bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the human GJA3 gene associated with congenital cataract
Authors: Zhang Mingzhou , Huang Chen , Wang Zhenyu , Lv Huibin , Li Xuemin 
Published: March 2020

AbstractBackgroundGap junction protein alpha 3 (GJA3), an important pathogenic gene of congenital cataracts, encodes the transmembrane protein connexin46, which functions as an intercellular channel for voltage and chemical gating by forming dodecamers. This study systematically collected nsSNP information for theGJA3gene from SNP databases and literature and screened for nsSNPs with high risks of pathogenicity.ResultsA total of 379 nsSNPs ofGJA3were identified. A total of 88 high-risk pathogenicGJA3nsSNPs were found, including 31 published nsSNPs associated with congenital cataracts and 57 novel nsSNPs predicted by all eight online tools. The 88 high-risk pathogenic mutations, which are related to 67 amino acids in the wild-type sequences, cause a decrease in protein stability according to I-Mutant 3.0, MUpro and INPS. G2 and R33 were predicted to participate in post-translational modification and ligand binding by ModPred, RaptorX Binding and COACH. Additionally, high-risk mutations were likely to involve highly conserved sites, random coils, alpha helixes, and extracellular loops and were accompanied by changes in amino acid size, charge, hydrophobicity and spatial structure.ConclusionsEighty-eight high-risk pathogenic nsSNPs ofGJA3were screened out in the study, 57 of which were newly reported. The combination of multiple in silico tools is highly efficient for targeting pathogenic sites.
Effects of ultrasound-guided paravertebral block on MMP-9 and postoperative pain in patients undergoing VATS lobectomy: a randomized, controlled clinical trial
Authors: Chu Haichen , Dong He , Wang Yongjie , Niu Zejun 
Published: March 2020

Abstract
Background
Local anesthesia can reduce the response to surgical stress and decrease the consumption of opioids, which may reduce immunosuppression and potentially delay postoperative tumor recurrence. We compared paravertebral block (PVB) combined with general anesthesia (GA) and general anesthesia regarding their effects on postoperative pain and matrix metalloproteinase-9 (MMP-9) after video-assisted thoracoscopic surgery (VATS) lobectomy.

Methods
54 patients undergoing elective VATS lobectomy at a single tertiary care, teaching hospital located in Qingdao between May 2, 2018 and Sep 28, 2018 were randomised by computer to either paravertebral block combined with general anesthesia or general anesthesia. The primary outcomes were pain scores at rest and on cough at 1, 4, 24, and 48 h after surgery. The secondary outcome were plasma concentrations of MMP-9, complications, and length of postoperative hospital stay.

Results
75 were enrolled to the study, of whom 21 were excluded before surgery. We analyzed lobectomy patients undergoing paravertebral block combined with general anesthesia (n = 25) or general anesthesia (n = 24). Both groups were similar regarding baseline characteristics. Pain scores at rest at 4 h and 24 h, on cough at 4 h were lower in PVB/GA group, compared with GA group (P < 0.05). There were no difference in pain scores at rest at 1 h, 48 h and on cough at 1 h, 24 h, and 48 h between groups. Patients in the PVB/GA group showed a greater decrease in plasma MMP-9 level at T1 and T2 after VATS lobectomy (P < 0.05). Postoperative complications and length of stay did not differ by anesthetic technique.

Conclusions
The paravertebral block/general anesthesia can provide statistically better pain relief and attenuate MMP-9 response to surgery and after VATS lobectomy. This technique may be beneficial for patients to recover rapidly after lung surgery and reduce postoperative tumor recurrence.

Trial registration
Chinese Clinical Trial registration number ChiCTR1800016379. Registered 28 May 2018.
Osteonecrosis of the femoral head due to brucellosis: a case report
Authors: Wang Peixu , Sun Wei , Shi Lijun , Li Tengqi 
Published: March 2020

Abstract
Background
Brucellosis is a zoonotic infection transmitted from infected animals to humans, osteonecrosis of the femoral head (ONFH) is a devastating disease that affects patients’ life with pain, dysfunction of walking and always lead to total hip arthroplasty (THA). We presented a case of ONFH which was very likely due to the infection of Brucella spp.

