bluuebunny/crossref_metadata_2025 huggingface dataset:
Selectively Targeting Breast Cancer Stem Cells By 8-Quinolinol and Niclosamide
Authors: Cámara-Sánchez Patricia , Díaz-Riascos Zamira V. , García-Aranda Natalia , Gener Petra , Seras-Franzoso Joaquin , Giani-Alonso Micaela , Royo Miriam , Vázquez Esther , Schwartz Simó , Abasolo Ibane
Published: August 2021

Background Cancer maintenance, metastatic dissemination and drug-resistance are sustained by cancer stem cells (CSCs). Triple negative breast cancer (TNBC) is the breast cancer subtype with the highest numbers of CSCs and poorest prognosis. Here, we aimed to identify potential drugs targeting CSCs to be further employed in combination with standard chemotherapy in TNBC treatment. Methods The anti-CSC efficacy of up to 17 small-drugs was tested in TNBC cell lines using cell viability assays on differentiated cancer cells and CSCs. Then, the effect of 2 selected drugs (8-quinolinol -8Q- and niclosamide -NCS-) in the cancer stemness hallmarks were evaluated using mammosphere growth, cell invasion, migration and anchorage-independent growth assays. Changes in the expression of stemness genes upon 8Q or NCS treatment were also evaluated. Moreover, the potential synergism of 8Q and NCS with PTX on the CSC proliferation and on stemness-related signaling pathways was evaluated using TNBC cell lines, CSC-reporter sublines, and CSCenriched mammospheres. Finally, the efficacy of the NCS in combination with PTX was analyzed in vivo using an orthotopic mice model of MDA-MB-231 cells. Results Among all tested drug candidates, 8Q and NCS showed remarkable specific anti-CSC activity in terms of CSC viability, migration, invasion and anchorage independent growth reduction in vitro. Moreover, specific 8Q/PTX and NCS/PTX ratios at which both drugs displayed a synergistic effect in different TNBC cell lines were identified. The solely use of PTX increased the relative presence of CSCs in TNBC cells, whereas the combination with 8Q and NCS counteracted this pro-CSC activity of PTX whilst significantly reducing cell viability. In vivo, the combination of NCS with PTX reduced tumor growth, and limited the dissemination of the disease by reducing the circulating tumor cells and the incidence of lung metastasis. Conclusions The combination of 8Q and NCS with PTX at established ratios inhibits both, the proliferation of differentiated cancer cells and the viability of CSCs, opening a way to more efficacious TNBC treatments.
Seismic Performance of a High-Rise Building by Using Linear and Non-Linear Methods
Authors: Çavdar Özlem
Published: August 2021

In this paper, the seismic behavior of existing reinforced concrete tall building is investigated by the linear and nonlinear dynamic analysis. The selected reinforced concrete structure was designed according to “Turkey Seismic Code-2007” (TEC-2007). A typical 41 story reinforced concrete building is designed. Turkey Building Earthquake Code-2018 (TBEC-2018) is utilized for evaluating the seismic performance of the selected building. Natural earthquake acceleration record selected and adjusted for compatibility with the adopted design spectrum, is used. A performance analysis according to the TBEC-2018 in a 41-story reinforced concrete shear wall-framed structure in Istanbul where active fault lines are located. The selected reinforced concrete shear wall unsymmetrical plan tall building is located in Istanbul, Turkey. The performance goals of the reinforced concrete shear wall structure are evaluated by applying procedures of the TBEC-2018 and nonlinear dynamic analysis. According to the Code, the reinforced concrete shear wall building is not expected to satisfy life safety performance levels under design earthquake.
Fulminant Myocarditis Complicated with Immune Checkpoint Inhibitor in Patients with Thymoma: Report of Three Cases and Literature Review
Authors: Huang Daozheng , Song Feier , Zhang Weidai , Ma Huan , Lin Xingtao , Qin Tiehe , Wang Shouhong
Published: August 2021

IntroductionImmune checkpoint inhibitors (ICIs) prevent the immune escape of tumor cells, which is beneficial to immune cells such as T lymphocytes to continuously monitor and kill tumor cells, and ultimately play an effective role in anti-tumor. ICI-associated myocarditis (irMyositis) was rarely reported, but its onset appeared latent, rapidly developed, and lethal, which has gradually attracted the attention of clinicians. Case ReportWe reported cases of fulminant myocarditis in 3 patients with thymoma who were treated with pembrolizumab, one of the programmed cell death protein 1 inhibitors (PD-1 inhibitors).Management & OutcomeThe 3 patients were treated with methylprednisolone, immunoglobulin. Temporary pacemaker implantation was performed when case 1 suffered atrioventricular dissociation and ventricular escape. Cardioversion was performed in case 2 for the onset of ventricular tachycardia. In case 3, Extra-Corporeal Membrane Oxygenation was implemented. Unfortunately, the heart function did not improve and was succeeded by multiple organ failure in all 3 cases. The family withdrew treatment and led to lethal outcomes.DiscussionAlthough ICIs have achieved encouraging results in anti-tumor, their adverse reactions cannot be ignored. Patients with thymoma are more prone to autoimmune reactions which are needed more attention1. We reported cases of immunotherapy-associated myocarditis in patients with previous PM, showing the clinical and pathological features in the specific populations.
Using Evolutionary Game Dynamics to Reproduce Phase Portrait Diversity in a Pandemic Scenario
Authors: Mendonça João , Brum Arthur , Lyra Marcelo , Lira Sérgio
Published: August 2021

