bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further delineation of phenotypic spectrum of SCN2A‐related disorder
Authors: Richardson Ruth , Baralle Diana , Bennett Christopher , Briggs Tracy , Bijlsma Emilia K. , Clayton‐Smith Jill , Constantinou Panayiotis , Foulds Nicola , Jarvis Joanna , Jewell Rosalyn , Johnson Diana S. , McEntagart Meriel , Parker Michael J. , Radley Jessica A. , Robertson Lisa , Ruivenkamp Claudia , Rutten Julie W. , Tellez James , Turnpenny Peter D. , Wilson Valerie , Wright Michael , Balasubramanian Meena 
Published: December 2021

AbstractSCN2A‐related disorders include intellectual disability, autism spectrum disorder, seizures, episodic ataxia, and schizophrenia. In this study, the phenotype–genotype association in SCN2A‐related disorders was further delineated by collecting detailed clinical and molecular characteristics. Using previously proposed genotype–phenotype hypotheses based on variant function and position, the potential of phenotype prediction from the variants found was examined. Patients were identified through the Deciphering Developmental Disorders study and gene matching strategies. Phenotypic information and variant interpretation evidence were collated. Seventeen previously unreported patients and five patients who had been previously reported (but with minimal phenotypic and segregation data) were included (10 males, 12 females; median age 10.5 years). All patients had developmental delays and the majority had intellectual disabilities. Seizures were reported in 15 of 22 (68.2%), four of 22 (18.2%) had autism spectrum disorder and no patients were reported with episodic ataxia. The majority of variants were de novo. One family had presumed gonadal mosaicism. The correlation of the use of sodium channel‐blocking antiepileptic drugs with phenotype or genotype was variable. These data suggest that variant type and position alone can provide some predictive information about the phenotype in a proportion of cases, but more precise assessment of variant function is needed for meaningful phenotype prediction.
Vein of Galen aneurysm, dilated cardiomyopathy, and slender habitus in a patient with a recurrent pathogenic variant in PACS2
Authors: Valenzuela Irene , Guillén Benítez Elena , Sanchez‐Montanez Angel , Limeres Javier , López‐Grondona Fermina , Cuscó Ivon , Tizzano Eduardo F. 
Published: December 2021

AbstractThe PACS2 gene encodes a multifunctional sorting protein involved in nuclear gene expression and pathway traffic regulation that has been shown to be highly expressed during human prenatal brain development. Pathogenic variants in PACS2 have been recently shown to be implicated in a phenotype with global developmental delay/intellectual disability, seizures, autistic traits, facial dysmorphic features, and cerebellar dysgenesis. Here, we report a 25‐year‐old male with intellectual disability, epileptic encephalopathy, cerebellar dysgenesis, facial dysmorphism, and a previously reported pathogenic variant in PACS2. To our knowledge, this is the oldest patient reported who, in addition to the known phenotype described in PACS2 patients, presented with a vein of Galen malformation and dilated cardiomyopathy as previously unreported findings.
Clinical and molecular response to dasatinib in an adult patient with Penttinen syndrome
Authors: Iznardo Helena , Bredrup Cecilie , Bernal Sara , Gladkauskas Titas , Mascaró José‐Manuel , Roé Esther , Baselga Eulalia 
Published: December 2021

