bluuebunny/crossref_metadata_2025_split huggingface dataset:
VCP Protects Neurons from Proteopathic Seeding
Authors: Zhu Jiang , Pittman Sara , Dhavale Dhruva , French Rachel , Patterson Jessica N. , Kaleelurrrahuman Mohamed Salman , Sun Yuanzi , Buscher William J. , Bieschke Jan , Kotzbauer Paul , Ayala Yuna , Davis Albert A. , Weihl Conrad C 
Published: August 2021

Abstract
Background: Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), tau, and TDP-43, contribute to neurodegeneration and disease progression. The cellular machinery necessary for this process is poorly understood. Methods: Cas9 expressing αS FRET biosensors were transduced with a whole-genome guide RNA (gRNA) library, seeded with αS fibrils, and flow-sorted. Candidate genes protective against αS seeding were identified following gRNA sequencing of FRET+ and FRET- cell populations. Secondary validation of the high probability candidate suppressor VCP, utilized VCP inhibitors or gene knockdown in αS biosensors and primary neurons. In vivo validation was performed in VCP disease mutation mice following intrastriatal injection of αS seeds. TDP-43 seeding was performed in primary neurons from control or VCP mutant mice.Results: We devised a genome-wide CRISPR-Cas9 screen to identify suppressors of αS seeding. This approach identified Valosin Containing Protein (VCP) as a suppressor of αS seeding. Dominant mutations in VCP cause multisystem proteinopathy (MSP) a phenotypically and pathologically variable neurodegeneraive disease characterized by myopathy, motor neuron disease and dementia with TDP-43, αS and tau inclusions. VCP inhibition or MSP disease mutations increased αS seeding in cells and primary cultured neurons. This was similar to treatment with the lysosomal damaging agent, LLoMe or knockdown of the endolysosomal damage response associated VCP cofactor, UBXD1. Intrastriatal injection of αS seeds into VCP disease mice demonstrated enhanced seeding efficiency as compared with controls. Finally, this phenomenon was not specific to αS since VCP disease mutant expression increased TDP-43 seeding in neurons.Conclusion: VCP surveillance of permeabilized late endosomes protects neurons against the proteopathic spread of pathogenic protein aggregates. The spread of distinct aggregate species may dictate the pleiotropic phenotypes and pathologies in VCP associated MSP.
Bone Metabolism In Patients With Type 1 Neurofibromatosis: Key Role of Sun Exposure and Physical Activity
Authors: Ferrara Ursula Pia , Tortora Cristina , BD Carmen Rosano , BD Antonia Assunto , Rossi Alessandro , Pagano Stefano , Falco Mariateresa , Simeoli Chiara , Ferrigno Rosario , D’Amico Alessandra , Salvio Dario , Cangemi Giuliana , Pivonello Rosario , Strisciuglio Pietro , Melis Daniela 
Published: August 2021

Abstract
Bone metabolism has been rarely investigated in children affected by Neurofibromatosis (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and BMD data obtained during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry (DXA) than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced BMD (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z.score (p = 0.000). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving BMD in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.
Deep Phenotyping Reveals Movement Phenotypes in Mouse Neurodevelopmental Models
Authors: Klibaite Ugne , Kislin Mikhail , Verpeut Jessica L. , Sun Xiaoting , Shaevitz Joshua W. , Wang Samuel S.-H. 
Published: August 2021

Abstract
Background: Repetitive action, resistance to environmental change, and fine motor disruptions are hallmarks of autism spectrum disorder (ASD) and other neurodevelopmental disorders, and vary considerably from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here, we aimed at investigating behavioral consequences of a cerebellum-specific deletion in Tsc1 protein and a whole-brain knockout in Cntnap2 protein in mice, both mutations are found in the clinical conditions and have been associated with ASD. We observed male and female C57BL/6J mice to methodically catalog adaptive movement over multiple days and examined two rodent models of developmental disorders against this dynamic baseline. Methods: Here, we use advances in computer vision and deep learning, a generalized form of high-dimensional statistical analysis, to develop a framework for characterizing mouse movement on multiple time scales using a single popular behavioral assay, the open field test. The pipeline takes virtual markers from pose estimation to find behavior clusters and generate wavelet signatures of behavior classes. We measured spatial and temporal habituation to a new environment across minutes and days, different types of self-grooming, locomotion and gait. Results: Both Cntnap2 knockout and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure-to-adapt took the form of maintained ambling, turning, and locomotion, and an overall decrease in grooming. Adaptation in Cntnap2 knockout mice more broadly resembled that of wild-type. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy. Limitations: Genetic risk factors for autism are numerous, and here we tested only two. Our pipeline was only applied to conditions of free behavior. Testing under task or social conditions would reveal more information about behavioral dynamics and variability. Conclusions: Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics. The reported deficits indicate that deep phenotyping constitutes a robust set of ASD symptoms that may be considered for implementation in clinical settings as a quantitative diagnosis criteria.
Impact of Dose Algorithm and Calculation Angle Interval on in Vivo Dose Verification of Stereotactic Body Radiation Therapy: A Phantom Study
Authors: Zhang Shuxu , Luo Songgui , Yu Hui , Lin Shengqu , Zhou Weibin , Zhang Guoquan , Zhang Quanbin , Zhou Pixiao , Zhang Ying , Liao Yuliang , Wang Ruihao 
Published: August 2021

