bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical Investigation about Traditional and Cortical Trajectory Screws of Static and Dynamic Lumbar Fixation
Authors: Liu Che-Wei , Wang Lu-Lin , Xu Yu-Kun , Chen Chun-Ming , Wang Jian-Cyuan , Tsai Wei-Tsung , lin Shang-Chih
Published: February 2020

Background

To evaluate kinetic and kinematic behavior in both static and dynamic CBT fixation a finite element study was designed. Two types of screw trajectories are commonly used in lumbar surgery. Both traditional trajectory (TT) and cortical bone trajectory (CBT) provide equivalent pull-out strengths of a screw. Dynesys fixation of TT screws, but not dynamization of CBT screws, has been used extensively in lumbar surgery. This study aimed to simulate the biomechanics of CBT-based dynamic system for an evaluation of CBT dynamization.

Methods

A validated nonlinearly lumbosacral finite-element model was used to simulate four variations of screw fixation. Responses of both implant (screw stress) and tissues (disc motion, disc stress, and facet force) at the upper adjacent (L3-L4) and fixed (L4-L5) segments were used as the evaluation indices. Flexion, extension, bending, and rotation of both TT and CBT screws were simulated in this study for comparison.

Results

The results showed that the TT static was the most effective stabilizer to the L4-L5 segment, followed by CBT static, TT dynamic, and the CBT dynamic, which was the least effective. Dynamization of the TT and CBT fixators decreased stability of the fixed segment and alleviate adjacent segment stress compensation. The 3.5-mm diameter CBT screw deteriorated stress distribution and rendered it vulnerable to bone-screw loosening and fatigue cracking.

Conclusions

A systematic analysis of the effects of TT and CBT fixation constructs on kinematic and kinetic responses in a full lumbosacral model is currently lacking. This study examined both the static fixation effect and its dynamic counterpart and identified that dynamization of CBT have slightly inferior structural stiffness than dynamic TT and cautious preoperative evaluation is essential if 3.5-mm diameter CBT screws are used. Therefore, 4.5-mm or 5.5-mm diameter CBT screws, or as big as tolerated, are recommended to avoid loosening and cracking.
Candidate methylation sites associated with endocrine therapy resistance in ER+/HER2- breast cancer
Authors: Soleimani Maryam , Borgoni Simone , Sofyalı Emre , Verschure Pernette J. , Wiemann Stefan , Moerland Perry , Kampen Antoine H.C. van
Published: February 2020

Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods: We used genome-wide DNA methylation profiles of primary ER+/HER2- tumours from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AI or TAM) that patients received (N=210 and N=172, respectively). We also identified multivariable methylation signatures associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results: We identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of tumour stage, age, AI treatment, and luminal status. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Also at the gene set level, several sets related to endocrine therapy and resistance were identified in both survival and T47D signatures. Conclusions: We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours prior to endocrine treatment are associated with development of endocrine resistance.
Cross-cultural adaptation and validation of the Romanian Knee disability and Osteoarthritis Outcome Score for Joint Replacement (KOOSJR)
Authors: Florescu Sorin , Vermesan Dinu , Haragus Horia , Patrascu Jenel M , Timar Bogdan , Todor Adrian
Published: February 2020

Aim: To perform validation of the Romanian Knee disability and Osteoarthritis Outcome Score for Joint Replacement (KOOSJR).
Method: 96 patients (101 knees) with advanced osteoarthritis (OA) scheduled for total knee replacement completed Romanian translations of KOOSJR and IKDC (International Knee Documentation Committee – subjective knee form) and Euroqol EQ-5D-5L, and the treating physician completed the original knee society score (KSS).
Results: Average age was 66.4 (range 50-83) years and male to female ratio 1:3.76. There was moderate correlation between the test-retest (average 4 days) KOOSJR (r=0.618, n=45) and IKDC (r=-0.671, n=99), weak between KOOSJR and EQ-5D-5L Index (r=-0.431, n=100) and VAS (r=-0.364, n=99) and very weak to KSS score (r=-0.133, n=98) and function (r=-0.072, n=97) For the first KOOSJR, Cronbach's alpha was 0.816 and intraclass correlation coefficient (ICC) 0.816 (95% CI 0.755-0.866) for average measures. For the retest, Cronbach's alpha was 0.841 (95% CI 0.760-0.903) for averages.
Conclusion: The Romanian Knee disability and Osteoarthritis Outcome Score for Joint Replacement (KOOSJR) is a valid, reliable, consistent and reproducible clinical score for patients with OA requiring arthroplasty.
Principal Component Analysis of Adipocytokines and Insulin Associate with Risk Factors of Cardiovascular Diseases
Authors: yarizadeh Habib , Setayesh Leila , Askarpour Moein , Pooyan Sara , Sajjadi Seyedeh Forough , Badrooj Negin , Roberts Caroline , Mirzaei Khadijeh
Published: February 2020

