bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel homozygous synonymous variant further expands the phenotypic spectrum of POLR3A‐related pathologies
Authors: Lessel Davor , Rading Katrin , Campbell Susan E. , Thiele Holger , Altmüller Janine , Gordon Leslie B. , Kubisch Christian 
Published: October 2021

AbstractPathogenic biallelic variants in POL3RA have been associated with different disorders characterized by progressive neurological deterioration. These include the 4H leukodystrophy syndrome (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) and adolescent‐onset progressive spastic ataxia, as well as Wiedemann–Rautenstrauch syndrome (WRS), a recognizable neonatal progeroid syndrome. The phenotypic differences between these disorders are thought to occur mainly due to different functional effects of underlying POLR3A variants. Here we present the detailed clinical course of a 37‐year‐old woman in whom we identified a homozygous synonymous POLR3A variant c.3336G>A resulting in leaky splicing r.[3336ins192, =, 3243_3336del94]. She presented at birth with intrauterine growth retardation, lipodystrophy, muscular hypotonia, and several WRS‐like facial features, albeit without sparse hair and prominent scalp veins. She had no signs of developmental delay or intellectual disability. Over the years, above characteristic facial features, she showed severe postnatal growth retardation, global lipodystrophy, joint contractures, thoracic hypoplasia, scoliosis, anodontia, spastic quadriplegia, bilateral hearing loss, aphonia, hypogonadotropic hypogonadism, and cerebellar peduncles hyperintensities in brain imaging. These manifestations partially overlap the clinical features of the previously reported POLR3A‐associated disorders, mostly mimicking the WRS. Thus, our study expands the POLR3A‐mediated phenotypic spectrum and suggests existence of a phenotypic continuum underlying biallelic POLR3A variants.
End‐Truncated LAMB1 Causes a Hippocampal Memory Defect and a Leukoencephalopathy
Authors: Aloui Chaker , Hervé Dominique , Marenne Gaelle , Savenier Florian , Le Guennec Kilan , Bergametti Francoise , Verdura Edgard , Ludwig Thomas E. , Lebenberg Jessica , Jabeur Waliyde , Morel Hélène , Coste Thibault , Demarquay Geneviève , Bachoumas Panagiotis , Cogez Julien , Mathey Guillaume , Bernard Emilien ,   FREX consortium, Chabriat Hugues , Génin Emmanuelle , Tournier‐Lasserve Elisabeth 
Published: October 2021

ObjectiveThe majority of patients with a familial cerebral small vessel disease (CSVD) referred for molecular screening do not show pathogenic variants in known genes. In this study, we aimed to identify novel CSVD causal genes.MethodsWe performed a gene‐based collapsing test of rare protein‐truncating variants identified in exome data of 258 unrelated CSVD patients of an ethnically matched control cohort and of 2 publicly available large‐scale databases, gnomAD and TOPMed. Western blotting was used to investigate the functional consequences of variants. Clinical and magnetic resonance imaging features of mutated patients were characterized.ResultsWe showed that LAMB1 truncating variants escaping nonsense‐mediated messenger RNA decay are strongly overrepresented in CSVD patients, reaching genome‐wide significance (p < 5 × 10−8). Using 2 antibodies recognizing the N‐ and C‐terminal parts of LAMB1, we showed that truncated forms of LAMB1 are expressed in the endogenous fibroblasts of patients and trapped in the cytosol. These variants are associated with a novel phenotype characterized by the association of a hippocampal type episodic memory defect and a diffuse vascular leukoencephalopathy.InterpretationThese findings are important for diagnosis and clinical care, to avoid unnecessary and sometimes invasive investigations, and also from a mechanistic point of view to understand the role of extracellular matrix proteins in neuronal homeostasis. ANN NEUROL 2021;90:962–975
Supercollimation of Light Beams by Axisymmetric Aperiodic Photonic Structures
Authors: Gailevičius Darius , Aleksandravičius Edvinas , Purlys Vytautas , Staliūnas Kęstutis 
Published: October 2021

