bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nebulized Exosomes Derived from Allogenic Adipose Tissue Mesenchymal Stromal Cells in Patients with Severe COVID-19: A Pilot Study
Authors: Zhu Yinggang , Shi Meng-meng , Monsel Antoine , Dai Cheng-xiang , Dong Xuan , Shen Hong , Li Su-ke , Chang Jing , Xu Cui-li , Li Ping , Wang Jing , Shen Mei-ping , Ren Cheng-jie , Chen De-chang , Qu Jie-ming 
Published: April 2022

Abstract
BackgroundExisting clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19.MethodsThe MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0×108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging.ResultsSeven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (IQR, 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61×109/L vs. 1.78×109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients.ConclusionsOur trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0×109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population.Trial RegistrationMEXCOVID, NCT04276987
Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR
Authors: Xie Boyu , Zuhair Hawra , Henrique Rui , Millar Michael , Robson Timothy , Thrasivoulou Christopher , Dickens Kerry , Pendjiky Jane , Muneer Asif , Patel Hiten , Ahmed Aamir 
Published: April 2022

Abstract
Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making.
Breeding Biology of Rufous-Bellied Woodpecker (Dendrocopos hyperythrus) in Rudraprayag District (Kedarnath Wildlife Sanctuary, Western Himalayas), Uttarakhand, India
Authors: Bhatnagar Parul 
Published: April 2022

Abstract
In the Indian subcontinent there is almost no scientific study about the breeding biology of Rufous-bellied woodpecker (RBW) (Dendrocopos hyperythrus). Keeping this fact in view an attempt was made to understand the breeding biology of RBW during its breeding season from March 2018 to July 2020 in Kedarnath Wildlife Sanctuary (Western Himalayas), Uttarakhand. Results indicated that the breeding season of RBW extends from March to July. RBW is a primary cavity nester in which male woodpecker builds the nest on selected tree species such as Buransh (Rhododendron arboreum), Utis (Alnus nepalensis), Kharsu (Quercus semecarpifolia), Akhrot (Juglans regia), and Moru (Quercus floribunda). The most preferred tree species to build cavity nest by the study species was Buransh (Rhododendron arboreum) (N =5). Twelve active nests were located on tree trunks and branches. A nest was found abandoned before completion by the pair due to conflict with Himalayan woodpecker (Dendrocopos himalayensis) which built the nest on the same tree (Rhododendron arboreum). One egg was laid daily. The clutch size ranged from 2 to 3 with an average of 2.72 ± 0.12 eggs and the incubation period ranged between 16 to 18 days (Mean 16.72 ± 0.20 days). The average provisioning period was 25.81±0.36 days (Range 24 – 28 days). The average depth of the nest was found 29.5±6.67 cm (range 22 to 45 cm) and diameter of the cavity opening was 7.09±0.07 cm (Range 7.0 to 7.2 cm). Nests (N=12) were made at the height between 7 and 28 feet above ground with an average height of 19.08±6.08 feet. All the nesting sites were found between 1700-2579 m (ASL). Nests were excavated in all the directions except for North and northeast.
Taurine, EGCG and Genistein regulate AMPK-mTOR pathway to inhibit hepatic stellate cells autophagy and alleviate liver fibrosis in rats
Authors: Song Pengshu , Hu Shaocong , Li Yalan , Guan Zhezhe , He Dongling , Huang Zhi , Cheng Xiaoyang , Mo Caifeng , Zhang Xuerong , Liao Ming 
Published: April 2022

Abstract
Activation of hepatic stellate cells (HSCs) is the most important factor in the hepatic fibrosis progression. Autophagy is closely related to the activation of HSCs. Based on our previous works, this research tried to explore the anti-fibrotic mechanism of combination therapy with Taurine, Epigallocatechin gallate（EGCG） and Genistein, referred to as TEG, by monitored autophagy in HSCs and CCl4-induced liver fibrosis rats. Transmission electron microscopy showed that there were many autophagosomes and autophagy lysosomes in HSCs and fibrotic rats. After TEG intervention, autophagosomes are decreased, HSCs proliferation is inhibited and liver tissue damage is repaired. Western blot and IHC results found that TEG reduced the expression of autophagy marker proteins LC3-II and Beclin1 in HSCs or fibrotic rats. mRFP-GFP-LC3 showed that green fluorescence increased after TEG treat HSCs. AMPK-mTOR pathway analysis revealed that TEG inhibited LC3, Beclin1, AMPK(Adenosine 5'-monophosphate (AMP)-activated protein kinase) and mTOR genes and phosphorylated protein expression in HSCs. Our results indicate that TEG anti-fibrotic may be associated with reduce autophagosomes by inhibit AMPK-mTOR pathway.
Impact of metabolic syndrome and metabolic dysfunction-associated fatty liver disease on cardiovascular risk by the presence or absence of type 2 diabetes and according to sex
Authors: Matsubayashi Yasuhiro , Fujihara Kazuya , Yamada-Harada Mayuko , Mitsuma Yurie , Sato Takaaki , Yaguchi Yuta , Osawa Taeko , Yamamoto Masahiko , Kitazawa Masaru , Yamada Takaho , Kodama Satoru , Sone Hirohito 
Published: April 2022

