bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β1 upregulates secreted protein acidic and rich in cysteine expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome
Authors: Dang Xuan , Fang Lanlan , Jia Qiongqiong , Wu Ze , Guo Yanjie , Liu Boqun , Cheng Jung-Chien , Sun Ying-Pu 
Published: May 2023

Abstract
Background
Ovarian hyperstimulation syndrome (OHSS) is a serious complication during in vitro fertilization (IVF) treatment. The upregulation of ovarian transforming growth factor-beta 1 (TGF-β1) is involved in the development of OHSS. The secreted protein acidic and rich in cysteine (SPARC) is a secreted multifunctional matricellular glycoprotein. Although the regulatory effects of TGF-β1 on SPARC expression have been reported, whether TGF-β1 regulates SPARC expression in the human ovary remains unknown. In addition, the role of SPARC in the pathogenesis of OHSS is unclear.

Methods
A steroidogenic human ovarian granulosa-like tumor cell line, KGN, and primary culture of human granulosa-lutein (hGL) cells obtained from patients undergoing IVF treatment were used as experimental models. OHSS was induced in rats, and ovaries were collected. Follicular fluid samples were collected from 39 OHSS and 35 non-OHSS patients during oocyte retrieval. The underlying molecular mechanisms mediating the effect of TGF-β1 on SPARC expression were explored by a series of in vitro experiments.

Results
TGF-β1 upregulated SPARC expression in both KGN and hGL cells. The stimulatory effect of TGF-β1 on SPARC expression was mediated by SMAD3 but not SMAD2. The transcription factors, Snail and Slug, were induced in response to the TGF-β1 treatment. However, only Slug was required for the TGF-β1-induced SPARC expression. Conversely, we found that the knockdown of SPARC decreased Slug expression. Our results also revealed that SPARC was upregulated in the OHSS rat ovaries and in the follicular fluid of OHSS patients. Knockdown of SPARC attenuated the TGF-β1-stimulated expression of vascular endothelial growth factor (VEGF) and aromatase, two markers of OHSS. Moreover, the knockdown of SPARC reduced TGF-β1 signaling by downregulating SMAD4 expression.

Conclusions
By illustrating the potential physiological and pathological roles of TGF-β1 in the regulation of SPARC in hGL cells, our results may serve to improve current strategies used to treat clinical infertility and OHSS.
Detection of mild cognitive impairment in Parkinson’s disease using gradient boosting decision tree models based on multilevel DTI indices
Authors: Chen Boyu , Xu Ming , Yu Hongmei , He Jiachuan , Li Yingmei , Song Dandan , Fan Guo Guang 
Published: May 2023

Abstract
Background
Cognitive dysfunction is the most common non-motor symptom in Parkinson’s disease (PD), and timely detection of a slight cognitive decline is crucial for early treatment and prevention of dementia. This study aimed to build a machine learning model based on intra- and/or intervoxel metrics extracted from diffusion tensor imaging (DTI) to automatically classify PD patients without dementia into mild cognitive impairment (PD-MCI) and normal cognition (PD-NC) groups.

Methods
We enrolled PD patients without dementia (52 PD-NC and 68 PD-MCI subtypes) who were assigned to the training and test datasets in an 8:2 ratio. Four intravoxel metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and two novel intervoxel metrics, local diffusion homogeneity (LDH) using Spearman’s rank correlation coefficient (LDHs) and Kendall’s coefficient concordance (LDHk), were extracted from the DTI data. Decision tree, random forest, and eXtreme gradient boosting (XGBoost) models based on individual and combined indices were built for classification, and model performance was assessed and compared via the area under the receiver operating characteristic curve (AUC). Finally, feature importance was evaluated using SHapley Additive exPlanation (SHAP) values.

Results
The XGBoost model based on a combination of the intra- and intervoxel indices achieved the best classification performance, with an accuracy of 91.67%, sensitivity of 92.86%, and AUC of 0.94 in the test dataset. SHAP analysis showed that the LDH of the brainstem and MD of the right cingulum (hippocampus) were important features.

