bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of Melatonin in Diabetic Retinopathy Is Effective and Improves the Efficacy of Mesenchymal Stem Cell Treatment
Authors: Abdel-Kawi Samraa H. , Hashem Khalid S. 
Published: April 2022

Stem cell transplantation is a promising therapeutic technique for the treatment of a variety of diseases; nevertheless, stem cell therapy may not always work as well as it could. The goal of this study was to test the hypothesis that employing a powerful antioxidant like melatonin improves stem cell transplantation success and potentiates stem cell function in the therapy of diabetic retinopathy. For this purpose, 50 adult male rats were divided into the following: control group: this group received 0.5 ml of 0.1 M of sodium citrate buffer (

pH
=
4.5

) (intraperitoneal (I.P.)). The confirmed diabetic rats were divided into 4 groups: diabetic group: confirmed diabetic rats received no treatments with a regular follow of the blood glucose profile for 8 weeks; melatonin group: confirmed diabetic rats received melatonin (5 mg/kg/day); stem cell group: the confirmed diabetic rats were given intravitreal injection of stem cells (2 μl cell suspension of stem cells (

3
×

10

4

cells
/
μ
l

)); and melatonin+stem cell group: confirmed diabetic rats received melatonin (5 mg/kg/day), orally once daily for 8 weeks, and 2 μl cell suspension of stem cells (

3
×

10

4

cells
/
μ
l

) was carefully injected into the vitreous cavity. Our results showed that administration of melatonin and/or stem cell restored the retinal oxidative/antioxidant redox and reduced retinal inflammatory mediators. Coadministration of melatonin and stem cells enhanced the number of transplanted stem cells in the retinal tissue and significantly reduced retinal BDEF, VEGF, APOA1, and RBP4 levels as compared to melatonin and/or stem alone. We may conclude that rats treated with melatonin and stem cells had their retinal oxidative/antioxidant redox values restored to normal and their histological abnormalities reduced. These findings support the hypothesis that interactions with the BDEF, VEGF, APOA1, and RBP4 signaling pathways are responsible for these effects.
Sounding the Alarm on Leiomyosarcoma Recurrence: Role of Circulating Tumor DNA
Authors: Kasper Bernd , Wilky Breelyn A. 
Published: April 2022

Summary
Recent work confirms a bench-to-bedside approach that circulating tumor DNA is associated with outcome and objective response to chemotherapy in patients with advanced leiomyosarcoma. Liquid biopsies may be used for risk stratification in future trials guiding treatment decisions by identifying patients who are likely to benefit from chemotherapy.
See related article by Madanat-Harjuoja et al., p. 2579
Automatic diagnosis and grading of patellofemoral osteoarthritis from the axial radiographic view: a deep learning-based approach
Authors: E Tuya , Wang Cen , Cui Yingpu , Nai Rile , Zhang Yaofeng , Zhang Xiaodong , Wang Xiaoying 
Published: April 2022

Background Patellofemoral osteoarthritis (PFOA) has a high prevalence and is assessed on axial radiography of the patellofemoral joint (PFJ). A deep learning (DL)-based approach could help radiologists automatically diagnose and grade PFOA via interpreting axial radiographs. Purpose To develop and assess the performance of a DL-based approach for diagnosing and grading PFOA on axial radiographs. Material and Methods A total of 1280 (dataset 1) axial radiographs were retrospectively collected and utilized to develop the high-resolution network (HRNet)-based classification models. The ground truth was the interpretation from two experienced radiologists in consensus according to the K-L grading system. A binary-class model was trained to diagnose the presence (K-L 2∼4) or absence (K-L 0∼1) of PFOA. A multi-class model was used to grade the stage of PFOA, i.e. from K-L 0 to K-L 4. Model performances were evaluated using the receiver operating characteristics (ROC), confusion matrix, and the corresponding evaluation metrics (positive predictive value [PPV], negative predictive value [NPV], F1 score, sensitivity, specificity, accuracy) of the internal test set (n = 129) from dataset 1 and an external validation set (dataset 2, n = 187). Results For the binary-class model, the area under the curve (AUC) was 0.91 in the internal test set and 0.90 in the external validation set. For grading PFOA, moderate to severe stage of PFOA exhibited a good performance in these two datasets (AUC = 0.91–0.98, PPV = 0.69–0.90, NPV = 0.92–0.99, F1 score = 0.72–0.87, sensitivity = 0.75–0.87, specificity = 0.90–0.99, accuracy = 0.87–0.98). Conclusion The HRNet-based approach performed well in diagnosing and grading radiographic PFOA, especially for the moderate to severe cases.
Supernormal foveal photoreceptor density in Alport syndrome: A case report
Authors: Ameln Julius , Reiniger Jenny L. , Hess Kristina , Holz Frank G. , Harmening Wolf M. 
Published: April 2022

