bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45–55 Deletion
Authors: Poyatos‐García Javier , Martí Pilar , Liquori Alessandro , Muelas Nuria , Pitarch Inmaculada , Martinez‐Dolz Luis , Rodríguez Benjamin , Gonzalez‐Quereda Lidia , Damiá Maria , Aller Elena , Selva‐Gimenez Marta , Vilchez Roger , Diaz‐Manera Jordi , Alonso‐Pérez Jorge , Barcena José Eulalio , Jauregui Amaia , Gámez Josep , Aladrén Jesus Angel , Fernández Ariadna , Montolio Marisol , Azorin Inmaculada , Hervas David , Casasús Ana , Nieto Marisa , Gallano Pia , Sevilla Teresa , Vilchez Juan Jesus 
Published: July 2022

ObjectiveDuchenne muscular dystrophy (DMD) exon 45–55 deletion (del45–55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset.MethodsThis cross‐sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies.ResultsThe series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index‐case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45–57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors.InterpretationWe confirmed that del45–55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793–806
Association between Human Blood Metabolome and the Risk of Alzheimer's Disease
Authors: Sun Lulu , Guo Daoxia , Jia Yiming , Shi Mengyao , Yang Pinni , Wang Yu , Liu Fanghua , Chen Guo‐Chong , Zhang Yonghong , Zhu Zhengbao 
Published: July 2022

ObjectiveAlzheimer's disease (AD) is the most common degenerative neurological disorder with limited therapeutic options. Therefore, it is particularly important to explore the potential biomarkers implicated in the occurrence and progression of AD prior to clinical testing.MethodsWe selected 119 unique blood metabolites from 3 metabolome genome‐wide association studies (GWASs) with 147,827 European participants. Summary data about AD were obtained from a GWAS meta‐analysis with 63,926 European individuals from the International Genomics of Alzheimer's Project. MR analyses were performed to assess the associations of blood metabolites with AD, and a phenome‐wide MR analysis was further applied to ascertain the potential on‐target side effects of metabolite interventions.ResultsFour metabolites were identified as causal mediators for AD, including epiandrosterone sulfate (odds ratio [OR] per SD increase: 0.60; 95% confidence interval [CI]: 0.51–0.71; p = 6.14 × 10−9), 5alpha‐androstan‐3beta‐17beta‐diol disulfate (OR per SD increase: 0.69; 95% CI: 0.57–0.84; p = 1.98 × 10−4), sphingomyelin (OR per SD increase: 2.53; 95% CI: 1.78–3.59; p = 2.10 × 10−7), and glutamine (OR per SD increase: 0.83; 95% CI: 0.77–0.89; p = 2.09 × 10−6). Phenome‐wide MR analysis showed that epiandrosterone sulfate, 5alpha‐androstan‐3beta‐17beta‐diol disulfate and sphingomyelin mediated the risk of multiple diseases, and glutamine had beneficial effects on the risk of 4 diseases.InterpretationGenetically predicted increased epiandrosterone sulfate, 5alpha‐androstan‐3beta‐17beta‐diol disulfate, and glutamine might be associated with a decreased risk of AD, while sphingomyelin was associated with an increased risk. Side‐effect profiles were characterized to help inform drug target prioritization, and glutamine might be a promising target for the prevention and treatment of AD with no predicted detrimental side effects. ANN NEUROL 2022;92:756–767
Influence of chloride and sulfate solution on the long‐term durability of modified rubberized concrete
Authors: Kumar Rahul , Verma Manvendra , Dev Nirendra , Lamba Nitin 
Published: July 2022