Conclusions
More comprehensive information on white matter changes can be obtained by combining intra- and intervoxel DTI indices, improving classification accuracy. Furthermore, machine learning methods based on DTI indices can be used as alternatives for the automatic identification of PD-MCI at the individual level.
A vector-free gene interference system using delaminated Mg–Al-lactate layered double hydroxide nanosheets as molecular carriers to intact plant cells
Authors: Zhang He , Li Xinyu , Yu Dong , Guan Junqi , Ding Hao , Wu Hongyang , Wang Qiang , Wan Yinglang 
Published: May 2023

Abstract
Background
The Mg–Al-lactate layered double hydroxide nanosheet (LDH-NS) has shown great potential as an optimal nanocarrier for extensive use in plants. However, previous studies in plant sciences have not provided a clear description of the application for the LDH-NSs-based double-stranded RNA (dsRNA) delivery (LDH-dsRNA) system in different tissues of both model and non-model species.

Results
LDH-NSs were synthesized by using the co-precipitation method, while the dsRNAs targeting genes of interest were prepared in vitro using T7 RNA polymerase. The LDH-dsRNA bioconjugates with a neutral charge were produced by incubating with the mass ratio of LDH-NSs to dsRNA at 3:1, which were then introduced into intact plant cells using three different approaches, including injection, spray, and soak. The LDH-dsRNA delivery method was optimized by inhibiting the expression of the Arabidopsis thaliana ACTIN2 gene. As a result, soaking A. thaliana seedlings in a medium containing LDH-dsRNA for 30 min led to the silencing of 80% of the target genes. The stability and effectiveness of the LDH-dsRNA system were further confirmed by the high-efficiency knockdown of plant tissue-specific genes, including that encoding phytoene desaturase (PDS), WUSCHEL (WUS), WUSCHEL-related homeobox 5 (WOX5), and ROOT HAIR DEFECTIVE 6 (RHD6). In addition, the LDH-dsRNA system was employed in cassava, where it was found that the expression of the gene encoding nucleotide-binding site and leucine-rich repeat (NBS-LRR) was significantly reduced. As a result, the resistance of cassava leaves to pathogens was weakened. Noteworthy, the injection of LDH-dsRNA into leaves resulted in a significant downregulation of target genes in both stems and flowers, indicating the successful transport of LDH-dsRNA from leaves to other parts of plants.

Conclusions
LDH-NSs have proven to be a highly effective molecular tool for delivering dsRNA into intact plant cells, enabling accurate control of target gene expression.
Panax notoginseng saponins inhibits NLRP3 inflammasome-mediated pyroptosis by downregulating lncRNA-ANRIL in cardiorenal syndrome type 4
Authors: Xu Ying , Cao Luxi , Zou Wenli , Yu Rizhen , Shen Wei 
Published: May 2023

Abstract
Objective
Cardiorenal syndrome type 4 (CRS4) is a complication of chronic kidney disease. Panax notoginseng saponins (PNS) have been confirmed to be efficient in cardiovascular diseases. Our study aimed to explore the therapeutic role and mechanism of PNS in CRS4.

Methods
CRS4 model rats and hypoxia-induced cardiomyocytes were treated with PNS, with and without pyroptosis inhibitor VX765 and ANRIL overexpression plasmids. Cardiac function and cardiorenal function biomarkers levels were measured by echocardiography and ELISA, respectively. Cardiac fibrosis was detected by Masson staining. Cell viability was determined by cell counting kit-8 and flow cytometry. Expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and ANRIL was examined using RT-qPCR. Pyroptosis-related protein levels of NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1 were measured by western blotting or immunofluorescence staining.

