bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of binocular game and patching in treating mild to moderate anisometropic amblyopia: a study protocol for a randomized controlled trial
Authors: Razavi Mohammad Etezad , Najjaran Marzieh , Mohseni Jaber , Aalaei Shokoufeh 
Published: October 2021

Abstract
Background
Amblyopia, as a neurodevelopmental preventable visual disorder, affects approximately 1.1 % in Asia. A binocular approach to treating amblyopia has been recently proposed. Whether the binocular playing game treatment is comparable to patching treatment needs further randomized clinical trials. To address this, the present research, designs, develops, and evaluates a new binocular game to treat amblyopia.

Methods
This study has been designed as a non-inferiority, randomized, two parallel-group, controlled trial. Forty-four patients between 4 and 12 years diagnosed with amblyopia will be randomly assigned to the control and intervention groups. In the intervention group, amblyopia treatment is provided with red-green anaglyphic glasses and a red filter placed in front of the amblyopic eye, along with a game to be played for 30 min twice a day. Those in the control group will receive patch therapy according to amblyopia treatment study protocol. The primary outcome is to change visual acuity in the amblyopic eye from the baseline to 3 months after randomization.

Ethics and dissemination
The Ethics Committee of Mashhad University of Medical sciences’ approval date was February 28, 2018, with a reference code of IR.MUMS.fm.REC.1396.783. Thus far, the recruitment of participants has not been completed and is scheduled to end in September 2021. The results will be disseminated in a peer-reviewed journal.

Trial registration
Iranian Registry of Clinical Trials IRCT20180217038768N1. Registered on 22 April 2019.
Exercise prevents HFD-induced insulin resistance risk: involvement of TNF-α level regulated by vagus nerve-related anti-inflammatory pathway in the spleen
Authors: Huang Zhengxi , Tang Jialing , Ji Kai 
Published: October 2021

Abstract
Objectives
Regular physical exercise can improve insulin resistance in insulin target tissues. However, the mechanisms about the beneficial effect of exercise on insulin resistance are not yet fully resolved. This study was carried out to address whether insulin resistance improvement by exercise is involved in an anti-inflammatory pathway in the spleen in high-fat diet (HFD) feeding mice.

Methods
Male C57Bl/6J mice with or without subdiaphragmatic vagotomy (sVNS) were subjected to medium-intensity treadmill exercise during HFD feeding. Glucose tolerance test and insulin tolerance test were detected, and spleen acetylcholine level, choline acetyltransferase activity (ChAT), protein kinase C (PKC) and tumor necrosis factor-alpha (TNF-α) were assayed.

Results
We found that exercise significantly improves HFD-induced glucose intolerance and insulin resistance, along with an increase in acetylcholine level, ChAT activity, and PKC activity, and decrease in TNF-α level in the system and the spleen from HFD-fed mice. However, sVNS abolished the beneficial effect of exercise on glucose intolerance and insulin resistance, decreased acetylcholine level, ChAT activity, and PKC activity, and increase TNF-α level of the spleen in HFD-mice exercise intervention.

Conclusions
These data reveal that the prevention of HFD-associated insulin resistance by exercise intervention involves reducing splenic TNF-α level, which is mediated by cholinergic anti-inflammatory activity via influencing PKC activity, ChAT activity, and acetylcholine concentration in mice spleen.
Impact of diabetes mellitus developing after kidney transplantation on patient mortality and graft survival: a meta-analysis of adjusted data
Authors: Lin Hailing , Yan Jiqiang , Yuan Lei , Qi Beibei , Zhang Zhujing , Zhang Wanlu , Ma Aihua , Ding Fuwan 
Published: October 2021

Abstract
Background
Post-transplant diabetes mellitus (PTDM) occurs in 10–30% of kidney transplant recipients. However, its impact on mortality and graft survival is still ambiguous. Therefore, the current study aimed to analyze if PTDM increases mortality and graft failure by pooling multivariable-adjusted data from individual studies.

Methods
PubMed, Embase, and CENTRAL, and Google Scholar were searched for studies comparing mortality and graft failure between PTDM and non-diabetic patients. Multivariable-adjusted hazard ratios (HR) were pooled in a random-effects model.

