bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics analysis of tumor angiogenesis characteristics and potential epigenetic regulation mechanisms in renal clear cell carcinoma
Authors: Zheng Wenzhong , Zhang Shiqiang , Guo Huan , Chen Xiaobao , Huang Zhangcheng , Jiang Shaoqin , Li Mengqiang 
Published: March 2021

Abstract
Background
Tumor angiogenesis, an essential process for cancer proliferation and metastasis, has a critical role in prognostic of kidney renal clear cell carcinoma (KIRC), as well as a target in guiding treatment with antiangiogenic agents. However, tumor angiogenesis subtypes and potential epigenetic regulation mechanisms in KIRC patient remains poorly characterized. System evaluation of angiogenesis subtypes in KIRC patient might help to reveal the mechanisms of KIRC and develop more target treatments for patients.

Method
Ten independent tumor angiogenesis signatures were obtained from molecular signatures database (MSigDB) and gene set variation analysis was performed to calculate the angiogenesis score in silico using the Cancer Genome Atlas (TCGA) KIRC dataset. Tumor angiogenesis subtypes in 539 TCGA-KIRC patients were identified using consensus clustering analysis. The potential regulation mechanisms was studied using gene mutation, copy number variation, and differential methylation analysis (DMA). The master transcription factors (MTF) that cause the difference in tumor angiogenesis signals were completed by transcription factor enrichment analysis.

Results
The angiogenesis score of a prognosis related angiogenesis signature including 189 genes was significantly correlated with immune score, stroma score, hypoxia score, and vascular endothelial growth factor (VEGF) signal score in 539 TCGA KIRC patients. MMRN2, CLEC14A, ACVRL1, EFNB2, and TEK in candidate gene set showed highest correlation coefficient with angiogenesis score in TCGA-KIRC patients. In addition, all of them were associated with overall survival in both TCGA-KIRC and E-MTAB-1980 KIRC data. Clustering analysis based on 183 genes in angiogenesis signature identified two prognosis related angiogenesis subtypes in TCGA KIRC patients. Two clusters also showed different angiogenesis score, immune score, stroma score, hypoxia score, VEGF signal score, and microenvironment score. DMA identified 59,654 differential methylation sites between two clusters and part of these sites were correlated with tumor angiogenesis genes including CDH13, COL4A3, and RHOB. In addition, RFX2, SOX13, and THRA were identified as top three MTF in regulating angiogenesis signature in KIRC patients.

Conclusion
Our study indicate that evaluation the angiogenesis subtypes of KIRC based on angiogenesis signature with 183 genes and potential epigenetic mechanisms may help to develop more target treatments for KIRC patients.
3D computational anatomy of the scaphoid and its waist for use in fracture treatment
Authors: Ahrend Marc-Daniel , Teunis Teun , Noser Hansrudi , Schmidutz Florian , Richards Geoff , Gueorguiev Boyko , Kamer Lukas 
Published: March 2021

Abstract
Background
A detailed understanding of scaphoid anatomy helps anatomic fracture reduction, and optimal screw position. Therefore, we analysed (1) the size and shape variations of the cartilage and osseous surface, (2) the distribution of volumetric bone mineral density (vBMD) and (3) if the vBMD values differ between a peripheral and a central screw pathway?

Methods
Forty-three fresh frozen hand specimens (17 females, 26 males) were analysed with high-resolution peripheral quantitative computed tomography (HR-pQCT) and dissected to compute a 3D-statistical osseous and cartilage surface model and a 3D-averaged vBMD model of the scaphoid. 3D patterns were analysed using principal component analysis (PCA). vBMD was analysed via averaging HR-pQCT grey values and virtual bone probing along a central and peripheral pathway.

Results
(1) PCA displayed most notable variation in length ranging from 1.7 cm (− 2SD) to 2.6 cm (mean) and 3.7 cm (+ 2SD) associated with differences of the width and configuration of the dorsal surface (curved and narrow (4 mm) to a wider width (9 mm)). (2) High vBMD was located in the peripheral zone. Lowest vBMD was observed in the centre and waist. (3) Virtual probing along a peripheral pathway near to the cartilage surfaces for the capitate and lunate allowed the center region to be bypassed, resulting in increased vBMD compared to a central pathway.

