bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximity ligation assay to detect DUX4 protein in FSHD1 muscle: a pilot study
Authors: Beermann Mary Lou , Homma Sachiko , Miller Jeffrey Boone 
Published: May 2022

Abstract
Objective
Aberrant expression in skeletal muscle of DUX4, a double homeobox transcription factor, underlies pathogenesis in facioscapulohumeral muscular dystrophy (FSHD). Although previous studies of FSHD muscle biopsies detected mRNAs encoding DUX4 and its target genes, no studies had reported detection of DUX4 protein. Our objective was to develop a proximity ligation assay (PLA) for DUX4 and to determine if this assay could detect DUX4 protein in FSHD muscle sections.

Results
We developed a PLA protocol using two DUX4 antibodies previously reported by Stephen Tapscott’s group: P2G4, a mouse mAb specific for an epitope in the N-terminal region, and E5-5, a rabbit mAb specific for an epitope in the C-terminal region, in combination with commercial PLA secondary reagents. We validated the DUX4 PLA using cultured human myogenic cells in which DUX4 was ectopically expressed in a small fraction of nuclei. Using this two primary mAb PLA on an FSHD1 biceps biopsy, we observed nuclei with apparent DUX4 PLA signals associated with a small subset of myofibers (~ 0.05–0.1%). Though a limited pilot study, these results suggest that the two primary mAb PLA protocol could be useful for detecting DUX4 protein in FSHD muscle biopsies.
Benign and malignant diagnosis of spinal tumors based on deep learning and weighted fusion framework on MRI
Authors: Liu Hong , Jiao Menglei , Yuan Yuan , Ouyang Hanqiang , Liu Jianfang , Li Yuan , Wang Chunjie , Lang Ning , Qian Yueliang , Jiang Liang , Yuan Huishu , Wang Xiangdong 
Published: May 2022

Abstract
Background
The application of deep learning has allowed significant progress in medical imaging. However, few studies have focused on the diagnosis of benign and malignant spinal tumors using medical imaging and age information at the patient level. This study proposes a multi-model weighted fusion framework (WFF) for benign and malignant diagnosis of spinal tumors based on magnetic resonance imaging (MRI) images and age information.

Methods
The proposed WFF included a tumor detection model, sequence classification model, and age information statistic module based on sagittal MRI sequences obtained from 585 patients with spinal tumors (270 benign, 315 malignant) between January 2006 and December 2019 from the cooperative hospital. The experimental results of the WFF were compared with those of one radiologist (D1) and two spine surgeons (D2 and D3).

Results
In the case of reference age information, the accuracy (ACC) (0.821) of WFF was higher than three doctors’ ACC (D1: 0.686; D2: 0.736; D3: 0.636). Without age information, the ACC (0.800) of the WFF was also higher than that of the three doctors (D1: 0.750; D2: 0.664; D3:0.614).

Conclusions
The proposed WFF is effective in the diagnosis of benign and malignant spinal tumors with complex histological types on MRI.
CD47xCD19 bispecific antibody triggers recruitment and activation of innate immune effector cells in a B-cell lymphoma xenograft model
Authors: Chauchet Xavier , Cons Laura , Chatel Laurence , Daubeuf Bruno , Didelot Gérard , Moine Valéry , Chollet Didier , Malinge Pauline , Pontini Guillemette , Masternak Krzysztof , Ferlin Walter , Buatois Vanessa , Shang Limin 
Published: May 2022

Abstract
Background
CD47/SIRPα axis is recognized as an innate immune checkpoint and emerging clinical data validate the interest of interrupting this pathway in cancer, particularly in hematological malignancies. In preclinical models, CD47/SIRPα blocking agents have been shown to mobilize phagocytic cells and trigger adaptive immune responses to eliminate tumors. Here, we describe the mechanisms afforded by a CD47xCD19 bispecific antibody (NI-1701) at controlling tumor growth in a mouse xenograft B-cell lymphoma model.

Methods
The contribution of immune effector cell subsets behind the antitumor activity of NI-1701 was investigated using flow cytometry, transcriptomic analysis, and in vivo immune-cell depletion experiments.