Abstract
Background
To determine the impact of metabolic syndrome (MetS) and/or metabolic dysfunction-associated fatty liver disease (MAFLD), which are pathophysiologically similar and include insulin resistance, on the development of new-onset cardiovascular disease with and without type 2 diabetes and according to sex.
Methods
This study included 570,426 individuals without a history of cardiovascular disease who were enrolled in a nationwide claims database from 2008–2016 and were classified by the presence or absence of MetS and/or MAFLD stratified by the presence or absence of type 2 diabetes and sex. Risks of developing coronary artery disease (CAD) and cerebrovascular disease (CVD) in each category were analyzed using a multivariate Cox proportional hazard model.
Results
During a median follow-up of 5.2 years, 2,252 CAD and 3,128 CVD events occurred. Without type 2 diabetes the hazard ratio (HR) (95% CI) for CAD/CVD compared with neither MAFLD nor MetS was 1.32 (1.17–1.50)/1.41(1.28–1.57) for MAFLD only, 1.78 (1.22–2.58)/1.66 (1.34–2.06) for MetS only, and 2.10 (1.84–2.39)/1.73 (1.54–1.95) for MAFLD + MetS. For those with type 2 diabetes, the HR for CAD for MAFLD only (compared with neither MAFLD nor MetS) was 1.29 (1.06–1.58), for MetS only 1.34 (0.84–2.13), and for MAFLD + MetS 1.22 (1.02–1.47). For CVD, there was a significant increase in HR only in MAFLD + MetS [1.44 (1.18–1.76)]. The results of the analysis stratified by sex showed that MAFLD had a greater impact in men, and MetS had a greater impact in women regarding the development of CAD.
Conclusions
Distinguishing between MetS and/or MAFLD in the presence or absence of type 2 diabetes and according to sex may aid in accurately identifying patients at high risk of cardiovascular disease.
Learning Analytics for Tracking Student Progress in LMS
Authors: QAZDAR Aimad , QASSIMI Sara , HASSIDI Oussama , HAFIDI Meriem , ABDELWAHED El Hassan , MELK Youssef 
Published: April 2022

Abstract
The pandemic of the COVID-19 has accelerated the digital transformation oflearning and training. Many industries, especially higher education institutions,have been using e-Learning platforms. Learning Management System (LMS) inparticular, has gained popularity as a tool capable of managing learning andtraining processes as well as supporting learning process and administration. Itpresents an important package of services and features capable of facilitating andenhancing the e-Learning experience. Nevertheless, LMS offers only a few, if notno, functionalities when it gets to tracking the instructional progress of students.Progress in a learning experience is indicative of how students interact withcourses and learning materials. Based on such interaction, the teacher can detectlower performers, project students’ progress, and anticipate the ones at risk aswell as those who need intervention. The use of the LMS generates an importantamount of data. This data can become extremely useful when analysed andtransformed into indicators reflecting the learner’s progress. To this end, ourresearch project used learning analytics to determine and define indicatorscapable of monitoring students’ progress. With such analytics, we were able todetermine struggling students, lower performers and ultimately those who needreinforcement and tutoring. The main goal was to greatly improve students’success rates and the overall effectiveness of the learning process. We present acase study in which students’ progress was tracked and monitored using a set ofstudent’s Key Performance Indicators (KPIs). The data used in this study wascollected from the Web technologies course from the e-campus platform at the Cadi Ayyad University. The defined indicators allowed for tracking students’progress during the course, but they were not able to determine the performance of students.
Systematic review of associations of polychlorinated biphenyl (PCB) exposure with declining semen quality in support of the derivation of reference doses for mixture risk assessments
Authors: Ermler Sibylle , Kortenkamp Andreas 
Published: April 2022

