bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
Authors: Panneman Daan M. , Hitti-Malin Rebekkah J. , Holtes Lara K. , de Bruijn Suzanne E. , Reurink Janine , Boonen Erica G. M. , Khan Muhammad Imran , Ali Manir , Andréasson Sten , De Baere Elfride , Banfi Sandro , Bauwens Miriam , Ben-Yosef Tamar , Bocquet Béatrice , De Bruyne Marieke , Cerda Berta de la , Coppieters Frauke , Farinelli Pietro , Guignard Thomas , Inglehearn Chris F. , Karali Marianthi , Kjellström Ulrika , Koenekoop Robert , de Koning Bart , Leroy Bart P. , McKibbin Martin , Meunier Isabelle , Nikopoulos Konstantinos , Nishiguchi Koji M. , Poulter James A. , Rivolta Carlo , Rodríguez de la Rúa Enrique , Saunders Patrick , Simonelli Francesca , Tatour Yasmin , Testa Francesco , Thiadens Alberta A. H. J. , Toomes Carmel , Tracewska Anna M. , Tran Hoai Viet , Ushida Hiroaki , Vaclavik Veronika , Verhoeven Virginie J. M. , van de Vorst Maartje , Gilissen Christian , Hoischen Alexander , Cremers Frans P. M. , Roosing Susanne 
Published: February 2023

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since &gt;280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies.Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases.Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
Additive manufacturing of Al2O3 ceramics with MgO/SiC contents by laser powder bed fusion process
Authors: Ur Rehman Asif , Ullah Abid , Liu Tingting , Ur Rehman Rashid , Salamci Metin U. 
Published: February 2023

Laser powder bed fusion is a laser-based additive manufacturing technique that uses a high-energy laser beam to interact directly with powder feedstock. LPBF of oxide ceramics is highly desirable for aerospace, biomedical and high-tech industries. However, the LPBF of ceramics remains a challenging area to address. In this work, a new slurry-based approach for LPBF of ceramic was studied, which has some significant advantages compared to indirect selective laser sintering of ceramic powders. LPBF of Al2O3 was fabricated at different MgO loads up to 80 wt%. Several specimens on different laser powers (70 W–120 W) were printed. The addition of magnesia influenced the microstructure of the alumina ceramic significantly. The findings show that when the laser power is high and the magnesia load is low, the surface quality of the printing parts improves. It is feasible to produce slurry ceramic parts without binders through LPBF. Furthermore, the effects of SiC and MgO loads on the microstructure and surface morphology of alumina are compared and analysed.
Inhibition of tiRNA-Gly-GCC ameliorates neointimal formation via CBX3-mediated VSMCs phenotypic switching
Authors: Rong Zhihua , Li Fengshi , Zhang Rui , Niu Shuai , Di Xiao , Ni Leng , Liu Changwei 
Published: February 2023

Background and aimtRNA-derived fragments (tRFs) are a new class of non-coding RNAs involved in a variety of pathological processes, but their biological functions and mechanisms in human aortic smooth muscle cells (HASMCs) phenotype transition and vascular intimal hyperplasia are unclear.Methods/resultstiRNA-Gly-GCC is upregulated in synthetic HASMCs, atherosclerotic arteries, plasma, and the balloon injured carotid artery of rats. Functionally, the inhibition of tiRNA-Gly-GCC represses HASMCs proliferation, migration, and reversed dedifferentiation, whereas the overexpression of tiRNA- Gly-GCC have contrary effects. Mechanistically, tiRNA-Gly-GCC performs these functions on HASMCs via downregulating chromobox protein homolog 3 (CBX3). Finally, the inhibition of tiRNA-Gly-GCC could ameliorate neointimal formation after vascular injury in vivo.ConclusionstiRNA-Gly-GCC is a mediator of HASMCs phenotypic switching by targeting CBX3 and inhibition of tiRNA-Gly-GCC suppresses neointimal formation.
Red cell distribution width (RDW) is correlated to time of oxygen desaturation < 90% and length of sleep apneas in patients with sleep disorder breathing (SDB) and acute heart failure with preserved ejection fraction (HFpEF)
Authors: Stamerra Cosimo A. , D'Elia Emilia , Gori Mauro , Roncali Federica , Cereda Alberto , Gavazzi Antonello , Ferri Claudio , Senni Michele 
Published: February 2023

