bluuebunny/crossref_metadata_2025 huggingface dataset:
Einstein’s Dream: Realization and Failure
Authors: Pandey S K
Published: January 2021

Several mathematicians and physicists are working all over the globe to get a unified theory. However, most of them are discarding Einstein’s view at the very first step of their theories. This article provides a brief non-mathematical introduction on this. Also, on the basis of Koga’s theory we point out two reasons which might have caused Einstein’s failure to get a unified theory.
Challenges and Experiences of Online Evaluation in Courses of Civil Engineering During the Lockdown Motivated by the COVID-19 Crisis
Authors: García-Alberti Marcos , Suárez Fernando , Chiyón Isabel , Mosquera Feijoo Juan Carlos
Published: January 2021

As a consequence of the global sanitary crisis in early 2020, universities had to tackle with a sudden shift in their teaching-learning strategies so that the preset competences could be fulfilled. This study presents the learning outcomes of the tasks implemented, student experiences and feedback, as well as some reflections from the instructors with a holistic perspective of the courses due to the measures and adaptations adopted. Six courses taught at Civil Engineering degrees of three universities, two from Spain and one from Peru, are analyzed. The teaching and evaluation strategies are described and some reflections are made by comparing the student’s performance with the previous course. Although the shift to online learning had to be made from day to day, with no time for preparation, the experience has proved that online learning can be beneficial in some aspects and have probably come to stay, although some others are difficult to replace with respect to face-to-face learning, especially students’ engagement and motivation.
Social Media and Local Government in Indonesia: Adoption, Use and Stakeholder Engagement
Authors: Santoso Anang Dwi , Rinjany Dhia , Bafadhal Oemar Madri
Published: January 2021

While social media has been extensively adopted by local governments, not all of its benefits have been achieved. One reason is that local government-owned social media is less appealing. This research argues that to increase public involvement in social media, the government needs to understand public behavior on social media by exploring public preferences on the content and media produced. This research applies a Stakeholder Engagement Index (SEI) to study public behavior on social media. The results of the study demonstrate that although content containing information about government activities has been produced, it has a low engagement level. Moreover, people prefer content with photos and videos, which apparently dominate local government posts and tweets. This research academically confirms that SEI is an alternative method for understanding public behavior on social media and practically presents choices of content categories preferred by the public.
USING GLOBAL CLIMATE INDICES TO PREDICT RAINFALL AND SUGARCANE PRODUCTIVITY IN DRYLANDS OF BANYUWANGI, EAST JAVA, INDONESIA
Authors: Ranomahera Muhammad Rasyid Ridla , Nugroho Bayu Dwi Apri , Riajaya Prima Diarini , Putra Rivandi Pranandita
Published: January 2021

In Indonesia, sugarcane (Saccharum officinarum L.) is mostly cultivated in drylands, thus depending on rainfall for crop growth and development. Rainfall is an essential factor affecting sugarcane productivity. The global climate indices can be used to investigate potential of rainfall within a given area and its relationship with crop productivity. This reserach aimed to analyze the relationship between the global climate index, rainfall, and sugarcane productivity in drylands near Glenmore sugar mill, i.e., Benculuk and Jolondoro, Banyuwangi, East Java, Indonesia. The global climate index data used were the Southern Oscillation Index (SOI) and Sea Surface Temperature (SST) between 1995 and 2014. Results of this research showed that SOI and SST can be used to predict the rainfall in both Benculuk and Jolondoro. Rainfall (y) can be predicted with SST data (x) using the equation of y = -352.49x + 7724.1 in Benculuk and y = -107.32 + 3443.4 in Jolondoro, as well as with SOI data (x) using the equation of y = 38.664x + 1555.1 in Benculuk and y = 10.541x + 1567.8 in Jolondoro. Sugarcane productivity (y) in Jolondoro can be predicted using data of total rainfall (x) between October and March with the following equation: y = -0.1672x + 1157.3. This equation can be used by sugar mills, sugarcane growers, and other sugarcane-relevant stakeholders for determining the appropriate growing season.
EFFECT OF LERAK (SAPINDUS RARAK) EXTRACT IN HIGH ROUGHAGE DIET ON RUMEN MICROBIAL PROTEIN SYNTHESIS AND PERFORMANCE OF SHEEP
Authors: Wina Elizabeth , Muetzel Stefan
Published: January 2021

Secondary compounds containing plant extract as feed additive may improve the performance of livestock consuming high roughage diet. An in vivo trial was conducted to investigate the effect of Sapindus rarak extract (SRE) on ruminal fermentation products, microbial protein synthesis, and growth performance of sheep. Sheep (male, 28 heads) fed high roughage diet were arranged in a completely randomized design with four treatments: addition of SRE to the diet at 0, 4, 8 and 12 g head-1 day-1. The experiment was conducted for 105 days with 2 weeks adaptation period. At the end of the experiment, total faeces was collected for 1 week and rumen liquor was taken. Variables measured were ruminal fermentation products, microbial protein synthesis, daily intake, digestibility, N retention, body weight, and average daily gain. Protozoal numbers were significantly decreased with increasing SRE dose. The ruminal NH3 concentration tended to reduce by SRE addition (P = 0.06). SRE significantly increased propionate and efficiency of microbial protein synthesis from 6.4 to 10.5 g N kg-1 DOMR. SRE significantly improved average daily gain of sheep during the first 70 days of experiment without affecting intake and digestibility. SRE did not alter carcass percentage but tended to lower pancreas and liver weights (P<0.1). In conclusion, SRE has a significant role in partially defaunated rumen microflora, hence, increased microbial protein synthesis and propionate production in the rumen. Addition of SRE is useful to increase daily gain of sheep fed high roughage diet in 70 days of feeding.
Genetic Rhabdomyolysis within the Spectrum of the Spinocerebellar Ataxia Type 2 Responsive to Pregabalin
Authors: Rossi Fabian , Ma Joe , Tsakadze Nina , Benes-Lima Lourdes , Gonzalez Julio Araque , Hoffmann Michael
Published: January 2021