AbstractLimited investigations are available on the influence of chloride and sulfate solutions on pozzolana‐based cement rubberized concrete after crumb rubber treatment. Mechanical and durability characteristics of rubberized concrete are assessed and compared to conventional concrete. Five contents of crumb rubber (10%–30% at 5% of increment) are utilized for partially replacing fine aggregate in concrete. The optimum amount of crumb rubber in concrete is revealed at a replacement level of 15%. The specimens remained in the crystalline form after being immersed in NaCl (sodium chloride), Na2SO4 (sodium sulfate), and MgSO4 (magnesium sulfate) solution, according to structural analyses by XRD (X‐ray diffraction). When rubberized concrete is submerged in both sulfate solutions with the same concentrations and for the same amount of time, the specimens immersed in Na2SO4 solution lose less weight and compressive strength than specimens submerged in MgSO4 solution. The losses in compressive strength of conventional concrete are 1.86%, 3.57%, and 4.82% when immersed in NaCl, Na2SO4, and MgSO4 solution. However, the losses are 1.67%, 2.79%, and 3.16% in rubberized concrete only at 24 weeks. Pozzolana‐based cement and after crumb rubber treatment, the rubberized concrete can resist chloride and sulfate solutions for a long duration.
Self‐healing and chemical resistance polyurethane elastomers based on 2‐ureido‐4[1H]pyrimidinone
Authors: Fu Wenyu , Mei Huifeng , Zhang Zhijia , Wang Qiang , Li Rui , Zhang Songsong , Wang Guojun , Wei Hao , Zhang Chenyuan , Lin Cunguo , Wang Lei 
Published: July 2022

AbstractSelf‐healing polyurethane elastomers allow increasing the life cycle, adapting to the circular economy, thus reducing the generation of waste. In this work, ureido‐4[1H]‐pyrimidinone (UPy) compounds was used to construct on supramolecular polymer. The self‐healing polyurethane elastomers were successfully prepared by supramolecular polymer based on UPy via a simple blending way. The self‐healing performance of the polyurethane elastomers with UPy were investigated by the scratch test and the cut‐off test, respectively. The scratch of the self‐healing polyurethane elastomer (PU‐15UPy) was totally healed in 1 h at 35°C. The tensile strength and the elongation at break of PU‐15UPy were 0.81 MPa and 563.8%. After the cut‐off test, the healing efficiencies of tensile strength were 63.8% (0.51 MPa) and 85.2% (0.69 MPa) after healing for 10 h at 35 and 80°C, respectively. The healing efficiency of tensile strength reached the value of 90.1% (0.73 MPa) after healing for 24 h at 80°C. The chemical resistance of the self‐healing polyurethane elastomers was tested by immersion in water, NaCl solution (3%), HCl solution (5%), NaOH solution (5%), and diesel, respectively. The mass loss of self‐healing polyurethane elastomers were all less than 2% after immersed in these solutions for 1 month, indicating the excellent chemical resistance performance of PU‐15UPy.
Hydrophobic transition of soluble polymer aerogel composites
Authors: He Hao , Liu Qiang , Gao Bing‐Bing , Zhang Shui‐Dong , Chen Hong‐Bing 
Published: July 2022

AbstractIn order to overcome the hydrophilic problem of aerogels based on soluble polymer, the transition of aerogel composites from hydrophilic to hydrophobic was achieved by grafting 1H, 1H, 2H, 2H‐Perfluorodecyltrimethoxysilane (FAS). Simply immersing in FAS ethanol solution and then ambient drying, this method is universal and efficient, we successfully achieved the soluble polymer aerogels hydrophobic transition. Taking polyvinyl alcohol (PVOH)/SiO2 as an example, the changes of structure and properties of aerogels before and after modification were characterized in detail. It was proved that FAS was successfully grafted and ethanol evaporation had little effect on the microstructure of aerogel. The resulting aerogels possess very good hydrophobicity, with water contact angle of up to 147.5° (3 wt.% FAS). The aerogel exhibits good stability in maintaining hydrophobicity in a harsh environment, such as in extreme pH and temperature. We introduced a universal method for hydrophobic modification, which is of great significance for the practical application of aerogels.
Assessing treatability with simulated lake drawdown: Quantifying drought‐driven turbidity in source water
Authors: Hannoun Deena , Belding Jeffrey , Tietjen Todd , Devaney Robert 
Published: July 2022

