bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decidual stromal cells-derived exosomes incurred insufficient migration and invasion of trophoblast by disturbing of β-TrCP-mediated snail ubiquitination and degradation in unexplained recurrent spontaneous abortion
Authors: Xiong Miao , Wang Qiaohong , Zhang Xiaoxin , Wen Liping , Zhao Aimin 
Published: January 2024

Abstract
Background
Exosomes released from decidual stromal cells (DSC-exos) play a crucial role in facilitating the epithelial–mesenchymal transition (EMT) of trophoblasts and insufficient trophoblasts EMT are associated with URSA (unexplained recurrent spontaneous abortion). However, the mechanisms underlying DSC-exos inducing EMT is not completely understood.

Methods
DSC-exos of normal pregnant women (N-DSC-exos) and URSA patients (URSA-DSC-exos) were extracted and characterized. Characterization of the isolated DSC-exos was performed using with TEM (transmission electron microscopy), NTA (nanoparticle tracking analysis), and WB (western blot) techniques. Subsequently, these DSC-exos were co-cultured with trophoblasts cell lines (HTR-8/SVneo). The influence of both N-DSC-exos and URSA-DSC-exos on trophoblasts proliferation, invasion and migration, as well as on the expression of EMT-related proteins, was evaluated through a series of assays including CCK8 assays, wound healing assays, transwell assays, and western blot, respectively. Then rescue experiments were performed by β-TrCP knockdown or β-TrCP overexpressing trophoblasts with snail-siRNA transfection or β-TrCP overexpressing Lentivirus infection, respectively. Finally, animal experiments were employed to explore the effect of N-DSC-exos on embryo absorption in mice.

Results
We found increased β-TrCP expression in the villus of URSA patients when compared to the normal pregnant women, alongside reduction in the levels of both snail and N-cadherin within URSA patients. N-DSC-exos can promote the EMT of the trophoblast by inhibiting β-TrCP-mediated ubiquitination and degradation of transcription factor snail. Moreover the capacity to promote EMT was found to be more potent in N-DSC-exos than URSA-DSC-exos. Down-regulation of snail or overexpression of β-TrCP can reverse the effects of N-DSC-exos on trophoblast. Finally, in vivo experiment suggested that N-DSC-exos significantly reduced the embryo resorption rate of spontaneous abortion mouse model.

Conclusions
Our findings indicate that URSA-DSC-exos caused insufficient migration and invasion of trophoblast because of disturbing of β-TrCP-mediated ubiquitination and degradation of EMT transcription factor snail. Elucidating the underlying mechanism of this dysregulation may shed light on the novel pathways through which DSC-exos influence trophoblast function, thereby contributing to our understanding of their role in URSA.
Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease
Authors: Zhang Tao , Kim Byeong Mo , Lee Tae Ho 
Published: January 2024

AbstractAlzheimer’s disease (AD) is the most prevalent form of dementia in the elderly and represents a major clinical challenge in the ageing society. Neuropathological hallmarks of AD include neurofibrillary tangles composed of hyperphosphorylated tau, senile plaques derived from the deposition of amyloid-β (Aβ) peptides, brain atrophy induced by neuronal loss, and synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) is ubiquitously expressed in the central nervous system. Dysregulation of DAPK1 has been shown to contribute to various neurological diseases including AD, ischemic stroke and Parkinson’s disease (PD). We have established an upstream effect of DAPK1 on Aβ and tau pathologies and neuronal apoptosis through kinase-mediated protein phosphorylation, supporting a causal role of DAPK1 in the pathophysiology of AD. In this review, we summarize current knowledge about how DAPK1 is involved in various AD pathological changes including tau hyperphosphorylation, Aβ deposition, neuronal cell death and synaptic degeneration. The underlying molecular mechanisms of DAPK1 dysregulation in AD are discussed. We also review the recent progress regarding the development of novel DAPK1 modulators and their potential applications in AD intervention. These findings substantiate DAPK1 as a novel therapeutic target for the development of multifunctional disease-modifying treatments for AD and other neurological disorders.
Revealing the true potential and prospects of augmented reality in education
Authors: Koumpouros Yiannis 
Published: January 2024

