bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/β-catenin signaling contributes to articular cartilage homeostasis through lubricin induction in the superficial zone
Authors: Xuan Fengjun , Yano Fumiko , Mori Daisuke , Chijimatsu Ryota , Maenohara Yuji , Nakamoto Hideki , Mori Yoshifumi , Makii Yuma , Oichi Takeshi , Taketo Makoto Mark , Hojo Hironori , Ohba Shinsuke , Chung Ung-il , Tanaka Sakae , Saito Taku 
Published: November 2019

AbstractBackgroundBoth loss- and gain-of-function of Wnt/β-catenin signaling in chondrocytes result in exacerbation of osteoarthritis (OA). Here, we examined the activity and roles of Wnt/β-catenin signaling in the superficial zone (SFZ) of articular cartilage.MethodsWnt/β-catenin signaling activity was analyzed using TOPGAL mice. We generatedPrg4-CreERT2;Ctnnb1fl/flandPrg4-CreERT2;Ctnnb1-ex3fl/wtmice for loss- and gain-of-function, respectively, of Wnt/β-catenin signaling in the SFZ. Regulation of Prg4 expression by Wnt/β-catenin signaling was examined in vitro, as were upstream and downstream factors of Wnt/β-catenin signaling in SFZ cells.ResultsWnt/β-catenin signaling activity, as determined by the TOPGAL reporter, was high specifically in the SFZ of mouse adult articular cartilage, where Prg4 is abundantly expressed. In SFZ-specific β-catenin-knockout mice, OA development was significantly accelerated, which was accompanied by decreased Prg4 expression and SFZ destruction. In contrast, Prg4 expression was enhanced and cartilage degeneration was suppressed in SFZ-specific β-catenin-stabilized mice. In primary SFZ cells, Prg4 expression was downregulated by β-catenin knockout, while it was upregulated by β-catenin stabilization by exon 3 deletion or treatment with CHIR99021. Among Wnt ligands, Wnt5a, Wnt5b, and Wnt9a were highly expressed in SFZ cells, and recombinant human WNT5A and WNT5B stimulated Prg4 expression. Mechanical loading upregulated expression of these ligands and further promoted Prg4 transcription. Moreover, mechanical loading and Wnt/β-catenin signaling activation increased mRNA levels ofCreb1, a potent transcription factor forPrg4.ConclusionsWe demonstrated that Wnt/β-catenin signaling regulates Prg4 expression in the SFZ of mouse adult articular cartilage, which plays essential roles in the homeostasis of articular cartilage.
Contribution of adipocyte precursors in the phenotypic specificity of intra-articular adipose tissues in knee osteoarthritis patients
Authors: Eymard Florent , Pigenet Audrey , Rose Cindy , Bories Anouchka , Flouzat-Lachaniette Charles-Henri , Berenbaum Francis , Chevalier Xavier , Houard Xavier , Nourissat Geoffroy 
Published: November 2019

Abstract
Background
Intra-articular adipose tissues (IAATs) are involved in osteoarthritis (OA) pathophysiology. We hypothesize that mesenchymal cells residing in IAATs may account for the specific inflammatory and metabolic patterns in OA patients.

Methods
Adipocyte precursors (preadipocytes and dedifferentiated fat cells (DFATc)) from IAATs (infrapatellar and suprapatellar fat pads) and autologous subcutaneous adipose tissues (SCATs) were isolated from knee OA patients. The ability of these precursors to differentiate into adipocytes was assessed by oil red O staining after 14 days of culture in adipogenic medium. The gene expression of adipocyte-related transcription factors (C/EBP-α and PPAR-γ) and development-related factors (EN1 and SFRP2) were analyzed. The inflammatory pattern was assessed by RT-qPCR and ELISA (interleukin 6 (IL-6), IL-8, Cox2, and prostaglandin E2 (PGE2)) after a 24-h stimulation by IL-1β (1 ng/mL) and by conditioned medium from OA synovium.

