bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary trabeculectomy for advanced glaucoma: pragmatic multicentre randomised controlled trial (TAGS)
Authors: King Anthony J , Hudson Jemma , Fernie Gordon , Kernohan Ashleigh , Azuara-Blanco Augusto , Burr Jennifer , Homer Tara , Shabaninejad Hosein , Sparrow John M , Garway-Heath David , Barton Keith , Norrie John , McDonald Alison , Vale Luke , MacLennan Graeme 
Published: May 2021

Abstract

Objective
To determine whether primary trabeculectomy or primary medical treatment produces better outcomes in term of quality of life, clinical effectiveness, and safety in patients presenting with advanced glaucoma.

Design
Pragmatic multicentre randomised controlled trial.

Setting
27 secondary care glaucoma departments in the UK.

Participants
453 adults presenting with newly diagnosed advanced open angle glaucoma in at least one eye (Hodapp classification) between 3 June 2014 and 31 May 2017.

Interventions
Mitomycin C augmented trabeculectomy (n=227) and escalating medical management with intraocular pressure reducing drops (n=226)

Main outcome measures
Primary outcome: vision specific quality of life measured with Visual Function Questionnaire-25 (VFQ-25) at 24 months. Secondary outcomes: general health status, glaucoma related quality of life, clinical effectiveness (intraocular pressure, visual field, visual acuity), and safety.

Results
At 24 months, the mean VFQ-25 scores in the trabeculectomy and medical arms were 85.4 (SD 13.8) and 84.5 (16.3), respectively (mean difference 1.06, 95% confidence interval −1.32 to 3.43; P=0.38). Mean intraocular pressure was 12.4 (SD 4.7) mm Hg for trabeculectomy and 15.1 (4.8) mm Hg for medical management (mean difference −2.8 (−3.8 to −1.7) mm Hg; P<0.001). Adverse events occurred in 88 (39%) patients in the trabeculectomy arm and 100 (44%) in the medical management arm (relative risk 0.88, 95% confidence interval 0.66 to 1.17; P=0.37). Serious side effects were rare.

Conclusion
Primary trabeculectomy had similar quality of life and safety outcomes and achieved a lower intraocular pressure compared with primary medication.

Trial registration

Health Technology Assessment (NIHR-HTA) Programme (project number: 12/35/38). ISRCTN registry:
ISRCTN56878850
.
Let It Out (LIO) study: protocol for a mixed-methods study to optimise the design and assess the feasibility of an online emotional disclosure-based intervention in UK hospices
Authors: McInnerney Daisy , Candy Bridget , Stone Patrick , Kupeli Nuriye 
Published: May 2021

IntroductionThe current COVID-19 pandemic has forced hospices to look for more ways to support people remotely, including psychological support. Emotional disclosure-based interventions hold potential as a way of providing support remotely. However, evidence of their efficacy in people with terminal illness is mixed. Reviews have highlighted this may be due to interventions not being tailored to the unique needs of this population. In response to this, we are developing Let It Out (LIO), an online, self-guided emotional disclosure-based intervention tailored for people living with terminal illness.AimsThe primary objective of the study is to optimise the design of the LIO intervention. Secondary objectives include assessing its acceptability and feasibility; exploring potential impact on well-being; identifying potential adverse effects; and informing choice of outcome measures for potential future evaluation.Methods and analysisA single arm, mixed-methods, multisite, longitudinal study. Up to 40 people living with a terminal illness under the care of hospices in England and Scotland will receive the online LIO intervention. LIO consists of 3, self-guided expression sessions over 2 weeks. The primary outcome measures are (1) a structured feedback form completed by participants after the final expression session; and (2) semi-structured interviews and focus groups with ≤15 patient participants, ≤30 hospice staff and ≤15 informal carers. These quantitative and qualitative data will be triangulated via process evaluation to inform optimisation of the intervention design. Secondary outcome measures include validated measures of physical and psychological health collected at baseline and after the final expression session (immediately, 1, 4 and 8 weeks after); and data on recruitment, retention and fidelity.Ethics and disseminationThe study is approved by the University College London Research Ethics Committee (reference: 15281/002). The findings will be shared through peer-reviewed scientific journals and conferences, and traditional, online and social media platforms.
Modification of maternal late pregnancy sleep position: a survey evaluation of a New Zealand public health campaign
Authors: Cronin Robin S , Thompson John M D , Taylor Rennae S , Wilson Jessica , Falloon Karen F , Skelton Sophie , Brown Elsie , Culling Vicki M , Mitchell Edwin A , McCowan Lesley M E 
Published: May 2021