Results
Fourteen retrospective studies comparing 9872 PTDM patients with 65,327 non-diabetics were included. On pooled analysis, we noted a statistically significant increase in the risk of all-cause mortality in patients with PTDM as compared to non-diabetics (HR: 1.67 95% CI 1.43, 1.94 I2 = 57% p < 0.00001). The meta-analysis also indicated a statistically significant increase in the risk of graft failure in patients with PTDM as compared to non-diabetics (HR: 1.35 95% CI 1.15, 1.58 I2 = 78% p = 0.0002). Results were stable on sensitivity analysis. There was no evidence of publication bias on funnel plots.

Conclusion
Kidney transplant patients developing PTDM have a 67% increased risk of all-cause mortality and a 35% increased risk of graft failure. Further studies are needed to determine the exact cause of increased mortality and the mechanism involved in graft failure.
Hepatitis D: challenges in the estimation of true prevalence and laboratory diagnosis
Authors: Chen Lin-Yuan , Pang Xiao-Yu , Goyal Hemant , Yang Rui-Xia , Xu Hua-Guo 
Published: October 2021

AbstractHepatitis delta virus (HDV) is a defective single negative chain RNA virus, as its envelope protein synthesis is dependent on hepatitis B virus (HBV). Studies have consistently shown that coinfection of HBV and HDV is the most serious form of viral hepatitis, with accelerated progression to liver cirrhosis and hepatocellular carcinoma. About 74 million of HBV surface antigen (HBsAg) positive patients worldwide are also co-infected with HDV. Besides, patients with intravenous drug use and high-risk sexual behavior are at higher risk of HDV infection. Therapeutic schedules for HDV are limited, and relapse of HDV has been observed after treatment with pegylated interferon alpha. To reduce the transmission of HDV, all people infected with HBV should be screened for HDV. At present, several serological and molecular detection methods are widely used in the diagnosis of HDV. However, due to the lack of international standards diagnostic results from different laboratories are often not comparable. Therefore, the true prevalence of HDV is still unclear. In this manuscript, we have analyzed various factors influencing the estimation of HDV prevalence. We have also discussed about the advantages and disadvantages of currently available HDV laboratory diagnostic methods, in order to provide some ideas for improving the detection of HDV.
Effect of early cardiac rehabilitation on prognosis in patients with heart failure following acute myocardial infarction
Authors: Cai He , Cao Pengyu , Zhou Wenqian , Sun Wanqing , Zhang Xinying , Li Rongyu , Shao Wangshu , Wang Lin , Zou Lin , Zheng Yang 
Published: October 2021

Abstract
Objective
The purpose of this retrospective study is to evaluate the effectiveness of early cardiac rehabilitation on patients with heart failure following acute myocardial infarction.

Methods
Two hundred and thirty-two patients who developed heart failure following acute myocardial infarction were enrolled in this study. Patients were divided into heart failure with reduced ejection fraction group (n = 54) and heart failure with mid-range ejection fraction group (n = 178). Seventy-eight patients who accepted a two-week cardiac rehabilitation were further divided into two subgroups based on major adverse cardiovascular events. Key cardio-pulmonary exercise testing indicators that may affect the prognosis were identified among the cardiac rehabilitation patients.

Results
Early cardiac rehabilitation significantly reduced cardiac death and re-hospitalization in patients. There was more incidence of diabetes, hyperkalemia and low PETCO2 in the cardiac rehabilitation group who developed re-hospitalization. Low PETCO2 at anaerobic threshold (≤ 33.5 mmHg) was an independent risk factor for re-hospitalization.

Conclusions
Early cardiac rehabilitation reduced major cardiac events in patients with heart failure following acute myocardial infarction. The lower PETCO2 at anaerobic threshold is an independent risk factor for re-hospitalization, and could be used as a evaluating hallmark for early cardiac rehabilitation.
Risk factors for development of nephropathy in patients with a diabetic Charcot foot
Authors: Jansen Rasmus Bo , Holstein Per E. , Jørgensen Bo , Møller Klaus Kirketerp , Svendsen Ole Lander 
Published: October 2021

Abstract
Objective
Charcot foot is a rare complication to neuropathy and can cause severe foot deformities and ulcerations, which often require prolonged antibiotical treatment. The objective of this retrospective study was to investigate whether this treatment is associated to impaired renal function.

