bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of exonic variants of uncertain significance in very long‐chain acyl‐CoA dehydrogenase identified through newborn screening
Authors: D'Annibale Olivia M. , Koppes Erik A. , Sethuraman Meena , Bloom Kaitlyn , Mohsen Al‐Walid , Vockley Jerry 
Published: February 2022

AbstractVery long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is an autosomal recessive disease resulting from mutations in the ACADVL gene and is among the disorders tested for in newborn screening (NBS). Confirmatory sequencing following suspected VLCADD NBS results often identifies variants of uncertain significance (VUS) in the ACADVL gene, leading to uncertainty of diagnosis and providing effective treatment regimen. Currently, ACADVL has >300 VUSs in the ClinVar database that requiring characterization to determine potential pathogenicity. In this study, CRISPR/Cas9 genome editing was used to knock out ACADVL in HEK293T cells, and targeted deletion was confirmed by droplet digital polymerase chain reaction (PCR). No VLCAD protein was detected and an 84% decrease in enzyme activity using the electron transfer flavoprotein fluorescence reduction assay and C21‐CoA as substrate was observed compared to control. Plasmids containing control or variant ACADVL coding sequence were transfected into the ACADVL null HEK293T. While transfection of control ACADVL restored VLCAD protein and enzyme activity, cells expressing the VLCAD Val283Ala mutant had 18% VLCAD enzyme activity and reduced protein compared to control. VLCAD Ile420Leu, Gly179Arg, and Gln406Pro produced protein comparable to control but 25%, 4%, and 5% VLCAD enzyme activity, respectively. Leu540Pro and Asp570_Ala572dup had reduced VLCAD protein and 10% and 3% VLCAD enzyme activity, respectively. VLCADD fibroblasts containing the same variations had decreased VLCAD protein and activity comparable to the transfection experiments. Generating ACADVL null HEK293T cell line allowed functional studies to determine pathogenicity of ACADVL exonic variants. This approach can be applied to multiple genes for other disorders identified through NBS.
Longitudinal Changes in Global Cerebral Blood Flow in Cognitively Normal Older Adults: A Phase‐Contrast MRI Study
Authors: Han Hualu , Lin Zixuan , Soldan Anja , Pettigrew Corinne , Betz Joshua F. , Oishi Kumiko , Li Yang , Liu Peiying , Albert Marilyn , Lu Hanzhang 
Published: February 2022

BackgroundCharacterization of blood supply changes in older individuals is important in understanding brain aging and diseases. However, prior studies largely focused on cross‐sectional design, thus change in cerebral blood flow (CBF) could not be assessed on an individual level.PurposeTo evaluate longitudinal short‐term changes in global CBF in cognitively normal older adults.Study TypeProspective, longitudinal, and cohort.PopulationOne‐hundred twenty‐seven cognitive‐normal participants (mean age 69 ± 7 years, 47 males) underwent serial MRI with an average follow‐up time of 2.1 years.Field Strength/Sequence3 T phase‐contrast (PC), three‐dimensional magnetization‐prepared‐rapid‐acquisition‐of‐gradient‐echo (MPRAGE) and fluid‐attenuated inversion recovery (FLAIR) MRI.AssessmentTotal CBF was measured with PC MRI allowing assessment of quantitative flow in four major feeding arteries by a trained radiologist with >3 years' experience (O.K.). Brain volume was obtained from MPRAGE MRI and measured by T1‐MultiAtlas MRICloud tool. The ratio between total CBF and brain volume yielded global CBF in mL/100 g/min. White matter hyperintensity (WMH) was measured automatically using a Bayesian probability approach on FLAIR.Statistical TestsLinear mixed effect model was used to simultaneously assess cross‐sectional age‐differences and longitudinal age‐changes in CBF. Spearman rank correlation was used to evaluate the relationship between CBF change and WMH progression. A P‐value of <0.05 (two‐tailed) was considered significant.ResultsGlobal CBF decreased with age at a longitudinal rate of −0.56 mL/100 g/min/year (95% confidence interval [CI]: −1.09, −0.03), compared to a cross‐sectional rate of −0.26 mL/100 g/min/year (95% CI: −0.41, −0.11). Changes in CBF were significantly associated with progression of WMH (Spearman rank correlation r = −0.25), as those participants who had a more rapid CBF reduction had greater increases in WMH volumes and the relationship remained significant when adjusting for baseline vascular risk scores. Additionally, age‐related changes in whole‐brain volume were found to be −0.151%/year (95% CI: −0.186, −0.116).Data ConclusionThese findings suggest that brain aging in older adults is accompanied by a rapid longitudinal reduction in CBF, the rate of which is associated with white matter damage.Level of Evidence1Technical Efficacy Stage2
On the relationship between western North Pacific tropical cyclone accumulated cyclone energy and the Pacific‐North American pattern
Authors: Song Jinjie , Klotzbach Philip J. , Duan Yihong 
Published: February 2022

