bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of G9a does not phenocopy the requirement for Prdm12 in the development of the nociceptive neuron lineage
Authors: Tsimpos Panagiotis , Desiderio Simon , Cabochette Pauline , Poelvoorde Philippe , Kricha Sadia , Vanhamme Luc , Poulard Coralie , Bellefroid Eric J. 
Published: January 2024

AbstractPrdm12 is an epigenetic regulator expressed in developing and mature nociceptive neurons, playing a key role in their specification during neurogenesis and modulating pain sensation at adulthood. In vitro studies suggested that Prdm12 recruits the methyltransferase G9a through its zinc finger domains to regulate target gene expression, but how Prdm12 interacts with G9a and whether G9a plays a role in Prdm12’s functional properties in sensory ganglia remain unknown. Here we report that Prdm12-G9a interaction is likely direct and that it involves the SET domain of G9a. We show that both proteins are largely co-expressed in dorsal root ganglia during early murine development, opening the possibility that G9a plays a role in DRG and may act as a mediator of Prdm12’s function in the development of nociceptive sensory neurons. To test this hypothesis, we conditionally inactivated G9a in neural crest using a Wnt1-Cre transgenic mouse line. We found that the specific loss of G9a in the neural crest lineage does not lead to dorsal root ganglia hypoplasia due to the loss of somatic nociceptive neurons nor to the ectopic expression of the visceral determinant Phox2b as observed upon Prdm12 ablation. These findings suggest that Prdm12 function in the initiation of the nociceptive lineage does not critically involves its interaction with G9a.
Discovery of dual rho-associated protein kinase 1 (ROCK1)/apoptosis signal–regulating kinase 1 (ASK1) inhibitors as a novel approach for non-alcoholic steatohepatitis (NASH) treatment
Authors: Zaky Yara A. , Rashad Mai W. , Zaater Marwa A. , El Kerdawy Ahmed M. 
Published: January 2024

AbstractIn the current study we suggest a novel approach to curb non-alcoholic steatohepatitis (NASH) progression, and we suggest privileged scaffolds for the design of novel compounds for this aim. NASH is an advanced form of non-alcoholic fatty liver disease that can further progress into fibrosis, cirrhosis, and hepatocellular carcinoma. It is a widely emerging disease affecting 25% of the global population and has no current approved treatments. Protein kinases are key regulators of cellular pathways, of which, Rho-associated protein kinase 1 (ROCK1) and apoptosis signal–regulating kinase 1 (ASK1) play an important role in the progression of NASH and they stand out as promising targets for NASH therapy. Interestingly, their kinase domains are found to be similar in sequence and topology; therefore, dual inhibition of ROCK1 and ASK1 is expected to be amenable and could achieve a more favourable outcome. To reach this goal, a training set of ROCK1 and ASK1 protein structures co-crystalized with type 1 (ATP-competitive) inhibitors was constructed to manually generate receptor-based pharmacophore models representing ROCK1 and ASK1 inhibitors’ common pharmacophoric features. The models produced were assessed using a test set of both ROCK1 and ASK1 actives and decoys, and their performance was evaluated using different assessment metrics. The best pharmacophore model obtained, showing a Mathew’s correlation coefficient (MCC) of 0.71, was then used to screen the ZINC purchasable database retrieving 6178 hits that were filtered accordingly using several medicinal chemistry and pharmacokinetics filters returning 407 promising compounds. To confirm that these compounds are capable of binding to the target kinases, they were subjected to molecular docking simulations at both protein structures. The results were then assessed individually and filtered, setting the spotlight on various privileged scaffolds that could be exploited as the nucleus for designing novel ROCK1/ASK1 dual inhibitors.
A chemometric approach based on response surface methodology for optimization of antibiotic and organic dyes removal from water samples
Authors: Hsu Chou-Yi , Ali Eyhab , Al-Saedi Haider Falih Shamikh , Mohammed Amjed Qasim , Mustafa Nadia Khalid , Talib Maysm Barzan , Radi Usama Kadem , Ramadan Montather F. , Ami Ahmed Ali , Al-Shuwaili Saeb Jasim , Alawadi Ahmed , Alsalamy Ali , Baharinikoo Leila 
Published: January 2024