AbstractAugmented Reality (AR) technology is one of the latest developments and is receiving ever-increasing attention. Many researches are conducted on an international scale in order to study the effectiveness of its use in education. The purpose of this work was to record the characteristics of AR applications, in order to determine the extent to which they can be used effectively for educational purposes and reveal valuable insights. A Systematic Bibliographic Review was carried out on 73 articles. The structure of the paper followed the PRISMA review protocol. Eight questions were formulated and examined in order to gather information about the characteristics of the applications. From 2016 to 2020 the publications studying AR applications were doubled. The majority of them targeted university students, while a very limited number included special education. Physics class and foreign language learning were the ones most often chosen as the field to develop an app. Most of the applications (68.49%) were designed using marker detection technology for the Android operating system (45.21%) and were created with Unity (47.95%) and Vuforia (42.47%) tools. The majority of researches evaluated the effectiveness of the application in a subjective way, using custom-made not valid and reliable tools making the results not comparable. The limited number of participants and the short duration of pilot testing inhibit the generalization of their results. Technical problems and limitations of the equipment used are mentioned as the most frequent obstacles. Not all key-actors were involved in the design and development process of the applications. This suggests that further research is needed to fully understand the potential of AR applications in education and to develop effective evaluation methods. Key aspects for future research studies are proposed.
Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells
Authors: Limanaqi Fiona , Zecchini Silvia , Saulle Irma , Strizzi Sergio , Vanetti Claudia , Garziano Micaela , Cappelletti Gioia , Parolin Debora , Caccia Sonia , Trabattoni Daria , Fenizia Claudio , Clerici Mario , Biasin Mara 
Published: January 2024

Abstract
Background
Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection.

Results
Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium.

Conclusions
Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.
De-bordering policies at the city scale: strategies for building resilience in Barcelona's migration governance
Authors: Zapata-Barrero Ricard 
Published: January 2024

AbstractThis article bridges the fields of urban politics, migration governance and border studies by exploring Barcelona as a case study. It raises a first critical question about what happens to so-called borderlands when "borders" move to other scales, such as cities that are not usually categorized as "border cities". Within this framing debate, this study explores two fundamental questions: (1) how border practices at the state level shape constrained relations between cities and migrants, and (2) how cities map de-bordering policies to resolve such constraints, which we conceptualise as an example of 'urban resilience'. The aim is to provide a focus that brings the analytical category of "urban resilience", recently proposed within the emerging debate on the "local turn" in migration studies, to bear on issues directly related to the social impacts of state bordering processes on urban systems. The article then argues that urban justice principles drive most cities to initiate resilient de-bordering policies, and can be seen as a distinctive normative factor underpinning urban resilience when applied to migration governance. After laying the groundwork for this theoretical framework and its application to the city of Barcelona, the final section briefly outlines the potential of this new and crucial critical area of migration research. This will provide yet another opportunity to highlight that we are likely to enter an era in which cities will increasingly become sovereign geopolitical entities within and beyond the traditional hierarchical reach of their own states.
Spinal dural arteriovenous fistula: a comprehensive review of the history, classification systems, management, and prognosis
Authors: Alkhaibary Ali , Alharbi Ahoud , Alnefaie Nada , Alammar Hajar , Arishy Alshaymaa M. , Alghanim Noor , Aldhfyan Yazeed M. , Albaiahy Arwa , Khormi Yahya H. , Alshaya Wael , AlQahatani Saad , Aloraidi Ahmed , Alkhani Ahmed , Khairy Sami 
Published: January 2024

AbstractSpinal dural arteriovenous fistulas account for the majority of spinal vascular malformations. They are typically located in the thoracolumbar region and are diagnosed in the middle-aged and elderly populations. Although spinal dural arteriovenous fistulas have been postulated to be acquired, their exact development remains uncertain. Typically, the arteriovenous shunt is situated close to the spinal nerve root, inside the dura mater, where the blood from the radiculomeningeal artery and radicular vein intermix. Throughout history, there have been multiple classification systems of spinal arteriovenous shunts since 1967. Those were mainly based on the evolution of diagnostic studies as well as the treatment of these lesions. Such classification systems have undergone significant changes over the years. Unlike intracranial dural arteriovenous fistula, spinal dural arteriovenous fistula is progressive in nature. The neurological manifestations, due to venous congestion, tend to be insidious as well as non-specific. These include sensory deficits, such as paresthesia, bilateral and/or unilateral radicular pain affecting the lower limbs, and gait disturbances. Spinal dural arteriovenous fistulas can be suspected on magnetic resonance imaging/magnetic resonance angiography and confirmed by digital subtraction angiography (DSA). The management includes surgery, endovascular therapy, and in selected cases, radiotherapy. The treatment goal of spinal dural arteriovenous fistula is to halt the progression of the disease. The prognosis depends on both the duration of symptoms as well as the clinical condition prior to therapy. The present article comprehensively reviews the pathophysiology, changes in classification systems, natural history, clinical manifestations, radiological features, management, and prognosis.
Preclinical evaluation of the theranostic potential of 89Zr/177Lu-labeled anti-TROP-2 antibody in triple-negative breast cancer model
Authors: Wu Yitian , li Tuo , Zhang Xianzhong , Jing Hongli , Li Fang , Huo Li 
Published: January 2024