Abstract
ObjectiveTo investigate the impact of different dose algorithms and calculation angle intervals (DCAI) on the in vivo dose (IVD) verification of small-field arc therapy in stereotactic body radiation therapy (SBRT).MethodsWe made an exit-dose-measuring and positioning device (EDPD) for the SRS MapCHECK (SMC) using polymethyl methacrylate (PMMA). Computed tomography data for the anthropomorphic head phantom, SMC, and EDPD combination were acquired with 1 mm slice thickness and spacing. SBRT partial arc plans were created using an SBRT cone, block, and a small square open field, with a gantry rotation angle of 60°. The dose distribution was calculated using three different dose algorithms [Pencil Beam (PB), CC Convolution (CCC), and Monte Carlo (MC)], with 1 mm isotropic resolution. We also used three different DCAIs (1°, 3°, 5°) with the PB and CCC algorithms to calculate the dose distribution of each plan three times. The uncertainty of each control point for the MC algorithm was set to 1%. The SMC was used to measure the exit dose outside the phantom for IVD verification, the detector plane was located 182.5 mm outside the scan center.ResultsWithin the phantom, the minimum passing rate of 3D gamma analysis (1%/1 mm) for the dose distributions calculated at different DCAIs was 99.1%, and the maximum relative deviation (RD) of the central point dose (CPD) was <0.2%. The average RD of the CPD for IVD verification was about 30% (range 16.71%–50.0%) for PB; -0.36% ± 1.82% (1° DCAI), -3.18% ± 7.83% (3° DCAI), and 3.69% ± 11.56% (1° DCAI) for CCC; and -0.38% ± 0.76 for the MC algorithm. The passing rates of 2D gamma analysis (3%/3 mm) between the predicted exit dose and the IVD were 100% for MC and >90% for the CCC algorithm at 1° DCAI.ConclusionThe DCAI for exit-dose calculations should be ≤1° using the CCC algorithm. Furthermore, among the three algorithms verified in the current study, the MC algorithm showed the highest accuracy, followed by CCC, with the PB algorithm having the worst performance. The PB algorithm is thus not suitable for exit-dose calculation or IVD verification of SBRT.
A Combined Experimental and Numerical Approach That Eliminates the Non-uniqueness Associated With the Johnson-cook Parameters Obtained Using Inverse Methods
Authors: Ojal Nishant , Cherukuri Harish P. , Schmitz Tony L. , Devlugt Kyle T. , Jaycox Adam W. 
Published: August 2021

Abstract
Johnson-Cook constitutive model is a commonly used material model for machining simulations. The model includes five parameters that capture the initial yield stress, strain-hardening, strain-rate hardening, and thermal softening behavior of the material. These parameters are difficult to determine using experiments since the conditions observed during machining (such as high strain-rates of the order of 10 5 /sec - 10 6 /sec) are challenging to recreate in the laboratory. To address this problem, several researchers have recently proposed inverse approaches where a combination of experiments and analytical models are used to predict the Johnson-Cook parameters. The errors between the measured cutting forces, chip thicknesses and temperatures and those predicted by analytical models are minimized and the parameters are determined.
In this work, it is shown that only two of the five Johnson-Cook parameters can be determined uniquely using inverse approaches. Two different algorithms, namely, Adaptive Memory Programming for Global Optimization (AMPGO) and Particle Swarm Optimization (PSO), are used for this purpose. The extended Oxley’s model is used as the analytical tool for optimization. For determining a parameter’s value, a large range for each parameter is provided as an input to the algorithms. The algorithms converge to several different sets of values for the five Johnson-Cook parameters when all the five parameters are considered as unknown in the optimization algorithm. All of these sets, however, yield the same chip shape and cutting forces in FEM simulations. Further analyses show that only the strain-rate and thermal softening parameters can be determined uniquely and the three parameters present in the strain-hardening term of the Johnson-Cook model cannot be determined uniquely using the inverse method. A combined experimental and numerical approach is proposed to eliminate this determine all parameters uniquely.
Analysis of Risk Factors Related to Acute Subarachnoid Hemorrhage After Spinal Surgery
Authors: Zhao Jianquan , Jiang Heng , Meng Yichen , Gao Rui , Ma Jun , Wang Ce , Zhou Xuhui 
Published: August 2021

