bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of hindrance stressors on the emotional exhaustion among front-line healthcare workers in the recuperation period during the COVID-19 epidemic in China: a prospective cross-sectional study
Authors: Wang Huan , Zhou Xinyao , Song Caiping , Yin Pengpeng , Shi Renzhong , Zhang Hua , Dan Yang , Wu Hao , Ye Junying 
Published: June 2022

ObjectivesThis study aimed to examine the influence and conditioning process of hindrance stressors on the emotional exhaustion of the front-line healthcare workers during recuperation, examine the potential mediating process of rumination, and explore the moderating role of organisational and family factors.SettingThis cross-sectional study was conducted during 12–20 July 2020. Total 418 questionnaires were collected from front-line healthcare workers by random cluster sampling. Hierarchical regression was performed to analyse the mediating effect of affective rumination using SPSS25.0, while PROCESS was used to further investigate the moderating role of servant leadership and family support.Participants418 healthcare workers were investigated randomly from front-line medical teams. Inclusion criteria included worked as front-line health workers and participated in the fight against COVID-19 in Hubei; age ≥18 years; normal cognitive and comprehension abilities under physical and mental health; volunteer to participate in this study. Exclusion criteria included recently affected by major events other than COVID-19 or those with a history of neurasthenia and trauma.ResultsUsing descriptive analysis of average value and SD measured by a five-item scale (MBI-GS), we found that front-line healthcare workers’ emotional exhaustion score (2.45±0.88) was at the medium level. Hindrance stressors, mediated by affective rumination, had a significant positive predictive effect on emotional exhaustion. Servant leadership negatively moderated the direct effect of hindrance stressors on emotional exhaustion (β=−0.106, p<0.01). Family support positively moderated the impact of hindrance stressors on emotional exhaustion (β=0.082, p<0.05).ConclusionsDuring the recuperation period, after successfully controlling COVID-19 at the front line, the first-line healthcare workers should be screened through affective rumination evaluation to gain insight for targeted interventions. We find that servant leadership is beneficial in alleviating emotional exhaustion while family support worsens emotional exhaustion. We suggest that servant leadership should be further promoted in medical organisations, and family support should be applied correctly and cautiously.
Aluminium adjuvants versus placebo or no intervention in vaccine randomised clinical trials: a systematic review with meta-analysis and Trial Sequential Analysis
Authors: Krauss Sara Russo , Barbateskovic Marija , Klingenberg Sarah Louise , Djurisic Snezana , Petersen Sesilje Bondo , Kenfelt Mette , Kong De Zhao , Jakobsen Janus C , Gluud Christian 
Published: June 2022

ObjectivesTo assess the benefits and harms of aluminium adjuvants versus placebo or no intervention in randomised clinical trials in relation to human vaccine development.DesignSystematic review with meta-analysis and trial sequential analysis assessing the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE).Data sourcesWe searched CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, Science Citation Index Expanded and Conference Proceedings Citation Index-Science until 29 June 2021, and Chinese databases until September 2021.Eligibility criteriaRandomised clinical trials irrespective of type, status and language of publication, with trial participants of any sex, age, ethnicity, diagnosis, comorbidity and country of residence.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias with Cochrane’s RoB tool 1. Dichotomous data were analysed as risk ratios (RRs) and continuous data as mean differences. We explored both fixed-effect and random-effects models, with 95% CI. Heterogeneity was quantified with I2 statistic. We GRADE assessed the certainty of the evidence.ResultsWe included 102 randomised clinical trials (26 457 participants). Aluminium adjuvants versus placebo or no intervention may have no effect on serious adverse events (RR 1.18, 95% CI 0.97 to 1.43; very low certainty) and on all-cause mortality (RR 1.02, 95% CI 0.74 to 1.41; very low certainty). No trial reported on quality of life. Aluminium adjuvants versus placebo or no intervention may increase adverse events (RR 1.13, 95% CI 1.07 to 1.20; very low certainty). We found no or little evidence of a difference between aluminium adjuvants versus placebo or no intervention when assessing serology with geometric mean titres or concentrations or participants’ seroprotection.ConclusionsBased on evidence at very low certainty, we were unable to identify benefits of aluminium adjuvants, which may be associated with adverse events considered non-serious.
Upstream interventions to promote oral health and reduce socioeconomic oral health inequalities: a scoping review protocol
Authors: Dawson Eleanor R , Stennett Michelle , Daly Blánaid , Macpherson Lorna M D , Cannon Paul , Watt Richard G 
Published: June 2022

