bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of methylation-regulated genes modulating microglial phagocytosis in hyperhomocysteinemia-exacerbated Alzheimer’s disease
Authors: Wang Xianwei , Liu Lu , Jiang Xiaohua , Saredy Jason , Xi Hang , Cueto Ramon , Sigler Danni , Khan Mohsin , Wu Sheng , Ji Yong , Snyder Nathaniel W. , Hu Wenhui , Yang Xiaofeng , Wang Hong 
Published: October 2023

Abstract
Background
Hyperhomocysteinemia (HHcy) has been linked to development of Alzheimer’s disease (AD) neuropathologically characterized by the accumulation of amyloid β (Aβ). Microglia (MG) play a crucial role in uptake of Aβ fibrils, and its dysfunction worsens AD. However, the effect of HHcy on MG Aβ phagocytosis remains unstudied.

Methods
We isolated MG from the cerebrum of HHcy mice with genetic cystathionine-β-synthase deficiency (Cbs−/−) and performed bulk RNA-seq. We performed meta-analysis over transcriptomes of Cbs−/− mouse MG, human and mouse AD MG, MG Aβ phagocytosis model, human AD methylome, and GWAS AD genes.

Results
HHcy and hypomethylation conditions were identified in Cbs−/− mice. Through Cbs−/− MG transcriptome analysis, 353 MG DEGs were identified. Phagosome formation and integrin signaling pathways were found suppressed in Cbs−/− MG. By analyzing MG transcriptomes from 4 AD patient and 7 mouse AD datasets, 409 human and 777 mouse AD MG DEGs were identified, of which 37 were found common in both species. Through further combinatory analysis with transcriptome from MG Aβ phagocytosis model, we identified 130 functional-validated Aβ phagocytic AD MG DEGs (20 in human AD, 110 in mouse AD), which reflected a compensatory activation of Aβ phagocytosis. Interestingly, we identified 14 human Aβ phagocytic AD MG DEGs which represented impaired MG Aβ phagocytosis in human AD. Finally, through a cascade of meta-analysis of transcriptome of AD MG, functional phagocytosis, HHcy MG, and human AD brain methylome dataset, we identified 5 HHcy-suppressed phagocytic AD MG DEGs (Flt1, Calponin 3, Igf1, Cacna2d4, and Celsr) which were reported to regulate MG/MΦ migration and Aβ phagocytosis.

Conclusions
We established molecular signatures for a compensatory response of Aβ phagocytosis activation in human and mouse AD MG and impaired Aβ phagocytosis in human AD MG. Our discoveries suggested that hypomethylation may modulate HHcy-suppressed MG Aβ phagocytosis in AD.
Gut microbial metabolite deoxycholic acid facilitates Th17 differentiation through modulating cholesterol biosynthesis and participates in high-fat diet-associated colonic inflammation
Authors: Li Dan , Zhou Jiefei , Wang Lingyu , Gong Zizhen , Le Huijuan , Huang Ye , Xu Congfeng , Tian Chunyan , Cai Wei , Wu Jin 
Published: October 2023

Abstract
Background
High-fat diet (HFD) is closely associated with the increased prevalence of inflammatory bowel disease (IBD). Excessive gut microbial metabolite deoxycholic acid (DCA) caused by HFD plays significant roles in eliciting intestinal inflammation, however, the mechanism underlining the induction of inflammatory response by DCA has not been fully elucidated. The purpose of this study was to investigate the role of DCA in the triggering of inflammation via affecting CD4+ T cell differentiation.

Results
Murine CD4+T cells were cultured under Th1, Th2 or Th17-polarizing conditions treated with or without different dosage of DCA, and flowcytometry was conducted to detect the effect of DCA on CD4+ T cell differentiation. Alteration of gene expression in CD4+ T cells upon DCA treatment was determined by RNA-sequencing and qRT-PCR. Bioinformatic analysis, cholesterol metabolic profiling, ChIP assay and immuno-fluorescent staining were further applied to explore the DCA-regulated pathway that involved in CD4+T cell differentiation. The results showed that DCA could dose-dependently promote the differentiation of CD4+ T cell into Th17 linage with pathogenic signature. Mechanistically, DCA stimulated the expression of cholesterol biosynthetic enzymes CYP51 and led to the increased generation of endogenous RORγt agonists, including zymosterol and desmosterol, therefore facilitating Th17 differentiation. Up-regulation of CYP51 by DCA was largely mediated via targeting transcription factor SREBP2 and at least partially through bile acid receptor TGR5. In addition, DCA-supplemented diet significantly increased intestinal Th17 cell infiltration and exacerbated TNBS-induced colitis. Administration of cholestyramine to eliminate fecal bile acid obviously alleviated colonic inflammation accompanied by decreased Th17 cells in HFD-fed mice.