AbstractPenttinen type of premature aging syndrome is an autosomal‐dominant disorder that can be caused by the c.1994T>A pVal665Ala pathogenic variant in platelet‐derived growth factor receptor‐B (PDGFRB). Imatinib, a receptor tyrosine kinase (RTK) inhibitor, has been used in Penttinen syndrome (PS) patients with good results. A 21‐year‐old male presented shortly after birth with a prematurely aged appearance with distinctive facial features and cutaneous atrophy with hypertrophic scar‐like lesions. Generalized brachydactyly with acro‐osteolysis was observed. Flexion contractures limited his daily activities. Cognitive impairment was not present. Genetic testing found a heterozygous variant c.1994T>A pVal665Ala in exon 14 of PDGFRB. A diagnosis of PS was made and imatinib treatment was started with partial response. After lack of further improvement, in vitro molecular studies with imatinib and dasatinib showed that the Val665Ala variant had greater sensitivity to dasatinib than imatinib. This was seen examining levels of P‐PDGFRB directly and on downstream ligands P‐AKT and P‐STAT. Improved clinical response was observed after treatment with dasatinib. We report a new case of PS with clinical and molecular response to dasatinib after incomplete response to imatinib. Our work provides further molecular and clinical evidence of RTK inhibitors' efficacy in this rare disorder.
Polyvinyl alcohol and allyl α, α'‐trehalose copolymers for a sustainable strengthening of degraded paper
Authors: Poggi Giovanna , Papacchini Alessandra , Baracani Sara , Cappitti Alice , Marini Gioia , Marrini Matteo , Giorgi Rodorico , Salvini Antonella 
Published: December 2021

AbstractAcid‐catalyzed hydrolysis of glycosidic bonds is the most important degradation mechanism affecting cellulose‐based materials. It results in the decrease of DP and in the loss of the original mechanical properties. The neutralization of acidity is therefore one of the most efficient ways to hamper the degradation of cellulosic artworks. However, in the case of acidic and strongly degraded artifacts, in addition to deacidification, a consolidation treatment must be performed. To this aim, a new class of biopolymers, obtained by a synthetic procedure that considers the principles of Sustainable Chemistry, was investigated. Three allyl saccharide/vinyl acetate copolymers, having different molar ratios between starting monomers, were prepared using α,α'‐trehalose, and used to synthesize the corresponding allyl saccharide/vinyl alcohol copolymers. The use of saccharide derivatives as monomers improves the affinity and compatibility of the biopolymer with the artifacts to be treated. After characterization, the efficacy of the copolymers in the strengthening of degraded paper was evaluated with mechanical tests. The most effective system was thus selected for further testing. Its performance was compared to that of Klucel G®, a commercial product belonging to the class of cellulose derivatives, which are largely used in conservation practice.
Porous superhydrophobic‐superoleophilic polytetrafluoroethylene fibrous membranes with tertiary structures for efficient oil/water separation
Authors: Zhang Xianggui , Li Xianglong , Wang Antuo , Yang Bin , Hou Teng , Lu Yishen , Zhou Jing 
Published: December 2021

AbstractThe separation of stable oil/water emulsions is an urgent global issue. In this work, a porous and superhydrophobic polytetrafluoroethylene (PTFE) fibrous membrane was obtained by first centrifugal spinning PTFE/potato starch fibers and then heat treating the fibers to remove the starch. Results showed that spherical protrusions and irregular striped protrusions appeared on the surface of the prepared PTFE fibers, which significantly increased the roughness and hydrophobicity of the fibrous membrane. In addition, number density and shapes of these protrusions could be tuned by changing the extent of the heat treatment and the potato amylose content during the fiber preparation. The water contact angle on the structured PTFE membranes was as high as 160°, and the water sliding angle was as low as 3.4°. The results of oil/water separation experiments showed that the oil removal rate reached 99.5% based a permeability of 3670 L/m2/h, which suggested that the obtained PTFE fibrous membrane has great potential for use in oil/water emulsions separation.
Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase
Authors: Ceyhun İlçim , Karaca Şevval , Osmaniye Derya , Sağlık Begüm N. , Levent Serkan , Özkay Yusuf , Kaplancıklı Zafer A. 
Published: December 2021

AbstractAccording to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new chalcones (2a–l) were designed and synthesized. In biological activity studies, the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 2d, 2f, 2j, and 2l displayed significant activity against AChE. The compounds 2d, 2f, 2j, and 2l displayed IC50 values of 0.042, 0.024, 0.053, and 0.033 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed significant inhibition of AChE. The inhibitory activities of these compounds for β‐amyloid plaque aggregation were investigated. The enzyme kinetic study was performed to observe the effect of the most active compound 2f on the substrate–enzyme relationship, and a mixed‐type inhibition of AchE was determined. Further, docking simulation also revealed that these compounds (2d, 2f, 2j, and 2l) interacted with the enzyme active site in a similar manner to donepezil. The most active derivative, compound 2f, interacted with the amino acids Trp286, Phe295, Tyr341, Trp86, and Glu202.
Effect of binocular disparity on learning anatomy with stereoscopic augmented reality visualization: A double center randomized controlled trial
Authors: Bogomolova Katerina , Vorstenbosch Marc A. T. M. , El Messaoudi Inssaf , Holla Micha , Hovius Steven E. R. , van der Hage Jos A. , Hierck Beerend P. 
Published: December 2021