IntroductionImproving oral health and reducing oral health inequalities is an important global health priority. ‘Upstream interventions’ are a vital part of the collective effort to reduce oral disease burdens, however it is a rather nebulous term. Furthermore, there is little evidence on the effectiveness, impact and sustainability of upstream interventions that have focused on oral health and wider public health measures that impact on oral health. The aim of this scoping review is to systematically map and synthesise evidence on the effectiveness, impact and sustainability of upstream interventions on population oral health and reducing socioeconomic oral health inequalities.Methods and analysisThis scoping review will be conducted in accordance with the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A detailed search strategy will be used to conduct a comprehensive search of electronic databases: Scopus, Embase and MEDLINE, PsycINFO and CINAHL, ASSIA and Cochrane Database of Systematic Reviews. A search of grey literature will also be completed to identify relevant dissertations, governmental reports and evaluations of implemented policies. Identification and extraction of data will be performed by two pairs of reviewers. Oversight and feedback will be provided by an independent expert advisory group.Ethics and disseminationThis study will review published and available grey literature and does not require an ethics review. The scoping review protocol has been registered with the Open Science Framework. The final report will be circulated and disseminated through publication and feed into the work of the ongoing Lancet Commission on Oral Health. Due to the policy relevance of this work, discussions will take place with key stakeholders regarding the implications of the findings for future policy development.
A health-education intervention to improve outcomes for children with emotional and behavioural difficulties: protocol for a pilot cluster randomised controlled trial
Authors: Garvey William , Schembri Rachel , Oberklaid Frank , Hiscock Harriet 
Published: June 2022

IntroductionOne in seven (14%) children aged 4–17 years old meet criteria for a mental illness over a 12-month period. The majority of these children have difficulty accessing clinical assessment and treatment despite evidence demonstrating the importance of early intervention. Schools are increasingly recognised as universal platforms where children with mental health concerns could be identified and supported. However, educators have limited training or access to clinical support in this area.Methods and analysisThis study is a pilot cluster randomised controlled trial of a co-designed health and education model aiming to improve educator identification and support of children with emotional and behavioural difficulties. Twelve Victorian government primary schools representing a range of socio-educational communities will be recruited from metropolitan and rural regions, with half of the schools being randomly allocated to the intervention. Caregivers and educators of children in grades 1–3 will be invited to participate. The intervention is likely to involved regular case-based discussions and paediatric support.Ethics and disseminationInformed consent will be obtained from each participating school, educator and caregiver. Participants are informed of their voluntary participation and ability to withdrawal at any time. Participant confidentiality will be maintained and data will be secured on a password protected, restricted access database on the Murdoch Children’s Research Institute server. Results will be disseminated via peer-reviewed journals and conference presentations. Schools and caregivers will be provided with a report of the study outcomes and implications at the completion of the study.Trial registration numberACTRN12621000652875.
Predicting the likelihood of aBRCA1/2pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer
Authors: Morgan Robert D , Burghel George J , Flaum Nicola , Bulman Michael , Smith Philip , Clamp Andrew R , Hasan Jurjees , Mitchell Claire , Salih Zena , Woodward Emma R , Lalloo Fiona , Shaw Joseph , Desai Sudha , Crosbie Emma J , Edmondson Richard J , Schlecht Helene , Wallace Andrew J , Jayson Gordon C , Evans D Gareth R 
Published: June 2022