BackgroundSpinocerebellar Ataxia type 2 is a slowly progressive adult onset ataxia with a broad clinical presentation. Case presentationWe describe a man with Spinocerebellar Ataxia type 2 with chronic, severe, and recurrent rhabdomyolysis, as part of the cerebellar ataxia genetic spectrum. Initially rhabdomyolysis was refractory to multiple medications, but entirely resolved and remained in chronic remission with pregabalin. ConclusionThis is the first report of Spinocerebellar Ataxia type 2 associated with chronic, severe, recurrent rhabdomyolysis as part of its genetic phenotype responsive to pregabalin.
Effect of Cognitive-behavioral Therapy on Domestic Violence and Its Consequences in Transgender Youth: a Randomized Clinical Trial, Parallel Group Study
Authors: Damanpak-Rizi Mahdieh , Farnam Farnaz , Khodakhah Parisa
Published: January 2021

Background: Family violence against transgender people is a common issue and affects their mental health. Very few if any interventions have been designed to reduce family violence against transgender youths. This RCT will evaluate the efficacy of cognitive-behavioral therapy for transgender parents on their violent behavior towards their children and transgender youth's mental health.Methods: This study is a randomized controlled trial conducted on 50 transgender youths with selected inclusion criteria in Iran. The intervention will be undertaken on the parents or guardians of these transgender youths in eight 1-hour online sessions for the intervention group to increase their knowledge of gender dysphoria, to help control their anger regarding their offspring's gender dysphoria and learn to manage stressful situations. This study's primary outcomes include frequency of family violence towards transgender youths, depression, anxiety, stress, self-esteem, suicidal thoughts, and suicide attempts in transgender youth and the secondary outcome is parental conflict resolution tactics before and after the intervention. Discussion: To the best of our knowledge, this is one of the first RCT on family violence against transgender youth in the world. Findings will help to provide better education and intervention for transgender parents to reduce violence against their children. Results: N/AConclusion: N/ATrial registration: IRCT20120609009975N7 (08/03/2020).
The Effect of Learning Style and General Self-Efficacy on Satisfaction of e-Learning in Dental Student
Authors: Baherimoghadam Tahereh , Hamedani Shahram , Mehrabi Manoosh , Naseri Navid , Marzban Nooshin
Published: January 2021

Introduction: The COVID-19 pandemic has had a significant impact on education. e-Learning has been becoming most popular. Satisfaction of the student is one of important goal of e-Learning, therefore factors affecting this satisfaction should be considered extensively. This study aims to evaluate the effect of learning style and General Self-Efficacy (GSE) on satisfaction of e-Learning in dental student. Method: Electronic questionnaires were sent to 85 fifth and sixth-year students who had passed the face-to-face orthodontics course in the previous semester and were studying online orthodontics at the time of this study. Three questionnaires were used including Soloman and Felder learning styles index, General self-efficacy questionnaire and Satisfaction questionnaire for online education. Results: The results of the reliability test showed that Cronbach’s alpha index for the self-efficacy and satisfaction questionnaire was 0.836 and 0.96, respectively. The correlation between satisfaction and the dimensions of learning style showed that the active dimension of processing information had a significant relationship with the level of satisfaction. In the understanding dimension, a relatively strong correlation was observed in the Global dimension. Moderate significant relationship between the total score of self-efficacy and the level of satisfaction has been found. Conclusion: The results of the present study highlight the necessity of more studies regarding defining effective on student satisfaction during e-Learning. GSES and active learning style in the processing dimension and global learning style in the understanding dimension affect students' satisfaction.
Leucyl-tRNA Synthetase Deficiency Systemically Induces Excessive Autophagy in Zebrafish
Authors: Shiraishi Hiroshi , Shimizu Nobuyuki , Tsumori Mika , Kiyota Kyoko , Maeda Miwako , Ishitani Tohru , Hanada Reiko , Ihara Kenji , Hanada Toshikatsu , Inoue Masanori , Miyahara Hiroaki
Published: January 2021

