bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel loss-of-function mutation in NRAP is associated with left ventricular non-compaction cardiomyopathy
Authors: Zhang Zhongman , Xu Kangkang , Ji Lianfu , Zhang Han , Yin Jie , Zhou Ming , Wang Chunli , Yang Shiwei 
Published: February 2023

BackgroundThe nebulin-related-anchoring protein (NRAP) gene encodes actin-associated ankyrin. Few studies reported the association of the NRAP gene with cardiomyopathy. Thus, the genetic role of this gene in cardiomyopathy remains to be investigated.MethodsThe clinical data of the rare case of left ventricular non-compaction (LVNC) were collected and analyzed. Whole-exome sequencing (WES) was performed on related family members. Western blot was used to detect the effect of mutation on the NRAP protein expression. The effect of the c.259delC variant on myocardial development was further evaluated in a zebrafish model.ResultsA novel homozygous frameshift mutation c.259delC of NRAP was found in the proband with LVNC. It was found that c.259delC decreased the expression of NRAP by Western blot. In the zebrafish model, the heart development was affected while knocking out the NRAP gene, which showed pericardial edema. The pathological manifestations were uneven hypertrophy, disordered arrangement of cardiomyocytes, enlarged intercellular space, and loose muscle fibers. RNA-sequencing (RNA-seq) showed that the expression of genes related to heart development decreased significantly, and the NRAP gene mutation could participate in biological processes (BPs) such as myocardial contraction, cell adhesion, myosin coarse filament assembly of striated muscle, myosin complex composition, and muscle α-actin binding.ConclusionWe identified a rare case of LVNC associated with a novel homozygous NRAP frameshift variant. This study further strengthened the evidence linking mutations in the NRAP gene with LVNC, providing a new clue for further study of LVNC. NRAP may be one of the pathogenic genes of cardiomyopathy.
Early rhythm control vs. rate control in atrial fibrillation: A systematic review and meta-analysis
Authors: Han Shaojie , Jia Ruikun , Cen Zhifu , Guo Ran , Zhao Shenyu , Bai Yixuan , Xie Min , Cui Kaijun 
Published: February 2023

ObjectiveIt has long been debated whether rhythm control vs. rate control strategies have differing effects on mortality and morbidity for atrial fibrillation (AF). Recently, several randomized controlled studies (RCTs) and observational trials described that an early rhythm management method was linked to a lower likelihood of negative clinical outcomes in individuals with AF. We wanted to see if an early rhythm management method may help patients with AF.MethodsWe performed a systematic search to retrieve studies assessing the outcomes of early rhythm control vs. rate control in AF by using PubMed, Web of Science, Cochrane Library, and Embase published between 01/01/2000 and 15/04/2022.ResultsFinally, two RCTs, one retrospective analysis of RCTs, and four observational studies were identified. Compared with rate control, early rhythm control has been linked to lower all-cause mortality. [risk ratio (RR), 0.76; 95% CI 0.69–0.83; P &lt; 0.00001; I2 = 77%]. The early rhythm control group was also associated with a lower risk of cardiovascular mortality (RR, 0.68; 95% CI 0.63–0.74; P &lt; 0.00001; I2 = 33), stroke (RR, 0.77; 95% CI 0.67–0.87; P &lt; 0.001; I2 = 64), and heart failure hospitalization (RR, 0.74; 95% CI 0.59–0.93; P = 0.0009; I2 = 93%). We found no significant difference in nights spent in hospital per year, acute coronary syndrome, major bleeding, and cardiac arrest/ventricular arrhythmia between the groups.ConclusionIn this meta-analysis, early rhythm therapy was linked to a lower risk of all-cause mortality, cardiovascular mortality, stroke, and heart failure hospitalization compared with the rate control group.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022333592.
Mid-cretaceous rapid denudation of Eastern Tibetan plateau: Insights from detrital records at the Southwestern corner of Sichuan basin
Authors: Wang Zijian , Li Zhiwu , Ran Bo , Liu Shugen , Wu Wenhui , Ye Yuehao , Tong Kui , Hua Tian , Li Jinxi 
Published: February 2023

