bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-VEGF Antibody Protects against Alveolar Exudate Leakage Caused by Vascular Hyperpermeability, Resulting in Mitigation of Pneumonitis Induced by Immunotherapy
Authors: Iwai Toshiki , Sugimoto Masamichi , Patel Hina , Yorozu Keigo , Kurasawa Mitsue , Kondoh Osamu 
Published: September 2021

Abstract
Immune-related pneumonitis is an important toxicity associated with checkpoint inhibitor therapy with anti–PD-1 or anti–PD-L1 antibodies, often necessitating discontinuation of treatment. Development of methods to mitigate checkpoint inhibitor–related pneumonitis is required.
The contributions of PD-L1, PD-L2, and VEGF to the pathogenesis of pneumonitis were examined in an IL2- plus IL18-induced mouse pneumonitis model (IL pneumonitis model). Furthermore, the incidences of pneumonitis were retrospectively examined in patients with non–small cell lung cancer treated with the anti–PD-L1 mAb atezolizumab plus chemotherapy, with or without the anti-VEGF mAb bevacizumab, in the phase III IMpower150 trial. PD-1 signal blockade by anti–PD-L1 and anti–PD-L2 antibodies aggravated pneumonitis in the IL pneumonitis model. An anti-VEGF antibody prevented PD-1 signal blockade from aggravating pneumonitis in this model. PD-1 signal blockade induced interstitial T-cell infiltration in the lungs, but VEGF blockade did not affect this T-cell infiltration. The anti-VEGF antibody protected against vascular-to-alveolar leakage of protein and fluid due to PD-1 signal blockade in a murine model. In the IMpower150 trial, incidence rates of pneumonitis of any grade were 4.3% in the group without bevacizumab and 2.8% in the group with bevacizumab. In patients with pneumonitis, outcomes of “Not recovered/Not resolved” were reported for 29.4% in the group without bevacizumab compared with 9.1% in the group with bevacizumab. Our findings suggest that anti-VEGF antibodies in combination with checkpoint inhibitors may be a treatment method that can control checkpoint inhibitor–related pneumonitis.
Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial
Authors: Martin-Broto Javier , Lopez-Alvarez Maria , Moura David S. , Ramos Rafael , Collini Paola , Romagosa Cleofe , Bagué Silvia , Renne Salvatore L. , Barisella Marta , Velasco Valerie , Coindre Jean-Michel , Lopez-Lopez Daniel , Dopazo Joaquin , Gambarotti Marco , Braglia Luca , Merlo Domenico Franco , Palmerini Emanuela , Stacchiotti Silvia , Quagliuolo Vittorio L. , Lopez-Pousa Antonio , Grignani Giovanni , Blay Jean-Yves , Brunello Antonella , Gutierrez Antonio , Valverde Claudia , Hindi Nadia , Dei Tos Angelo Paolo , Picci Piero , Casali Paolo G. , Gronchi Alessandro 
Published: September 2021

Abstract
MRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS. MRP-1 expression was assessed by IHC in tissue microarrays from patients with STS and tested for correlation with disease-free survival (DFS) and overall survival (OS). In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. The effect of combinations of the most active MRP-1 inhibitors and chemotherapy was measured on the basis of apoptosis. MRP-1 was evaluable in 231 of 264 cases who entered the study. MRP-1 expression (strong intensity) was independently associated with worse DFS [HR, 1.78; 95% confidence interval (CI), 1.11–2.83; P = 0.016], in the multivariate analysis, with a trend for a worse OS (HR, 1.78; 95% CI, 0.97–3.25; P = 0.062). In vitro studies showed that the addition of MRP-1 inhibitors (nilotinib or avapritinib) to doxorubicin plus palifosfamide, significantly increased cell death in SK-UT-1 and CP0024 cell lines. MRP-1 is an adverse predictive factor in localized high-risk patients with STS treated with neoadjuvant anthracyclines plus ifosfamide followed by surgery. In vitro findings support the clinical assessment of the combination of chemotherapy and MRP-1 inhibitors as a promising strategy to overcome the drug ceiling effect for chemotherapy.
Genome-wide analysis and expression profiles of PdeMYB transcription factors in colored-leaf poplar (Populus deltoids)
Authors: Zhuang Weibing , Shu Xiaochun , Lu Xinya , Wang Tao , Zhang Fengjiao , Wang Ning , Wang Zhong 
Published: September 2021

Abstract
Background
MYB transcription factors, comprising one of the largest transcription factor families in plants, play many roles in secondary metabolism, especially in anthocyanin biosynthesis. However, the functions of the PdeMYB transcription factor in colored-leaf poplar remain elusive.