Leucyl-tRNA synthetase (LARS) is an enzyme that catalyses the ligation of leucine with leucine tRNA. LARS is also essential to sensitize the intracellular leucine concentration to the mammalian target of rapamycin complex 1 (mTORC1) activation. Biallelic mutation in the LARS gene causes infantile liver failure syndrome type 1 (ILFS1), which is characterized by acute liver failure, anaemia, and neurological disorders, including microcephaly and seizures. However, the molecular mechanism underlying ILFS1 under LARS deficiency has been elusive. Here, we generated Lars deficient (larsb-/-) zebrafish that showed progressive liver failure and anaemia, resulting in early lethality within 12 days post fertilization. The atg5-morpholino knockdown and bafilomycin treatment partially improved the size of the liver and survival rate in larsb-/- zebrafish. These findings indicate the involvement of autophagy in the pathogenesis of larsb-/- zebrafish. Indeed, excessive autophagy activation was observed in larsb-/- zebrafish. Therefore, our data clarify a mechanistic link between LARS and autophagy in vivo. Furthermore, autophagy regulation by LARS could lead to development of new therapeutics for IFLS1.
Radioactive Iodine and Female Fertility, Less Innocent Than we Thought
Authors: Navarro Pino , Rocher Sandra , Miró Pau , Oltra Sandra
Published: January 2021

Radioactive iodine (I131) is used after surgery in the treatment of Differentiated Thyroid Carcinoma (DTC). There is no solid evidence about the potential deleterious effect of I131 on women fertility. The objective of this study is to assess the impact that I131 may have on fertility in women. All women followed by DTC in our department have been analyzed and women younger than 45 years old at the time of diagnosis and initial treatment were included. There were 40 women exposed to I131 (study group) and 11 women who were only treated with thyroidectomy (control group). Of the women exposed to I131, 40% went through early menopause, while no cases were reported among their controls. Furthermore, 29.2% of women exposed to I131 had decreased Antimüllerian Hormone (AMH), compared to the only 11% of unexposed women (not significant). Regarding the fertility impairment "perceived" by patients, in the group of women exposed to iodine, 17.9% described being unable to complete their genesic desire whereas, none was registered in the control group. We conclude that radioactive iodine can affect a woman's fertility and shorten her reproductive life, so this is an aspect that should be taken into consideration.
Label-Free High-Throughput Screening Assay for the Identification of Norepinephrine Transporter (NET / SLC6A2) Inhibitors
Authors: Sijben Hubert , Oostveen Wieke van , Hartog Peter , Stucchi Laura , Maresca Giovanna , Scarabottolo Lia , IJzerman Adriaan , Heitman Laura
Published: January 2021

The human norepinephrine transporter (NET) is an established drug target for a wide range of neurological disorders. Conventional methods that are used to functionally characterize NET inhibitors are based on the use of radiolabeled or fluorescent substrates. These methods are highly informative, but pose limitations to either high-throughput screening (HTS) adaptation or physiologically accurate representation of the endogenous uptake events. Recently, we developed a label-free functional assay based on the activation of G protein-coupled receptors by a transported substrate, termed the TRACT assay. In this study, the TRACT assay technology was applied to NET inducibly expressed in a modified HEK293-JumpIn cell line. Three endogenous substrates of NET – norepinephrine (NE), dopamine (DA) and epinephrine (EP) – were each assessed in characterization of the reference NET inhibitor nisoxetine. The resulting assay, using NE as a substrate, was validated in a manual HTS set-up with a Z’ = 0.55. The inhibitory potencies of several reported NET inhibitors from the TRACT assay showed positive correlation with those from an established fluorescent substrate uptake assay. These findings demonstrate the suitability of the TRACT assay for HTS characterization and screening of NET inhibitors and provide a basis for investigation of other solute carrier transporters with label-free biosensors.
LISA VS. INSURE_Which One is Appropriate? -A Cohort Study of PS Administration Technology in Preterm RDS in Multicenter of Anhui Province
Authors: Song Feifei , Zhang Lan
Published: January 2021

Background: Pulmonary surfactant(PS) replacement therapy is well known as a necessary method to preterm respiratory distress syndrome(RDS). INSURE technique bring up injury of trachea and high incidence rate of bronchopulmonary dysplasia(BPD), while less invasive surfactant administration(LISA) caught increasingly attention. Objective: Compare the outcomes and side effect between LISA group and INSURE group. Methods: We collected 20 cases from eight neonatal intensive care units (NICU) in Anhui Province in China for LISA group and 36 cases from the first Hospital Affiliated of USTC for INSURE group, and the outcomes and side effect were analyzed. Results: Re-intubation rate(20% vs 22.2%) and the incidence of BPD(40% vs 47.2%) in LISA group were lower than those in INSURE group, but there were no statistical differences. The mortality in two group show no diffrence. Conclusion: LISA technique can decrease the re-intubation rate and BPD incidence without increasing mortality.
TLR7 Is Expressed by Support Cells, but Not Sensory Neurons, in Ganglia 
Authors: Proskocil Becky J. , Wai Karol , Lebold Katherine M. , Norgard Mason , Michaelis Katherine A , Marks Daniel L. , Fryer Allison D. , Jacoby David B. , Drake Matthew Georgenson
Published: January 2021