BackgroundHeart failure with preserved ejection fraction (HFpEF) is very frequently associated to sleep breathing disorders (SDB). Red blood cell distribution width (RDW) has been shown to be a potential inflammatory index linked to the degree of hypoxia and oxidative stress.AimTo identify the existence of a possible relationship between sleep apnea, oxygen saturation (SaO2) and RDW in a population of subjects affected by acute HFpEF (AHFpEF).MethodsAHFpEF patients with known history of SDB were enrolled and performed blood chemistry, echocardiography, and 24-h polysomnography (PSG).ResultsA total of 34 acute HFpEF patients (mean age 72.8 +/−8.63) were enrolled in the study. A control group of 24 non-HF patients were considered. Compared to controls, HFpEF patients showed a higher mean apnea hypopnea index (AHI), with prevalence of central apneas. A moderate to severe desaturation pattern was observed in AHFpEF vs. controls. RDW was significantly higher in AHFpEF patients vs. controls (mean value 14.7 +/−2.6 % vs. 9.1 +/−2.2, p &lt; 0.05). In AHFpEF, RDW showed a positive correlation with time of SaO2 &lt; 90% (r = 0.35, p = 0.04), and with mean length of apneic events (60 +/−28 s, r = 0.29, p = 0.03).ConclusionIn patients with AHFpEF and SDB, a dependence relationship between RDW and duration of oxygen desaturation was observed, as if oxidative stress and inflammation related to RDW increase could also be linked to severity of sleep disorders in this population.
Evolution characteristics of impact weather system and SST signals during years of anomalous Meiyu onset over the Yangtze-Huaihe River Basin
Authors: Jin Xiaoxia , Ma Yutong , Liu Mei , Zhong Shanshan 
Published: February 2023

This article investigates the climatic characteristics of Meiyu over the Yangtze-Huaihe River Basin and the primary impact system based on Meiyu onset data from 1954 to 2020, precipitation during the Meiyu Period, NCEP/NCAR reanalysis data, sea surface temperature (SST) data of NOAA, and western Pacific subtropical high (sub-high) data provided by the National Climate Center. The main analytical method used is synthetic analysis. The results indicate that the Meiyu onset date has enormous interannual variation. The date of the earliest Meiyu emergence is 27 days prior to the latest. There is a strong relationship between the duration of Meiyu and rainfall. The start of Meiyu correlates with the northward motion of the South Asia High, the northward jump of the westerly jet, the northward jump of the subtropical high, and the northward motion of the low-level jet. In the early Meiyu years featured in this study, the northward jump of the aforementioned systems occurred earlier and the position of the westerly jet shifted from 34–35°N to 38–40°N, which is much further north than its position under typical climatic circumstances. From late May to early June, the subtropical high was extraordinarily powerful, the ridgeline reached 20°N, and its position was further to the north. In years with a late Meiyu onset, the position of the westerly jet and the ridgeline were further south than the climatological average from early to late June; the jump to the north was not evident until late June. In addition, SST anomalies of the Indian Ocean and Pacific Ocean are significant external forcing variables that influence the Meiyu start date. The high SST of the equatorial Indian Ocean and the equatorial tropical eastern Pacific in the autumn of the preceding year and the high SST of the equatorial Indian Ocean in the spring of that year are prophase indicators of an early Meiyu start in the Yangtze-Huaihe River Basin.
Identification of thyroid hormone response genes in the remodeling of dorsal muscle during Microhyla fissipes metamorphosis
Authors: Liu Lusha , Liu Qi , Zou Xue , Chen Qiheng , Wang Xungang , Gao Zexia , Jiang Jianping 
Published: February 2023