Results
In total, 163 patients were included, of whom 105 (64%) had received β-lactam antibiotics for a mean total duration of 13.0 months. There was a significant increase in the urine albumin/creatinine ratio in the group that received antibiotics (p = 0.017), and the use of antibiotics was associated to a subsequent diagnosis of nephropathy (p = 0.01). Patients treated with antibiotics had a 21.9% risk of developing subsequent nephropathy versus 5.2% for patients not treated with antibiotics. We suggest increased awareness on signs of nephropathy in patients with severe Charcot foot.
Gender representation in food and beverage print advertisements found in corner stores around schools in Peru and Guatemala
Authors: Mus Sophia , Rozas Lucila , Barnoya Joaquin , Busse Peter 
Published: October 2021

Abstract
Objective
The objective of this study is to assess gender representation in food and beverage print advertisements.

Results
The study follows a quantitative descriptive approach. Using a content analysis technique, we assessed the gender representation in 200 food and beverage print advertisements found in corner stores located in four areas around schools in Lima, Peru, and Guatemala City, Guatemala (100 advertisements per country). A total of 36% of the print advertisements exhibited a male main character for the case of Guatemala, while in Peru 14% of the print advertisements presented a male main character. Furthermore, in Guatemala, 22% of the main characters were male animated characters. Moreover, 27% of the print advertisements in Guatemala and 17%, in Peru were visually male-oriented. Overall, male characters appeared alongside sports references and in varied settings, whereas female characters were usually holding or consuming the product. In conclusion, although the majority of variables used to assess the representation of gender in food and beverage print advertisements were gender-neutral, those showing gender representation were mostly male-oriented. Despite its limited findings, the study provides evidence for the formulation of public policies and educational content aimed to protect children’s and adolescents’ health from the effects of food marketing.
Imaging of congenital lung diseases presenting in the adulthood: a pictorial review
Authors: Durhan Gamze , Ardali Duzgun Selin , Akpınar Meltem Gülsün , Demirkazık Figen , Arıyürek Orhan Macit 
Published: October 2021

AbstractCongenital lung diseases in adults are rare diseases that can present with symptoms or be detected incidentally. Familiarity with the imaging features of different types of congenital lung diseases helps both in correct diagnosis and management of these diseases. Congenital lung diseases in adults are classified into three main categories as bronchopulmonary anomalies, vascular anomalies, and combined bronchopulmonary and vascular anomalies. Contrast-enhanced computed tomography, especially 3D reconstructions, CT, or MR angiography, can show vascular anomalies in detail. The tracheobronchial tree, parenchymal changes, and possible complications can also be defined on chest CT, and new applications such as quantitative 3D reconstruction CT images, dual-energy CT (DECT) can be helpful in imaging parenchymal changes. In addition to the morphological assessment of the lungs, novel MRI techniques such as ultra-short echo time (UTE), arterial spin labeling (ASL), and phase-resolved functional lung (PREFUL) can provide functional information. This pictorial review aims to comprehensively define the radiological characteristics of each congenital lung disease in adults and to highlight differential diagnoses and possible complications of these diseases.
Decoding intra-tumoral spatial heterogeneity on radiological images using the Hilbert curve
Authors: Wang Lu , Xu Nan , Song Jiangdian 
Published: October 2021