Modeling the time evolution of a pandemic in distinct social and economic environments has proven to be a great challenge for scientists due to the strong coupling of infection dynamics to complex collective human behavior. In this work, we propose a relatively simple extension of the classical Susceptible-InfectedRecovered (SIR) model that encompasses evolutionary game imitation dynamics and is capable of reproducing basic features of real data such as recurrent waves with suppression and re-bounce of cases. In particular, we depict different quantitative and qualitative aspects of infection time series by representing them as trajectories in the modified phase portrait.
Description and Interrelationship Analysis of the Phenotypic and Genotypic Characteristics of MSSA and MRSA Strains Isolated From Healthcare Workers in North-eastern Brazil
Authors: de Oliveira Maraiza Alves , Andrade Yasmin Monara Ferreira Sousa , Souza Alisson da Costa , Silva Icaro Bonyek Santos da , Campos Guilherme Barreto , Marques Lucas Miranda , Doria Grace Anne Azevedo , Cavalcante Rafael Ciro Marques
Published: August 2021

Purpose: This study therefore sought to analyse the interrelationship between the phenotypic and genotypic characteristics of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA strains isolated from healthcare workers in north-eastern Brazil.Patients and methods: Staphylococcus aureus strains were isolated from nasal mucosa of nursing professionals. They are identified by biochemical analysis and the sensibility drug test were carried out by agar diffusion method. Biofilm formation was detected on the polystyrene plastic surface. Molecular characterization was conducted by polymerase chain reaction (PCR). The Chi-squared or Fisher's exact tests were applied for the analysis of associations between phenotypic and genotypic characteristics.Results: A total of 118 workers were involved, 49.15% of whom presented S. aureus. The most frequently observed strain was resistance to penicillin (86.21%), while the inducible clindamycin resistance (iMLSB) phenotype was detected in 48.84% of isolates. MRSA was found in 41.37% of isolates, while SCCmec type I was seen in 75%. A strain with intermediate resistance to vancomycin was also found. In terms of virulence genes, eta, tst, pvl, spa, clfA, icaA, icaC and icaD genes were detected at least once. Biofilm formation was detected in 89.65% of the strains - 18.97% of these were classified as strongly adherent. No associations with ica genes were detected. Multivariate analyses of clusters demonstrated variability between the strains, with the notable formation of three main clusters, according to phenotypic and genotypic characteristics.Conclusion: High prevalence, multidrug resistance and presence of MRSA strains were all observed. Most isolates had significant virulence genes and the ability to form biofilms, increasing the severity of potential infections. It is therefore necessary to monitor the strains circulating in this hospital and to intensify precautionary measures in order to prevent their spread.
A Clinical Prediction Model to Estimate the Risk for Coarctation of the Aorta: From Fetal to Newborn Life
Authors: Wang Hui-Hui , Zhu Mei , Liang Hao , Feng Juan , Zhang Nan , Wang Xi-Ming , Wang Yue-Mei , Yu Yong-Hui , Wang An-Biao
Published: August 2021

Purpose: This study aimed to develop a coarctation probability model incorporating prenatal cardiac sonographic markers to estimate the probability of an antenatal diagnosis of coarctation of the aorta (CoA). Methods: We reviewed 89 fetuses as a“investigation” cohort with prenatal suspicion for CoA and allotted to three ssubgroups:(1) severe CoA: symptoms onset of CoA and surgery within the first three months (15);(2) mild CoA: surgery within four months-one year (29); (3) false-positive CoA: this outcome does not require surgery (45). Using logistic regression to creat the multi-parametric model, and validated using a “validation” cohort of 86 fetuses with suspected CoA subsequently.Results: The prediction model had optimal criterion >0.25 with sensitivity 97.7% and specificity 59.1%, the area under the receiver operator curve is 0.8 which makes sense in diagnosis of CoA and risk stratification. The risk assessment demonstrated that fetuses with model probability>60% should make an inpatient observation for high risk of CoA whereas <15% should not undergo clinical follow-up imaging.Conclusion: Based on these results, we recommend measuring the model in all fetuses with suspected CoA may improve the accuracy of risk assessment. The objectivity of its parameters may allow its implementation working in multicenter studies of fetal cardiology.
Assessment of Interaction Between A Waste Storage Dam And Instability In Downstream Right-Side Slope By 3D Numerical Analyses
Authors: Gokceoğlu Candan , Unutmaz Berna
Published: August 2021

