bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ1+CCR5+ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice
Authors: Li Jinbo , Yao Zhenqiang , Liu Xin , Duan Rong , Yi Xiangjiao , Ayoub Akram , Sanders James O. , Mesfin Addisu , Xing Lianping , Boyce Brendan F. 
Published: January 2023

AbstractTGFβ1 induces age-related bone loss by promoting degradation of TNF receptor-associated factor 3 (TRAF3), levels of which decrease in murine and human bone during aging. We report that a subset of neutrophils (TGFβ1+CCR5+) is the major source of TGFβ1 in murine bone. Their numbers are increased in bone marrow (BM) of aged wild-type mice and adult mice with TRAF3 conditionally deleted in mesenchymal progenitor cells (MPCs), associated with increased expression in BM of the chemokine, CCL5, suggesting that TRAF3 in MPCs limits TGFβ1+CCR5+ neutrophil numbers in BM of young mice. During aging, TGFβ1-induced TRAF3 degradation in MPCs promotes NF-κB-mediated expression of CCL5 by MPCs, associated with higher TGFβ1+CCR5+ neutrophil numbers in BM where they induce bone loss. TGFβ1+CCR5+ neutrophils decreased bone mass in male mice. The FDA-approved CCR5 antagonist, maraviroc, reduced TGFβ1+CCR5+ neutrophil numbers in BM and increased bone mass in aged mice. 15-mon-old mice with TGFβRII specifically deleted in MPCs had lower numbers of TGFβ1+CCR5+ neutrophils in BM and higher bone volume than wild-type littermates. We propose that pharmacologic reduction of TGFβ1+CCR5+ neutrophil numbers in BM could treat or prevent age-related osteoporosis.
Symmetry-breaking host–guest assembly in a hydrogen-bonded supramolecular system
Authors: Horiuchi Shinnosuke , Yamaguchi Takumi , Tessarolo Jacopo , Tanaka Hirotaka , Sakuda Eri , Arikawa Yasuhiro , Meggers Eric , Clever Guido H. , Umakoshi Keisuke 
Published: January 2023

AbstractBio-inspired self-assembly is invaluable to create well-defined giant structures from small molecular units. Owing to a large entropy loss in the self-assembly process, highly symmetric structures are typically obtained as thermodynamic products while formation of low symmetric assemblies is still challenging. In this study, we report the symmetry-breaking self-assembly of a defined C1-symmetric supramolecular structure from an Oh-symmetric hydrogen-bonded resorcin[4]arene capsule and C2-symmetric cationic bis-cyclometalated Ir complexes, carrying sterically demanding tertiary butyl (tBu) groups, on the basis of synergistic effects of weak binding forces. The flexible capsule framework shows a large structural change upon guest binding to form a distorted resorcin[4]arene hexameric capsule, providing an asymmetric cavity. Location of the chiral guest inside the anisotropic environment leads to modulation of its Electric Dipole (ED) and Magnetic Dipole (MD) transition moments in the excited state, causing an increased emission quantum yield, longer emission lifetime, and enhancement of the dissymmetry factor (glum) in the circularly polarized luminescence.
Machine learning-based discovery of vibrationally stable materials
Authors: Tawfik Sherif Abdulkader , Rashid Mahad , Gupta Sunil , Russo Salvy P. , Walsh Tiffany R. , Venkatesh Svetha 
Published: January 2023