AbstractBinocular disparity provides one of the important depth cues within stereoscopic three‐dimensional (3D) visualization technology. However, there is limited research on its effect on learning within a 3D augmented reality (AR) environment. This study evaluated the effect of binocular disparity on the acquisition of anatomical knowledge and perceived cognitive load in relation to visual‐spatial abilities. In a double‐center randomized controlled trial, first‐year (bio)medical undergraduates studied lower extremity anatomy in an interactive 3D AR environment either with a stereoscopic 3D view (n = 32) or monoscopic 3D view (n = 34). Visual‐spatial abilities were tested with a mental rotation test. Anatomical knowledge was assessed by a validated 30‐item written test and 30‐item specimen test. Cognitive load was measured by the NASA‐TLX questionnaire. Students in the stereoscopic 3D and monoscopic 3D groups performed equally well in terms of percentage correct answers (written test: 47.9 ± 15.8 vs. 49.1 ± 18.3; P = 0.635; specimen test: 43.0 ± 17.9 vs. 46.3 ± 15.1; P = 0.429), and perceived cognitive load scores (6.2 ± 1.0 vs. 6.2 ± 1.3; P = 0.992). Regardless of intervention, visual‐spatial abilities were positively associated with the specimen test scores (η2 = 0.13, P = 0.003), perceived representativeness of the anatomy test questions (P = 0.010) and subjective improvement in anatomy knowledge (P < 0.001). In conclusion, binocular disparity does not improve learning anatomy. Motion parallax should be considered as another important depth cue that contributes to depth perception during learning in a stereoscopic 3D AR environment.
Dinucleotide tag‐based parallel reporter gene assay method enables efficient identification of regulatory mutations
Authors: Ren Naixia , Li Bo , Liu Qingqing , Yang Lele , Liu Xiaodan , Huang Qilai 
Published: December 2021

AbstractBackgroundThe causal single nucleotide polymorphisms (SNPs) leading to increased cancer predisposition mainly function as gene regulatory elements, the evaluation of which largely relies on the parallel reporter gene assay system. However, the common DNA barcodes used in parallel reporter gene assay systems typically because nucleotide composition bias, and many barcodes must be allocated for each sequence to reduce the bias effect.Main methods and major resultsHere, a versatile dinucleotide‐tag reporter system (DiR) that enables parallel analysis of regulatory elements with minimized bias based on next‐generation sequencing is described. The DiR system is more robust than the classical luciferase assay method, particularly for the investigation of moderate‐level regulatory elements. The authors applied the DiR‐seq assay in the functional evaluation of SNPs with prostate cancer risk and nominated two and six regulatory SNPs in PC‐3 and LNCaP cells, respectively.Conclusions and implicationsThe DiR system has great potential to advance the functional study of SNPs associated with polygenic disease risks.
Lipidomics reveals the dysregulated ceramide metabolism in oxidized low‐density lipoprotein‐induced macrophage‐derived foam cell
Authors: Liu Jie , Li Tong , Pei Wenxuan , Zhao Ye , Zhang Xin , Shi Xiujia , Li Yanping , Xu Wenjuan 
Published: December 2021