Results
IAAT preadipocytes displayed a significantly higher ability to differentiate into adipocytes and expressed significantly more C/EBP-α mRNA than SCAT preadipocytes. IAAT preadipocytes expressed significantly less EN-1 and SFRP2 mRNA than SCAT preadipocytes. Unstimulated IAAT preadipocytes displayed a less inflammatory pattern (IL-6, IL-8, and Cox2/PGE2) than SCAT preadipocytes. In contrast, the response of IAAT preadipocytes to an inflammatory stimulus (IL-1β and conditioned media of OA synovium) was exacerbated compared to that of SCAT preadipocytes. Similar results were obtained with DFATc.

Conclusion
IAAT adipocyte precursors from OA patients have a specific phenotype, which may account for the unique phenotype of OA IAATs. The exacerbated response of IAAT preadipocytes to inflammatory stimulation may contribute to OA pathophysiology.
Dataset for file fragment classification of image file formats
Authors: Fakouri Reyhane , Teimouri Mehdi 
Published: November 2019

Abstract
Objectives
File fragment classification of image file formats is a topic of interest in network forensics. There are a few publicly available datasets of files with image formats. Therewith, there is no public dataset for file fragments of image file formats. So, a big research challenge in file fragment classification of image file formats is to compare the performance of the developed methods over the same datasets.

Data description
In this study, we present a dataset that contains file fragments of ten image file formats: Bitmap, Better Portable Graphics, Free Lossless Image Format, Graphics Interchange Format, Joint Photographic Experts Group, Joint Photographic Experts Group 2000, Joint Photographic Experts Group Extended Range, Portable Network Graphic, Tagged Image File Format, and Web Picture. Corresponding to each format, the dataset contains the file fragments of image files with different compression settings. For each pair of file format and compression setting, 800 file fragments are provided. Totally, the dataset contains 25,600 file fragments.
Alzheimer’s disease-associated (hydroxy)methylomic changes in the brain and blood
Authors: Lardenoije Roy , Roubroeks Janou A. Y. , Pishva Ehsan , Leber Markus , Wagner Holger , Iatrou Artemis , Smith Adam R. , Smith Rebecca G. , Eijssen Lars M. T. , Kleineidam Luca , Kawalia Amit , Hoffmann Per , Luck Tobias , Riedel-Heller Steffi , Jessen Frank , Maier Wolfgang , Wagner Michael , Hurlemann René , Kenis Gunter , Ali Muhammad , del Sol Antonio , Mastroeni Diego , Delvaux Elaine , Coleman Paul D. , Mill Jonathan , Rutten Bart P. F. , Lunnon Katie , Ramirez Alfredo , van den Hove Daniël L. A. 
Published: November 2019

Abstract
Background
Late-onset Alzheimer’s disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD.

Results
We identified epigenetic differences in AD patients (n = 45) as compared to age-matched controls (n = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (− 3.76% 5mC, pŠidák = 1.07E−06), CHRNB1 (+ 1.46% 5hmC, pŠidák = 4.01E−04), RHBDF2 (− 3.45% UC, pŠidák = 4.85E−06), and C3 (− 1.20% UC, pŠidák = 1.57E−03). In parallel, in an independent cohort, we compared the blood methylome of converters to AD dementia (n = 54) and non-converters (n = 42), at a preclinical stage. DNA methylation in the same region of the OXT promoter as found in the brain was found to be associated with subsequent conversion to AD dementia in the blood of elderly, non-demented individuals (+ 3.43% 5mC, pŠidák = 7.14E−04).

Conclusions
The implication of genome-wide significant differential methylation of OXT, encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.
Histone methyltransferases EHMT1 and EHMT2 (GLP/G9A) maintain PARP inhibitor resistance in high-grade serous ovarian carcinoma
Authors: Watson Zachary L. , Yamamoto Tomomi M. , McMellen Alexandra , Kim Hyunmin , Hughes Connor J. , Wheeler Lindsay J. , Post Miriam D. , Behbakht Kian , Bitler Benjamin G. 
Published: November 2019