AimsClinical guidelines recommend testing both germline and tumour DNA forBRCA1/2pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumourBRCA1/2PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germlineBRCA1/2PVs.MethodsAn observational study that included all tumourBRCA1/2PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumourBRCA1/2PVs were compared with PVs recorded in a prospectively gathered pan-cancer germlineBRCA1/2(gBRCA) testing database for the same geographical region (gBRCA1PVs=910 and gBRCA2PVs=922). TumourBRCA1/2PVs were categorised as common (≥1%), uncommon (<1%) or absent from the germline database.ResultsOne hundred and thirteen tumourBRCA1/2PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCAand somaticBRCA1/2(sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test p<0.0001). All sBRCAPVs were detected in non-familial cases. All tumourBRCA1/2PVs with a variant allele frequency (VAF) <35% in non-familial cases were somatic variants. Eighty-one per cent of germline-tumourBRCA1/2PVs were present (common=31, uncommon=25) in the gBRCAtesting database, while 89% of somatic-tumourBRCA1/2PVs were absent (n=39).ConclusionsWe predict the likelihood of a tumourBRCA1/2PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality.
Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis
Authors: Guo Weinan , Wu Zhenjie , Chen Jianru , Guo Sen , You Weiming , Wang Sijia , Ma Jinyuan , Wang Huina , Wang Xiangxu , Wang Hao , Ma Jingjing , Yang Yuqi , Tian Yangzi , Shi Qiong , Gao Tianwen , Yi Xiuli , Li Chunying 
Published: June 2022

BackgroundAlthough anti-programmed cell death protein 1 (PD-1) immunotherapy is greatly effective in melanoma treatment, low response rate and treatment resistance significantly hinder its efficacy. Tumor cell ferroptosis triggered by interferon (IFN)-γ that is derived from tumor-infiltrating CD8+T cells greatly contributes to the effect of immunotherapy. However, the molecular mechanism underlying IFN-γ-mediated ferroptosis and related potentially promising therapeutic strategy warrant further clarification. MicroRNAs (miRNAs) participate in ferroptosis execution and can be delivered systemically by multiple carriers, which have manifested obvious therapeutic effects on cancer.MethodsMiRNAs expression profile in IFN-γ-driven ferroptosis was obtained by RNA sequencing. Biochemical assays were used to clarify the role of miR-21-3p in IFN-γ-driven ferroptosis and the underlying mechanism. MiR-21-3p-loaded gold nanoparticles were constructed and systemically applied to analyze the role of miR-21-3p in anti-PD-1 immunotherapy in preclinical transplanted tumor model.ResultsMiRNAs expression profile of melanoma cells in IFN-γ-driven ferroptosis was first obtained. Then, upregulated miR-21-3p was proved to facilitate IFN-γ-mediated ferroptosis by potentiating lipid peroxidation. miR-21-3p increased the ferroptosis sensitivity by directly targeting thioredoxin reductase 1 (TXNRD1) to enhance lipid reactive oxygen species (ROS) generation. Furthermore, miR-21-3p overexpression in tumor synergized with anti-PD-1 antibody by promoting tumor cell ferroptosis. More importantly, miR-21-3p-loaded gold nanoparticles were constructed, and the systemic delivery of them increased the efficacy of anti-PD-1 antibody without prominent side effects in preclinical mice model. Ultimately, ATF3 was found to promote miR-21-3p transcription in IFN-γ-driven ferroptosis.ConclusionsMiR-21–3 p upregulation contributes to IFN-γ-driven ferroptosis and synergizes with anti-PD-1 antibody. Nanoparticle delivery of miR-21–3 p is a promising therapeutic approach to increase immunotherapy efficacy without obvious systemic side effects.
Targeting of Nrf2 improves antitumoral responses by human NK cells, TIL and CAR T cells during oxidative stress
Authors: Renken Stefanie , Nakajima Takahiro , Magalhaes Isabelle , Mattsson Jonas , Lundqvist Andreas , Arnér Elias S J , Kiessling Rolf , Wickström Stina Linnea 
Published: June 2022