Case presentation
The patient was a 49 years-old male who was a herder living in Inner Mongolia, the northern part of China. He first showed recurrent fever then presented bilateral hip pain, which was confirmed to be brucellosis and ONFH on the right side of the hip. He was admitted to our center showed bilateral ONFH with the restrictive movement of both hips. We performed THA after it was confirmed that the infection has been cured. The patient can walk with the help of the walker the second day after surgery.

Conclusion
Brucellosis is still a common epidemic disease worldwide, which can lead to many complications, brucellosis arthritis is the most common complication of Brucellosis. Osteonecrosis of the femoral head can also present in the patients with brucellosis. All the patients presented with recurrent fever and hip pain, who is from the epidemic region, should be taken both septic arthritis and ONFH into consideration.
Higher risk of revision in total knee arthroplasty after high tibial osteotomy: a systematic review and updated meta-analysis
Authors: Chen Xi , Yang Zhen , Li Hairui , Zhu Shibai , Wang Yiou , Qian Wenwei 
Published: March 2020

Abstract
Background
High tibial osteotomy is commonly performed in young patients with high activity demand. Several studies have reported outcome of HTO. The reported 10-year survival ranged from 79 to 97.6%. The reported 15-year survival ranged from 56 to 65.5%, resulting in the need for conversion to TKA. Primary TKA now provides satisfactory long-term outcome in terms of function and survival. Researches have been conducted to compare clinical outcome between primary TKA and TKA after HTO to see if TKA should be the prior treatment rather than HTO in some cases. But the results were inconsistent. This study aims to compare the risk of revision and other parameters between total knee arthroplasty after high tibial osteotomy and primary total knee arthroplasty.

Methods
Searches and screens of the relevant literature were conducted, after which data were extracted and pooled analysis was performed to compare the clinical outcomes between the two groups.

Results
A total of 14 studies with 144,692 cases were included. Pooled analysis showed significantly more revisions and complications, and more tibial component loosening and impingement in postoperative X-ray in the HTO-TKA group. Surgical complexity during conversion to total knee arthroplasty was summarised and listed in table.

Conclusion
High tibial osteotomy offers satisfactory pain relief and functional outcome in selected patients with high activity demand. However, the need for subsequent TKA should be noted, which might be a technically challenging procedure with significantly higher risk of revision comparing to primary TKA.
Organic extracts from Cleome droserifolia exhibit effective caspase-dependent anticancer activity
Authors: Panicker Neena Gopinathan , Balhamar Sameera Omar Mohammed Saeed , Akhlaq Shaima , Qureshi Mohammed Mansoor , Rehman Najeeb Ur , Al-Harrasi Ahmed , Hussain Javid , Mustafa Farah 
Published: March 2020

AbstractBackgroundThis study investigated the anticancer potential of the medicinal herb,Cleome droserifolia(CD),a local plant of the Arabian Peninsula.C. droserifoliais traditionally known for its rubefacient, anti-diabetic, anti-oxidant, and anti-inflammatory properties.MethodsOrganic fractions of the aerial parts ofCleome droserifoliaharvested from the Arabian Peninsula were tested in human breast and cervical cancer cell lines for their anticancer potential. This was accomplished by using biochemical and cellular assays, including MTT, caspase Glo, western blot, and annexin V/propidium iodide-based flow cytometry analyses.ResultsTest of the dichloromethane fraction of the methanolic extract ofC. droserifolia,(CDD) revealed potent cytotoxic activity (from 70 to 90%) against several human cancer cell lines, including MCF-7, MDA-MB-231, and HeLa. Further characterization of the CDD fraction in MCF-7 cells revealed that it could activate the enzymatic activity of various caspases in a statistically significant manner, and induce cleavage of both caspase 7 and poly ADB ribose polymerase (PARP) proteins, but not the ethyl acetate fraction. Test of the ability of CDD to induce early signs of apoptosis was validated by annexin V/propidium iodide assay using FACS analysis. Induction of apoptosis was completely reversed by the classic pan inhibitor of apoptosis, Z-VAD-FMK, reducing early apoptosis from 29.7 to 0.6%, confirming that CDD could induce caspase-dependent apoptosis.ConclusionsAltogether, our results reveal thatC. droserifoliais a valuable medicinal plant with bioactive molecules that can induce apoptosis in human cancer cells. Thus, this plant should be explored further for its potential as an anticancer natural therapy as well as the isolation of novel molecules with anticancer properties.
Models and methods for determining the optimal number of beds in hospitals and regions: a systematic scoping review
Authors: Ravaghi Hamid , Alidoost Saeide , Mannion Russell , Bélorgeot Victoria D. 
Published: March 2020