IntroductionA ‘Sleep-On-Side When Baby’s Inside’ public health campaign was initiated in New Zealand in 2018. This was in response to evidence that maternal supine going-to-sleep position was an independent risk factor for stillbirth from 28 weeks’ gestation. We evaluated the success of the campaign on awareness and modification of late pregnancy going-to-sleep position through nationwide surveys.Methods and analysisTwo web-based cross-sectional surveys were conducted over 12 weeks in 2019–2020 in a sample of (1) pregnant women ≥28 weeks, primary outcome of going-to-sleep position; and (2) health professionals providing pregnancy care, primary outcome of knowledge of going-to-sleep position and late stillbirth risk. Univariable logistic regression was performed to identify factors associated with supine going-to-sleep position.DiscussionThe survey of pregnant women comprised 1633 eligible participants. Going-to-sleep position last night was supine (30, 1.8%), non-supine (1597, 97.2%) and no recall (16, 1.0%). Supine position had decreased from 3.9% in our previous New Zealand-wide study (2012–2015). Most women (1412, 86.5%) had received sleep-on-side advice with no major resultant worry (1276, 90.4%). Two-thirds (918, 65.0%) had changed their going-to-sleep position based on advice, with most (611 of 918, 66.5%) reporting little difficulty. Supine position was associated with Māori (OR 5.05, 95% CI 2.10 to 12.1) and Asian-non-Indian (OR 4.20, 95% CI 1.27 to 13.90) ethnicity; single (OR 10.98, 95% CI 4.25 to 28.42) and cohabitating relationship status (OR 2.69, 95% CI 1.09 to 6.61); hospital-based maternity provider (OR 2.55, 95% CI 1.07 to 6.10); education overseas (OR 3.92, 95% CI 1.09 to 14.09) and primary-secondary level (OR 2.80, 95% CI 1.32 to 6.08); and not receiving sleep-on-side advice (OR 6.70, 95% CI 3.23 to 13.92). The majority of health professionals (709 eligible participants) reported awareness of supine going-to-sleep position and late stillbirth risk (543, 76.6%).ConclusionMost pregnant women had received and implemented sleep-on-side advice without major difficulty or concern. Some groups of women may need a tailored approach to acquisition of going-to-sleep position information.
DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells
Authors: Cueto Francisco J , del Fresno Carlos , Brandi Paola , Combes Alexis J. , Hernández-García Elena , Sánchez-Paulete Alfonso R , Enamorado Michel , Bromley Christian P , Gomez Manuel J , Conde-Garrosa Ruth , Mañes Santos , Zelenay Santiago , Melero Ignacio , Iborra Salvador , Krummel Matthew F. , Sancho David 
Published: May 2021

BackgroundConventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet.MethodsB16 and MC38 tumor cell lines were inoculated subcutaneously into wild-type (WT) and DNGR-1-deficient mice. To overexpress Flt3L systemically, we performed gene therapy through the hydrodynamic injection of an Flt3L-encoding plasmid. To characterize the immune response, we performed flow cytometry and RNA-Seq of tumor-infiltrating cDC1s.ResultsHere, we found that cross-presentation of tumor antigens in the steady state was DNGR-1-independent. However, on Flt3L systemic overexpression, tumor growth was delayed in DNGR-1-deficient mice compared with WT mice. Of note, this protection was recapitulated by anti-DNGR-1-blocking antibodies in mice followingFlt3Lgene therapy. This improved antitumor immunity was associated withBatf3-dependent enhanced accumulation of CD8+T cells and cDC1s within tumors. Mechanistically, the deficiency in DNGR-1 boosted an Flt3L-induced specific inflammatory gene signature in cDC1s, includingCcl5expression. Indeed, the increased infiltration of cDC1s within tumors and their protective effect rely on CCL5/CCR5 chemoattraction. Moreover,FLT3LGandCCL5orCCR5gene expression signatures correlate with an enhanced cDC1 signature and a favorable overall survival in patients with cancer. Notably, cyclophosphamide elevated serum Flt3L levels and, in combination with the absence of DNGR-1, synergized against tumor growth.ConclusionDNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression.
Diagnostic Value of Combined Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Diffusion Tensor Imaging in Predicting Parametrial Infiltration in Cervical Cancer
Authors: Lin Ting-Ting , Li Xin-Xiang , Lv Wei-Fu , Dong Jiang-Ning , Wei Chao , Wang Ting-Ting , Wang Chuan-Bin , Zhang Ping 
Published: May 2021