Background: Toll like receptor 7 (TLR7) is an innate immune receptor that detects viral single-stranded RNA and triggers production of proinflammatory cytokines and type 1 interferons in immune cells. TLR7 agonists also modulate sensory nerve function by increasing neuronal excitability, although studies are conflicting whether sensory neurons specifically express TLR7. This uncertainty has confounded development of a mechanistic understanding of TLR7 function in nervous tissues.Methods: TLR7 expression was tested using in situ hybridization with species-specific RNA probes in vagal and dorsal root sensory ganglia in wild-type and TLR7 knockout mice, and in guinea pigs. In situ labeling was compared to immunohistochemistry using TLR7 antibody probes. Pulmonary afferent neurons in vagal ganglia were also specifically tested since respiratory viruses are a common TLR7 ligand. Guinea pig vagal afferents were labeled by intranasal instillation of wheat germ agglutinin, isolated using flow cytometry and analyzed for TLR7 by RT-PCR. The effects of influenza A infection on TLR7 expression in sensory ganglia and in spleen were also assessed.Results: In situ probes detected TLR7 in the spleens and in small support cells adjacent to sensory neurons in dorsal root and vagal ganglia in wild type mice and guinea pig, but not in TLR7 KO mice. TLR7 was co-expressed with the macrophage and satellite glial cell marker Iba1, but was absent in sensory nerves in vagal and dorsal root ganglia in both mice and guinea pigs. In contrast, a TLR7 antibody labeled small and medium-sized neurons in wild-type and TLR7 KO mice in a TLR7-independent manner. Wheat germ agglutinin-positive cells sorted by flow cytometry expressed both TLR7 and Iba1, indicating that TLR7-expressing support cells sort alongside neurons despite ganglia dissociation. Influenza A infection caused significant weight loss and upregulation of TLR7 in spleens, but not in vagal ganglia, in mice.Conclusion: TLR7 is expressed by macrophages and satellite glial cells, but not neurons in sensory ganglia suggesting TLR7’s neuromodulatory effects are mediated indirectly via activation of neuronally-associated support cells, not through activation of neurons directly. Our data also suggest TLR7’s role in neuronal tissues is not primarily related to antiviral immunity.
Categorization of Common Pigmented Skin Lesions (CPSL) using Multi-Deep Features and Support Vector Machine
Authors: BEHERA SANTI , SETHY PRABIRA
Published: January 2021

The skin is the main organ. It is approximately 8 pounds for the average adult. Our skin is a truly wonderful organ. It isolates us and shields our bodies from hazards. However, the skin is also vulnerable to damage and distracted from its original appearance; brown, black, or blue, or combinations of those colors, known as pigmented skin lesions. These common pigmented skin lesions (CPSL) are the leading factor of skin cancer, or can say these are the primary causes of skin cancer. In the healthcare sector, the categorization of CPSL is the main problem because of inaccurate outputs, overfitting, and higher computational costs. Hence, we proposed a classification model based on multi-deep feature and support vector machine (SVM) for the classification of CPSL. The proposed system comprises two phases: first, evaluate the 11 CNN model's performance in the deep feature extraction approach with SVM. Then, concatenate the top performed three CNN model's deep features and with the help of SVM to categorize the CPSL. In the second step, 8192 and 12288 features are obtained by combining binary and triple networks of 4096 features from the top performed CNN model. These features are also given to the SVM classifiers. The SVM results are also evaluated with principal component analysis (PCA) algorithm to the combined feature of 8192 and 12288. The highest results are obtained with 12288 features. The experimentation results, the combination of the deep feature of Alexnet, VGG16 & VGG19, achieved the highest accuracy of 91.7% using SVM classifier. As a result, the results show that the proposed methods are a useful tool for CPSL classification.
Secular Crustal Deformation Characteristics Prior to the 2011 Tohoku-Oki Earthquake of Mw 9.1 Detected from IGS Array, 2002-2011
Authors: Xu Keke , He Rong , Li Kezhao , Ren Ankang , Jiang Siyuan
Published: January 2021

In order to reveal the secular deformation evolution and strain accumulation progress along subduction zone, we focus on high-precision Global Positioning System (GPS) data processing, GPS time series analysis and regional spatiotemporal filtering. The GPS position time series is modeled as a combination of the long-term plate movements, short-term noise and the frequency-dependent variations and tectonic deformation information. Common Mode Errors (CME) is removed and the deformation signals is then extracted from the residual time series by Principal Component Analysis (PCA). Combing the filtered displacement array and the dynamic regional strain array derived from GPS baseline, a spatiotemporal tectonic evolution map is exhibited obviously. We process IGS time series over the 2002-2011 period in Japan island and reveal the dynamic evolution of crustal deformation along subduction zone. The results show that the regional reference frame transformation by constraining one site location and one stable GPS baseline direction can further improve the Signal-to-Noise Ratio (SNR) of GPS observations. A integrated analysis combining the baseline length with azimuth change can show the crustal motion feature more comprehensively. The observed behaviors agree well with the simulation experiment results of the rock rupture in the laboratory. We divide the pre-seismic deformation into four stages, the stable linear strain accumulation stage, the formation stage of the local locked area, local decoupling stage, and strain release stage. We also give an appropriate dynamical model for the interplate coupling to explain the observed deformation characteristics. Research result provides some of the observational new evidence for inter-seismic deformation anomaly detection and the medium- to longer-term seismic hazard assessments.
Palatal Bone Thickness of MSE Implantation area in Adult Patients with Skeletal Class Ⅲ Malocclusion: A Cone-beam Computed Tomographic Study
Authors: Chen Weiting , Zhang Kaili , Liu Dongxu
Published: January 2021

