bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array
Authors: Grant Olivia A. , Wang Yucheng , Kumari Meena , Zabet Nicolae Radu , Schalkwyk Leonard 
Published: May 2022

Abstract
Background
Sex differences are known to play a role in disease aetiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using the Illumina EPIC array in human whole blood by performing a discovery (n = 1171) and validation (n = 2471) analysis.

Results
We identified and validated 396 sex-associated differentially methylated CpG sites (saDMPs) with the majority found to be female-biased CpGs (74%). These saDMP’s are enriched in CpG islands and CpG shores and located preferentially at 5’UTRs, 3’UTRs and enhancers. Additionally, we identified 266 significant sex-associated differentially methylated regions overlapping genes, which have previously been shown to exhibit epigenetic sex differences, and novel genes. Transcription factor binding site enrichment revealed enrichment of transcription factors related to critical developmental processes and sex determination such as SRY and ESR1.

Conclusion
Our study reports a reliable catalogue of sex-associated CpG sites and elucidates several characteristics of these sites using large-scale discovery and validation data sets. This resource will benefit future studies aiming to investigate sex specific epigenetic signatures and further our understanding of the role of DNA methylation in sex differences in human whole blood.
Diagnostic and prognostic performance to detect Alzheimer’s disease and clinical progression of a novel assay for plasma p-tau217
Authors: Groot Colin , Cicognola Claudia , Bali Divya , Triana-Baltzer Gallen , Dage Jeffrey L. , Pontecorvo Michael J. , Kolb Hartmuth C. , Ossenkoppele Rik , Janelidze Shorena , Hansson Oskar 
Published: May 2022

AbstractBackgroundRecent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer’s disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217Lilly, within two independent cohorts.MethodsThe study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/−) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays.ResultsBoth assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+JanssenAUC = 0.91 vs plasma p-tau217LillyAUC = 0.89), distinguishing MCI from controls (plasma p-tau217+JanssenAUC = 0.91 vs plasma p-tau217LillyAUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+JanssenAUC = 0.88 vs p-tau217LillyAUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+Janssenrho = −0.39 vs p-tau217Lillyrho = −0.35), and annual change in MMSE scores (plasma p-tau217+Janssenr= −0.45 vs p-tau217Lillyr= −0.41). Correlations between the two plasma measures were rho = 0.69,p< 0.001 in cohort 1 and rho = 0.70,p< 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+Janssenand plasma p-tau217Lillyin both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI).ConclusionsTaken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+Janssenassay, similar to the p-tau217Lillyassay.
Idiopathic combined retinal vessels occlusion in a pregnant woman: a case report
Authors: Bahar Mohammadreza Mehrabi , Ghalandarpoor-Attar Seyedeh Noushin , Shabani Azadeh , Hantoushzadeh Sedigheh , Tabatabaei Seyed Ali , Ghalandarpoor-Attar Seyedeh Mojgan 
Published: May 2022

Abstract
Background
Ocular vascular occlusion is an extremely rare event, especially in the young population. This diagnosis is always associated with active systemic diseases in young adults and needs thrombophilia workup. Nevertheless, we present the case of a pregnant woman suffering from idiopathic combined central retinal vein and cilioretinal artery occlusion.

Case presentation
A 36-year-old pregnant Iranian woman at the 36th week of her second pregnancy complained of subacute unilateral painless decreased vision of her left eye. She had experienced a transient vision loss that lasted several minutes, but attacks gradually became more frequent and finally persistent over a several-day period. Finally combined central retinal vein and cilioretinal artery occlusion was established. Her visual acuity improved to 4/10 in a month without any ocular intervention except for a short duration of prophylactic dose enoxaparin, and the acuity reached 8/10 without any complications in the third month follow-up visit. At 1 year follow-up, the visual acuity had not changed and no macular edema was seen.

Conclusions
Ocular vascular occlusion is extremely rare among young adults, and even rarer among pregnant women. According to this, any suspected retinal vascular event in this population should raise suspicion for underlying diseases such as hypertension, diabetes, autoimmune diseases, migraine, preeclampsia syndrome, and thrombophilia. However, as seen in this presented case, idiopathic ocular vascular occlusion events can occur also.
Butanol–isopropanol fermentation with oxygen-tolerant Clostridium beijerinckii XH29
Authors: Yao Xiuqing , Zhang Quan , Fan Yixuan , Xu Xinyang , Liu Ziyong 
Published: May 2022