Abstract
Background
Triple-negative breast cancer (TNBC) is one of the most lethal malignant tumors among women, characterized by high invasiveness, high heterogeneity, and lack of specific therapeutic targets such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Trophoblast cell-surface antigen-2 (TROP-2) is a transmembrane glycoprotein over-expressed in 80% of TNBC patients and is associated with the occurrence, progress, and poor prognosis of TNBC. The TROP-2 targeted immunoPET imaging allows non-invasive quantification of the TROP-2 expression levels of tumors, which could help to screen beneficiaries most likely to respond to SG and predict the response. This study aimed to develop a 89Zr/177Lu-radiolabeled anti-TROP-2 antibody (NY003) for immunoPET and SPECT imaging, as well as radioimmunotherapy (RIT) in TROP-2 (+)TNBC tumor-bearing model. Based on the camelid antibody, we developed a TROP-2 targeted recombinant antibody NY003. NY003 was conjugated with DFO and DTPA for 89Zr and 177Lu radiolabelling, respectively. The theranostic potential of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 was evaluated through immunoPET, SPECT imaging, and RIT studies in the subcutaneous TROP-2 positive TNBC xenograft mice model.

Results
The high binding affinity of NY003 to TROP-2 was verified through ELISA. The radiochemical purity of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 exceeded 95% and remained stable within 144h p.i. in vitro. ImmunoPET and SPECT imaging showed the specific accumulation of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 in MDA-MB-231 tumors and gradually increased with the time tested, significantly higher than that in control groups (P < 0.05). The strongest anti-tumor efficacy was observed in the high-dose of [177Lu]Lu-DTPA-NY003 group, followed by the low-dose group, the tumor growth was significantly suppressed by [177Lu]Lu-DTPA-NY003, the tumor volumes of both high- and low-dose groups were smaller than the control groups (P < 0.05). Ex vivo biodistribution and histological staining verified the results of in vivo imaging and RIT studies.

Conclusion
As a drug platform for radiotheranostics, 89Zr/177Lu-radiolabeled anti-TROP-2 antibody NY003 could not only non-invasively screen the potential beneficiaries for optimizing SG ADC treatment but also suppressed the growth of TROP-2 positive TNBC tumors, strongly supporting the theranostic potential of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003.
Uncovering the mechanisms underlying pear leaf apoplast protein-mediated resistance against Colletotrichum fructicola through transcriptome and proteome profiling
Authors: Han Chenyang , Su Zhiyuan , Zhao Yancun , Li Chaohui , Guo Baodian , Wang Qi , Liu Fengquan , Zhang Shaoling 
Published: January 2024

AbstractPear anthracnose, caused by the fungus Colletotrichum fructicola, is a devastating disease for the pear industry. The apoplast, an extracellular compartment outside the plasma membrane, plays a crucial role in water and nutrient transport, as well as plant-microbe interactions. This study aimed to uncover the molecular mechanism of pear leaf apoplastic protein-mediated resistance to C. fructicola. Apoplast fluid was isolated using the vacuum infiltration method, and defence-related apoplastic proteins were identified through protein mass spectrometry and transcriptome sequencing. We found 213 apoplastic proteins in the leaf apoplast fluid during early C. fructicola infection, with the majority (74.64%) being enzymes, including glycosidases, proteases, and oxidoreductases. Gene Ontology analysis revealed their involvement in defence response, enzyme inhibition, carbohydrate metabolism, and phenylpropanoid biosynthesis. Transcriptome analysis showed the infection induced expression of certain apoplast proteins, potentially contributing to pear leaf resistance. Notably, the expression of PbrGlu1, an endo-β-1,3-glucanase from the glycoside hydrolase 17 family, was significantly higher in infected leaves. Silencing of the PbrGlu1 gene increased pear leaf susceptibility to C. fructicola, leading to more severe symptoms and higher reactive oxygen species content. Overall, our study provides insights into the apoplast space interaction between pear leaves and C. fructicola, identifies a key gene in infected pears, and offers a foundation and new strategy for understanding the molecular mechanisms underlying pear anthracnose and breeding disease-resistant pears.
Deconstructive endovascular technique for dissecting posterior cerebral artery aneurysms: a single-center case series study
Authors: Hassan Farouk , Osman Ashraf Abdel Latif , Issa Ahmed S. 
Published: January 2024

