bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
Authors: Peteri Ulla‐Kaisa , Pitkonen Juho , de Toma Ilario , Nieminen Otso , Utami Kagistia Hana , Strandin Tomas M. , Corcoran Padraic , Roybon Laurent , Vaheri Antti , Ethell Iryna , Casarotto Plinio , Pouladi Mahmoud A. , Castrén Maija L. 
Published: August 2021

AbstractThe function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell‐derived components shape neuronal plasticity. Astrocyte abnormalities have been reported in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC‐derived astrocyte cultures and correlated inversely with intracellular Ca2+ responses to activation of L‐type voltage‐gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB within the docking site for the phospholipase‐Cγ1 (PLCγ1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS‐specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)‐responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.
Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2
Authors: Console Lara , Tolomeo Maria , Cosco Jessica , Massey Keith , Barile Maria , Indiveri Cesare 
Published: August 2021

AbstractRiboflavin transporter deficiency 2 (RTD2) is a rare neurological disorder caused by mutations in the Solute carrier family 52 member 2 (Slc52a2) gene encoding human riboflavin transporter 2 (RFVT2). This transporter is ubiquitously expressed and mediates tissue distribution of riboflavin, a water‐soluble vitamin that, after conversion into FMN and FAD, plays pivotal roles in carbohydrate, protein, and lipid metabolism. The 3D structure of RFVT2 has been constructed by homology modeling using three different templates that are equilibrative nucleoside transporter 1 (ENT1), Fucose: proton symporter, and glucose transporter type 5 (GLUT5). The structure has been validated by several approaches. All known point mutations of RFVT2, associated with RTD2, have been localized in the protein 3D model. Six of these mutations have been introduced in the recombinant protein for functional characterization. The mutants W31S, S52F, S128L, L312P, C325G, and M423V have been expressed in E. coli, purified, and reconstituted into proteoliposomes for transport assay. All the mutants showed impairment of function. The Km for riboflavin of the mutants increased from about 3 to 9 times with respect to that of WT, whereas Vmax was only marginally affected. This agrees with the improved outcome of most RTD2 patients after administration of high doses of riboflavin.
Medication access: Policy and practice opportunities for pharmacists
Authors: Sobeski Linda M. , Schumacher Christine A. , Alvarez Nancy A. , Anderson Keri C. , Bradley Bridget , Crowe Susie J. , Merlo Jessica R. , Nyame Adwoa , Rivera Kelley S. , Shapiro Nancy L. , Spencer Dustin D. , Van Dril Elizabeth 
Published: August 2021

AbstractMedication access is critical to achieving optimal patient outcomes. The 2020 Task Force on Medication Access was charged with developing an ACCP white paper on improving medication access that addresses barriers such as cost, health disparities, and utilization management practices. This white paper outlines major barriers to medication access and provides pharmacists and professional organizations with policy and practice recommendations to help reduce barriers, enhance medication access, and fulfill the goal of optimal patient outcomes.
Application of Multiparametric Magnetic Resonance Imaging to Monitor the Early Antitumor Effect of CuS@GOD Nanoparticles in a 4 T1 Breast Cancer Xenograft Model
Authors: Ye Yao‐Jiang , Huang Xiu‐Jie , Luo Bi‐Chong , Wang Xiao‐Ying , Cai Xiang‐Ran 
Published: August 2021

