bluuebunny/crossref_metadata_2025_split huggingface dataset:
Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with Critical limb ischemia (CLI)
Authors: Shirbaghaee Zeinab , Keshel Saeed Heidari , Rasouli Mehdi , Valizadeh Majid , Nazari Seyed Saeed Hashemi , Hassani Mohammad , Soleimani Masoud 
Published: March 2023

Abstract
Background
Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI.
Methods
This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 106 and 60 × 106 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes.
Results
All dosages of P-MSCs, including the highest tested dose of 60 × 106 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly.
Conclusion
The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI.
Trial registration:
IRCT, IRCT20210221050446N1. Registered May 09, 2021.
Identifying Areas of Low-Access to the COVID-19 Vaccine: A New Objective Framework Incorporating Mobility Data
Authors: Tao Defeng , Agor Joseph , McGregor Jessina , Douglass Trevor , Gibler Andrew , Vergara Hector 
Published: March 2023

Abstract
Background
Methods have been proposed to identify areas of low access to resources that are embedded with subjective parameters. In this work, we propose and validate a new Mobility Data-Driven (MDD) framework to identify areas that have low access to the COVID-19 vaccine.

Methods
We collected geospatial mobility data to an objective approach for determining areas of low access. We identify census tracts in Oregon with low access to the COVID-19 vaccine through two approaches: (1) An adapted United States Department of Agriculture (USDA) food desert definition and (2) our proposed MDD framework. Ten spatial and social measures of access are utilized to compare these two approaches.

Results
Tracts identified by the MDD definition have lower spatial accessibility scores (0.072 – 0.162) than those identified by the USDA adapted definition (0.239 – 0.32). During the Spring season, the MDD identified census tracts have a higher rate of poverty (15.2%), unemployment (8.4%), uninsured individuals (7.1%), and a lower per capita income ($28,261). Moreover, we find that the proportion the American Indian and Alaskan Native population in MDD identified low-access census tracts is higher than that in USDA definition (4.85% versus 0.95%) which indicates the framework’s ability to capture known disparities in access amongst this population.

Conclusions
During the creation of plans for equitable distribution of a resource like the COVID-19 vaccine, leaders should utilize objective data (like mobility data) to assist them in determining parameters that represent a populations ability to obtain that resource. Our proposed framework provides a starting point for achieving this goal.
Abnormal hypo-methylation of CAP1 (adenylate cyclase associated protein 1) gene enhances biological characteristics of lung adenocarcinoma cells
Authors: Li Guoshu , Xie Shuanshuan , Wang Kai , Tan Min , Zhou Guo-Lei , Zhan Jushan , Zou Junyong , Fan Lihong , Wang Changhui 
Published: March 2023

Abstract
Background
Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer, which is a serious threat to human health. Adenylate cyclase associated protein 1 (CAP1) is an important functional protein, which is closely related to the occurrence and progression of cancer.
Methods
In this study, we used the CRISPR-dCas9-Dnmt3a system to target the CAP1 promoter to construct LUAD cell strains that can steadily up-regulate the methylation of CAP1 promoter. The methylation specific PCR and Massarray methylation sequencing were used to detect the methylation of CAP1 promoter. The western blot and immunohistochemistry were used to detect protein expression. The functional changes of LUAD cells were detected by CCK-8 assay, colony formation assay, flow cytometry assay, wound healing assay and trans-well assay.
Results
In this study, we found that the CAP1 promoter was abnormally hypo-methylated in LUAD cells and tissues. The expression of CAP1 protein was higher in cancerous tissues compared to para-carcinoma tissues in early stage LUAD, and higher in A549, H1299 and PC9 cells than in Beas-2B control cells (P < 0.05). Up-regulating methylation of CAP1 promoter can reduce the expression of CAP1 protein, promote apoptosis of LUAD cells through Bax/Bcl-2/Caspase-3 pathway, and inhibit the migration and invasion of LUAD cells by acting together with Actin and Cofilin. The methylation of CAP1 promoter is regulated by Dnmt3a, Tet1 and/or Tet2.
Conclusions
These results suggest that abnormal hypo-methylation of CAP1 gene enhances biological characteristics of LUAD cells and up-regulating methylation of CAP1 promoter may be a potential treatment for LUAD.
Novel SnO 2 @Cu 3 (BTC) 2 composites as a highly efficient Photocatalyst and Fluorescent Sensor
Authors: Deepika - , Heena - , Kaur Manpreet , Dhaliwal Karamjit Singh , Malik Ashok Kumar 
Published: March 2023