Results
PNS improved cardiac function, and inhibited cardiac fibrosis and pyroptosis in a dose-dependent manner in model rats and injured H9c2 cells (p < 0.01). The expression of fibrosis-related genes (COL-I, COL-III, TGF-β, α-SMA) and pyroptosis-related proteins (NLRP3, ASC, IL-1β, TGF-β1, GSDMD-N, and caspase-1) was inhibited by PNS in injured cardiac tissues and cells (p < 0.01). Additionally, ANRIL was upregulated in model rats and injured cells, but PNS reduced its expression in a dose-dependent manner (p < 0.05). Additionally, the inhibitory effect of PNS on pyroptosis in injured H9c2 cells was enhanced by VX765 and reversed by ANRIL overexpression, respectively (p < 0.05).

Conclusion
PNS inhibits pyroptosis by downregulating lncRNA-ANRIL in CRS4.
Home-based enzyme replacement therapy in children and adults with Pompe disease; a prospective study
Authors: Ditters Imke A. M. , van der Beek Nadine A. M. E. , Brusse Esther , van der Ploeg Ans T. , van den Hout Johanna M. P. , Huidekoper Hidde H. 
Published: May 2023

Abstract
Background
Pompe disease is a lysosomal storage disease treated with life-long enzyme replacement therapy (ERT). Home-based ERT has been provided in the Netherlands since 2008 because it diminishes the burden of treatment, increases patient flexibility and autonomy, and is thus a more patient-centred approach to ERT.

Methods
All Dutch Pompe patients receiving alglucosidase alfa infusions at home were approached to participate in a questionnaire to validate the safety of home-based ERT. Prospective data on symptoms occurring during or within 48 h after infusion and retrospective data on infusion associated reactions (IARs) in the last three months were collected four times during one year.

Results
In total, 116 out of 120 eligible patients (17 classic infantile, 2 atypical infantile, 15 childhood onset and 82 adult) filled out 423 questionnaires (response rate: 88.1%). Symptoms during or after infusion were reported 27 times in 17 patients. Fatigue was the most commonly reported health complaint (in 9.5% of patients). Four health complaints were judged to be IARs and reported to the Erasmus MC University Medical Center. None of the IARs reported in this study warranted emergency clinical care.

Conclusions
Our data demonstrate that home-based ERT in Pompe disease can be safely implemented as few, mostly mild, symptoms were reported during or after infusion. Insights from this study can be used as a base for implementing home-based ERT in other countries and to further optimize patient care, as unreported mild symptoms do not pose a health risk but may still be relevant to the patient.
Comparing telemedicine and in-person gastrointestinal cancer genetic appointment outcomes during the COVID-19 pandemic
Authors: Williams Samantha , Ebrahimzadeh Jessica E. , Clay Daniel , Constantino Gillian , Heiman Jordan , Wangensteen Kirk J. , Valverde Kathleen , Mahmud Nadim , Katona Bryson W. 
Published: May 2023

Abstract
Background
The study purpose is to compare outcomes associated with completion of genetic testing between telemedicine and in-person gastrointestinal cancer risk assessment appointments during the COVID-19 pandemic.

Methods
Data was collected on patients with scheduled appointments between July 2020 and June 2021 in a gastrointestinal cancer risk evaluation program (GI-CREP) that utilized both telemedicine and in-person visits throughout the COVID-19 pandemic, and a survey was administered.

Results
A total of 293 patients had a GI-CREP appointment scheduled and completion rates of in-person versus telemedicine appointments were similar. Individuals diagnosed with cancer and those with Medicaid insurance had lower rates of appointment completion. Although telehealth was the preferred visit modality, there were no differences in recommending genetic testing nor in the consent rate for genetic testing between in-person and telemedicine visits. However, of patients who consented for genetic testing, more than three times more patients seen via telemedicine did not complete genetic testing compared to those seen in-person (18.3% versus 5.2%, p = 0.008). Furthermore, telemedicine visits had a longer turnaround time for genetic test reporting (32 days versus 13 days, p < 0.001).