AbstractBackgroundCurrent intra-tumoral heterogeneous feature extraction in radiology is limited to the use of a single slice or the region of interest within a few context-associated slices, and the decoding of intra-tumoral spatial heterogeneity using whole tumor samples is rare. We aim to propose a mathematical model of space-filling curve-based spatial correspondence mapping to interpret intra-tumoral spatial locality and heterogeneity.MethodsA Hilbert curve-based approach was employed to decode and visualize intra-tumoral spatial heterogeneity by expanding the tumor volume to a two-dimensional (2D) matrix in voxels while preserving the spatial locality of the neighboring voxels. The proposed method was validated using three-dimensional (3D) volumes constructed from lung nodules from the LIDC-IDRI dataset, regular axial plane images, and 3D blocks.ResultsDimensionality reduction of the Hilbert volume with a single regular axial plane image showed a sparse and scattered pixel distribution on the corresponding 2D matrix. However, for 3D blocks and lung tumor inside the volume, the dimensionality reduction to the 2D matrix indicated regular and concentrated squares and rectangles. For classification into benign and malignant masses using lung nodules from the LIDC-IDRI dataset, the Inception-V4 indicated that the Hilbert matrix images improved accuracy (85.54% vs. 73.22%,p < 0.001) compared to the original CT images of the test dataset.ConclusionsOur study indicates that Hilbert curve-based spatial correspondence mapping is promising for decoding intra-tumoral spatial heterogeneity of partial or whole tumor samples on radiological images. This spatial-locality-preserving approach for voxel expansion enables existing radiomics and convolution neural networks to filter structured and spatially correlated high-dimensional intra-tumoral heterogeneity.
Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review
Authors: Smeringaiova Ingrida , Utheim Tor Paaske , Jirsova Katerina 
Published: October 2021

AbstractThe corneal endothelium plays a key role in maintaining corneal transparency. Its dysfunction is currently treated with penetrating or lamellar keratoplasty. Advanced cell therapy methods seek to address the persistent global deficiency of donor corneas by enabling the renewal of the endothelial monolayer with tissue-engineered grafts. This review provides an overview of recently published literature on the preparation of endothelial grafts for transplantation derived from cadaveric corneas that have developed over the last decade (2010–2021). Factors such as the most suitable donor parameters, culture substrates and media, endothelial graft storage conditions, and transplantation methods are discussed. Despite efforts to utilize alternative cellular sources, such as induced pluripotent cells, cadaveric corneas appear to be the best source of cells for graft preparation to date. However, native endothelial cells have a limited natural proliferative capacity, and they often undergo rapid phenotype changes in ex vivo culture. This is the main reason why no culture protocol for a clinical-grade endothelial graft prepared from cadaveric corneas has been standardized so far. Currently, the most established ex vivo culture protocol involves the peel-and-digest method of cell isolation and cell culture by the dual media method, including the repeated alternation of high and low mitogenic conditions. Culture media are enriched by additional substances, such as signaling pathway (Rho-associated protein kinase, TGF-β, etc.) inhibitors, to stimulate proliferation and inhibit unwanted morphological changes, particularly the endothelial-to-mesenchymal transition. To date, this promising approach has led to the development of endothelial grafts for the first in-human clinical trial in Japan. In addition to the lack of a standard culture protocol, endothelial-specific markers are still missing to confirm the endothelial phenotype in a graft ready for clinical use. Because the corneal endothelium appears to comprise phenotypically heterogeneous populations of cells, the genomic and proteomic expression of recently proposed endothelial-specific markers, such as Cadherin-2, CD166, or SLC4A11, must be confirmed by additional studies. The preparation of endothelial grafts is still challenging today, but advances in tissue engineering and surgery over the past decade hold promise for the successful treatment of endothelial dysfunctions in more patients worldwide.
Synergistic stimulation of osteoblast differentiation of rat mesenchymal stem cells by leptin and 25(OH)D3 is mediated by inhibition of chaperone-mediated autophagy
Authors: He Qiting , Qin Ruixi , Glowacki Julie , Zhou Shuanhu , Shi Jie , Wang Shaoyi , Gao Yuan , Cheng Lei 
Published: October 2021

Abstract
Background
Vitamin D is important for the mineralization of bones by stimulating osteoblast differentiation of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs are a target of vitamin D action, and the metabolism of 25(OH)D3 to biologically active 1α,25(OH)2D3 in BMMSCs promotes osteoblastogenesis in an autocrine/paracrine manner. Our previous study with human BMMSCs showed that megalin is required for the 25(OH)D3-DBP complex to enter cells and for 25(OH)D3 to stimulate osteoblast differentiation in BMMSCs. Furthermore, we reported that leptin up-regulates megalin in those cells. Leptin is a known inhibitor of PI3K/AKT-dependent chaperone-mediated autophagy (CMA). In this study, we tested the hypothesis that leptin acts synergistically with 25(OH)D3 to promote osteoblastogenesis in rat BMMSCs by a mechanism that entails inhibition of PI3K/AKT-dependent CMA.