Objective. This study sought to determine the diagnostic value of combined intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) in predicting parametrial infiltration (PMI) in patients with cervical cancer. Materials and Methods. We enrolled 65 patients with cervical cancer confirmed by radical hysterectomy (25 PMI-negative and 40 PMI-positive) who underwent IVIM and DTI pretreatment. The parameters of IVIM (ADC, D, D

∗

, and f) and DTI (average diffusion coefficient (DCavg) and fractional anisotropy (FA)) were recorded by two observers. All parameter differences were tested, and the receiver operating characteristic (ROC) curves were generated to estimate the diagnostic performance of significant metrics and their combinations. Results. Compared to the PMI-negative group, the PMI-positive group had significantly lower D (0.632 ± 0.017 vs. 0.773 ± 0.024,

p
<
0.001

) and lower FA (0.073 ± 0.002 vs. 0.085 ± 0.003,

p
=
0.003

). The area under the ROC curve (AUC) of D and FA was 0.801 and 0.726, respectively, and the combination of D and FA improved the AUC to 0.931, with a sensitivity and specificity of 80.0% and 97.5%, respectively. Conclusion. D and FA values could be used to help diagnose PMI in patients with cervical cancer. The combination of IVIM and DTI was more valuable than either option alone.
Visualization of Intratumor Pharmacokinetics of [fam-] Trastuzumab Deruxtecan (DS-8201a) in HER2 Heterogeneous Model Using Phosphor-integrated Dots Imaging Analysis
Authors: Suzuki Mikiko , Yagishita Shigehiro , Sugihara Kiyoshi , Ogitani Yusuke , Nishikawa Tadaaki , Ohuchi Mayu , Teishikata Takashi , Jikoh Takahiro , Yatabe Yasushi , Yonemori Kan , Tamura Kenji , Hasegawa Kosei , Hamada Akinobu 
Published: May 2021

Abstract

Purpose:
We assessed the intratumor pharmacokinetics of [fam-] trastuzumab deruxtecan, T-DXd (known as DS-8201a), a novel HER2-targeted antibody–drug conjugate, using phosphor-integrated dots (PID)-imaging analysis to elucidate its pharmacologic mechanism.

Experimental Design:
We used two mouse xenograft models administered T-DXd at the concentration of 4 mg/kg: (i) a heterogeneous model in which HER2-positive and HER2-negative cell lines were mixed, and (ii) a homogeneous model in which both cell types were transplanted separately into the same mouse. PID imaging involved immunostaining using novel high-intensity fluorescent nanoparticles. The distribution of T-DXd was assessed by PID imaging targeting the parent antibody, trastuzumab, and the payload, DXd, in serial frozen sections, respectively.

Results:
After T-DXd administration in the heterogeneous model, HER2 expression tended to decrease in a time-dependent manner. The distribution of trastuzumab and DXd was observed by PID imaging along the HER2-positive area throughout the observation period. A detailed comparison of the PID distribution between trastuzumab and DXd showed that trastuzumab matched almost perfectly with the HER2-positive area. In contrast, DXd exhibited widespread distribution in the surrounding HER2-negative area as well. In the HER2-negative tumor of the homogeneous model, the PID distribution of trastuzumab and DXd remained extremely low throughout the observation period.