AbstractEfficient beam supercollimation is proposed and shown experimentally by axisymmetric aperiodic photonic structures. The structure consists of equidistant layers of concentric refraction index rings, with the transverse period of the rings varying from layer to layer along the structure. Numerically designed and optimized axisymmetric photonic structures are inscribed in silica glass by femtosecond pulses. Strong enhancement (more than by one order of magnitude) of the axial beam component is demonstrated, resulting in the record performance of the beam supercollimation.
Chemische Synthese und Semisynthese von lipidierten Proteinen
Authors: Hanna Cameron C. , Kriegesmann Julia , Dowman Luke J. , Becker Christian F. W. , Payne Richard J. 
Published: October 2021

AbstractLipidierung ist eine ubiquitäre Modifikation von Peptiden und Proteinen, die entweder co‐ oder posttranslational auftreten kann. Für die Vielzahl von Lipidklassen wurde gezeigt, dass diese viele entscheidende biologische Aktivitäten, z. B. die Regulierung der Signalweiterleitung, Zell‐Zell‐Adhäsion sowie die Anlagerung von Proteinen an Lipid‐Rafts und Phospholipidmembranen, beeinflussen. Während die Natur Enzyme nutzt, um Lipidmodifikationen in Proteine einzubringen, ist ihre Nutzung für die chemoenzymatische Herstellung von lipidierten Proteinen häufig ineffizient. Eine Alternative ist die Kombination moderner synthetischer und semisynthetischer Techniken, um lipidierte Proteine in reiner und homogen modifizierter Form zu erhalten. Dieser Aufsatz erörtert Fortschritte in der Entwicklung der Lipidierungs‐ und Ligationschemie und deren Anwendung in der Synthese und Semisynthese homogen lipidierter Proteine, die es ermöglichen, den Einfluss dieser Modifikationen auf die Proteinstruktur und ‐funktion zu untersuchen.
Rapid upper airway obstruction after arteriovenous malformation rupture in a patient with neurofibromatosis
Authors: Davidson A. , Beddoes P. , Patel J. , Hunningher A. 
Published: October 2021

SummaryNeurofibromatosis type 1 is rarely associated with arteriovenous malformation rupture. We present a case of a rapidly compromised upper airway due to extrinsic compression as a consequence of the rupture of an arteriovenous malformation fed by the inferior thyroid artery which required emergency cricothyroidotomy following failed attempts at orotracheal intubation. While the patient had a good overall outcome, our reflection on the management of this case highlights several important learning points. These include the importance of clear communication between different medical specialties to promote shared situation awareness, the importance of training anaesthetists in the limitations of standard difficult airway management algorithms, and the implications of the skillset mix of doctors responding to airway emergencies in district general hospitals.
Compatibilization of polyvinyl chloride ‐ polymethyl methacrylate polymer blends with maleic anhydride‐styrene‐methyl methacrylate terpolymer
Authors: Yilmaz Ersen 
Published: October 2021

AbstractIn this study, nonmiscible polyvinyl chloride (PVC) and polymethyl methacrylate (PMMA) polymers were made miscible by using MA‐St‐MMA terpolymer as a compatibilizer. Maleic anhydride‐styrene‐methyl methacrylate (MA‐St‐MMA) terpolymer was synthesized in our laboratory and used. The synthesized terpolymer was determined by FT‐IR spectroscopy. Equal mass PVC/PMMA mixture samples were prepared in series and the compatibilizer terpolymer varying between 2% and 10% by mass was added to the samples and the effect of the added terpolymer on the miscibility was determined viscometrically, thermally, mechanically and, visually. With the addition of the compatibilizer, the two components in the mixture behave like a single polymer with a single glass transition temperature (Tg) and the mixture became compatible. As a result of viscometric experiments, it has been determined that with the added MA‐St‐MMA terpolymer, the Δb value derivated from the Krigbaum‐Wall equation which is the miscibility parameter of a mixture shifted into the positive (+) zone indicating that the two polymers became miscible. By visual analysis, it was observed that the added terpolymer reduced the opaque appearance and the phase separations of the mixture. From the tensile test, a significant improvement in impact toughness was observed. When all the data obtained were evaluated, it was determined that the synthesized MA‐St‐MMA terpolymer was a suitable compatibilizer for the mixture of PVC and PMMA.
Effective number of breeders and reconstructed sibships reveal low reproductive output by a reintroduced population of endangered fish
Authors: Diver Tracy A. , Mussmann Steven M. , Durst Scott L. , Franssen Nathan R. 
Published: October 2021

