bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystallization Control of N,N′-Dioctyl Perylene Diimide by Amphiphilic Block Copolymers Containing poly(3-Hexylthiophene) and Polyethylene Glycol
Authors: Yang Xiaohui , Lu Wanlong , Cao Jingning , Zhai Chenyang , Li Weili , Zha Fangwen , Lu Guanghao , Tian Hongkun , Yu Demei , Bu Laju 
Published: June 2021

The preparation of micron- to nanometer-sized functional materials with well-defined shapes and packing is a key process to their applications. There are many ways to control the crystal growth of organic semiconductors. Adding polymer additives has been proven a robust strategy to optimize semiconductor crystal structure and the corresponding optoelectronic properties. We have found that poly(3-hexylthiophene) (P3HT) can effectively regulate the crystallization behavior of N,N′-dioctyl perylene diimide (C8PDI). In this study, we combined P3HT and polyethylene glycol (PEG) to amphiphilic block copolymers and studied the crystallization modification effect of these block copolymers. It is found that the crystallization modification effect of the block copolymers is retained and gradually enhanced with P3HT content. The length of C8PDI crystals were well controlled from 2 to 0.4 μm, and the width from 210 to 35 nm. On the other hand, due to the water solubility of PEG block, crystalline PEG-b-P3HT/C8PDI micelles in water were successfully prepared, and this water phase colloid could be stable for more than 2 weeks, which provides a new way to prepare pollution-free aqueous organic semiconductor inks for printing electronic devices.
A Novel Strategy to Coat Dopamine-Functionalized Titanium Surfaces With Agarose-Based Hydrogels for the Controlled Release of Gentamicin
Authors: Soylu H. Melis , Chevallier Pascale , Copes Francesco , Ponti Federica , Candiani Gabriele , Yurt Fatma , Mantovani Diego 
Published: June 2021

IntroductionThe use of spinal implants for the treatment of back disorders is largely affected by the insurgence of infections at the implantation site. Antibacterial coatings have been proposed as a viable solution to limit such infections. However, despite being effective at short-term, conventional coatings lack the ability to prevent infections at medium and long-term. Hydrogel-based drug delivery systems may represent a solution controlling the release of the loaded antibacterial agents while improving cell integration. Agarose, in particular, is a biocompatible natural polysaccharide known to improve cell growth and already used in drug delivery system formulations. In this study, an agarose hydrogel-based coating has been developed for the controlled release of gentamicin (GS).MethodsSand blasted Ti6Al4V discs were grafted with dopamine (DOPA) solution. After, GS loaded agarose hydrogels have been produced and additioned with tannic acid (TA) and calcium chloride (CaCl2) as crosslinkers. The different GS-loaded hydrogel formulations were deposited on Ti6Al4V-DOPA surfaces, and allowed to react under UV irradiation. Surface topography, wettability and composition have been analyzed with profilometry, static contact angle measurement, XPS and FTIR spectroscopy analyses. GS release was performed under pseudo-physiological conditions up to 28 days and the released GS was quantified using a specific ELISA test. The cytotoxicity of the produced coatings against human cells have been tested, along with their antibacterial activity against S. aureus bacteria.ResultsA homogeneous coating was obtained with all the hydrogel formulations. Moreover, the coatings presented a hydrophilic behavior and micro-scale surface roughness. The addition of TA in the hydrogel formulations showed an increase in the release time compared to the normal GS-agarose hydrogels. Moreover, the GS released from these gels was able to significantly inhibit S. aureus growth compared to the GS-agarose hydrogels. The addition of CaCl2 to the gel formulation was able to significantly decrease cytotoxicity of the TA-modified hydrogels.ConclusionsDue to their surface properties, low cytotoxicity and high antibacterial effects, the hereby proposed gentamicin-loaded agarose-hydrogels provide new insight, and represent a promising approach for the surface modification of spinal implants, greatly impacting their application in the orthopedic surgical scenario.
Association of Autism Spectrum Disorder, Neuroticism, and Subjective Well-Being With Cardiovascular Diseases: A Two-Sample Mendelian Randomization Study
Authors: Sun Xingang , Chen Lu , Wang Zhen , Lu Yunlong , Chen Miao , He Yuxian , Xu Hongfei , Zheng Liangrong 
Published: June 2021