Abstract
Background: Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon receptor (AhR)-agonists and androgen receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to derive a reference dose for declines in semen quality for individual PCB congeners for use in a mixture risk assessment.Methods: We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners.Results: Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day. Conclusions: We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other anti-androgenic chemicals.
Comparison of the Amount of Artifacts Induced by Zirconium and Titanium Implants in Cone-Beam Computed Tomography Images
Authors: Shokri Abbas , Vafaee Fariborz , Haghighat Leila , Shahabi Shiva , Farhadian Maryam , Jamalpour Mohammad Reza 
Published: April 2022

Abstract
Background: This study aimed to compare the amount of artifacts induced by the titanium and zirconium implants on cone-beam computed tomography (CBCT) and assess the effect of different exposure settings on the image quality for both materials.Methods: In this experimental study, zirconium and titanium implants were placed in bovine rib bone blocks. CBCT images were taken in two different fields of view (FOV: 4×6 cm2 and 6×8 cm2) and at two resolutions (133 µ and 200 µ voxel size). Subsequently, two observers assessed the images and detected the amount of artifacts around the implants through gray values. Data were analyzed using SPSS 21 and the significance level was set at 0.05.Results: The results showed that titanium implants caused lower amounts of artifacts than zirconium implants, which was statistically significant (P<0.001). By increasing the FOV, the amount of artifacts was decreased in both groups, although the results were only statistically significant in the zirconium group (P<0.001). The amount of artifacts was increased by increasing the resolution in both groups, which was only significant in the zirconium group (P<0.001).Conclusion: Our results suggest that zirconium implants induce higher amounts of artifacts than titanium ones. We also concluded that the artifacts could be minimized by increasing the FOV and decreasing the resolution.
Association Between Dietary Selenium Intake and Bone Mineral Density: A Cross-sectional Study Using National Health and Nutrition Examination Survey
Authors: Xue Guangze , Liu Rong 
Published: April 2022

Abstract
Assessments of whether dietary selenium intake is related to bone health are scarce, with few relevant studies limited by its small sample. The aim of present study was to investigated the association between dietary selenium intake and bone mineral density (BMD) levels in different sites, including total femur, femur neck, trochanter and intertrochanter in femur and lumbar spine in the National Health and Nutrition Examination Survey (NHANES) database. Generalized linear models for the association between dietary selenium intake and BMD and generalized additive model for the dose-response relationship were used. A total of 21939 participants were included, and the mean age was 40.68 ± 22.42 years, and 51.28% were male. In multivariable adjustment model, participants had highest quintiles of dietary selenium intake (Q5) were associated with increased BMD levels in total femur (β=0.014, 95CI%: 0.008, 0.020, P＜0.001), femur neck (β=0.010, 95CI%: 0.004, 0.016, P=0.001), trochanter (β=0.011, 95CI%: 0.005, 0.017, P＜0.001), intertrochanter (β=0.017, 95CI%: 0.010, 0.025, P＜0.001) and lumbar spine (β=0.013, 95CI%: 0.005, 0.020, P＜0.001) compared with those in quintiles 1 (Q1). The dose-response relationship showed the inverted U-shape relationship between dietary selenium relationship and BMD levels (P for non-linearity ＜0.05). Participants tended to have increased levels of BMD as the dietary selenium intake increased when dietary selenium was below the turning point, and then a negative relation was observed when dietary was higher than the turning point. Our study indicated that higher dietary selenium intake was associated with increased BMD levels in total femur, femur neck, trochanter, intertrochanter, and lumbar spine, and these relationships were nonlinear. Future high-quality, prospective longitudinal studies are needed to confirm these findings.
The sialidase NEU3 promotes pulmonary fibrosis in mice
Authors: Gomer Richard H. , Pilling Darrell , Sahlberg Kyle , Karhadkar Tejas R. , Chen Wensheng 
Published: April 2022

