bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the National System for Rare Diseases in China from the Point of Drug Access: Progress and Challenges
Authors: Qiao Luyao , Liu Xin , Shang Junmei , Zuo Wei , Xu Tingting , Qu Jinghan , Jiang Jiandong , Bo Zhang , Zhang Shuyang 
Published: May 2022

Abstract
Background: There are about 7000 rare diseases worldwide, of which only 5% of the diseases can be treated with medicines, showing that it’s important to improve patient access to orphan drugs. Recently, China has actively worked to set up a national system for rare diseases to improve the diagnosis and treatment capabilities and ensure the accessibility of drugs. However, the benefits of the system have yet not to be measured. This study aimed to provide an overview of orphan drug access based on the Compendium of China’s First List of Rare Diseases and National Network to Collaborate on Diagnosis and Treatment of Rare Diseases, expecting to map a blueprint for orphan drug access in China. Methods: Framework of China’s national system for rare diseases was summarized. We surveyed the availability and affordability of 79 approved orphan drugs based on the Compendium of China’s First List of Rare Diseases in 30 leading provincial institutions from 2017 to 2020. The availability was measured annually at 3 levels (market, hospital and drug), and affordability was reflected by comparing costs of daily defined dose with per capita income of urban and rural residents, with the National Basic Medical Insurance considered. Results: The market availability of orphan drugs in China showed an upward trend. As of 2020, the median hospital-level availability was 41.1% (increased by 1.5 times), highly available drugs increased by 16.5%. There were 64 / 74 orphan drugs that were affordable to rural/urban residents with the National Basic Medical Insurance considered (an increase of 14.1%), and the urban-rural gap of affordability ratio was narrowed (down by 6.0%). Comprehensive analysis showed the proportions of drugs with better availability and affordability in urban and rural areas by 2020 were 26.53% and 21.43%, respectively, which had increased but were still at a low level.Conclusions: China’s national system for rare diseases has made great progress in orphan drug access, indicating that it’s been functioning under the joint reformation of medical treatment, medical insurance and medicines supply. The list of rare diseases will be updated and collaboration in networks will be enhanced to further improve the system.
Introgression of the RppQ gene from field corn improves southern rust resistance in sweet corn
Authors: Zhang Nan , Qi Xitao , Li Xiaofeng , Li Guangyu , Li Gaoke , Hu Jianguang 
Published: May 2022

Abstract
Southern rust, one of the most destructive foliar diseases of sweet corn (Zea mays convar. saccharata var. rugosa), is caused by Puccinia polysora Underw. and leads to enormous yield losses and reduced quality of sweet corn in China. Utilization of resistance genes is an effective and environmentally friendly strategy for improving southern rust resistance of sweet corn. However, improvement is hampered by a lack of resistance genes in Chinese sweet corn germplasm. In this study, we used marker-assisted backcross breeding to introgress the southern rust resistance gene RppQ from Qi319, an inbred line of southern rust resistant field corn, into four elite sweet corn inbred lines, 1401, 1413, 1434, and 1445. These are parental inbred lines of the popular sweet corn varieties Yuetian 28, Yuetian 13, Yuetian 16, and Yuetian 27. We developed five RppQ-based markers, M0607, M0801, M0903, M3301, and M3402, and employed these for foreground selection; 92.3 to 97.9% of the recurrent parent genomes were recovered following three or four rounds of backcrossing. The four newly developed sweet corn lines all showed significant improvement of southern rust resistance compared with their respective parent lines. Meanwhile, there was no significant difference in phenotypic data for agronomic traits. In addition, reconstituted hybrids derived from the converted lines retained resistance to southern rust, while other agronomic traits and sugar content remained unchanged. Our study provides an example of successful development of southern rust resistant sweet corn using a resistance gene from field corn.
Theoretical calculation and experiment of the impact characteristics in the plane ultrasonic rolling
Authors: Lan Shuai-ling , Qi Meng , Liu Ming-xian , Bie Wen-bo 
Published: May 2022