AbstractThe Colorado River Basin is experiencing a significant drought that began in 2000. As water supplies are projected to continue declining, water managers are concerned with the ongoing treatability of Lake Mead water, which provides 90% of the source water for the Las Vegas Valley, and is a crucial link to downstream source water. The drinking water intake currently draws high‐quality, low‐turbidity water; however, turbidity is projected to increase. This study assesses treatability by quantifying projected turbidity of source water withdrawn from a drinking water intake in Lake Mead, Nevada. The water quality modeling results provide projections for Lake Mead water turbidities in the case of extreme drawdown and provide guidance for treatment staff. The underlying process incorporated existing water quality data and identified potential problems, yielding a template for hydrodynamic and water quality modeling that utilities can take advantage of to plan for future changes in source water quality.
Synthesis and characterization of N‐rich fluorescent bio‐dots as a reporter in the design of dual‐labeled FRET probe for TaqMan PCR: A feasibility study
Authors: Imani Mahsa , Mohajeri Nasrin , Rastegar Mojgan , Zarghami Nosratollah 
Published: July 2022

AbstractDNA‐based analytical techniques have provided an advantageous sensing assay in the realm of biotechnology. Bio‐inspired fluorescent nanodots are a novel type of biological staining agents with excellent optical properties widely used for cellular imaging and diagnostics. In the present research, we successfully synthesized bio‐dots with excellent optical properties and high‐quantum yield from DNA sodium salt through the hydrothermal method. We conjugated the bio‐dots with 3' Eclipse Dark Quencher (Eclipse)‐labeled single‐strand oligodeoxyribonucleotide according to carbodiimide chemistry, to design a fluorescence resonance energy transfer (FRET) probe. The results confirmed the prosperous synthesis and surface functionalization of the bio‐dot. Analysis of size, zeta potential, and FTIR spectroscopy verified successful bioconjugation of the bio‐dots with probes. UV‐visibility analysis and fluorescence intensity profile of the bio‐dot and bio‐dot@probes represented a concentration‐dependent quenching of fluorescent signal of bio‐dot by Eclipse after probe conjugation. The results demonstrated that TaqMan PCR was not feasible using the designed bio‐dot@probes. Our results indicated that bio‐dot can be used as an efficient fluorescent tag in the design of fluorescently labeled oligonucleotides with high biocompatibility and optical features.
Exosomes: Biogenesis, targeting, characterization and their potential as "Plug & Play" vaccine platforms
Authors: Dyball Laura E , Smales C. Mark 
Published: July 2022

AbstractExosomes are typically characterized as spherical extracellular vesicles less than 150 nm in diameter that have been released into the extracellular environment via fusion of multivesicular bodies (MVBs) to the plasma membrane. Exosomes play a key role in cell‐cell communication, vary widely in their composition and potential cargo, and are reportedly involved in processes as diverse as angiogenesis, apoptosis, antigen presentation, inflammation, receptor‐mediated endocytosis, cell proliferation, and differentiation, and cell‐signaling. Exosomes can also act as biomarkers of health and disease and have enormous potential use as therapeutic agents. Despite this, the understanding of how exosome biogenesis can be utilized to generate exosomes carrying specific targets for particular therapeutic uses, their manufacture, detailed analytical characterization, and methods of application are yet to be fully harnessed. In this review, the author describes the current understanding of these areas of exosome biology from a biotechnology and bioprocessing aspect, but also highlight the challenges that remain to be overcome to fully harness the power of exosomes as therapeutic agents, with a particular focus on their use and application as vaccine platforms.
Recent developments in cell shipping methods
Authors: Heydarzadeh Shabnam , Kheradmand Kia Sima , Boroomand Seti , Hedayati Mehdi 
Published: July 2022