AbstractThis study investigates the influence of the Pacific‐North American (PNA) pattern on the accumulated cyclone energy (ACE) of tropical cyclones (TCs) over the western North Pacific (WNP). There is a significant inverse relationship between ACE during July–October and the simultaneous PNA index during 1970–2020. Lower (greater) basinwide ACE is observed when the PNA is positive (negative), primarily as a result of lesser (greater) TC frequency, while the effects of duration and intensity are found to be relatively minor. When examining the results spatially, we find lower ACE over almost the entire WNP when the PNA index is positive compared with when the PNA is negative. Significant decreases in ACE are observed over the region to the north and east of Guam (10°–35°N, 135°–165°E) and near the Philippines (10°–25°N, 110°–130°E). These decreases when the PNA is positive are primarily induced by a decrease in TC formation as well as a reduction in average intensity in a region north and east of Guam, possibly linked to decreased low‐level vorticity and upper‐level divergence as well as increased vertical wind shear. These changes in dynamic variables are predominantly driven by large‐scale flow patterns related to the PNA.
Complement component 3 and its activation split‐products in saliva associate with periodontitis
Authors: Damgaard Christian , Massarenti Laura , Danielsen Anne Katrine , Graversen Jonas H. , Holmstrup Palle , Nielsen Claus H. , Palarasah Yaseelan 
Published: February 2022

AbstractBackgroundPeriodontitis (PD) is classified by Grades A through C according to the risk of further progression, PD Grade C (PD‐C) being the most severe progressing form. It is a matter of controversy, whether the disease activity observed in PD‐C is due to impaired immune reactivity toward bacteria embedded in biofilms or a hyper‐reactive immune response causing tissue damage as a bystander phenomenon. Little is known about the role of complement in this respect.MethodsPlasma and unstimulated saliva samples were collected from patients with PD‐B (n = 34) or ‐C (n = 27) and healthy controls (HCs) (n = 28). Salivary and plasma levels of total C3, C3c, and C3dg were quantified using sandwich enzyme‐linked immunosorbent assay (ELISA).ResultsSalivary levels of total C3 and C3dg were elevated in PD‐B and PD‐C patients compared to HCs (both P < 0.05), while the levels of C3c were elevated in PD‐C compared to HCs. Plasma levels of C3c were higher in PD‐B patients than in HCs (P < 0.05).ConclusionPD‐B and PD‐C patients show increased complement activation compared to HCs, but no difference was found between the two disease grades. PD‐B, but not PD‐C, is associated with increased systemic complement activation as assessed by C3c in plasma.
Genetic variation in skin traits in New Zealand lambs
Authors: McRae Kathryn M , Cooper Sue M , McEwan John C , Anderson Rayna , Bain Wendy E , Baird Hayley J , Dodds Ken G , Clarke Shannon M , Pickering Natalie K , Holmes Geoff 
Published: March 2022

AbstractBACKGROUNDThis study explored the genetic variability in the New Zealand sheep population for economically important skin traits. Skins were collected at slaughter from two progeny test flocks, resulting in 725 skins evaluated for grain strain, flatness, crust leather strength and overall suitability for shoe leather. DNA profiles collected from skins post‐slaughter were matched to individual animals using previously collected high‐density genotypes.RESULTSConsiderable phenotypic variation for skin traits was observed, with around 40% of the skins being identified as suitable for high‐value shoe leather production. Several key traits associated with leather production, including flatness, tear strength, grain strength and grain strain were found to be moderate to highly heritable (h2 = 0.28–0.82).There were no major significant genome‐wide association study (GWAS) peaks associated with many of the traits examined, however, one single‐nucleotide polymorphism (SNP) reached significance for the flatness of the skin over the hindquarters.CONCLUSIONThis research confirms that suitable lamb skins can be bred for use as high‐value shoe leather. While moderately to highly heritable, skin traits in New Zealand lambs appear to be polygenic with no genes of major effect underlaying the traits of interest. Given the complex nature of these traits, the identification and selection of animals with higher‐value skins may be enabled by geomic selection. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Feasibility and effectiveness of opioid‐free anesthesia in cytoreductive surgery with or without heated intraperitoneal chemotherapy
Authors: Tejedor Ana , Bijelic Lana , Deiros Carmen , Pujol Elisenda , Bassas Eva , Fernanz Jesús , Bernat Maria José 
Published: February 2022

