bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered DNA methylome profiles of blood leukocytes in Chinese patients with mild cognitive impairment and Alzheimer’s disease
Authors: Wu Shaochang , Yang Fan , Chao Shan , Wang Bo , Wang Wuqian , Li He , Yu Limei , He Lin , Li Xingwang , Sun Liya , Qin Shengying 
Published: June 2023

Objective: DNA methylation plays a potential role in the pathogenesis of Alzheimer’s disease (AD). However, little is known about the global changes of blood leukocyte DNA methylome profiles from Chinese patients with mild cognitive impairment (MCI) and with AD, or the specific DNA methylation-based signatures associated with MCI and AD. In this study, we sought to dissect the characteristics of blood DNA methylome profiles in MCI- and AD-affected Chinese patients with the aim of identifying novel DNA methylation biomarkers for AD.Methods: In this study, we profiled the DNA methylome of peripheral blood leukocytes from 20 MCI- and 20 AD-affected Chinese patients and 20 cognitively healthy controls (CHCs) with the Infinium Methylation EPIC BeadChip array.Results: We identified significant alterations of the methylome profiles in MCI and AD blood leukocytes. A total of 2,582 and 20,829 CpG sites were significantly and differentially methylated in AD and MCI compared with CHCs (adjusted p &lt; 0.05), respectively. Furthermore, 441 differentially methylated positions (DMPs), aligning to 213 unique genes, were overlapped by the three comparative groups of AD versus CHCs, MCI versus CHCs, and AD versus MCI, of which 6 and 5 DMPs were continuously hypermethylated and hypomethylated in MCI and AD relative to CHCs (adjusted p &lt; 0.05), respectively, such as FLNC cg20186636 and AFAP1 cg06758191. The DMPs with an area under the curve &gt;0.900, such as cg18771300, showed high potency for predicting MCI and AD. In addition, gene ontology and pathway enrichment results showed that these overlapping genes were mainly involved in neurotransmitter transport, GABAergic synaptic transmission, signal release from synapse, neurotransmitter secretion, and the regulation of neurotransmitter levels. Furthermore, tissue expression enrichment analysis revealed a subset of potentially cerebral cortex-enriched genes associated with MCI and AD, including SYT7, SYN3, and KCNT1.Conclusion: This study revealed a number of potential biomarkers for MCI and AD, also highlighted the presence of epigenetically dysregulated gene networks that may engage in the underlying pathological events resulting in the onset of cognitive impairment and AD progression. Collectively, this study provides prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.
Phosphorylated STAT3 as a potential diagnostic and predictive biomarker in ALK- ALCL vs. CD30high PTCL, NOS
Authors: Xiang Chenxi , Wu Wanna , Fan Meiting , Wang Zhen , Feng Xiaoli , Liu Cuiling , Liu Jia , Liu Guangzhen , Xia Lei , Si Haipeng , Gu Ying , Liu Nian , Luo Dan , Wang Yubo , Ma Dongshen , Hu Shimin , Liu Hui 
Published: June 2023

AimsThe differential diagnosis between ALK-negative anaplastic large cell lymphoma (ALK- ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with high expression of CD30 (CD30high) are essential. However, no reliable biomarker is available in daily practice except CD30. STAT3 is characteristically activated in ALCL. We aimed to investigate whether the status of STAT3 phosphorylation could help the differential diagnosis.MethodsThe status of phosphorylation of STAT3 was examined using two antibodies against pSTAT3-Y705 and pSTAT3-S727 by immunohistochemistry in ALK+ ALCL (n=33), ALK- ALCL (n=22) and PTCL, NOS (n=34). Ten PTCL, NOS with diffuse CD30 expression were defined as CD30high PTCL, NOS. Flowcytometric analysis were performed to evaluate the expression of pSTAT3-Y705/S727 in PTCL, NOS (n=3).ResultsThe median H-scores of pSTAT3-Y705 and S727 were 280 and 260 in ALK+ ALCL, 250 and 240 in ALK- ALCL, and 45 and 75 in CD30high subgroup, respectively. Using H score of 145 as the cutoff value, pSTAT3-S727 alone distinguished between ALK- ALCL and CD30high PTCL, NOS with a sensitivity of 100% and specificity of 83%. Additionally, pSTAT3-S727, but not pSTAT3-Y705, was also expressed by background tumor-infiltrating lymphocytes (S727TILs) in PTCL, NOS. PTCL, NOS patients with high S727TILs H score had a favorable prognosis than those with no TILs (3-year OS rate: 43% vs. 0, p=0.013) or low S727TILs (3-year OS rate: 43% vs. 0, p=0.099). Flowcytometric analysis revealed that of the three patients investigated, two had enhanced pSTAT-S727 signals in neoplastic cell populations, and all three patients were negative for pSTAT3-Y705 expression in both tumor cells and background lymphocytes.ConclusionspSTAT3-Y705/S727 can be used to help distinguish ALK- ALCL from CD30high PTCL, NOS and pSTAT3-S727 expression by TILs predicts the prognosis of a subset of PTCL, NOS.
Predictors of high SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors: a cross-sectional study in China
Authors: Tang Jingyun , Liu Humin , Wang Qing , Gu Xiaobo , Wang Jia , Li Wenjun , Luo Yinglan , Li Yan , Deng Lan , Luo Yue , Du Xinman , Tan Donglin , Fu Xuemei , Chen Xue 
Published: June 2023