Abstract
A novel SnO2@Cu3(BTC)2 composite was synthesized using a quick and affordable bottom-up approach via impregnation of SnO2 nanoparticles into the porous Cu3(BTC)2 metal-organic framework (MOF). The photocatalytic degradation of the methylene blue (MB) dye has been studied for the first time using this novel recyclable SnO2@Cu3(BTC)2 composite. It was found that SnO2@Cu3(BTC)2 composite photo catalytically degrades methylene blue (MB) dye with a degradation efficiency of 85.12% within 80 min under solar irradiation. The most appropriate benefit of this composite is the easy recyclability up to numerous cycles with retention of its photocatalytic activity. Therefore, this cheaper and greener composite photocatalyst is more suitable for large-scale industrial applications than the traditional photocatalysts employed in the degradation of MB dye. Furthermore, this composite has also been investigated as a fluorescence sensor for the detection of nitroaromatic compounds (NACs). It was observed that the 88.2% quenching of the intense fluorescent signal of this composite happens in the presence of 2,4,6-trinitrophenol (TNP) showing it incredibly selectivity towards TNP with no interference of other NACs. With a detection limit of 2.82 µM, this composite exhibits outstanding sensitivity towards TNP. The Stern-Volmer plot for TNP is linearly fitted displays large quenching coefficient, correlation coefficient, and linear ranges KSV = 1.04x104 M-1, R2 = 0.9901, and 0-10 µM, respectively. This quenching response of this composite towards TNP was well-explained by the two mechanisms: one is photo-induced electron transfer (PET), and the other is fluorescence resonance energy transfer (FRET), in addition to theoretical calculations based on density functional theory (DFT). Our findings imply that the synthetic composite can be used as a superior fluorescence sensor and photocatalyst.
Mechanical properties and long-term antibacterial activity of dental composite resins added with a strontium-modified phosphate-based glass microfiller
Authors: Go Hye-Bin , Lee Myung-Jin , Seo Ji-Young , Kwon Jae-Sung 
Published: March 2023

Abstract
Dental composite resins are widely used in dental restorations. However, their clinical application is limited by the occurrence of secondary caries. As strontium-modified phosphate-based glass is known to have long-term antibacterial properties, in this study, we incorporated a strontium-modified phosphate-based glass microfiller at 3, 6, and 9 wt.% concentrations into a commercially available composite resin and investigated the mechanical properties (flexural strength, elastic modulus, and microhardness), ion release characteristics, and color of the resultant resins. In addition, we examined the antibacterial effects of the composite resins against Streptococcus mutans (S. mutans). The mechanical properties of the Sr-modified phosphate-based glass groups differed only slightly from those of the control group (p > 0.05). However, the optical density at 600 nm of S. mutans incubated on the experimental group was significantly lower compared to that observed with the control (p < 0.05) both before and after thermocycling between 5 and 55 ℃ for 850 cycles (dwell time: 45 s). This study demonstrates that the addition of the Sr-containing phosphate-based glass filler to composite resins can enhance their long-term antibacterial activity and help prevent secondary caries.
Risk factors for preterm labor: An Umbrella Review of meta-analyses of observational studies
Authors: Mitrogiannis Ioannis , Evangelou Evangelos , Efthymiou Athina , Kanavos Theofilos , Birbas Effrosyni , Makrydimas George , Papatheodorou Stefania 
Published: March 2023