AbstractBackgroundEuchromatic histone-lysine-N-methyltransferases 1 and 2 (EHMT1/2, aka GLP/G9A) catalyze dimethylation of histone H3 lysine 9 (H3K9me2) and have roles in epigenetic silencing of gene expression. EHMT1/2 also have direct roles in DNA repair and are implicated in chemoresistance in several cancers. Resistance to chemotherapy and PARP inhibitors (PARPi) is a major cause of mortality in high-grade serous ovarian carcinoma (HGSOC), but the contribution of the epigenetic landscape is unknown.ResultsTo identify epigenetic mechanisms of PARPi resistance in HGSOC, we utilized unbiased exploratory techniques, including RNA-Seq and mass spectrometry profiling of histone modifications. Compared to sensitive cells, PARPi-resistant HGSOC cells display a global increase of H3K9me2 accompanied by overexpression of EHMT1/2. EHMT1/2 overexpression was also observed in a PARPi-resistant in vivo patient-derived xenograft (PDX) model. Genetic or pharmacologic disruption of EHMT1/2 sensitizes HGSOC cells to PARPi. Cell death assays demonstrate that EHMT1/2 disruption does not increase PARPi-induced apoptosis. Functional DNA repair assays show that disruption of EHMT1/2 ablates homologous recombination (HR) and non-homologous end joining (NHEJ), while immunofluorescent staining of phosphorylated histone H2AX shows large increases in DNA damage. Propidium iodide staining and flow cytometry analysis of cell cycle show that PARPi treatment increases the proportion of PARPi-resistant cells in S and G2 phases, while cells treated with an EHMT1/2 inhibitor remain in G1. Co-treatment with PARPi and EHMT1/2 inhibitor produces an intermediate phenotype. Immunoblot of cell cycle regulators shows that combined EHMT1/2 and PARP inhibition reduces expression of specific cyclins and phosphorylation of mitotic markers. These data suggest DNA damage and altered cell cycle regulation as mechanisms of sensitization. RNA-Seq of PARPi-resistant cells treated with EHMT1/2 inhibitor showed significant gene expression changes enriched in pro-survival pathways that remain unexplored in the context of PARPi resistance, including PI3K, AKT, and mTOR.ConclusionsThis study demonstrates that disrupting EHMT1/2 sensitizes HGSOC cells to PARPi, and suggests a potential mechanism through DNA damage and cell cycle dysregulation. RNA-Seq identifies several unexplored pathways that may alter PARPi resistance. Further study of EHMT1/2 and regulated genes will facilitate development of novel therapeutic strategies to successfully treat HGSOC.
Proteomic features characterization of Hymenoptera venom allergy
Authors: Matuszewska Eliza , Matysiak Joanna , Bręborowicz Anna , Olejniczak Katarzyna , Kycler Zdzisława , Kokot Zenon J. , Matysiak Jan 
Published: November 2019

Abstract
Background
Hymenoptera venom allergy is one of the most frequent causes of anaphylaxis. In its most severe form, the reaction to wasp and honey bee stings may be life-threatening. Therefore, immediate and proper diagnosis of venom allergy and implementation of suitable therapy are extremely important. Broadening the knowledge on the mechanism of the allergic reaction may contribute to the improvement of both diagnostic and treatment methods. Thus, this study aimed to discover changes in protein expression in serum of patients allergic to Hymenoptera (wasp and honeybee) venom and to point out proteins and peptides involved in the allergic inflammation.

Methods
Serum proteomic patterns typical to allergic patients and healthy volunteers were obtained with MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) mass spectrometer. The spectra were processed, analyzed and compared using advanced bioinformatics tools. The discriminative peaks were subjected to identification with liquid chromatography coupled with tandem mass spectrometry.

Results
This methodology allowed for the identification of four features differentiating between allergy and control groups. They were: fibrinogen alpha chain, coagulation factor XIII chain A, complement C4-A, and inter-alpha-trypsin inhibitor heavy chain H4. All of these proteins are involved in allergic inflammatory response.