AbstractIn this study, the Fe3O4/rGO/Ag magnetic nanocomposite was synthesized and employed as an adsorbent for the removal of tetracycline (TC), crystal violet (CV), and methylene blue (MB) from water samples. The influential parameters in the removal process were identified and optimized using response surface methodology (RSM). Characterization of the product was performed through field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), vibrating-sample magnetometer (VSM), and X-ray diffraction (XRD) analysis. XRD and SEM analysis revealed the successful synthesis of the Fe3O4/rGO/Ag nanocomposite. EDX analysis elucidated the accuracy and clarity of the chemical composition of the magnetic nanocomposite structure. Additionally, the separation of the nano-adsorbent from the solution can be achieved using a magnetic field. Maximum removal of analytes was obtained at pH of 6, amount of nanocomposite 0.014 g, ultrasonic time of 8 min and concentration of 21 mg L−1. Under optimal conditions, the removal efficiencies for TC, CV, and MB were 91.33, 95.82, and 98.19%, respectively. Also, it was observed that after each adsorption–desorption cycle, Fe3O4/rGO/Ag magnetic nanocomposite had good stability to remove TC, CV, and MB. Achieving nearly 98% removal efficiency in optimal conditions showed that Fe3O4/rGO/Ag magnetic nanocomposite is an effective adsorbent for removing TC, CV, and MB from wastewater samples.
Monocyte-derived transcriptomes explain the ineffectiveness of abatacept in rheumatoid arthritis
Authors: Iwasaki Takeshi , Watanabe Ryu , Ito Hiromu , Fujii Takayuki , Ohmura Koichiro , Yoshitomi Hiroyuki , Murata Koichi , Murakami Kosaku , Onishi Akira , Tanaka Masao , Matsuda Shuichi , Matsuda Fumihiko , Morinobu Akio , Hashimoto Motomu 
Published: January 2024

Abstract
Background
The biological mechanisms underlying the differential response to abatacept in patients with rheumatoid arthritis (RA) are unknown. Here, we aimed to identify cellular, transcriptomic, and proteomic features that predict resistance to abatacept in patients with RA.

Methods
Blood samples were collected from 22 RA patients treated with abatacept at baseline and after 3 months of treatment. Response to treatment was defined by the European League Against Rheumatism (EULAR) response criteria at 3 months, and seven patients were classified as responders and the others as non-responders. We quantified gene expression levels by RNA sequencing, 67 plasma protein levels, and the expression of surface molecules (CD3, 19, and 56) by flow cytometry. In addition, three gene expression data sets, comprising a total of 27 responders and 50 non-responders, were used to replicate the results.

Results
Among the clinical characteristics, the number of monocytes was significantly higher in the non-responders before treatment. Cell type enrichment analysis showed that differentially expressed genes (DEGs) between responders and non-responders were enriched in monocytes. Gene set enrichment analysis, together with single-cell analysis and deconvolution analysis, identified that Toll-like receptor 5 (TLR5) and interleukin-17 receptor A (IL17RA) pathway in monocytes was upregulated in non-responders. Hepatocyte growth factor (HGF) correlated with this signature showed higher concentrations in non-responders before treatment. The DEGs in the replication set were also enriched for the genes expressed in monocytes, not for the TLR5 and IL17RA pathway but for the oxidative phosphorylation (OXPHOS) pathway.

Conclusions
Monocyte-derived transcriptomic features before treatment underlie the differences in abatacept efficacy in patients with RA. The pathway activated in monocytes was the TLR5 and IL17RA-HGF signature in the current study, while it was the OXPHOS pathway in the replication set. Elevated levels of HGF before treatment may serve as a potential biomarker for predicting poor responses to abatacept. These findings provide insights into the biological mechanisms of abatacept resistance, contributing valuable evidence for stratifying patients with RA.
Clinical characteristics of hypertrophic cranial pachymeningitis in granulomatosis with polyangiitis: a retrospective single-center study in China
Authors: Chen Yiran , Gou Lijuan , Wang Li , Qian Min , Wu Qingjun , Zheng Wenjie , Li Mengtao , Zeng Xiaofeng , Zhang Fengchun 
Published: January 2024

Abstract
Background
Hypertrophic cranial pachymeningitis (HCP) is uncommon but a poorly understood complication of granulomatosis with polyangiitis (GPA).