AbstractAs opposed to remarkable advances in the cell therapy industry, research reveal inexplicable difficulties associated with preserving and post‐thawing cell death. Post cryopreservation apoptosis is a common occurrence that has attracted the attention of scientists to use apoptosis inhibitors. Transporting cells without compromising their survival and function is crucial for any experimental cell‐based therapy. Preservation of cells allows the safe transportation of cells between distances and improves quality control testing in clinical and research applications. The vitality of transported cells is used to evaluate the efficacy of transportation strategies. For many decades, the conventional global methods of cell transfer were not only expensive but also challenging and had adverse effects. The first determination of some projects is optimizing cell survival after cryopreservation. The new generation of cryopreservation science wishes to find appropriate and alternative methods for cell transportation to ship viable cells at an ambient temperature without dry ice or in media‐filled flasks. The diversity of cell therapies demands new cell shipping methodologies and cryoprotectants. In this review, we tried to summarize novel improved cryopreservation methods and alternatives to cryopreservation with safe and viable cell shipping at ambient temperature, including dry preservation, hypothermic preservation, gel‐based methods, encapsulation methods, fibrin microbeads, and osmolyte solution compositions.
Screening of small molecular biomarker candidates using untargeted metabolomics strategy in peripheral blood from rats with neuroinflammatory injury induced by whole‐brain irradiation
Authors: Meng Xianshuang , Bai Hua , Ma Qiang , Zhang Peng , Ma Hong , Deng Yulin 
Published: July 2022

AbstractNeuroinflammatory injury is one of the typical brain injuries after the body is exposed to radiation. It is mainly characterized by the release of inflammatory factors by activated microglia and peripherally invading lymphocytes. To provide early warning for nerve injury and early diagnosis of neurodegenerative diseases, it is of great significance to explore the biomarker candidates of neuroinflammatory injury. This study focused on the screening of small molecular biomarker candidates in peripheral blood from rats with neuroinflammatory injury induced by whole‐brain irradiation. The rats were exposed to 0, 10, 10 × 3, and 30 Gy of cobalt‐60 γ‐rays. Serum was collected on the 30th day after exposure and analyzed using reversed‐phase liquid chromatography and hydrophilic interaction liquid chromatography coupled with high‐resolution mass spectrometry based on untargeted metabolomics. Biomarker candidates were investigated by comparing the 0‐Gy group and three irradiation groups using univariate statistical analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. Eleven biomarker candidates were putatively identified, and four major altered metabolic pathways were found. The screened small molecular biomarker candidates could be used as a useful supplement to traditional biomacromolecule markers and may be valuable for radiation protection, target therapy of inflammatory injury, and discovery of new target drugs for the prevention and cure of related neurodegenerative diseases.
Advanced Strategies of Enzyme Activity Regulation for Biomedical Applications
Authors: Chen Zihan , Zhao Yu , Liu Yang 
Published: July 2022

AbstractEnzymes are important macromolecular biocatalysts that accelerate chemical and biochemical reactions in living organisms. Most human diseases are related to alterations in enzyme activity. Moreover, enzymes are potential therapeutic tools for treating different diseases, such as cancer, infections, and cardiovascular and cerebrovascular diseases. Precise remote enzyme activity regulation provides new opportunities to combat diseases. This review summarizes recent advances in the field of enzyme activity regulation, including reversible and irreversible regulation. It also discusses the mechanisms and approaches for on‐demand control of these activities. Furthermore, a range of stimulus‐responsive inhibitors, polymers, and nanoparticles for regulating enzyme activity and their prospective biomedical applications are summarized. Finally, the current challenges and future perspectives on enzyme activity regulation are discussed.
Regulation of immune cell metabolism in health and disease: Special focus on T and B cell subsets
Authors: Chakraborty Sayan , Khamaru Poulomi , Bhattacharyya Arindam 
Published: July 2022