Abstract
Preterm birth defined as delivery before 37 gestational weeks, is a leading cause of neonatal and infant morbidity and mortality. Understanding its multifactorial nature may improve prediction, prevention and the clinical management. We performed an umbrella review to summarize the evidence from meta-analyses of observational studies on risks factors associated with PTB, evaluate whether there are indications of biases in this literature and identify which of the previously reported associations are supported by robust evidence.
We included 1511 primary studies providing data on 170 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections and vaccines. Only seven risk factors provided robust evidence. The results from synthesis of observational studies suggests that sleep quality and mental health, risk factors with robust evidence should be routinely screened in clinical practice, should be tested in large randomized trial. Identification of risk factors with robust evidence will promote the development and training of prediction models that could improve public health, in a way that offers new perspectives in health professionals.
Biophysical models resolution affects coral connectivity estimates
Authors: Saint-Amand Antoine , Lambrechts Jonathan , Hanert Emmanuel 
Published: March 2023

Abstract
Estimating connectivity between coral reefs is essential to inform reef conservation and restoration. Given the vastness of coral reef ecosystems, connectivity can only be simulated with biophysical models whose spatial resolution is often coarser than the reef scale. Here, we assess the impact of biophysical models resolution on connectivity estimates by comparing the outputs of five different setups of the same model with resolutions ranging from 250 m to 4 km. We show that increasing the model resolution around reefs yields more complex and less directional dispersal patterns. With a fine-resolution model, connectivity graphs have more connections but of weaker strength. The resulting community structure therefore shows larger clusters of well-connected reefs. Virtual larvae also tend to stay longer close to their source reef with a fine-resolution model, leading to an increased local retention and self-recruitment for species with a short pre-competency period. Overall, only about half of the reefs with the largest connectivity indicator values are similar for the finest and coarsest resolution models. Our results suggest that reef management recommendations should only be made at scales coarser than the model resolution. Reef-scale recommendations can hence only be made with models not exceeding about 500 m resolution.
Cheque Processing using Traditional Blockchain Issues and An Approach to Secure Processing
Authors: Natarajan M , Bharathi A. 
Published: March 2023

Abstract
Blockchain technologies, particularly cryptocurrency, have piqued the interest of academics, governments, and business in recent times. Despite the availability of a wide range of blockchain-based solutions, the lack of tools to analyses these dynamic and distributed networks may stymie the field's advancement. Many of the benefits of block chain technology can only be seen at large scales. This paper conducts a thorough investigation of blockchain-related concerns. Summarizes the issues with traditional blockchain techniques. The paper also offers a framework for secure transaction processing and suggests the steps involved in creating a blockchain. Furthermore, suggestions have been made for possible futre study directions in the topic. The purpose of this study is to evaluate the current Applications that are based on the Blockchain Technology in various fields and to build a better model for an application that is used in the financial sector. It is necessary to adapt the banking system in the financial sector to the current situation in order to meet the requirements. Checks are processed using the present technique, which, although having certain restrictions, is more focused. Following the analysis, the study proceeded with the goal of resolving the limits of the system for the processing and clearing of cheques by shortening the amount of time required for processing and increasing the level of security. The disruptive nature of Blockchain technology was helpful in applying the technology to the creation of a secure system for the processing of cheques. In order to offer a sufficiently upgraded framework, already existing techniques for the processing of cheques were discovered, and their limitations were determined. To achieve the same goals, smart contracts were utilized to automatically finish the operation of check processing by issuing a valid tokenized cheque to update the information in IPFS blockchain. This allowed for the same goals to be achieved. The cheque processing system is composed of many stages, such as the administrator phase and the phase in which checks are generated by utilizing ERC20 tokens. This is to validate the tokenized check that was produced by a bank that has been granted permission. The subsequent step is known as the check details phase. After this, the user phase will come into play, at which point the beneficiary data will be entered. At this point, validation is carried out by signing the cheque and then cancelling the transaction after it has been initiated. After the completed transaction is published in the IPFS blockchain, the bank will validate the compliance features. In order to check for issues connected to the issue, several security technologies are utilized. The performance is evaluated, and then recommendations for enhancing the performance on mathematical models are provided.
Design and experimental study of Mechanical Milling deicing device
Authors: Zhu Zi-cheng , Chu Wei-jun , Diao Yan , Li Xiang-hui 
Published: March 2023