Waste dams (tailings) are used for storing the byproducts of mining operations and very common in mine industry. As the material they are storing can be harmful for the environment and the people in the vicinity, the construction of these dams is of high importance. During the construction phase, the topography of the site and geological- geotechnical parameters of the soils around the dam are as important as the stability and the leakage issues of the main dam body. In this paper, a nickel-ore waste dam located in Manisa-Gördes, Turkey is investigated in detail. At the downstream side of the dam, there was a slope instability at the right-hand side slopes due to improper loading on the top of these slopes. Whether this slope failure will affect the stability of main dam body or not is the main question of this study. Within these confines, 3D finite element analyses that cover a large area, including the dam, upstream and downstream sides and the waste have been performed before and after the planned downstream slope rehabilitation. The results show that after the rehabilitation of the slopes, the deformations decreased considerably and the waste dam became safer.
Fungal Community Diversity of a Heavy Metal Contaminated Soils Revealed by Metagenomics
Authors: Passarini Michel Rodrigo Zambrano , Ottoni Júlia Ronzella , Costa Paulo Emílio Santos , Hissa Denise Cavalvante , Falcão Raul Maia , Melo Vânia Maria Maciel , Balbino Valdir Queiroz , Mendonça Luiz Alberto Ribeiro , Lima Maria Gorethe de Sousa , Coutinho Henrique Douglas Melo , Verde Leandro Costa Lima
Published: August 2021

The inappropriate disposal of toxic compounds generated by industrial activity has been impacting to the environment considerably. Microbial communities inhabiting contaminated sites may represent interesting ecological alternatives for the decontamination of environments. The present work aimed to investigate the fungal diversity inhabiting sediments from industrial waste containing heavy metals by using metagenomic approach. A total of twelve fungal orders were retrieved from datasets and, at phylum level, Ascomycota was the most abundant, followed by Basidiomycota, Chytridiomycota and Blastocladiomycota. Higher abundance of sequences was encountered within the less contaminated site, while the lower abundance was found in the sample with the higher contamination with lead. Gene sequences related to DNA repair and heavy metals biosorption processes were found in the four samples analyzed. The genera Aspergillus and Chaetomium, and Saccharomycetales order were highly present within all samples, showing their potential to be used for bioremediation studies. The present work demonstrated the importance of using the metagenomic approach to understand the dynamics of fungal communities and their behavior under heavy metal contamination, aiming the use in bioremediation processes of environments contaminated with heavy metals.
The Mechanism of Improvement of Film Solubility: Design and Evaluation of Film Forming System with Terbinafine as a Model Drug
Authors: Zhang Jing , lu bohong , Ma Qiuyan , Om Shelke , Wu William , lin huaqing
Published: August 2021

Purpose: Film forming system (FFS) combines the advantages of patch and gel, it is expected to replace small doses of topical administration in the future. This work targets the design and evaluation of HPC-acrylic FFS with different excipients in appearance, rheology and in vitro properties. Also, the reason of improving the solubility of terbinafine film was illustrated by melting enthalpy thermo analysis.Methods: In this work, we prepared 8 HPC-acrylic FFS samples with different excipients, and characterized the film forming solutions and films in appearance, rheological properties, drug crystallization and in vitro performance. Then used melting enthalpy thermo-analysis to explain the mechanism of improvement of film solubility.Results: According to appearance evaluation, the samples which had a small amount of plasticizer could achieve an uniform surface morphology. The XRD and DSC demonstrated HPC could maintain drug amorphous in films. Based on oscillation frequency sweep, short chain plasticizer tributyl citrate (TBC) leading to strong entanglement and hydrogen bonding among the molecules. In vitro release test showed FP1 had favorable release. And the melting enthalpy thermo-analysis explained why FP1 had favorable release. Conclusions: HPC acted as an effective crystallization inhibitor. TBC could lead stronger intermolecular hydrogen bonds. The poloxamer had favorite miscibility with HPC-acrylic FFS. The combination of MCT and poloxamer with HPC resulted in a high Terbinafine solubility.
Three Novel Mutations in CYB5R3 Gene Causing NADH-cytochrome b5 Reductase Enzyme Deficiency Leads to Recessive Congenital Methaemoglobinemia
Authors: Deorukhkar Anuradha , KULKARNI Anuja , Kedar Prabhakar S
Published: August 2021

Two types of recessive congenital methaemoglobinemia (RCM) is caused by NADH-dependent cytochrome b5 reductase enzyme deficiency encoded by CYB5R3 gene. RCM-I is characterized by higher methaemoglobin levels (>2 g/dL), causing only cyanosis, whereas RCMR-II is associated with cyanosis with neurological impairment. The present study discovered three novel homozygous pathogenic variants of CYB5R3 causing RCM I and II in four unrelated Indian patients. In patient-1 and patient-2 of are of RCM type I caused due to novel c.175C>T (p.Arg59Cys) and other reported c.469T>C (p.Phe157Ser) missense pathogenic variants respectively, whereas patient-3 and patient-4 presented with the RCM type II are related to developmental delay with cyanosis since birth due to a novel homozygous (g.25679_25679delA) splice-site deletion and novel homozygous c.824_825insC (p.Pro278ThrfsTer367) single nucleotide insertion. The CYB5R3 transcript levels were estimated by qRT-PCR in the splice-site deletion, which was 0.33fold of normal healthy control. The insertion of nucleotide C resulted in a frame-shift of termination codon are associated with neurological impairment. This study can help to conduct genetic counselling and, subsequently, prenatal diagnosis of high-risk genetic disorders.
Serum miR-192-5p Levels Predict the Efficacy of Pegylated Interferon Therapy for Chronic Hepatitis B
Authors: Nagura Yoshihito , Matsuura Kentaro , Iio Etsuko , Fujita Koji , Inoue Takako , Matsumoto Akihiro , Tanaka Eiji , Nishiguchi Shuhei , Kang Jong-Hon , Matsui Takeshi , Enomoto Masaru , Ikeda Hiroki , Watanabe Tsunamasa , Okuse Chiaki , Tsuge Masataka , Atsukawa Masanori , Tateyama Masakuni , Kataoka Hiromi , Tanaka Yasuhito
Published: August 2021