AbstractAcetone–butanol–ethanol (ABE) fermentation is a traditional way for solvents production through bioconversion by Clostridium species. It is still a challenge to obtain metabolic engineering strains with high ABE yield. Screening strains with remarkable characteristics from nature and improving ABE yield by mutation are viable approaches. Clostridium beijerinckii XH 0906, a newly isolated strain, produces butanol and isopropanol (BI) as the main end-products (9.1 g/L BI) during fermentation with glucose as the sole carbon source. The screening process for this strain was performed under aerobic conditions rather than anaerobic environment. Thus, it is a robust stain capable of oxygen-tolerant BI fermentation. Furthermore, C. beijerinckii XH 0906 fermented xylose and glucose simultaneously to produce BI. A mutant strain obtained by ultraviolet (UV) mutagenesis, C. beijerinckii XH 29, had improved BI production capacity and could produce 17.0 g/L BI and 18.4 g/L BI using glucose or corn stover hydrolysate, respectively as the carbon source. Interestingly, C. beijerinckii XH 29 also produced up to 19.3 g/L isopropanol through fermentation of a glucose–acetone mix. These results indicate that C. beijerinckii XH 29 is an excellent BI producer with great potential for industrial applications.
Graphical Abstract
Nanotechnological engineering of extracellular vesicles for the development of actively targeted hybrid nanodevices
Authors: Dumontel Bianca , Susa Francesca , Limongi Tania , Vighetto Veronica , Debellis Doriana , Canta Marta , Cauda Valentina 
Published: May 2022

Abstract
Background
We propose an efficient method to modify B-cell derived EVs by loading them with a nanotherapeutic stimuli-responsive cargo and equipping them with antibodies for efficient targeting of lymphoma cells.

Results
The post-isolation engineering of the EVs is accomplished by a freeze–thaw method to load therapeutically-active zinc oxide nanocrystals (ZnO NCs), obtaining the so-called TrojanNanoHorse (TNH) to recall the biomimetism and cytotoxic potential of this novel nanoconstruct. TNHs are further modified at their surface with anti-CD20 monoclonal antibodies (TNHCD20) achieving specific targeting against lymphoid cancer cell line. The in vitro characterization is carried out on CD20+ lymphoid Daudi cell line, CD20-negative cancerous myeloid cells (HL60) and the healthy counterpart (B lymphocytes). The TNH shows nanosized structure, high colloidal stability, even over time, and good hemocompatibility. The in vitro characterization shows the high biocompatibility, targeting specificity and cytotoxic capability. Importantly, the selectivity of TNHCD20 demonstrates significantly higher interaction towards the target lymphoid Daudi cell line compared to the CD20-negative cancerous myeloid cells (HL60) and the healthy counterpart (lymphocytes). An enhanced cytotoxicity directed against Daudi cancer cells is demonstrated after the TNHCD20 activation with high-energy ultrasound shock-waves (SW).

Conclusion
This work demonstrates the efficient re-engineering of EVs, derived from healthy cells, with inorganic nanoparticles and monoclonal antibodies. The obtained hybrid nanoconstructs can be on-demand activated by an external stimulation, here acoustic pressure waves, to exploit a cytotoxic effect conveyed by the ZnO NCs cargo against selected cancer cells.

Graphical Abstract
RNA sequencing profiles reveal dynamic signaling and glucose metabolic features during bone marrow mesenchymal stem cell senescence
Authors: Sun Yanan , Yu Xiao , Gao Xingyu , Zhang Chang , Sun Hui , Xu Kaiyi , Wei Dongxu , Wang Qianwen , Zhang Haiying , Shi Yingai , Li Lisha , He Xu 
Published: May 2022

Abstract
Background
Stem cell senescence is considered as a significant driver of organismal aging. As individuals age, the number of stem cells is declined, and the ability to proliferate and survive is also weakened. It has been reported that metabolism plays an important role in stem cell self-renewal, multilineage differentiation, senescence and fate determination, which has aroused widespread concerns. However, whether metabolism-related genes or signalling pathways are involved in physiological aging remain largely undetermined.

Results
In the current study, we showed 868 up-regulated and 2006 down-regulated differentially expressed genes (DEGs) in bone marrow mesenchymal stem cells (MSCs) from old rats in comparison with that from young rats by performing RNA sequence. And DEGs functions and pathways were further selected by function enrichment analysis. The results indicated that the high expression of DEGs might participate in cell differentiation, growth factor binding and etc., while the down-regulated DEGs were majorly enriched in metabolism process, such as the cellular metabolic process and mitochondria. Then, we screened and verified DEGs related to glucose metabolism and investigated the glycolysis levels. We identified that glucose uptake, lactate secretion, ATP production and relative extracellular acidification rates (ECAR) were all diminished in MSCs from old rats. More importantly, we conducted microRNA prediction on the key DEGs of glycolysis to elucidate the potential molecular mechanisms of glucose metabolism affecting MSC senescence.