IntroductionExtensive morphological, biochemical, and cellular changes occur during anuran metamorphosis, which is triggered by a single hormone, thyroid hormone (TH). The function of TH is mainly mediated through thyroid receptor (TR) by binding to the specific thyroid response elements (TREs) of direct response genes, in turn regulating the downstream genes in the cascade. The remodeling of dorsal skeletal muscle during anuran metamorphosis provides the perfect model to identify the immediate early and direct response genes that are important during apoptosis, proliferation, and differentiation of the muscle.MethodsIn our current study, we performed Illumina sequencing combined with single-molecule real-time (SMRT) sequencing in the dorsal muscle of Microhyla fissipes after TH, cycloheximide (CHX), and TH_CHX treatment.Results and DiscussionWe first identified 1,245 differentially expressed transcripts (DETs) after TH exposure, many of which were involved in DNA replication, protein processing in the endoplasmic reticulum, cell cycle, apoptosis, p53 signaling pathway, and protein digestion and absorption. In the comparison of the TH group vs. control group and TH_CHX group vs. CHX group overlapping gene, 39 upregulated and 6 downregulated genes were identified as the TH directly induced genes. Further analysis indicated that AGGTCAnnTnAGGTCA is the optimal target sequence of target genes for TR/RXR heterodimers in M. fissipes. Future investigations on the function and regulation of these genes and pathways should help to reveal the mechanisms governing amphibian dorsal muscle remodeling. These full-length and high-quality transcriptomes in this study also provide an important foundation for future studies in M. fissipes metamorphosis.
Network pharmacology and experimental validation to explore the potential mechanism of Sanjie Zhentong Capsule in endometriosis treatment
Authors: Guo Ruoyi , Yi Zhihui , Wang Yun , Wang Li 
Published: February 2023

PurposeSanjie Zhentong Capsule (SZC) is gradually becoming widely used in the treatment of endometriosis (EMs) and has demonstrated an excellent curative effect in the clinic. However, the active components and mechanisms of Sanjie Zhentong Capsule (SZC) in the treatment of endometriosis (EMs) remain unclear, and further research is needed to explore the effects of Sanjie Zhentong Capsule (SZC).Materials and methodsFirst, a drug target database of Sanjie Zhentong capsule (SZC) was established by consulting the TCMSP database and related literature. An endometriosis (EMs) disease target database was then established by consulting the GeneCards, OMIM and Drug Bank databases. The overlapping genes of SZC and EMs were determined, and protein-protein interactions (PPIs), gene ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) analyses were performed to predict the potential therapeutic mechanisms. Molecular docking was used to observe whether the key active ingredients and targets predicted by network pharmacology had good binding energy. Finally, in vitro experiments such as CCK-8, flow cytometry and RT-PCR assays were carried out to preliminarily verify the potential mechanisms.ResultsThrough the construction of a pharmacological network, we identified a total of 28 active components in SZC and 52 potential therapeutic targets. According to GO and KEGG enrichment analyses, the effects of SZC treatment may be related to oxidative stress, steroid metabolism, apoptosis and proliferation. We also experimentally confirmed that SZC can regulate the expression of steroid hormone biosynthesis-related genes, inhibit ectopic endometrial stromal cell (EESC) proliferation and oxidative stress, and promote apoptosis.ConclusionThis study explored the potential mechanism of SZC in the treatment of EMs through network pharmacology and experiments, providing a basis for further future research on SZC in the treatment of EMs.
Circulating biomarkers during progression to type 1 diabetes: A systematic review
Authors: Brenu Ekua W. , Harris Mark , Hamilton-Williams Emma E. 
Published: February 2023