Results
In the present study, genome-wide characterization of the PdeMYB genes in colored-leaf poplar (Populus deltoids) was conducted. A total of 302 PdeMYB transcription factors were identified, including 183 R2R3-MYB, five R1R2R3-MYB, one 4R-MYB, and 113 1R-MYB transcription factor genes. Genomic localization and paralogs of PdeMYB genes mapped 289 genes on 19 chromosomes, with collinearity relationships among genes. The conserved domain, gene structure, and evolutionary relationships of the PdeMYB genes were also established and analyzed. The expression levels of PdeMYB genes were obtained from previous data in green leaf poplar (L2025) and colored leaf poplar (QHP) as well as our own qRT-PCR analysis data in green leaf poplar (L2025) and colored leaf poplar (CHP), which provide valuable clues for further functional characterization of PdeMYB genes.

Conclusions
The above results provide not only comprehensive insights into the structure and functions of PdeMYB genes but also provide candidate genes for the future improvement of leaf colorization in Populus deltoids.
Process evaluation of an implementation study in dementia care (EIT-4-BPSD): stakeholder perspectives
Authors: Behrens Liza , Boltz Marie , Riley Kiernan , Eshraghi Karen , Resnick Barbara , Galik Elizabeth , Ellis Jeanette , Kolanowski Ann , Van Haitsma Kimberly 
Published: September 2021

Abstract
Background
Behavioral and psychological symptoms of distress in dementia (BPSD) are major drivers of poor quality of life, caregiver burden, institutionalization, and cost of care in nursing homes. The Evidence Integration Triangle (EIT)-4-BPSD in nursing homes was a pragmatic Hybrid III trial of an implementation strategy to help staff use evidence-based non-pharmacological interventions to prevent and manage BPSD. This study aimed to describe and explore the stakeholders’ perceptions of the process to implement the EIT-4-BPSD strategy including its utility, and the barriers and facilitators to implementation in real-world settings.

Methods
EIT-4-BPSD was a multi-layer implementation strategy that engaged nursing home stakeholder groups to define community specific goals towards reducing BPSD over a 12-month period. Stakeholder groups from nursing homes that completed all 12-months of the implementation strategy were invited to participate in this process evaluation study. Qualitative data from focus group transcripts were analyzed using a conventional content analysis. Emerging codes were sorted into categories, then organized in meaningful clusters based on the domains of the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework.

Results
The EIT-4-BPSD implementation strategy was completed in 21 nursing homes; 93 stakeholders participated in focus groups. Over half of participating nursing homes reported meeting their BPSD goals as expected or more. Challenges, facilitators, and contextual factors reported by stakeholder members explains variability in the implementation of EIT-4-BPSD strategy in 11 key categories: family; staff; organizational; staff, environmental, and resident outcomes; utility of EIT resources; adoption barriers and facilitators; care process adaptations; and future planning.

Conclusion
Stakeholders offered guidance on salient factors influencing the feasibility and utility of EIT-4-BPSD adoption and implementation to consider in future implementation research that aims to improve behavioral well-being in NH residents living with dementia. Engagement of family and staff at all levels of the organization (Management, leadership, and direct care); and measurement of staff, environmental, and resident outcomes were perceived as critical for future implementation success. While regulations, finances, and competing demands on staff time were perceived as reducing implementation success.

Trial Registration
The Testing the Implementation of EIT-4-BPSD study was registered in the ClinicalTrials.gov (NCT03014570) January 9, 2017.
Whole genome sequencing in the diagnosis of primary ciliary dyskinesia
Authors: Wheway Gabrielle , Thomas N. Simon , Carroll Mary , Coles Janice , Doherty Regan ,   Genomics England Research Consortium, Goggin Patricia , Green Ben , Harris Amanda , Hunt David , Jackson Claire L. , Lord Jenny , Mennella Vito , Thompson James , Walker Woolf T. , Lucas Jane S. 
Published: September 2021

Abstract
Background
It is estimated that 1–13% of cases of bronchiectasis in adults globally are attributable to primary ciliary dyskinesia (PCD) but many adult patients with bronchiectasis have not been investigated for PCD. PCD is a disorder caused by mutations in genes required for motile cilium structure or function, resulting in impaired mucociliary clearance. Symptoms appear in infancy but diagnosis is often late or missed, often due to the lack of a “gold standard” diagnostic tool and non-specific symptoms. Mutations in > 50 genes account for around 70% of cases, with additional genes, and non-coding, synonymous, missense changes or structural variants (SVs) in known genes presumed to account for the missing heritability.