Background: Previous observational studies have reported an association between psychiatric traits and cardiovascular diseases (CVDs). In this two-sample Mendelian randomization (MR) study, we aimed to investigate the causality between psychiatric traits and CVDs.Methods: Single-nucleotide polymorphisms (SNPs) associated with autism spectrum disorder (ASD), neuroticism, and subjective well-being at genome-wide significance (P &lt; 1 × 10−8) were identified from genome-wide association studies. Summary-level data of the outcomes, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF), were obtained from several largest datasets. The inverse-variance weighted (IVW) method was used as our main analyses to conduct this MR study. Sensitivity analyses included the weighted median, the MR-robust adjusted profile score (MR-RAPS), and the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Repeated MR analyses using a more relaxed threshold (P &lt; 1 × 10−6) for instruments selection and multivariable MR analyses were also applied to evaluate the robustness of results.Results: The MR analyses showed that genetic predisposition to ASD was associated with a higher risk of AF [odds ratio (OR), 1.109; 95% confidence interval (CI), 1.023–1.201; P = 0.011] and HF (OR, 1.138; 95% CI, 1.036–1.251; P = 0.007). Neuroticism was casually associated with an increased risk of AF (OR, 1.201; 95% CI, 1.037–1.392; P = 0.015), whereas subjective well-being had a protective effect on HF (OR, 0.732; 95% CI, 0.574–0.933; P = 0.012). No other causal association between psychiatric traits and CVDs was observed. Consistent results were obtained in sensitivity analyses.Conclusion: This study provided evidence of causal associations of ASD with a higher risk of AF and HF. Besides, neuroticism was casually associated with an increased risk of AF, and subjective well-being was associated with a decreased risk of HF.
Earthquake Early Warning System in Israel—Towards an Operational Stage
Authors: Nof Ran N. , Lior Itzhak , Kurzon Ittai 
Published: June 2021

The Geological Survey of Israel has upgraded and expanded the national Israeli Seismic Network (ISN), with more than 110 stations country-wide, as part of the implementation of a governmental decision to build a national Earthquake Early Warning (EEW) system named TRUAA. This upgraded seismic network exhibits a high station density and fast telemetry. The stations are distributed mainly along the main fault systems, the Dead Sea Transform, and the Carmel-Zfira Fault, which may potentially produce Mw7.5 earthquakes. The system has recently entered a limited operational phase, allowing for initial performance estimation. Real-time performance during eight months of operation (41 earthquakes) matches expectations. Alert delays (interval between origin-time and Earthquake Early Warning alert time) are reduced to as low as 3 s, and source parameter errorstatistics are within expected values found in previous works using historical data playbacks. An evolutionary alert policy is implemented based on a magnitude threshold of Mw 4.2 and peak ground accelerations exceeding 2 cm/s2. A comparison between different ground motion prediction equations (GMPE) is presented for earthquakes from Israel and California using median ground motion prediction equations values. This analysis shows that a theoretical GMPE produced the best agreement with observed ground motions, with less bias and lower uncertainties. The performance of this GMPE was found to improve when an earthquake specific stress drop is implemented.
Novel AQP2 Mutations and Clinical Characteristics in Seven Chinese Families With Congenital Nephrogenic Diabetes Insipidus
Authors: Li Qian , Tian Dan , Cen Jing , Duan Lian , Xia Weibo 
Published: June 2021

ObjectiveMutations in AQP2 (aquaporin-2) lead to rare congenital nephrogenic diabetes insipidus (NDI), which has been limitedly studied in Chinese population.MethodsTwenty-five subjects from seven families with NDI in a department (Beijing, PUMCH) were screened for AQP2 mutations. Clinical characteristics were described and genotype-phenotype correlation analysis was performed.ResultsWe identified 9 AQP2 mutations in 13 patients with NDI, including 3 novel AQP2 mutations (p.G165D, p.Q255RfsTer72 and IVS3-3delC). Missense mutations were the most common mutation type, followed by splicing mutations, and frameshift mutations caused by small deletion or insertion. The onset-age in our patients was younger than 1 year old. Common manifestations included polydipsia, polyuria (7/7) and intermittent fever (6/7). Less common presentations included short stature (3/7) and mental impairment (1/7). High osmotic hypernatremia and low osmotic urine were the main biochemical features. Dilation of the urinary tract was a common complication of NDI (3/6). Level of serum sodium in NDI patients with compound het AQP2 mutations was higher than non-compound het mutations.ConclusionIn the first and largest case series of NDI caused by AQP2 mutation in Chinese population, we identified 9 AQP2 mutations, including 3 novel mutations. Phenotype was found to correlate with genotypes, revealed by higher level of serum sodium in patients with compound het AQP2 mutations than non-compound het mutations. This knowledge broadens genotypic and phenotypic spectrum for rare congenital NDI and provided basis for studying molecular biology of AQP2.
Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients
Authors: Chiu Yen-Ling , Lin Wei-Chou , Shu Kai-Hsiang , Fang Yi-Wen , Chang Fan-Chi , Chou Yu-Hsiang , Wu Ching-Fang , Chiang Wen-Chih , Lin Shuei-Liong , Chen Yung-Ming , Wu Ming-Shiou 
Published: June 2021

BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.
SARS-CoV-2 Infection in Spondyloarthritis Patients Treated With Biotechnological Drugs: A Study on Serology
Authors: Ortolan Augusta , Lorenzin Mariagrazia , Cosma Chiara , Cozzi Giacomo , Padoan Andrea , Doria Andrea , Plebani Mario , Ramonda Roberta 
Published: June 2021

ObjectiveSerology could help to define the real extent of SARS-CoV-2 diffusion, especially in individuals considered at higher risk of COVID-19, such as spondyloarthritis (SpA) patients undergoing immunosuppressant. Our aim was to detect, by serology, previous SARS-CoV-2 contact in SpA, compared to health care workers (HCW), and healthy controls.MethodsSera from consecutive patients affected by SpA undergoing cytokine-targeted therapy, HCW and healthy controls from 2015 were analysed through chemiluminescent analytical system for the presence of IgG and IgM anti-SARS-CoV-2. Positive patients (IgM or IgG, or both) additionally underwent real-time Polymerase-Chain-Reaction (RT-PCR) to test for active infection. Serology was repeated at 3-months in SpA. Data across 3 groups were compared by Kruskal Wallis/Chi-square, and between 2 groups by Wilcoxon rank test/Chi-Square. P ≤ 0.05 were considered significant.Results200 SpA, 95 HCW and 101 controls were recruited. Positive serology was found in 25(12.5%) SpA, 8(8.4%) HCW, 0(0%) controls (p=0.001). SpA patients with positive serology more frequently reported COVID-19-like symptoms than those with negative serology (20% vs. 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, non severe. No HCW reported symptoms or had positive RT-PCR. In SpA patients, at 3 months, mean IgM titres decreased from 2.76 ± 2.93 to 2.38 ± 2.95 (p=0.001), while IgG titres from 0.89 ± 3.25 to 0.31 ± 0.87 (p=ns).ConclusionsSerology revealed that exposure to SARS-CoV-2 in SpA patients and HCW was higher than expected based on reported symptoms. In SpA, anti-cytokine therapy could act as a protective factor for a severe disease course. However, a seroconversion was not observed at 3-months.
Determination of Thermal Expansion, Defect Formation Energy, and Defect-Induced Strain of α-U Via ab Initio Molecular Dynamics
Authors: Beeler Benjamin , Mahbuba Khadija , Wang Yuhao , Jokisaari Andrea 
Published: June 2021

Uranium (U) is often alloyed with molybdenum (Mo) or zirconium (Zr) in order to stabilize its high-temperature body-centered cubic phase for use in nuclear reactors. However, in all metallic fuel forms, the α phase of U remains in some fraction. This phase decomposition due to temperature or compositional variance can play an outsized role on fuel performance and microstructural evolution. Relatively little is known about fundamental point defect properties in α-U at non-zero temperatures, from either computational or experimental studies. This work performs the first thorough evaluation of the α phase of U via ab initio molecular dynamics (AIMD). A number of thermophysical properties are calculated as a function of temperature, including equilibrium lattice parameters, thermal expansion, and heat capacity. These results indicate a two-region behavior, with the transition at 400 K. The thermal expansion/contraction in the a/b direction occurs rapidly from 100 up to 400 K, after which a more linear and gradual change in the lattice constant takes place. The volumetric expansion matches experiments quantitatively, but the individual lattice constant expansion only matches experiments qualitatively. Point defect formation energies and induced lattice strains are also determined as a function of temperature, providing insight on defect populations and the fundamentals of irradiation growth in α-U. Interstitials induce significantly more strain than vacancies, and the nature of that strain is highly dependent on the individual lattice directions. The direction of point defect-induced lattice strain is contrary to the irradiation growth behavior of α-U. This work shows that isolated point defects cannot be the primary driving force responsible for the significant irradiation-induced growth of α-U observed experimentally.
Quality of and Recommendations for Relevant Clinical Practice Guidelines for COVID-19 Management: A Systematic Review and Critical Appraisal
Authors: Wang Yun-Yun , Huang Qiao , Shen Quan , Zi Hao , Li Bing-Hui , Li Ming-Zhen , He Shao-Hua , Zeng Xian-Tao , Yao Xiaomei , Jin Ying-Hui 
Published: June 2021