Abstract
Study Design: A retrospective single-center study.Background: Subarachnoid hemorrhage (SAH) is a rare complication secondary to cerebrospinal fluid (CSF) leakage during spinal surgery, but the specific cause of the bleeding is still unclear. Objective：In this study, we studied cases of acute SAH after spinal surgery to find the related risk factors for bleeding.Methods: A total of 441 patients with CSF leakage who underwent spinal surgery in [BLINDED FOR REVIEW] from 2011 to 2020 were retrospectively analyzed. According to whether postoperative SAH occurred, they were divided into SAH group and Control group. By comparing the two groups of demographic data, past history, imaging data, intraoperative findings, perioperative complications, treatment conditions to find the risk factors of SAH, to provide guidance for the prevention of SAH after spinal surgery.Results: In SAH group, 17 cases (73.9%) had preoperative hypertension and 3 cases (13.0%) had diabetes. The intraoperative CSF leakage was about 118.4±56.9 ml. The mean postoperative drainage was 15.4±5.8 ml/h; Compared with SAH group, Control group had 123 cases (29.4%) with hypertension before operation, 40 cases (9.6%) with diabetes, intraoperative CSF leakage was about 76.3±23.0ml, and the mean postoperative continuous drainage 9.7±2.1ml/h. Binary logistic regression analysis showed that hypertension, intraoperative CSF leakage, and postoperative CSF continuous drainage speed are related to SAH. Conclusion: The rapid leakage of CSF caused by the rupture of the dural sac during operation and the rapid drainage of CSF after surgery are closely related to the occurrence of such complications. In addition, hypertension is a related factor of SAH during spinal surgery.
Elucidation of Adsorption Mechanisms And Mass Transfer Controlling Resistances During Single And Binary Adsorption of Caffeic And Chlorogenic Acids
Authors: Hernández-Padilla Eyden S. , Zárate-Guzmán Ana I. , González-Ortega Omar , Padilla-Ortega Erika , Gómez-Durán Azael , Delgado-Sánchez Pablo , Aguilar-Aguilar Angélica , Cortés Farid B. , Ocampo-Perez Raul 
Published: August 2021

Abstract
In this work, the potential of activated carbon to remove caffeic and chlorogenic acids was investigated. The study focused on evaluating the single and binary adsorption equilibrium, as well as investigating the mass transfer resistances present during the process by applying kinetic and diffusional models for a future scale-up of the process. For both compounds, the single adsorption equilibrium was studied at pH values of 3, 5, and 7. The experimental adsorption isotherms were interpreted using the Langmuir and Freundlich models, obtaining maximum adsorption capacities of 1.33 and 1.62 mmol/g for caffeic and chlorogenic acid, respectively. It was found that the adsorption mechanisms for both compounds was derived from π-π and electrostatic interactions. Also, the binary adsorption equilibrium was performed and the experimental data were interpreted using the extended multicomponent Langmuir model. The results evidenced that the binary adsorption of caffeic acid and chlorogenic acid is antagonistic in nature. The application of the first and second order kinetic models showed that the latter interpreted better the experimental data, obtaining R2 values close to one. Finally, the experimental adsorption rate data were interpreted by a diffusional model, finding the presence of different mass transfer resistances during the adsorption process. For both compounds, intraparticle diffusion mechanisms were meaningful.
Effect of Spermidine on Ameliorating Spermatogenic Disorders in Diabetic Mice Via Regulating Glycolysis Pathway.
Authors: Wang Jin Yuan , Ma Duo , Luo Min , Tan Yong-Peng , Zhong Ou , Tian Ge , Lv Yong-Ting , Li Mei-Xiang , Chen Xi , Tang Zhi-Han , Hu Linlin , Lei Xiao-Can 
Published: August 2021