Abstract

Fishes with periodic life histories are long‐lived, slow to mature, and have intermittent periods of successful recruitment, limiting the ability of managers to recover their populations rapidly.
Endangered razorback sucker (Xyrauchen texanus) in the Colorado River Basin, USA, is a periodic strategist whose persistence is largely dependent on hatchery augmentation. Stocking efforts have increased population sizes in the basin; however, natural recruitment remains extremely limited.
Annual reproductive output of a reintroduced population of razorback sucker was evaluated over a 10‐year period in a Colorado River tributary by estimating the effective number of breeders (Nb) and numbers of repeat spawning adults through genetic analysis of wild‐spawned larval cohorts. Comparative estimates were also obtained for a self‐sustaining sympatric periodic strategist, flannelmouth sucker (Catostomus latipinnis).
Given known trade‐offs between delayed maturation and long lifespan, population size and age‐structure of razorback sucker was quantified to assess potential demographic constraints to reproductive output.
The results showed consistently low annual Nb estimates for razorback sucker (
= 127), compared with flannelmouth sucker (
= 3,022) and within the same period (2013–2018) an order of magnitude more repeat spawning individual razorback sucker (n = 41) were detected compared with flannelmouth sucker (n = 4). Given the relatively young age structure of the razorback sucker population (median = age 4), the results indicate that successful recruitment may be limited by the number of spawning adults.
These results highlight the importance of understanding how life history characteristics may affect the rate and success of reintroductions and where life‐stage specific bottlenecks to reproduction and recruitment may occur. Given the increasing necessity of stocking for most reintroductions, management of periodic strategists may need to aim at increasing the relative age‐structure of adults to bolster reproductive output in addition to increasing juvenile survival.
VEXAS Syndrome: A Case Series From a Single‐Center Cohort of Italian Patients With Vasculitis
Authors: Muratore Francesco , Marvisi Chiara , Castrignanò Paola , Nicoli Davide , Farnetti Enrico , Bonanno Orsola , Longo Rosina , Zaldini Piera , Galli Elena , Balanda Nicholas , Beck David B. , Grayson Peter C. , Pipitone Nicolò , Boiardi Luigi , Salvarani Carlo 
Published: October 2021

ObjectiveTo identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome) from a single‐center cohort of Italian patients with vasculitis, using a clinically oriented phenotype‐first approach.MethodsWe retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment‐resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin‐activating enzyme E1 (UBA‐1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue.ResultsSeven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA‐1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients.ConclusionTo our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA‐associated vasculitis reported herein warrants further investigation.
Thermostable trypsin‐like protease by Penicillium roqueforti secreted in cocoa shell fermentation: Production optimization, characterization, and application in milk clotting
Authors: Nogueira Laísa Santana , Tavares Iasnaia Maria de Carvalho , Santana Nívio Batista , Ferrão Sibelli Passini Barbosa , Teixeira Jabson Meneses , Costa Floriatan Santos , Silva Tatielle Pereira , Pereira Hugo Juarez Vieira , Irfan Muhammad , Bilal Muhammad , de Oliveira Julieta Rangel , Franco Marcelo 
Published: October 2021

AbstractThe increased demand for cheese and the limited availability of calf rennet justifies the search for milk‐clotting enzymes from alternative sources. Trypsin‐like protease by Penicillium roqueforti was produced by solid‐state fermentation using cocoa shell waste as substrate. The production of a crude enzyme extract that is rich in this enzyme was optimized using a Doehlert‐type multivariate experimental design. The biochemical characterization showed that the enzyme has excellent activity and stability at alkaline pH (10–12) and an optimum temperature of 80°C, being stable at temperatures above 60°C. Enzymatic activity was maximized in the presence of Na+ (192%), Co2+ (187%), methanol (153%), ethanol (141%), and hexane (128%). Considering the biochemical characteristics obtained and the milk coagulation activity, trypsin‐like protease can be applied in the food industry, such as in milk clotting and in the fabrication of cheeses.
Sustainable production of jojobyl alcohols and cell viability study
Authors: Acherki Hassan , Hurtado Olivia , Bouaid Abderrahim 
Published: October 2021