Objectives : Obesity plays an important role in the development of chronic diseases like cardiovascular diseases and diabetes. The possible underlying mechanism for this connection is that adipose tissue secretes an array of chemical messenger adipokines proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). This study aimed to investigate the linkage between adipocytokines and insulin with the cardiovascular disease risk, with particular reference to the adipokines galectin-3, plasminogen activator inhibitor-1, interleukin-1-beta, C-reactive protein, and monocyte chemoattractant protein. Result: Two patterns were identified. The first pattern was galectin-3, plasminogen activator inhibitor-1 and interleukin-1-beta and the second one was C-reactive protein, insulin and monocyte chemoattractant protein-1. The second pattern was strongly associated with the higher scores for resting metabolic rate, diastolic blood pressure, homeostasis model insulin resistance index, lipid profile (except low density lipoprotein, total cholesterol), and body composition parameters (except fat free mass index and waist hip ratio), while negatively associated with age and high density lipoprotein level (all p < 0.05). The first pattern was, however, significantly associated with body fat mass, obesity degree percentage, waist circumference, fat mass index, and waist hip ratio (P < 0.05 for all).
A key genomic signature associated with lymphovascular invasion in head and neck squamous cell carcinoma
Authors: Zhang Jian , Lin Huaming , Jiang Huali , Jiang Hualong , Xie Tao , Wang Baiyao , Huang Xiaoting , Lin Jie , Xu Anan , Li Rong , Zhang Jiexia , Yuan Yawei
Published: February 2020

Background: Lymphovascular invasion (LOI), a key pathological feature of head and neck squamous cell carcinoma (HNSCC), is predictive of poor survival; however, the associated clinical characteristics and underlying molecular mechanisms remain largely unknown.
Methods: We performed weighted gene co-expression network analysis to construct gene co-expression networks and investigate the relationship between key modules and the LOI clinical phenotype. Functional enrichment and KEGG pathway analyses were performed with differentially expressed genes. A protein–protein interaction network was constructed using Cytoscape, and module analysis was performed using MCODE. Prognostic value, expression analysis, and survival analysis were conducted using hub genes; GEPIA and the Human Protein Atlas database were used to determine the mRNA and protein expression levels of hub genes, respectively. Multivariable Cox regression analysis was used to establish a prognostic risk formula and the areas under the receiver operating characteristic curve (AUCs) were used to evaluate prediction efficiency. Finally, potential small molecular agents that could target LOI were identiﬁed with DrugBank.
Results: Ten co-expression modules in two key modules (turquoise and pink) associated with LOI were identiﬁed. Functional enrichment and KEGG pathway analysis revealed that turquoise and pink modules played signiﬁcant roles in HNSCC progression. Seven hub genes (CNFN, KIF18B, KIF23, PRC1, CCNA2, DEPDC1, and TTK) in the two modules were identiﬁed and validated by survival and expression analyses, and the following prognostic risk formula was established: [risk score = EXP DEPDC1 * 0.32636 + EXP CNFN * (−0.07544)]. The low-risk group showed better overall survival than the high-risk group ( P < 0.0001), and the AUCs for 1-, 3-, and 5-year overall survival were 0.582, 0.634, and 0.636, respectively. Eight small molecular agents, namely XL844, AT7519, AT9283, alvocidib, nelarabine, benzamidine, L-glutamine, and zinc, were identified as novel candidates for controlling LOI in HNSCC ( P < 0.05).
Conclusions: The two-mRNA signature (CNFN and DEPDC1) could serve as an independent biomarker to predict LOI risk and provide new insights into the mechanisms underlying LOI in HNSCC. In addition, the small molecular agents appear promising for LOI treatment.
Association between Dietary Energy Density with Mental Health and Sleep Quality in Women with Overweight/Obesity
Authors: Maddahi Niloofarsadat , Yarizadeh Habib , Setayesh Leila , Nasir Yasaman , Alizadeh Shahab , Mirzaei Khadijeh
Published: February 2020

Objectives : Mental health, sleep quality and dietary intake are interlinked. Impairment of mental health and low sleep quality may contribute to obesity through the consumption of diets high in energy density. Nevertheless, it is not clear whether dietary energy density (DED) influences mental health. This study aimed to examine the association of DED with mental health indices, including depression, anxiety, stress, and sleep quality in overweight/obese women. Results: After adjustment for age, BMI, and physical activity, subjects in the highest quartile of DED had higher systolic and diastolic blood pressure, but lower serum triglyceride, than those in the lowest quartile (p <0.05). DED was significantly associated with increased odds of stress in the crude (OR =2.15, 95%CI: 1.01-4.56, p= 0.04) and adjusted model for age, BMI, and physical activity (OR = 2.56, 95%CI: 1.13-5.79, p=0.02). No significant relationship was observed between DED and depression, anxiety and sleep quality.
Hepatocellular carcinoma with right atrial tumor thrombus: a systematic review
Authors: Yuan Shi-Min , Guo Yi-Xian
Published: February 2020