Objectives
We conducted this retrospective study to elucidate the clinical characteristics and factors independently associated with granulomatosis with polyangiitis (GPA) complicated by hypertrophic cranial pachymeningitis (HCP) in China.

Methods
We collected the medical records of 78 patients diagnosed with GPA who were admitted to the inpatient department of Peking Union Medical College Hospital between January 2003 and September 2021. Clinical features, laboratory and radiological findings, and Birmingham Vasculitis Activity Scores (excluding meningitis score) were recorded. A binary logistic regression analysis was performed to analyze factors independently associated with GPA-related HCP.

Results
Headache (100%) and cranial nerve palsy (61.5%) were common manifestations of HCP. Compared to 52 GPA patients without HCP, 26 patients with HCP required more time from initial symptoms to diagnosis, with a lower ratio of pulmonary and renal involvement, a higher ratio of myeloperoxidase–antineutrophil cytoplasmic antibody (MPO-ANCA) positivity, conductive or sensorineural hearing loss, mastoiditis, and decreased vision or sudden visual loss. Binary logistic regression analysis indicated that proteinase 3–antineutrophil cytoplasmic antibody (PR3-ANCA) negativity (OR 10.698, p = 0.001), conductive or sensorineural hearing loss (OR 10.855, p = 0.005), and decreased vision or sudden visual loss (OR 8.647, p = 0.015) were significantly associated with GPA-related HCP. Of the 26 patients, 18 received methylprednisolone pulse treatment, and 18 received intrathecal injections of dexamethasone and methotrexate.

Conclusions
HCP was a severe manifestation of GPA in our study. Independent factors associated with the occurrence of HCP in patients with GPA included PR3-ANCA negativity, conductive or sensorineural hearing loss, and decreased vision or sudden visual loss. Furthermore, GPA-related HCP was associated with higher disease activity, requiring more intensive treatments.
Evaluating the reliability of the athlete sleep behavior questionnaire (ASBQ): a meta-analysis of Cronbach’s alpha and intraclass correlation coefficient
Authors: Trabelsi Khaled , Saif Zahra , Driller Matthew W , Vitiello Michael V. , Jahrami Haitham 
Published: January 2024

Abstract
Background
The Athlete Sleep Behavior Questionnaire (ASBQ) was designed to identify maladaptive sleep practices among athletes. The aim of this meta-analysis was to evaluate the internal consistency and the test-retest reliability coefficients of the ASBQ.

Methods
A systematic search across 10 databases from inception of the ASBQ to August 2023 was performed. Publications that reported estimates of internal consistency and/or test-retest reliability of the ASBQ were included. A random-effects model was employed to estimate the overall reliability measures of the ASBQ.

Results
Meta-analytic results demonstrated a good level of internal consistency within the ASBQ, evidenced by a Cronbach’s alpha of 0.73 (95% CI: 0.63 to 0.80). This suggests a modest correlation among the questionnaire items, supporting its reliability as an effective measure of sleep behavior. In terms of test-retest reliability, our meta-analysis revealed a very good degree of consistency (ICC = 0.88; 95% CI: 0.87 to 0.89), suggesting that the ASBQ can serve as an instrument for monitoring and evaluating changes in athletes’ sleep behavior over time. No evidence of publication bias was identified.

