bluuebunny/crossref_metadata_2025_split huggingface dataset:
GREM1,LRPPRC and SLC39A4 as Potential Biomarkers of Intervertebral Disc Degeneration:A Bioinformatics Analysis based on Multiple Microarray and Single-cell Sequencing Data
Authors: Zhang ZhaoLiang , Ji XingHua , Wei LinDong , Zhang Jinfeng , Huo JianZhong 
Published: February 2023

Abstract
Background:The issue of low back pain (LBP) has received considerable critical attention and has been a worldwide health problem. Intervertebral disc degeneration (IVDD) is always the subject of many classic studies in this field. The mechanistic basis of IVDD is poorly understood and has produced equivocal results.
Methods: Gene expression profiles (GSE34095,GSE147383) of IVDD patients together with control groups were analyzed in order to identify differentially expressed genes (DEGs) in GEO database.GSE23130 and GSE70362 were applied to validate the obtained key genes from DEGs by means of a best subset selection regression. Four machine-learning models were established to assess their predictive ability. Single-sample gene set enrichment analysis (ssGSEA) was used to profile correlation between overall immune infiltration levels with pfirmann grades and key genes. We also analyzed the upstream targeting miRNAs of key genes (GSE63492).We used single-cell transcriptome sequencing data (GSE160756) to define several cell clusters of nucleus pulposus (NP),annulus fibrosus (AF) and cartilaginous endplate (CEP) of degenerated disc and obtained the distribution of key genes in different cell clusters.
Results: By developing appropriate p-values and logFC values, we obtained a total of 6 DEGs. We validated 3 key genes (LRPPRC, GREM1 and SLC39A4) by an externally validated predictive modeling method. The ssGSEA results indicated that key genes were correlated with the infiltration abundance of multiple immune cells, such as dendritic cells and macrophages. Accordingly these 4 key miRNAs (miR-103a-3p,miR-484,miR-665,miR-107)were identified as upstream regulators targeting key genes using miRNet database and external GEO datasets. Finally, we plotted the spatial distribution of key genes in AF, CEP and NP.
Conclusions: Our study offered a new perspective to identify the creadible and effective gene therapy targets in IVDD.
Effect of ammonium stress on phosphorus solubilization of a novel marine mangrove microorganism Bacillus aryabhattai NM1-A2 as revealed by integrated omics analysis
Authors: Lu Zhaomei , He Sheng , Kashif Muhammad , Zhang Zufan , Mo Shuming , Du Linfang , Jiang Chengjian 
Published: February 2023

Abstract
Background
Phosphorus (P) is one of the essential nutrients for plant growth. Phosphate-solubilizing microorganisms (PSMs) can alleviate P deficiency in an eco-friendly way. Ammonium toxicity is widespread, but is not very well known about the effect of ammonium stress on phosphorus solubilization (PS) of PSMs.
Results
In this study, seven PSMs were isolated from mangrove sediments. Among them, Bacillus aryabhattai NM1-A2 showed a high PS ability under ammonium stress, which reached a maximum of 196.96 mg/L at 250 mM (NH4)2SO4. Whole-genome analysis showed that B. aryabhattai NM1-A2 contained various genes related to ammonium transporter (amt), ammonium assimilation (i.e., gdhA, glnA, and gltD), organic acid synthesis (i.e., ackA, fdhD, and idh), and phosphate transport (i.e., pstB and pstS). Furthermore, transcriptome data showed that the expression level of amt was downregulated. This phenomenon contributed to reducing the intake of external ammonium. For ammonium assimilation under ammonium stress, accompanied by protons efflux, the glutamate dehydrogenase pathway was the main approach. The overall upregulated glycolysis and tricarboxylic acid cycle could provide abundant carbon skeletons. Among them, the upregulated expression of idh indicated that more 2-oxoglutarate (2-OG) was induced under NH4+ stress. High performance liquid chromatography results showed that the concentrations of formic acid and acetic acid were significantly increased under ammonium stress, while succinic acid was significantly decreased.
Conclusions
In conclusion, the secretion of protons and organic acids was related to the high PS ability of B. aryabhattai NM1-A2 under ammonium stress. The accumulation of 2-OG and the inhibition of GS/GOGAT pathway might play a key role in ammonium detoxification. Our work provides new insights into the PS mechanism, which will provide theoretical guidance for the application of PSMs to promote environment-friendly agricultural development.
An optimized UHPLC-MS/MS method for simultaneous determination of erythrocyte methotrexate and polyglutamylated metabolites: Application in pediatric patients with acute lymphoblastic leukemia
Authors: Wang Jian , Guan Yanping , Qian Minlin , Yang San , Guo Chenchen , Liu Songze , Huang Min , Zhang Yating , Fang Jianpei , Zhou Dun-hua , Wang Xueding 
Published: February 2023