Conclusions
Extending the knowledge of the Hymenoptera venom sensitization will contribute to the development of novel, sensitive and specific methods for quick and unambiguous allergy diagnosis. Understanding the basis of the allergy at the proteomic level will support the improvement of preventive and therapeutic measures.
Does unified allergic airway disease impact on lung function and type 2 biomarkers?
Authors: Kuo Chris RuiWen , Chan Rory , Lipworth Brian 
Published: November 2019

AbstractThe concept of the unified allergic airway disease (UAD) recognises the association between allergic inflammation in the upper and lower airways. Patients with asthma and concomitant allergic rhinitis experience more asthma-related primary and secondary care visits. We therefore aimed to determine differences in asthma control (asthma control questionnaire ACQ-6), lung function (spirometry) and T2 biomarkers (FeNO and Eos) in relation to the presence of allergic rhinitis in patients with allergic asthma. Retrospectively, we evaluated a cohort of 60 consecutive patients with persistent asthma attending our research unit for screening into clinical trials. All included subjects were receiving inhaled corticosteroids (ICS) and had a positive skin prick test (SPT) to at least one common aeroallergen to fulfil the criterion of allergic asthma. Patients with UAD had a diagnosis of allergic asthma in addition to established concomitant allergic rhinitis. T2 biomarkers were significantly higher in patients with allergic rhinitis in contrast to those without. FEV1 % predicted and FEF25-75 % predicted were also significantly lower in patients with concomitant allergic rhinitis. However, there was no difference in ACQ-6 observed between groups. In summary, patients with allergic asthma, the presence of concomitant allergic rhinitis is associated with worse lung function and higher type 2 biomarkers.
Type A insulin resistance syndrome misdiagnosed as polycystic ovary syndrome: a case report
Authors: Lin Lu , Chen Cunren , Fang Tuanyu , Chen Daoxiong , Chen Kaining , Quan Huibiao 
Published: November 2019

Abstract
Background
Type A insulin resistance syndrome, one type of the hereditary insulin resistance syndromes, is a rare disorder. Patients with type A insulin resistance syndrome are nonobese and demonstrate severe hyperinsulinemia, hyperandrogenism, and acanthosis nigricans. The clinical features are more severe in affected females than in males, and they mostly become apparent at the age of puberty. In many cases, when severe insulin resistance is covered up by other signs or symptoms of type A insulin resistance syndrome, patients are often easily misdiagnosed with other diseases, such as polycystic ovary syndrome.

Case presentation
Our patient was a 27-year-old Han Chinese woman who sought treatment because of a menstrual disorder and hirsutism. Tests showed that her levels of insulin and testosterone were elevated, and gynecological color Doppler ultrasound suggested multiple cystic changes in the bilateral ovaries. After a diagnosis of polycystic ovary syndrome was made, pulsatile gonadotropin-releasing hormone therapy and metformin were administered, but the patient’s symptoms did not improve in 1 year of follow-up. Considering that the previous diagnosis might have been incorrect, venous blood samples were collected from the patient and her relatives for genetic analysis. Subsequently, using Illumina sequencing, it was found that the proband, her father, and two brothers all had the c.3601C>T heterozygous missense mutation in exon 20 of the insulin receptor gene. The diagnosis was corrected to type A insulin resistance syndrome, and the patient’s treatment was modified.

Conclusion
We report a case of a young woman with type A insulin resistance syndrome that was misdiagnosed as polycystic ovary syndrome. We discuss the causes, clinical features, diagnosis, and treatment of type A insulin resistance syndrome to improve the recognition of the disease and reduce its misdiagnosis. Female patients with high androgen levels and severe hyperinsulinemia should be considered for the possibility of hereditary insulin resistance syndromes (such as type A insulin resistance syndrome). Gene sequencing helps in making an early diagnosis and developing a targeted treatment strategy.
Comparison of uterine fibroids’ growth pattern during pregnancy according to fetal sex: an observational study
Authors: Delli Carpini Giovanni , Verdecchia Valeria , Papiccio Maria , Grelloni Camilla , Ciavattini Andrea 
Published: November 2019

Abstract
Background
To investigate the effect of fetal sex on fibroids’ growth during pregnancy according to the hCG serum levels

Methods
Observational study conducted from January 2007 to December 2016 on women with ultrasound identification of uterine fibroids who had a pregnancy within 1 year from diagnosis. The fibroids diameter was determined during the pre-pregnancy ultrasound, early first trimester (5–7 weeks), late first trimester (11–13 weeks), second trimester (19–21 weeks), and third trimester (31–33 weeks). The diameter growth was calculated in each interval between two ultrasounds. The hCG serum levels were determined both in early and late first trimester. The correlation between hCG levels and fibroid diameter was evaluated. Obstetric outcomes collected were gestational weeks at birth and the rate of cesarean section. Neonatal outcomes were birthweight and Apgar score at 1 min.