AimProgression to type 1 diabetes (T1D) is defined in stages and clinical disease is preceded by a period of silent autoimmunity. Improved prediction of the risk and rate of progression to T1D is needed to reduce the prevalence of diabetic ketoacidosis at presentation as well as for staging participants for clinical trials. This systematic review evaluates novel circulating biomarkers associated with future progression to T1D.MethodsPubMed, Ovid, and EBSCO databases were used to identify a comprehensive list of articles. The eligibility criteria included observational studies that evaluated the usefulness of circulating markers in predicting T1D progression in at-risk subjects &lt;20 years old.ResultsTwenty-six studies were identified, seventeen were cohort studies and ten were case control studies. From the 26 studies, 5 found evidence for protein and lipid dysregulation, 11 identified molecular markers while 12 reported on changes in immune parameters during progression to T1D. An increased risk of T1D progression was associated with the presence of altered gene expression, immune markers including regulatory T cell dysfunction and higher short-lived effector CD8+ T cells in progressors.DiscussionSeveral circulating biomarkers are dysregulated before T1D diagnosis and may be useful in predicting either the risk or rate of progression to T1D. Further studies are required to validate these biomarkers and assess their predictive accuracy before translation into broader use.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42020166830).
Microplastics in a pelagic squid (Dosidicus gigas) from the Eastern tropical Pacific Ocean: Characteristics, spatial variation, and preliminary risk assessment
Authors: Wang Yaxin , Chen Xinjun 
Published: February 2023

Despite concerns about the environmental impact of microplastics (MPs), knowledge of MP contamination levels in pelagic squid is lacking. This study investigated the stomach of an ecologically and commercially important but poorly known squid species, the jumbo squid Dosidicus gigas, found in the tropical and Southern temperate Pacific. We examined the characteristics and spatial distribution of MPs in fifty D. gigas (16.0–37.8 cm mantle length) and assessed potential MP pollution risks. MPs were detected in 50.0% of specimens and had an average abundance of 0.88 ± 1.12 items/individual and 0.24 ± 0.36 items/g stomach weight, and were sized 58.42–2,944.85 μm. The MPs were dominated by polyethylene terephthalate (31.82%) in polymer type, fragments (54.55%) and fibers (43.18%) in shape, and blue (59.59%) in color. All specimens could be evaluated as low risk. No statistically significant correlations were found between the MP abundances and D. gigas stomach weight, stomach fullness index, distance from the coast, and mantle length. While regression analyses showed that fuller stomachs contained larger MPs. Spatial variations in shape and polymer composition suggest that low-density fibrous MPs could be easily transported offshore by upwelling and/or ocean currents. These results indicate intraspecific variation in D. gigas MP contaminants and underscore the need to assess the potential site-specific ecotoxicological consequences of increased plastic pollution to pelagic squid.
Simulations reveal climate and legacy effects underlying regional beta diversity in alpine vegetation
Authors: Malanson George P. , Pansing Elizabeth R. , Testolin Riccardo , Jiménez-Alfaro Borja 
Published: February 2023

IntroductionWhether the distribution and assembly of plant species are adapted to current climates or legacy effects poses a problem for their conservation during ongoing climate change. The alpine regions of southern and central Europe are compared to those of the western United States and Canada because they differ in their geographies and histories.MethodsIndividual-based simulation experiments disentangled the role of geography in species adaptations and legacy effects in four combinations: approximations of observed alpine geographies vs. regular lattices with the same number of regions (realistic and null representations), and virtual species with responses to either climatic or simple spatial gradients (adaptations or legacy effects). Additionally, dispersal distances were varied using five Gaussian kernels. Because the similarity of pairs of regional species pools indicated the processes of assembly at extensive spatiotemporal scales and is a measure of beta diversity, this output of the simulations was correlated to observed similarity for Europe and North America.ResultsIn North America, correlations were highest for simulations with approximated geography and location-adapted species; those in Europe had their highest correlation with the lattice pattern and climate-adapted species. Only SACEU correlations were sensitive to dispersal limitation.DiscussionThe southern and central European alpine areas are more isolated and with more distinct climates to which species are adapted. In the western United States and Canada, less isolation and more mixing of species from refugia has caused location to mask climate adaptation. Among continents, the balance of explanatory factors for the assembly of regional species pools will vary with their unique historical biogeographies, with isolation lessening disequilibria.
Rare copy number variation analysis identifies disease-related variants in atrioventricular septal defect patients
Authors: Hu Huan , Geng Zilong , Zhang Shasha , Xu Yuejuan , Wang Qingjie , Chen Sun , Zhang Bing , Sun Kun , Lu Yanan 
Published: February 2023