Conclusions
Our study unravelled the profiles of DEGs in age-associated MSC senescence and their functions and pathways. We also clarified DEGs related to glucose metabolism and down-regulated glycolysis level in age-associated MSC senescence. This study will uncover the metabolic effects on regulating stem cell senescence, and provide novel therapeutic targets for ameliorating age-associated phenotypes.
m6A demethylase FTO promotes tumor progression via regulation of lipid metabolism in esophageal cancer
Authors: Duan Xiaoran , Yang Li , Wang Liuya , Liu Qinghua , Zhang Kai , Liu Shasha , Liu Chaojun , Gao Qun , Li Lifeng , Qin Guohui , Zhang Yi 
Published: May 2022

Abstract
Background
Epitranscriptomics studies have contributed greatly to the development of research on human cancers. In recent years, N6-methyladenosine (m6A), an RNA modification on the N-6 position of adenosine, has been found to play a potential role in epigenetic regulation. Therefore, we aimed to evaluate the regulation of cancer progression properties by m6A.

Results
We found that m6A demethylase fat mass and obesity-associated protein (FTO) was highly expressed in esophageal cancer (EC) stem-like cells, and that its level was also substantially increased in EC tissues, which was closely correlated with a poor prognosis in EC patients. FTO knockdown significantly inhibited the proliferation, invasion, stemness, and tumorigenicity of EC cells, whereas FTO overexpression promoted these characteristics. Furthermore, integrated transcriptome and meRIP-seq analyses revealed that HSD17B11 may be a target gene regulated by FTO. Moreover, FTO promoted the formation of lipid droplets in EC cells by enhancing HSD17B11 expression. Furthermore, depleting YTHDF1 increased the protein level of HSD17B11.

Conclusions
These data indicate that FTO may rely on the reading protein YTHDF1 to affect the translation pathway of the HSD17B11 gene to regulate the formation of lipid droplets in EC cells, thereby promoting the development of EC. The understanding of the role of epitranscriptomics in the development of EC will lay a theoretical foundation for seeking new anticancer therapies.
Sporadic worldwide “clusters” of feed driven Zilpaterol identifications in racing horses: a review and analysis
Authors: Machin Jacob , Brewer Kimberly , Morales-Briceno Abelardo , Fenger Clara , Maylin George , Tobin Thomas 
Published: May 2022

AbstractZilpaterol is a β2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary “identifications” of Zilpaterol. These “identifications” occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presents in horse urine, yielding clusters of feed related Zilpaterol identifications in racehorses. The first cluster, April 2013, involved 48 racehorses in California; the second cluster, July 2013, involved 15 to 80 racehorses in Hong Kong. The third cluster, March 2019, involved 24 racehorses in Mauritius; this cluster traced to South African feedstuffs, triggering an alert concerning possible Zilpaterol feed contamination in South African racing. The fourth cluster, September/October 2020 involved 18 or so identifications in French racing, reported by the French Laboratories des Courses Hippiques, (LCH), and in July 2021, a fifth cluster of 10 Zilpaterol identifications in South Africa.The regulatory approach to these identifications has been to alert horsemen and feed companies and penalties against horsemen are generally not implemented. Additionally, given their minimal exposure to Zilpaterol, there is little likelihood of Zilpaterol effects on racing performance or adverse health effects for exposed horses.The driving factor in these events is that Zilpaterol is dissolved in molasses for incorporation into cattle feed. Inadvertent incorporation of Zilpaterol containing molasses into horse feed was the source of the California and Hong Kong Zilpaterol identifications. A second factor in the 2019 Mauritius and 2020 French identifications was the sensitivity of testing for Zilpaterol in Mauritius and France, with the French laboratory reportedly testing at a “more sensitive level for Zilpaterol”. As of January 1st, 2021, the new FEI Atypical Finding (ATF) policy specifies Zilpaterol as a substance to be treated as an Atypical Finding (ATF), allowing consideration of inadvertent feed contamination in the regulatory evaluation of Zilpaterol identifications.
Do social relationships mediate or moderate social inequalities in health? A systematic review protocol
Authors: Khaliq Nadia , McMunn Anne , Machuca-Vargas Carolina , Heilmann Anja 
Published: May 2022

Abstract
Introduction
Explanations for health inequalities include material, behavioural and psychosocial pathways. Social relationships are an important determinant of health, and research has consistently found that a lack of support networks may diminish favourable health outcomes. There is some evidence that social network structures, partly shaped by socioeconomic factors, contribute to health inequalities. This protocol will summarise the systematic review process.