Background: Hepatocellular carcinoma with right atrial tumor thrombus is uncommon but with a dismal prognosis.
Methods: By comprehensive literature retrieval of 2000–2019, 53 reports were obtained with 187 patients recruited into this study. The extracted data included patient characteristics, tumor characteristics, treatment, follow-up and outcomes. Statistical analyses applied were student t, Fisher exact and I2 tests. Patients were divided into 6 groups according to the treatment of choices: transarterial chemoembolization (TACE), surgery, radiotherapy, chemotherapy, intervention and supportive care.
Results: The overall survival rate of this cohort was 40.8%. The survival rate of patients receiving TACE was 33.3% and that of surgical patients was 41.9%. The survival time of patients with TACE treatment was longer than surgical patients, but lack of statistical significance. Patients were under a follow-up of 15.7±16.6 (median 10) months. Patients receiving radiotherapy had under a longest follow-up among all groups. Intra- and/or extrahepatic recurrence of hepatocellular carcinoma was the major morbidity and also often causes of death. The mortality rates of patients with different treatments in a decremental sequence were supportive care >radiotherapy >surgery >TACE >intervention. No difference was noted in mortality between patients reported from case reports and those from non-case reports.
Conclusions: Even though advanced hepatocellular carcinoma with right atrial thrombus is an aggressive malignancy, the present study showed that patients’ prognoses were improved and survival time elongated with active treatments such as TACE and surgery. Active treatments were thus advised to patients with hepatocellular carcinoma with right atrial tumor thrombus.
Could remnant-like particle cholesterol become a risk factor in diabetic menopausal women with coronary artery disease? A cross-sectional study of single academic center in China
Authors: Feng Xunxun , Guo Qianyun , Zhou Shu , Sun Tienan , Liu Yuyang , Zhou Zhiming , Zhou Yujie
Published: February 2020

Background and aims It has been confirmed that remnant-like particle cholesterol (RLP-C) mediates the progression of coronary artery disease (CAD). Currently there is limited information on RLP-C in menopausal women. With the special status of diabetes mellitus (DM) combined with the special body changes of the menopausal women, the RLP-C is particularly important when studying the changes that occurred in response to CAD and its associated risk factors. This study discussed whether RLP-C could be an independent risk factor for menopausal women with CAD and DM. Methods The cohort consisted of 4753 menopausal women who had undergone coronary angiography. Subjects were separated into CAD and non-CAD groups, and univariate and multivariate logistic regression analysis of CAD risk factors were performed. All patients with a history of DM were divided into DM subgroups. Then, the univariate and multivariate logistic regression analysis of the risk factors of CAD and the comparison among age groups in the DM subgroup were performed. After age stratification of the DM group, the Kruskal-Wallis test was used to analyze the differences of various lipid indexes among age groups. Results The multivariate logistic regression showed that RLP-C was an independent risk factor for CAD in menopausal women (OR 1.232, 95%CI 1.070-1.419). In the DM subgroup, it was also found that RLP-C was an independent risk factor for CAD (OR 1.366, 95%CI 1.043-1.791). Kruskal-Wallis test analysis found that RLP-C had no significant difference among three groups (P>0.05). Conclusions RLP-C was proved to be an independent risk factor for menopausal women with CAD and DM.
Multi-omics analysis reveals the influence of genetic and environmental risk factors on developing gut microbiota in infants at risk of celiac disease
Authors: Leonard Maureen M , Karathia Hiren , Pujolassos Meritxell , Troisi Jacopo , Valitutti Francesco , Subramanian Poorani , Camhi Stephanie , Kenyon Victoria , Colucci Angelo , Serena Gloria , Cucchiara Salvatore , Montuori Monica , Malamisura Basilio , Francavilla Ruggiero , Elli Luca , Fanelli Brian , Colwell Rita , Hasan Nur , Zomorrodi Ali R , Fasano Alessio , Team CDGEMM Study
Published: February 2020

Background : Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery, exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. Results : Toward this end, we took advantage of a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional and longitudinal analyses using metagenomic and metabolomic data collected at birth, three months and six months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway, and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniforms and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. Conclusions : Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD ultimately linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. Keywords: Microbiota; Celiac disease; Multi-omics analysis, gut microbiome
Prediction and analysis of Metagenomic operons via MetaRon: a Pipeline for Prediction of Metagenomic OpeRons
Authors: Zaidi Syed Shujaat Ali , Kayani Masood Ur Rehman , Zhang Xuegong , Shamsi Imran Haider
Published: February 2020