Abstract
Background Sialic acid is often the distal sugar on glycoconjugates, and sialidases are enzymes that remove this sugar. In fibrotic lesions in human and mouse lungs, there is extensive desialylation of glycoconjugates, and upregulation of sialidases including the extracellular sialidase NEU3. In the bleomycin model of pulmonary fibrosis, mice lacking NEU3 (Neu3-/-) showed strongly attenuated bleomycin-induced weight loss, lung damage, inflammation, and fibrosis. This indicates that NEU3 is necessary for the full spectrum of bleomycin-induced pulmonary fibrosis. MethodsTo determine if NEU3 is sufficient to induce pulmonary fibrosis, recombinant murine NEU3 and a mutated inactive recombinant murine NEU3 protein were produced. Mice were given recombinant NEU3 proteins by oropharyngeal aspiration, either alone or 10 days after bleomycin challenge. Over the course of 21 days, mice were assessed for weight change, and after euthanasia, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis.ResultsAspiration of recombinant murine NEU3 caused inflammation and fibrosis in the lungs, while inactive NEU3 caused inflammation but not fibrosis. Mice were also treated with recombinant murine NEU3 starting 10 days after bleomycin. In male but not female mice, recombinant murine NEU3 increased inflammation and fibrosis. Inactive NEU3 did not enhance bleomycin-induced lung fibrosis. ConclusionThese results suggest that NEU3 is sufficient to induce fibrosis in the lungs, that aspiration of NEU3 has a greater effect on male mice, and that this effect is mediated by NEU3’s enzymic activity.
Investigation of Metal Toxicity Response and Health Risk Assessment of Commonly Consumed Marine Fish Species along the Turkish coast
Authors: DOĞAN Serdar , KILIÇ Ece , UĞURLU Erkan , DUYSAK Önder 
Published: April 2022

Abstract
Marine environments are suffered from several types of pollution. Marine organisms take pollutants into their bodies which result in heavy metal accumulation in their tissues. Therefore, consumption of marine organisms may pose a risk to human health. This study was undertaken to estimate metal accumulation and metal toxicity responses of M. barbatus, B.boops, T. trachurus from Marmara Sea, Aegean Sea and Mediterranean Sea. Also, since these species were commonly consumped by Turkish people, health risk assessment employing The Target Hazard Quotient (THQ) and lifetime cancer risk (CR) was conducted. For that purpose, aluminum (Al), chrome (Cr), cobalt (Co), nickel (Ni), cadmium (Cd), lead (Pb), manganese (Mn), iron (Fe), copper (Cu) and zinc (Zn) concentrations in the muscle, gill and liver. To test the impact of metal toxicity on studies species, oxidative stress biomarkers (catalase-CA, Malondialdehyde-MDA) in muscle and liver were investigated. Metal accumulation levels showed differences depending on tissues, species and/or bays. Also, strong correlation was observed between biostress parameters and metal accumulation levels. Both, THQ and CR calculations showed safe consumption depending on the consumption of M. barbatus, B.boops, T. trachurus at all stations. Results obtained in this study showed that biostress parameters could be effectively used to monitor environmental pollution and contribute to the knowledge of metal toxicity along Turkish coast.
Transcriptome profiling of Rhipicephalus annulatus reveals differential gene expression of metabolic detoxifying enzymes in response to acaricide treatment
Authors: Achuthkumar Amritha , U Shamjana , Arvind Kumar , Varghese Sincy , Ravindran Reghu , Grace Tony 
Published: April 2022

Abstract
BackgroundTicks are hematophagous ectoparasites of economic consequence by virtue of being carriers of infectious diseases damaging for livestock and agro-industry. A widely prevalent tick variety, Rhipicephalus (Boophilus) annulatus is recognized as a prime vector of tick-borne diseases in Southern Indian conditions. Tick control using chemical acaricides over time has helped it to evolve resistant properties to widely-used compounds through metabolic detoxification. Identifying detoxification genes is extremely important because it helps to detect valid insecticide targets and will aid to develop novel control strategies for effective insect control. Methods and ResultsIn this study, high quality RNA-seq data of untreated and amitraz treated R. (B.) annulatus were assembled, annotated and analyzed. The annotated unigenes were significantly enriched in the pathways of metabolism, signal transduction, cellular community, transport, and catabolism. Overall, 38472 pathways were identified based on Gene ontology enrichment and pathway analysis. Differential gene expression analysis followed by the annotation of differentially expressed genes revealed significant expression of 70 detoxifying genes in response to amitraz treatment. Further, examination of expression level of candidate genes was across differential development stages of R. (B.) annulatus as performed using real time PCR. The results revealed significant differences in the gene expression level across stagesConclusionThe high expression of CYP and GST genes in R. (B) annulatus during acaricide stressed condition may implicate their role in resistance development and increased survival rate of R. (B) annulatus. Identified gene targets from this study may be used as valid targets for developing gene-based management strategies.