Results
Eighty-seven of the included women had a male fetus, and 70 had a female fetus. A progressive increase of fibroid diameter was observed from pre-pregnancy to second trimester for both fetal sexes. In third trimester, the mean ± SD fibroid diameter of female fetuses showed a slowdown, while the mean ± SD fibroid diameter of male fetuses continued to grow. Women carrying a female fetus presented a higher fibroid diameter in early first trimester (33.5 ± 13.3 mm vs 27.4 ± 11.0 mm, p < 0.01), late first trimester (40.2 ± 13.9 mm vs 34.6 ± 11.7 mm, p < 0.01), and second trimester (40.5 ± 14.9 mm vs 34.7 ± 10.3 mm, p < 0.01). The hCG serum levels resulted higher in women with a female fetus: 61406 (50554-71760) mU/ml vs 46016 (37160-56744) mU/ml (p < 0.01). A positive correlation between hCG levels and fibroid diameter was found both for male and female fetuses (male r = 0.77, 95% CI 0.71–0.82, p < 0.01 and female r = 0.82, 95% CI 0.76–0.86, p < 0.01).

Conclusion
Women with female fetus seem to have a higher growth of fibroids up to second trimester of pregnancy. This process may be mediated by the higher serum hCG levels found in women expecting a female fetus.
Reduced expression of miR-146a in human bronchial epithelial cells alters neutrophil migration
Authors: Kivihall Anet , Aab Alar , Soja Jerzy , Sładek Krzysztof , Sanak Marek , Altraja Alan , Jakiela Bogdan , Bochenek Grazyna , Rebane Ana 
Published: November 2019

AbstractBackgroundThe role of miRNAs in the pathogenesis and determining the phenotypes of asthma is not fully elucidated. miR-146a has been previously shown to suppress inflammatory responses in different cells. In this study, we investigated the functions of miR-146a in human bronchial epithelial cells (HBECs) in association with neutrophilic, eosinophilic, and paucigranulocytic phenotypes of asthma.MethodsBronchial brushing specimens and brochial mucosal biopsy samples were collected from adult patients with asthma and from age- and gender-matched non-asthmatic individuals. The expression of miR-146a in bronchial brushing specimens, bronchial biopsy tissue sections or cultured primary bronchial epithelial cells was analyzed by RT-qPCR or by in situ hybridization. The expression of direct and indirect miR-146a target genes was determined by RT-qPCR or ELISA. The migration of neutrophils was studied by neutrophil chemotaxis assay and flow cytometry. For statistical analysis, unpaired two-way Student’sttest, one-way ANOVA or linear regression analysis were used.ResultsReduced expression of miR-146a was found in bronchial brushing specimens from asthma patients as compared to non-asthmatics and irrespective of the phenotype of asthma. In the same samples, the neutrophil attracting chemokines IL-8 and CXCL1 showed increased expression in patients with neutrophilic asthma and increased IL-33 expression was found in patients with eosinophilic asthma. Linear regression analysis revealed a significant negative association between the expression of miR-146a in bronchial brushings and neutrophil cell counts in bronchoalveolar lavage fluid of patients with asthma. In bronchial biopsy specimens, the level of miR-146a was highest in the epithelium as determined with in situ hybridization. In primary conventional HBEC culture, the expression of miR-146a was induced in response to the stimulation with IL-17A, TNF-α, and IL-4. The mRNA expression and secretion of IL-8 and CXCL1 was inhibited in both stimulated and unstimulated HBECs transfected with miR-146a mimics. Supernatants from HBECs transfected with miR-146a had reduced capability of supporting neutrophil migration in neutrophil chemotaxis assay.ConclusionOur results suggest that decreased level of miR-146a in HBECs from patients with asthma may contribute to the development of neutrophilic phenotype of asthma.