Conclusions
Our data establish a link between DCA-induced cholesterol biosynthesis in immune cells and gut inflammation. Modulation of bile acid level or targeting cholesterol metabolic pathway may be potential therapeutic measurements for HFD-related colitis.
Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer’s disease brains
Authors: Gamache Julia , Gingerich Daniel , Shwab E. Keats , Barrera Julio , Garrett Melanie E. , Hume Cordelia , Crawford Gregory E. , Ashley-Koch Allison E. , Chiba-Falek Ornit 
Published: October 2023

Abstract
Background
The genetic underpinnings of late-onset Alzheimer’s disease (LOAD) are yet to be fully elucidated. Although numerous LOAD-associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain is composed of heterogenous cell subtypes, it is imperative to study the brain on a cell subtype specific level to explore the biological processes underlying LOAD.

Methods
Here, we present the largest parallel single-nucleus (sn) multi-omics study to simultaneously profile gene expression (snRNA-seq) and chromatin accessibility (snATAC-seq) to date, using nuclei from 12 normal and 12 LOAD brains. We identified cell subtype clusters based on gene expression and chromatin accessibility profiles and characterized cell subtype-specific LOAD-associated differentially expressed genes (DEGs), differentially accessible peaks (DAPs) and cis co-accessibility networks (CCANs).

Results
Integrative analysis defined disease-relevant CCANs in multiple cell subtypes and discovered LOAD-associated cell subtype-specific candidate cis regulatory elements (cCREs), their candidate target genes, and trans-interacting transcription factors (TFs), some of which, including ELK1, JUN, and SMAD4 in excitatory neurons, were also LOAD-DEGs. Finally, we focused on a subset of cell subtype-specific CCANs that overlap known LOAD-GWAS regions and catalogued putative functional SNPs changing the affinities of TF motifs within LOAD-cCREs linked to LOAD-DEGs, including APOE and MYO1E in a specific subtype of microglia and BIN1 in a subpopulation of oligodendrocytes.

Conclusions
To our knowledge, this study represents the most comprehensive systematic interrogation to date of regulatory networks and the impact of genetic variants on gene dysregulation in LOAD at a cell subtype resolution. Our findings reveal crosstalk between epigenetic, genomic, and transcriptomic determinants of LOAD pathogenesis and define catalogues of candidate genes, cCREs, and variants involved in LOAD genetic etiology and the cell subtypes in which they act to exert their pathogenic effects. Overall, these results suggest that cell subtype-specific cis–trans interactions between regulatory elements and TFs, and the genes dysregulated by these networks contribute to the development of LOAD.
Model-based clustering of multipath propagation in powerline communication channels
Authors: Mokise Kealeboga L. , Myburgh Herman C. 
Published: October 2023