AbstractAtherosclerosis (AS) is associated with increasing lipid peroxidation. Oxidative modification of low‐density lipoproteins (ox‐LDL) is one most important factors contributing to the pathogenesis and clinical features of AS. The lipid composition influenced by ox‐LDL is not known clearly. In this work, a UHPLC/Orbitrap MS‐based lipidomics approach integrated pathway analysis was performed to advance understanding of the lipid composition and feature pathway in an ox‐LDL‐induced foamy macrophage cell. In the lipid metabolic profiling, 196 lipid species from 15 (sub)classes were identified. Lipid profiling indicated that increasing ox‐LDL caused lipid metabolic alternations, manifesting as phospholipids being down‐regulated and sphingolipids being up‐regulated. Pathway analysis explored glycerophospholipid and sphingolipid metabolism, which was involved in atherogenic changes. Notably, dysregulated ceramide metabolism was a typical feature of foamy cell formation. qRT‐PCR analysis was conducted to explore the differentially expressed genes. It indicated that ceramide metabolic balance might be disordered, performing higher synthesis and lower hydrolysis, with the ratio of SMPD1/SGMS2 being significantly up‐regulated (p < 0.05) in the ox‐LDL induced group. Our work offers a comprehensive understanding of macrophage‐derived foam cells and screen feature pathways associated with foamy cell formation, which provides a reference for the clinic diagnosis of AS and drug interventions.
Identifying patient verbal coaching in psychotherapy
Authors: Bugas John , McCollum James , Kealy David , Silberschatz George , Curtis John T. , Reid Jay 
Published: December 2021

AbstractAccording to control‐mastery theory (CMT), patients enter therapy with a plan (often unconscious) for how to work on their problems and disconfirm pathogenic beliefs. Patients want therapists to understand their plans and help them master their problems. CMT proposes that patients frequently coach their therapist to get them oriented and attuned to critical aspects of their treatment plan. The theory views patients coaching their therapists as an important part of the therapeutic process. The present study represents the first empirical research on this concept of coaching. It was designed to assess whether trained clinical judges could reliably identify and rate instances of patients coaching their therapists from psychotherapy transcript material. Segments from the beginning sessions of three brief (16‐session) psychotherapy cases were presented to clinical judges to rate on the following dimensions: the degree to which a patient communication is coaching; the degree to which a patient communication is intended to help the therapist understand the plan; and the degree to which a patient communication is intended to influence the therapist's behaviour. The results provide empirical evidence that patient coaching communications can be reliably distinguished from non‐coaching communications. Moreover, there was consensus among clinical judges on both the degree to which a coaching communication was intended to help the therapist understand the patient's treatment plan, and the degree to which a coaching communication was intended to influence the therapist's behaviour. Further research is necessary to better understand the vicissitudes of this coaching dynamic in therapy.
Nickel‐Catalyzed Thioesterification Enabled by a Visible‐Light Organophotoredox Catalyst under Mild Conditions
Authors: Zheng Wanyao , Xu Yongjie , Lin Luqing 
Published: December 2021

AbstractA nickel‐catalyzed thioesterification of aryl, heteroaryl, and vinyl iodides to afford thioesters is reported. The reaction involves a single‐electron transfer (SET) process induced by an organophotoredox catalyst under irradiation with blue LEDs at room temperature. This newly developed protocol provides a simple, mild method to access different thioesters with broad functional group exhibits excellent performance in aqueous solution and on a gram scale.
Challenges and future perspectives of transcatheter tricuspid valve interventions: adopt old strategies or adapt to new opportunities?
Authors: Russo Giulio , Taramasso Maurizio , Pedicino Daniela , Gennari Marco , Gavazzoni Mara , Pozzoli Alberto , Muraru Denisa , Badano Luigi P. , Metra Marco , Maisano Francesco 
Published: December 2021

AbstractTricuspid regurgitation (TR) is a highly prevalent valvular heart disease and is associated with an increased risk of cardiovascular events and death at long‐term follow‐up. Functional TR accounts for over 90% of TR and is mainly due to annular or right ventricular dilatation. Most often, TR is observed in patients with left‐sided valvular heart disease (with or without previous surgical correction) and pulmonary hypertension. Isolated TR is less frequent, though burdened by high surgical mortality. This, together with an incomplete understanding of the disease, has brought to a significant undertreatment in spite of the growing evidence of the impact of severe TR on mortality. Moreover, uncertainties about the appropriate timing for intervention and the predictors of procedural success have contributed to limit TR treatment. Transcatheter tricuspid valve replacement or repair interventions represent novel and less invasive alternatives to surgery and have shown early promising results. The purpose of this review is to provide a complete and updated overview of TR pathology with a special focus on current percutaneous treatment options, future challenges and directions.
Sample displacement chromatography of monoclonal antibody charge variants and aggregates
Authors: Černigoj Urh , Nemec Blaž , Štrancar Aleš 
Published: December 2021