Background: Efficient regulation of bacterial genes against the environmental stimulus results in unique operonic organizations. Lack of complete reference and functional information makes metagenomic operon prediction challenging and therefore opens new perspectives on the interpretation of the host-microbe interactions. Methods: Here we present MetaRon (pipeline for the prediction of Metagenomic operons), an open-source pipeline explicitly designed for the metagenomic shotgun sequencing data. It recreates the operonic structure without functional information. MetaRon identifies closely packed co-directional gene clusters with a promoter upstream and downstream of the first and last gene, respectively. Promoter prediction marks the transcriptional unit boundary (TUB) of closely packed co-directional gene clusters.Results: Escherichia coli (E. coli) K-12 MG1655 presents a gold standard for operon prediction. Therefore, MetaRon was initially implemented on two simulated illumina datasets: (1) E. coli MG1655 genome (2) a mixture of E. coli MG1655, Mycobacterium tuberculosis H37Rv and Bacillus subtilis str. 168 genomes. Operons were predicted in the single genome and mixture of genomes with a sensitivity of 97.8% and 93.7%, respectively. In the next phase, operons predicted from E. coli c20 draft genome isolated from chicken gut metagenome achieved a sensitivity of 94.1%. Lastly, the application of MetaRon on 145 paired-end gut metagenome samples identified 1,232,407 unique operons. Conclusion: MetaRon removes two notable limitations of existing methods: (1) dependency on functional information, and (2) liberates the users from enormous metagenomic data management. Current study showed the idea of using operons as subset to represent the whole-metagenome in terms of secondary metabolites and demonstrated its effectiveness in explaining the occurrence of a disease condition. This will significantly reduce the hefty whole-metagenome data to a small more precise data set. Furthermore, metabolic pathways from the operonic sequences were identified in association with the occurrence of type 2 diabetes (T2D). Presumably, this is the first organized effort to predict metagenomic operons and perform a detailed analysis in association with a disease, in this case T2D. The application of MetaRon to metagenome data at diverse scale will be beneficial to understand the gene regulation and therapeutic metagenomics.
Discriminatory ability and prognostic evaluation of presepsin for sepsis-related acute respiratory distress syndrome
Authors: Zhao Jiangnan , Tan Yan , Wang Li , Shi Yi
Published: February 2020

Background Sepsis-related acute respiratory distress syndrome (ARDS) has worse clinical outcomes than non-sepsis-related ARDS. Early identification of sepsis-related or non-sepsis-related ARDS is challenging. Presepsin is known to be elevated in sepsis, but little is known about its discriminatory ability and prognostic evaluation in patients with sepsis-related ARDS.Methods This study was a multicenter prospective cohort study of 225 consecutive patients, enrolled based on the Berlin criteria for ARDS between September 2017 and August 2019. The patients were stratified into two groups: sepsis-related ARDS and non-sepsis-related ARDS. Plasma presepsin and serum procalcitonin (PCT) were measured, and the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated to evaluate disease severity.Results Patients with sepsis-related ARDS had higher presepsin levels at admission than patients with non-sepsis-related ARDS (P<0.001). The area under the receiver operating characteristic (ROC) curve of presepsin (0.81) was significantly greater than that of PCT (0.62) in diagnosing sepsis-related ARDS (P=0.001). Among patients with sepsis-related ARDS, presepsin levels were significantly higher in non-survivors than in survivors (P<0.001). Presepsin was found to be an independent predictor of in-hospital mortality in sepsis-related ARDS. Based on ROC analysis, the addition of presepsin improved discrimination based on SOFA or APACHE II scores from 0.77 to 0.87 or 0.73 to 0.85 (all P<0.05), respectively. The levels of plasma presepsin were positively correlated with disease severity, as determined by the SOFA score in the sepsis-related ARDS group (P<0.001).Conclusions Presepsin is a valuable biomarker for early stratification of sepsis-related ARDS. Higher plasma presepsin levels are associated with increased mortality in sepsis-related ARDS.
Expression and function of an HAC1-regulated multi-copy xylanase gene in Saccharomyces cerevisiae
Authors: Zhang Sitong , Bao Changjie , Li Jiping , Chen Huan , Sun Yang , Wang Gang , Chen Guang
Published: February 2020

To investigate the effects of transcription factor HAC1, which is involved in the unfolded protein response pathway, on the expression of xynB in Saccharomyces cerevisiae , we used overlap extension polymerase chain reaction (PCR), rDNA integration, and droplet digital PCR technology to generate a S . cerevisiae strain (S8) containing eight copies of the xylanase gene, allowing high-yield secretory expression of xylanase. HAC1 was then overexpressed in the S8 strain, and the GeXP system was used to study the effects of HAC1 overexpression on the expression of genes associated with protein folding in the endoplasmic reticulum (ER). Results confirmed the constitutive secretory expression of the multiple copies of the xylanase gene in S . cerevisiae following rDNA-based integration of the expression cassette. Specifically, recombinant S . cerevisiae strain S8, containing eight copies of the xylanase gene, showed maximum xylanase expression, with a yield of 325 U/mL. However, overexpression of HAC1 further improved xylanase production by strain S8, resulting in a yield of 381 U/mL. These results confirmed that overexpression of HAC1 improves the expression of genes associated with protein folding in the ER, enhancing the protein folding and assembly functions of the ER and increasing xylanase expression.
Microglial and neuronal cell pyroptosis induced by oxygen-glucose deprivation/reoxygenation aggravates cell injury via activation of the caspase-1/GSDMD signaling pathway
Authors: Dong Zhaofei , Peng Qingxia , Pan Kuang , Lin Weijye , Wang Yidong
Published: February 2020