Results
We showed that NI-1701 treatment transformed the tumor microenvironment (TME) into a more anti-tumorigenic state with increased NK cells, monocytes, dendritic cells (DC) and MHCIIhi tumor-associated macrophages (TAMs) and decreased granulocytic myeloid-derived suppressor cells. Notably, molecular analysis of isolated tumor-infiltrating leukocytes following NI-1701 administration revealed an upregulation of genes linked to immune activation, including IFNγ and IL-12b. Moreover, TAM-mediated phagocytosis of lymphoma tumor cells was enhanced in the TME in the presence of NI-1701, highlighting the role of macrophages in tumor control. In vivo cell depletion experiments demonstrated that both macrophages and NK cells contribute to the antitumor activity. In addition, NI-1701 enhanced dendritic cell-mediated phagocytosis of tumor cells in vitro, resulting in an increased cross-priming of tumor-specific CD8 T cells.

Conclusions
The study described the mechanisms afforded by the CD47xCD19 bispecific antibody, NI-1701, at controlling tumor growth in lymphoma mouse model. NI-1701 is currently being evaluated in a Phase I clinical trial for the treatment of refractory or relapsed B-cell lymphoma (NCT04806035).
Malaria from hyperendemicity to elimination along international borders in Yunnan, China during 2003‒2020: a case study
Authors: Liu Hui , Zhou Yaowu , Deng Yan , Lin Zurui , Zhang Canglin , Chen Qiyan , Wei Chun , Duan Kaixia , Tian Peng , Zhou Hongning , Xu Jianwei 
Published: May 2022

Abstract
Background
Border malaria is one of the most intractable problems hindering malaria elimination worldwide. Movement of both the human population and anopheline mosquitoes infected with Plasmodium spp. can cause cross-border malaria transmission. The Yunnan border area was still hyperendemic for malaria in the early part of this century. The objective of this case study was to analyze the strategies, interventions and impacts of malaria control and elimination in the Yunnan border area.

Main text
A total of 10,349 malaria cases and 17.1 per 10,000 person-years of annual parasite incidence (API) were reported in the border area in 2003. Based on natural village-based stratification, integrated interventions, including mass drug administration for radical cures and preventive treatment, clinically presumptive treatment of all febrile patients for malaria and indoor residual spraying or dipping bed nets with insecticides were successfully carried out from 2003 to 2013. The overall API was reduced to 0.6 per 10,000 person-years by 2013, while effective cross-border collaboration interventions dramatically reduced the malaria burden in the neighbouring border areas of Myanmar. From 2014 forward, the comprehensive strategy, including universal coverage of surveillance to detect malaria cases, a rapid response to possible malaria cases and effective border collaboration with neighbouring areas, successfully eliminated malaria and prevented reintroduction of malaria transmission in the Yunnan border area.

Conclusions
In Yunnan malaria burden has successfully reduced by dynamically accurate stratification and comprehensive interventions; and then the region achieved elimination and prevented reintroduction of malaria transmission through intensive surveillance, rapid response and border collaboration. Other border areas should perform their own intervention trials to develop their own effective strategy.

Graphical Abstract
EFL learners’ engagement in different activities of blended learning environment
Authors: Huang Min , Kuang Fangtao , Ling Ying 
Published: May 2022

AbstractWith the blended learning widespread in higher education, the research on the factors which can influence the students’ engagement and their working mechanism has become more and more valuable. In this study, college students’ perception on three aspects, i.e. their cognitive engagement and emotional engagement in two different activities, the activity features and teachers’ roles, has been collected through both questionnaires and interviews. Repeated variance measurement, Pearson correlation analysis and General linear regression have been used to process the quantitative data. Thematic analysis has been used to process the qualitative data. The results show that the cognitive engagement and emotional engagement in Teacher’s Q & A and Online discussion are significantly different (FCE = 10.32**, ŋ2 = 0.07; FEE = 29.60***, ŋ2 = 0.17). Students’ emotional engagement and cognitive engagement in activities are affected by various task features and teacher’s roles. Pedagogical implication and suggestions for further research have also been provided.
Analysis of missense SNPs in the SLC47A1 and SLC47A2 genes affecting the pharmacokinetics of metformin: Computational approach
Authors: Avsar Orcun 
Published: May 2022

Abstract
Background
Metformin as an anti-hyperglycaemic drug is commonly used for the treatment of type 2 diabetes mellitus (T2DM). The metformin response is variable due to the interindividual variation of pharmacokinetics which is based on strong genetic background. MATE1 and MATE2 proteins are significantly implicated in the pharmacokinetics of metformin. Missense SNPs with high risk of pathogenicity are expected to affect response to metformin via pharmacokinetics. Therefore, the aim of the current study is to determine the effects of missense SNPs in the SLC47A1 and SLC47A2 genes. The structural and functional consequences of all known SLC47A1 and SLC47A2 missense SNPs of the human MATE1 and MATE2 proteins were identified by various bioinformatics methods (SIFT, PhD-SNP, PolyPhen-2, PROVEAN, PMut, MUpro, I-Mutant 3.0, COACH, RaptorX Binding, ConSurf, STRING).