Reconstruction of the Cretaceous tectonic evolution of the eastern margin of the Tibetan Plateau is of great significance to understanding the formation and early evolution of the Tibetan Plateau. The thick late Mesozoic sedimentary sequence in the Western Sichuan Basin may record the evolution of the basin itself and the tectonic uplift history of the eastern margin of the Tibetan Plateau during the Cretaceous period. Here we provide new multi-proxy provenance data from conglomerate clast populations, sandstone petrography, heavy mineral assemblages, U-Pb dating of detrital zircon, paleocurrent data, and detrital garnet geochemistry from the Cretaceous clastic units in the southwest corner of Sichuan Basin. Our analysis reveals two distinct changes in sediment provenance recorded in the Cretaceous strata at the southwest corner of the Sichuan Basin. The first significant change of detrital provenance was identified in the mid-Cretaceous Jiaguan Formation. Metamorphic rocks and volcanic rocks clast, as well as feldspar and mica, increased significantly, a heavy mineral assemblage dominated by hematite–limonite and ilmenite with high ATi and RuZi and low ZTR values, predominantly type Bi garnet and mostly 164 Ma, 207 Ma, 440 Ma, 780 Ma–824 Ma, and 1840 Ma detrital zircon ages, interpreted to be sourced from the Songpan-Ganzi fold belt and Longmenshan orogenic belt. The second shift, in the Guankou Formation, is marked by a low compositional maturity, a distinct increase in fossiliferous carbonate clasts and high GZi index with type Bii garnet, and Triassic zircon ages, indicating the exhumation of Longmenshan orogenic belt during the late Cretaceous. These data collectively indicate that the significant surface uplift and rapid denudation of the eastern margin of the Tibetan Plateau were probably initiated in the mid-Cretaceous (∼120 Ma). In conclusion, a detailed hands-on provenance analysis of the clastic sedimentary sequences in the southwest corner of the Sichuan Basin enabled us to determine catchment areas and shifts hitherto unstudied, thus contributing to the exhumation history of the eastern margin of the Tibetan Plateau.
A novel role for Teneurin C-terminal Associated Peptide (TCAP) in the regulation of cardiac activity in the Sydney rock oyster, Saccostrea glomerata
Authors: Abramov Tomer , Suwansa-ard Saowaros , da Silva Patricia Mirella , Wang Tianfang , Dove Michael , O’Connor Wayne , Parker Laura , Russell Fraser D. , Lovejoy David A. , Cummins Scott F. , Elizur Abigail 
Published: February 2023

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioural stress in vertebrate and urochordate models, yet despite numerous studies in higher animals, there is limited knowledge of its role in invertebrates. In particular, there are no studies on TCAP’s effects on the heart of any metazoan, which is a critical organ in the stress response. We used the Sydney rock oyster (SRO) as an invertebrate model to investigate a potential role for sroTCAP in regulating cardiac activity, including during stress. sroTCAP is localized to the neural innervation network of the SRO heart, and suggested binding with various heart proteins related to metabolism and stress, including SOD, GAPDH and metabotropic glutamate receptor. Intramuscular injection of sroTCAP (10 pmol) significantly altered the expression of heart genes that are known to regulate remodelling processes under different conditions, and modulated several gene families responsible for stress mitigation. sroTCAP (1 and 10 pmol) was shown to cause transient bradycardia (heart rate was reduced by up to 63% and for up to 40 min post-administration), indicative of an unstressed state. In summary, this study has established a role for a TCAP in the regulation of cardiac activity through modulation of physiological and molecular components associated with energy conservation, stress and adaptation. This represents a novel function for TCAP and may have implications for higher-order metazoans.
The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings – The utility of a new screening assay
Authors: Atapattu Navoda , Amoroso Marie , Powell Michael , de Silva D. G. Harendra , de Silva K. Shamya H. , Furmaniak Jadwiga , Rees Smith Bernard , Premawardhana Lakdasa D. 
Published: February 2023

BackgroundThere is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka.ObjectivesTo assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA).MethodsWe selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo.ResultsThe median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up.ConclusionsThe 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.
A cross-sectional analysis of association between visceral adiposity index and serum anti-aging protein Klotho in adults
Authors: Cui Jianwei , Yang Zhenzhen , Wang Jiahao , Yin Shan , Xiao Yunfei , Bai Yunjin , Wang Jia 
Published: February 2023