Background Pyroptosis is a new type of programmed cell death, which induces a strong pro-inflammatory reaction. However, the mechanism of pyroptosis after brain ischemia/reperfusion (I/R) and the interaction between different neural cells are still unclear. This study comprehensively explored the mechanisms and interactions of microglial and neuronal pyroptosis in the simulated I/R environment in vitro. Methods The BV2 and HT22 cells were treated by oxygen-glucose deprivation/reoxygenation (OGD/R). The pyroptotic cells were detected by dye uptake method. The expression levels of pyroptotic-related proteins were determined by western blotting, immunofluorescence and enzyme linked immunosorbent assay. The cell viability was assessed using MTT assay Kit. AC-YVAD-CMK, necrosulfonamide and the siRNA of Gasdermin D (GSDMD) were used to observe the inhibited effect on caspase-1 and GSDMD, respectively. A transwell co-culture model was applied to observe pyroptosis and interactions between BV2 and HT22 cell after OGD/R. Results Both BV2 and HT22 cells underwent pyroptosis after OGD/R, and the pyroptosis occurred at earlier time point in HT22 than that of BV2. Caspase-11 and Gasdermin E (GSDME) expression in BV2 and HT22 cells did not change significantly after OGD/R. Inhibition of caspase-1 or GSDMD activity, or down-regulation of GSDMD expression, alleviated pyroptosis in both BV2 and HT22 cells after OGD/R. Transwell studies further showed that OGD/R-treated HT22 or BV2 cells aggravated pyroptosis of adjacent non-OGD/R-treated cells, which could be relieved by inhibition of caspase-1 or GSDMD. Conclusions OGD/R induces pyroptosis of microglia and neuronal cells and aggravates cell injury via activation of caspase-1/GSDMD signaling pathway. Our findings suggest that caspase-1 and GSDMD may be therapeutic targets after cerebral I/R. Necrosulfonamide, a chemical inhibitor of GSDMD, may be a potential drug to prevent cerebral I/R-induced brain injury.
Oncological resection, myasthenia gravis and staging as prognostic factors in thymic tumors: A Chilean case series
Authors: Salas Patricio , Solovera Maria Eliana , Bannura Felipe , Muñoz-Medel Matias , Cordova-Delgado Miguel , Sanchez Cesar , Ibañez Carolina , Garrido Marcelo , Koch Erica , Acevedo Francisco , Mondaca Sebastian , Nervi Bruno , Madrid Jorge , Peña Jose , Pinto Mauricio P. , Valbuena José , Galindo Hector
Published: February 2020

Background: Thymic epithelial tumors are rare and highly heterogeneous. Reports from the United States suggest an overall incidence of 0.15 per 100,000/year. In contrast, the incidence of these tumors in Latin America is largely unknown and reports are scarce, somewhat limited to case reports.Methods: Herein, we report a series of 38 thymic tumors from a single institution, retrospectively incorporated into this study. Patient characteristics and outcomes including age, sex, stage, paraneoplastic syndromes, treatment regimens and the date of decease were obtained from medical records.Results: Most cases in our series were females and young age (<50 years-old) and early stage by Masaoka-Koga or the Moran staging systems. Also, a 34% of patients had myasthenia gravis (MG). Next, we analyzed overall survival (OS) rates in our series and found that the quality of surgery (R0, R1 or R2), MG status, and staging (Masaoka-Koga or Moran) were prognostic factors. Finally, we compared our data to larger thymic tumor series.Conclusions: Overall, our study confirms complete surgical resection as the standard, most effective treatment for thymic epithelial tumors. Also, the Masaoka-Koga staging system remains as a reliable prognostic factor but also the Moran staging system should be considered for thymomas.
Clinical aspects and detection of Zika virus RNA in several tissues of experimentally infected BALB/c mice
Authors: Bandeira Derick Mendes , Caldas Gabriela Cardoso , Jácome Fernanda Cunha , Rasinhas Arthur da Costa , Almeida Ana Luisa Teixeira de , Tourinho Renata Santos , Amorim Juliana Fernandes da Silva , Trindade Gisela Freitas , Barth Ortrud Monika , Barreto-Vieira Debora Ferreira
Published: February 2020