AbstractThe identification of the ground state phases of a chemical space in the convex hull analysis is a key determinant of the synthesizability of materials. Online material databases have been instrumental in exploring one aspect of the synthesizability of many materials, namely thermodynamic stability. However, the vibrational stability, which is another aspect of synthesizability, of new materials is not known. Applying first principles approaches to calculate the vibrational spectra of materials in online material databases is computationally intractable. Here, a dataset of vibrational stability for ~3100 materials is used to train a machine learning classifier that can accurately distinguish between vibrationally stable and unstable materials. This classifier has the potential to be further developed as an essential filtering tool for online material databases that can inform the material science community of the vibrational stability or instability of the materials queried in convex hulls.
An atlas of substrate specificities for the human serine/threonine kinome
Authors: Johnson Jared L. , Yaron Tomer M. , Huntsman Emily M. , Kerelsky Alexander , Song Junho , Regev Amit , Lin Ting-Yu , Liberatore Katarina , Cizin Daniel M. , Cohen Benjamin M. , Vasan Neil , Ma Yilun , Krismer Konstantin , Robles Jaylissa Torres , van de Kooij Bert , van Vlimmeren Anne E. , Andrée-Busch Nicole , Käufer Norbert F. , Dorovkov Maxim V. , Ryazanov Alexey G. , Takagi Yuichiro , Kastenhuber Edward R. , Goncalves Marcus D. , Hopkins Benjamin D. , Elemento Olivier , Taatjes Dylan J. , Maucuer Alexandre , Yamashita Akio , Degterev Alexei , Uduman Mohamed , Lu Jingyi , Landry Sean D. , Zhang Bin , Cossentino Ian , Linding Rune , Blenis John , Hornbeck Peter V. , Turk Benjamin E. , Yaffe Michael B. , Cantley Lewis C. 
Published: January 2023

AbstractProtein phosphorylation is one of the most widespread post-translational modifications in biology1,2. With advances in mass-spectrometry-based phosphoproteomics, 90,000 sites of serine and threonine phosphorylation have so far been identified, and several thousand have been associated with human diseases and biological processes3,4. For the vast majority of phosphorylation events, it is not yet known which of the more than 300 protein serine/threonine (Ser/Thr) kinases encoded in the human genome are responsible3. Here we used synthetic peptide libraries to profile the substrate sequence specificity of 303 Ser/Thr kinases, comprising more than 84% of those predicted to be active in humans. Viewed in its entirety, the substrate specificity of the kinome was substantially more diverse than expected and was driven extensively by negative selectivity. We used our kinome-wide dataset to computationally annotate and identify the kinases capable of phosphorylating every reported phosphorylation site in the human Ser/Thr phosphoproteome. For the small minority of phosphosites for which the putative protein kinases involved have been previously reported, our predictions were in excellent agreement. When this approach was applied to examine the signalling response of tissues and cell lines to hormones, growth factors, targeted inhibitors and environmental or genetic perturbations, it revealed unexpected insights into pathway complexity and compensation. Overall, these studies reveal the intrinsic substrate specificity of the human Ser/Thr kinome, illuminate cellular signalling responses and provide a resource to link phosphorylation events to biological pathways.
Dataset on child vaccination in Brazil from 1996 to 2021
Authors: Boccolini Patricia de Moraes Mello , Boccolini Cristiano Siqueira , de Almeida Relvas-Brandt Laís , Alves Ronaldo Fernandes Santos 
Published: January 2023

AbstractWe present a machine-readable and open-access dataset on vaccination results among children under five years old in Brazil from 1996 to 2021. This dataset is interoperable with epidemiological data from the VAX*SIM project and reusable by the research community worldwide for other purposes, such as monitoring vaccination coverage and studying its determinants and impacts on child morbidity and mortality. The dataset gathers official and public information from the Brazilian National Immunisation Program, the Institute of Geography and Statistics, the Institute for Applied Economic Research, and the Ministry of Health. It includes 2,442,863 observations and 35 attributes aggregated by years, policy-relevant geographic units (country, macroregions, states, municipalities, and capitals), and age groups on 1,344,480,329 doses of 28 vaccines aimed to prevent 15 diseases, estimates of their target-population coverage, indicators of the vaccination coverage’s homogeneity, dropout rates, and spatial, demographic, and socioeconomic data. We automated all data processing and curation in the free and open software R. The codes can be audited, replicated, and reused to produce alternative analyses.
Metabolomics-based study of potential biomarkers of sepsis
Authors: Li Yang , Wang Chenglin , Chen Muhu 
Published: January 2023