Abstract
Methotrexate (MTX), a widely used chemotherapeutic drug, is critical for achieving long-term complete remission in contemporary maintenance therapy of acute lymphoblastic leukemia (ALL). MTX is intracellularly converted into methotrexate polyglutamates (MTXPGn) by folylpolyglutamate synthase after transporting into the cells. The intracellular levels of active MTXPGn regulate the clinical efficacy and drug-related side effects, but it is still challenged by large inter-individual differences and narrow therapeutic index. Therefore, it is of great significance to develop a sensitive and stable method to monitor MTXPGs concentrations in the erythrocyte. To facilitate clinical application, an ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantification of MTX and MTXPGn in erythrocyte. Solid phase extraction was applied to sample clean-up followed by a gradient chromatographic separation. The elution consisting of methanol/water/2 mM ammonium acetate (flow rate: 0.4 mL/min). Linearity of the assay was assured in the range of 1-500 nM (R2 > 0.99). The co-efficient of variation ranged from 2–11% for intraday precision and 0.4–8% for inter day precision. Recovery ranged from 62.51–99.75%, and the matrix-effect varied from 63.24–96.33%. Blood samples from 89 pediatric ALL patients were detected. The concentrations and distribution of MTXPGn in these samples were basically consistent with the current literatures, which confirmed that the optimized method for quantitative detection of MTXPGn in red blood cells had high sensitivity and accuracy. The sensitive method has been fully validated and successfully applied to determine the erythrocyte MTXPGn in pediatric ALL patients during continuation therapy.
Self-Supervised Approaches to the Classification of Spectra: Application to Phase Transitions in X-ray Diffraction Data
Authors: Sun Yue , Brockhauser Sandor , Hegedűs Péter , Plückthun Christian , Gelisio Luca , de Lima Danilo Enoque Ferreira 
Published: February 2023

Abstract
The ability to detect interesting events is instrumental to effectively steer experiments and maximize their scientific efficiency. To address this, here we introduce and validate three frameworks based on self-supervised learning which are capable of classifying 1D spectral data using a limited amount of labeled data. In particular, in this work we focus on the identification of phase transitions in samples investigated by x-ray diffraction. We demonstrate that the three frameworks, based either on relational reasoning, contrastive learning, or a combination of the two, are capable of accurately identifying phase transitions. Furthermore, we discuss in detail the selection of data augmentations, crucial to ensure that scientifically meaningful information is retained.
A Catchment and Location-Allocation Analysis of Mammography Access in Delaware, US: Implications for disparities in geographic access to breast cancer screening
Authors: Webster Jessica L. , Goldstein Neal D. , Rowland Jennifer R. , Tuite Catherine M. , Siegel Scott D. 
Published: February 2023

Abstract
Background: Despite a 40% reduction in breast cancer mortality over the last 30 years, not all groups have benefited equally from these gains. A consistent link between later stage of diagnosis and disparities in breast cancer mortality has been observed by race, socioeconomic status, and rurality. Therefore, ensuring equitable geographic access to screening mammography represents an important priority for reducing breast cancer disparities. This study conducted a catchment and location-allocation analysis of mammography access in Delaware, a state that is representative of the US in terms of race and urban-rural characteristics and experiences an elevated burden from breast cancer.
Methods: A catchment analysis using the ArcGIS Pro Service Area analytic tool characterized the geographic distribution of mammography sites and Breast Imaging Centers of Excellence (BICOEs). Poisson regression analyses identified census tract-level correlates of access. Next, the ArcGIS Pro Location-Allocation analytic tool identified candidate locations for the placement of additional mammography sites in Delaware according to several sets of breast cancer screening guidelines.
Results: The catchment analysis showed that for each standard deviation increase in the number of Black women in a census tract, there were 64% (95% CI, 0.18-0.66) fewer mammography units and 85% (95% CI, 0.04-0.48) fewer BICOEs. The more rural counties in the state accounted for 41% of the population but only 22% of the BICOEs. The results of the location-allocation analysis depended on which set of screening guidelines were adopted, which included increasing mammography sites in communities with a greater proportion of younger Black women and in rural areas.
Conclusions: The results of this study illustrate how catchment and location-allocation analytic tools can be leveraged to guide the equitable selection of new mammography facility locations as part of a larger strategy to close breast cancer disparities.
Covid-19 infection outcomes and testing outreach efforts among people living with HIV in Milwaukee, WI
Authors: Birkey Trevor , Woodbury Joanna , Aldrete Sol Del Mar 
Published: February 2023