The aim of the present study was to infect BALB/c mice with ZIKV to evaluate clinical signs and to quantify the viral load in different tissues at three different kinetic points. For this purpose, fifteen mice were inoculated with a 100µl of a viral solution and five other mice were used as negative controls. After euthanasia, nine different tissues were collected and macerated for RNA extraction and quantification. The infections were not lethal. Some of them, however, showed great agitation, hair bristling and itchy skin. Viral RNA was detected in one heart sample, eight samples of spleen and two of skeletal muscle. Seven out of eleven positive samples were from mice euthanized on the third day after infection. Only spleen yielded positive results at a later time of infection. These results contribute to a better understanding of clinical signs and replication dynamics of Zika virus in different organs of BALB/c mice, which are still scarce data in the scientific literature.
Evaluation Of The Morphometric Covariation Between Palatal And Craniofacial Skeletal Morphology In Class III Malocclusion Growing Subjects
Authors: Paoloni Valeria , Gastaldi Giorgio , Franchi Lorenzo , De Razza Francesca Chiara , Cozza Paola
Published: February 2020

Background: To study the covariation between palatal and craniofacial skeletal morphology in Class III growing patients through geometric morphometric analysis (GMM).Methods: In this retrospective study, 54 Class III subjects (24F,30M;7.6±0.8yy) were enrolled following these inclusion criteria: European ancestry, Class III skeletal and dental relationship, early mixed dentition, prepubertal skeletal maturation, familiarity for Class III malocclusion, no pseudo Class III malocclusion. Each patient provided upper digital cast and cephalogram before starting the therapy. Landmarks and semilandmarks were digitized (239 on the casts;121 on the lateral radiographs) and GMM was used. Procrustes analysis and principal component analysis (PCA) were applied to show the principal components of palatal and craniofacial skeletal shape variation. Two-block partial least squares analysis (PLS) was used to assess pattern of covariation between palatal and craniofacial morphology.Results: Regarding palatal shape variation, PC with largest variance (PC1) described morphological changes in the three space dimensions, while, concerning the craniofacial complex components, PC1 revealed morphological differences along the vertical plane. A significant covariation was found between palatal and craniofacial shape. PLS1 accounted for more than 61,7% of the whole covariation, correlating the craniofacial divergence to palatal height and width.Conclusions: In Class III subjects increments of angle divergence are related to a narrow and high palate.
Survival curve identifies critical period for postoperative mortality in cardiac patients undergoing emergency general surgery
Authors: Martines Diego , Nii Fernanda , Medeiros Kayo , Carvalho Barbara , Pipek Leonardo , Mesquita Gustavo , Iuamoto Leandro , Oliveira Gustavo , Bianco Antonio Carlos , Meyer Alberto
Published: February 2020

Introduction: The number of non-cardiac major surgeries carried out has significantly increased in recent years to around 200 million procedures carried out annually. Approximately 30% of patients submitted to non-cardiac surgery present some form of cardiovascular comorbidity. In emergency situations, with less surgery planning time and greater clinical severity, the risks become even more significant. The aim of this study is to determine the incidence and clinical outcomes in patients with cardiovascular disease submitted to non-cardiac surgical procedures in a single cardiovascular referral center. Methods: This is a prospective cohort study of patients with cardiovascular disease submitted to non-cardiovascular surgery. All procedures were carried out by the same surgeon, between January 2006 and January 2018. Results: 240 patients included were elderly, 154 were male (64%), 8 patients presented two diagnoses. Of the resulting 248 procedures carried out, 230 were emergency (92.8%). From the data obtained it was possible to estimate the day from which the occurrence of mortality is less probable in the postoperative phase. Conclusion: Our research evaluated the epidemiological profile of the surgeries and we were able to estimate the survival and delimit the period of greatest risk of mortality in these patients. The high rate of acute mesenteric ischemia was notable, a serious and frequently fatal condition.
Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and Treatment of Prostate Cancer
Authors: Lan Minmin , Zhu Lianhua , Wang Yixuan , Shen Dajia , Fang Kejing , Liu Yu , Peng Yanli , Qiao Bin , Guo Yanli
Published: February 2020

Background: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and high resolution, thereby enabling rapid and direct measurement and tracking of tumor growth and metastasis. At the same time, ultrasound targeted nanobubble destruction (UTND) provides an effective way to drug accumulation; effectively increasing the content of the drug in the tumor area and reducing potential side effects, thereby contributing effectively to the treatment of the tumors.Result: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs), and study their application in ultrasound imaging of prostate cancer as well as their therapeutic effect on prostate cancer when combined with ultrasound targeted nanobubble destruction (UTND). ICG-PTX NBs were prepared by mechanical oscillation method. Their particle size and Zeta potential of ICG-PTX NBs were 469.5±32.87 nm and -21.70±1.222 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 6.2%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect is positively correlated with their concentration. The imaging effect of tumor xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumor xenografts in vivo, the ICG-PTX NBs+US group showed more significant inhibition of cell proliferation and promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs group and the ICG-PTX NBs+US group were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organ showed no obvious abnormalities in the ICG-PTX NBs group and the ICG-PTX NBs+US group.Conclusions: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent for both diagnosis and treatment that can achieve enhanced imaging, effective inhibition and killing of prostate cancer under the guidance of multimodal imaging including ultrasound, fluorescence and photoacoustic imaging.
Osteopontin promoter polymorphisms and risk of urolithiasis: a candidate gene association and meta-analysis study
Authors: Amar Ali , Afzal Ayesha , Hameed Athar , Ahmad Mumtaz , Khan Abdul Rafay , Najma Humaira , Abid Aiysha , Khaliq Shagufta
Published: February 2020

