bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finite element analysis of dual small plate fixation and single plate fixation for treatment of midshaft clavicle fractures
Authors: Zhang Fangxue , Chen Fancheng , Qi Yuhan , Qian Zhi , Ni Shuo , Zhong Zeyuan , Zhang Xu , Li Dejian , Yu Baoqing 
Published: April 2020

Abstract
Background
Midshaft clavicle fractures are one of the most familiar fractures. And, dual small plate fixation has been reported as can minimize hardware-related complications. However, the biomechanical properties of the dual small plate fixation have not yet been thoroughly evaluated. Here, we report the results of a finite element analysis of the biomechanical properties of midshaft clavicle fractures treated with dual small plating and superior and anteroinferior single plate fixation.

Methods
A three-dimensional (3D) finite element model of the midshaft clavicle fractures was created, whose 4-mm transverse fracture gap, having an angle < 30 degree and devoid of overlapping triangles, was simulated between the fractured segments of the middle-shaft of the clavicle. The equivalent von Mises stress and displacement of the model was used as the output measures for analysis.

Results
No significant differences were found between dual plating, superior or anteroinferior single plating in cantilever bending, axial compression, and axial torsion. Dual plating with a smaller plate-screw construct is biomechanically eligible to compare with superior and anteroinferior single plate fixation using larger plate-screw constructs.

Conclusions
This study demonstrated that larger plate-screw constructs for the treatment of simple are placed clavicular fractures; however, weight-bearing and exorbitant shoulder activity should be avoided after the operation. Therefore, dual plating may provide a viable option for fixing midshaft clavicle fractures and, thus, may be preferred for patients who need early activity.
Preoperative low scores of Life Satisfaction Rating predicts poor outcomes after total knee arthroplasty: a prospective observational study
Authors: Liu Kaiyuan , Yang Dong , Zan Pengfei , Fan Aoyuan , Zheng Zhi , Jiang Wenwei , Li Guodong 
Published: April 2020

Abstract
Background
Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient’s current mental state is suitable enough to accept a TKA surgery.

Methods
Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated.

Results
Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA.

Conclusion
Our outcomes can help clinicians evaluate whether a patient’s current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery.
Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the “kidney governing bone” theory
Authors: Yao Baojin , Liu Jia , Zhang Mei , Leng Xiangyang , Zhao Daqing 
Published: April 2020

Abstract
Background
Guzhi Zengsheng Zhitongwan (GZZSZTW) is an effective Chinese medicinal formulation for the treatment of osteoarthritis (OA) designed according to the “kidney governing bone” theory, which has been widely used as a golden guide for treating bone and cartilage diseases in traditional Chinese medicine. The aim of this study was to explore the molecular mechanism underlying its effects on the bone and kidney.

Methods
Preparation and quality control were performed as previously described. Since GZZSZTW is orally administered in the form of pills prepared in boiled water, the Chinese materia medica (CMM) mixture of this formula was extracted with distilled water by a reflux method and was then filtered through a 0.45-μm Hollow Fiber Cartridge (GE Healthcare, USA). The filtrate was freeze-dried by a Heto PowerDry LL3000 Freeze Dryer (Thermo, USA) and stored at − 80 °C. The effects of GZZSZTW on gene expression and regulation of both kidney and bone tissues were investigated using a state-of-the-art RNA-seq technology.

Results
We demonstrated that GZZSZTW could enhance kidney function and suppress bone formation and resorption by modulating the activities of osteoblast and osteoclast, and might subsequently contribute to the inhibition of osteophyte formation during the process of OA. These effects might be achieved by the synergistic interactions of various herbs and their active components in GZZSZTW, which increased the expression levels of functional genes participating in kidney function, regulation, and repair, and then decreased the expression levels of genes involved in bone formation and resorption. Thus, our findings were consistent with the “kidney governing bone” theory, which has been widely used as a guide in clinical practice for thousands of years.

Conclusions
This study has deepened the current knowledge about the molecular effects of GZZSZTW on bone and kidney regulation. Furthermore, this study might be able to provide possible strategies to further prevent and treat joint diseases by using traditional Chinese medicinal formulations following the “kidney governing bone” theory.
The efficacy of hydrogel foams in talc Pleurodesis
Authors: Baxter Joy , Lima Thamires A. , Huneke Richard , Kanach Colin Joseph , Johal Priya , Reimold Emily , Alvarez Nicolas J. , Laub Glenn W. 
Published: April 2020

Abstract
Background
Malignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life. Pleurodesis with talc slurry is a standard treatment option, but clinical failures occur, possible due to poor talc delivery. A novel drug-delivery system was developed that fills the entire thoracic cavity with a liquid foam containing talc. The foam is designed to gel and adhere to the tissue walls at body temperature, to improve talc deposition and efficacy.