Conclusions
Compared to in-person GI-CREP appointments, telemedicine was associated with lower rates of genetic testing completion, and longer turnaround time for results.
Identification and validation of miR-583 and mir-877-5p as biomarkers in patients with breast cancer: an integrated experimental and bioinformatics research
Authors: Foruzandeh Zahra , Alivand Mohammad Reza , Ghiami-Rad Mehdi , Zaefizadeh Mohammad , Ghorbian Saeid 
Published: May 2023

Abstract
Objectives
Breast cancer (BC) is one of the most common cancers with a high mortality rate in women worldwide. The advantages of early cancer diagnosis are apparent, and it is a critical factor in increasing the patient’s life and survival. According to mounting evidence, microRNAs (miRNAs) may be crucial regulators of critical biological processes. miRNA dysregulation has been linked to the beginning and progression of various human malignancies, including BC, and can operate as tumor suppressors or oncomiRs. This study aimed to identify novel miRNA biomarkers in BC tissues and non-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for differentially expressed genes (DEGs) and GSE45666, GSE57897, and GSE40525 for differentially expressed miRNAs (DEMs) retrieved from the Gene Expression Omnibus (GEO) database were analyzed using “R” software. A protein-protein interaction (PPI) network was created to identify the hub genes. MirNet, miRTarBase, and MirPathDB databases were used to predict DEMs targeted genes. Functional enrichment analysis was used to demonstrate the topmost classifications of molecular pathways. The prognostic capability of selected DEMs was evaluated through a Kaplan-Meier plot. Moreover, the specificity and sensitivity of detected miRNAs to discriminate BC from adjacent controls were assessed by area under the curve (AUC) using the ROC curve analysis. In the last phase of this study, gene expression on 100 BC tissues and 100 healthy adjacent tissues were analyzed and calculated by using the Real-Time PCR method.

Results
This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05). Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69). Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC.
Under storm risk, economic productivity of Norway spruce (Picea abies (L.) H. Karst) in monoculture shows sharper decline than in mixture with European beech (Fagus sylvatica L.)
Authors: Bourke Robin , Yousefpour Rasoul , Hanewinkel Marc 
Published: May 2023

Abstract
Key message
By calibrating and validating a forest growth model for seven species in Germany and coupling it with a wind damage simulator, we specifically estimated the impact of wind damage on the net present value of Norway spruce and European beech in mixture and monoculture. Under risk, the net present value of spruce managements saw the sharpest declines, although the highest end net present value was still obtained through a heavily thinned spruce monoculture.

Context
Wind damage is one of the most important risks to Central European forests, and adaptation measures are essential.

Aim
Adaptive management strategies should simultaneously account for forest production and wind risk. We simulated the effect of adaptive measures on wind-risk in German forests.

Methods
A process-based forest growth model, “3-PG Mix”, was recalibrated and coupled with the storm damage risk model “Lothar”. We investigated the effect of thinning regimes on wind risk in monoculture and mixed species stands. The net present value of the simulated regimes was calculated and compared (risk vs. no risk).

Results
Spruce regimes achieved the highest net present values when risk was not considered. Considering risk in spruce and beech mixtures and monoculture, all regimes reached values below 3000 € ha−1 by year 120. The exception was a heavily thinned spruce monoculture at 4507 € ha−1, being the most profitable regime under risk.

Conclusion
We conclude, on the basis of this modelling study, that heavy thinning reduced storm risk and maintained a higher net present value in spruce. Species mixture of beech and spruce saw net present values levels remain more constant under risk, while beech monoculture increased.
Solutions to a $(p(x),q(x))$-biharmonic elliptic problem on a bounded domain
Authors: Khaleghi Ali , Razani Abdolrahman 
Published: May 2023

AbstractUsing variational methods and critical point results, we prove the existence and multiplicity of weak solutions of a $(p(x),q(x))$
(
p
(
x
)
,
q
(
x
)
)
-biharmonic elliptic equation along with a singular term under Navier boundary conditions.
Overview of the role of robots in upper limb disabilities rehabilitation: a scoping review
Authors: Moulaei Khadijeh , Bahaadinbeigy Kambiz , Haghdoostd Ali Akbar , Nezhad Mansour Shahabi , Sheikhtaheri Abbas 
Published: May 2023