Background Urolithiasis is a worldwide urological problem with significant contribution of genetic factors. Pakistan, which resides within the Afro-Asian stone belt, has a high reported prevalence (12%) of urolithiasis. Osteopontin (SPP1) is a urinary macromolecule with a suggested critical role in modulating renal stone formation, genetic polymorphisms of which may determine individual risk of developing urolithiasis. However, results of previous studies regarding SPP1 polymorphisms and susceptibility to urolithiasis have apparent inconsistencies with no data available for local population. Methods 483 Pakistani subjects, including 235 urolithiasis patients and 248 healthy controls, were genotyped for 6 SPP1 genetic polymorphisms to investigate association with urolithiasis in an indigenous candidate gene association study. Further, a comprehensive meta-analysis following a systematic literature search was also performed to provide evidence based account of any existent association between SPP1 promoter polymorphisms and urolithiasis risk. Results Three SPP1 promoter polymorphisms, rs2853744:G>T, rs11730582:T>C and rs11439060:delG>G, were found to be significantly associated with risk of urolithiasis in indigenous genetic association study (OR = 3.14; p = 0.006, OR = 1.78; p = 0.006 and OR = 1.60; p = 0.012, respectively). We also observed a 1.68-fold positive association of a tri-allelic haplotype of these SPP1 promoter polymorphisms (G-C-dG) with risk of urolithiasis (OR = 1.68; p = 0.0079). However, no association was evident when data were stratified according to gender, age at first presentation, stone recurrence, family history of urolithiasis, parental consanguinity and stone multiplicity. The overall results from meta-analysis, which included 4 studies, suggested a significant association of SPP1 rs2853744:G>T polymorphism with susceptibility of urolithiasis (OR = 1.37; p = 0.004), but not for other SPP1 polymorphic variants analyzed. Conclusions In conclusion, we report significant association of 3 SPP1 polymorphisms with urolithiasis for the first time from South Asia, however, this association persisted only for SPP1 rs2853744:G>T polymorphism after meta-analysis of pooled studies. Further studies with a larger sample size will be required to validate this association and assess any potential usefulness in diagnosis and prognosis of renal stone disease.
Association of MUC1 5640G>A and PSCA 5057C>T polymorphisms with the Risk of Gastric Cancer in Northern Iran
Authors: Alikhani Reza , Taravati Ali , Hashemi-Soteh Mohammad Bagher
Published: February 2020

Background: Gastric cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. Genome-Wide Association Studies (GWAS) have shown that genetic diversities MUC1 (Mucin 1) and PSCA (prostate cell surface antigen) genes are involved in gastric cancer. The aim of this study was to determine the association between rs4072037G>A polymorphism in MUC1 and rs2294008 C>T in PSCA gene with gastric cancer in northern Iran. Methods: DNA was extracted from 99 formalin fixed paraffin-embedded (FFPE) tissue samples of gastric cancer and 96 blood samples from healthy individuals (sex matched) as controls. DNA was extracted followed by PCR using specific primers. Two desired polymorphisms, 5640G>A and 5057C>T for MUC1 and PSCA genes were genotyped using PCR-RFLP method. Results: The G allele at rs4072037 of MUC1 gene was associated with a significant decreased gastric cancer risk (OR= 0.50, 95% CI: 0.32 –0.79, p=0.003). A significant decreased risk of gastric cancer was observed in people with either AG vs AA and AG+AA vs GG genotype of MUC1 polymorphism (OR= 4.29, 95% CI: 1.19–15.51, p=0.01) and (OR= 3.54, 95% CI: 0.99–12.61, p=0.04) respectively. People with CT or TT genotype in PSCA polymorphism did not show any increased risk (OR = 1.139, 95% CI = 0.634-2.047, P = 0.662). Conclusion: Results indicated that the MUC1 polymorphism could be a risk factor in gastric cancer and could be considered a potential molecular marker in gastric cancer.
Plant and mouse EB1 proteins have opposite intrinsic properties on the dynamic instability of microtubules.
Authors: Molines Arthur T , Stoppin-Mellet Virginie , Arnal Isabelle , Coquelle Frédéric M
Published: February 2020