Purpose To investigate foveal photoreceptor configuration in Alport syndrome, a rare inherited disease characterized by Collagen IV dysfunction. Methods Adaptive optics scanning laser ophthalmoscope (AOSLO) in vivo imaging of the foveal center and quantitative analysis of cone photoreceptor topography in a 17-year-old male patient with Alport syndrome presenting absence of a foveal avascular zone (FAZ) and foveal hypoplasia in both eyes. Results Cone density analysis based on AOSLO images revealed an unusual linear cone topography profile displaying supernormal densities within the fovea (z-scores up to + 3.57 and + 2.97 in right and left eyes, respectively). Conclusion Foveal hypoplasia has previously been associated with normal or reduced cone density. Our observation is the first case of disease-related supernormal cone density within the foveola, shedding light upon the role of Collagen IV in foveal maturation.
Multi-objective optimization of gearbox based on panel acoustic participation and response surface methodology
Authors: Qi Le , Zhou Jianxing , Xu Huachao 
Published: April 2022

Aiming at noise problem of two-stage gearbox, this paper uses the panel acoustic contribution analysis (PACA) and response surface methodology to conduct structural-borne acoustics analysis and multi-objective optimization of gearbox. Using this optimization, optimal layout and parameters of the added ribs can be determined. The dynamic model of a spur gear-shaft-bearing system is built in consideration of the time-varying mesh stiffness, the time-varying bearing stiffness, and the flexibility of the shaft, while dynamic load of the bearing is obtained through solving the model. The dynamic load of bearings is considered as excitation to analyze the vibration and noise radiation characteristics of housing. Furthermore, acoustic transfer vector, modal acoustic contribution and PACA are used to select the region with the most acoustic contribution. The variable ribs structure model (VRSM) is established in this region. Finally, the VRSM are adopted to optimize the housing. The optimization model based on the peak sound pressure level (PSPL) and the ribs mass (Rm) is established by using response surface method. Through multi-objective optimization, the variable in VRSM can be modified or deleted to reduce the radiated noise of the gearbox. The optimization results demonstrate that the PSPL after optimization is decreased by 4.88 dB at frequency of 3130 Hz. At the same mass, the noise reduction effect of VRSM is 12% higher than that of standard rib. Therefore, the optimization effect of the housing structure is obvious. PACA-VRSM-RSM- NSGA-II technology provides a new research scheme for reducing the vibration and noise of the gearbox.
Sex differences in the symptom presentation of stroke: A systematic review and meta-analysis
Authors: Shajahan Sultana , Sun Lingli , Harris Katie , Wang Xia , Sandset Else Charlotte , Yu Amy YX , Woodward Mark , Peters Sanne AE , Carcel Cheryl 
Published: April 2022