Background: Analyze the palatal bone thickness of maxillary skeletal expander (MSE) implantation area in adult patients with skeletal class Ⅲ malocclusion based on Cone-beam computed tomography (CBCT) data, and to provide a reference for the implantation of the miniscrew.Methods: A total of 80 adult patients (40 M, 40 F) with an normal angle before treatment were divided into two groups; skeletal class Ⅲ malocclusion group and skeletal Ⅰ malocclusion group according to sagittal facial type, with 40 patients in each group, with a male to female ratio of 1: 1. CBCT scanner was used to obtain DICOM data from all patients.The palatal bone thickness was measured at 45 sites with MIMICS 21.0 and SPSS 22.0 was employed for statistical analysis. The bone thickness of different regions of the palate in the same group was analyzed by one-way analysis of variance (ANOVA) method; Fisher’s least significant difference (LSD)-t method was used for comparison in pairs, and an independent sample t-test was employed to test the difference of bone thickness in the same area between the two groups.Results: (1) There was no significant difference among the anterior, middle, and posterior regions of the midline area in patients with skeletal class Ⅲ malocclusion (P > 0.05). Palatal bone thickness decreased gradually from front to back in the middle and lateral areas in both groups (P < 0.001). (2) The bone thickness of the anterior, middle, and posterior regions of the two groups gradually decreased from the middle area to the parapalatine region. (3) The palatal bone were significant thinner in the area 9.0 mm before the transverse palatine suture in midline area, 9.0 mm before and after the transverse palatine suture in the middle area, and 9.0 mm after the transverse palatine suture in the lateral area.Conclusion: (1) The palatal bone of patients with class Ⅲ malocclusion was thinner in some areas, so the MSE implant anchorage position could be moved forward appropriately. (2) The thin palatal bone increased the risk of MSE anchorage screw penetrating nasal mucosa and even inferior turbinate. Patients should be given a more precise and personalized implantation scheme based on factors such as palatine bone thickness and palatal morphology.
Augmented Rehabilitation Program for Young Patients Following Total Hip Arthroplasty
Authors: Negm Ahmed , Yavarai Milad , Jhangri Gian , Haennel Robert , Jones Allyson
Published: January 2021

BackgroundThe increase rate seen in Total Hip Arthroplasty (THA) for younger patients has implications for future rehabilitation demands for primary and revision THA surgery. This study aims to determine the impact of a 6-week post-operative rehabilitation program designed for THA patients ≤ 60 years on physical activity (PA) and function compared to age- and a sex-matched control group received usual postoperative care at 12-week post-THA. MethodsIn this quasi-experimental study, a cohort of THA candidates was recruited during their 6-week postoperative visit to their surgeons. The out-patient rehabilitation program consisted of 12 structured exercise classes (2 hrs/class) over 6 weeks. Physical activity was assessed using Sense Wear Pro ArmbandTM [SWA]. Participants completed the Hip Osteoarthritis Outcome Score (HOOS), and THA satisfaction questionnaire before and immediately after the intervention. ResultsThe intervention group took significantly more steps/day at the follow-up compared to baseline. The intervention group had a higher mean change in the number of weekly PA bouts than the control group. Within the intervention groups, all HOOS subscales were significantly higher at the follow-up compared to baseline. ConclusionThe augmented rehabilitation program may have immediate effects on pain relief and symptom reduction for patients (≤60 years) following THA.
Comparison of Plasma and Cerebrospinal Fluid Proteomes Identifies Gene Products Guiding Adult Neurogenesis and Neural Differentiation in Birds
Authors: Voukali Eleni , Veetil Nithya Kuttiyarthu , Němec Pavel , Stopka Pavel , Vinkler Michal
Published: January 2021

Cerebrospinal fluid (CSF) proteins regulate neurogenesis, brain homeostasis and participate in signalling during neuroinflammation. Even though birds represent valuable models for constitutive adult neurogenesis, current proteomic studies of the avian CSF are limited to chicken embryos. Here we use liquid chromatography–tandem mass spectrometry (nLC-MS/MS) to explore the proteomic composition of CSF and plasma in adult chickens (Gallus gallus) and evolutionarily derived parrots: budgerigar (Melopsittacus undulatus) and cockatiel (Nymphicus hollandicus). Because cockatiel lacks a complete genome information, we compared the cross-species protein identifications using the reference proteomes of three model avian species: chicken, budgerigar and zebra finch (Taeniopygia guttata) and found the highest identification rates when mapping against the phylogenetically closest species, the budgerigar. In total, we identified 483, 641 and 458 unique proteins consistently represented in the CSF and plasma of all chicken, budgerigar and cockatiel conspecifics, respectively. Comparative pathways analyses of CSF and blood plasma then indicated clusters of proteins involved in neurogenesis, neural development and neural differentiation overrepresented in CSF in each species. This study provides the first insight into the proteomics of adult avian CSF and plasma and brings novel evidence supporting the adult neurogenesis in birds.
Blocking the EGFR/p38/NF-κB Signal Pathway Alleviates Disruption of BSCB and Subsequent Inflammation After Spinal Cord Injury
Authors: Li Zai-Wang , Zhao Jing-Jing , Li Su-Ya , Cao Ting-Ting , Wang Yi , Guo Yi , Xi Guang-Jun
Published: January 2021