AbstractBackgroundNeuromotor rehabilitation and improvement of upper limb functions are necessary to improve the life quality of patients who have experienced injuries or have pathological outcomes. Modern approaches, such as robotic-assisted rehabilitation can help to improve rehabilitation processes and thus improve upper limb functions. Therefore, the aim of this study was to investigate the role of robots in upper limb disability improvement and rehabilitation.MethodsThis scoping review was conducted by search in PubMed, Web of Science, Scopus, and IEEE (January 2012– February 2022). Articles related to upper limb rehabilitation robots were selected. The methodological quality of all the included studies will be appraised using the Mixed Methods Appraisal Tool (MMAT). We used an 18-field data extraction form to extract data from articles and extracted the information such as study year, country, type of study, purpose, illness or accident leading to disability, level of disability, assistive technologies, number of participants in the study, sex, age, rehabilitated part of the upper limb using a robot, duration and frequency of treatment, methods of performing rehabilitation exercises, type of evaluation, number of participants in the evaluation process, duration of intervention, study outcomes, and study conclusions. The selection of articles and data extraction was made by three authors based on inclusion and exclusion criteria. Disagreements were resolved through consultation with the fifth author. Inclusion criteria were articles involving upper limb rehabilitation robots, articles about upper limb disability caused by any illness or injury, and articles published in English. Also, articles involving other than upper limb rehabilitation robots, robots related to rehabilitation of diseases other than upper limb, systematic reviews, reviews, and meta-analyses, books, book chapters, letters to the editor, and conference papers were also excluded. Descriptive statistics methods (frequency and percentage) were used to analyses the data.ResultsWe finally included 55 relevant articles. Most of the studies were done in Italy (33.82%). Most robots were used to rehabilitate stroke patients (80%). About 60.52% of the studies used games and virtual reality rehabilitate the upper limb disabilities using robots. Among the 14 types of applied evaluation methods, “evaluation and measurement of upper limb function and dexterity” was the most applied evaluation method. “Improvement in musculoskeletal functions”, “no adverse effect on patients”, and “Safe and reliable treatment” were the most cited outcomes, respectively.ConclusionsOur findings show that robots can improve musculoskeletal functions (musculoskeletal strength, sensation, perception, vibration, muscle coordination, less spasticity, flexibility, and range of motion) and empower people by providing a variety of rehabilitation capabilities.
Experimental Analysis and Evaluation of the Compressive Strength of Rubberized Concrete During Freeze–Thaw Cycles
Authors: Sun Sheng , Han Xiaoyan , Chen Aijiu , Zhang Qing , Wang Zhihao , Li Keliang 
Published: May 2023

AbstractRecycling scrap tires provides an alternative source of fine aggregates for the production of rubberized concrete and this will lead to significant increase in concrete frost resistance, environmental protection, and conservation of natural sand and gravel resources. In this paper, a total of 25 groups of rubberized concrete were produced by adding scrap tire rubber particles of different sizes, contents, and pretreatment methods to replace the fine aggregate, and their compressive strength during freeze–thaw cycles was studied from both the macro- and meso-perspectives. The results indicated that the decrease in concrete strength and weight was notably restricted by the presence of rubber particles during freeze–thaw cycles. The rubber fine aggregate with smaller particle sizes enhanced the concrete frost resistance more significantly, and the F100 of concrete with rubber particles of 1.0–2.0 mm increased from 76.6 to 86.5% by increasing the rubber content from 0.0 to 5.6%. The effects of rubber fine aggregate on concrete compressive strength during freeze–thaw cycles were quantified. On this basis, a forecast model for rubberized concrete compressive strength in freeze–thaw cycles was proposed, and the effects of the particle size, content, and pretreatment of the rubber particles were considered. The calculated results agreed well with the test results both in this study and the relevant peer studies, indicating that the model can provide a good reference for the design and engineering application of rubberized concrete in frigid environments.