Methods
UK patients with no identified genetic confirmation for the cause of their PCD or bronchiectasis were eligible for whole genome sequencing (WGS) in the Genomics England Ltd 100,000 Genomes Project. 21 PCD probands and 52 non-cystic fibrosis (CF) bronchiectasis probands were recruited in Wessex Genome Medicine Centre (GMC). We carried out analysis of single nucleotide variants (SNVs) and SVs in all families recruited in Wessex GMC.

Results
16/21 probands in the PCD cohort received confirmed (n = 9), probable (n = 4) or possible (n = 3) diagnosis from WGS, although 13/16 of these could have been picked up by current standard of care gene panel testing. In the other cases, SVs were identified which were missed by panel testing. We identified variants in novel PCD candidate genes (IFT140 and PLK4) in 2 probands in the PCD cohort. 3/52 probands in the non-CF bronchiectasis cohort received a confirmed (n = 2) or possible (n = 1) diagnosis of PCD. We identified variants in novel PCD candidate genes (CFAP53 and CEP164) in 2 further probands in the non-CF bronchiectasis cohort.

Conclusions
Genetic testing is an important component of diagnosing PCD, especially in cases of atypical disease history. WGS is effective in cases where prior gene panel testing has found no variants or only heterozygous variants. In these cases it may detect SVs and is a powerful tool for novel gene discovery.
AprGPD: the apricot genomic and phenotypic database
Authors: Chen Chen , Liu Huimin , Gou Ningning , Huang Mengzhen , Xu Wanyu , Zhu Xuchun , Yin Mingyu , Bai Haikun , Wang Lin , Wuyun Ta-na 
Published: September 2021

Abstract
Background
Apricot is cultivated worldwide because of its high nutritive content and strong adaptability. Its flesh is delicious and has a unique and pleasant aroma. Apricot kernel is also consumed as nuts. The genome of apricot has been sequenced, and the transcriptome, resequencing, and phenotype data have been increasely generated. However, with the emergence of new information, the data are expected to integrate, and disseminate.

Results
To better manage the continuous addition of new data and increase convenience, we constructed the apricot genomic and phenotypic database (AprGPD, http://apricotgpd.com). At present, AprGPD contains three reference genomes, 1692 germplasms, 306 genome resequencing data, 90 RNA sequencing data. A set of user-friendly query, analysis, and visualization tools have been implemented in AprGPD. We have also performed a detailed analysis of 59 transcription factor families for the three genomes of apricot.

Conclusion
Six modules are displayed in AprGPD, including species, germplasm, genome, variation, product, tools. The data integrated by AprGPD will be helpful for the molecular breeding of apricot.
Teoria crítica racial: direito como definição da condição dos negros
Authors: Batista Waleska Miguel , Almeida Silvio Luiz de 
Published: September 2021

Busca-se apresentar que Teoria Crítica Racial surgida a partir das lutas pelos direitos civis nos Estados Unidos contribuiu para evidenciar que o direito nunca foi universal, mas um instrumento de poder do Estado que determina as relações sociais, políticas e econômicas, de tal forma que o racismo é uma relação social normalizada, produzida e reproduzida, apesar de haver leis antirracistas, sendo mantido no Estado Social e Democrático de Direito sem qualquer problema de contradição. Assim, através de uma revisão bibliográfica de livros e periódicos qualificados sobre a articulação entre raça, racismo e o sistema socioeconômico, conclui-se que não adianta buscar o combate ao racismo pelo direito enquanto não for compreendido que ele é um poder que utiliza da força para estabelecer a ordem social em que o racismo é normal, ou seja, é incapaz de lutar contra formas de acumulação de capital.
Has God Indeed Said? Skeptical Theism and Scriptural Hermeneutics
Authors: Panchuk Michelle 
Published: September 2021

This paper demonstrates that the skeptical theist’s response to the problem of evil deprives the analytic theologian of theoretical resources necessary to avoid accepting as veridical merely apparent divine commands that endorse cruelty. In particular, I argue that the same skeptical considerations that lead analytic theologians to endorse skeptical theism also lead to what I call “divine command skepticism”—an inability to make certain kinds of judgements about what a good God would or would not command. The danger of divine command skepticism is not that it generates new reasons to think that God has commanded horrors, but, rather, that it undercuts the defeaters we might otherwise have for thinking that God has commanded those horrors. It does so both by rendering illicit certain theological and hermeneutical methodologies employed within liberatory frameworks (i.e., various kinds of liberation theologies) and by depriving the theologian of some of the more “traditional” mechanisms for resolving such apparent conflicts.
Consummation Anyway: A Reformed Proposal
Authors: Sutanto N. Gray 
Published: September 2021