Atrioventricular septal defect (AVSD) is a deleterious subtype of congenital heart diseases (CHD) characterized by atrioventricular canal defect. The pathogenic genetic changes of AVSD remain elusive, particularly for copy number variation (CNV), a large segment variation of the genome, which is one of the major forms of genetic variants resulting in congenital heart diseases. In the present study, we recruited 150 AVSD cases and 100 healthy subjects as controls for whole exome sequencing (WES). We identified total 4255 rare CNVs using exon Hidden Markov model (XHMM) and screened rare CNVs by eliminating common CNVs based on controls and Database of Genomic Variants (DGV). Each patient contained at least 9 CNVs, and the CNV burden was prominently presented in chromosomes 19,22,21&amp;16. Small CNVs (&lt;500 kb) were frequently observed. By leveraging gene-based burden test, we further identified 20 candidate AVSD-risk genes. Among them, DYRK1A, OBSCN and TTN were presented in the core disease network of CHD and highly and dynamically expressed in the heart during the development, which indicated they possessed the high potency to be AVSD-susceptible genes. These findings not only provided a roadmap for finally unveiling the genetic cause of AVSD, but also provided more resources and proofs for clinical genetics.
RASGRP2 is a potential immune-related biomarker and regulates mitochondrial-dependent apoptosis in lung adenocarcinoma
Authors: Liu Yongting , Ouyang Yanhong , Feng Ziyang , Jiang Zhaohui , Ma Jiayao , Zhou Xin , Cai Changjing , Han Ying , Zeng Shan , Liu Shanshan , Shen Hong 
Published: February 2023

BackgroundRas guanine nucleotide-releasing protein 2 (RASGRP2), one of the guanine nucleotide exchange factors (GEFs), has attracted much attention in recent years. However, the correlation between RASGRP2 and immune infiltration and malignant features in lung adenocarcinoma (LUAD) has rarely been mentioned.MethodsThe Limma package and the LASSO regression model were performed to screen for differentially expressed genes. Data from the TCGA and 5 GEO databases were used to explore the expression level of RASGRP2 in LUAD patients. A weighted co-expression network and LinkFinder module were established to find the related genes of RASGRP2. The ESTIMATE algorithm was used to analyze the correlation between RASGRP2 and immune infiltration in LUAD. Tumor-infiltrating immune cells were sorted and sequenced at the single-cell level to analyze differences in RASGRP2. Real-time PCR and immunohistochemistry were performed in the real-world cohort to verify the expression of RASGRP2 and its correlation with immune-related genes. Clone formation and EdU assays were used to verify the proliferation ability. The proportion of apoptotic cells was analyzed by flow cytometry. Observation of mitochondrial membrane potential (MMP) changes by fluorescence microscopy.ResultsOur results suggested that decreased RASGRP2 was associated with worse clinical parameters and prognosis in LUAD patients. And we constructed a FLI1-HSA-miR-1976-RASGRP2 transcriptional network to support the role of RASGRP2. Enrichment analysis revealed that RASGRP2 was involved in lymphocyte activation and leukocyte adhesion. RASGRP2 was found to be positively correlated with the infiltration of most immune cells, immunoregulators, and chemokines in a subsequent study. Meanwhile, the real-world cohort confirmed that the expression levels of PDCD1, CTLA4, CD40LG, CCL14, CXCR5, and CCR7 were higher in the high-RASGRP2 expression group. Cytological experiments proved that RASGRP2 inhibited cell proliferation in LUAD by regulating mitochondrial-dependent apoptosis.ConclusionRASGRP2 was a potential immune-related biomarker of LUAD. In addition, RASGRP2 was involved in the malignant progression of LUAD through the regulation of mitochondrial-dependent apoptosis.