Abstract
Background
Determining the optimal number of hospital beds is a complex and challenging endeavor and requires models and techniques which are sensitive to the multi-level, uncertain, and dynamic variables involved. This study identifies and characterizes extant models and methods that can be used to determine the required number of beds at hospital and regional levels, comparing their advantages and challenges.

Methods
A systematic search was conducted using Web of Science, Scopus, Embase and PubMed databases, with the search terms hospital bed capacity, hospital bed need, hospital, bed size, model, and method.

Results
Twenty-three studies met the criteria to be included in the review. Of these studies, a total of 11 models and 5 methods were identified, mainly designed to determine hospital bed capacity at the regional level. Common determinants of the required number of hospital beds in these models included demographic changes, average length of stay, admission rates, and bed occupancy rates.

Conclusions
There are no specific norms for the required number of beds at hospital and regional levels, but some of the identified models and methods may be used to estimate this number in different contexts. Moreover, it is important to consider alternative approaches to planning hospital capacity like care pathways to fix the limitations of “bed numbers”.
Inhibition of miR-153 ameliorates ischemia/reperfusion-induced cardiomyocytes apoptosis by regulating Nrf2/HO-1 signaling in rats
Authors: Hou Wei , Zhu Xianting , Liu Juan , Map Jiaguo 
Published: March 2020

Abstract
Background
Previous in vitro studies demonstrated that suppression of microRNAs might protect cardiomyocytes and neurons against oxygen–glucose deprivation and reoxygenation (OGD/R)-induced cell apoptosis. However, whether the protective effect of miR-153-inhibition on cardiomyocytes can be observed in the animal model is unknown. We aimed to address this question using a rat model of ischemia–reperfusion (I/R).

Methods
Rats were received the intramyocardial injection of saline or adenovirus-carrying target or control gene, and the rats were subjected to ischemia/reperfusion (I/R) treatment. The effects of miR-153 on I/R-induced inflammatory response and oxidative stress in the rat model were assessed using various assays.

Results
We found that suppression of miR-153 decreased cleaved caspase-3 and Bcl-2-associated X (Bax) expression, and increased B cell lymphoma 2 (Bcl-2) expression. We further confirmed that Nuclear transcription factor erythroid 2-like 2 (Nrf2) is a functional target of miR-153, and Nrf2/Heme oxygenase-1 (HO-1) signaling was involved in miR-153-regulated I/R-induced cardiomyocytes apoptosis. Inhibition of miR-153 reduced I/R-induced inflammatory response and oxidative stress in rat myocardium.

Conclusion
Suppression of miR-153 exerts a cardioprotective effect against I/R-induced injury through the regulation of Nrf2/HO-1 signaling, suggesting that targeting miR-153, Nrf2, or both may serve as promising therapeutic targets for the alleviation of I/R-induced injury.
Caspase-1 as a regulatory molecule of lipid metabolism
Authors: Molla Meseret Derbew , Ayelign Birhanu , Dessie Gashaw , Geto Zeleke , Admasu Tesfahun Dessale 
Published: March 2020

AbstractCaspase-1 is an evolutionarily conserved inflammatory mediated enzyme that cleaves and activates inflammatory cytokines. It can be activated through the assembly of inflammasome and its major effect is to activate the pro-inflammatory cytokines; interleukin 1β (IL-1β) and interluekine-18 (IL-18). In addition to IL-1β and IL-8, several lines of evidence showed that caspase-1 targets the substrates that are involved in different metabolic pathways, including lipid metabolism. Caspase-1 regulates lipid metabolism through cytokine dependent or cytokine independent regulation of genes that involved in lipid metabolism and its regulation. To date, there are several reports on the role of caspase-1 in lipid metabolism. Therefore, this review is aimed to summarize the role of caspase-1 in lipid metabolism and its regulation.
An improved protein lipid overlay assay for studying lipid–protein interactions
Authors: Han Xiuli , Yang Yongqing , Zhao Fengyun , Zhang Tianren , Yu Xiang 
Published: March 2020

Abstract
Background
Lipids perform multiple functions in the cell, and lipid–protein interactions play a key role in metabolism. Although various techniques have been developed to study lipid–protein interactions, the interacting protein partners that bind to most lipids remain unknown. The protein lipid overlay (PLO) assay has revealed numerous lipid–protein interactions, but its application suffers from unresolved technical issues.