The central claim of a Consummation Anyway (CA) model is that God could bring about eschatological consummation sans the fall—the intended telos of created humanity—apart from the incarnation of Christ. As such, the CA model is an alternative to an Incarnation Anyway (IA) model, according to which Christ’s incarnation is a necessary means by which a state of eschatological glory would be achieved sans the fall. This essay seeks to propose an argument for the CA model by drawing from the covenant theology of the Reformed tradition, and it moves in four steps. Firstly, I shall summarize Marc Cortez’s recent arguments for IA, homing in on the major moves that are most relevant for sketching a CA model. Secondly, I will highlight the challenges Cortez has offered against those interested in defending a CA model. Thirdly, I shall sketch a Reformed account of the CA model that seeks to address Cortez’s objections. Fourthly, then, I’ll consider two potential objections against the sketch I have offered for CA, inspired by a recent argument offered by James T. Turner (2019). Finally, I close with a brief conclusion that summarizes some salient features of the proposed thesis. This paper thus proposes at least one way in which the CA thesis could remain a real and live option within this debate.
Exploring women’s development group leaders’ support to maternal, neonatal and child health care: A qualitative study in Tigray region, Ethiopia
Authors: Ashebir Fisseha , Medhanyie Araya Abrha , Mulugeta Afework , Persson Lars Åke , Berhanu Della 
Published: September 2021

Background
Community health workers and volunteers are vital for the achievement of Universal Health Coverage also in low-income countries. Ethiopia introduced community volunteers called women’s development group leaders in 2011. These women have responsibilities in multiple sectors, including promoting health and healthcare seeking.

Objective
We aimed to explore women’s development group leaders’ and health workers’ perceptions on these volunteers’ role in maternal, neonatal and child healthcare.

Methods
A qualitative study was conducted with in-depth interviews and focus group discussions with women’s development group leaders, health extension workers, health center staff, and woreda and regional health extension experts. We adapted a framework of community health worker performance, and explored perceptions of the women’s development group program: inputs, processes and performance. Interviews were recorded, transcribed, and coded prior to translation and thematic analysis.

Results
The women’s development group leaders were committed to their health-related work. However, many were illiterate, recruited in a sub-optimal process, had weak supervision and feedback, lacked training and incentives and had weak knowledge on danger signs and care of neonates. These problems demotivated these volunteers from engaging in maternal, neonatal and child health promotion activities. Health extension workers faced difficulties in managing the numerous women’s development group leaders in the catchment area.

Conclusion
The women’s development group leaders showed a willingness to contribute to maternal and child healthcare but lacked support and incentives. The program requires some redesign, effective management, and should offer enhanced recruitment, training, supervision, and incentives. The program should also consider continued training to develop the leaders’ knowledge, factor contextual influences, and be open for local variations.
A prospective population-based multicentre study on the impact of maternal body mass index on adverse pregnancy outcomes: Focus on normal weight
Authors: van Hoorn Fieke , de Wit Leon , van Rossem Lenie , Jambroes Marielle , Groenendaal Floris , Kwee Anneke , Lamain - de Ruiter Marije , Franx Arie , van Rijn Bas B. , Koster Maria P. H. , Bekker Mireille N. 
Published: September 2021

Background
Maternal body mass index (BMI) below or above the reference interval (18.5–24.9 kg/m2) is associated with adverse pregnancy outcomes. Whether BMI exerts an effect within the reference interval is unclear. Therefore, we assessed the association between adverse pregnancy outcomes and BMI, in particular within the reference interval, in a general unselected pregnant population.

Methods
Data was extracted from a prospective population-based multicentre cohort (Risk Estimation for PrEgnancy Complications to provide Tailored care (RESPECT) study) conducted between December 2012 to January 2014. BMI was studied in categories (I: <18.5, II: 18.5–19.9, III: 20.0–22.9, IV: 23.0–24.9, V: 25.0–27.4, VI: 27.5–29.9, VII: >30.0 kg/m2) and as a continuous variable within the reference interval. Adverse pregnancy outcomes were defined as composite endpoints for maternal, neonatal or any pregnancy complication, and for adverse pregnancy outcomes individually. Linear trends were assessed using linear-by-linear association analysis and (adjusted) relative risks by regression analysis.