BackgroundThe visceral adiposity index (VAI) is regarded as a reliable indicator to assess body fat distribution and dysfunction. Klotho protein is a hormone with anti-aging biological functions. However, the relationship between them has not been researched.ObjectsThis study aimed to evaluate the association between VAI and serum anti-aging protein klotho in American adults.MethodsA cross-sectional study of participants was conducted based on the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. Visceral adiposity was determined using the VAI score, while the klotho protein concentration was measured by ELISA kit. After adjusting some possible confounding variables, multivariate regression model was conducted to estimate the relationship between VAI and klotho protein. Furthermore, the smooth curve fitting and the segmented regression model were applied to examine the threshold effect and to calculate the inflection point.ResultIn total, 6 252 adults were eligible, with a mean VAI of 2.04 ± 0.03 and a mean klotho protein concentration of 848.79 ± 6.98 pg/ml. Multivariate regression analysis indicated that serum klotho protein concentration was lower in participants with high VAI score. When VAI was divided into quartiles, participants in the fourth quartiles of higher VAI had lower klotho protein levels (Q4: -32.25 pg/ml) than participants in the lowest quartile (Q1) after full adjustment (P &lt; 0.05). Segmented regression suggested that the turning point value of VAI was 3.21. A 1-unit increase in VAI was significantly associated with lower klotho protein levels by -18.61 pg/ml (95% CI: -28.87, -8.35; P &lt; 0.05) when VAI ranged from 0.29 to 3.21(accounting for 83.7% of the participants), however, the association was not significant when VAI ranged from 3.21 to 11.81 (P = 0.77).ConclusionThere was a nonlinear correlation between VAI score and the serum anti-aging protein klotho concentrations, showing a saturation effect. When VAI was less than 3.21, they were negatively correlated, and when VAI was greater than 3.21, they had no obvious correlation.
Genome-wide association study reveals genetic loci and candidate genes for meat quality traits in a four-way crossbred pig population
Authors: Wang Huiyu , Wang Xiaoyi , Li Mingli , Sun Hao , Chen Qiang , Yan Dawei , Dong Xinxing , Pan Yuchun , Lu Shaoxiong 
Published: February 2023

Meat quality traits (MQTs) have gained more attention from breeders due to their increasing economic value in the commercial pig industry. In this genome-wide association study (GWAS), 223 four-way intercross pigs were genotyped using the specific-locus amplified fragment sequencing (SLAF-seq) and phenotyped for PH at 45 min post mortem (PH45), meat color score (MC), marbling score (MA), water loss rate (WL), drip loss (DL) in the longissimus muscle, and cooking loss (CL) in the psoas major muscle. A total of 227, 921 filtered single nucleotide polymorphisms (SNPs) evenly distributed across the entire genome were detected to perform GWAS. A total of 64 SNPs were identified for six meat quality traits using the mixed linear model (MLM), of which 24 SNPs were located in previously reported QTL regions. The phenotypic variation explained (PVE) by the significant SNPs was from 2.43% to 16.32%. The genomic heritability estimates based on SNP for six meat-quality traits were low to moderate (0.07–0.47) being the lowest for CL and the highest for DL. A total of 30 genes located within 10 kb upstream or downstream of these significant SNPs were found. Furthermore, several candidate genes for MQTs were detected, including pH45 (GRM8), MC (ANKRD6), MA (MACROD2 and ABCG1), WL (TMEM50A), CL (PIP4K2A) and DL (CDYL2, CHL1, ABCA4, ZAG and SLC1A2). This study provided substantial new evidence for several candidate genes to participate in different pork quality traits. The identification of these SNPs and candidate genes provided a basis for molecular marker-assisted breeding and improvement of pork quality traits.
Differential expression and effect analysis of lncRNA-mRNA in congenital pseudarthrosis of the tibia
Authors: Li Zhuoyang , Mei Haibo , Liu Kun , Yang Ge 
Published: February 2023

Background: To analyze the lncRNA-mRNA differential expression and co-expression network of periosteal stem cells (PSCs) from congenital pseudarthrosis of the tibia (CPT) and normal patients, and to explore the role of key lncRNAs.Methods: Differentially expressed lncRNAs and mRNAs in PSCs were obtained by sequencing, and biological functions of differentially expressed mRNAs were detected by gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein -protein interaction (PPI) analysis. The co-expression network of lncRNA-mRNA was constructed by correlation analysis of differentially expressed lncRNAs and mRNAs, and the key lncRNAs were screened according to the connectivity degree. After that, the cis-regulated target genes of differential expressed lncRNAs and mRNAs were predicted.Results: A total of 194 differentially expressed lncRNAs were identified, including 73 upregulated and 121 downregulated genes. A total of 822 differentially expressed mRNAs were identified, including 311 upregulated and 511 downregulated genes. GO, KEGG and PPI enrichment analysis showed that the regulatory function of differentially expressed mRNAs were mainly gathered in skeletal system development and tissue morphogenesis. The co-expression network with 226 nodes and 3,390 edges was constructed based on correlation analysis. A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147 and AC103702, were screened according to connectivity degree. Prediction of target genes indicated that FAM227B-FGF7 and AC103702-HOXB4/5/6 may play an important role in the pathogenesis of CPT.Conclusion: A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147, and AC103702, occupy the core position in the co-expression network, suggesting that these lncRNAs and their target genes may play an important role in the pathogenesis of CPT.
Hyaluronan promotes intracellular ROS production and apoptosis in TNFα-stimulated neutrophils
Authors: Niemietz Iwona , Brown Kelly L. 
Published: February 2023