Abstract
Background
- Since the beginning of the Covid-19 pandemic, the incidence and severity of Covid-19 co-infection in people living with HIV (PLWH) has been an area of investigative research. Clinic databases of PLWH provide opportunities to investigate outcomes of Covid-19 co-infection and efficacy of outreach efforts, which are integral to patient care during health crises.
Methods
- All PLWH over 18 years of age in the Froedtert and Medical College of Wisconsin (F&MCW) with a Covid-19 test performed between May 2020 and March 2021 were included for analysis. All patients received an individualized phone call with Covid-19 testing education and information. Automated data collection and manual chart review were used to acquire information on demographics, outreach efforts, Covid-19 testing results, and Covid-19 clinical course.
Results
− 462 Covid-19 tests completed on 793 PLWH at F&MCW were included, with 40 (8.7%) positive tests and 422 (91.3%) negative tests, on a predominantly male and virally suppressed cohort. Most patients had mild-moderate Covid-19 infection with one patient requiring hospitalization and zero deaths. Outreach efforts from the F&MCW infectious disease clinic were associated with a significant increase in Covid-19 testing, most of which occurred after one phone call.
Conclusions
- Outcomes of Covid-19 infection in this cohort support most existing data suggesting co-infection in PLWH is not associated with significantly worse outcomes than patients without HIV. An individualized approach to outreach efforts may have utility in other public health arenas, though could be limited by larger patient populations.
A downscaling and bias correction method for climate model ensemble simulations of local-scale hourly precipitation
Authors: Yoshikane Takao , Yoshimura Kei 
Published: February 2023

Abstract
Ensemble simulations of climate models are used to assess the impact of climate change on precipitation, and require downscaling at the local scale. Statistical downscaling methods have been used to estimate daily and monthly precipitation from observed and simulated data. Downscaling of short-term precipitation data is necessary for more accurate prediction of extreme precipitation events and related disasters at the regional level. In this study, we developed and investigated the performance of a downscaling method for climate model simulations of hourly precipitation. Our method was designed to recognize time-varying precipitation systems that can be represented at the same resolution as the numerical model. Downscaling improved the estimation of the spatial distribution of hourly precipitation frequency, monthly average, and 99th percentile values. The climate change characteristics of precipitation was clearly shown by using the 50 ensemble averages of estimated precipitation, although the natural variability was too large to compare with observations. The changes in precipitation were consistent with simulations. Therefore, our downscaling method improved the evaluation of the climatic characteristics of extreme precipitation events and more comprehensively represented the influence of local factors, such as topography, which have been difficult to evaluate using previous methods.
Identification of ferroptosis-related genes in patients with renal ischemia-reperfusion injury
Authors: Jiang Guangwei , Li Jikuan , Chen Yuyan , Dong Ruoyu , Zhang Xiaoyu , Shi Xiaoming 
Published: February 2023