Conclusion
High anatomical variations regarding the osseous and cartilage surfaces were associated with three distinct concentrically arranged zones with notable different vBMD. The complex scaphoid anatomy with its waist might alter the strategy of fracture fixation, education and research.
Predicting osteoporosis with body compositions in postmenopausal women: a non-invasive method
Authors: Hsu Wei-Hsiu , Hsu Wei-Bin , Fan Chun-Hao , Hsu Robert Wen-Wei 
Published: March 2021

Abstract
Background
The prevalence of osteoporosis is rising steadily as the aging population increases. Bone mineral density (BMD) assessment is a golden standard to establish the diagnosis of osteoporosis. However, the accessibility and radiation exposure limited its role in community screening. A more convenient approach for screening is suggested.

Methods
A total of 363 postmenopausal women over the age of 50 were included in this study and assessed with the body composition [including fat-free mass (FFM), fat mass (FM), and basal metabolic rate (BMR)] and BMD. Normal distributions and correlation coefficients among variables were calculated using the Shapiro-Wilk test and Pearson’s correlation analysis, respectively. A receiver operating characteristic (ROC) curve was plotted, and the area under ROC curves (AUC) was determined to obtain the optimal cutoff values of the body composition variables for osteoporosis prediction.

Results
The correlation coefficient of FFM, FM, FM ratio, and BMR with femur neck T-score was 0.373, 0.266, 0.165, and 0.369, respectively, while with spine T-score was 0.350, 0.251, 0.166, and 0.352, respectively (p < 0.01 for all). FFM, FM, and BMR showed an optimal cutoff value of 37.9 kg, 18.6 kg, and 1187.5 kcal, respectively, for detecting osteoporosis.

Conclusions
The present study provided a model to predict osteoporosis in postmenopausal women, and the optimal cutoff value of FFM, FM, and BMR could be calculated in the Asian population. Among these factors, BMR seemed a better predictor than others. The BMR could be a target for exercise intervention in postmenopausal women for maintaining or improving BMD.

Trial registration
ClinicalTrials.gov, NCT02936336. Retrospectively registered on13 October 2016.
Simultaneous or staged operation for tandem spinal stenosis: surgical strategy and efficacy comparison
Authors: Cao Junming , Gao Xianda , Yang Yipeng , Lei Tao , Shen Yong , Wang Linfeng , Tian Zheng 
Published: March 2021

Abstract
Background
Tandem spinal stenosis (TSS) has a complex clinical presentation, and there is no consensus on the optimal surgical strategy. This study retrospectively compared the efficacy of different staged operations and simultaneous decompression for patients with TSS.

Methods
We reviewed data from 132 patients with TSS who received surgical procedures from January 2011 to June 2018. Patients were classified into three groups according to the most symptomatic area of compression (group C: first-stage surgery for cervical compression; group L: first-stage surgery for lumbar compression; group CL: simultaneous surgery for both). Medical records were reviewed for age, gender, comorbidities, operation time, combined estimated blood loss, and time of hospitalization. The JOA-C, JOA-L, NDI, and ODI scores, and complications were also examined.

Results
Postoperative outcomes were followed for 32.1 ± 5.4 months. There were significant differences in the re-operation rate and the interval time between the two types of staged operations (p = 0.005 and p = 0.001, respectively). There were no significant differences in gender (p = 0.639), operation time (p = 0.138), combined estimated blood loss (p = 0.116), or complications (p = 0.652) among the three groups, while the simultaneous group was significantly younger (p = 0.027), with fewer comorbidities (p < 0.001) and a shorter hospitalization time (p < 0.001). At the final follow-up, the JOA-C and JOA-L scores were increased, while the NDI and ODI scores were decreased, compared with the preoperative scores.