Conclusions:
Our results suggest that T-DXd is distributed to tumor tissues via trastuzumab in a HER2-dependent manner and then to adjacent HER2-negative areas. We successfully visualized the intratumor distribution of T-DXd and its mechanism of action, the so-called “bystander effect.”
Uma Respublica Cristã Seiscentista na Accomodatio Jesuítica: as fundações e a polêmica no caso de Madurai, entre Ásia e ecos americanos
Authors: Agnolin Adone 
Published: May 2021

Esse trabalho analisa o peculiar projeto missionário proposto pelo jesuíta italiano Roberto de’ Nobili, em Madurai, no Sul da Índia, a partir do começo do século XVII e a decorrente polêmica suscitada no interior da própria Companhia de Jesus, além que junto a algumas autoridades de Goa e junto a uma parte da Congregação de Propaganda Fide de Roma. A proposta de de’ Nobili se realiza a partir desse contexto polêmico e do eco da reflexão de seu irmão na ordem jesuítica, no Peru, José de Acosta. Os dois âmbitos missionários são ligados às estratégias da “acomodação” e da “redução” e se entrelaçaram entre si estabelecendo uma dialética que envolvia um eco e uma correspondência tipicamente ortopráticos entre rituais e sacramentos em toda sua capacidade de construir uma “grelha jurídica” de cristianização do mundo: mas, observe-se atentamente, enquanto uma específica forma de “civilização”, jurídica e antropológica, construída no interior do Ocidente.
Standard ECG in Brugada Syndrome as a Marker of Prognosis: From Risk Stratification to Pathophysiological Insights
Authors: Vitali Francesco , Brieda Alessandro , Balla Cristina , Pavasini Rita , Tonet Elisabetta , Serenelli Matteo , Ferrari Roberto , Delise Pietro , Rapezzi Claudio , Bertini Matteo 
Published: May 2021

Background
The 12‐lead ECG plays a key role in the diagnosis of Brugada syndrome (BrS). Since the spontaneous type 1 ECG pattern was first described, several other ECG signs have been linked to arrhythmic risk, but results are conflicting.

Methods and Results

We performed a systematic review to clarify the associations of these specific ECG signs with the risk of syncope, sudden death, or equivalents in patients with BrS. The literature search identified 29 eligible articles comprising overall 5731 patients. The ECG findings associated with an incremental risk of syncope, sudden death, or equivalents (hazard ratio ranging from 1.1–39) were the following: localization of type 1 Brugada pattern (in V2 and peripheral leads), first‐degree atrioventricular block, atrial fibrillation, fragmented QRS, QRS duration >120 ms, R wave in lead aVR, S wave in L1 (≥40 ms, amplitude ≥0.1 mV, area ≥1 mm
2
), early repolarization pattern in inferolateral leads, ST‐segment depression, T‐wave alternans, dispersion of repolarization, and Tzou criteria.

Conclusions
At least 12 features of standard ECG are associated with a higher risk of sudden death in BrS. A multiparametric risk assessment approach based on ECG parameters associated with clinical and genetic findings could help improve current risk stratification scores of patients with BrS and warrants further investigation.

Registration

URL:
https://www.crd.york.ac.uk/prospero/
. Unique identifier: CRD42019123794.
A large-scale validation of the relationship between cross-disciplinary research and its uptake in policy-related documents, using the novel Overton altmetrics database
Authors: Pinheiro Henrique , Vignola-Gagné Etienne , Campbell David 
Published: May 2021

Abstract
Cross-disciplinary research (multi-/interdisciplinarity) is incentivized by funding agencies to foster research outcomes addressing complex societal challenges. This study focuses on the link between cross-disciplinary research and its uptake in a broad set of policy-related documents. Using the new policy-oriented database Overton, matched to Scopus, logistic regression was used in assessing this relationship in publications from FP7- and H2020-supported projects. Cross-disciplinary research was captured through two lenses at the paper level, namely from the disciplinary diversity of contributing authors (DDA) and of cited references (DDR). DDA increased the likelihood that publications were cited in policy documents, with DDR possibly making a contribution, but only when publications result from the work of few authors. Citations to publications captured by Overton were found to originate in scientific advice documents, rather than in legislative or executive records. Our approach enables testing in a general way the assumption underlying many funding programs, namely that cross-disciplinary research will increase the policy relevance of research outcomes. Findings suggest that research assessments could benefit from measuring uptake in policy-related literature, following additional characterization of the Overton database; of the science-policy interactions it captures; and of the contribution of these interactions within the larger policymaking process.
Owning Virtue
Authors: Piñeros Glasscock Allison 
Published: May 2021

Abstract
At the end of the Meno, Socrates suggests that genuine virtue is knowledge. This is surprising because he has recently concluded that virtue is (mere) true opinion. I show that Socrates’ new position is motivated by two commitments. First, that being virtuous requires being responsible for the correctness of one’s actions. Second, that only a knower has this kind of ownership of action. An implication of my argument is that, despite his emphasis on virtuous action in the Meno, Socrates endorses an agent-centred ethics. He thinks the epistemic status of the agent is essential to the assessment of her goodness.
Catching John in Four Nets? Competition, Qumran, Sacramentalism and Messianism
Authors: Adinolfi Federico , Taylor Joan 
Published: May 2021