BackgroundWe have developed hybrid nanoparticles (NPs) by co‐loading copper sulfide (CuS) NPs and glucose oxidase (GOD) (CuS@GOD NPs) to explore their antitumor properties.PurposeTo investigate the feasibility of using multiparametric magnetic resonance imaging (MRI) including intravoxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) and R2* mapping to quantitatively assess the early antitumor effect of CuS@GOD NPs.Study typeProspective.Animal modelThe orthotopic BALB/c mice 4 T1 breast cancer model. The 4 T1 xenografts in group 1 mice received normal saline, group 2 received CuS@GOD NPs, group 3 received CuS NPs plus laser, and group 4 received CuS@GOD NPs plus laser (n = 28 for each group).Field Strength/SequenceA 3.0 T/IVIM‐DWI MRI single‐shot echo‐planar imaging, R2* mapping spoiled gradient recalled echo (SPGR) sequence, T2‐weighted images (T2WI) and T1‐weighted images (T1WI) fast spin echo (FSE) sequence.AssessmentThe IVIM‐DWI and R2* mapping were performed before and after treatment at 0 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, and 24 hours in four groups and the MRI parameters were obtained. Correlation analysis between the MRI parameters and histological analyses was conducted.Statistical TestsOne‐way ANOVA, Pearson's correlation analysis, two independent samples t test, intraclass correlation coefficient. P < 0.05 was considered to be statistically significant.ResultsIn group 4, the tumoral D value was significantly higher than that of group 2 at 24 hours (0.541 ± 0.065 vs. 0.492 ± 0.051). The f value of group 4 was significantly lower than that of groups 1 and 2 at 2 hours (10.83 ± 2.16 vs. 14.28 ± 1.86, 16.67 ± 3.53, respectively). The R2* value was significantly increased at 0 hour in group 4 compared to that of groups 1 and 2 (64.552 ± 4.663 vs. 42.441 ± 1.516, 43.165 ± 1.709, respectively). D, f, and R2* were correlated with the histological staining results (r = 0.695–0.970).Data ConclusionThe IVIM‐DWI‐derived D and f and R2* mapping‐derived R2* could monitor early response to CuS@GOD NPs treatment in vivo.Evidence Level2Technical EfficacyStage 2
Effect of mutation and vaccination on spread, severity, and mortality of COVID‐19 disease
Authors: Zawbaa Hossam M. , Osama Hasnaa , El‐Gendy Ahmed , Saeed Haitham , Harb Hadeer S. , Madney Yasmin M. , Abdelrahman Mona , Mohsen Marwa , Ali Ahmed M. A. , Nicola Mina , Elgendy Marwa O. , Ibrahim Ihab A. , Abdelrahim Mohamed E. A. 
Published: August 2021

AbstractCoronavirus disease 2019 (COVID‐19) has had different waves within the same country. The spread rate and severity showed different properties within the COVID‐19 different waves. The present work aims to compare the spread and the severity of the different waves using the available data of confirmed COVID‐19 cases and death cases. Real‐data sets collected from the Johns Hopkins University Center for Systems Science were used to perform a comparative study between COVID‐19 different waves in 12 countries with the highest total performed tests for severe acute respiratory syndrome coronavirus 2 detection in the world (Italy, Brazil, Japan, Germany, Spain, India, USA, UAE, Poland, Colombia, Turkey, and Switzerland). The total number of confirmed cases and death cases in different waves of COVID‐19 were compared to that of the previous one for equivalent periods. The total number of death cases in each wave was presented as a percentage of the total number of confirmed cases for the same periods. In all the selected 12 countries, Wave 2 had a much higher number of confirmed cases than that in Wave 1. However, the death cases increase was not comparable with that of the confirmed cases to the extent that some countries had lower death cases than in Wave 1, UAE, and Spain. The death cases as a percentage of the total number of confirmed cases in Wave 1 were much higher than that in Wave 2. Some countries have had Waves 3 and 4. Waves 3 and 4 have had lower confirmed cases than Wave 2, however, the death cases were variable in different countries. The death cases in Waves 3 and 4 were similar to or higher than Wave 2 in most countries. Wave 2 of COVID‐19 had a much higher spread rate but much lower severity resulting in a lower death rate in Wave 2 compared with that of the first wave. Waves 3 and 4 have had lower confirmed cases than Wave 2; that could be due to the presence of appropriate treatment and vaccination. However, that was not reflected in the death cases, which were similar to or higher than Wave 2 in most countries. Further studies are needed to explain these findings.
Analysis of serum cytokine and protective vitamin D levels in severe cases of COVID‐19
Authors: Bayraktar Nihayet , Turan Hamdiye , Bayraktar Mehmet , Ozturk Ali , Erdoğdu Hamza 
Published: August 2021