Conclusions
TSS can be effectively managed by either simultaneous or staged decompressions. First-stage surgery for cervical stenosis significantly lowers the requirement for second-stage lumbar surgery. One-stage simultaneous decompression is safe and effective with the advantage of reduce hospitalization time, without an increase in operative time or bleeding. However, the surgical indications should be strictly controlled and is recommended for younger patients with fewer comorbidities.
Observation of the natural course of type 3 spinal muscular atrophy: data from the polish registry of spinal muscular atrophy
Authors: Lusakowska Anna , Jedrzejowska Maria , Kaminska Anna , Janiszewska Katarzyna , Grochowski Przemysław , Zimowski Janusz , Sierdzinski Janusz , Kostera-Pruszczyk Anna 
Published: March 2021

Abstract
Background
Spinal muscular atrophy (SMA) is one of the most frequent and severe genetic diseases leading to premature death or severe motor disability. New therapies have been developed in recent years that change the natural history of the disease. The aim of this study is to describe patients included in the Polish Registry of SMA, with a focus on the course of type 3 SMA (SMA3) before the availability of disease-modifying treatments.

Results
790 patients with SMA were included in the registry (173 with type 1 [SMA1], 218 with type 2 [SMA2], 393 with SMA3, and six with type 4 SMA [SMA4]), most (52%) of whom were adults. Data on SMN2 gene copy number were available for 672 (85%) patients. The mean age of onset was 5 months for SMA1, 11.5 months for SMA2, and 4.5 years for SMA3. In patients with SMA3, the first symptoms occurred earlier in those with three copies of SMN2 than in those with four copies of SMN2 (3.2 years vs. 6.7 years). The age of onset of SMA3 was younger in girls than in boys (3.1 years vs. 5.7 years), with no new cases observed in women older than 16 years. Male patients outnumbered female patients, especially among patients with SMA3b (49 female vs. 85 male patients) and among patients with SMA3 with four copies of SMN2 (30 female vs. 69 male patients). 44% of patients with SMA3 were still able to walk; in those who were not still able to walk, the mean age of immobilization was 14.0 years. Patients with SMA3a (age of onset < 3 years) and three copies of SMN2 had significantly worse prognosis for remaining ambulant than patients with SMA3b (age of onset ≥ 3 years) and four copies of SMN2.

Conclusions
The Registry of SMA is an effective tool for assessing the disease course in the real world setting. SMN2 copy number is an important prognostic factor for the age of onset and ambulation in SMA3. Sex and age of disease onset also strongly affect the course of SMA. Data supplied by this study can aid treatment decisions.
Attenuated TGFB signalling in macrophages decreases susceptibility to DMBA-induced mammary cancer in mice
Authors: Sun Xuan , Bernhardt Sarah M. , Glynn Danielle J. , Hodson Leigh J. , Woolford Lucy , Evdokiou Andreas , Yan Cong , Du Hong , Robertson Sarah A. , Ingman Wendy V. 
Published: March 2021

AbstractBackgroundTransforming growth factor beta1 (TGFB1) is a multi-functional cytokine that regulates mammary gland development and cancer progression through endocrine, paracrine and autocrine mechanisms. TGFB1 also plays roles in tumour development and progression, and its increased expression is associated with an increased breast cancer risk. Macrophages are key target cells for TGFB1 action, also playing crucial roles in tumourigenesis. However, the precise role of TGFB-regulated macrophages in the mammary gland is unclear. This study investigated the effect of attenuated TGFB signalling in macrophages on mammary gland development and mammary cancer susceptibility in mice.MethodsA transgenic mouse model was generated, wherein a dominant negative TGFB receptor is activated in macrophages, in turn attenuating the TGFB signalling pathway specifically in the macrophage population. The mammary glands were assessed for morphological changes through wholemount and H&E analysis, and the abundance and phenotype of macrophages were analysed through immunohistochemistry. Another cohort of mice received carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), and tumour development was monitored weekly. Human non-neoplastic breast tissue was also immunohistochemically assessed for latent TGFB1 and macrophage marker CD68.ResultsAttenuation of TGFB signalling resulted in an increase in the percentage of alveolar epithelium in the mammary gland at dioestrus and an increase in macrophage abundance. The phenotype of macrophages was also altered, with inflammatory macrophage markers iNOS and CCR7 increased by 110% and 40%, respectively. A significant decrease in DMBA-induced mammary tumour incidence and prolonged tumour-free survival in mice with attenuated TGFB signalling were observed. In human non-neoplastic breast tissue, there was a significant inverse relationship between latent TGFB1 protein and CD68-positive macrophages.ConclusionsTGFB acts on macrophage populations in the mammary gland to reduce their abundance and dampen the inflammatory phenotype. TGFB signalling in macrophages increases mammary cancer susceptibility potentially through suppression of immune surveillance activities of macrophages.
The time is now: role of pragmatic clinical trials in guiding response to global pandemics
Authors: Almufleh Aws , Joseph Jacob 
Published: March 2021