Abstract
To quickly and economically remove the accumulated ice and snow on airport runways, urban roads and bridge decks is an important subject to ensure smooth traffic and driving safety under the condition of snow and ice climate. Based on analysis of different mechanical deicing techniques and the combination of thermal and water jet cutting deicing methods, a mechanical milling deicing method was proposed. Through the establishment of a milling deicing cutting model and the force analysis of the deicing cutter, the optimal deicing angle of the milling cutter was obtained, and the rationality of the design of the milling deicing cutter was verified based on ANSYS. The feasibility of the design scheme is verified by the test of mechanical milling deicing device.
The Sherpa hypothesis: Phenotype-Protecting Disordered Proteins stabilize the phenotypes of neurons and oligodendrocytes
Authors: Norris Vic , Oláh Judit , Krylov Sergey , Uversky Vladimir , Ovadi Judit 
Published: March 2023

Abstract
Intrinsically disordered proteins (IDPs) are central to many physiological functions and to various pathologies that include neurodegeneration. They can interact with numerous partner proteins. Here, we introduce the Sherpa hypothesis, according to which a subset of stable IDPs, which we term Phenotype-Preserving Disordered Proteins (PPDP), play a central role in protecting cell phenotypes from perturbations. To illustrate and test this hypothesis, we computer-simulate some salient features of how cells evolve and differentiate in the presence of either a single PPDP or two incompatible PPDPs. We relate this virtual experiment to the pathological interactions between two PPDPs, α-synuclein and Tubulin Polymerization Promoting Protein/p25, in neurodegenerative disorders. Finally, we discuss the implications of the Sherpa hypothesis for aptamer-based therapies of such disorders.
Construction and validation of an IHC-based risk model predicting postoperative disease- free survival and overall survival in Chinese endometrial cancer patients
Authors: Li Xingchen , Yang Fengbo , Zhao Lijun , Wang Jianliu 
Published: March 2023

Abstract
Background: The objective of this study was to characterize the expression features base on three genes, including DUSP1, BUB1 and MCM7, and investigate their clinical significance in Chinese cohort with endometrial carcinoma.
Materials and methods. Immunohistochemistry (IHC) was performed for assessing the expression of DUSP1, BUB1, and MCM7 in these patients. The associations between the expressions of three genes and the clinicopathological features were analyzed. The risk model was finally validated in TCGA cohort.
Results: The expressions of DUSP1, BUB1, and MCM7 were associated with clinicopathological features (P＜0.05 for all). Patients with high expression level of DUSP1 and low expression level of BUB1 and MCM7 had better prognosis. The construction combining these three genes is an independent risk factor and had a high accuracy in predicting overall survival (OS, AUC=0.923) and disease-free survival (DFS, AUC=0.963). The three-gene risk signature was validated in TCGA-EC cohort, and the results showed a great precision for predicting OS and DFS (both AUC>0.7) in an external group.
Conclusions: Our study revealed a three-gene prognostic signature, including DUSP1, BUB1, and MCM7, and its related nomogram could guide personalized strategy, providing a basis for the molecular analysis in EC, thereby improving their OS and DFS.
MEX3A determines in vivo hepatocellular carcinoma progression and induce resistance to sorafenib in a Hippo-dependent way
Authors: Fang Shiji , Zheng Liyun , Chen Xiaoxiao , Guo Xiaoju , Ding Yiming , Ma Ji , Ding Jiayi , Chen Weiqian , Yang Yang , Chen Minjiang , Zhao Zhongwei , Tu Jianfei , Ji Jiansong 
Published: March 2023