Background:Epidermal growth factor receptor (EGFR) activation may play an important role in blood spinal cord barrier (BSCB) disruption and secondary injury after SCI as it is significantly upregulated in the astrocytes (AS) and microvascular endothelial cells (MEC), which are the main component of cells in BSCB. EGFR inhibition alleviates the disruption of BSCB and improves the functional recovery in rats following spinal cord injury (SCI). However, the biological mechanisms underlying EGFR activation mediating secondary damage after SCI remain unclear. Methods:An in vitro model of Oxygen and glucose deprivation/reoxygenation (OGD/R) induced BSCB damage and in vivo rat SCI model was employed to define the role of EGFR activation and its induced inflammatory injury during this pathological process in AS and MEC. AS and MEC were exposed to EGFR or p38 MAPK up-regulation in the presence and absence of EGFR inhibitor, p38 MAPK inhibitor, NF-κB inhibitor, and/or appropriate shRNA. RT-PCR, ELISA and western blotting were used for mRNA and protein expression analyses of TNF-α, iNOS, COX-2 and IL-1β. Immunohistochemical staining and confocal microscopy were used to demonstrate cellular EGFR activation and to investigate the expression of tight junction (TJ) protein (ZO-1 and occludin). Measurement of transendothelial electrical resistance (TEER) and transendothelial FITC-dextran permeability were used to measure permeability of BSCB in vitro, while Evans blue dye extravasation test and evaluation spinal cord edema were used to detect permeability of BSCB in vivo.Results:The expression of pEGFR was significantly increased in BSCB component cells (AS and MEC) after SCI and BSCB damage model. EGFR activation induced inflammation injury by upregulating the expression of TNF-α, iNOS, COX-2, and IL-1β and BSCB disruption with loss of TJ protein by downregulating the expression of ZO-1 and occludin in BSCB damage model and SCI rats. Moreover, EGFR or p38 activation leads to NF-κB nuclear translocation in primary AS and MEC after OGD/R. The EGFR inhibitor as well as shRNA against EGFR markedly attenuated pro-inflammatory factor excessive producing and loss of TJ protein, and activation of the EGFR/p38/NF-κB pathway. While, EGFR overexpression significantly increased the expression of TNF-α, iNOS, COX-2, and IL-1β and decrease the expression of ZO-1 and occludin, inducing activation of the EGFR/p38/NF-κB pathway in both AS and MEC. Conclusion:This study strongly suggests that EGFR activation in BSCB component cells after SCI and BSCB damage model mediates both upregulation of pro-inflammation expression and downregulation of TJ protein downregulation via the EGFR/p38/NF-κB pathway. These findings contribute to a better understanding of the biological mechanisms underlying BSCB disruption and secondary injury following SCI mediating by EGFR activation.
LINC01094 Upregulates LIN28B Expression by Sponging miR-577 to Promote Pancreatic Cancer Proliferation and Metastasis
Authors: Luo Chen , Lin Kang , Hu Cegui , Zhu Xiaojian , Zhu Jinfeng , Zhu Zhengming
Published: January 2021

Backgroud: The leading cause of death in pancreatic cancer (PC) patients is the progression of cancer metastasis. Long non-coding RNAs (lncRNAs) play an important role in regulating cancers, however its molecular basis in pancreatic cancer (PC) remains to be explored.Methods: In this study, bioinformatics methods are used to predict the potential pairs of lncRNAs in PC. The clinical significance of LINC01094 are determined by qRT-PCR and explored its correlation with clinicopathological parameters. The biological functions and potential mechanisms of LINC01094 in PC progression are studied in vivo and in vitro. Results: We observe that LINC01094 is markedly overexpressed in pancreatic tumors and is associated with poorer prognosis. Downregulation of LINC01094 decreases PC cell invasion and inhibits tumorigenesis and metastasis in mouse xenografts. LINC01094 acts as a sponge for miR-577, sequestering it and derepressing the expression of its endogenous target the RNA‐binding protein lin‐28 homolog B (LIN28B). Conclusions: Overall, LINC01094 upregulates LIN28B by sponging miR-577, thereby promoting PC proliferation and metastasis. This indicates that LINC01094 can be regarded as a new biomarker or therapeutic target for the treatment of PC.
Mitochondrial Malic Enzyme 2 Promotes Breast Cancer Metastasis via Stabilizing HIF-1α Under Hypoxia
Authors: You Duo , Du Danfeng , Zhao Xueke , Li Xinmin , Ying Minfeng , Hu Xun
Published: January 2021

Background: α-ketoglutarate (α-KG) is the substrate to hydoxylate collagen and hypoxia-inducible factor-1α (HIF-1α), which are important for cancer metastasis. Previous studies showed that upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes HIF-1α via depleting α-KG in breast cancer cells. We propose that mitochondrial malate enzyme 2 (ME2) may also affect HIF-1α via modulating α-KG level in breast cancer cells. Methods: ME2 protein expression was evaluated by immunohistochemistry on 100 breast cancer patients and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated by an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α protein in breast cancer cell lines (4T1 and MDA-MB-231) was determined in vitro and in vivo.Results: The high expression of ME2 was observed in the human breast cancerous tissues compared to the matched precancerous tissues (P=0.000). The breast cancer patients with a high expression of ME2 had an inferior survival than the patients with low expression of ME2 (P=0.019). ME2 high expression in breast cancer tissues was also related with lymph node metastasis (P=0.016), pathological staging (P=0.033) and vascular cancer embolus (P=0.014). In a 4T1 orthotopic breast cancer model, ME2 knockout significantly inhibited lung metastasis. In the tumors formed by ME2 knockout 4T1 cells, α-KG level significantly increased, collagen hydroxylation level did not change significantly, but HIF-1α protein level significantly decreased, in comparison to control. In cell culture, ME2 knockout or knockdown cells demonstrated a significantly higher α-KG level but significantly lower HIF-1α protein level than control cells under hypoxia. Exogenous malate and α-KG exerted similar effect on HIF-1α in breast cancer cells to ME2 knockout or knockdown. Treatment with malate significantly decreased 4T1 breast cancer lung metastasis. ME2 expression was associated with HIF-1α level in human breast cancer samples (P=0.027).Conclusion: We provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis.
Soluble Guanylate Cyclase Reduced the Gastrointestinal Fibrosis in Bleomycin-induced Mouse Model of Systemic Sclerosis.
Authors: Yamamoto Yuzuru , Okano Takaichi , Yamada Hirotaka , Akashi Kengo , Sendo Sho , Ueda Yo , Morinobu Akio , Saegusa Jun
Published: January 2021