AbstractThe purpose of our study was to explore potential characteristic biomarkers in patients with sepsis. Peripheral blood specimens from sepsis patients and normal human volunteers were processed by liquid chromatography-mass spectrometry-based analysis. Outlier data were excluded by principal component analysis and orthogonal partial least squares-discriminant analysis using the metabolomics R software package metaX and MetaboAnalyst 5.0 (https://www.metaboanalyst.ca/home.xhtml) online analysis software, and differential metabolite counts were identified by using volcano and heatmaps. The obtained differential metabolites were combined with KEGG (Kyoto Gene and Kyoto Encyclopedia) analysis to screen out potential core differential metabolites, and ROC curves were drawn to analyze the changes in serum metabolites in sepsis patients and to explore the potential value of the metabolites in the diagnosis of sepsis patients. By metabolomic analysis, nine differential metabolites were screened for their significance in guiding the diagnosis and differential diagnosis of sepsis namely: 3-phenyl lactic acid, N-phenylacetylglutamine, phenylethylamine, traumatin, xanthine, methyl jasmonate, indole, l-tryptophan and 1107116. In this study, nine metabolites were finally screened based on metabolomic analysis and used as potential characteristic biomarkers for the diagnosis of sepsis.
Reproducibility of cerebellar involvement as quantified by consensus structural MRI biomarkers in advanced essential tremor
Authors: Wang Qing , Aljassar Meshal , Bhagwat Nikhil , Zeighami Yashar , Evans Alan C. , Dagher Alain , Pike G. Bruce , Sadikot Abbas F. , Poline Jean-Baptiste 
Published: January 2023

Abstract
Essential tremor (ET) is the most prevalent movement disorder with poorly understood etiology. Some neuroimaging studies report cerebellar involvement whereas others do not. This discrepancy may stem from underpowered studies, differences in statistical modeling or variation in magnetic resonance imaging (MRI) acquisition and processing. To resolve this, we investigated the cerebellar structural differences using a local advanced ET dataset augmented by matched controls from PPMI and ADNI. We tested the hypothesis of cerebellar involvement using three neuroimaging biomarkers: VBM, gray/white matter volumetry and lobular volumetry. Furthermore, we assessed the impacts of statistical models and segmentation pipelines on results. Results indicate that the detected cerebellar structural changes vary with methodology. Significant reduction of right cerebellar gray matter and increase of the left cerebellar white matter were the only two biomarkers consistently identified by multiple methods. Results also show substantial volumetric overestimation from SUIT-based segmentation—partially explaining previous literature discrepancies. This study suggests that current estimation of cerebellar involvement in ET may be overemphasized in MRI studies and highlights the importance of methods sensitivity analysis on results interpretation. ET datasets with large sample size and replication studies are required to improve our understanding of regional specificity of cerebellum involvement in ET.

Protocol registration
The stage 1 protocol for this Registered Report was accepted in principle on 21 March 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.19697776.
Cardiovascular risk factors in diabetic patients with and without metabolic syndrome: a study based on the Rafsanjan cohort study
Authors: Bazmandegan Gholamreza , Abbasifard Mitra , Nadimi Ali Esmaeili , Alinejad Hasan , Kamiab Zahra 
Published: January 2023

AbstractCardiovascular disease (CVD) is the leading cause of death and disability in people with diabetes mellitus (DM), since finding the correlation between DM and CVD risk factors can be effective in preventing the incidence of morbidity and mortality in patients. This study aimed to determine the prevalence of cardiovascular risk factors in people with and without metabolic syndrome (MtS) in DM. This cross-sectional study was part of the Rafsanjan Cohort Study as part of the comprehensive Persian (Prospective Epidemiological Research Studies in IRAN) on 35–70-year old adults with and without MtS in DM. Indicators of CVD risk factors, including gender, age, blood pressure, dyslipidemia, smoking, alcohol consumption, fasting blood sugar, creatinine, blood urea, waist circumference, body mass index, family history, physical inactivity, and fruit and vegetable consumption, were collected in the Persian Cohort Questionnaire. The data was analyzed by SPSS software version 22. The prevalence of MtS in 1933 participants was estimated to be 80% (95% confidence interval 78.1–81.8%). In the logistic regression model, smoking, alcohol consumption, and triglycerides were identified as the factors associated with MtS. Our results show that, based on our study, the prevalence of cardiovascular risk factors in DM was high. The suggested solutions in this field are to reduce smoking and alcohol consumption, as well as to control hypertension, hyperlipidemia, and being overweight.
Development and psychometric evaluation of public stigma of stroke scale (PSSS)
Authors: Wan Meijuan , Tan Yibing , Huang Yimin , Zhang Qishan , Qin Fengyin , Sun Xinglan , Wang Fen , Wang Jia , Zhang Xiaopei 
Published: January 2023