BackgroundAdoptive cell therapy using cytotoxic lymphocytes is an efficient immunotherapy against solid and hematological cancers. However, elevated levels of reactive oxygen species (ROS) in the hostile tumor microenvironment can impair NK cell and T cell function. Auranofin, a gold (I)-containing phosphine compound, is a strong activator of the transcription factor Nrf2. Nrf2 controls a wide range of downstream targets important for the cells to obtain increased resistance to ROS. In this study, we present a strategy using auranofin to render human cytotoxic lymphocytes resistant toward oxidative stress.MethodsMelanoma patient-derived tumor infiltrating lymphocytes (TIL) and healthy donor-derived NK cells and CD19-directed CAR T cells were pretreated with a low dose of auranofin. Their resistance toward oxidative stress was assessed by measuring antitumoral responses (killing-assay, degranulation/CD107a, cytokine production) and intracellular ROS levels (flow cytometry) in conditions of oxidative stress. To confirm that the effects were Nrf2 dependent, the transcription level of Nrf2-driven target genes was analyzed by qPCR.ResultsPretreatment of human TIL and NK cells ex vivo with a low-dose auranofin significantly lowered their accumulation of intracellular ROS and preserved their antitumoral activity despite high H2O2levels or monocyte-derived ROS. Furthermore, auranofin pretreatment of CD19 CAR-T cells or TIL increased their elimination of CD19 +tumor cells or autologous tumor spheroids, respectively, especially during ROS exposure. Analysis of Nrf2-driven target genes revealed that the increased resistance against ROS was Nrf2 dependent.ConclusionThese novel findings suggest that Nrf2 activation in human cytotoxic lymphocytes could be used to enhance the efficacy of adoptive cell therapy.
Gut microbiota and metabolites associate with outcomes of immune checkpoint inhibitor–treated unresectable hepatocellular carcinoma
Authors: Lee Pei-Chang , Wu Chi-Jung , Hung Ya-Wen , Lee Chieh Ju , Chi Chen-Ta , Lee I-Cheng , Yu-Lun Kuo , Chou Shih-Hsuan , Luo Jiing-Chyuan , Hou Ming-Chih , Huang Yi-Hsiang 
Published: June 2022

BackgroundImmune checkpoint inhibitors (ICIs) are promising agents for unresectable hepatocellular carcinoma (uHCC), but lack effective biomarker to predict outcomes. The gut microbiome can modulate tumor response to immunotherapy, but its effect on HCC remains unclear.MethodsFrom May 2018 to February 2020, patients receiving ICI treatment for uHCC were prospectively enrolled; their fecal samples were collected before treatment. The fecal microbiota and metabolites were analyzed from 20 patients with radiology-proven objective responses (OR) and 21 randomly selected patients with progressive disease (PD). After March 2020, 33 consecutive Child-Pugh-A patients were recruited as a validation cohort. Additionally, feces from 17 healthy volunteers were collected for comparison of background microbes.ResultsA significant dissimilarity was observed in fecal bacteria between patients with OR and patients with PD before immunotherapy.Prevotella 9was enriched in patients with PD, whereasLachnoclostridium, Lachnospiraceae,andVeillonellawere predominant in patients with OR. Ursodeoxycholic acid and ursocholic acid were significantly enriched in the feces of patients with OR and strongly correlated with the abundance ofLachnoclostridium. The coexistence ofLachnoclostridiumenrichment andPrevotella 9depletion significantly predicted better overall survival (OS). In the validation cohort, better progression-free survival (PFS) and OS were noted in patients who had a preferable microbial signature in comparison with counter-group (PFS: 8.8 months vs 1.8 months; OS: not reached vs 6.5 months, both p<0.001).ConclusionsFecal microbiota and bile acids were associated with outcomes of immunotherapy for uHCC. These findings highlight the potential role of gut microbiota and metabolites as biomarkers to predict outcomes of ICI-treated HCC.
Habitual exercise, chronic exposure to fine particulate matter and high-sensitivity C reactive protein in Asian adults
Authors: Zeng Yi Qian , Chan Shin Heng Teresa , Guo Cui , Chang Ly-yun , Bo Yacong , Lin Changqing , Yu Zengli , Lau Alexis K.H. , Tam Tony , Lao Xiang Qian 
Published: June 2022