AbstractPowerline communication (PLC) channels are known to exhibit multipath propagation behaviour. The authors present a model-based framework to address the challenge of clustering multipath propagation components (MPCs) in PLC channels for indoor low-voltage (LV) environments. The framework employs a range of finite-mixture models (FMMs), including the gamma mixture model, the inverse gamma mixture model, the Gaussian mixture model, the inverse Gaussian mixture model, the Nakagami mixture model, the inverse Nakagami mixture model (INMM) and the Rayleigh mixture model, to identify clusters of MPCs. A measurement campaign of an unknown indoor LV PLC channel is conducted to obtain a channel response. From the channel response, the delay and magnitude parameters of the MPCs are extracted using the space-alternating generalised expectation maximisation algorithm adopted only for these parameters. A maximum likelihood approach and the expectation–maximisation algorithm are employed to fit the FMMs to the MPC delay-magnitude dataset to cluster MPCs in the delay domain. The results of the model-fitting process are then evaluated using the corrected Akaike information criterion (AICc), which enables a fair comparison of the candidate models over the feasible and finite range of clusters. A novel algorithm is introduced for estimating the feasible and finite range of clusters using the extracted delay and magnitude MPC parameters. The AICc’s ranking results show that the INMM model provides the best fit. Davies–Bouldin (DB) and Calinski–Harabasz (CH) indexes are used to compare the model-based clustering approach to the conventional distance-based clustering methods. Validation results show that CH and DB indexes closely agree in the optimal number of MPC clusters for model-based clustering, which corresponds to the most within-cluster compactness of MPCs and to the most between-cluster separation in the delay domain.
Whole-exome sequencing reveals candidate high-risk susceptibility genes for endometriosis
Authors: Nousiainen Susanna , Kuismin Outi , Reinikka Siiri , Manninen Roosa , Khamaiseh Sara , Kuivalainen Mari , Terho Anna , Koivurova Sari , Niinimäki Maarit , Salokas Kari , Varjosalo Markku , Ahtikoski Anne , Bützow Ralf , Lindgren Outi , Uimari Outi , Vahteristo Pia 
Published: October 2023

Abstract
Background
Endometriosis is a common, chronic disease among fertile-aged women. Disease course may be highly invasive, requiring extensive surgery. The etiology of endometriosis remains elusive, though a high level of heritability is well established. Several low-penetrance predisposing loci have been identified, but high-risk susceptibility remains undetermined. Endometriosis is known to increase the risk of epithelial ovarian cancers, especially of endometrioid and clear cell types. Here, we have analyzed a Finnish family where four women have been diagnosed with surgically verified, severely symptomatic endometriosis and two of the patients also with high-grade serous carcinoma.

Results
Whole-exome sequencing revealed three rare candidate predisposing variants segregating with endometriosis. The variants were c.1238C>T, p.(Pro413Leu) in FGFR4, c.5065C>T, p.(Arg1689Trp) in NALCN, and c.2086G>A, p.(Val696Met) in NAV2. The only variant predicted deleterious by in silico tools was the one in FGFR4. Further screening of the variants in 92 Finnish endometriosis and in 19 endometriosis–ovarian cancer patients did not reveal additional carriers. Histopathology, positive p53 immunostaining, and genetic analysis supported the high-grade serous subtype of the two tumors in the family.

Conclusions
Here, we provide FGFR4, NALCN, and NAV2 as novel high-risk candidate genes for familial endometriosis. Our results also support the association of endometriosis with high-grade serous carcinoma. Further studies are required to validate the findings and to reveal the exact pathogenesis mechanisms of endometriosis. Elucidating the genetic background of endometriosis defines the etiology of the disease and provides opportunities for expedited diagnostics and personalized treatments.
Relationship between disgust and orthorexia nervosa and psychometric properties of the Italian Dusseldorf orthorexia scale in a general population sample
Authors: Aloi Matteo , Moniaci Martina , Rania Marianna , Carbone Elvira Anna , Martino Gabriella , Segura-Garcia Cristina , Liuzza Marco Tullio 
Published: October 2023

Abstract
Background
It remains unclear among clinicians and researchers whether orthorexia nervosa (ON) is a part of the obsessive–compulsive disorder spectrum or eating disorders. Disgust seems to be a shared psychopathological factor in these clinical presentations, indicating a potentially crucial role in ON. On the other hand, numerous psychometric tools have been developed to evaluate ON. The Dusseldorf Orthorexia Scale (DOS) was recently validated in an Italian sample. However, the study's primary limitation was that the scale was only administered to undergraduate university students. This study aimed to investigate the psychometric properties (including factorial structure, reliability, and measurement invariance conditional on sex) of the Italian version of the DOS (I-DOS) on a sample from the general population. Additionally, the study sought to determine the nomological validity of the I-DOS by examining its relationship with disgust sensitivity.

Methods
A sample of 521 participants took part in this study and completed a battery that assessed ON and disgust sensitivity. To assess the I-DOS structure, reliability, and measurement invariance we respectively conducted confirmatory factor analysis (CFA), computed McDonalds’s omega, and performed hierarchical series of multigroup CFAs. Then, we tested the relationship between ON and disgust sensitivity.