Background: Early diagnosis through symptom recognition is vital in the management of acute stroke. However, women who experience stroke are more likely than men to be initially given a nonstroke diagnosis and it is unclear if potential sex differences in presenting symptoms increase the risk of delayed or missed stroke diagnosis. Aims: To quantify sex differences in the symptom presentation of stroke and assess whether these differences are associated with a delayed or missed diagnosis. Methods: PubMed, EMBASE, and the Cochrane Library were systematically searched up to January 2021. Studies were included if they reported presenting symptoms of adult women and men with diagnosed stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA) and were published in English. Mean percentages with 95% confidence intervals (CIs) of each symptom were calculated for women and men. The crude relative risks (RRs) with 95% CI of symptoms being present in women, relative to men, were also calculated and pooled. Any data on the delayed or missed diagnosis of stroke for women compared to men based on symptom presentation were also extracted. Results: Pooled results from 21 eligible articles showed that women and men presented with a similar mean percentage of motor deficit (56% in women vs 56% in men) and speech deficit (41% in women vs 40% in men). Despite this, women more commonly presented with nonfocal symptoms than men: generalized nonspecific weakness (49% vs 36%), mental status change (31% vs 21%), and confusion (37% vs 28%), whereas men more commonly presented with ataxia (44% vs 30%) and dysarthria (32% vs 27%). Women also had a higher risk of presenting with some nonfocal symptoms: generalized weakness (RR 1.49, 95% CI 1.09–2.03), mental status change (RR 1.44, 95% CI 1.22–1.71), fatigue (RR 1.42, 95% CI 1.05–1.92), and loss of consciousness (RR 1.30, 95% CI 1.12–1.51). In contrast, women had a lower risk of presenting with dysarthria (RR 0.89, 95% CI 0.82–0.95), dizziness (RR 0.87, 95% CI 0.80–0.95), gait disturbance (RR 0.79, 95% CI 0.65–0.97), and imbalance (RR 0.68, 95% CI 0.57–0.81). Only one study linking symptoms to definite stroke/TIA diagnosis found that pain and unilateral sensory loss are associated with lower odds of a definite diagnosis in women compared to men. Conclusion: Although women showed a higher prevalence of some nonfocal symptoms, the prevalence of focal neurological symptoms, such as motor weakness and speech deficit, was similar for both sexes. Awareness of sex differences in symptoms in acute stroke evaluation, careful consideration of the full constellation of presenting symptoms, and further studies linking symptoms to diagnostic outcomes can be helpful in improving early diagnosis and management in both sexes.
Identification of multimodal brain imaging association via a parameter decomposition based sparse multi-view canonical correlation analysis method
Authors: Zhang Jin , Wang Huiai , Zhao Ying , Guo Lei , Du Lei ,   Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

AbstractBackgroundWith the development of noninvasive imaging technology, collecting different imaging measurements of the same brain has become more and more easy. These multimodal imaging data carry complementary information of the same brain, with both specific and shared information being intertwined. Within these multimodal data, it is essential to discriminate the specific information from the shared information since it is of benefit to comprehensively characterize brain diseases. While most existing methods are unqualified, in this paper, we propose a parameter decomposition based sparse multi-view canonical correlation analysis (PDSMCCA) method. PDSMCCA could identify both modality-shared and -specific information of multimodal data, leading to an in-depth understanding of complex pathology of brain disease.ResultsCompared with the SMCCA method, our method obtains higher correlation coefficients and better canonical weights on both synthetic data and real neuroimaging data. This indicates that, coupled with modality-shared and -specific feature selection, PDSMCCA improves the multi-view association identification and shows meaningful feature selection capability with desirable interpretation.ConclusionsThe novel PDSMCCA confirms that the parameter decomposition is a suitable strategy to identify both modality-shared and -specific imaging features. The multimodal association and the diverse information of multimodal imaging data enable us to better understand the brain disease such as Alzheimer’s disease.
Elevated N-terminal pro C-type natriuretic peptide is associated with mortality in patients undergoing transcatheter aortic valve replacement
Authors: Hu Po , Chen Han , Wang Li-Han , Jiang Ju-Bo , Li Jia-Min , Tang Meng-Yao , Guo Yu-Chao , Zhu Qi-Feng , Pu Zhao-Xia , Lin Xin-Ping , Ng Stella , Liu Xian-Bao , Wang Jian-An 
Published: April 2022

Abstract
Background
Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR).

Methods
A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1–4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis.