AbstractStroke patients suffer from public stigma because strokes cause visible disability and heavy social burden. However, existing tools measuring stroke-related stigma do not consider public stigma. The aim of this study was to develop and evaluate a public stigma of stroke scale (PSSS). This cross-sectional study recruited 730 participants, aged above 18 years, with no diagnosis of stroke before. Scale items were generated after reviewing relevant literature and conducting interviews. An expert panel evaluated the validity and reliability of a preliminary scale. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), bifactor CFA (B-CFA), Exploratory structural equation modelling (ESEM), bifactor-ESEM (B-ESEM) were performed to extract factors and evaluate fit on the factor structures. The Omega coefficient was 0.93, and the test–retest reliability coefficient was 0.721. The EFA extracted four factors: inherent ideology, aesthetic feelings, avoidance behaviour, and policy attitudes. These explained 61.57% of the total variance in the data. The four-factor model was confirmed by B-CFA, and met the fitness criteria. The PSSS yields satisfactory psychometric properties and can be used to assess stroke-related public stigma.
Comprehensive study upon physicochemical properties of bio-ZnO NCs
Authors: Król-Górniak Anna , Railean Viorica , Pomastowski Paweł , Płociński Tomasz , Gloc Michał , Dobrucka Renata , Kurzydłowski Krzysztof Jan , Buszewski Bogusław 
Published: January 2023

AbstractIn this study, for the first time, the comparison of commercially available chemical ZnO NCs and bio-ZnO NCs produced extracellularly by two different probiotic isolates (Latilactobacillus curvatusMEVP1 [OM736187] andLimosilactobacillus fermentum MEVP2 [OM736188]) were performed. All types of ZnO formulations were characterized by comprehensive interdisciplinary approach including various instrumental techniques in order to obtain nanocomposites with suitable properties for further applications, i.e. biomedical. Based on the X- ray diffraction analysis results, all tested nanoparticles exhibited the wurtzite structure with an average crystalline size distribution of 21.1 nm (CHEM_ZnO NCs), 13.2 nm (1C_ZnO NCs) and 12.9 nm (4a_ZnO NCs). The microscopy approach with use of broad range of detectors (SE, BF, HAADF) revealed the core–shell structure of bio-ZnO NCs, compared to the chemical one. The nanoparticles core of 1C and 4a_ZnO NCs are coated by the specific organic deposit coming from the metabolites produced by two probiotic strains,L. fermentumandL. curvatus. Vibrational infrared spectroscopy, photoluminescence (PL) and mass spectrometry (LDI-TOF-MS) have been used to monitor the ZnO NCs surface chemistry and allowed for better description of bio-NCs organic coating composition (amino acids residues). The characterized ZnO formulations were then assessed for their photocatalytic properties against methylene blue (MB). Both types of bio-ZnO NCs exhibited good photocatalytic activity, however, the effect of CHEM_ZnO NCs was more potent than bio-ZnO NCs. Finally, the colloidal stability of the tested nanoparticles were investigated based on the zeta potential (ZP) and hydrodynamic diameter measurements in dependence of the nanocomposites concentration and investigation time. During the biosynthesis of nano-ZnO, the increment of pH from 5.7 to around 8 were observed which suggested possible contribution of zinc aquacomplexes and carboxyl-rich compounds resulted in conversion of zinc tetrahydroxy ion complex to ZnO NCs. Overall results in present study suggest that used accessible source such us probiotic strains,L. fermentumandL. curvatus, for extracellular bio-ZnO NCs synthesis are of high interest. What is important, no significant differences between organic deposit (e.g. metabolites) produced by tested strains were noticed—both of them allowed to form the nanoparticles with natural origin coating. In comparison to chemical ZnO NCs, those synthetized via microbiological route are promising material with further biological potential once have shown high stability during 7 days.
Hybrid mesh for magnetotelluric forward modeling based on the finite element method
Authors: Yu Nian , Wu Xialan , Liu Xinyu , Li Ruiheng , Zhang Hongye , Gao Lei 
Published: January 2023