Results
CFA confirmed the unifactorial model of I-DOS and it respected the configural, metric, and strict invariance while a partial scalar invariance was achieved. It also showed good reliability with an omega of 0.87. In addition, we found a positive relationship between ON and disgust sensitivity, thus confirming the nomological validity of I-DOS.

Conclusions
Our findings suggest that the Italian version of the Dusseldorf orthorexia scale (I-DOS) exhibits strong psychometric properties and can be an effective instrument for assessing ON in a general population sample. Notably, the most significant and innovative outcome was the positive correlation between ON and disgust sensitivity. As disgust has been linked to other clinical presentations, this preliminary result could serve as a foundation for future research exploring this phenomenon in greater detail.
Butyrate alleviates renal inflammation and fibrosis in a rat model of polycystic ovarian syndrome by suppression of SDF-1
Authors: Bashir Al-Amin M. , Olaniyi Kehinde S. 
Published: October 2023

Abstract
Background
Polycystic ovarian syndrome (PCOS) is a multifactorial condition with metabolic-related complications, such as diabetic nephropathy and chronic renal disorder, which are the leading cause of renal transplant globally. Protective effects of histone deacetylase (HDAC) inhibitors (HDACi) have been documented in metabolic-linked pathologies. Nonetheless, the current study investigated the restorative role of HDACi, butyrate in experimental PCOS-induced renal disorder.

Materials and methods
Female Wistar rats (8-week-old) were divided into groups; control, butyrate-treated, letrozole and letrozole + butyrate-treated groups. To induce PCOS, 1 mg/kg of letrozole was given (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate (oral gavage) was administered for 6 weeks.

Results
Rats with PCOS revealed disruption in glucose homeostasis (hyperinsulinemia and impaired glucose tolerance and insulin resistance) and presented with the phenotypes of PCOS (hyperandrogenism, multiple ovarian cysts and elevated LH/FSH ratio). Increased plasma and renal triglycerides and inflammatory (TNF-α/SDF-1/NF-κB) markers were observed with elevated levels of TGFβ-1, renal lipid peroxidation and redox imbalance (GGT, GSH, HIF-1α). Interestingly, animals with PCOS reported increased body weight as well as renal mass. Whereas, heightened levels of plasma urea, creatinine and creatine kinase indicating renal dysfunction, characterized by renal apoptosis (Caspase-6) and increased HDAC2 levels. Notwithstanding, administration of butyrate averted the alterations.

Conclusion
The present investigation demonstrates that PCOS declines renal function, which is accompanied by renal inflammation, apoptosis and fibrosis. The study further suggests that butyrate, an HDAC2i restores renal function by suppressing renal SDF-1 with subsequent attenuation of renal inflammation, apoptosis and fibrosis.
Proposal for a new method for sustainable and advanced utilization of oil palm trunk waste
Authors: Horiyama Hiroaki , Fujimoto Waka , Kojiro Keisuke , Itoh Takafumi , Kajita Hiromu , Furuta Yuzo 
Published: October 2023

AbstractA method to more easily separate vascular bundles and parenchyma was investigated for the purpose of proposing a sustainable and advanced utilization of oil palm trunk (OPT). In addition, particleboard made from vascular bundles was produced as one of the effective ways to utilize the obtained vascular bundles. The following results were obtained. A Zephyr rolling equipment was used for separation, and it was found that the vascular bundles could be easily separated with the veneer in a dry state. SEM observations showed that the vascular bundles could be separated while maintaining the tissue structure. However, some parenchyma remained on the surface of the vascular bundles. The presence of starch was also confirmed within the parenchyma. Particleboard was produced using the separated vascular bundles. The MOR and MOE of the three-layered particleboards with long vascular bundles obtained by Zephyr treatment were about 74.2 MPa and 7.3 GPa, respectively, which are much higher than those of previous wood materials made from OPTs. These results may be the result of extracting the potential of vascular bundles.
Graphical Abstract
Interannual variation of the Warm Arctic–Cold Eurasia pattern modulated by Ural blocking and the North Atlantic Oscillation under changing sea ice conditions
Authors: Zhou Xiling , Sato Tomonori , Li Shixue 
Published: October 2023