AbstractBackgroundOpioid‐free anesthesia (OFA) provides analgesia minimizing opioids. OFA has not been evaluated in cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy. We aim to evaluate OFA feasibility and effectiveness in CRS.MethodsRetrospective cohort study of adult patients (84) undergoing CRS in a tertiary center from May 2020 until June 2021. Predefined protocols for either opioid‐based anesthesia (OBA) or OFA were followed.ResultsOFA protocol patients (41) had better mean pain scores (1 ± 0.8 vs. 2 ± 1; p = 0.00) despite the avoidance of intravenous and epidural fentanyl intraoperatively (220 ± 104 and 194 ± 73 µg, respectively, in OBA vs. 0; p = 0.00). Postoperative epidural levobupivacaine was also lower in the OFA group (575 ± 192 vs. 706 ± 346 mg; p = 0.034) despite the lack of epidural fentanyl without difference in duration (4.3 ± 1.2 vs. 4 ± 1.2 days; p = 0.22). Morphine consumption was very low (4.1 ± 10 vs. 1.7 ± 5 mg; p = 0.16). Intraoperative hypertensive events and postoperative nausea and vomiting (PONV) were higher for OBA (43) (30.2% vs. 7.3%; p = 0.01% and 69.8% vs. 34.1%; p = 0.001, respectively). Postoperative epidural fentanyl was independently associated with PONV (p = 0.004). There was no difference in total complications or length of stay.ConclusionOFA is feasible, safe, and offers optimal pain control while minimizing the use of opioids in CRS.
Amino functionalized magnetic covalent organic framework for magnetic solid‐phase extraction of sulfonylurea herbicides in environmental samples from tobacco land
Authors: Tian Cong , Wu Zhekuan , He Man , Chen Beibei , Hu Bin 
Published: February 2022

An amino‐functionalized magnetic covalent organic framework composite TpBD‐(NH2)2@Fe3O4 (Tp=Tp1,3,5‐triformylphloroglucinol, BD‐(NH2)2 is 3,3',4,4'‐biphenyltetramine) was prepared by post‐synthesis modification. Due to its abundant benzene rings and amino groups, large specific surface area and porous structure, the prepared TpBD‐(NH2)2@Fe3O4 exhibits high extraction efficiency toward sulfonylurea herbicides. Based on this, a new method of magnetic solid‐phase extraction with TpBD‐(NH2)2@Fe3O4 as the sorbent combined with high‐performance liquid chromatography and ultraviolet detection was developed for trace analysis of sulfonylurea herbicides in environmental water, soil and tobacco leaves samples from tobacco land. Under the optimized conditions, the limits of detection within 0.05–0.14 μg/L were achieved with a high enrichment factor of 217‐260‐fold, and the relative standard deviations were 4.9–7.5% (n = 7, c = 0.5 μg/L). The linear range was around three orders of magnitude with the square of correlation coefficient higher than 0.9936. The method was applied to analyze five sulfonylurea herbicides in the environmental water, soil, and tobacco leave samples collected from tobacco land. No sulfonylurea herbicides were detected in these samples. The recoveries of target sulfonylurea herbicides in spiked environmental water, soil, and tobacco leaf samples were found in the range of 90.7–104, 70.7–99.0, and 59.3–97.8%, respectively. The results illustrate that the established TpBD‐(NH2)2@Fe3O4‐magnetic solid‐phase extraction‐ high‐performance liquid chromatography–ultraviolet detection method is efficient for the analysis of trace sulfonylurea herbicides in environmental samples.
Measurement of microplastic settling velocities and implications for residence times in thermally stratified lakes
Authors: Elagami Hassan , Ahmadi Pouyan , Fleckenstein Jan H. , Frei Sven , Obst Martin , Agarwal Seema , Gilfedder Benjamin S. 
Published: February 2022

