bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.