Methods
Rheology, foam stability, and ex-vivo coating and bio-adhesion studies were performed on three concentrations of a novel hydrogel talc foam system that was developed to improve delivery of talc to the pleural surfaces. A New Zealand rabbit model of pleurodesis was used to evaluate effectiveness of the foams at inducing adhesion formation and compared to talc slurry. The rabbits were recovered after they had one of the test agents instilled into their pleura, and then sacrificed after 28 days. Pleurodesis was assessed by a blinded pathologist using a standardized pathological scoring system.

Results
All talc foam formulations produced foams that gelled at physiological temperatures and were relatively stable for at least two hours. As the concentration of the formulation increased the gelation temperature decreased and the foam adhesiveness increased. Rabbits that received talc foam had significantly greater adhesion formation than talc slurry (mean score of 2.21 vs. 1.18 (p < 0.05)). Rabbits that received the 20% foam developed the most adhesions.

Conclusions
This study demonstrates that our triblock copolymer hydrogel foam delivery system enhances adhesion formation in an experimental model. This novel approach can have important clinical impact, potentially improving efficacy of existing therapies and reducing the need for more invasive treatments.
The use of cIMT as a predictor of postoperative stroke in patients undergoing surgical repair of acute type a aortic dissection
Authors: Zhang Kai , Qian Si-Chong , Pan Xu-Dong , Dong Song-Bo , Zheng Jun , Liu Hong , Wang Yue-Li , Sun Li-Zhong 
Published: April 2020

Abstract
Background
Acute type A aortic dissection (ATAAD) is a life-threatening condition that requires surgical intervention. Stroke remains an extremely serious adverse outcome that can occur in ATAAD patients undergoing aortic arch repair, leading to higher rates of patient mortality and decreased postoperative quality of life. In the present study, we sought to determine whether carotid intima–media thickness (cIMT) is a reliable predictor of postoperative stroke risk.

Materials and methods
This was a prospective study of 76 patients with ATAAD undergoing aortic arch repair. For all patients, cIMT was determined preoperatively through a Doppler-based method. Incidence of different forms of neurological dysfunction, including temporary neurological dysfunction (TND) and stroke, was monitored in these patients, and the relationship between cIMT and stroke incidence was assessed using a receiver-operating characteristic (ROC) curve. Prognostic variables associated with stroke risk were further identified through univariate and multivariate analyses.

Results
A total of 26/76 (34.2%) patients in the present study suffered from neurological dysfunction, of whom 16 (21.0%) suffered from TND and 10 (13.2%) suffered a stroke. The remaining 50 patients (65.8%) did not suffer from neurological dysfunction. The cIMT values in the stroke, TND, and neurological dysfunction-free patients in this study were 1.12 ± 0.19 (mm), 0.99 ± 0.13 (mm), and 0.87 ± 0.13 (mm), respectively. A total of 4 patients in this cohort died during the study, including 1 in the TND group and 3 in the stroke group. An ROC curve analysis indicated that cIMT could predict stroke with an area under the curve value of 0.844 (95% CI, 0.719–0.969; p < 0.001). A multivariate analysis revealed that cIMT > 0.9 mm was independently associated with stroke risk (p = 0.018).

Conclusion
We found that cIMT can be used to predict postoperative stroke risk in ATAAD patients undergoing aortic arch repair, with a cIMT > 0.9 mm coinciding with increased stroke risk in these patients.

Trial registration
ChiCTR1900022289. Date of registration 4 April 2019 retrospectively registered.
Increased visceral arterial tortuosity in Marfan syndrome
Authors: Ágg Bence , Szilveszter Bálint , Daradics Noémi , Benke Kálmán , Stengl Roland , Kolossváry Márton , Pólos Miklós , Radovits Tamás , Ferdinandy Péter , Merkely Béla , Maurovich-Horvat Pál , Szabolcs Zoltán 
Published: April 2020