Results
The SLC47A1 variants P186T, L116P and the SLC47A2 variants I158N, L112P, V118G exhibited ΔΔG values less than − 1 kcal/mol, and these variants are considered to disrupt the structure and function of MATE1 and MATE2 proteins. SLC47A1 R118Q and SLC47A2 Y273C, V118G may significantly disturb protein function and transporting activities according to the analysis of ligand-binding regions.

Conclusion
It is suggested that high-risk deleterious missense SNPs may mediate the pharmacokinetics of metformin and may be associated with altered tissue distribution, renal clearance and metformin toxicity. We suppose that our results might serve as potential targets for the studies composed of the development of potential diagnostic and therapeutic strategies based on the relationship between mutations and metformin response.
Lived experiences of transgender forced migrants and their mental health outcomes: systematic review and meta-ethnography
Authors: Hermaszewska Susannah , Sweeney Angela , Camminga B , Botelle Riley , Elliott Kate , Sin Jacqueline 
Published: May 2022

Background
Owing to multiple, complex and intersecting health inequities, systemic oppression and violence and discrimination in their home countries, some transgender people are forced to migrate to countries that offer them better legal protection and wider social acceptance.

Aims
This review sought to explore and understand the multiple factors that shape the mental health outcomes of transgender forced migrants (TFMs).

Method
We systematically searched nine electronic databases for multidisciplinary literature (PROSPERO ID: CRD42020183062). We used a meta-ethnographic approach to synthesise data. We completed a quality appraisal and developed a socio-ecological model to draw together our findings.

Results
We retrieved 3399 records and screened titles, abstracts and full text to include 24 qualitative studies in this review. The synthesis identified individual survival strategies and factors in interpersonal, organisational and societal environments that contributed to profound deprivation and mental distress in TFMs. Pervasive and persistent violence and discrimination, economic exclusion, barriers to healthcare and a dependency on legal documentation were identified as key factors leading to poor mental health outcomes. Sources of resilience included community acceptance and support, being granted asylum, societal affirmation of gender, fulfilment of basic rights and healthcare access. Individual strategies for survival, such as hope and having purpose in life, were important in bringing relief from distress.

Conclusions
Improved communication and knowledge about the unique needs and concerns of TFMs through interventions at the individual, interpersonal, organisational and societal levels are necessary to improve mental health outcomes.
Key questions: research priorities for student mental health
Authors: Sampson Katie , Priestley Michael , Dodd Alyson L. , Broglia Emma , Wykes Til , Robotham Dan , Tyrrell Katie , Ortega Vega Marta , Byrom Nicola C. 
Published: May 2022

Background
The high prevalence of mental distress among university students is gaining academic, policy and public attention. As the volume of research into student mental health increases, it is important to involve students to ensure that the evidence produced can translate into meaningful improvements.

Aims
For the first time, we consult UK students about their research priorities on student mental health.

Method
This priority setting exercise involved current UK university students who were asked to submit three research questions relating to student mental health. Responses were aggregated into themes through content analysis and considered in the context of existing research. Students were involved throughout the project, including inception, design, recruitment, analysis and dissemination.

Results
UK university students (N = 385) submitted 991 questions, categorised into seven themes: epidemiology, causes and risk factors, academic factors and work–life balance, sense of belonging, intervention and services, mental health literacy and consequences. Across themes, respondents highlighted the importance of understanding the experience of minority groups.