Background: Systemic sclerosis (SSc) is a chronic autoimmune-mediated connective tissue disorder. Although the etiology of the disease remains undermined, SSc is characterized by fibrosis and proliferative vascular lesions of the skin and internal organs. SSc involves the gastrointestinal tract in more than 90% of patients. Soluble guanylate cyclase (sGC) is used to treat pulmonary artery hypertension (PAH), and has been shown to inhibit experimental skin fibrosis.Methods: Female C57BL/6J mice were treated with BLM or normal saline by subcutaneous implantation of osmotic minipump. These mice were sacrificed on day 28 or day 42. Gastrointestinal pathologies were examined by Masson Trichrome staining. The expression of fibrosis-related genes in gastrointestinal tract were analyzed by real-time PCR, and the levels of collagen in the tissue was measured by Sircol collagen assay. To evaluate peristaltic movement, the small intestinal transport (ITR%) was calculated as [Dyeing distance×(Duodenum- Appendix)] -1 ×100 (%). We treated BLM-treated mice with soluble guanylate cyclase (sGC) or DMSO orally and analyzed them on day 42.Results: Histological examination revealed that fibrosis from lamina propria to muscularis mucosa in the esophagus was significantly increased in BLM-treated mice, suggesting that BLM induces esophageal fibrosis in C57BL/6J mice. In addition, the levels of Col3a1 and CTGF were significantly increased in BLM-treated mice. More severe fibrosis was observed in the mice sacrificed on day 42 than the mice sacrificed on day 28. The ITR% was found to be significantly lower in BLM-treated mice, suggesting that gastrointestinal peristaltic movement was reduced in BLM-treated mice. Furthermore, we demonstrated that sGC treatment significantly reduced fibrosis of esophagus and intestine in BLM-treated mice, by histological examination and Sircol collagen assay. Conclusions: These findings suggest that BLM induces gastrointestinal fibrosis in C57BL/6J mice, and treatment with sGC improves the BLM-induced gastrointestinal lesion.
Effects of WeChat-based Educational Intervention on Depression and Quality of Life in Patients with Ankylosing Spondylitis: A Randomized Controlled Trail
Authors: Song Yuqing , Xie Xia , Chen Yanlin , Wang Ying , Yang Hui , Nie Anliu , Chen Hong
Published: January 2021

Background: Ankylosing spondylitis(AS), as a common inflammatory rheumatic disease, often cause depression and impaired health-related quality of life(QoL). Although positive effects of patient education have been demonstrated, limited studies explored the benefits of education via mobile applications for AS patients. This study aimed to evaluate the effects of the WeChat-based educational intervention on depression and health-related QoL in AS patients.Methods: We conducted a single-blind randomized controlled trial from March to December 2017. Potential patients were recruited and randomized into the intervention group who received a 12-week WeChat-based educational intervention (consisting of four individual online educational sessions, online health information) or the control group receiving standard care. Data was collected at baseline and 12 weeks after the intervention. Outcomes were measured by Beck Depression Inventory-Ⅱ, the Medical Outcomes Study Short Form 36-item Health Survey, Bath Ankylosing Spondylitis Patient Global Score, visual analogue scales. Results: A total of 118 patients with AS were included and analysed. Measures at baseline were comparable between groups. After the intervention, the intervention group reported significant higher scores of all dimensions of QoL except for physical function and validity, compared with the control group. Additionally, patients in the intervention group had lower depressive symptom than the control group. No significant difference in other outcomes was observed at 12 weeks. Conclusions: This study found that the 12-week educational intervention via WeChat had positive effects on reducing depressive symptom and improving health related QoL in Chinese patients with AS. We suggest that this intervention can be integrated into current routine care of AS patients. Trial registration: Chinese Clinical Trail Registry (registry number: ChiCTR-IPR-16009293). Registered September 29, 2016.
Unmet Needs for Informal Care Among People With Type 2 Diabetes in Rural Communities in Vietnam.
Authors: Meyrowitsch Dan Wolf , Nielsen Jannie , Bygbjerg Ib Christian , Søndergaard Jens , Thi Diep Khong , Huyen Dieu Bui Thi , Gammeltoft Tine M. , Duc Thanh Nguyen
Published: January 2021