AbstractThe rise of biosimilar monoclonal antibodies has renewed the interest in monoclonal antibody (mAb) charge variants composition and separation. The sample displacement chromatography (SDC) has the potential to overcome the low separation efficiency and productivity associated with bind‐elute separation of mAb charge variants. SDC in combination with weak cation exchanging macroporous monolithic chromatographic column was successfully implemented for a separation of charge variants and aggregates of monoclonal IgG under overloading conditions. The charge variants composition was at‐line monitored by a newly developed, simple and fast analytical method, based on weak cation exchange chromatography. It was proven that basic charge variants acted as displacers of IgG molecules with lower pI, when the loading was performed 1 to 1.5 pH unit below the pI of acidic charge variants. The efficiency of the SDC process is flow rate independent due to a convection‐based mass transfer on the macroporous monolith. The productivity of the process at optimal conditions is 35 mg of purified IgG fraction per milliliters of monolithic support with 75–80% recovery. As such, an SDC approach surpasses the standard bind‐elute separation in the productivity for a factor of 3, when performed on the same column. The applicability of the SDC approach was confirmed for porous particle‐based column as well, but with 1.5 lower productivity compared to the monoliths.
Proteomic analysis of serum in workers exposed to diesel engine exhaust
Authors: Rahman Mohammad L. , Bassig Bryan A. , Dai Yufei , Hu Wei , Wong Jason Y. Y. , Blechter Batel , Hosgood H. Dean , Ren Danzhi , Duan Huawei , Niu Yong , Xu Jun , Fu Wei , Meliefste Kees , Zhou Baosen , Yang Jufang , Ye Meng , Jia Xiaowei , Meng Tao , Bin Ping , Silverman Debra T. , Vermeulen Roel , Rothman Nathaniel , Zheng Yuxin , Lan Qing 
Published: December 2021

AbstractDiesel engine exhaust (DEE) is classified as a Group 1 human carcinogen. Using a targeted proteomics approach, we aimed to identify proteins associated with DEE and characterize these markers to understand the mechanisms of DEE‐induced carcinogenicity. In this cross‐sectional molecular epidemiology study, we measured elemental carbon (EC) using a personal air monitor and quantified 1317 targeted proteins in the serum using the SOMAScan assay (SOMALogic) among 19 diesel exposed factory workers and 19 unexposed controls. We used linear regressions to identify proteins associated with DEE and examined their exposure‐response relationship across levels of EC using linear trend tests. We further examined pathway enrichment of DEE‐related proteins using MetaCore. Occupational exposure to DEE was associated with altered levels of 22 serum proteins (permutation p < .01). Of these, 13 proteins (CXCL11, HAPLN1, FLT4, CD40LG, PES1, IGHE.IGK..IGL, TNFSF9, PGD, NAGK, CCL25, CCL4L1, PDXK, and PLA2G1B) showed an exposure‐response relationship with EC (p trend < .01), with serum levels of all but PLA2G1B declining with increasing air levels of EC. For instance, C‐X‐C Motif Chemokine Ligand 11 (CXCL11) showed the most significant association with DEE (β = −0.25; permutation p = .00004), where mean serum levels were 4121.1, 2356.7, and 2298.8 relative fluorescent units among the unexposed, lower exposed (median, range : 56.9, 40.2–62.1 μg/m3 EC), and higher exposed (median, range of EC: 72.9, 66.9–107.7 μg/m3 EC) groups, respectively (p trend = .0005). Pathway analysis suggested that these proteins are enriched in pathways related to inflammation and immune regulation. Our study suggests that DEE exposure is associated with altered serum proteins, which play a role in inflammation and immune regulation.