AbstractMicroplastics residence times in lakes are currently poorly understood. In this work, settling experiments with pristine and biofilm‐colonized microplastic particles were combined with model calculations to evaluate settling velocities, particle distributions, and residence times in the epilimnion, metalimnion, and hypolimnion of a hypothetical stratified lake broadly based on Upper Lake Constance. Settling velocities of various biodegradable and nonbiodegradable polymers of various shapes, sizes, and biofilm colonization were measured in a settling column. The settling velocities ranged between ~ 0.30 and ~ 50 mm s−1. Particle sizes and polymer densities were identified as primary controls on settling rates. Microplastic particles that had been exposed to a lake environment for up to 30 weeks were colonized by a range of biofilms and associated extracellular polymeric substances; surprisingly, however, the settling velocity did not vary significantly between pristine and colonized microplastic particles. Simulated microplastic residence times in the model lake varied over a wide range of time scales (10−1 to 105 d) and depended mainly on the size of the particles and depth of the lake layer. Long residence times on the order of 105 d (for 1‐μm microplastic particles) imply that for small microplastic particles there is a high probability that they will be taken up at some stage by lake organisms. As the lake retention time (~ 4.5 years) is considerably shorter than the residence time of small microplastics, negligible quantities of these microplastic particles should be found in the lake sediment unless some other process increases their settling velocity.
Corrosion resistance of iron‐containing experimental titanium alloys exposed to simulated body fluids
Authors: Leshetla Mogomotsi , Klenam Desmond E. , van der Merwe Josias , Potgieter Herman , Whitefield David , Bodunrin Michael O. 
Published: February 2022

AbstractIn this study, experimental Ti–6Al–1V–3Fe, Ti–4.5Al–1V–3Fe, and Ti–3Fe alloys, as well as commercial Ti–6Al–4V alloy that were scaled up utilizing vacuum induction melting technology, were assessed for corrosion performance in simulated body fluids. The selected simulated body fluids were 0.9 wt% NaCl solution and Hanks balanced salt solution (HBSS). Open circuit potential and linear polarization scans were performed to understand the corrosion performance of the alloys. The surface of the alloys was examined before and after exposure to corrosive solutions using scanning electron microscopy. The results show that all the alloys exhibit good corrosion performance in simulated body fluids. The corrosion rates were less than 0.5 mm/year. Owing to higher corrosion potential and lower corrosion rate, Ti–6Al–1V–3Fe and Ti–4.5Al–1V–3Fe had the best resistance to corrosion in 0.9 wt% NaCl and HBSS, respectively. All the alloys consist of a fully lamellar structure with α and β phases. There was no evidence of severe deterioration on the exposed surface of alloys in the simulated body fluids.
Lithium Salt‐Induced In Situ Polymerizations Enable Double Network Polymer Electrolytes
Authors: Zhang Chi , Jiang Ke , Zhang Yong , Wang Jirong , Xue Zhigang 
Published: February 2022

AbstractStructural design is an intriguing strategy to improve the physical and electrochemical performance of polymer electrolytes (PEs) for lithium‐ion batteries. However, the complex synthetic process and introduction of nonelectrolyte composition severely limit the development and practical application of PEs. Here, a facile method is reported for the fabrication of a double network polymer electrolyte (DN‐PE) through combining the lithium salt‐accelerated thiol‐Michael addition and lithium salt‐catalyzed radical polymerization. By adjusting the reaction temperature, the double network with the cross‐linking structure can be in situ formed step by step at room temperature and 80 °C. Notably, using lithium salt as the accelerator and catalyst avoids the addition of extra species and the related side reactions in the electrolyte system. Compared with single network polymer electrolyte (SN‐PE), DN‐PE has a distinctly improved mechanical strength and a better interfacial compatibility with the electrode, which leads to a stable cycling of the symmetric Li|DN‐PE|Li cell over 1000 h at a current density of 0.05 mA cm–2. In addition, the Li|DN‐PE|LiFePO4 cell shows a high discharge specific capacity of 150.3 mAh g–1 at 0.1 C and coulomb efficiency of 99%.
Two nonsense GLI3 variants are associated with polydactyly and syndactyly in two families by affecting the sonic hedgehog signaling pathway
Authors: Shen Xiaofang , Zhang Shun , Zhang Xin , Zhou Taifeng , Rui Yongjun 
Published: February 2022