We examined the association between serum miRNA (-192-5p, -122-3p, -320a and − 6126-5p) levels and the efficacy of pegylated interferon (Peg-IFN) monotherapy for chronic hepatitis B (CHB) patients. We enrolled 61 CHB patients treated with Peg-IFNα-2a weekly for 48 weeks, of whom 12 had a virological response (VR) and 49 did not VR (non-VR). A VR was defined as HBV DNA < 2,000 IU/ml, hepatitis B e antigen (HBeAg)-negative, and nucleos(t)ide analogue free at 48 weeks after the end of treatment. The non-VR group showed a significantly higher HBeAg-positivity rate, ALT, HBV DNA, and serum miR-192-5p levels at baseline (P = 0.024, P = 0.020, P = 0.007, P = 0.021, respectively). Serum miR-192-5p levels at 24 weeks after the start of treatment were also significantly higher in the non-VR than the VR group (P = 0.011). Multivariate logistic regression analysis for predicting VR showed that miR-192-5p level at baseline was an independent factor. Serum miR-192-5p levels were significantly correlated with the levels of HBV DNA, hepatitis B core-related antigen, and hepatitis B surface antigen (r = 0.484, 0.384 and 0.759, respectively). The serum miR-192-5p level was useful as a biomarker for the therapeutic efficacy of Peg-IFN in CHB treatment.
Naringenin Enhances Anti-Proliferation Effect of FMSP On K562 Human Chronic Myelogenous Leukemia Cells Via Targeting Calmodulin Signaling Pathway
Authors: Rajabi Sadegh , Noori Shokoofe , Ashrafi Mohammad Reza , Movahed Mahsa Azami , Farzaneh Shabnam , Zarghi Afshin
Published: August 2021

Background: FMSP is a synthesized ferrocene derivative which possesses strong anti-proliferative and apoptosis inducing characteristics on tumor cells. Naringenin as a polyphenolic flavonoid is also able to reduce cell viability in tumors.Methods: Cell viability and proliferation of cancer cells after treatment with these agents were determined with MTT assay. To predict the possible interaction between calmodulin (CaM) and FMSP and naringenin, docking stuies were performed. By using fluorescence emission spectra, effects of FMSP and naringenin on CaM structure and activity were studied. CaM-dependent activation of phosphodiesterase 1 (PDE1) by FMSP in relation to naringenin and their combination were compared. Effects of these compounds on PDE1 inhibition, cAMP accumulation, and cAMP-dependent protein kinase A (PKA) activation were assayed. Results: Our results showed that combination of FMSP and naringenin had more inhibitory effects on CaM structure than FMSP and naringenin alone. Results of docking analyses also confirmed efficient intraction of the two compunds with hydrophobic pocket of calmodulin active site. Kinetic analyses of these agents interaction with CaM showed FMSP and naringenin both competitively inhibited PDE1 activation without changing Vmax parameter. FMSP and naringenin synergistically increased Km values in a higher level compared to FMSP or naringenin alone. Combination of these two agents also had more cytotoxic effects on K562 cells than FMSP alone. Conclusions: It was shown that mechanism of K562 cell proliferation inhibition by these compounds is based on CaM and consequent PDE inhibition followed by intracellular cAMP level elevation and increased PKA activity in a dose-dependent manner.
Systematic Analysis of Plasma Exosome MiRNA in Patients with Postmenopausal Osteoporosis
Authors: Zhu Chengxin , Xu Jingze , Cao Shu , Yang Changqing , Li Renhu , Wang Changqing , Shao Song
Published: August 2021

Background: More and more studies have shown that exosomes are involved in many aspects of bone metabolism. As the content of exosomes, miRNA plays an important role in the early diagnosis, treatment and prognosis evaluation of osteoporosis.Objective: To determine the potential molecular markers of osteoporosis by analyzing the differences of plasma exosome miRNA expression between postmenopausal women with osteoporosis and healthy controls.Methods: Serum samples of postmenopausal osteoporosis (PMOP) patients over 65 years old (n = 12) and healthy controls (n = 12) were collected. The exosomes were separated by molecular size exclusion chromatography(SEC).The differentially expressed miRNAs were analyzed by cluster analysis. The target genes of miRNAs were predicted and annotated by relevant software.The target genes were classified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The appropriate biomarkers were screened out.Results: The miRNA spectrum of the patients was significantly different from that of the control group. Validation studies showed that 14 up-regulated miRNAs had a high probability of prediction, which could distinguish osteoporosis patients from healthy controls. Thirty-one genes were predicted to be targets for these miRNAs. GO enrichment analysis showed that miRNAs were mainly concentrated in protein binding, carbohydrate-binding, chromatin binding and protein kinase binding. KEGG enrichment analysis showed that miRNAs were mainly concentrated in the p53 signalling pathway, mineral absorption, glycerin metabolism, insulin secretion, glycosaminoglycan biosynthesis heparin sulfate /heparin pathway. This study identified a large number of differentially expressed miRNAs in plasma samples from postmenopausal women with osteoporosis. It may help to obtain new diagnosis and treatment strategies for PMOP.Conclusion: Our study identified the characteristics of plasma miRNAs in patients with osteoporosis and identified 14 candidate miRNAs, which may be useful biomarkers of osteoporosis. We speculate that these differentially expressed miRNAs may play a key role in the process of bone marrow mesenchymal stem cells osteogenic metabolism and transformation.
Thermo-Responsive Hydrogels Based on Methylcellulose/Persian Gum Loaded With Taxifolin Enhance Bone Regeneration: An in Vitro / in Vivo Study
Authors: Sajadi-Javan Zahra Sadat , Varshosaz Jaleh , Mirian Mina , Manshaei Maziar , Aminzadeh Atousa
Published: August 2021