Conclusion
While the ASBQ demonstrates a moderate level of internal consistency, its test-retest reliability suggests that it can serve as an instrument for longitudinal assessments of athletes’ sleep behavior. Future studies focusing on refining the ASBQ to optimize its internal consistency and validate its applicability across diverse athletic populations are warranted.
Identification of transcriptional networks controlling leaf sheath growth in Sorghum bicolor
Authors: De Riseis Samuel , Harmon Frank G. 
Published: January 2024

Abstract
Objectives
The objective of this data set was to identify transcriptional networks that control elongation of seedling leaf sheaths in the C4 grass Sorghum bicolor. One motivation was that leaf sheaths are a primary constituent of stems in grass seedlings; therefore, genes that control growth of this organ are important contributors to successful transition from the seedling stage to the mature plant stage and, ultimately, crop success. Since diurnal rhythms contribute to regulation of signaling networks responsible for growth, a time course representing the late afternoon and early evening was anticipated to pinpoint important control genes for stem growth. Ultimately, the expected outcome was discovery of transcript networks that integrate internal and external signals to fine tune leaf sheath growth and, consequently, plant height.

Data description
The data set is RNAseq profiling of upper leaf sheaths collected from wild type Sorghum bicolor (BTx623 line) plants at four-hour intervals from 12.5 h after dawn to 20 h after dawn. Global transcript levels in leaves were determined by deep sequencing of mRNA from four individual seedlings at each time point. This data set contains sequences representing the spectrum of mRNAs from individual genes. This data set enables detection of significant changes in gene-level expression caused by the progression of the day from late afternoon to the middle of the night. This data set is useful to identify gene expression networks regulating growth in the leaf sheath, an organ that is a major contributor to the sorghum seedling stem and defines seedling height.
Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Authors: Liu Andi , Fernandes Brisa S. , Citu Citu , Zhao Zhongming 
Published: January 2024

AbstractBackgroundRecently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains.MethodsWe systematically assessed the intercellular communication networks by using a discovery snRNA-seq dataset comprising 69,499 nuclei from 48 human postmortem prefrontal cortex (PFC) samples. We replicated the findings using an independent snRNA-seq dataset of 56,440 nuclei from 18 PFC samples. By integrating genetic signals from AD genome-wide association studies (GWAS) summary statistics and whole genome sequencing (WGS) data, we prioritized AD-associated Gene Ontology (GO) terms containing dysregulated LR interactions. We further explored drug repurposing for the prioritized LR pairs using the Therapeutic Targets Database.ResultsWe identified 190 dysregulated LR interactions across six major cell types in AD PFC, of which 107 pairs were replicated. Among the replicated LR signals, we found globally downregulated communications in the astrocytes-to-neurons signaling axis, characterized, for instance, by the downregulation ofAPOE-related and Calmodulin (CALM)-related LR interactions and their potential regulatory connections to target genes. Pathway analyses revealed 44 GO terms significantly linked to AD, highlighting Biological Processes such as ‘amyloid precursor protein processing’ and ‘ion transmembrane transport,’ among others. We prioritized several drug repurposing candidates, such as cromoglicate, targeting the identified dysregulated LR pairs.ConclusionsOur integrative analysis identified key dysregulated LR interactions in a cell type-specific manner and the associated GO terms in AD, offering novel insights into potential therapeutic targets involved in disrupted cell–cell communication in AD.
Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Authors: Iworima Diepiriye G. , Baker Robert K. , Ellis Cara , Sherwood Chris , Zhan Lisa , Rezania Alireza , Piret James M. , Kieffer Timothy J. 
Published: January 2024

Abstract
Background
Diabetes is a disease affecting over 500 million people globally due to insulin insufficiency or insensitivity. For individuals with type 1 diabetes, pancreatic islet transplantation can help regulate their blood glucose levels. However, the scarcity of cadaveric donor islets limits the number of people that could receive this therapy. To address this issue, human pluripotent stem cells offer a potentially unlimited source for generating insulin-producing cells through directed differentiation. Several protocols have been developed to make stem cell-derived insulin-producing cells. However, there is a lack of knowledge regarding the bioprocess parameters associated with these differentiation protocols and how they can be utilized to increase the cell yield.

Methods
We investigated various bioprocess parameters and quality target product profiles that may influence the differentiation pipeline using a seven-stage protocol in a scalable manner with CellSTACKs and vertical wheel bioreactors (PBS-Minis).