Abstract
Diabetes mellitus (DM), a high incidence metabolic disease, is related to the impairment of male spermatogenic function. Spermidine (SPM), one of the biogenic amines, was identified from human seminal plasma and believed to have multiple pharmacological functions. However, there exists little evidence that reported SPM's effects on moderating diabetic male spermatogenic function. Thus, the objective of this study was to investigate the SPM's protective effects on testicular spermatogenic function in streptozotocin (STZ)-induced type 1 diabetic mice. Therefore, 40 mature male C57BL/6J mice male were divided into four main groups: the control group (n=10), the diabetic group (n=10), the 2.5 mg/kg SPM-treated diabetic group (n=10) and the 5 mg/kg SPM-treated diabetic group (n=10), which was given intraperitoneally for 8 weeks. The type 1 diabetic mice model was established by a single intraperitoneal injection of STZ 120 mg/kg. The results showed that, compare to the control group, the body and testis weight, as well the number of sperm were decreased, while the rate of sperm malformation was significantly increased in STZ-induced diabetic mice. Then the testicular morphology was observed, which showed that seminiferous tubule of testis were arranged in mess, the area and diameter of which was decreased, along with downregulated anti-apoptotic factor (Bcl-2) expression, and upregulated pro-apoptotic factor (Bax) expression in the testes. Furthermore, testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4) and Vimentin detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased. Compared to the saline-treated DM mice, SPM treatment markedly improved testicular function, with an increment in the body and testis weight as well as sperm count. Pro-apoptotic factor (Bax) was down-regulated expression with the up-regulated expression of Bcl-2 and suppression of apoptosis in the testes. What’s more, expression of WT1, GATA4, Vimentin and the expressions of glycolytic rate-limiting enzyme genes (HK2, PKM2, LDHA) in diabetic testes were also upregulated by SPM supplement. The evidence derived from this study indicated that the SMP's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation.
Drilling of Additive Manufactured Poly Lactic Acid Modified byDrilling of Additive Manufactured Poly Lactic Acid Modified by Ultrasonic Vibration Ultrasonic Vibration
Authors: Baraheni Mohammad , Shabgard Mohammad Reza , Amini Saeid 
Published: August 2021

Abstract
Complex geometries can be produced by using additively manufacturing method (AM). As usual, the AM parts have rough surfaces in which post processing operations are needed. One of the useful operations is ultrasonic drilling process. In this process, an additional movement is added to the cutting tool to improve the machinability factors. In this study, poly lactic acid(+) was selected as workpiece where the quality of the holes generated by ultrasonic drilling, were investigated. The examination parameters were delamination, circularity, and cylindricality. As a result, it was shown that UD process could properly improve the examination parameters. It was explained that harmonic movement of drill bit in UD improved the stability of the process by a decrease in cutting forces and chip adhesion. Moreover, a significant reduction was observed in delamination factor by using ultrasonic vibrations.
Pediatric Focal Segmental Glomerulosclerosis: Favorable Transplantation Outcome With Plasma Exchange
Authors: Fadel Fatina I , Bazaraa Hafez M , Mawla Mohamed A Abdel , Salah Doaa M 
Published: August 2021

Abstract
Background: Although kidney transplantation (KT) is the treatment of choice for pediatric kidney failure (KF); concerns for recurrence in cases of focal segmental glomerulosclerosis (FSGS) are still present. This study aimed to investigate the outcome of KT in children with KF secondary to FSGS, with implementation of preemptive perioperative plasma exchange (PE) for non-genetically proven patients.Methods: Forty FSGS pediatric kidney transplant recipients were studied. Of them: 12 patients (30%) had genetically proven NPHS2 mutations/familial and 28 (70%) were sporadic FSGS patients. Sporadic patients electively received 6 preoperative PE sessions. Recurrence of proteinuria was managed with PE and Rituximab (RTX). Kaplan-Meier curves were used to analyze graft and recurrence free survival data.Results: The mean follow-up duration after KT was 3.8 ± 2.86 years. Recurrence of proteinuria was encountered early postoperative in 11 patients (27.5%) and late (1.6 and 2.9 years after KT) in 2 patients (5%). Proteinuria was less in patients underwent native nephrectomy than others immediately postoperative and at assessment (p= 0.002 & 0.0031 respectively). One-year graft and patient survival was 93.8% with a mean 1-year serum creatinine of 0.67 ± 0.25 mg/dl. Three graft losses (7.5%) were due to chronic rejection 3.3, 3.75 and 4.17 years after KT and 2 patients' mortality (5%) occurred early postoperative (first 2 weeks) due to infection.Conclusion: FSGS transplanted children have favorable outcomes with perioperative PE for non-genetically proven cases. Early recurrence after KT can be successfully managed with PE and RTX.