Conclusions
Students are interested in understanding the causes and consequences of poor mental health at university, across academic and social domains. They would like to improve staff and students’ knowledge about mental health, and have access to evidence-based support. Future research should take a broad lens to evaluate interventions; considering how services are designed and delivered, and investigating institutional and behavioural barriers to accessibility, including how this varies across different groups within the student population.
Circulating Tumor DNA in Adults With Glioma: A Systematic Review and Meta-Analysis of Biomarker Performance
Authors: McMahon James Tanner , Studer Matthew , Ulrich Bryan , Revuelta Barbero Juan M. , Pradilla Ivan , Palacios-Ariza Maria A. , Pradilla Gustavo 
Published: May 2022

BACKGROUND:
Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined.

OBJECTIVE:
To (1) review the primary literature about ctDNA in adults with glioma to compare the sensitivity and specificity of ctDNA in the cerebrospinal fluid vs the plasma and (2) to evaluate the effect of tumor grade on detection of ctDNA.

METHODS:
PRISMA-guided systematic review and meta-analysis was performed using published studies that assessed ctDNA in either plasma or cerebrospinal fluid among adult patients with confirmed glioma. Summary receiver operating characteristic curves were generated using the Rücker-Schumacher method, and area under the curve (AUC) was calculated.

RESULTS:
Meta-analysis revealed improved biomarker performance for CSF (AUC = 0.947) vs plasma (AUC = 0.741) ctDNA, although this did not reach statistical significance (P = .141). Qualitative analysis revealed greater sensitivities among single-allele PCR and small, targeted next-generation sequencing panels compared with broader panels. It additionally demonstrated higher sensitivity of ctDNA detection in high-grade vs low-grade gliomas, although these analyses were limited by a lack of specificity reporting in many studies.

CONCLUSION:
ctDNA seems to be a highly sensitive and specific noninvasive biomarker among adults with gliomas. To maximize its performance, CSF should be studied with targeted genetic analysis platforms, particularly in high-grade gliomas. Further studies on ctDNA are needed to define its clinical utility in diagnosis, prognostication, glioblastoma pseudoprogression, and other scenarios wherein neoadjuvant therapies may be considered.
Fluorescent Nanofibers Self-assembled from a Diphenylanthracene Scissor-shaped Dyad
Authors: Suda Natsuki , Arima Hironari , Saito Takuho , Aizawa Takumi , Yagai Shiki 
Published: May 2022

Abstract
A scissor-shaped foldable diphenylanthracene dyad has been synthesized and found to self-assemble in a nonpolar solvent into elongated thin nanofibers, showing intense blue emission. At a millimolar concentration, efficient gelation was observed while the emission property of the building block was retained in the gel state.
Superhydrophobic/Superoleophilic Copper Mesh for Heavy Oil-water Separation
Authors: Liu Bing , Fu Ye , Guo Zhiguang 
Published: May 2022

Abstract
By etching copper mesh with ammonia-base and depositing titanium dioxide nanoparticles (TiO2 NPs) on it, nanoneedle-like Cu(OH)2 was formed, and then modified with n-hexadecyltrimethoxysilane (HDTMS) to achieve superhydrophobicity/superoleophilicity for heavy oil-water mixtures separation. The method has the advantages of simple operation, high efficiency, good repeatability and worth in industrial applications.
Deep learning in breast imaging
Authors: Bhowmik Arka , Eskreis-Winkler Sarah 
Published: May 2022

Abstract
Millions of breast imaging exams are performed each year in an effort to reduce the morbidity and mortality of breast cancer. Breast imaging exams are performed for cancer screening, diagnostic work-up of suspicious findings, evaluating extent of disease in recently diagnosed breast cancer patients, and determining treatment response. Yet, the interpretation of breast imaging can be subjective, tedious, time-consuming, and prone to human error. Retrospective and small reader studies suggest that deep learning (DL) has great potential to perform medical imaging tasks at or above human-level performance, and may be used to automate aspects of the breast cancer screening process, improve cancer detection rates, decrease unnecessary callbacks and biopsies, optimize patient risk assessment, and open up new possibilities for disease prognostication. Prospective trials are urgently needed to validate these proposed tools, paving the way for real-world clinical use. New regulatory frameworks must also be developed to address the unique ethical, medicolegal, and quality control issues that DL algorithms present. In this article, we review the basics of DL, describe recent DL breast imaging applications including cancer detection and risk prediction, and discuss the challenges and future directions of artificial intelligence-based systems in the field of breast cancer.
Rejection of the Jewish Idea of the Chosen People as a Consequence of Theological Egalitarianism in the Thought of Mordecai Kaplan
Authors: Szczerbiński Waldemar Piotr 
Published: May 2022