Methods
BMMSCs were isolated from rat bone marrow (4-week-old male SD rats); qRT-PCR and western immunoblots or immunofluorescence were used to evaluate the expression of megalin, ALP, COL1A1, RUNX2, OSX, OSP, and CMA in rBMMSCs. The osteoblast differentiation was evaluated by ALP activity, ALP staining, and calcium deposition. The viability of rBMMSCs was assessed with the CCK-8 kit. Biosynthesis of 1α,25(OH)2D3 was measured by a Rat 1α,25(OH)2D3 ELISA Kit.

Results
The combination of leptin and 25(OH)D3 treatment significantly enhanced osteoblast differentiation as shown by ALP activity, ALP staining, and calcium deposition, the expression of osteogenic genes ALP, COL1A1, RUNX2, OSX, and OSP by qRT-PCR and western immunoblots in rBMMSCs. Leptin enhanced the expression of megalin and synthesis of 1α,25(OH)2D3 in rBMMSCs. Our data showed that leptin inhibited CMA activity of rBMMSCs by activating PI3K/AKT signal pathway; the ability of leptin to enhance 25(OH)D3 promoted osteoblast differentiation of rBMMSCs was weakened by the PI3K/AKT signal pathway inhibitor.

Conclusions
Our data reveal the mechanism by which leptin and 25(OH)D3 promote osteoblast differentiation in rBMMSCs. Leptin promoted the expression of megalin by inhibiting CMA, increased the utilization of 25(OH)D3 by rBMMSCs, and enhanced the ability of 25(OH)D3 to induce osteoblast differentiation of rBMMSCs. PI3K/AKT is at least partially involved in the regulation of CMA. These data indicate the importance of megalin in BMMSCs for vitamin D’s role in skeletal health.
Wharton’s jelly mesenchymal stem cells embedded in PF-127 hydrogel plus sodium ascorbyl phosphate combination promote diabetic wound healing in type 2 diabetic rat
Authors: Jiao Yiren , Chen Xiaolin , Niu Yongxia , Huang Sunxing , Wang Jingwen , Luo Mingxun , Shi Guang , Huang Junjiu 
Published: October 2021

Abstract
Background
Diabetic cutaneous ulcers (DCU) are a complication of diabetes with diabetic foot ulcers being the most common, and the wounds are difficult to heal, increasing the risk of bacterial infection. Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe burns. Wharton’s jelly mesenchymal stem cell (WJMSC) with PF-127 hydrogel and sodium ascorbyl phosphate (SAP) improved skin wound healing in mice. Whether this combination strategy is helpful to diabetic ulcers wound healing remains to be explored.

Methods
Firstly, the WJMSCs embedded in PF-127 and SAP combination were transplanted onto excisional cutaneous wound bed in type 2 diabetic Sprague Dawley (SD) rats. Two weeks after transplantation, the skin tissue was collected for histological and immunohistochemical analysis. Further, overexpressing-EGFP WJMSCs were performed to investigate cell engraftment in the diabetic cutaneous ulcer. The apoptosis of WJMSCs which encapsulated with combination of PF-127 and SAP was detected by TUNEL fluorescence assay and RT-PCR in vitro. And the mitochondrial damage induced by oxidative stress assessed by MitoTracker and CMH2DCFDA fluorescence assay.

Results
In diabetic cutaneous wound rat model, PF-127 plus SAP-encapsulated WJMSCs transplantation promoted diabetic wound healing, indicating improving dermis regeneration and collagen deposition. In diabetic wound healing, less pro-inflammatory M1 macrophages, more anti-inflammatory M2 tissue-healing macrophages, and neovascularization were observed in PF-127 + SAP + WJMSCs group compared with other groups. SAP supplementation alleviated the apoptosis ratio of WJMSCs embedded in the PF-127 in vitro and promoted cell survival in vivo.

Conclusion
PF-127 plus SAP combination facilitates WJMSCs-mediated diabetic wound healing in rat through promoting cell survival, the macrophage transformation, and angiogenesis. Our findings may potentially provide a helpful therapeutic strategy for patients with diabetic cutaneous ulcer.