ObjectivesExercise may increase the inhaled amount of air pollutants and exacerbate the adverse health effects. We investigated the combined effects of chronic exposure to fine particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and habitual exercise on C reactive protein (CRP), a sensitive marker of inflammation.MethodsWe selected 40 209 Taiwanese adults who joined a standard medical screening programme between 2001 and 2016. The PM2.5exposure was estimated at each participant’s address using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. Mixed-effects linear regression models were used to investigate the associations of CRP with PM2.5and exercise. An interaction term of PM2.5and exercise was introduced in the models to test the modifying effects.ResultsA greater amount of habitual exercise was associated with a decreased level of CRP, while a higher concentration of PM2.5exposure was associated with an increased level of CRP. The inverse associations of habitual exercise with CRP were not modified by chronic exposure to PM2.5. The participants in the group with a low level of exercise and a high level of PM2.5exposure exhibited a 19.1% higher level of CRP than those in the group with a high level of exercise and a low level of PM2.5exposure (95% CI: 13.7% to 24.8%; p<0.001). The longitudinal and sensitivity analyses yielded similar results.ConclusionsIncreased levels of exercise and reduced exposure levels of PM2.5are associated with a lower CRP level. Habitual exercise reduces CRP level regardless of the levels of chronic PM2.5exposure. Our results support that habitual exercise is a safe approach for reducing systemic inflammation to improve cardiovascular health even for people residing in relatively polluted areas.
Equilibrium and nonequilibrium quantum correlations between two detectors in curved spacetime
Authors: Wang He , Wang Jin 
Published: June 2022

AbstractWe investigate the equilibrium and nonequilibrium quantum information correlations encoded in a two-qubit system in curved spacetime near the horizon of a Kerr black hole. We study the impact of mass and the angular momentum and further the local curvature or accelerations on the behaviors of the quantum correlations between the two qubits. We show that the quantum information of the two qubits is encoded in the spacetime structure. Concretely, the quantum correlations in the two-qubit system vary non-monotonically with the mass of the black hole and are amplified by the angular momentum, while the curvature suppresses the quantum correlations in the system. We show that the nonequilibrium can also contribute to the quantum correlations. Remarkably, the nonequilibrium can lead to the increase of quantum correlations in the steady state under the curved spacetime shown in this black hole example.
Renormalizing the vacuum energy in cosmological spacetime: implications for the cosmological constant problem
Authors: Moreno-Pulido Cristian , Solà Peracaula Joan 
Published: June 2022

AbstractThe renormalization of the vacuum energy in quantum field theory (QFT) is usually plagued with theoretical conundrums related not only with the renormalization procedure itself, but also with the fact that the final result leads usually to very large (finite) contributions incompatible with the measured value of$$\Lambda $$Λin cosmology. As a consequence, one is bound to extreme fine-tuning of the parameters and so to sheer unnaturalness of the result and of the entire approach. We may however get over this adversity using a different perspective. Herein, we compute the zero-point energy (ZPE) for a nonminimally coupled (massive) scalar field in FLRW spacetime using the off-shell adiabatic renormalization technique employed in previous work. The on-shell renormalized result first appears at sixth adiabatic order, so the calculation is rather cumbersome. The general off-shell result yields a smooth function$$\rho _{\mathrm{vac}}(H)$$ρvac(H)made out of powers of the Hubble rate and/or of its time derivatives involving different (even) adiabatic orders$$\sim H^N$$∼HN($$N=0, 2,4,6,\ldots )$$N=0,2,4,6,…), i.e. it leads, remarkably enough, to the running vacuum model (RVM) structure. We have verified the same result from the effective action formalism and used it to find the$$\beta $$β-function of the running quantum vacuum. No undesired contributions$$\sim m^4$$∼m4from particle masses appear and hence no fine-tuning of the parameters is needed in$$\rho _{\mathrm{vac}}(H)$$ρvac(H). Furthermore, we find that the higher power$$\sim H^6$$∼H6could naturally drive RVM-inflation in the early universe. Our calculation also elucidates in detail the equation of state of the quantum vacuum: it proves to be not exactly$$-1$$-1and is moderately dynamical. The form of$$\rho _{\mathrm{vac}}(H)$$ρvac(H)at low energies is also characteristic of the RVM and consists of an additive term (the so-called ‘cosmological constant’) together with a small dynamical component$$\sim \nu H^2$$∼νH2($$|\nu |\ll 1$$|ν|≪1). Finally, we predict a slow ($$\sim \ln H$$∼lnH) running of Newton’s gravitational couplingG(H). The physical outcome of our semiclassical QFT calculation is revealing: today’s cosmic vacuum and the gravitational strength should be both mildly dynamical.