Abstract
In his recent study on John the Baptist Joel Marcus suggests that John founded a sect that was in competition with the early Jesus movement. Marcus also suggests that John himself was a former member of the 'Qumran community'. His baptism is considered as a kind of sacrament in which the Holy Spirit was imparted. How secure are these proposals? In this discussion, we conclude that in the oldest literary witnesses – Q, Mark and Matthew – the relationship between John and Jesus is seen in terms of mutual agreement (despite Jesus’s obvious superiority) and there are no recognizable traces of serious competition with John’s disciples, even less a ‘Baptist sect’. The evidence used by Marcus to suggest that John was once a member of the ‘Qumran community’ connects John with broader patterns of thought in Second Temple Judaism, not simply sectarians at one location. That John imparted the Holy Spirit in a sacramental rite can only be supported by radically altering biblical readings. However, Marcus has suggested that in light of all this that John thought of himself not only as Elijah but as a kind of Messiah, with the role of his successor, the Coming One, being to destroy the chaff. In doing this, Marcus redesigns John as a kind of alternative Christ of Faith. However, the underlying ‘competition model’ needs to be rejected and replaced with one that sees Jesus as claiming to be a successor to John, his highly esteemed teacher.
Naturalizing Christians: A Response to Joel Marcus, John the Baptist in History and Theology
Authors: Roberts Erin 
Published: May 2021

Abstract
This essay examines the conceptual framework that informs Marcus’s distinction between history and theology, and considers what stands to be gained by this manner of classification. The essay observes that Marcus’s classification hinges upon a theory of religion that views gospels as artifacts expressive of sincere belief and, further, suggests this approach serves to mystify the origins of the Christian theological metanarrative by replicating the explanation asserted within the gospels themselves. By reversing the conceptual framework and the explanatory priority, one could deploy a theory of religion that sees gospels as artifacts of persuasion and thereby argue that they aim to naturalize the initially unnatural truth claim that Jesus was the christ by connecting him to a known social type: John. From this approach, it would not be belief in Jesus as the christ that explains the modified constructions of John the Baptist; rather, modifications of John the Baptist would be precisely what construct belief in Jesus as the christ.
Virtue, Knowledge, and Political Instability in Aristotle’s Politics: Lessons from the Eudemian Ethics
Authors: Miller Benjamin 
Published: May 2021

Abstract
I argue that we cannot fully understand Aristotle’s position on political stability and state preservation in the Politics with paying close attention to his Eudemian Ethics. We learn from considering the Politics and the Eudemian Ethics in concert that even ‘correct’ regimes are unstable when citizens do not possess full virtue. Aristotle introduces his formal account of the knowledge requirements for virtue in Eudemian Ethics 8.3, and he applies these knowledge requirements as an explanation for state decline in Politics 2.9 when discussing the Spartans. If we primarily focus on the Nicomachean Ethics as Aristotle’s single essential ethical work, we will not learn the lesson he intends his readers to take away from the Spartan discussion in the Politics: that virtue requires correct understanding of the hierarchy and structure of the good life. This knowledge prevents the erosion of the virtues of character and the decline of political regimes.
Comparative Global Humanities Now
Authors: Denecke Wiebke 
Published: May 2021

Abstract
This essay proposes to energize the mission of the humanities by radically globalizing their subject matter and methods, taking inspiration from the world’s monumental archive of humanistic creativity over 5000 years of recorded experience. It advocates for Comparative Global Humanities as a crucial complement to the more presentist new humanities fields of medical, environmental, or public humanities. Comparative Global Humanities aims to be inclusively global in terms of subject matter and participants, conceptually comparative, and based on rigorous historical and philological research. A Global Humanities for the 21st century is no antiquarian endeavor, but a head-on response to the greatest challenges of our times: systemic racism, inequality, and fundamentalisms, which are rooted in the unresolved aftermath of wars, colonization, and violence, and use classical heritage for nationalist propaganda. To create more equal societies in the present we need to create more equality for other pasts – and learn from all they offer.