AbstractAlong with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research response. The slow and inefficient process of carrying out traditional randomized clinical trials led regulatory authorities to hastily approve treatments and tests without sufficient evidence of safety and efficacy.We here outline issues with the current research platform, summarize shortcomings of traditional randomized clinical trials particularly apparent at the time of pandemics, and highlight the advantages of pragmatic clinical trials as an alternative to rapidly generate the needed clinical evidence. We further discuss barriers and challenges to pragmatic clinical trials implementation and explore opportunities for research institutions and regulatory authorities to facilitate widespread adoption of this vital research tool.As a subsequent wave of COVID-19, and/or another epidemic, are all but inevitable in our lifetime, we must ensure that our research infrastructure is conducive to carrying out pragmatic clinical trials to expeditiously generate the needed evidence and blunt the epidemic’s toll on human lives and livelihoods.
Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors
Authors: Li Chen , Wang Yan , Gong Yueqing , Zhang Tengrui , Huang Jiaqi , Tan Zhen , Xue Lixiang 
Published: March 2021

AbstractEnhancer of zeste homolog 2 inhibitors (EZH2i) have garnered increased attention owing to their anticancer activity by targeting EZH2, a well-known cancer-promoting factor. However, some lymphomas are resistant to EZH2i, and EZH2i treatment alone is ineffective in case of EZH2-overexpressing solid tumors. The anti-cancer efficacy of EZH2i may be improved through safe and effective combinations of these drugs with other treatment modalities. Preclinical evidence indicates that combining EZH2i with other therapies, such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy, has complementary or synergistic antitumor effects. Therefore, elucidating the underlying mechanisms of the individual constituents of the combination therapies is fundamental for their clinical application. In this review, we have summarized notable clinical trials and preclinical studies using EZH2i, their progress, and combinations of EZH2i with different therapeutic modalities, aiming to provide new insights for tumor treatment.
Transplantation of human amniotic epithelial cells promotes morphological and functional regeneration in a rat uterine scar model
Authors: Fan Yihui , Sun Junyan , Zhang Qiuwan , Lai Dongmei 
Published: March 2021

Abstract
Background
Cesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. Human amniotic epithelial cells (hAECs) have shown great promise in tissue regeneration. This study aims to investigate whether hAEC transplantation has the therapeutic effects on the rat uterine scar following full-thickness injury.

Methods
A rat uterine scar model was established by excising the full-thickness uterine wall of about 1.0 cm in length and 1/2–2/3 of the total circumference in width. At day 30 post-surgery, hAECs were transplanted into the uterine scar. At day 30 and 60 post-transplantation, hematoxylin and eosin (H&E) staining, Masson staining, and IHC staining for vWF, VEGFA, α-SMA, and MMP-8 were performed to evaluate the regeneration of the scarred uterus and the underlying mechanism. Pregnancy outcomes were assessed at day 60 after hAEC transplantation. Finally, hAECs were incubated with hydrogen peroxide to verify the paracrine effect of hAECs.

Results
Collagen deposition, thin myometrium, and injured endometrium were observed in the rat uterine scar model. After hAEC transplantation, collagen deposition in the uterine scar decreased, and myometrial and endometrial recovery was facilitated. hAEC transplantation also increased the fetus number implanted within the scarred area. Moreover, we found hAECs promoted angiogenesis via upregulation of VEGFA and decreased collagen deposition by upregulating MMP-8 in the uterine scar. The in vitro studies further demonstrated an increase in the expression level of MMP-8 in hAECs cultured with hydrogen peroxide.