Results
A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05–1.12, P < 0.001). Elevated NT-proCNP was associated with a higher risk of cardiovascular mortality (HR 1.02, 95% CI 1.00–1.03, P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00–1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) < 50% [(Area under the curve (AUC)-values of 0.79 (0.69; 0.87) vs. 0.59 (0.48; 0.69), P = 0.0453].

Conclusions
NT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF < 50%.
Trial registration NCT02803294, 16/06/2016.
Semantic clustering analysis of E3-ubiquitin ligases in gastrointestinal tract defines genes ontology clusters with tissue expression patterns
Authors: Iatsiuk Veronika , Malinka Frantisek , Pickova Marketa , Tureckova Jolana , Klema Jiri , Spoutil Frantisek , Novosadova Vendula , Prochazka Jan , Sedlacek Radislav 
Published: April 2022

Abstract
Background
Ubiquitin ligases (Ub-ligases) are essential intracellular enzymes responsible for the regulation of proteome homeostasis, signaling pathway crosstalk, cell differentiation and stress responses. Individual Ub-ligases exhibit their unique functions based on the nature of their substrates. They create a complex regulatory network with alternative and feedback pathways to maintain cell homeostasis, being thus important players in many physiological and pathological conditions. However, the functional classification of Ub-ligases needs to be revised and extended.

Methods
In the current study, we used a novel semantic biclustering technique for expression profiling of Ub-ligases and ubiquitination-related genes in the murine gastrointestinal tract (GIT). We accommodated a general framework of the algorithm for finding tissue-specific gene expression clusters in GIT. In order to test identified clusters in a biological system, we used a model of epithelial regeneration. For this purpose, a dextran sulfate sodium (DSS) mouse model, following with in situ hybridization, was used to expose genes with possible compensatory features. To determine cell-type specific distribution of Ub-ligases and ubiquitination-related genes, principal component analysis (PCA) and Uniform Manifold Approximation and Projection technique (UMAP) were used to analyze the Tabula Muris scRNA-seq data of murine colon followed by comparison with our clustering results.

Results
Our established clustering protocol, that incorporates the semantic biclustering algorithm, demonstrated the potential to reveal interesting expression patterns. In this manner, we statistically defined gene clusters consisting of the same genes involved in distinct regulatory pathways vs distinct genes playing roles in functionally similar signaling pathways. This allowed us to uncover the potentially redundant features of GIT-specific Ub-ligases and ubiquitination-related genes. Testing the statistically obtained results on the mouse model showed that genes clustered to the same ontology group simultaneously alter their expression pattern after induced epithelial damage, illustrating their complementary role during tissue regeneration.

Conclusions
An optimized semantic clustering protocol demonstrates the potential to reveal a readable and unique pattern in the expression profiling of GIT-specific Ub-ligases, exposing ontologically relevant gene clusters with potentially redundant features. This extends our knowledge of ontological relationships among Ub-ligases and ubiquitination-related genes, providing an alternative and more functional gene classification. In a similar way, semantic cluster analysis could be used for studding of other enzyme families, tissues and systems.
Ipsilesional arm training in severe stroke to improve functional independence (IPSI): phase II protocol
Authors: Maenza Candice , Sainburg Robert L. , Varghese Rini , Dexheimer Brooke , Demers Marika , Bishop Lauri , Jayasinghe Shanie A. L. , Wagstaff David A. , Winstein Carolee ,   For the IPSI Investigative Team
Published: April 2022