In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25-1.5 w/v% PG and 1-7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells.
Novel ideas for the comprehensive evaluation of varus knee osteoarthritis: radiological measurements of the morphology of the lateral knee joint
Authors: Ma Wenru , Wang Fengkun , Sun Shengnan , Han Zengshuai , Ding Lei , Zhang Yingze , Yu Tengbo , Zhang Yi
Published: August 2021

BackgroundThe lateral anatomical and morphological characteristics of knees with varus knee osteoarthritis (OA) have not received sufficient attention. This study used several radiological parameters to describe the morphological characteristics of the lateral knee with OA to determine whether there are relationships between varus knee OA and parameters such as lateral plateau widening (LPW), proximal fibula curvature (PFC), and fibula height (FH).MethodsThe study retrospectively analyzed 1072 subjects [376 males, 696 females; mean age 66.84 ± 7.04 (range 46–83) years; mean body mass index (BMI) 26.98 ± 3.22 kg/m²] who underwent standard radiography for diagnosing or evaluating symptomatic knee joint disease. The 163 Kellgren and Lawrence (K-L) grades 0 and I knees were categorized into the no-knee-OA group, and the 909 K-L grades II–IV knees were classified into the knee-OA group. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), and hip-knee-ankle angle (HKAA) were measured to investigate varus knee deformity. The LPW, PFC, and FH were measured. T-tests and chi-square tests were used to compare each index between the two groups. Binary logistic regression was performed to examine the correlation between indexes and knee OA occurrence. Principal component analysis was used to calculate the comprehensive principal component score of varus deformity, which was used to comprehensively evaluate the knee varus deformity degree by reducing the original data's dimension. Multiple logistic and linear regression analyses were performed to examine the correlations between the three parameters and K-L grades and the comprehensive principal component score of varus deformit.ResultsLPW and PFC were significantly greater and FH was significantly smaller in the knee-OA group than in the no-knee-OA group. LPW, PFC, and FH were correlated with knee OA occurrence. One principal component, named the comprehensive principal component score of varus deformity, was extracted from the three indexes, and the total variance of the principal component interpretation was 76.60%. Multivariate logistics and linear regression analysis showed that after adjusting for age and BMI, LPW and PFC were positively correlated with K-L grading and varus deformity. FH was significantly and negatively associatedwith K-L grading and varus deformity (all P < 0.05).ConclusionsRegular morphological changes take place in the lateral knee with varus OA, including lateral dislocation of the tibial plateau, proximal fibula bending, and upward movement of the fibular head. Changes in LPW, PFC, and FH could enable a more comprehensive assessment of varus knee OA occurrence, severity, and deformity.Level of EvidenceRetrospective Study Level III
A Finite Element Analysis and Cyclic Load Experiment on an Additional Transcortical-Type Hole Formed Around The Proximal Femoral Nail System’s Distal Locking Screw
Authors: Cho Hong Man , Choi Seung Min , Park JiYeon , Lee Young , Bae Jung Hyung
Published: August 2021

Background
A complication associated with the distal locking screw used in the proximal femoral nail (PFN) system is the formation of accidental additional holes. We hypothesized that an increase in stress around additional holes is a relevant factor contributing to fractures. This study aimed to evaluate stress changes in the cortical bone around additional screw holes using finite element analysis.
Methods
Proximal femoral nail PFN antirotation (PFNA)-II (Synthes, Solothurn, Switzerland) was inserted into a femur model. An additional 4.9-mm transcortical hole was made either anteriorly (anterior hole model) or posteriorly (posterior hole model) to the distal locking screw. Finite element analysis was used to calculate compression, tension, and load limits to investigate stress around additional holes with respect to the direction of screw penetration and degree of osteoporosis. The results were then compared with those of mechanical testing. A 31A-21 type intertrochanteric fracture was applied. As a control group, a model without additional holes (no-hole model) was developed. Repeated load-loading tests were performed on 10 model bones per model group.
Results
Tensile stress was significantly greater in the no-hole model when additional screw holes were present, and the anterior hole showed a higher maximum stress value than the posterior hole did, suggesting that the anterior hole was more susceptible to fracture. The change in tensile stress first appeared in the hole around the lateral cortical bone and proceeded to the medial side. Biomechanical testing showed that fractures around the distal locking screw occurred in 0 cases of the no-hole, 10 of anterior hole, and 9 of the posterior hole models.
Conclusions
During PFN surgery for intertrochanteric fracture, holes with distal locking screws fixed and removed at the anterior and posterior of the nail can be a risk factor for fractures in the surrounding area.
Study on a Risk Model and Target Detection for Prediction and Avoidance of Unmanned Environmental Hazard
Authors: Qiu Chengqun , Zhong Yuan , Ji Jie , Zhang Shuai , Zhang Hui , Zhao Shiqiang , Meng Mingyu
Published: August 2021