AbstractIn this study, we investigated the role and relationship between the cytokine profile and protective vitamin D by measuring their serum levels in COVID‐19 intensive care unit patients with severe illnesses. A total of 74 patients were included in our study. Patients were divided into two groups. Patients in the COVID‐19 group (n = 31) and individuals without a history of serious illness or infection were used as the control group (n = 43). The serum concentrations of interleukin‐1 (IL‐1), IL‐6, IL‐10, IL‐21, and tumor necrosis factor‐α (TNF‐α) were measured by enzyme‐linked immunosorbent assays. Levels of serum vitamin D were detected with Liquid chromatography–mass spectrometry methodologies. TNF‐α, IL‐1, IL‐6, IL‐10, IL‐21, and vitamin D levels were measured in all patients. The serum cytokine levels in the COVID‐19 patient group were significantly higher (151.59 ± 56.50, 140.37 ± 64.32, 249.02 ± 62.84, 129.04 ± 31.64, and 123.58 ± 24.49, respectively) than control groups. Serum vitamin D was also significantly low (6.82 ± 3.29) in patients in the COVID‐19 group than the controls (21.96 ± 5.39). Regarding the correlation of vitamin D with cytokine levels, it was significantly variable. Our study shows that COVID‐19 patients are associated with lower serum vitamin D and higher pro‐inflammatory cytokines associated with increased virus presence. Our data provide more evidence of the anti‐inflammatory effect of vitamin D on COVID‐19 patients and the protective effects of vitamin D on risk were demonstrated.
Metformin accelerates wound healing by Akt phosphorylation of gingival fibroblasts in insulin‐resistant prediabetes mice
Authors: Kominato Hiromi , Takeda Kohei , Mizutani Koji , Mikami Risako , Kido Daisuke , Buranasin Prima , Saito Natsumi , Takemura Shu , Nakagawa Keita , Nagasawa Toshiyuki , Iwata Takanori 
Published: August 2021

AbstractBackgroundThis study aimed to investigate the effects of metformin on gingival wound healing in insulin‐resistant prediabetes.MethodsC57BL/6J mice were fed normal diet (ND) or high‐fat diet (HFD) for 10 weeks; half of the HFD mice were treated with metformin (HFD+ Met) for the last 2 weeks. Insulin and glucose tolerance tests were performed. The palatal gingiva (2.0 × 0.5 mm) was surgically removed adjacent to the maxillary molars. Post‐surgical wound closure was histomorphometrically evaluated for 1 week. The mRNA expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) in the tissue were quantified by real‐time polymerase chain reaction. In vitro, the proliferation and migration of human gingival fibroblasts (HGFs) cultured under high‐glucose or control conditions with/without metformin were analyzed. Akt phosphorylation and VEGF expression following the insulin stimulation were evaluated with/without metformin in high‐glucose or control media.ResultsHFD mice showed significantly higher plasma glucose levels and insulin resistance than ND mice. Gingival wound healing was delayed in HFD group compared with ND group but significantly improved in HFD + MET group. The decreased expression of VEGF and eNOS in HFD group was significantly elevated in the HFD + MET group. The proliferation and migration of HGFs were significantly impaired in high‐glucose conditions compared with control; metformin treatment partially attenuated these effects. Metformin treatment significantly recovered the downregulated Akt phosphorylation and VEGF expression in high‐glucose conditions.ConclusionsMetformin improved delayed gingival wound healing in insulin‐resistant prediabetes by accelerating HGFs proliferation and migration via Akt phosphorylation in insulin signaling pathway.
Marine biofilms on different fouling control coating types reveal differences in microbial community composition and abundance
Authors: Papadatou Maria , Robson Samuel C. , Dobretsov Sergey , Watts Joy E. M. , Longyear Jennifer , Salta Maria 
Published: August 2021

AbstractMarine biofouling imposes serious environmental and economic impacts on marine applications, especially in the shipping industry. To combat biofouling, protective coatings are applied on vessel hulls which are divided into two major groups: biocidal and non‐toxic fouling release. The current study aimed to explore the effect of coating type on microbial biofilm community profiles to better understand the differences between the communities developed on fouling control biocidal antifouling and biocidal‐free coatings. Biocidal (Intersmooth® 7460HS SPC), fouling release (Intersleek® 900), and inert surfaces were deployed in the marine environment for 4 months, and the biofilms that developed on these surfaces were investigated using Illumina NGS sequencing, targeting the prokaryotic 16S rRNA gene. The results confirmed differences in the community profiles between coating types. The biocidal coating supported communities dominated by Alphaproteobacteria (Loktanella, Sphingorhabdus, Erythrobacter) and Bacteroidetes (Gilvibacter), while other taxa, such as Portibacter and Sva0996 marine group, proliferated on the fouling‐release surface. Knowledge of these marine biofilm components on fouling control coatings will serve as a guide for future investigations of marine microfouling as well as informing the coatings industry of potential microbial targets for robust coating formulations.
Gray and White Matter Correlates of Dysphagia in Progressive Supranuclear Palsy
Authors: Clark Heather M. , Tosakulwong Nirubol , Weigand Stephen D. , Ali Farwa , Botha Hugo , Pham Nha Trang Thu , Schwarz Christopher G. , Reid Robert I. , Senjem Matthew L. , Jack Clifford R. , Lowe Val J. , Ahlskog J. Eric , Josephs Keith A. , Whitwell Jennifer L. 
Published: August 2021