AbstractUnstructured tetrahedral grids have been applied in magnetotelluric (MT) forward modeling using the finite element (FE) method because of their adaptability to complex anomalies. However, high-quality results require an extreme refinement of the near-surface area, which leads to excessive meshes and an increased degree of freedom (DoF) of the governing equation of the finite element system. To reduce the computational cost, we have developed a hybrid mesh based on triangular prisms and tetrahedrons. The required elements in the near-surface area are reduced because the quality of the triangular prism is not limited by the element aspect ratio. The deep area is discretized by tetrahedral elements to ensure the flexibility of the unstructured grids. The superiority of this hybrid mesh has been tested on a layered model, the DTM1 model and terrain relief models. The results show that the modeling efficiency has been improved, especially for high-frequency data. The accuracy of the modeling using the hybrid mesh is significantly higher than that of the tetrahedral mesh with a similar DoF. Usage of the hybrid mesh can be easily adapted to complex geoelectric models with strong terrain fluctuations, which requires less computational cost than using conventional unstructured elements.
Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
Authors: Kaefer Martin , Rink Richard , Misseri Rosalia , Winchester Paul , Proctor Cathy , Ben Maamar Millissia , Beck Daniel , Nilsson Eric , Skinner Michael K. 
Published: January 2023

AbstractAbnormal penile foreskin development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. A number of environmental factors have been shown to be associated with hypospadias development. The current study investigated the role of epigenetics in the etiology of hypospadias and compared mild (distal), moderate (mid shaft), and severe (proximal) hypospadias. Penile foreskin samples were collected from hypospadias and non-hypospadias individuals to identify alterations in DNA methylation associated with hypospadias. Dramatic numbers of differential DNA methylation regions (DMRs) were observed in the mild hypospadias, with reduced numbers in moderate and low numbers in severe hypospadias. Atresia (cell loss) of the principal foreskin fibroblast is suspected to be a component of the disease etiology. A genome-wide (> 95%) epigenetic analysis was used and the genomic features of the DMRs identified. The DMR associated genes identified a number of novel hypospadias associated genes and pathways, as well as genes and networks known to be involved in hypospadias etiology. Observations demonstrate altered DNA methylation sites in penile foreskin is a component of hypospadias etiology. In addition, a potential role of environmental epigenetics and epigenetic inheritance in hypospadias disease etiology is suggested.
Inhibition of the TRIM24 bromodomain reactivates latent HIV-1
Authors: Horvath Riley M. , Brumme Zabrina L. , Sadowski Ivan 
Published: January 2023

AbstractExpression of the HIV-1 genome by RNA Polymerase II is regulated at multiple steps, as are most cellular genes, including recruitment of general transcription factors and control of transcriptional elongation from the core promoter. We recently discovered that tripartite motif protein TRIM24 is recruited to the HIV-1 Long Terminal Repeat (LTR) by interaction with TFII-I and causes transcriptional elongation by stimulating association of PTEF-b/ CDK9. Because TRIM24 is required for stimulation of transcription from the HIV-1 LTR, we were surprised to find that IACS-9571, a specific inhibitor of the TRIM24 C-terminal bromodomain, induces HIV-1 provirus expression in otherwise untreated cells. IACS-9571 reactivates HIV-1 in T cell lines bearing multiple different provirus models of HIV-1 latency. Additionally, treatment with this TRIM24 bromodomain inhibitor encourages productive HIV-1 expression in newly infected cells and inhibits formation of immediate latent transcriptionally repressed provirus. IACS-9571 synergizes with PMA, ionomycin, TNF-α and PEP005 to activate HIV-1 expression. Furthermore, co-treatment of CD4 + T cells from individuals with HIV-1 on antiretroviral therapy (ART) with PEP005 and IACS-9571 caused robust provirus expression. Notably, IACS-9571 did not cause global activation of T cells; rather, it inhibited induction of IL2 and CD69 expression in human PBMCs and Jurkat T cells treated with PEP005 or PMA. These observations indicate the TRIM24 bromodomain inhibitor IACS-9571 represents a novel HIV-1 latency reversing agent (LRA), and unlike other compounds with this activity, causes partial suppression of T cell activation while inducing expression of latent provirus.