Abstract
To achieve high machining efficiency in optimal surface integrity manufacturing, a relationship model between rolling depth and rolling force was established based on Hertz contact theory, and a theoretical model of impact characteristics was established according to the indentation geometry to evaluate the machining efficiency. Subsequently, the plane ultrasonic rolling experiment of 7075 aluminum alloy was carried out to verify the relationship between rolling depth and rolling force, meanwhile, the mapping between process parameters and surface characteristics, impact characteristics and surface morphology were studied, respectively. On this basis, the surface integrity prediction model was established by using nonlinear curve fitting method, and the optimal parameter solution was obtained by using quantum genetic algorithm (NSGA-Ⅱ). The results show that the rolling force increases linearly with the increase in rolling depth. The impact characteristics increase with the increase in static force and amplitude, and decreases with the increase in step and feed rate, and the impact characteristics is negatively correlated with the processing efficiency. The optimization results provide a reference for engineering applications.
Light orthodontic force with high-frequency vibration accelerates tooth movement with minimal root resorption in rats
Authors: Tangtanawat Porntip , Thammanichanon Peungchaleoy , Sutthapreyasri Srisurang , Leethanakul Chidchanok 
Published: May 2022

Abstract
Objectives
To determine and compare the effects of high-frequency mechanical vibration (HFV) with light force and optimal force on the tooth movement and root resorption in rat model.
Materials and Methods
Seventy-two sites in 36 male Wistar rats were randomly assigned using a split-mouth design to control (no force/no vibration) or experimental groups: HFV (125 Hz), light force (5 g), optimal force (10 g), light force with HFV, and optimal force with HFV for 14 and 21days. The amount of tooth movement, three-dimensional root volume and root resorption area were assessed by micro-computed tomography and histomorphometric analysis.
Results
Adjunction of HFV with light force significantly increased the amount of tooth movement by 1.8-fold (p = 0.01), 2.0-fold (p = 0.01) at days 14 and 21 respectively. The HFV combine with optimal force significantly increased the amount of tooth movement by 2.1-fold (p = 0.01), 2.2-fold (p = 0.01) at days 14 and 21 respectively. The root volume in control (distobuccal root (DB): 0.60 ± 0.19 mm3, distopalatal root (DPa): 0.60 ± 0.07 mm3) and HFV (DB: 0.60 ± 0.08 mm3, DPa: 0.59 ± 0.11 mm3) were not different from the other experimental group (range from 0.44 ± 0.05 mm3 to 0.60 ± 0.1 mm3) with the lowest volume in optimal force group.
Conclusions
Adjunction of HFV with orthodontic force significantly increased tooth movement without causing root resorption
Clinical Relevance
Using light force with HFV could help to identify alternative treatment option to reduce the risk of root resorption.
Triptolide-mediated Downregulation of FLIPs in Hepatoma Cells Occurs at the Post-transcriptional Level Independently of Proteasome-mediated Pathways
Authors: Liu Weixia , Yang Ying , Wang Jing , Wu Shanshan , Chen Zhi 
Published: May 2022

Abstract
Cellular c-FLIP prevents apoptosis mediated by death receptor through inhibiting activation of caspase-8. Therefore, when c-FLIP is downregulated or eliminated, caspase-8 activation is promoted, and death receptor ligand-induced apoptosis is activated. It was reported that triptolide (TPL) sensitized tumor cells to TNF-α-induced apoptosis by blocking TNF-α-induced activation of NF-κB and transcription of c-IAP1 and c-IAP2. However, the effect of TPL on basal c-FLIP expression was not understood. In this study, we found that the combination of TNF-α and TPL accelerated apoptosis in human hepatocellular carcinoma cells and TNF-α-induced elevated as well as basal level of FLIPs protein were downregulated. Additionally, we demonstrated that basal level of FLIPs in Huh7 cells was continuously downregulated following the incubation of TPL and downregulated more when dosage of TPL for treatment was increased. Subsequently, we showed that TPL reduced FLIPs level in a transcription- and degradation-independent mechanism. Our findings suggest that TPL induces loss of FLIPs at the post-transcriptional level independently of proteasome-mediated pathway, an additional mechanism of TPL sensitizing cancer cells to TNF-α-induced apoptosis.
A novel method to evaluate transverse pedicle angle of lower lumbar using digital radiography
Authors: Wu Shixun , Liu Shizhang , Ling Ming , Huang Minggang , Liu Zhe , Duan Xianglong 
Published: May 2022