AbstractBackgroundDysphagia is a common symptom of progressive supranuclear palsy often leading to aspiration pneumonia and death.ObjectiveThe aim of this study was to examine how impairments of the oral and pharyngeal phases of the swallow and airway incursion during liquid swallows relate to gray and white matter integrity.MethodsThirty‐eight participants with progressive supranuclear palsy underwent videofluorographic swallowing assessment and structural and diffusion tensor head magnetic resonance imaging. Penalized linear regression models assessed relationships between swallowing metrics and regional gray matter volumes and white matter fractional anisotropy and mean diffusivity.ResultsOral phase impairments were associated with reduced superior parietal volumes and abnormal diffusivity in parietal and sensorimotor white matter, posterior limb of the internal capsule, and superior longitudinal fasciculus. Pharyngeal phase impairments were associated with disruption to medial frontal lobe, corticospinal tract, and cerebral peduncle. No regions were predictive of airway incursion.ConclusionsDifferential patterns of neuroanatomical impairment corresponded to oral and pharyngeal phase swallowing impairments. © 2021 International Parkinson and Movement Disorder Society
Reaction Data Curation I: Chemical Structures and Transformations Standardization
Authors: Gimadiev Timur R. , Lin Arkadii , Afonina Valentina A. , Batyrshin Dinar , Nugmanov Ramil I. , Akhmetshin Tagir , Sidorov Pavel , Duybankova Natalia , Verhoeven Jonas , Wegner Joerg , Ceulemans Hugo , Gedich Andrey , Madzhidov Timur I. , Varnek Alexandre 
Published: August 2021

AbstractThe quality of experimental data for chemical reactions is a critical consideration for any reaction‐driven study. However, the curation of reaction data has not been extensively discussed in the literature so far. Here, we suggest a 4 steps protocol that includes the curation of individual structures (reactants and products), chemical transformations, reaction conditions and endpoints. Its implementation in Python3 using CGRTools toolkit has been used to clean three popular reaction databases Reaxys, USPTO and Pistachio. The curated USPTO database is available in the GitHub repository (Laboratoire‐de‐Chemoinformatique/Reaction_Data_Cleaning).
Radiobiology of the FLASH effect
Authors: Friedl Anna A. , Prise Kevin M. , Butterworth Karl T. , Montay‐Gruel Pierre , Favaudon Vincent 
Published: August 2021

AbstractRadiation exposures at ultrahigh dose rates (UHDRs) at several orders of magnitude greater than in current clinical radiotherapy (RT) have been shown to manifest differential radiobiological responses compared to conventional (CONV) dose rates. This has led to studies investigating the application of UHDR for therapeutic advantage (FLASH‐RT) that have gained significant interest since the initial discovery in 2014 that demonstrated reduced lung toxicity with equivalent levels of tumor control compared with conventional dose‐rate RT. Many subsequent studies have demonstrated the potential protective role of FLASH‐RT in normal tissues, yet the underlying molecular and cellular mechanisms of the FLASH effect remain to be fully elucidated. Here, we summarize the current evidence of the FLASH effect and review FLASH‐RT studies performed in preclinical models of normal tissue response. To critically examine the underlying biological mechanisms of responses to UHDR radiation exposures, we evaluate in vitro studies performed with normal and tumor cells. Differential responses to UHDR versus CONV irradiation recurrently involve reduced inflammatory processes and differential expression of pro‐ and anti‐inflammatory genes. In addition, frequently reduced levels of DNA damage or misrepair products are seen after UHDR irradiation. So far, it is not clear what signal elicits these differential responses, but there are indications for involvement of reactive species. Different susceptibility to FLASH effects observed between normal and tumor cells may result from altered metabolic and detoxification pathways and/or repair pathways used by tumor cells. We summarize the current theories that may explain the FLASH effect and highlight important research questions that are key to a better mechanistic understanding and, thus, the future implementation of FLASH‐RT in the clinic.
The COVID‐19 pandemic and healthcare workers psychological well‐being: a cross‐sectional survey in Indonesia
Authors: Ni’matuzahroh  , Ningrum Valendriyani , Widayat  , Dyah Artaria Myrtati , Suen Mein‐Woei 
Published: August 2021