Results
Herein, we found that blocking proteins may interfere with interactions between lipids and their binding proteins if a separate blocking step is carried out before the incubation step in the PLO assay. To overcome this, we modified the PLO assay by combining an incubation step alongside the blocking step. Verification experiments included phosphatidylinositol-3-phosphate (PI3P) and its commercially available interacting protein G302, C18:1, C18:2, C18:3 and the Arabidopsis plasma membrane H+-ATPase (PM H+-ATPase) AHA2 C-terminus, phosphatidylglycerol (PG) and AtROP6, and phosphatidylserine (PS) and the AHA2 C-terminus. The lipid–protein binding signal in the classical PLO (CPLO) assay was weak and not reproducible, but the modified PLO (MPLO) assay displayed significantly improved sensitivity and reproducibility.

Conclusions
This work identified a limitation of the CPLO assay, and both sensitivity and reproducibility were improved in the modified assay, which could prove to be more effective for investigating lipid–protein interactions.
Variants in RETN gene are associated with steroid-induced osteonecrosis of the femoral head risk among Han Chinese people
Authors: An Feimeng , Zhang Litian , Gao Hongyan , Wang Jiaqi , Liu Chang , Tian Ye , Ma Chao , Zhao Jian , Wang Kunzheng , Wang Jianzhong 
Published: March 2020

Abstract
Background
Gene polymorphism has an important influence on RETN gene expression level, and the increased level of resistin encoded in RETN will lead to metabolic disorder, especially lipid metabolism. Moreover, steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is closely related to lipid metabolism level, so this study is intended to explore the relationship of RETN polymorphisms with susceptibility to steroid-induced ONFH in the Chinese Han population.

Methods
In this case-control study, eight single-nucleotide polymorphisms (SNPs) of RETN were genotyped by the Agena MassARRAY system in 199 steroid-induced ONFH patients and 200 healthy controls. The relationship between RETN polymorphisms and steroid-induced ONFH risk was assessed using genetic models and haplotype analyses. Odds ratio (OR) and 95% confidence intervals (CIs) were obtained by logistic regression adjusted for age.

Results
We found significant differences in the distribution of HDL-C, TG/HDL-C, and LDL-C/HDL-C between the patients and the control group (p < 0.05). In allele model and genotype model analysis, rs34861192, rs3219175, rs3745368, and rs1477341 could reduce the risk of steroid-induced ONFH. Further stratified analysis showed that rs3745367 was related to the clinical stage of patients, and rs1477341 was significantly correlated with an increased TG level and a decreased TC/HDL-C level. The linkage analysis showed that two SNPs (rs34861192 and rs3219175) in RETN even significant linkage disequilibrium.

Conclusions
Our results provide the firstly evidence that RETN gene polymorphisms were associated with a reduced risk of steroid-induced ONFH in Chinese Han population.
The efficacy and safety of selective COX-2 inhibitors for postoperative pain management in patients after total knee/hip arthroplasty: a meta-analysis
Authors: Jiang Mingyang , Deng Huachu , Chen Xuxu , Lin Yunni , Xie Xiaoyong , Bo Zhandong 
Published: March 2020

Abstract
Background
Many selective cyclooxygenase (COX-2) inhibitors are currently used in clinical practice. COX-2 inhibitors have good anti-inflammatory, analgesic, antipyretic effects, and gastrointestinal safety. However, the analgesic effects and adverse reactions of COX-2 after total knee/hip arthroplasty (TKA/THA) are not fully known.

Objective
To evaluate the efficacy and safety of selective COX-2 inhibitors in postoperative pain management in patients receiving TKA/THA.