Objective Most eukaryotic cells contain microtubule filaments, which play central roles in intra-cellular organization. However, microtubule networks have a wide variety of architectures from one cell type and organism to another. Nonetheless, the sequences of tubulins, of Microtubule Associated proteins (MAPs) and the structure of microtubules are usually well conserved throughout the evolution. MAPs being known to be responsible for regulating microtubule organization and dynamics, this raises the question of the conservation of their intrinsic properties. Indeed, knowing how the intrinsic properties of individual MAPs differ between organisms might enlighten our understanding of how distinct microtubule networks are built. End-Binding protein 1 (EB1), first described as a MAP in yeast, is conserved in plants and mammals. The intrinsic properties of the mammalian and the yeast EB1 proteins have been well described in the literature but, to our knowledge, the intrinsic properties of EB1 from plant and mammals have not been compared thus far.Results Here, using an in vitro assay, we discovered that plant and mammalian EB1 purified proteins have different intrinsic properties on microtubule dynamics. Indeed, the mammalian EB1 protein increases microtubules dynamic while the plant EB1 protein stabilizes them.
New-onset diabetes mellitus after liver transplantation in the patients with acute liver failure: is there any effect of pretransplant hypoglycemia?
Authors: Topaloğlu Ömercan , Cengiz Muhammet , Cengiz Ayşe , Evren Bahri , Yoloğlu Saim , Yılmaz Sezai , Şahin İbrahim
Published: February 2020

Background:The frequency of new-onset diabetes after transplant(NODAT) is 5-30% in liver transplant recipients. Aims: We aimed to analyze the frequency and predictors of NODAT in the patients undergoing liver transplantation(LTx) due to acute liver failure(ALF), and to investigate whether pretransplant hypoglycemia had any effect on NODAT. Methods:Adult patients undergoing LTx due to ALF were analyzed retrospectively. The patients with chronic liver failure or diabetes were excluded. We measured pretransplant random blood glucose(RBG) and posttransplant fasting blood glucose(FBG). NODAT was diagnosed according to principally 1 st month FBG (group 1:<100, group 2:100-125, group 3:>125 mg/dL). The participants were subgrouped according to age, gender, BM, etiology, antiviral medication, thyroid function, pretransplant RBG, donor type, immunosuppressive drug, common infection, and surgical complication. Results:A total of 91 patients were analyzed; mean age was 33.48(±13.35), and 52.7%(n=48) of them was female. The etiology was Budd-Chiari syndrome in 3(3.29%), acute viral hepatitis in 38(41.75%), drug or toxin-related in 21(23.07%), and other/unknown causes in 29(31.86%) patients. The ratio of NODAT was 26.98% on the 1 st month. NODAT group had a higher pretransplant RBG than the others. Pretransplant hypoglycemia did not have any effect on NODAT; however, pretransplant hyperglycemia increased the risk of NODAT by 4.065 times(p=0.018). Conclusions:We showed that pretransplant hyperglycemia increased the risk of NODAT by 4 times, but hypoglycemia did not affect. The frequency of NODAT decreased progressively during follow-up. We recommend perioperative glycemic control should be maintained as early as possible to manage NODAT; however, it might be complicated in such a clinical condition.
Comparing the efficacy and safety of long and short acting drugs targeting Granulocyte Colony-stimulating Factor in cancer patients after chemotherapy: A systematic review and meta-analysis of randomized controlled trials
Authors: Zhang Xinwei , Wang Yong , Liu Fen , Chen Lin , Peng Lihong , Qiu Xiaotong , Fang Chen , Qian Xiaoyin , Li Yong
Published: February 2020

Background: Granulocyte Colony-Stimulating Factor (G-CSF) is widely targeted for the treatment of cancer patients after chemotherapy. However, the safety and efficacy comparisons of long (L-G-CSF) and short-acting (S-G-CSF) drugs targeting G-CSF are still lacking. Thus, herein, we attempted to address this issue by undertaking meta-analyses of existing studies using different drugs targeting G-CSF. Methods: The relevant studies were identified by searching Pubmed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. Febrile neutropenia (FN) was considered as the direct primary efficacy endpoint, while severe neutropenia (SN) and the duration of severe neutropenia (DSN) served as secondary efficacy endpoints. Bone pain (BP) was used as an indicator for safety analysis. All identified trials were assessed using the Cochrane Collaboration Tool and meta-analysis was performed using Review Manager 5.3 and STATA 15.0 software. Results: Our meta-analyses based on 20 randomized controlled trials (RCTs) revealed that L-G-CSF drugs including empegfilgrastim, L-G-CSF biosimilars, and pegfilgrastim were overall better in reducing FN incidence compared to S-G-CSF drugs like filgrastim and lenograstim (odds ratio [OR]=0.70, 95% confidence interval [CI]=0.54~0.92, p=0.01). Specifically, filgrastim resulted in higher FN risk than pegfilgrastim (OR=0.66, 95% CI=0.50~0.87, p=0.004). However, L-G-CSF and S-G-CSF drugs revealed no differences in terms of SN, DSN, and BP endpoints (SN: OR=0.92, 95% CI=0.78~1.09, p=0.33; DSN: RR=-0.04, 95% CI=0.17~0.09, p=0.53; BP: OR=0.87, 95% CI=0.67~1.14, p=0.31). Conclusion: Based on our analyses, L-G-CSF drugs in comparison to S-G-CSF drugs resulted in significantly lower FN incidence, but no difference in terms of the SN, DSN, and BP endpoints.