Abstract
Background
Effective and curable treatment for kidney injury caused by renal ischemia/reperfusion (I/R) have been poor reported. Severe inflammation and ferroptosis resulting from the formation of reactive oxygen species (ROS)，is the main cause of kidney injury. Thus, identify the biomarkers associated with ferroptosis in renal ischemia-reperfusion injury (RIRI) is emergency and crucial.
Methods
Bioinformatics analysis was used to discover differentially expressed genes (DEGs) from the GSE43974 dataset. Differentially expressed ferroptosis-related genes were discovered as the intersection of DEGs and ferroptosis-related genes (DEFRGs). Using the "clusterProfiler" R package, gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were done on DEFRGs. The Cytoscape plugin Molecular Complex Detection (MCODE)was used to extract hub genes from a protein-protein interaction (PPI) network. Finally, regulatory networks for TF-hub genes and miRNA-hub genes were predicted and created using the miRNet software.
Results
There found a total of 3,950 DEGs between the RIRI and control samples. After taking the intersection of DEGs and ferroptosis-related genes, 74 DEFRGs are obtained. DEFRGs were enriched in reaction to oxidative stress, cellular response to chemical stress, response to nutritional levels, and cellular response to oxidative stress, according to the GO analysis. The KEGG enrichment analysis revealed that these DEFRGs were substantially related with the mitophagy-animal, kaposi sarcoma-associated herpesvirus infection, autophagy-animal, and IL17 signaling pathways. MCODE found ATF3, ATF4, ATG3, ATG5, BECN1, DDIT3, HSPA5, NFE2L2, WIPI1, and XBP1 as the hub genes. Finally，the receiver operating characteristic (ROC) analysis of the GSE43974 data set reveals ATF3, DDIT3, ATF4, and ATG3 with AUC greater than 0.70,which were identified as the biomarkers related RIRI.
Conclusion
ATF3, DDIT3, ATF4, and ATG3 were identified as ferroptosis-related hub genes and proven to have diagnostic value for RIRI.
Isolated adrenocorticotropic hormone deficiency following immune checkpoint inhibitors treatment often occurred in polyglandular endocrinopathies
Authors: Chen Hong , Zhang Lei , Zhao Lin , Li Xiaomu 
Published: February 2023

Abstract
Background: With the increasing application of immune checkpoint inhibitors (ICI) in tumor therapy, the occurrence of isolated adrenocorticotropic hormone deficiency (IAD), as one of its adverse effects, is on the rise. Nevertheless, there are only a few studies regarding IAD induced by ICI. This study aimed at investigating the characteristics of IAD induced by ICI and its relationship with other endocrine adverse events.
Methods: A retrospective study was conducted in patients with ICI-induced endocrinopathies in Endocrinology Department from January 2019 to August 2022. Clinical features, laboratory findings and therapy information were collected. All patients underwent 3-6-month follow-up.
Results: 28 patients with IAD were enrolled. All of them were treated with anti-PD-1/ PD-L1. The median occurrence time of IAD was 24 weeks after starting ICI treatment.Over half of patients (53.5%) also had primary hypothyroidism or fulminant type 1 diabetes mellitus (FT1DM). Other types of endocrinopathy were not found. The interval between two gland damages was 4-21 weeks or at the same time. In the 28patients, primary hypothyroidism (46.4%) was more common than FT1DM (7.1%). Fatigue and nausea were the chief manifestation. Hyponatremia was also easily to be detected. All patients continued oral cortisol during follow-up.
Conclusions: IAD induced by ICI could occur independently, and more often in combination with hypothyroidism or FT1DM. This damage could happen at any stage of ICI treatment. Given that IAD can be life-threatening, it is critical to evaluate pituitary function dynamically in patients undergoing immunotherapy.
Lower extremity performance in older women as influenced by total body composition versus thigh muscularity
Authors: Kishigami Keiko , Kanehisa Hiroaki , Arimitsu Takuma , Miyachi Motohiko , Iemitsu Motoyuki , Sanada Kiyoshi 
Published: February 2023