Abstract
Background
This study aimed to evaluate the safety and efficacy of the endovascular deconstructive artery technique in the treatment of dissecting posterior cerebral artery (PCA) aneurysms (P1 and P2 segments). We retrospectively analyzed the angiographic characteristics, technical data, and clinical outcomes of nine consecutive patients with dissecting PCA aneurysms treated by our team using the endovascular deconstructive technique between January 2019 and December 2022. The patients consisted of six males and three females ranging in age from 36 to 63 years (mean: 48.1 ± 9). Four patients had a P1 segment dissecting aneurysm, and five patients had a P2 segment dissecting aneurysm. Five patients presented with a headache, one patient presented with epilepsy and headache, and three patients presented with subarachnoid hemorrhage.

Results
A balloon occlusion test (BOT) was performed for one patient. Eight patients were treated by parent artery occlusion (PAO) using micro-coils, whereas one patient was treated by occluding the P2 segment dissecting aneurysm using NBCA glue. There were no cortical infarctions following the occlusion of the parent artery. Two patients with P1 occlusion experienced post-procedural small thalamic infarctions that resolved to mRs:1 at three months of follow-up. P2 segment occlusion was asymptomatic in all patients. One patient showed partial aneurysmal recurrence.

Conclusions
Endovascular parent artery occlusion is an effective and safe treatment approach for the dissecting aneurysms of PCA, even without an occlusion test. In addition, the risk of perforator infarction must be considered in P1 occlusion.

Level of evidence
Level 4, Case Series.
Importance of Patient Health Insurance Coverage and Out-of-Pocket Costs for Genomic Testing in Oncologists' Treatment Decisions
Authors: Yabroff K. Robin , Sylvia Shi Kewei , Zhao Jingxuan , Freedman Andrew N. , Zheng Zhiyuan , Nogueira Leticia , Han Xuesong , Klabunde Carrie N. , de Moor Janet S. 
Published: January 2024

PURPOSE Use of genomic testing, especially multimarker panels, is increasing in the United States. Not all tests and related treatments are covered by health insurance, which can result in substantial patient out-of-pocket (OOP) costs. Little is known about oncologists' treatment decisions with respect to patient insurance coverage and OOP costs for genomic testing. METHODS We identified 1,049 oncologists who used multimarker tumor panels from the 2017 National Survey of Precision Medicine in Cancer Treatment. Separate multivariable ordinal logistic regressions examined associations of oncologist-, practice-, and area-level characteristics and oncologists' ratings of importance (very, somewhat, or a little/not important) of insurance coverage and OOP costs for genomic testing in treatment decisions, adjusting for oncologist years of experience, sex, race and ethnicity, specialty, use of next-generation sequencing (NGS) tests, region, tumor boards, patient insurance mix, and area-level socioeconomic characteristics. RESULTS Among oncologists, 47.3%, 32.7%, and 20.0% reported that patient insurance coverage for genomic testing was very, somewhat, or a little/not important, respectively, in treatment decisions. In addition, 56.9%, 28.0%, and 15.2% reported that OOP costs for testing were very, somewhat, or a little/not important, respectively. In adjusted analyses, oncologists who used NGS tests were more likely to report patient insurance and OOP costs as important (odds ratio [OR], 2.00 [95% CI, 1.16 to 3.45] and OR, 2.12 [95% CI, 1.22 to 3.68], respectively) in treatment decisions compared with oncologists who did not use these tests, as were oncologists who treated solid tumors, rather than only hematological cancers. More years of experience and higher percentages of Medicaid or self-paid/uninsured patients in the practice were associated with reporting insurance coverage (OR, 1.43 [95% CI, 1.09 to 1.89]) and OOP costs (OR, 1.51 [95% CI, 1.13 to 2.01]) as important. Oncologists in practices with molecular tumor boards for genomic tests were less likely to report coverage (OR, 0.63 [95% CI, 0.47 to 0.85]) and OOP costs (OR, 0.72 [95% CI, 0.53 to 0.97]) as important than their counterparts in practices without these tumor boards. CONCLUSION Most oncologists rate patient health insurance and OOP costs for genomic tests as important considerations in subsequent treatment recommendations. Modifiable factors associated with these ratings can inform interventions to support patient-physician decision making about care.