Results
Cells maintained > 80% viability through all stages of differentiation and appropriately expressed stage-specific markers. During the initial four stages leading up to the development of pancreatic progenitors, there was an increase in cell numbers. Following pancreatic progenitor stage, there was a gradual decrease in the percentage of proliferative cells, as determined by Ki67 positivity, and a significant loss of cells during the period of endocrine differentiation. By minimizing the occurrence of aggregate fusion, we were able to enhance cell yield during the later stages of differentiation. We suggest that glucose utilization and lactate production are cell quality attributes that should be considered during the characterization of insulin-producing cells derived from stem cells. Our findings also revealed a gradual metabolic shift from glycolysis, during the initial four stages of pancreatic progenitor formation, to oxidative phosphorylation later on during endocrine differentiation. Furthermore, the resulting insulin-producing cells exhibited a response to several secretagogues, including high glucose.

Conclusion
This study demonstrates process parameters such as glucose consumption and lactate production rates that may be used to facilitate the scalable manufacture of stem cell-derived insulin-producing cells.
Pan PPAR agonist stimulation of induced MSCs produces extracellular vesicles with enhanced renoprotective effect for acute kidney injury
Authors: Kim Hongduk , Lee Seul Ki , Hong Sungok , Park Tae Sub , Kim Jimin , Kim Soo , Kim Tae Min 
Published: January 2024

Abstract
Background
Acute kidney injury (AKI) has a complex pathophysiology and imposes serious health concerns worldwide. Extracellular vesicles (EVs) derived from induced mesenchymal stem cells (iMSCs) have been recognized as novel cell-free therapeutics for various inflammatory and degenerative disorders. In this study, we investigated whether iMSCs stimulated with a pan-peroxisome proliferator-activated receptor (PPAR) agonist could enhance the therapeutic efficacy of EVs against AKI.

Methods
Human iMSCs were primed with or without lanifibranor, a PPAR agonist for 24 h, and EVs were collected after an additional 24 h. The basic characteristics of EVs were evaluated using cryo-transmission electron microscopy imaging, immunoblot detection of EV markers, nanoparticle tracking analysis, and localization in AKI kidneys. In vitro, the potential of the EVs to promote the growth and survival of HK-2 cells undergoing cisplatin-induced apoptosis and anti-inflammatory effects in M1-polarized THP-1 was compared. Subsequently, AKI was induced in BALB/c mice using cisplatin. After 8 and 24 h of cisplatin treatment, iMSC-EVs or pan-PPAR-iMSC-EVs were injected intravascularly. At 96 h after cisplatin administration, the renoprotective effects of iMSC-EVs or pan-PPAR-iMSC-EVs in inhibiting inflammation and apoptosis were compared using serum biochemistry, histology, immunohistochemistry, and gene expression analysis by qPCR.

Results
Both EV types expressed EV markers and had typical EV morphology, and their localization in the renal tissue was confirmed. The proliferation and survival of HK-2 cells were higher in pan-PPAR-iMSC-EVs than those in iMSC-EVs. In M1-polarized THP-1 cells, the reduction in the mRNA expression of inflammatory cytokines was more significant in pan-PPAR-iMSC-EVs than that in iMSC-EVs. In the mouse model of cisplatin-induced AKI, pan-PPAR-iMSC-EVs markedly enhanced renoprotective effects compared to iMSC-EVs. Specifically, pan-PPAR-iMSC-EVs reduced tissue inflammation, immune cell infiltration, and apoptosis. Pan-PPAR-iMSC-EVs also increased renal capillary density.

Conclusion
Priming iMSCs with a PPAR agonist significantly improved the therapeutic potential of EVs by reducing inflammation and apoptosis. The reported strategy may contribute to the development of a novel cell-free option for AKI treatment.
Trial registration: Not applicable.
Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy
Authors: Yu Tong , Yang Li-Li , Zhou Ying , Wu Min-Fei , Jiao Jian-Hang 
Published: January 2024

AbstractSpinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.