In traditional Judaism, the truth that Jews are God’s Chosen People was universal and constitutive of both individual and collective identity. Most modern currents of Judaism (Orthodoxy, Conservatism, Reformed) continue to preach the belief in chosenness, based on religious obligations, the so-called mitzvot, which define a uniquely Jewish way of life and lead to moral holiness. However, Jewish Reconstructionism — the most recent and the most liberal paradigms of the Jewish religion — negates the idea of a chosen people completely, reflecting the notions espoused by its founder, Mordecai M. Kaplan, a staunch opponent of the belief that God chooses one people over another, one nation over other nations. This paper demonstrates how Kaplan re-envisioned the traditional truth about the Jews as the Chosen People. Relying on his analyses, the author demonstrates that Kaplan’s proposal arises from theological egalitarianism, on which the entire agenda of this current in Judaism is founded. The doctrine of chosenness is replaced in this case by the axiom of vocation, which does not elevate the Jews above other peoples, but presumes them to be equal with others. At the same time, Jews do not have to renounce their own path to salvation as a part of their civilization.
GRADIÊNCIA E MUDANÇA LINGUÍSTICA: O CASO DE “ENTRETANTO”
Authors: Paiva Maria da Conceição De , Medeiros Priscila Thaiss da Conceição de 
Published: May 2022

A categorização dos diferentes tipos de unidades linguísticas em classes estanques constitui um problema central para qualquer modelo linguístico. No entanto, ganham relevo e tem despertado a atenção de estudiosos que defendem a inexistência de fronteiras entre sistema e uso. Na perspectiva dos Modelos Baseados no Uso, gradiência é concebida como uma característica inerente aos sistemas linguísticos e uma decorrência natural da gradualidade da mudança linguística. Neste artigo, retomamos essa questão com base em uma análise diacrônica do desenvolvimento de entretanto como elemento de conexão de unidades discursivas a partir de seus usos adverbiais. Através do levantamento de dados em textos dos períodos arcaico, clássico e moderno/contemporâneo do português, mostramos que a construção temporal entretanto incorporou propriedades dos elementos juntivos e estendeu-se para o domínio do contraste. Segundo as evidências atestadas, esse processo pode ter sido impulsionado pelo fato de que a construção adverbial e a construção juntiva partilham diversas propriedades morfossintáticas e contextuais. Destaca-se a importância da posição de entretanto na periferia esquerda da oração, sua coocorrência com outros elementos de ligação, o tipo de estado de coisas codificado na oração, assim como suas propriedades aspectuais e de modo. Essa convergência conduz a uma gradação de usos que se situam num continuum entre advérbio e conector.
Economic outcomes associated with deep surgical site infection from lower limb fractures following major trauma
Authors: Png May Ee , Petrou Stavros , Knight Ruth , Masters James , Achten Juul , Costa Matthew L. 
Published: May 2022

AimsThis study aims to estimate economic outcomes associated with 30-day deep surgical site infection (SSI) from closed surgical wounds in patients with lower limb fractures following major trauma.MethodsData from the Wound Healing in Surgery for Trauma (WHiST) trial, which collected outcomes from 1,547 adult participants using self-completed questionnaires over a six-month period following major trauma, was used as the basis of this empirical investigation. Associations between deep SSI and NHS and personal social services (PSS) costs (£, 2017 to 2018 prices), and between deep SSI and quality-adjusted life years (QALYs), were estimated using descriptive and multivariable analyses. Sensitivity analyses assessed the impact of uncertainty surrounding components of the economic analyses.ResultsCompared to participants without deep SSI, those with deep SSI had higher mean adjusted total NHS and PSS costs (adjusted mean difference £1,577 (95% confidence interval (CI) -951 to 4,105); p = 0.222), and lower mean adjusted QALYs (adjusted mean difference -0.015 (95% CI -0.032 to 0.002); p = 0.092) over six months post-injury, but this difference was not statistically significant. The results were robust to the sensitivity analyses performed.ConclusionThis study found worse economic outcomes during the first six months post-injury in participants who experience deep SSI following orthopaedic surgery for major trauma to the lower limb. However, the increase in cost associated with deep SSI was less than previously reported in the orthopaedic trauma literature. Cite this article: Bone Jt Open 2022;3(5):398–403.