Comprehensive research is conducted on the design and control of the unmanned systems for electric vehicles. The environmental risk prediction and avoidance system is divided into the prediction part and the avoidance part. The prediction part is divided into environmental perception, environmental risk assessment, and risk prediction. In the avoidance part, the conservative driving strategy based on speed restriction is adopted according to the results of risk prediction. Additionally, the core function is achieved through the target detection technology based on deep learning algorithm and the data conclusion based on deep learning method. Moreover, the location of bounding box is further optimized to improve the accuracy of SSD target detection method based on solving the problem of unbalanced sample categories. Software such as MATLAB and Carsim are applied in the system. From the comparison results of the simulations of unmanned vehicles with or without a system, it that the system can provide effective safety guarantee for unmanned driving.
A Conserved MTMR Lipid Phosphatase Increasingly Suppresses Autophagy in Brain Neurons During Aging
Authors: Kovács Tibor , Szinyákovics Janka , Billes Viktor , Murányi Gábor , Varga Virginia B. , Bjelik Annamária , Légrádi Ádám , Szabó Melinda , Sándor Sára , Kubinyi Enikő , Szekeres-Paracky Cecília , Szocsics Péter , Lőke János , Mulder Jun , Gulyás Balázs , Palkovits Miklós , Gulya Károly , Maglóczky Zsófia , Vellai Tibor
Published: August 2021

The authors have requested that this preprint be removed from Research Square.
Growth, Feed Intake And Conversion Ratio of Improved Goats Fed Brachiaria Grass And Napier Grass Mixed With or Without Leucaena Leaf Meal
Authors: Mutimura Mupenzi , Hitimana Pierre Celestin , Shumbusho Felicien , Manzi Maximillian
Published: August 2021

This study assessed the growth and feed intake performances of Galla goats and their crosses with local goats fed on Brachiaria grass cultivar Mulato II and Napier grass mixed with Leucaena leaf meal. Twenty-four Galla goats and 24 crossbred goats were selected and divided into four groups of three goats for each genotype and put in a partitioned house for goats’ stall feeding. Goats from each group were identified using ear tags, randomised and then allotted one of the dietary treatments. Feed rations used as treatments were hay of Mulato II, silage of Napier grass, Mulato II, ML (67% Mulato + 33% Leucaena leaf meal) and NL (67% Napier grass + 33% Leucaena leaf meal). Individual goat weights were taken on a weekly basis. Feed samples of each diet were collected every week and analysed for nutritive values. The chemical composition of feed showed significant differences (P<0.05) among diets. Absolute and relative nutrient intakes showed that Galla goat had a higher DM intake of NL compared to other diets and in crossbreds. Galla goats had a higher feed conversion ratio for DM from Napier and NL diets. Mulato II increased body weight up to 29% and 47% over Napier grass in crossbreds and pure Galla goats, respectively. The findings suggest that Mulato II could be a better feed resource for growing goats. Further studies should be conducted by increasing the levels of Leucaena leaf-meal in the diets and determine nitrogen retention and quality of meat under the same feeding regime.
A Method of Predicting The Best Conditions for Clamping a Large-Size Workpiece in Order To Reduce Vibrations in The Milling Process
Authors: Kaliński Krzysztof J. , Stawicka-Morawska Natalia , Galewski Marek A. , Mazur Michał R.
Published: August 2021

The paper presents an innovative method of solving the problem of vibration suppression during milling of large-size details. It consists in searching for the best conditions for clamping the workpiece based on a rapid modal identification of the dominant natural frequencies only and requires repetitive changes in the tightening torque of the clamping screws. Then, by estimating the minimum work of the cutting forces acting in the direction of the width of the cutting layer, it is possible to predict the best fixing of the workpiece. Application of the method does not require the creation and identification of a computational model of the process or preliminary numerical simulations. The effectiveness of this method was confirmed by the evaluation of the Root Mean Square (RMS) of the vibration level in the time domain observed during the actual face milling process.
M-line TTN Mutations in Salih Myopathy: Novel Biallelic Mutation and Review of the Literature
Authors: Kadiri Youssef El , Ratbi Ilham , Lyahyai Jaber , Sefiani Abdelaziz
Published: August 2021