Abstract
Hepatocellular carcinoma (HCC) is most common malignant tumor worldwide, and one of the most lethal malignancies. MEX3A, an RNA-binding protein, is profoundly implicated in tumor initiation and progression. But its role and potential mechanism in HCC remains fully unclear. In this study, MEX3A expression was upregulated in HCC tissue and cell lines. Knockdown or overexpression of MEX3A disturbed the proliferation, migration and apoptosis of HCC cells by modulating the activation of Hippo signaling pathway. The expression of MEX3A was negatively associated with sorafenib sensitivity and upregulated in sorafenib resistant HCC cells. MEX3A knockdown facilitated the expression of WWC1, a negative modulator of Hippo signaling pathway, and led to increase of the phosphorylation of LATS1 and YAP1. Pharmacological inhibition of LATS1 or WWC1 overexpression alleviated the proliferative and migrated suppression and increased sorafenib sensitivity, whereas WWC1 inhibition using genetic interference strategy showed opposite trend in MEX3A knockdown HCC cells. Importantly, MEX3A knockdown led to growth and lung metastasis inhibition using xenograft model established by means of subcutaneous or tail vein injection. In addition, a combination of MEX3A knockdown and WWC1 overexpression dramatically enhances the growth inhibition of sorafenib in vivo. Collectively, our results demonstrated that MEX3A may facilitate HCC progression and hinder sorafenib sensitivity via inactivating Hippo signaling. The present study suggested that targeting MEX3A can be served as a novel therapeutic strategy for HCC.
Screening for Antibody Deficiencies in Adults by Serum Electrophoresis
Authors: Piza Cristina Frias Sartorelli de Toledo , Aranda Carolina Sanchez , Solé Dirceu , Jolles Stephen , Condino-Neto Antonio 
Published: March 2023

Abstract
Purpose
This study aimed to investigate the correlation between calculated globulin (CG, total protein level minus albumin level) and the gamma globulin fraction (Gamma), obtained from serum protein electrophoresis with serum IgG levels in adults (≥ 18 years).
Methods
Using linear regression models, analyses of CG and Gamma levels correlation with IgG levels in adults were performed. Receiver-operator curves were created to determine cutoff values and the respective sensitivity and specificity measures.
Results
A total of 886 samples were analyzed. CG and Gamma were positively and statistically correlated with IgG levels (r2 = 0.4628 for CG, and = 0.7941 for Gamma, p < 0.0001 for both analyses). For the detection of hypogammaglobulinemia, i.e., IgG level below the reference value (6 g/L), a CG cutoff value of 24 g/L showed a sensitivity of 86.2% (95% CI 69.4–94.5) and a specificity of 92% (90.0-93.6). A Gamma cutoff value of 7.15 g/L yielded a sensitivity of 100% (88.3–100) and a specificity of 96.8 (95.3-97-8).
Conclusion
Both CG and Gamma levels determined by protein electrophoresis analysis may be used to screen for antibody deficiencies in adults, enabling earlier diagnosis of antibody deficiencies in a routine clinical setting.
Deciphering the global spread of canine rabies virus in the modern era
Authors: Holtz Andrew , Baele Guy , Bourhy Herve , Zhukova Anna 
Published: March 2023

Abstract
Despite the rapid growth in viral genome sequencing, statistical methods face challenges in handling historical viral endemic diseases with large amounts of underutilized partial sequence data. We propose a phylogenetic pipeline that harnesses both full and partial viral genome sequences to investigate historical pathogen spread between countries. Its application to Rabies virus (RABV) yields precise dating and confident estimates of its geographic dispersal. By using full genomes and partial sequences, we reduce both geographic and genetic biases that often hinder studies that focus on specific genes. Our pipeline reveals an emergence of the present canine-mediated RABV between years 1301 and 1401 and reveals regional introductions over a 700-year period. This geographic reconstruction enables us to locate episodes of human-mediated introductions of RABV and examine the role that European colonization played in its spread. Our approach enables phylogeographic analysis of large and genetically diverse data sets for many viral pathogens.