BACKGROUND From a diabetes management perspective, informal care has proven at least as important as care from health professionals when targeting poorly controlled diabetes. The objective of this study was to identify determinants associated with unmet needs for informal support among people with type-2 diabetes in rural communities of Vietnam. METHODS A cross-sectional survey was conducted from December 2018 to February 2019 in a rural area of northern Vietnam. From 2 districts in Thai Binh Province, Vietnam, 806 people with type-2 diabetes participated in a survey designed to assess who were their most important informal caregivers (ICGs) and to measure the association between demographic and socio-economic predictors and unmet needs of informal support of relevance for diabetes self-care using bivariate and multivariate analyses. RESULTS The spouse was reported as the most important ICG (62.9%) followed by a daughter or son (28.4%). 32.0% of the people with type-2 diabetes reported at least one type of unmet need for informal support. The most commonly reported unmet needs of informal care were: transport to health facilities and company when seeking formal care (20.5%), financial support related to costs of diabetes self-management (18.5%), and reminders to engage in physical exercise (14.5%). People living alone reported the highest odds ratio (OR) for unmet need of informal care (OR=4.41; CI95%: 2.19-8.88), followed by those being poor as compared to being wealthy (OR=3.79; CI95%: 1.25-11.52) and those being unemployed as compared to being retired (OR=2.85; CI95%: 1.61-5.05). CONCLUSIONS Almost one-third of people with type-2 diabetes reported at least one type of unmet need for informal care. These findings provide a basis for development of new modalities for strengthening support provided by ICGs in rural communities in Vietnam and in other low- and middle-income countries.
Research on mechanism of the effect of charred hawthorn on digestive by SCF /c-kit pathway
Authors: He Qian , Liu Cui , Wang Ting , Sun Jingying , Zhou Xia , Wang Yun , Ma Li , Wan Jun
Published: January 2021

Background

Hawthorn is the dry ripe fruit of Crataegus pinnatifida Bge in rose family which is a traditional Chinese medicine(TCM) for High-calorie-diet-induced dyspepsia (HC-DID). This study aimed to investigate whether the charred hawthorn coupled with its odor could alleviate HC-DID by brain-gut interaction and stem cell factor(SCF) /c-kit pathway.
Methods

Rats were randomly divided into 7 groups: control group, model group, cisapride group, hawthorn group (HT), charred hawthorn group (CHT), odor of charred hawthorn (OCHT), CHT + OCHT group. HC-DID rat model was established by high calorie diet for 10 days, hawthorn decoction was administered by gavage, and the self-developed solid drug odor delivery device was used for odor administration. The body weight, food intake, gastrointestinal motility, gastric fluid and gastric acid flow index were determined. HE staining was used to observe the pathological changes of rats. Electrophysiology was used to evaluate the effect of hawthorn combined with its charred odor therapy on electroencephalogram and Electrogastrogram. The SCF and c-kit levels or expressions by immunohistochemistry(IHC), enzyme linked immunosorbent assay (ELISA).
Results

We found that the odor of charred hawthorn (OCHT) affects the brain (central nervous system) of rats, and hawthorn decoction (raw hawthorn and charred hawthorn) coupled with the odor of charred hawthorn alleviated the symptoms of diet-induced dyspepsia in rats by modulating SCF/c-Kit pathway.
Conclusion

Thus, we concluded that odor of charred hawthorn has therapeutic effect on dyspepsia and hawthorn may alleviate dyspepsia related symptoms by affecting SCF/c-Kit signal pathway.
Deficiency and absence of endogenous isoprene in adults, disqualified its putative origin
Authors: Sukul Pritam , Richter Anna , Schubert Jochen K , Miekisch Wolfram
Published: January 2021

Background: Isoprene (C5H8) is a clinically important breath metabolite. Although, hundreds of studies have reported differential expressions in isoprene exhalation as breath biomarker for diverse diseases, the substance couldn’t enter to clinical practice as diagnostic marker. Moreover, many experimental/basic observations upon breath isoprene remained unrelated to the corresponding pathophysiological effects on its putative metabolic origin (i.e. mevalonate pathway). Here, we investigated the fundamental reason that hindered the rational interpretation and translation of this marker from basic to clinical science.Methods: Via high-resolution mass-spectrometry based breathomics in 1026 human subjects, we discovered adults with significant deficiency (order of magnitude lower than the normal) and complete absence of breath isoprene. We prospectively applied real-time breathomics, quantitative gene expression analysis of the mevalonate pathway enzymes, lipid-profiling and hemodynamic monitoring on those isoprene deficient subjects and controls. Additionally, the subject with absence of isoprene was followed up throughout different phases of her womanhood.Results: In contrast to convention, we witnessed that adults can live healthy without exhaling isoprene or with significant deficiency. This rare phenotype represents a recessive inheritance. Despite physio-metabolic changes during menstrual cycle (that is known to profoundly affect isoprene exhalation) and profoundly increased plasma cholesterol during pregnancy and after childbirth, isoprene remained absent. All genes of mevalonate pathway enzymes were normally expressed in all participants, without any down-regulation or compensatory up-regulation.Conclusions: Absence/deficiency of isoprene despite normal lipid profiles and no mevalonate pathway malfunction disqualifies the long-believed metabolic origin of isoprene from cholesterol biosynthesis. Thus, clinical translation of breath isoprene expressions should not be generally attributed to corresponding pathophysiological effects onto mevalonate/cholesterol pathway. Our finding has refined and optimized the clinical interpretation of isoprene as biomarker in volatile metabolomics and breathomics. Future studies will address the correct metabolic origin of isoprene to imply this important marker to routine practice.