AbstractBackgroundPolydactyly and syndactyly are congenital limb deformities, segregating in an autosomal‐dominant fashion. The variants in the GLI3 gene are closely related to congenital limb malformations. However, the causes underlying polydactyly and syndactyly are not well understood.MethodsWe conducted a whole‐exome sequencing on two four‐generation Chinese families with polydactyly and syndactyly. Then c.2374C>T and c.1728C>A mutant plasmids were transfected to HEK293T cells and mice limb bud cells to explore the functional consequences of these variants. Western blot and real‐time quantitative PCR were used to analyze the expression of GLI3 and Shh.ResultsIn these two families, the known GLI3 variant (NM_000168.6:c.2374C>T) and the novel GLI3 variant (NM_000168.6:c.1728C>A) contributed to polydactyly and syndactyly. Additionally, the GLI3 c.2374C>T mutant plasmid led to truncated GLI3 protein, and the GLI3 c.1728C>A mutant plasmid led to degraded GLI3 protein. Simultaneously, we demonstrated that the GLI3‐mutant plasmids led to decreased Shh expression in mice limb bud cells.ConclusionWe demonstrated that the novel GLI3 variant (c.1728C>A) and known GLI3 variant (c.2374C>T) contributed to the malformations in two four‐generation pedigrees with polydactyly and syndactyly by affecting SHH signaling.
Magnetic resonance imaging contrast enhancement synthesis using cascade networks with local supervision
Authors: Xie Huiqiao , Lei Yang , Wang Tonghe , Roper Justin , Axente Marian , Bradley Jeffrey D. , Liu Tian , Yang Xiaofeng 
Published: March 2022

AbstractPurposeGadolinium‐based contrast agents (GBCAs) are widely administrated in MR imaging for diagnostic studies and treatment planning. Although GBCAs are generally thought to be safe, various health and environmental concerns have been raised recently about their use in MR imaging. The purpose of this work is to derive synthetic contrast enhance MR images from unenhanced counterpart images, thereby eliminating the need for GBCAs, using a cascade deep learning workflow that incorporates contour information into the network.Methods and materialsThe proposed workflow consists of two sequential networks: (1) a retina U‐Net, which is first trained to derive semantic features from the non‐contrast MR images in representing the tumor regions; and (2) a synthesis module, which is trained after the retina U‐Net to take the concatenation of the semantic feature maps and non‐contrast MR image as input and to generate the synthetic contrast enhanced MR images. After network training, only the non‐contrast enhanced MR images are required for the input in the proposed workflow. The MR images of 369 patients from the multimodal brain tumor segmentation challenge 2020 (BraTS2020) dataset were used in this study to evaluate the proposed workflow for synthesizing contrast enhanced MR images (200 patients for five‐fold cross‐validation and 169 patients for hold‐out test). Quantitative evaluations were conducted by calculating the normalized mean absolute error (NMAE), structural similarity index measurement (SSIM), and Pearson correlation coefficient (PCC). The original contrast enhanced MR images were considered as the ground truth in this analysis.ResultsThe proposed cascade deep learning workflow synthesized contrast enhanced MR images that are not visually differentiable from the ground truth with and without supervision of the tumor contours during the network training. Difference images and profiles of the synthetic contrast enhanced MR images revealed that intensity differences could be observed in the tumor region if the contour information was not incorporated in network training. Among the hold‐out test patients, mean values and standard deviations of the NMAE, SSIM, and PCC were 0.063±0.022, 0.991±0.007 and 0.995±0.006, respectively, for the whole brain; and were 0.050±0.025, 0.993±0.008 and 0.999±0.003, respectively, for the tumor contour regions. Quantitative evaluations with five‐fold cross‐validation and hold‐out test showed that the calculated metrics can be significantly enhanced (p‐values ≤ 0.002) with the tumor contour supervision in network training.ConclusionThe proposed workflow was able to generate synthetic contrast enhanced MR images that closely resemble the ground truth images from non‐contrast enhanced MR images when the network training included tumor contours. These results suggest that it may be possible to minimize the use of GBCAs in cranial MR imaging studies.