AbstractBackground:This study aimed to elucidate whether total body composition or thigh muscularity is more closely associated with lower extremity performance in older women.Methods:Sixty-seven Japanese women aged 60-77 years voluntarily participated in this study. Fat mass (FM) and lean soft tissue mass (LSTM) of each body segment and total body were determined using a dual-energy X-ray absorptiometry scanner and expressed as values relative to body mass (FM/BM and LSTM/BM, respectively). In addition, cross-sectional area (CSA) was determined for each of the quadriceps femoris (QF), hamstrings (HAM), and adductors at mid-thigh using magnetic resonance imaging and expressed as the value relative to the two-third power of body mass (CSA/BM2/3). Participants conducted three performance tests: 5-m walking at normal speed, Timed Up and Go (TUG), and Two-step.Results:FM and FM/BM of the legs and total body were significantly correlated with scores of the three tests, and LSTM/BM of the legs and total body with 5-m walking time and Two-step length. QF CSA/BM2/3was correlated with scores of the three tests, and HAM CSA/BM2/3with Two-step length and TUG time. Multiple regression analyses identified LSTM/BM of the legs as an explanatory factor for 5-m walking time, waist circumference and QF CSA/BM2/3　for Two-step length, and age and QF CSA/BM2/3for TUG time.Conclusion:In older women, compared to total body composition, LSTM of the legs and CSA of the QF, expressed as values relative to body mass, are more closely associated with lower extremity performance.Trial registration number:UMIN000024651 (2016.10.31.)
Development and evaluation of case video-based debriefing on a simulation of high-risk neonatal care for nursing students in South Korea: a mixed-methods study
Authors: Koo Hyun Young , Lee Bo Ryeong , An Hyeran 
Published: February 2023

Abstract
Background: The debriefing process after health care simulations should provide a psychologically safe learning environment for nursing students. Case video-based debriefing on a simulation of high-risk neonatal care can be used to help nursing students to feel psychologically safe and make learning more effective. This study was conducted to develop case video-based debriefing materials for a simulation of high-risk neonatal care for nursing students in South Korea and to evaluate their effects.
Methods: This mixed-methods study, consisting of a survey and an in-depth interview, was conducted between August and December 2022. The participants were 27 nursing students for the development of the case video-based debriefing and 51 nursing students for the evaluation of its effects (25 in the experimental group and 26 in the control group) at a university in South Korea. A case video-based debriefing on a simulation of high-risk neonatal care was developed, and the experimental group took part in case video-based debriefing. The participants’ self-efficacy, critical thinking, state anxiety, and satisfaction with practice were examined. The experimental group’s learning experiences were explored. Quantitative data were analyzed using the chi-square test, the unpaired t-test, and repeated-measures analysis of variance. Qualitative content analysis was conducted.
Results: In the experimental group, critical thinking and satisfaction with practice increased to a greater extent than in the control group. However, the changes in self-efficacy and state anxiety were not significantly different between the experimental and control groups. Four categories were extracted from nursing students who participated in the case video-based debriefing: “definitely learned,” “expansion of learning,” “comfortable learning environment,” and “efficient utilization of case videos.”
Conclusions: Case video-based debriefing on a simulation of high-risk neonatal care effectively enhanced nursing students’ critical thinking and satisfaction with practice, and it will be utilized to improve nursing students’ competency in high-risk neonatal care.
Disparate behavioral types in wild and reared juveniles of gilthead seabream
Authors: Sanllehi Javier , Signaroli Marco , Pons Aina , Martorell-Barceló Martina , Mulet Júlia , Lana Arancha , Barcelo-Serra Margarida , Aspillaga Eneko , Grau Amalia , Catalán Ignacio A. , Viver Tomeu , Alós Josep 
Published: February 2023

Abstract
Fish differ consistently in behavior within the same species and population, reflecting distinct behavioral types (BTs). Comparing the behavior of wild and reared individuals provides an excellent opportunity to delve into the ecological and evolutionary consequences of BTs. In this work, we evaluated the behavioral variation of wild and reared juvenile gilthead seabreams, Sparus aurata, a highly relevant species for aquaculture and fisheries. We quantified behavioral variation along the five major axes of fish behavioral traits (exploration-avoidance, aggressiveness, sociability, shyness-boldness, and activity) using standardized behavioral tests and a deep learning tracking algorithm for behavioral annotation. Results revealed significant repeatability in all five behavior traits, suggesting high consistency of individual behavioral variation across the different axes in this species. We found reared fish to be more aggressive, social and active compared to their wild conspecifics. Reared individuals also presented less variance in their aggressiveness, lacking very aggressive and very tame individuals. Phenotypic correlation decomposition between behavioral types revealed two different behavioral syndromes: exploration-sociability and exploration-activity. Our work establishes the first baseline of repeatability scores in wild and reared gilthead seabreams, providing novel insight into the behavior of this important commercial species with implications for fisheries and aquaculture.