Abstract
To investigate a novel approach of establishment for transverse pedicle angle (TPA) of lower lumbar spine using preoperative digital radiography(DR). CT dataset of the lower lumbar were reconstructed using MIMICS 17.0 software, then imported into the 3matic software for surgical simulation and anatomical parameters measurement. Mathematical algorithm of TPA based on Pythagorean theorem was established, all obtained data was analysised by SPSS software. CT dataset from 66 samples were reconstructed as digital model of lower lumbar vertebrate(L3-L5), AP length / estimated lateral length for L3 between right and left were significant statistically(P = 0.015, P = 0.005). AP length of right for L4 was smaller than that of left after Paired t-test was executed(P = 0.006). Both width of pedicle and length of pedicle (P2C1) are consistent with TPA(L3 < L4 < L5). No statistical differences in TAN-TPA and DR-TPA compared with real TPA. ICC for real TPA and DR-TPA within L3 is good reliability, ICC for real TPA and DR-TPA within both L4 and L5 are moderate reliability. Our novel approach can be well considered as a reliable way to determine the transverse pedicle angle from routine DR, width and length of pedicle within lumbar DR should be considered to determine the length and trajectory of screw during preoperation planning.
Hold tight or loosen up? Functional consequences of a shift in anther architecture depend substantially on bee body size
Authors: Wilkins Rachel V. , Mayberry Maggie M. , Vallejo-Marín Mario , Russell Avery Leigh 
Published: May 2022

Abstract
A fundamental question in pollination ecology is how pollinators affect the evolution of different floral forms. Yet functional effects of shifts in floral form for plant and pollinator are frequently unclear. For instance, flowers that conceal pollen within tube-like anthers that are spread apart and move freely (free architecture) or are tightly joined together (joined architecture) have evolved independently across diverse plant families and are geographically widespread. Surprisingly, how their bee pollinators affect the function of both architectures remains unknown. We hypothesized that bee body size would affect foraging success and pollination differently for free and joined anther architectures. We therefore modified the anther architecture of a single plant species (Solanum elaeagnifolium) and used a single species of generalist bumble bee (Bombus impatiens), which varies greatly in body size. We found that on free anther architecture, larger bees were better pollinators. More pollen on their bodies was available for pollination and they deposited more pollen on stigmas. Conversely, on joined anther architecture, smaller bees were better pollinators. They collected less pollen into their pollen baskets, had more pollen on their bodies available for pollination, and deposited more pollen on stigmas. While we also found modest evidence that plants benefit more from joined versus free anther architecture, further investigation will likely reveal this also depends on pollinator traits. We discuss potential mechanisms by which pollinator size and anther architecture interact and implications for floral evolution.
Seismic vulnerability of southern parts of South India in the context of the recent earth tremors (22 March 2022) occurred in Dindigul region, Tamil Nadu, India
Authors: Joshua R.Melwyn , R Rajaperumal , A Vijay , R Kathiravan , J Saravanavel , K Palanivel , CJ Kumanan 
Published: May 2022

Abstract
The seismicity witnessed on 22 March 2022 in parts of Dindigul, Tamilnadu again indicates the seismic alertness of the southern part of the Indian peninsula. So, an integrated study was carried out between the lineaments and the present episode and the historical seismicity of the region as well. It revealed the coincidence of the maximum seismic episodes of 54% − 88% with N15o-60oE / S15o-60oW oriented tectonic lineaments/faults and the lineaments/faults associated with geomorphic anomalies. Since, these are inferred to be the regional sinistral strike slip faults related to the ongoing post collision tectonic compression of the Indian plate, the lineaments in general and the lineaments of NE-SW group in particular warrant detailed study.
Lambda-vector: Modeling temporal and channel interactions for text-independent speaker verification
Authors: Wei Guangcun , Min Hang , Xu Yunfei , Zhang Yanna 
Published: May 2022

Abstract
Most of the current excellent models in speaker verification are ResNet-based deep models and attention-based models. These models have a general weakness, which is the large number of parameters and high hardware requirements have limited their application on small devices. On the other hand, many deep structures only generate embedding features from the features extracted by the last frame-level layer, which causes shallow features and channel-related features to be ignored. To solve these problems, this paper proposed a shallow speaker verification model based on Lambda-vector, its main structure is composed of three Lambda-SE modules. The module extracts long-distance dependencies between frame-level features and channel-related interaction information to enhance representation of features. Meanwhile, so that adequately mine the information in deep and shallow features, the model introduces multi-layer feature aggregation to fuse the features of different frame-level layers together. It can increase the detailed information in the deep features and improve the model's ability to represent complex information. The experimental results on the public datasets Voxceleb1 and Voxceleb2 show that the model has more stable training speed, fewer model parameters, and better identification performances than baseline models.
Effect of Intralymphatic Allergen-specific Immunotherapy on House Dust Mite in a Murine Model of Allergic Rhinitis
Authors: Jung Joo Hyun , Lee Sang Min , Cho Min Young , Cha Heung Eog , Kim Seon Tae 
Published: May 2022