Methods
Randomized controlled trials (RCTs) were retrieved from medical literature databases. Risk ratios (RR) Std mean difference (SMD) and 95% confidence intervals (CI) were calculated to analyze the primary and safety endpoints.

Results
In total, 18 articles (23 trial comparisons) were retrieved comprising 3104 patients. Among them, 1910 patients (61.5%) were randomized to the experimental group whereas 1194 patients (38.5%) were randomized to the control group. The primary endpoints were the patients’ VAS score at rest or on ambulation (within 3 days). We found that VAS score in patients that received selective COX-2 inhibitor was significantly lower compared to those of the control group.

Conclusion
This meta-analysis shows that selective COX-2 inhibitor therapy is effective, safe, and reliable in relieving postoperative pain of THA/TKA.
Initiation and propagation of α-synuclein aggregation in the nervous system
Authors: Hijaz Baraa A. , Volpicelli-Daley Laura A. 
Published: March 2020

AbstractThe two main pathological hallmarks of Parkinson’s disease are loss of dopamine neurons in the substantia nigra pars compacta and proteinaceous amyloid fibrils composed mostly of α-synuclein, called Lewy pathology. Levodopa to enhance dopaminergic transmission remains one of the most effective treatment for alleviating the motor symptoms of Parkinson’s disease (Olanow, Mov Disord 34:812–815, 2019). In addition, deep brain stimulation (Bronstein et al., Arch Neurol 68:165, 2011) to modulate basal ganglia circuit activity successfully alleviates some motor symptoms. MRI guided focused ultrasound in the subthalamic nucleus is a promising therapeutic strategy as well (Martinez-Fernandez et al., Lancet Neurol 17:54–63, 2018). However, to date, there exists no treatment that stops the progression of this disease. The findings that α-synuclein can be released from neurons and inherited through interconnected neural networks opened the door for discovering novel treatment strategies to prevent the formation and spread of Lewy pathology with the goal of halting PD in its tracks. This hypothesis is based on discoveries that pathologic aggregates of α-synuclein induce the endogenous α-synuclein protein to adopt a similar pathologic conformation, and is thus self-propagating. Phase I clinical trials are currently ongoing to test treatments such as immunotherapy to prevent the neuron to neuron spread of extracellular aggregates. Although tremendous progress has been made in understanding how Lewy pathology forms and spreads throughout the brain, cell intrinsic factors also play a critical role in the formation of pathologic α-synuclein, such as mechanisms that increase endogenous α-synuclein levels, selective expression profiles in distinct neuron subtypes, mutations and altered function of proteins involved in α-synuclein synthesis and degradation, and oxidative stress. Strategies that prevent the formation of pathologic α-synuclein should consider extracellular release and propagation, as well as neuron intrinsic mechanisms.
Heparinized chitosan stabilizes the bioactivity of BMP-2 and potentiates the osteogenic efficacy of demineralized bone matrix
Authors: Kim Soyon , Fan Jiabing , Lee Chung-Sung , Chen Chen , Bubukina Ksenia , Lee Min 
Published: March 2020

Abstract
Background
Demineralized bone matrix (DBM), an allograft bone processed to better expose osteoinductive factors such as bone morphogenetic proteins (BMPs), is increasingly used for clinical bone repair. However, more extensive use of DBM is limited by its unpredictable osteoinductivity and low bone formation capacity. Commercial DBM products often employ polymeric carriers to enhance handling properties but such carriers generally do not possess bioactive functions. Heparin is a highly sulfated polysaccharide and is shown to form a stable complex with growth factors to enhance their bioactivities. In this study, a new heparinized synthetic carrier for DBM is developed based on photocrosslinking of methacrylated glycol chitosan and heparin conjugation.

Results
Heparinized chitosan exerts protective effects on BMP bioactivity against physiological stressors related to bone fracture healing. It also enhances the potency of BMPs by inhibiting the activity of BMP antagonist, noggin. Moreover, heparinized chitosan is effective to deliver bone marrow stromal cells and DBM for enhanced osteogenesis by sequestering and localizing the cell-produced or DBM-released BMPs.

Conclusions
This research suggests an essential approach of developing a new hydrogel carrier to stabilize the bioactivity of BMPs and improve the clinical efficacy of current bone graft therapeutics for accelerated bone repair.