AbstractAn innovative biorefinery approach has been applied to evaluate jojoba oil (JO) in high value‐added products. It consists of enzymatic transesterification using short (1‐propanol, 1‐butanol), medium linear (1‐octanol), and branched (2‐ethylhexanol) chain alcohols. The proposed biorefinery approach uses an integrated process for the production of jojobyl alcohol (JA) mixtures (11‐eicosenol, 13‐docosenol and 15‐tetracosenol) as products that can be used in pharmaceutical applications. The remaining fraction of fatty acid alkyl esters (FAAE) has a wide range of industrial uses and could be used as a promising alternative to conventional fuels, as it complies with EN14214, the European Biodiesel Norm. The separation of JA from FAAE was carried out by crystallization using a binary mixture of hexane and diethyl ether. After the separation step, the main properties of FAAE were determined. The results showed that the cold flow properties and oxidation stability of the FAAE fraction, obtained as co‐product during the process, have been improved with respect to transesterified JO. The use of 2‐ethylhexanol as an alcohol in the transesterification reaction increases the amount of the most valuable fraction containing JAs. In vitro cell viability was measured in HEK293T cells using the tetrazolium dye reduction (MTT) assay. The results showed that this oily liquid mixture of JA components (cis‐11‐eicosenol, cis‐13‐docosenol, and cis‐15‐tetracosenol) had a cytotoxic effect at concentrations of 10 and 100 μmol L−1 and no cytotoxic activity at 1 μmol L−1. The concentration of 1 μmol L−1 does not, therefore, modify the cell viability, does not produce toxic effects in the tested cells and could be used as a therapeutic compound. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
3D printing of self‐standing and vascular supportive multimaterial hydrogel structures for organ engineering
Authors: Liu Suihong , Hu Qingxi , Shen Zhipeng , Krishnan Sasirekha , Zhang Haiguang , Ramalingam Murugan 
Published: October 2021

AbstractThree dimensional printable formulation of self‐standing and vascular‐supportive structures using multi‐materials suitable for organ engineering is of great importance and highly challengeable, but, it could advance the 3D printing scenario from printable shape to functional unit of human body. In this study, the authors report a 3D printable formulation of such self‐standing and vascular‐supportive structures using an in‐house formulated multi‐material combination of albumen/alginate/gelatin‐based hydrogel. The rheological properties and relaxation behavior of hydrogels were analyzed before the printing process. The suitability of the hydrogel in 3D printing of various customizable and self‐standing structures, including a human ear model, was examined by extrusion‐based 3D printing. The structural, mechanical, and physicochemical properties of the printed scaffolds were studied systematically. Results supported the 3D printability of the formulated hydrogel with self‐standing structures, which are customizable to a specific need. In vitro cell experiment showed that the formulated hydrogel has excellent biocompatibility and vascular supportive behavior with the extent of endothelial sprout formation when tested with human umbilical vein endothelial cells. In conclusion, the present study demonstrated the suitability of the extrusion‐based 3D printing technique for manufacturing complex shapes and structures using multi‐materials with high fidelity, which have great potential in organ engineering.
The role of information and communication technology on green total factor energy efficiency: Does environmental regulation work?
Authors: Hao Yu , Guo Yunxia , Wu Haitao 
Published: October 2021