BackgroundHyaluronan (HA) is an important structural component of the extracellular matrix and has well-described roles in maintaining tissue integrity and homeostasis. With inflammation, HA metabolism (synthesis and degradation) increases and results in higher concentrations of soluble HA. Previously, we demonstrated that (soluble) HA primed resting neutrophils for the oxidative burst in response to a secondary stimulus. Notably, HA-mediated priming was not dependent on degranulation, which is a hallmark of priming by classical agents such as TNFα. In this study, we queried the ability of HA to prime neutrophils to different stimuli and its capacity to modulate neutrophil function in the presence of TNFα.MethodsBlood neutrophils from healthy donors were stimulated ex vivo with HA in the absence and presence of classic neutrophil agonists, inclusive of TNFα. Western blotting was used to assess the activation (phosphorylation) of p38 MAPK, and key neutrophil functions associated with priming and activation, such as intracellular and extracellular ROS production, degranulation, and apoptosis, were evaluated by standard chemiluminescence assays (ROS) and flow cytometry.ResultsHyaluronan is capable of atypical priming and, with TNFα, co-priming neutrophils for an enhanced (rate and/or magnitude) oxidative burst to various secondary stimuli. In addition, HA can augment intracellular ROS production that is directly induced by TNFα in resting neutrophils, which coincided with the activation of p38 MAPK and apoptosis.ConclusionsThese data demonstrate that the extracellular matrix component HA is a key modulator of neutrophil function(s) in the presence of inflammatory agents such as TNFα. Moreover, it provides additional evidence for the diversity and complexity of neutrophil priming and activation during inflammation.
Utilization of sodium carbonate activator in strain-hardening ultra-high-performance geopolymer concrete (SH-UHPGC)
Authors: Lao Jian-Cong , Xu Ling-Yu , Huang Bo-Tao , Zhu Ji-Xiang , Khan Mehran , Dai Jian-Guo 
Published: February 2023

In this study, strain-hardening ultra-high-performance geopolymer concrete (SH-UHPGC) was produced using Na2CO3, Na2SiO3 and their hybridization (1:1 in mole ratio) as alkaline activators. An ultra-high compressive strength was achieved for all the developed strain-hardening ultra-high-performance geopolymer concrete (i.e., over 130 MPa). Strain-hardening ultra-high-performance geopolymer concrete with hybrid Na2CO3 and Na2SiO3 activators showed the highest compressive strength (186.0 MPa), tensile strain capacity (0.44%), and tensile strength (11.9 MPa). It should be highlighted that very significant multiple cracking can be observed for all the strain-hardening ultra-high-performance geopolymer concrete even at a very low tensile strain level (e.g., 0.1%). According to the reaction heat, microstructures, and chemical composition analyses, strain-hardening ultra-high-performance geopolymer concrete with hybrid activators had the highest reaction degree, while that of Na2CO3-based strain-hardening ultra-high-performance geopolymer concrete was the lowest. It was found that the Na2CO3-based strain-hardening ultra-high-performance geopolymer concrete showed the best sustainability, and the strain-hardening ultra-high-performance geopolymer concrete with hybrid Na2SiO3 and Na2CO3 presented the best overall performance (considering the mechanical performance, energy consumption, environmental impact, and economical potential). The findings of this work provide useful knowledge for improving the sustainability and economic potential of strain-hardening ultra-high-performance geopolymer concrete materials.
Mathematical model of mechanobiology of acute and repeated synaptic injury and systemic biomarker kinetics
Authors: Gharahi Hamidreza , Garimella Harsha T. , Chen Zhijian J. , Gupta Raj K. , Przekwas Andrzej 
Published: February 2023

BackgroundBlast induced Traumatic Brain Injury (bTBI) has become a signature casualty of military operations. Recently, military medics observed neurocognitive deficits in servicemen exposed to repeated low level blast (LLB) waves during military heavy weapons training. In spite of significant clinical and preclinical TBI research, current understanding of injury mechanisms and short- and long-term outcomes is limited. Mathematical models of bTBI biomechanics and mechanobiology of sensitive neuro-structures such as synapses may help in better understanding of injury mechanisms and in the development of improved diagnostics and neuroprotective strategies.Methods and resultsIn this work, we formulated a model of a single synaptic structure integrating the dynamics of the synaptic cell adhesion molecules (CAMs) with the deformation mechanics of the synaptic cleft. The model can resolve time scales ranging from milliseconds during the hyperacute phase of mechanical loading to minutes-hours acute/chronic phase of injury progression/repair. The model was used to simulate the synaptic injury responses caused by repeated blast loads.ConclusionOur simulations demonstrated the importance of the number of exposures compared to the duration of recovery period between repeated loads on the synaptic injury responses. The paper recognizes current limitations of the model and identifies potential improvements.