BackgroundDemographic information has been shown to help predict high antibody titers of COVID-19 convalescent plasma (CCP) in CCP donors. However, there is no research on the Chinese population and little evidence on whole-blood donors. Therefore, we aimed to investigate these associations among Chinese blood donors after SARS-CoV-2 infection.MethodsIn this cross-sectional study, 5,064 qualified blood donors with confirmed or suspected SARS-CoV-2 infection completed a self-reported questionnaire and underwent tests of SARS-CoV-2 Immunoglobulin G (IgG) antibody and ABO blood type. Logistic regression models were used to calculate odds ratios (ORs) for high SARS-CoV-2 IgG titers according to each factor.ResultsTotally, 1,799 participants (with SARS-CoV-2 IgG titers≥1:160) had high-titer CCPs. Multivariable analysis showed that a 10-year increment in age and earlier donation were associated with higher odds of high-titer CCP, while medical personnel was associated with lower odds. The ORs (95% CIs) of high-titer CCP were 1.17 (1.10–1.23, p&lt; 0.001) and 1.41 (1.25-1.58, p&lt; 0.001) for each 10-year increment in age and earlier donation, respectively. The OR of high-titer CCP was 0.75 (0.60-0.95, p = 0.02) for medical personnel. Female early donors were associated with increased odds of high-titer CCP, but this association was insignificant for later donors. Donating after 8 weeks from the onset was associated with decreased odds of having high-titer CCP compared to donating within 8 weeks from the onset, and the HR was 0.38 (95% CI: 0.22-0.64, p &lt;0.001). There was no significant association between ABO blood type or race and the odds of high-titer CCP.DiscussionOlder age, earlier donation, female early donors, and non-medical-related occupations are promising predictors of high-titer CCP in Chinese blood donors. Our findings highlight the importance of CCP screening at the early stage of the pandemic.
Transcriptome-wide analyses of early immune responses in lumpfish leukocytes upon stimulation with poly(I:C)
Authors: Rao Shreesha S. , Lunde Harald S. , Dolan David W. P. , Fond Amanda K. , Petersen Kjell , Haugland Gyri T. 
Published: June 2023

BackgroundBoth bacterial and viral diseases are a major threat to farmed fish. As the antiviral immune mechanisms in lumpfish (Cyclopterus lumpus L.) are poorly understood, lumpfish leukocytes were stimulated with poly(I:C), a synthetic analog of double stranded RNA, which mimic viral infections, and RNA sequencing was performed.MethodsTo address this gap, we stimulated lumpfish leukocytes with poly(I:C) for 6 and 24 hours and did RNA sequencing with three parallels per timepoint. Genome guided mapping was performed to define differentially expressed genes (DEGs).ResultsImmune genes were identified, and transcriptome-wide analyses of early immune responses showed that 376 and 2372 transcripts were significantly differentially expressed 6 and 24 hours post exposure (hpe) to poly(I:C), respectively. The most enriched GO terms when time had been accounted for, were immune system processes (GO:0002376) and immune response (GO:0006955). Analysis of DEGs showed that among the most highly upregulated genes were TLRs and genes belonging to the RIG-I signaling pathway, including LGP2, STING and MX, as well as IRF3 and IL12A. RIG-I was not identified, but in silico analyses showed that genes encoding proteins involved in pathogen recognition, cell signaling, and cytokines of the TLR and RIG-I signaling pathway are mostly conserved in lumpfish when compared to mammals and other teleost species.ConclusionsOur analyses unravel the innate immune pathways playing a major role in antiviral defense in lumpfish. The information gathered can be used in comparative studies and lay the groundwork for future functional analyses of immune and pathogenicity mechanisms. Such knowledge is also necessary for the development of immunoprophylactic measures for lumpfish, which is extensively cultivated for use as cleaner fish in the aquaculture for removal of sea lice from Atlantic salmon (Salmo salar L.).
Estimating potential menhaden consumption by double-crested cormorants along the coast of North Carolina
Authors: Watts Bryan D. , Paxton Barton J. , Hines Chance , Anderson Scott K. 
Published: June 2023