AbstractChina is gradually changing its pursuit of rapid economic growth into a pursuit of economic development quality. In this context, whether “cyberpower” and “digital China” strategies are truly conducive to China's sustainable development still needs to be further tested. This paper constructs China's provincial information and communication technology (ICT) comprehensive development level index from the four dimensions of penetration, coverage, information resources, and business and then innovatively undertakes a theoretical framework integrating ICT, environmental regulations, and green total factor energy efficiency (GTFEE) for the analysis. Using panel data from China's 30 provincial administrative regions from 2006 to 2017, this study explores the direct impact, moderating effect, nonlinear relationship, and regional differences of ICT development on GTFEE. It is indicated that ICT development plays a positive role in promoting GTFEE and that this role is moderated by environmental regulations. The regression results of the dynamic threshold model indicate that diverse environmental regulation intensities lead to different influences of ICT development on GTFEE. Moreover, the impact of ICT development on GTFEE is heterogeneous among different regions. Specifically, the western region may gain more benefits from ICT development by virtue of the late‐mover advantage.
Prognostic implication of PD‐L1 polymorphisms in non‐small cell lung cancer treated with radiotherapy
Authors: Kang Min Kyu , Lee Shin Yup , Choi Jin Eun , Do Sook Kyung , Cho Moon‐June , Kim Jun‐Sang , Park Jae Yong 
Published: October 2021

AbstractBackgroundTo investigate the impact of programmed death‐ligand 1 (PD‐L1) polymorphisms on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with curative radiotherapy.MethodsFour single nucleotide polymorphisms (SNPs) (rs822336G>C, rs822337T>A, rs822338C>T, and rs2297136A>G) in the PD‐L1 gene were evaluated in 124 NSCLC patients. Clinical stage was I in 28, II in 17, and III in 79 patients. Fifty‐seven patients received radiotherapy alone, including 28 patients who received stereotactic body radiotherapy. Sixty‐seven patients received sequential or concurrent chemoradiotherapy. Risk factors for survival outcomes were analyzed with the log‐rank test and multivariate Cox proportional hazards models.ResultsThe rs822336GC+CC genotype was associated with better overall survival (OS) (hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37–0.97, p = 0.036) and regional failure‐free survival (RFFS) (HR = 0.32, 95% CI = 0.14–0.76, p = 0.009), compared with rs822336GG genotype. The rs822337TA+AA genotype was associated with better OS (HR =0.54, 95% CI = 0.34–0.88, p = 0.014), progression‐free survival (PFS) (HR = 0.64, 95% CI = 0.41–0.99, p = 0.046), and RFFS (HR = 0.38, 95% CI = 0.17–0.81, p = 0.013), compared with rs822337TT genotype. Three SNPs (rs822336, rs822337, and rs822338) were in linkage disequilibrium. Combined GTC and GTT (GT*) haplotype was associated with significantly worse OS (p = 0.018), PFS (p = 0.044), and RFFS (p = 0.038), compared with those with other combined haplotypes. Patients with diplotypes of two GT* haplotypes showed significantly worse OS (p = 0.023) and RFFS (p = 0.014) than those with other diplotypes.ConclusionsThese findings suggest that PD‐L1 polymorphisms could be predictive markers for NSCLC patients receiving radiotherapy.
Visual Detection of Adenosine Triphosphate by Taylor Rising: A Simple Point‐of‐Care Testing Method Based on Rolling Circle Amplification
Authors: Pan Yong , Zhu Chen , Zeng Wen Bin , Fu Pei , Chen Chi , Xu Bao Ming , Gao Zhong Feng 
Published: October 2021

AbstractRapid and sensitive point‐of‐care testing (POCT) is an extremely critical mission in practical applications, especially for rigorous military medicine, home health care, and in the third world. Here, we report a visual POCT method for adenosine triphosphate (ATP) detection based on Taylor rising in the corner of quadratic geometries between two rod surfaces. We discuss the principle of Taylor rising, demonstrating that it is significantly influenced by contact angle, surface tension, and density of the sample, which are controlled by ATP‐dependent rolling circle amplification (RCA). In the presence of ATP, RCA reaction effectively suppresses Taylor‐rising behavior, due to the increased contact angle, density, and decreased surface tension. Without addition of ATP, untriggered RCA reaction is favorable for Taylor rising, resulting in a significant height. With this proposed method, visual sensitive detection of ATP without the aid of other instruments is realized with only a 5 μL droplet, which has good selectivity and a low detection limit (17 nM). Importantly, this visual method provides a promising POCT tool for user‐friendly molecular diagnostics.