Results
The median BMI of the 3671 included women was 23.2 kg/m2 (IQR 21.1–26.2). Adverse pregnancy outcomes were reported in 1256 (34.2%). Linear associations were observed between BMI categories and all three composite endpoints, and individually for pregnancy-induced hypertension (PIH), preeclampsia, gestational diabetes mellitus (GDM), large-for-gestational-age (LGA) neonates; but not for small-for-gestational-age neonates and preterm birth. Within the reference interval, BMI was associated with the composite maternal endpoint, PIH, GDM and LGA, with adjusted relative risks of 1.15 (95%CI 1.06–1.26), 1.12 (95%CI 1.00–1.26), 1.31 (95%CI 1.11–1.55) and 1.09 (95%CI 1.01–1.17).

Conclusions
Graded increase in maternal BMI appears to be an indicator of risk for adverse pregnancy outcomes even among women with a BMI within the reference interval. The extent to which BMI directly contributes to the increased risk in this group should be evaluated in order to determine strategies most valuable for promoting safety and long-term health for mothers and their offspring.
Enthalpies of mixing in ternary Al–Gd–Mn liquid alloys
Authors: Ivanov Michael , Usenko Natalia , Kotova Natalia 
Published: September 2021

Abstract
The enthalpies of mixing in liquid alloys of the ternary Al–Gd–Mn system were determined over a wide range of compositions by means of isoperibolic calorimetry at 1650 K. The measurements of the partial enthalpies of components were performed along five sections: for the ΔH̅
Al (sections with x
Gd/x
Mn = 0.30/0.70 and 0.65/0.35 for x
Al changed from 0 up to 0.30); for the ΔH̅
Gd (x
Al/x
Mn = 0.80/ 0.20 and 0.50/0.50 for x
Gd changed from 0 up to 0.30); for the ΔH̅
Mn (x
Al/x
Gd = 0.29/0.71 for x
Mn changed from 0 up to 0.26). The enthalpies of mixing in the ternary system were found to be exothermic and steadily increasing in absolute values from the Mn corner towards the Al–Gd constituent binary system, reaching the minimum value of approximately – 37 kJ · mol–1 in the vicinity of the Al0.6Gd0.4 composition, evidently related to the formation of stable Al2Gd phase.
The crystal structure of poly[(μ
4-4,4′-(azanediylbis(methylene))dibenzoato-κ
4
O:N:O′:Oʺ)zinc(II)], C16H13NO4Zn
Authors: Chen Hai-Lin , Yao Dong-Mei , Wang Yan-Ping , Lao Ya-Xin 
Published: September 2021

Abstract
C16H13NO4Zn, triclinic, P

1
‾

$&#x203e;{1}$

(no. 2), a = 7.5223(6) Å, b = 8.0977(8) Å, c = 11.7739(11) Å, α = 76.410(8)∘, β = 75.495(8)∘, γ = 75.902(8)∘, V = 661.76(11) Å3, Z = 2, R

gt
(F) = 0.0532, wR

ref
(F
2) = 0.1041, T = 293(2) K.
The properties of nano-CaCO3/nano-ZnO/SBR composite-modified asphalt
Authors: Li Zhenxia , Guo Tengteng , Chen Yukun , Liu Qi , Chen Yuanzhao 
Published: September 2021

Abstract
To solve the problem of the pavement being aged due to the influence of temperature, light and other environmental factors are brought in service. Nano-CaCO3 surface was activated by 6% KH-550, and nano-ZnO surface was activated by 6% aluminate. Nano-CaCO3/nano-ZnO/SBR composite-modified asphalt was prepared. The optimum proportion of composite-modified asphalt was determined by orthogonal test. The influence of modifiers on asphalt pavement performance was comprehensively studied. The microstructure of composite-modified asphalt was characterized by scanning electron microscopy and infrared spectroscopy. The mechanism of composite-modified asphalt was analyzed. The results show that the optimum combination of composite-modified asphalt is 4% nano-CaCO3 + 5% nano-ZnO + 4% SBR, the aging performance of the composite-modified asphalt is reduced by 6.9%, and the viscosity is increased by 14.6–23.1%. The complex shear modulus is increased by 24.1% at 82°C, the stiffness modulus is decreased, on average, by 21.1%. and the creep curve slope is increased by 9% on average. In the meantime, during the preparation process of composite-modified asphalt, it mainly occurred due to chemical reaction with surface-modified nanomaterials and physical change with SBR polymer materials.