AbstractBackgroundClinical evidence suggests that the currently recommended approach to estimate the risk of aortic dissection in Marfan syndrome (MFS) is not reliable enough. Therefore, we investigated the possible role of visceral arterial tortuosity in the risk stratification.Methods and resultsSplenic and renal arteries of 37 MFS patients and 74 age and gender matched control subjects were segmented using CT angiography imaging. To measure tortuosity, distance metric (DM), sum of angles metric (SOAM), inflection count metric (ICM), and the ratio of ICM and SOAM (ICM/SOAM) were calculated. DM of the splenic, right and left renal artery was significantly higher in MFS patients than in controls (2.44 [1.92-2.80] vs. 1.75 [1.57-2.18]p < 0.001; 1.16 [1.10-1.28] vs. 1.11 [1.07-1.15]p = 0.011; 1.40 [1.29-1.70] vs. 1.13 [1.09-1.23]p < 0.001, respectively). A similar tendency for ICM and an opposite tendency for SOAM were observed. ICM/SOAM was significantly higher in the MFS group compared to controls in case of all three arteries (73.35 [62.26-93.63] vs. 50.91 [43.19-65.62]p < 0.001; 26.52 [20.69-30.24] vs. 19.95 [16.47-22.95]p < 0.001; 22.81 [18.64-30.96] vs. 18.38 [15.29-21.46]p < 0.001, respectively). MFS patients who underwent aortic root replacement had increased right and left renal DM and ICM/SOAM compared to MFS patients without surgery.ConclusionTo our knowledge this is the first demonstration of increased arterial tortuosity in MFS on visceral arteries. Visceral arterial tortuosity, dominated by curves of lower frequency but higher amplitude according to the observed opposite tendency between the DM and SOAM metrics, could be a possible new predictor of serious manifestations of MFS.
NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma
Authors: Chen Hui , Deng Yang , Gan Xiaoliang , Li Yonghao , Huang Wenyong , Lu Lin , Wei Lai , Su Lishi , Luo Jiawen , Zou Bin , Hong Yanhua , Cao Yihai , Liu Yizhi , Chi Wei 
Published: April 2020

Abstract
Background
Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death.

Methods
A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma.

Results
Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades.

Conclusions
These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.
Detection of human cytomegalovirus in patients with epithelial ovarian cancer and its impacts on survival
Authors: Yin Min , Chen Aiping , Zhao Fei , Ji Xuechao , Li Chuan , Wang Guangning 
Published: April 2020

AbstractBackgroundThe cause of epithelial ovarian cancer (EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial.ObjectiveTo investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival.MethodsFormalin-fixed paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were analyzed for expression of HCMV immediate early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry.ResultsHCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive HCMV-IE protein expression was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surgery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months,P = 0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034).ConclusionsThis study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.
An Auristatin nanoconjugate targeting CXCR4+ leukemic cells blocks acute myeloid leukemia dissemination
Authors: Pallarès Victor , Unzueta Ugutz , Falgàs Aïda , Sánchez-García Laura , Serna Naroa , Gallardo Alberto , Morris Gordon A. , Alba-Castellón Lorena , Álamo Patricia , Sierra Jorge , Villaverde Antonio , Vázquez Esther , Casanova Isolda , Mangues Ramon 
Published: April 2020

Abstract
Background
Current acute myeloid leukemia (AML) therapy fails to eliminate quiescent leukemic blasts in the bone marrow, leading to about 50% of patient relapse by increasing AML burden in the bone marrow, blood, and extramedullar sites. We developed a protein-based nanoparticle conjugated to the potent antimitotic agent Auristatin E that selectively targets AML blasts because of their CXCR4 receptor overexpression (CXCR4+) as compared to normal cells. The therapeutic rationale is based on the involvement of CXCR4 overexpression in leukemic blast homing and quiescence in the bone marrow, and the association of these leukemic stem cells with minimal residual disease, dissemination, chemotherapy resistance, and lower patient survival.

Methods
Monomethyl Auristatin E (MMAE) was conjugated with the CXCR4 targeted protein nanoparticle T22-GFP-H6 produced in E. coli. Nanoconjugate internalization and in vitro cell viability assays were performed in CXCR4+ AML cell lines to analyze the specific antineoplastic activity through the CXCR4 receptor. In addition, a disseminated AML animal model was used to evaluate the anticancer effect of T22-GFP-H6-Auristatin in immunosuppressed NSG mice (n = 10/group). U of Mann-Whitney test was used to consider if differences were significant between groups.

Results
T22-GFP-H6-Auristatin was capable to internalize and exert antineoplastic effects through the CXCR4 receptor in THP-1 and SKM-1 CXCR4+ AML cell lines. In addition, repeated administration of the T22-GFP-H6-Auristatin nanoconjugate (9 doses daily) achieves a potent antineoplastic activity by internalizing specifically in the leukemic cells (luminescent THP-1) to selectively eliminate them. This leads to reduced involvement of leukemic cells in the bone marrow, peripheral blood, liver, and spleen, while avoiding toxicity in normal tissues in a luminescent disseminated AML mouse model.