Background: The morbidity and mortality of coronavirus disease 2019 (COVID-19) are still increasing. This study aimed to assess the quality of relevant COVID-19 clinical practice guidelines (CPGs) and to compare the similarities and differences between recommendations.Methods: A comprehensive search was conducted using electronic databases (PubMed, Embase, and Web of Science) and representative guidelines repositories from December 1, 2019, to August 11, 2020 (updated to April 5, 2021), to obtain eligible CPGs. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to evaluate the quality of CPGs. Four authors extracted relevant information and completed data extraction forms. All data were analyzed using R version 3.6.0 software.Results: In total, 39 CPGs were identified and the quality was not encouragingly high. The median score (interquartile range, IQR) of every domain from AGREE II for evidence-based CPGs (EB-CPGs) versus (vs.) consensus-based CPG (CB-CPGs) was 81.94% (75.00–84.72) vs. 58.33% (52.78–68.06) in scope and purpose, 59.72% (38.89–75.00) vs. 36.11% (33.33–36.11) in stakeholder involvement, 64.58% (32.29–71.88) vs. 22.92% (16.67–26.56) in rigor of development, 75.00% (52.78–86.81) vs. 52.78% (50.00–63.89) in clarity of presentation, 40.63% (22.40–62.50) vs. 20.83% (13.54–25.00) in applicability, and 58.33% (50.00–100.00) vs. 50.00% (50.00–77.08) in editorial independence, respectively. The methodological quality of EB-CPGs were significantly superior to the CB-CPGs in the majority of domains (P &lt; 0.05). There was no agreement on diagnosis criteria of COVID-19. But a few guidelines show Remdesivir may be beneficial for the patients, hydroxychloroquine +/– azithromycin may not, and there were more consistent suggestions regarding discharge management. For instance, after discharge, isolation management and health status monitoring may be continued.Conclusions: In general, the methodological quality of EB-CPGs is greater than CB-CPGs. However, it is still required to be further improved. Besides, the consistency of COVID-19 recommendations on topics such as diagnosis criteria is different. Of them, hydroxychloroquine +/– azithromycin may be not beneficial to treat patients with COVID-19, but remdesivir may be a favorable risk-benefit in severe COVID-19 infection; isolation management and health status monitoring after discharge may be still necessary. Chemoprophylaxis, including SARS-CoV 2 vaccines and antiviral drugs of COVID-19, still require more trials to confirm this.
Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome
Authors: Koopen Annefleur M. , Almeida Eduardo L. , Attaye Ilias , Witjes Julia J. , Rampanelli Elena , Majait Soumia , Kemper Marleen , Levels Johannes H. M. , Schimmel Alinda W. M. , Herrema Hilde , Scheithauer Torsten P. M. , Frei Werner , Dragsted Lars , Hartmann Bolette , Holst Jens J. , O’Toole Paul W. , Groen Albert K. , Nieuwdorp Max 
Published: June 2021

BackgroundRecent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.DesignTwenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.ResultsConsumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.ConclusionsIn this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.
Varied Contribution of Phospholipid Shedding From Membrane to Daptomycin Tolerance in Staphylococcus aureus
Authors: Shen Tianwei , Hines Kelly M. , Ashford Nathaniel K. , Werth Brian J. , Xu Libin 
Published: June 2021

It has been suggested that daptomycin can be inactivated by lipids released by Staphylococcus aureus and that this effect is antagonized by phenol soluble modulins (PSMs), which bind to the shed lipids. PSM production is regulated by the Agr system, and others have shown that loss of the Agr function enhances S. aureus survival in the presence of daptomycin. Here we assessed the impact of Agr function on daptomycin activity and lipid metabolism under various conditions. Daptomycin activity was evaluated against three sets of isogenic strain series with wild-type or dysfunctional Agr using static daptomycin time-kills over 24 h and against one strain pair using in vitro pharmacokinetic/pharmacodynamic (PK/PD) models simulating clinical daptomycin exposure for 48 h. We performed comprehensive lipidomics on bacterial membranes and the spent media to correlate lipid shedding with survival. In static time-kill experiments, two agr-deficient strains (SH1000- and USA300 LAC ΔagrA) showed improved survival for 8 h compared with their corresponding wild-type strains as seen in previous studies, but this difference did not persist for 24 h. However, four other agr-deficient strains (SH1001 and JE2 agr KOs) did not demonstrate improved survival compared to isogenic wild-type strains at any time in the time-kills. Lipidomics analysis of SH1000, SH1001, and SH1000- strains showed daptomycin exposure increased lipid shedding compared to growth controls in all strains with phosphatidylglycerols (PGs), lysylPGs and cardiolipins predominating. In the cell pellets, PGs and lysylPGs decreased but cardiolipins were unchanged with daptomycin exposure. The shed lipid profiles in SH1001 and SH1000- were similar, suggesting that the inability to resist daptomycin by SH1001 was not because of differences in lipid shedding. In the PK/PD model, the agr mutant SH1000- strain did not show improved survival relative to SH1000 either. In conclusion, inactivation of daptomycin by shed lipids may be dependent on genetic background, the specific agr mutations, or the techniques used to generate these KOs rather than the overall function of the Agr system, and its contribution to daptomycin tolerance seems to be varied, transient, and growth-condition dependent.