AbstractTogether with rapid Arctic warming and sea ice decline, especially over the Barents–Kara seas (BKS), extreme cold winters have occurred frequently in mid-latitudes, particularly in Central Eurasia. A pattern with two distinct winter temperature anomalies centered over the BKS and Central Eurasia is known as the Warm Arctic–Cold Eurasia (WACE) pattern. The impacts of sea ice loss over the BKS and internal atmospheric variability on past WACE formation remain under discussion mainly due to the large internal atmospheric variability in the mid-latitudes. This study analyzed a large-ensemble historical experiment prescribing observed sea ice condition to investigate the role of internal atmospheric variability in the observed interannual variation of the WACE pattern. Comparison of ensemble members suggests that internal atmospheric variability is important for regulating the magnitude of the WACE pattern. Besides the strong effect of local sea ice loss, winter temperature over the BKS increases due to warm advection driven by the Ural blocking and positive phase of the North Atlantic Oscillation. A decrease in winter temperature over Central Eurasia is mainly attributable to the cold advection enhanced by Ural blocking rather than the remote effect of sea ice decline over the BKS. Our study reveals the importance of internal atmospheric variability in elucidating the observed interannual variation of the WACE pattern.
Right hepatectomy under cardiopulmonary bypass for hepatocellular carcinoma with inferior vena cava tumor thrombus: a case report
Authors: Kushiya Hiroki , Ambo Yoshiyasu , Takada Minoru , Masuda Takahiko , Naraoka Shuichi , Hirano Satoshi 
Published: October 2023

Abstract
Background
The prognosis of hepatocellular carcinoma (HCC) with vascular invasion is extremely poor, especially in patients with tumor thrombus (TT) of the inferior vena cava (IVC), which is an oncological emergency with a high risk of sudden death due to TT extension or migration. Herein, we describe a case of HCC with TT of the IVC that rapidly extended into the right atrium (RA), in which right hepatectomy was performed under cardiopulmonary bypass.

Case presentation
A 64-year-old man was diagnosed with HCC with IVC TT, and right hepatic lobectomy was scheduled. While awaiting surgery, he complained of respiratory distress and rushed to the emergency room. The TT had reached the RA, and the patient was in a state of oncologic emergency. We requested the cooperation of the cardiovascular surgery department, and under artificial cardiopulmonary support, the right atrium was incised, and a part of the TT was removed. The IVC was clamped to prevent tumor dispersal, and right hepatic lobectomy was performed. The remaining thrombus was excised along with the right lobe of the liver by incising the IVC. There were no serious postoperative complications, and the patient is alive 1 year and 5 months postoperatively.

Conclusion
Hepatic resection with cardiopulmonary bypass could be an option for HCC with TT reaching the RA.
Uniportal thoracoscopic extended right apical segmentectomy with virtual-assisted lung mapping: a case report
Authors: Yanagiya Masahiro , Wada Ami , Awano Nobuyasu , Izumo Takehiro , Furuhata Yoshiaki 
Published: October 2023

Abstract
Background
Pulmonary extended segmentectomy is an optional surgical treatment for early-stage non-small cell lung cancer that helps to achieve optimal surgical margins. Here, we describe a challenging instance of extended segmentectomy via uniportal video-assisted thoracic surgery with virtual-assisted lung mapping, a preoperative bronchoscopic dye marking procedure.

Case presentation
A 72-year-old woman presented with two tumors that were clinically diagnosed as early-stage lung cancer; extended right apical segmentectomy was indicated. Because the tumors had appeared unidentifiable intraoperatively, we performed virtual-assisted lung mapping for tumor localization and delineation of the optimal resection area. Surgery was conducted through a single port. All virtual-assisted lung mapping markings were visible. After dissection of the apical vessels and bronchi, a putative intersegmental line was determined using collateral ventilation. Based on the putative intersegmental plane identified by collateral ventilation and the virtual-assisted lung mapping markings, the resection line was delineated. Extended apical segmentectomy along the resection line was successfully performed via uniportal video-assisted thoracic surgery. The postoperative course was uneventful. The pathological diagnosis was minimally invasive adenocarcinoma and adenocarcinoma in situ.

Conclusions
Virtual-assisted lung mapping can help to achieve optimal extended segmentectomy via uniportal video-assisted thoracic surgery.