Background: Salih myopathy (SALMY), also known as early-onset myopathy with fatal cardiomyopathy (EOMFC) is a rare, heterogeneous, and severe form of titinopathies with autosomal recessive inherited neuromuscular disorders that affects both skeletal and cardiac muscles. It was previously identified only in the Arab population with unknown incidence. TTN mutations that have been reported in congenital myopathies are associated with a variety of phenotypic spectrum of titinopathies, which are scattered along the 364 exons of the gene. We report a Moroccan family with an affected patient diagnosed with Salih myopathy by next-generation sequencing (NGS) with a literature review of this rare entity.Methods: Genetic investigation by NGS was performed in a consanguineous Moroccan female child aged 29 months with congenital myopathy. Sanger sequencing confirmation was performed on the patient and both of her parents. Clinical and molecular data of the patient were correlated with 14 patients reported in the literature for congenital myopathy associated with a heart defect or development of dilated cardiomyopathy with at least one mutation in the M-band titin protein as inclusion criteria. Results: Bioinformatics analysis of Clinical Exome Sequencing (CES) data identified a novel homozygous truncating mutation c.106541delA p.(Asp35514Valfs*32) in exon 361 of the TTN gene. Sanger sequencing confirmed the mutation at a homozygous state in the proband and that both her parents are heterozygous carriers. Conclusions: Application of next-generation sequencing in rare genetic heterogeneous forms as SALMY provides more evidently an increasing proportion of congenital myopathies than currently recognized and expands the mutation spectrum of the TTN gene for better guiding the genetic diagnosis with adequate genetic counseling to the Moroccan families.
Prevalence of Leptospirosis Among Patients Attending Renal and General Outpatient Clinics in Mulago Hospital, Kampala, Uganda
Authors: Wambi Rogers , Worodria William , Muleme James , Aggrey Siya , Mugisha Lawrence
Published: August 2021

In this study we sought to establish the prevalence and associated factors of Leptospirosis among renal patients and general outpatients attending Mulago National Referral Hospital, Uganda. This cross-sectional study recruited and collected blood samples from a total of 254 patients attending Mulago hospital from July to October 2018. Additionally, the semi-structured questionnaires were administered to enrolled patients to collect data on socio-demographics and occupational practices that may be risks of getting infected with Leptospirosis. The blood samples were analyzed using the standard Microscopic Agglutination Test (MAT) with a panel of 14 Leptospira-serovars belonging to 10 serogroups. We identified 12 seropositivity of Hebdomadis, Hebdomadis (L.borgapetersenii serovar Nona), Icterohaemorrhagiae (L.interrogans Serovar Icterohaemorrhagiae, Canicola (L. interrogans serovarCanicola), Djasiman (L. interrogansserovarDjasiman), Pomona (L. interrogans serovar Pomona) and Ballum (L. borgpetersenii serovar Kenya). The overall prevalence of leptospirosis in examined samples was 4.7% (CI = 2.6-8.3, P<0.05) among patients attending Renal and General Outpatient clinics in Mulago hospital. The participants who reported with fever were 15.4 times more likely to be diagnosed with leptospirosis. The study reveals that leptospirosis may be among the causative agents among renal patients and should be included among the differential diagnostic list to consider for further testing and diagnosis.
Mid-Term Outcomes of Cemented Stem and Subtrochanteric Shortening Derotational Osteotomy in Total Hip Arthroplasty for Crowe IV Developmental Dysplasia
Authors: Huang Zhe-Yu , Ling Jing , Zeng Zhi-Min , Di Zheng-Lin , Zhang Jun-Hui , Tao Kun
Published: August 2021

Background Performing total hip arthroplasty (THA) in patients with Crowe IV developmental dysplasia of the hip (DDH) is technically challenging. Subtrochanteric shortening osteotomy is typically required for placing the acetabular component within the anatomic hip center. However, the outcomes of subtrochanteric osteotomy using cemented components are not widely reported. This study aimed to evaluate the outcomes of cemented stem THA with subtrochanteric femoral shortening and transverse derotational osteotomy in patients with Crowe IV DDH.Methods We retrospectively evaluated data of patients with Crowe IV DDH who underwent cemented stem THA with subtrochanteric femoral shortening and transverse derotational osteotomy between 2010 and 2018. Patients who underwent surgery at the hip joint were excluded. Data regarding pre- and postoperative clinical and radiological parameters were collected and reviewed.Results Among 14 patients included (14 hips), the mean age was 60.4 (range, 47–73) years. The mean Harris hip score improved from 40.7 to 87.7. The mean limb length discrepancy reduced from 52 mm to 12.7 mm. No neurologic deficits were noted. The mean osteotomy union time was 10.6 months. Delayed union and postoperative dislocation were observed in one and two patients, respectively. Cement leakage into the osteotomy gap was observed in one patient. No revisions were required. No signs of loosening or migration were observed. Conclusions Cemented stem THA combined with subtrochanteric femoral shortening and transverse derotational osteotomy is safe and effective for the treatment of patients with Crowe IV DDH. The cemented femoral component showed promising mid-term follow up results. However, cement leakage affects bone healing. Osteotomy and cementing should be performed meticulously.Trial Registration: Retrospectively registered
Impact of Management Factors on Seminal Attributes and Frozen Semen Doses Production in Holstein Friesian Crossbred Dairy Bulls
Authors: Mandal Dilip Kumar , Kumar Mahesh , Tyagi Shrikant
Published: August 2021