AbstractMetabolism is a dynamic process and keeps changing from time to time according to the demand of a particular cell to meet its bio‐energetic requirement. Different immune cells rely on distinct metabolic programs which allow the cell to balance its requirements for energy, molecular biosynthesis, and effector activity. In the aspect of infection and cancer immunology, effector T and B cells get exhausted and help tumor cells to evade immunosurveillance. On the other hand, T cells become hyperresponsive in the scenario of autoimmune diseases. In this article, we have explored the uniqueness and distinct metabolic features of key CD4+ T and B helper cell subsets, CD4+ T, B regulatory cell subsets and CD8+ T cells regarding health and disease. Th1 cells rely on glycolysis and glutaminolysis; inhibition of these metabolic pathways promotes Th1 cells in Treg population. However, Th2 cells are also dependent on glycolysis but an abundance of lactate within TME shifts their metabolic dependency to fatty acid metabolism. Th17 cells depend on HIF‐1α mediated glycolysis, ablation of HIF‐1α reduces Th17 cells but enhance Treg population. In contrast to effector T cells which are largely dependent on glycolysis for their differentiation and function, Treg cells mainly rely on FAO for their function. Therefore, it is of utmost importance to understand the metabolic fates of immune cells and how it facilitates their differentiation and function for different disease models. Targeting metabolic pathways to restore the functionality of immune cells in diseased conditions can lead to potent therapeutic measures.
Transcatheter vacuum‐assisted left‐sided mass extraction with the AngioVac system
Authors: Qintar Mohammed , Wang Dee Dee , Lee James , Villablanca Pedro , Eng Marvin H. , Frisoli Tiberio , O'Neill Brian P. , O'Neill William W. 
Published: July 2022

AbstractObjectivesTo study the safety and efficacy of AngioVac for left‐sided transcatheter vacuum‐assisted mass extraction (TVME).BackgroundThe AngioVac system is approved for right‐sided TVME and has emerged as an effective and safe alternative for open surgical treatment. The use of the AngioVac device for aspiration of left‐sided TVME has been limited.MethodsConsecutive patients from two Michigan centers who underwent left‐sided TVME were included. Data on patient demographics, procedural information, in‐hospital and follow‐up events were collected through electronic medical records review. Technical success was defined as aspirating of 70%–100% of the material.ResultsTen patients (mean age 58.3 [±17.3] years, 50% male) were included. Indications for TMVE were in large for recurrent embolic events. All patients underwent bilateral cerebro‐embolic protection using the Sentinel device. The total mean procedure time was 192.5 (±47.5) min of which the meantime for active aspiration (bypass time) was 9.3 (±4.2) min. The circuit configuration was: arteriovenous (AV) in four cases and arterioarterial (AA) in six cases. Successful aspiration was achieved in 80% of cases. No complications were reported (range follow‐up 1–16 months).ConclusionsOur small case series demonstrates the feasibility and safety of the AngioVac system in left‐sided mass extraction. Larger trials are needed to further demonstrate its effectiveness and safety and potentially apply for on‐label use.
Particle Generation with Liquid Carbon Dioxide Emulsions
Authors: Lauscher Clara , Schaldach Gerhard , Thommes Markus 
Published: July 2022

AbstractSpray drying is a common technique for particle generation. However, due to limitations in the droplet size, the production of solid submicron particles using conventional atomizers has proven to be challenging. With the aim of overcoming this limitation, the generation and expansion of emulsions of an aqueous solution and liquid carbon dioxide with a subsequent drying step was investigated. Potassium chloride concentrations in the solution between 0.1 and 10 wt. % and mass loads of the aqueous disperse phase between 0.01 and 0.09 were used in order to study their impact on the droplet and particle size. For the lowest potassium chloride concentration, median particle diameters in the submicron size range were measured for all mass loads of the disperse phase.
Photochromic Fentanyl Derivatives for Controlled μ‐Opioid Receptor Activation
Authors: Lahmy Ranit , Hübner Harald , Schmidt Maximilian F. , Lachmann Daniel , Gmeiner Peter , König Burkhard 
Published: July 2022

AbstractPhotoswitchable ligands as biological tools provide an opportunity to explore the kinetics and dynamics of the clinically relevant μ‐opioid receptor. These ligands can potentially activate or deactivate the receptor when desired by using light. Spatial and temporal control of biological activity allows for application in a diverse range of biological investigations. Photoswitchable ligands have been developed in this work, modelled on the known agonist fentanyl, with the aim of expanding the current “toolbox” of fentanyl photoswitchable ligands. In doing so, ligands have been developed that change geometry (isomerize) upon exposure to light, with varying photophysical and biochemical properties. This variation in properties could be valuable in further studying the functional significance of the μ‐opioid receptor.