AbstractBackgroundWe previously characterized hemisphere-specific motor control deficits in the ipsilesional, less-impaired arm of unilaterally lesioned stroke survivors. Our preliminary data indicate these deficits are substantial and functionally limiting in patients with severe paresis.MethodsWe have designed an intervention (“IPSI”) to remediate the hemisphere-specific deficits in the ipsilesional arm, using a virtual-reality platform, followed by manipulation training with a variety of real objects, designed to facilitate generalization and transfer to functional behaviors encountered in the natural environment. This is a 2-site (primary site – Penn State College of Medicine, secondary site – University of Southern California), two-group randomized intervention with an experimental group, which receives unilateral training of the ipsilesional arm throughout 3 one-hour sessions per week for 5 weeks, through our Virtual Reality and Manipulation Training (VRMT) protocol. Our control group receives a conventional intervention on the contralesional arm, 3 one-hour sessions per week for 5 weeks, guided by recently released practice guidelines for upper limb rehabilitation in adult stroke. The study aims to include a total of 120 stroke survivors (60 per group) whose stroke was in the territory of the middle cerebral artery (MCA) resulting in severe upper-extremity motor impairments. Outcome measures (Primary: Jebsen-Taylor Hand Function Test, Fugl-Meyer Assessment, Abilhand, Barthel Index) are assessed at five evaluation points: Baseline 1, Baseline 2, immediate post-intervention (primary endpoint), and 3-weeks (short-term retention) and 6-months post-intervention (long-term retention). We hypothesize that both groups will improve performance of the targeted arm, but that the ipsilesional arm remediation group will show greater improvements in functional independence.DiscussionThe results of this study are expected to inform upper limb evaluation and treatment to consider ipsilesional arm function, as part of a comprehensive physical rehabilitation strategy that includes evaluation and remediation of both arms.Trial RegistrationThis study is registered with ClinicalTrials.gov (Registration ID:NCT03634397; date of registration: 08/16/2018).
Identification of a key glioblastoma candidate gene, FUBP3, based on weighted gene co-expression network analysis
Authors: Li Jianmin , Zhang Zhao , Guo Ke , Wu Shuhua , Guo Chong , Zhang Xinfan , Wang Zi 
Published: April 2022

Abstract
Background
Glioblastoma multiforme (GBM) is the most common aggressive malignant brain tumor. However, the molecular mechanism of glioblastoma formation is still poorly understood. To identify candidate genes that may be connected to glioma growth and development, weighted gene co-expression network analysis (WGCNA) was performed to construct a gene co-expression network between gene sets and clinical characteristics. We also explored the function of the key candidate gene.

Methods
Two GBM datasets were selected from GEO Datasets. The R language was used to identify differentially expressed genes. WGCNA was performed to construct a gene co-expression network in the GEO glioblastoma samples. A custom Venn diagram website was used to find the intersecting genes. The GEPIA website was applied for survival analysis to determine the significant gene, FUBP3. OS, DSS, and PFI analyses, based on the UCSC Cancer Genomics Browser, were performed to verify the significance of FUBP3. Immunohistochemistry was performed to evaluate the expression of FUBP3 in glioblastoma and adjacent normal tissue. KEGG and GO enrichment analyses were used to reveal possible functions of FUBP3. Microenvironment analysis was used to explore the relationship between FUBP3 and immune infiltration. Immunohistochemistry was performed to verify the results of the microenvironment analysis.

Results
GSE70231 and GSE108474 were selected from GEO Datasets, then 715 and 694 differentially expressed genes (DEGs) from GSE70231 and GSE108474, respectively, were identified. We then performed weighted gene co-expression network analysis (WGCNA) and identified the most downregulated gene modules of GSE70231 and GSE108474, and 659 and 3915 module genes from GSE70231 and GSE108474, respectively, were selected. Five intersection genes (FUBP3, DAD1, CLIC1, ABR, and DNM1) were calculated by Venn diagram. FUBP3 was then identified as the only significant gene by survival analysis using the GEPIA website. OS, DSS, and PFI analyses verified the significance of FUBP3. Immunohistochemical analysis revealed FUBP3 expression in GBM and adjacent normal tissue. KEGG and GO analyses uncovered the possible function of FUBP3 in GBM. Tumor microenvironment analysis showed that FUBP3 may be connected to immune infiltration, and immunohistochemistry identified a positive correlation between immune cells (CD4 + T cells, CD8 + T cells, and macrophages) and FUBP3.

Conclusion
FUBP3 is associated with immune surveillance in GBM, indicating that it has a great impact on GBM development and progression. Therefore, interventions involving FUBP3 and its regulatory pathway may be a new approach for GBM treatment.