AbstractAimThis study was conducted to investigate the relationships amongst psychological well‐being (PWB), emotional intelligence and coping strategies.DesignThis study employed a cross‐sectional survey design.MethodA total of 146 healthcare workers (HCWs) were enrolled in this study. They were asked to finish several questionnaires, including the Wong and Law Emotional Intelligence Scale, the Brief‐Coping Orientation to Problems Experienced Scale and the PWB Scale. The obtained data were analysed using partial least squares structural equation modelling, employee SmartPLS, to estimate the contributions of influencing factors and evaluate the moderating effect of coping strategy (CS) on the relationship between emotional intelligence and PWB.ResultsResults revealed that emotional intelligence influenced PWB, and CS moderated both emotional intelligence and PWB. Furthermore, CS plays an essential role in improving PWB related to emotional intelligence amongst HCWs during the COVID‐19 outbreak.
Counseling for personal health implications identified during reproductive genetic carrier screening
Authors: Gbur Samantha , Mauney Logan , Gray Kathryn J. , Wilkins‐Haug Louise , Guseh Stephanie 
Published: August 2021

AbstractObjectivePreconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X‐linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre‐ and post‐test counseling.MethodsTwelve genetic conditions with personal health risks for carriers included on carrier screening panels but not otherwise screened routinely were identified (e.g., Gaucher disease with Parkinson's disease risk). A retrospective review was performed of patients with a positive carrier screen for one of these conditions at our center from 2012 to 2019.ResultsOf 6147 individuals that had carrier screening for one of the twelve conditions, 96 (1.56%) did not report a known family history and screened positive for one of the conditions. Testing was ordered largely by reproductive endocrinologists (51.0%) and genetic counselors (35.4%). Most individuals did not receive pre‐ (96.8%) or post‐test (64.6%) counseling about personal health risks. Post‐test counseling was performed principally by genetic counselors (97.1%). For carriers of conditions with guidelines for specialist referral, most individuals (75.9%) were referred.ConclusionExpanded genetic carrier screening increasingly identifies individuals with personal health implications, but patients are frequently not counseled before or after testing. These findings stress the importance of developing guidelines for practitioners about expanded carrier screening counseling and follow‐up.
Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin‐1β/transforming growth factor‐β‐mediated activation of renal fibroblasts
Authors: Wang Meng , Wang Lingchen , Zhou Yuan , Feng Xiaoxuan , Ye Chaoyang , Wang Chen 
Published: August 2021

Icariin (ICA) is a bioactive flavonoid extracted from Epimedium brevicornum Maxim and exhibits a variety of pharmacological activities including antiinflammatory and antioxidant effects. Recently, icariin has shown renoprotective role by inhibiting pathological matrix. However, the underlying mechanisms of the efficacy remain unknown. This study aimed to determine the effects of icariin on renal fibrosis and explore its molecular mechanisms. Chronic kidney disease (CKD) was induced in rats with 5/6 ablation and infarction (A/I) operation. Four weeks later, rats were treated with vehicle or 20 mg/kg (low dose) or 40 mg/kg (high dose) of icariin by daily gavage. Furthermore, to further elucidate the effect mechanisms of icariin, in vitro, NRK‐49F cells stimulated by 8 ng/ml IL‐1β were treated with icariin in the presence or absence of SB431542 or the neutralizing antibody of transforming growth factor‐β (TGF‐β) for 24 h. We showed that icariin treatment for 8 weeks dose‐dependently improved 5/6 (A/I)‐induced kidney injury and fibrosis, and blocked the release of inflammatory cytokine IL‐1β. In vitro, icariin inhibited IL‐1β/TGF‐β‐mediated activation of renal fibroblasts. In summary, anti‐fibrotic effects of icariin were interconnected with the inhibition of renal fibroblast activation caused by IL‐1β/TGF‐β signaling.