This study reports on important management factors that have impacts on semen characteristics, sperm production ability and cryo-preservability in dairy bulls. Except volume, bull types (FSD i.e. frozen semen dose producer vs Non-FSD bulls) differentiated most of the semen traits (P < 0.01). Age showed significant impacts on seminal attributes both in FSD and Non-FSD bulls. In FSD bulls semen traits increased significantly even up to 5 years age, in contrast, only 2 years in Non-FSD bulls. Overall semen quality index improved almost linearly with age advancement in FSD bulls (P < 0.01) but not in Non-FSD bulls, which showed very irrational trends. Seasons significantly (P < 0.01) influenced ejaculate characteristics. Overall semen quality, total sperm output and FSD production was the highest during summer and lowest in rainy seasons. Within a bull type (FSD/non-FSD) influence of age and season, and within age group impact of seasons was significant in most of the semen attributes. It was concluded that dependent on season, age of bull significantly influenced qualitative and quantitative attributes of semen; improvement being substantial in FSD bulls, but negligible in non-FSD bulls beyond 2 years age. Seasons of collection significantly influenced semen quality, sperm productivity and FSD production of bulls being highest in summer, followed by winter and least in rainy seasons. The study recommended that for effective FSD production, poor semen producer bulls should be culled as early as 2 years of age and during rainy season stress amelioration measures might mitigate FSD production losses from crossbred bulls.
The effect of low dose γ-irradiation on the optoelectric properties of n-GaN based MSM structure
Authors: Barghamadi Leyla , Alam Shahab Norouzian , Ghafari Bijan , Sedighy Seyed Hassan
Published: August 2021

The room temperature effect of a low dose rate (10-4 rad (Si)/s) 60 Co γ-irradiation on the structural propertiesand dark current of the GaN-based metal-semiconductor-metal (MSM) structure has been studied. In contrast to previous studies, a non-monotonous dependence of the dark current with the γ-irradiation dose is observed. The intensity and linewidth of the photoluminescence (PL) peaks correlate with the changes in electrical characteristics and eventually degrade after prolonged exposure to the γ-radiation. The abnormal behavior of the MSM structure and particularly its I-V and PL characteristics are explained by considering the carrier transfer mechanism in the localized states. These phenomena are associated with the decrease of shallow donors’ density in localized states and the activation of the non-radiative centers as radiation dose increases. These experimental results and the mechanism presented are essential for understanding the interaction of the γ-irradiation with n-GaN and for estimation of reliability of GaN-based (opto)electronics in harsh conditions of γ-radiation (space applications, liquidation of consequences of technogenic catastrophes, etc.).
Network Analysis of Trauma in Patients With Early-Stage Psychosis
Authors: Kheirabad Maryam Karami , Yun Je-Yeon , Nguyen Thong Ba , Rami Fatima Zahra , Piao Yan Hong , Li Ling , Lee Bo Mi , Kim Woo-Sung , Sui Jing , Kim Sung-Wan , Lee Bong Ju , Kim Jung Jin , Yu Je-Chun , Lee Kyu Young , Won Seung-Hee , Lee Seung-Hwan , Kim Seung-Hyun , Kang Shi Hyun , Kim Eui Tae , Chung Young Chul
Published: August 2021

Objectives: Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls.Methods: We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated.Results: The nodes with the highest predictability and expected influence in both patients and controls were cognitive (Co) and emotional domains (Em) of the BS and emotional abuse (EMO) of the ETI. The EMO was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative other (NO) and negative self (NS) of the BCSS mediated EMO to other BCSS or BS for patients and controls, respectively.Conclusion: Our findings suggest that rumination and EMO were central symptoms in both groups and that NO and NS played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002
Mxene-Assisted Organic Electrochemical Transistor Biosensor With Multiple Spiral Interdigitated Electrodes for Sensitive Determination of fPSA/tPSA.
Authors: Zhu Yi-Cheng , Cai Biao , Jiang Quan , Zhang Yuan , Sha Jianjun , Xie Shaowei
Published: August 2021

Background: The ratio of fPSA/tPSA in the “grey zone” of tPSA with the concentration range between 4 ng/ml and 10 ng/ml is significant for diagnosis of prostate cancer, and highly efficiency quantification of the ratio of fPSA/tPSA remain elusive mainly because of their extremely low concentration in patients’ peripheral blood with high biosample complexity.Methods: We presented an interdigitated spiral-based MXene-assisted organic electrochemical transistors (isMOECTs) biosensor for highly sensitive determination of fPSA/tPSA. The combination of MXene and the interdigitated multiple spiral architecture synergistically assisted the amplification of amperometric signal of biosensor with dual functionalizations of anti-tPSA and anti-fPSA.Results: The ultrasensitivity of the biosensor was enhanced by tunable multiple spiral architecture and MXene nanomaterials; and the sensor demonstrated enhanced detection limit of tPSA and fPSA down to 0.01 pg/ml, as well as satisfactory selectivity, reproducibility and reliability, which was comparable to the best previous literatures; Moreover, the isMOECTs displayed area under the curve (AUC) value of 0.8138, confirming the potential applications of isMOECTs in clinics.Conclusions: The merits of isMOECTs biosensor demonstrated the reliability of MXene-assisted organic electrochemical transistor biosensor with multiple interdigitated spiral for ultrasensitive quantification of fPSA/tPSA, suggesting potential current and future point-of-care testing applications.