a possible influence from specific cubic contractions of the Riemann tensor. After proposing the corresponding action, the associated modified Friedmann relations are deduced, in the case where the generic functional has the following decomposition, $$\tilde{f}(R,P)=f(R)+g(P)$$

f
~

(
R
,
P
)

=
f

(
R
)

+
g

(
P
)

. The present study takes into account the power-law and the exponential decomposition for the specific form of the corresponding generic functional. For the analytical approach the specific method of dynamical system analysis is employed, revealing the fundamental properties of the phase space structure, discussing the dynamical consequences for the cosmological solutions obtained. It is revealed that the cosmological solutions associated to the critical points can explain various dynamical eras, with a high sensitivity to the values of the corresponding parameters, encoding different effects due to the geometrical nature of the specific couplings.
A Formal Framework for Complex Event Recognition
Authors: Grez Alejandro , Riveros Cristian , Ugarte Martín , Vansummeren Stijn 
Published: December 2021

Complex event recognition (CER) has emerged as the unifying field for technologies that require processing and correlating distributed data sources in real time. CER finds applications in diverse domains, which has resulted in a large number of proposals for expressing and processing complex events. Existing CER languages lack a clear semantics, however, which makes them hard to understand and generalize. Moreover, there are no general techniques for evaluating CER query languages with clear performance guarantees.In this article, we embark on the task of giving a rigorous and efficient framework to CER. We propose a formal language for specifying complex events, calledcomplex event logic(CEL), that contains the main features used in the literature and has a denotational and compositional semantics. We also formalize the so-called selection strategies, which had only been presented as by-design extensions to existing frameworks. We give insight into the language design trade-offs regarding the strict sequencing operators of CEL and selection strategies.With a well-defined semantics at hand, we discuss how to efficiently process complex events by evaluating CEL formulas with unary filters. We start by introducing a formal computational model for CER, calledcomplex event automata(CEA), and study how to compile CEL formulas with unary filters into CEA. Furthermore, we provide efficient algorithms for evaluating CEA over event streams using constant time per event followed by output-linear delay enumeration of the results.
Influence of GermlineBRCAGenotype on the Survival of Patients with Triple-Negative Breast Cancer
Authors: Villarreal-Garza Cynthia , Ferrigno Ana S. , Aranda-Gutierrez Alejandro , Frankel Paul H. , Ruel Nora H. , Fonseca Alan , Narod Steven , Chavarri-Guerra Yanin , Sifuentes Erika , Magallanes-Hoyos Maria Cristina , Herzog Josef , Castillo Danielle , Alvarez-Gomez Rosa M. , Mohar-Betancourt Alejandro , Weitzel Jeffrey N. 
Published: December 2021

The presence of BRCA pathogenic variants (PV) in triple-negative breast cancer (TNBC) is associated with a distinctive genomic profile that makes the tumor particularly susceptible to DNA-damaging treatments. However, patients with BRCA PVs can develop treatment resistance through the appearance of reversion mutations and restored BRCA expression. As copy-number variants (CNV) could be less susceptible to reversion mutations than point mutations, we hypothesize that carriers of BRCA CNVs may have improved survival after treatment compared with carriers of other BRCA PVs or BRCA wild-type. Women diagnosed with stage I–III TNBC at ≤50 years at a cancer center in Mexico City were screened for BRCA PVs using a recurrent PV assay (HISPANEL; 77% sensitivity). Recurrence-free survival (RFS) and overall survival (OS) were compared according to the mutational status. Among 180 women, 17 (9%) were carriers of BRCA1 ex9–12del CNVs and 26 (14%) of other BRCA PVs. RFS at ten years for the whole cohort was 79.2% [95% confidence interval (CI), 72.3–84.6], with no significant differences according to mutational status. 10-year OS for the entire cohort was 85.3% (95% CI, 78.7–90.0), with BRCA CNV carriers demonstrating numerically superior OS rates other PV carriers and noncarriers (100% vs. 78.6% and 84.7%; log-rank P = 0.037 and P = 0.051, respectively). This study suggests that BRCA1 ex9–12del CNV carriers with TNBC may have a better OS, and supports the hypothesis that the genotype of BRCA PVs may influence survival by limiting treatment resistance mediated by reversion mutations among CNV carriers.Significance:Large CNV BRCA carriers in a cohort of young Mexican patients with TNBC had superior OS rates than carriers of other BRCA pathogenic variants (i.e., small indels or point mutations). We hypothesize that this is due to the resistance of CNVs to reversion mutations mediating resistance to therapy. If validated, these findings have important prognostic and clinical treatment implications for BRCA-associated breast cancers.
Salvation and Victory by Christ’s Death and Resurrection in the Ancient Church
Authors: Roukema Riemer 
Published: December 2021

Abstract
The theme of this article arises from Reformed theology, namely, how did authoritative Christian authors of the second to the fifth centuries AD think about salvation by Christ’s substitutionary and atoning death? How do their views relate to the ‘Christus Victor’ theology that is sometimes propagated nowadays as a more biblical alternative to the traditional Reformed soteriology, and which is considered the dominant approach in the ancient church? Can traces of Christ giving ‘satisfaction’ for God’s offended honor or for his wrath against sin be found in the first centuries? Did any church fathers hold that Christ vicariously bore God’s punishment for the sins of humankind? What was meant by the ransom that Christ had to pay, and to whom did he pay it: to God or to the devil, or were these considered invidious alternatives? This article demonstrates that in their interpretations of biblical texts, the church fathers did indeed address most of these questions. However, a continuous debate on such questions remained, so that the church of those centuries did not create a standard doctrine about the rationale of salvation by Christ, which testifies to varied understandings of it.
Eclectic Theory and Foreign Direct Investment in Nigeria: A Contextual Overview
Authors: Idowu Samuel S. 
Published: December 2021

Abstract
Foreign direct investment (FDI) is an integral and indispensable source of foreign capital for both the developed and developing countries aside its catalytic economic growth accompanying it. Hence, the competition to court more to maximizing its positives by countries is intensified in the contemporary world and eclectic theory offers significant insights on the tripartite and interrelated platforms of ownership, location, and internalization advantages to the appropriation of FDI to an economy. Therefore, this article main objective is to examine Nigeria’s experience in this regard. The case study research method is adopted to carry out a contextual assessment of Nigeria’s FDI position within the eclectic theory framework using secondary data sources. The findings reveal that Nigeria’s location advantages are not too conducive for FDI attraction and optimum exploitation of the internalization advantages by firms which consequently deprived the country of its benefits of export-driven economy objective and employment generation amongst others. The study recommends diversification of her economy and recalibration of the country’s political, economic and policy environment to enable positive predictability, FDI attraction, and its inherent returns appropriation.