Conclusions
These results suggested that hAEC transplantation may be efficacious in the functional repair and collagen degradation of uterine scars, which provides a new therapeutic strategy to CSD.
The combination of G-CSF and AMD3100 mobilizes bone marrow-derived stem cells to protect against cisplatin-induced acute kidney injury in mice
Authors: Chen Zhi , Ren Xiang , Ren Ruimin , Wang Yonghong , Shang Jiwen 
Published: March 2021

Abstract
Background
Several studies have confirmed that mobilizing bone marrow-derived stem cells (BMSCs) ameliorates renal function loss following cisplatin-induced acute kidney injury (AKI). The aim of this study was to explore whether the combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor (AMD3100) exerts beneficial effects on renal function recovery in a model of cisplatin-induced nephrotoxicity.

Methods
C57BL/6J mice received intraperitoneal injections of G-CSF (200 μg/kg/day) for 5 consecutive days. On the day of the last injection, the mice received a single subcutaneous dose of AMD3100 (5 mg/kg) 1 h before cisplatin 20 mg/kg injection. Ninety-six hours after cisplatin injection, the mice were euthanized, and blood and tissue samples were collected to assess renal function and tissue damage. Cell mobilization was assessed by flow cytometry (FCM).

Results
Mice pretreated with G-CSF/AMD3100 exhibited longer survival and lower serum creatinine and blood urea nitrogen (BUN) levels than mice treated with only G-CSF or saline. Combinatorial G-CSF/AMD3100 treatment attenuated tissue injury and cell death, enhanced cell regeneration, and mobilized a higher number of stem cells in the peripheral blood than G-CSF or saline treatment. Furthermore, the mRNA expression of proinflammatory factors was lower, whereas that of anti-inflammatory factors was higher, in the G-CSF/AMD3100 group than in the G-CSF or saline group (all P < 0.05).

Conclusions
These results suggest that combinatorial G-CSF/AMD3100 therapy mobilizes BMSCs to accelerate improvements in renal functions and prevent cisplatin-induced renal tubular injury. This combinatorial therapy may represent a new therapeutic option for the treatment of AKI and should be further investigated in the future.
Does motor deficit in children with cerebral palsy correlate with diffusion tensor metrics abnormalities in thalamocortical pathways?
Authors: Mahanna Amal Mohammed , El-Toukhy Nahed Abd El-Gaber , Mousa Amani Ezzat , Megahed Khaled Fathy , Ashamallah Germeen Albair 
Published: March 2021

Abstract
Background
Cerebral palsy (CP) is a group of motor-impairment signs secondary to many disorders that interfere with early brain development and are usually related to white matter injury in children. Most studies are focused on the study of motor tracts, mainly the corticospinal tract (CST). Diffusion tensor imaging (DTI) is a reliable imaging modality providing an appropriate method of detection of white matter microstructure abnormalities. The purpose of this study is to investigate the relationship between DTI observed motor CST injury, sensory pathways (thalamic radiations) injury, and motor functions.

Results
This study shows significant involvement (reduction in DTI fiber count) of the superior thalamic radiation (in severe cases) with atrophy of the anterior thalamic radiations (ATR) or posterior thalamic radiations (PTR) in most cases with a significant reduction in fractional anisotropy (FA) and elevation in mean diffusivity (MD) values. In addition, the degree of motor affection shows a significant negative correlation with FA and a significant positive correlation with MD values. Diffusion tensor imaging shows a significant reduction in FA within the examined tracts between CP and control at the Rt CST, Lt CST, Rt corticothalamic radiation (CTR), and Lt CTR with significant cutoff values of ≤ 0.449, ≤ 0.472, ≤ 0.432, and ≤ 0.44, respectively.

Conclusions
This study demonstrates disruption of thalamocortical and corticospinal tracts in CP patients, which reflects that both sensory and motor tract affection have a valuable role in the pathophysiology of motor dysfunction in CP patients.