Abstract
BackgroundIntralymphatic immunotherapy (ILIT) is a promising alternative for the treatment of patients with allergic rhinitis, providing similar therapeutic efficacy to conventional allergen-specific immunotherapy (AIT). However, the allergic mechanism of ILIT is not completely known. The aim of this study was to determine the efficacy of ILIT in a house dust mite (HDM) mouse model of allergic rhinitis.Methods Six-week-old female BALB/c mice were divided into four groups. Four groups were established: Group 1 (G1, n=10), control group without allergy; Group 2 (G2, n=10), allergy group sensitized with HDM without ILIT; Group 3 (G3, n=10), allergy group with ILIT (L1: starting with HDM 1.25 mg/mL); and Group 4 (G4, n=10), allergy group with ILIT (L2: starting with HDM 2.5 mg/mL) After the murine model of allergic rhinitis with HDM was established, mice were administered an intralymphatic injection through the inguinal lymph nodes with HDM once per week for 5 weeks. Thereafter, the levels of total serum IgE, interleukin IL-6, IL-13, IL-17A, IL-25, IL-33, and interferon (IFN)-γ in serum and spleen were measured using ELISA kits. Eosinophils in nasal mucosa were also evaluated via hematoxylin and eosin staining. Cytokine expression in nasal mucosa were determined using RT-PCR and the effects of ILIT on FoxP3(+) Treg cell in splenocytes were assessed using flow cytometry. ResultsILIT significantly decreased serum total IgE and eosinophil counts in nasal mucosa; IL-6 IL-17A, IL-25, and IFN-γ in serum (P< 0.05); and IL-17A and IL-33 in splenocyte supernatant (P< 0.05). ILIT also reduced the mRNA expression of IL-4, IL-6, IL-17A, and IL-33 cytokines in nasal mucosa. FoxP3(+) Treg cell expression was significantly decreased in the allergic group and significantly increased in the ILIT group (P< 0.05). ConclusionOur results suggest that ILIT regulates the specific immunotherapy immunologic mechanism by downregulating Th1, Th2, and Th17 cytokines and upregulating FoxP3(+) T reg cells in the HDM allergic mouse model.
Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy
Authors: Vezain Myriam , Thauvin-Robinet Christel , Vial Yoann , Coutant Sophie , Drunat Séverine , Urtizberea Jon Andoni , Rolland Anne , Jacquin-Piques Agnès , Fehrenbach Séverine , Nicolas Gaël , Lecoquierre François , Saugier-Veber Pascale 
Published: May 2022

Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder resulting from biallelic alterations of the SMN1 gene: deletion, gene conversion or, in rare cases, intragenic variants. The disease severity is mainly influenced by the copy number of SMN2, a nearly identical gene, which produces only low amounts of full-length (FL) mRNA. Here we describe the first example of retrotransposon insertion as a pathogenic SMN1 mutational event. The 50-year-old patient is clinically affected by SMA type III with a diagnostic odyssey spanning nearly 30 years. Despite a mild disease course, he carries a single SMN2 copy. Using Exome Sequencing and Sanger sequencing, we characterized a SVA-F retrotransposon inserted in SMN1 intron 7. Using RT-PCR and RNASeq experiments on lymphoblastoid cell lines, we documented the dramatic decrease of FL transcript production in the patient compared to subjects with the same SMN1 and SMN2 copy number, thus validating the pathogenicity of this SVA insertion. We characterized the mutant FL-SMN1-SVA transcript and showed that it is subject to degradation by nonsense-mediated mRNA decay. The stability of the SMN-SVA protein may explain the mild course of the disease. This observation exemplifies the role of retrotransposons in human genetic disorders.
Mesenchymal stem cells improve liver fibrosis and protect hepatocytes by promoting microRNA-148a-5p mediated inhibition of Notch signaling pathway
Authors: Zhou Qing , Rong Chao , Gu Tengfei , Li Hongda , Wu Lei , Zhuansun Xuemei , Zhao Xin , Xiao Zuorun , Kuang Yuting , Xu Sanrong , Wang Shouli 
Published: May 2022