Conclusions
A novel nanoconjugate for targeted drug delivery of Auristatin reduces significantly the acute myeloid leukemic cell burden in the bone marrow and blood and blocks its dissemination to extramedullar organs in a CXCR4+ AML model. This selective drug delivery approach validates CXCR4+ AML cells as a target for clinical therapy, not only promising to improve the control of leukemic dissemination but also dramatically reducing the severe toxicity of classical AML therapy.
Exosome-mediated transfer of miR-93-5p from cancer-associated fibroblasts confer radioresistance in colorectal cancer cells by downregulating FOXA1 and upregulating TGFB3
Authors: Chen Xijuan , Liu Junqi , Zhang Qinglan , Liu Baoxing , Cheng Yan , Zhang Yonglei , Sun Yanan , Ge Hong , Liu Yingqiang 
Published: April 2020

Abstract
Background
Cancer-associated fibroblasts (CAFs) have been intensively studied in recent studies with aims of finding more concrete evidence on their mechanism of involvement in tumor progression, which is currently unknown. CAFs can secrete exosomes which are loaded with proteins, lipids and RNAs, all of which affect tumor microenvironment. The present study identified microRNA-93-5p (miR-93-5p) as a novel exosomal cargo responsible for the pro-tumorigenic effects of CAFs on colorectal cancer (CRC).

Methods
CAFs and normal fibroblasts (NFs) were isolated from cancerous tissues and matched with paracancerous tissues that had been surgically resected from CRC patients. The interaction among miR-93-5p, forkhead box A1 (FOXA1) and TGFB3 was identified through ChIP and dual luciferase reporter assays. The proliferation and apoptosis of SW480 cells co-cultured with CAFs-derived exosomes under irradiation were evaluated by CCK-8, colony formation, and flow cytometric assays. Tumorigenesis of SW480 cells in nude mice was assessed under the irradiation.

Results
FOXA1 was found to be associated with reduced radioresistance in CRC cells and was verified as a target of miR-93-5p. CAFs-derived exosomes contained higher miR-93-5p than those from NFs, which augmented SW480 cell proliferation and rescued them from radiation-induced apoptosis. miR-93-5p was identified as a mediator of the exosomal effects of CAFs on SW480 cells, possibly through downregulating FOXA1 and upregulating TGFB3. FOXA1 could bind to the promoter of TGFB3, thereby inhibiting nuclear accumulation of TGFB3. Also, CAFs-derived exosomes containing miR-93-5p increased the tumor growth of SW480 cells in irradiated nude mice.

Conclusion
The present study identifies miR-93-5p as a specific exosomal cargo that rescues CRC cells against radiation-induced apoptosis.
Distinct gene expression profiles associated with clinical outcomes in patients with ovarian clear cell carcinoma and high-grade serous ovarian carcinoma
Authors: Zhou Huimei , Liu Qian , Shi Xiaohua , Liu Yue , Cao Dongyan , Yang Jiaxin 
Published: April 2020

Abstract
Background
Ovarian clear cell carcinoma (OCCC) is the second most common ovarian cancer after serous carcinoma in Southeast Asia. OCCC has a more unfavourable clinical outcome due to a poor response to platinum-based chemotherapy compared with serous carcinoma. The identification of biomarkers related to the prognosis of OCCC is critically important for an improved understanding of the biology that drives OCCC progression and leads to poor outcomes. To detect differences in gene expression profiles between OCCC and high-grade serous ovarian carcinoma (HGSOC), twelve patients with OCCC and twelve patients with HGSOC were recruited in whom the pathological diagnosis was confirmed on surgically resected specimens.

Results
Compared with HGSOC, OCCC has 609 differentially expression genes, and 199 are significantly different (P < 0.05). These genes are involved in the cell cycle, apoptosis, DNA damage repair, the PI3K pathway and so on. There were 164 differentially expressed genes in the PI3K pathway. There were 35 overexpressed genes in OCCC, while there were 12 overexpressed genes in HGSOC. Among these differentially expressed genes, we found that the MET gene and the CCNE1 gene were overexpressed in OCCC and associated with a worse prognosis.

Conclusions
In conclusion, there are many differentially expressed genes in OCCC and HGSOC, which indicates that the two kinds of tumours differ greatly in tumourigenesis and provides a theoretical basis for targeted therapy in the future. Further studies need to be performed to clarify the association of the differentially expressed genes with the unfavourable prognosis in OCCC.