Methods and analyses
The Systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An electronic database search of MEDLINE, Embase Classic + Embase and PsychINFO using the OvidSP platform will be undertaken. Databases will be searched from the earliest date of entry until 10 June 2022. Articles that have quantitatively assessed the role of social relationships in mediating or moderating health inequalities will be included and any health outcome (mental/physical) will be considered. The database search will be supplemented by reference list screening of all relevant full-text articles identified through the search. Two independent reviewers will be responsible for screening of articles, data extraction and assessment of bias. Observational studies will be risk assessed for bias using a modified version of the Newcastle-Ottawa Quality Assessment Scale, and intervention studies will be assessed using the revised Cochrane risk-of-bias tool. It is anticipated that the eligible studies will be highly variable; therefore, a meta-analysis will only be considered if the available data of the selected studies are similar. If the studies are too heterogeneous, a narrative synthesis of the extracted data will be presented.

Conclusion
The results of the systematic review will examine the link between social relationships and health inequalities. The findings of the review will identify gaps in knowledge where further research is needed.

Systematic review registration
PROSPERO CRD42020181706
Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells
Authors: Guo Rongqun , Li Wei , Li Yadan , Li Yingmei , Jiang Zhongxing , Song Yongping 
Published: May 2022

AbstractEngineered T cells have been shown to be highly effective in cancer immunotherapy, although T cell exhaustion presents a challenge for their long-term function. Additional T-cell sources must be exploited to broaden the application of engineered T cells for immune defense and reconstitution. Unlimited sources of pluripotent stem cells (PSCs) have provided a potential opportunity to generate precise-engineered therapeutic induced T (iT) cells. Single-cell transcriptome analysis of PSC-derived induced hematopoietic stem and progenitor cells (iHSPC)/iT identified the developmental pathways and possibilities of generating functional T cell from PSCs. To date, the PSC-to-iT platforms encounter several problems, including low efficiency of conventional T subset specification, limited functional potential, and restrictions on large-scale application, because of the absence of a thymus-like organized microenvironment. The updated PSC-to-iT platforms, such as the three-dimensional (3D) artificial thymic organoid (ATO) co-culture system and Runx1/Hoxa9-enforced iT lymphopoiesis, provide fresh perspectives for coordinating culture conditions and transcription factors, which may greatly improve the efficiency of T-cell generation greatly. In addition, the improved PSC-to-iT platform coordinating gene editing technologies will provide various functional engineered unconventional or conventional T cells. Furthermore, the clinical applications of PSC-derived immune cells are accelerating from bench to bedside.
Integrative analysis of multi-omics data to detect the underlying molecular mechanisms for obesity in vivo in humans
Authors: Zhang Qiang , Meng Xiang-He , Qiu Chuan , Shen Hui , Zhao Qi , Zhao Lan-Juan , Tian Qing , Sun Chang-Qing , Deng Hong-Wen 
Published: May 2022

AbstractBackgroundObesity is a complex, multifactorial condition in which genetic play an important role. Most of the systematic studies currently focuses on individual omics aspect and provide insightful yet limited knowledge about the comprehensive and complex crosstalk between various omics levels.Subjects and methodsTherefore, we performed a most comprehensive trans-omics study with various omics data from 104 subjects, to identify interactions/networks and particularly causal regulatory relationships within and especially those between omic molecules with the purpose to discover molecular genetic mechanisms underlying obesity etiology in vivo in humans.ResultsBy applying differentially analysis, we identified 8 differentially expressed hub genes (DEHGs), 14 differentially methylated regions (DMRs) and 12 differentially accumulated metabolites (DAMs) for obesity individually. By integrating those multi-omics biomarkers using Mendelian Randomization (MR) and network MR analyses, we identified 18 causal pathways with mediation effect. For the 20 biomarkers involved in those 18 pairs, 17 biomarkers were implicated in the pathophysiology of obesity or related diseases.ConclusionsThe integration of trans-omics and MR analyses may provide us a holistic understanding of the underlying functional mechanisms, molecular regulatory information flow and the interactive molecular systems among different omic molecules for obesity risk and other complex diseases/traits.