Abstract
Background
Mesenchymal stem cells (MSCs) are considered to be a potential therapeutic tool for liver fibrosis. Inhibiting the activation of hepatic stellate cells (HSCs) and protecting hepatocytes are important mechanisms for the anti-fibrotic effect of MSCs. However, how MSCs inhibit liver fibrosis by regulating the expression of microRNAs (miRNAs) has not been fully clarified.
Methods
Transforming growth factor-β1 (TGF-β1) activated HSCs LX-2 were single cultured or co-cultured with human umbilical cord mesenchymal stem cells (HUC-MSCs). High-throughput sequencing was used to evaluate the differentially expressed microRNAs (DEMs) between the two groups. Quantitative real-time PCR (qRT-PCR), Western blot, and transfection experiments were used to investigate and screen the most significantly up-regulated DEM. Bioinformatics analysis was used to predict the target mRNAs and the potential functions of the DEM. The possible mechanism of HUC-MSCs against liver fibrosis was analyzed by co-culture experiment of HUC MSCs with LX-2 cells, and HUC-MSCs treatment of Bile duct ligation (BDL) induced liver fibrosis in mice. Finally, the mechanism of the DEM regulating liver fibrosis was confirmed in human liver fibrosis specimens.
Results
MicroRNA-148a-5p (miR-148a-5p) was the most significantly up-regulated DEM in activated LX-2 cells co-cultured with HUC-MSCs compared with LX-2 cells single cultured. Up-regulation the expression of miR-148a-5p in activated LX-2 cells could significantly inhibit the expression of hepatic fibrosis markers α-SMA and Col1α1. Notch2 was one target gene of miR-148a-5p. Co-cultured with HUC-MSCs could inhibit the activation of LX-2 cells by inhibiting the expression of the Notch2 and the Notch signaling pathway. In addition, HUC-MSCs treatment could up-regulate the expression of miR-148a-5p in liver tissue and hepatocytes, promote the proliferation and avoid the apoptosis of hepatocytes, and reduce the degree of fibrosis by inhibiting expression of the Notch2 and the Notch signaling pathway in BDL-induced liver fibrosis mice. Moreover, miR-148a-5p was down-regulated and Notch2 was up-regulated in fibrotic human liver tissues compared with the normal livers.
Conclusions
HUC-MSCs treatment could inhibit HSCs activation, protect hepatocytes, and alleviate BDL-induced liver fibrosis in mice by up-regulating the expression of miR-148-5p and inhibiting the Notch signaling pathway. The down-regulation of miR-148-5p and up-regulation of Notch2 could be used as biomarkers to monitor the progression of liver fibrosis.
Weld morphology, microstructure evolution and mechanical properties of laser beam welding of wire arc additive manufactured Al-Cu substrate
Authors: Shi Bowen , Wang Leilei , Zhan Xiaohong , Lyu Feiyue , Gao Zhuanni , Shi Huizi 
Published: May 2022

Abstract
Additive manufacturing (AM) cannot meet the manufacturing requirements of specific large structures, so use the welding method to joint the small size parts of AM to solve the problem. In work, the laser weld 3mm thick samples cut from WAAM block under different laser powers and welding directions to explore the feasibility of technology. The properties evolution, and weldability of the laser-welded wire arc additive manufactured Al-Cu alloy joints are investigated. The results indicate that the wire arc additive manufactured Al-Cu alloy has excellent laser weldability without apparent detection. The microstructures of the laser-welded joints consist of columnar grains, dendrites and fine equiaxed grains. The 3500 W laser power joint has higher tensile strength and elongation than other laser powers, reaching 203.48 MPa, 4.13%. Compared with the different welding direction joints, “0°and 0°” has the higher tensile strength and elongation, reaching 180.77 MPa, 2.40%. The microstructures have a weak effect, but the anisotropy plays a significant role in the tensile properties. This study has demonstrated that it is possible to laser-welded WAAM samples, and provide solutions that AM technology difficultly produces large size parts.