The south Atlantic coast supports one of the highest assemblages of non-breeding double-crested cormorants (Nannopterum auritum) known and is a convergence area for Atlantic menhaden (Brevoortia tyrannus) during the winter months. We surveyed cormorants along the coast of North Carolina and used a bioenergetics approach to estimate potential menhaden consumption. We estimated cormorant numbers using a network of repeatable aerial transects along the outer coast (366 km) and within sounds (266 km) during fall migration, winter and spring migration (2019-2021). We estimated the number of bird days, metabolic demand and menhaden equivalents of demand. Cormorant numbers peaked around 122,000 to 131,000 during southward migration, reached a low of 30,000 to 39,000 in winter and then increased to 67,000 to 68,000 during northward migration. We did not capture the peak of spring migration during the study period (20 November through 24 March). We estimated the number of cormorant days within the study period to be 8.6 x 106and 9.2 x 106for the two field seasons respectively. We estimated that cormorants consumed approximately 5,334 and 5,660 mt of menhaden equivalents within the study area. Estimated consumption peaked between 76 and 81 mt-dduring fall passage and reached a low of 19 and 24 mt-dduring the winter. Annual menhaden take by humans and predatory fish is around 354,000 mt. Menhaden consumption by cormorants within the study area represents 4% of the commercial and recreational take and 7% of the estimated consumption by predatory fish or 2.5% of the known take.
A group of three miRNAs can act as candidate circulating biomarkers in liquid biopsies from melanoma patients
Authors: De Martino Eleonora , Gandin Ilaria , Azzalini Eros , Massone Cesare , Pizzichetta Maria Antonietta , Giulioni Erika , Javor Sanja , Pinzani Caterina , Conforti Claudio , Zalaudek Iris , Bonin Serena 
Published: June 2023

BackgroundStaging of melanoma and follow up after melanoma diagnosis aims at predicting risk and detecting progression or recurrence at early stage, respectively in order to timely start and/or change treatment. Tumor thickness according to Breslow, status of the sentinel node and value of the lactate dehydrogenase (LDH) are well-established prognostic markers for metastatic risk, but reliable biomarkers identifying early recurrence or candidates who may benefit best from medical treatment are still warranted. Liquid biopsy has emerged to be a suitable method for identifying biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows analyzing circulating analytes, including extracellular vesicles.MethodsIn this study we have explored the use of 7 miRNAs, namely hsa-miR-149-3p, hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-200c-3p, hsa-miR-134-5p, hsa-miR-144-3p and hsa-miR-221-3p in plasma exosomes to discriminate melanoma patients from controls without melanoma in a cohort of 92 individuals.Results and discussionOur results showed that three out seven miRNAs, namely hsa-miR-200c-3p, hsa-miR-144-3p and hsa-miR-221-3p were differentially expressed in plasma-derived exosomes from melanoma patients and controls. Furthermore, the expression of the three miRNAs may be a promising ancillary tool as a melanoma biomarker, even for discriminating between nevi and melanoma.
COVID-19 and brain-heart-lung microbial fingerprints in Italian cadavers
Authors: Javan Gulnaz T. , Finley Sheree J. , Moretti Matteo , Visonà Silvia D. , Mezzari Melissa P. , Green Robert L. 
Published: June 2023

Introduction: The fact that SARS-CoV-2, the coronavirus that caused COVID-19, can translocate within days of infection to the brain and heart and that the virus can survive for months is well established. However, studies have not investigated the crosstalk between the brain, heart, and lungs regarding microbiota that simultaneously co-inhabit these organs during COVID-19 illness and subsequent death. Given the significant overlap of cause of death from or with SARS-CoV-2, we investigated the possibility of a microbial fingerprint regarding COVID-19 death.Methods: In the current study, the 16S rRNA V4 region was amplified and sequenced from 20 COVID-19-positive and 20 non-COVID-19 cases. Nonparametric statistics were used to determine the resulting microbiota profile and its association with cadaver characteristics. When comparing non-COVID-19 infected tissues versus those infected by COVID-19, there is statistical differences (p &lt; 0.05) between organs from the infected group only.Results: When comparing the three organs, microbial richness was significantly higher in non-COVID-19-infected tissues than infected. Unifrac distance metrics showed more variance between control and COVID-19 groups in weighted analysis than unweighted; both were statistically different. Unweighted Bray-Curtis principal coordinate analyses revealed a near distinct two-community structure: one for the control and the other for the infected group. Both unweighted and weighted Bray-Curtis showed statistical differences. Deblur analyses demonstrated Firmicutes in all organs from both groups.Discussion: Data obtained from these studies facilitated the defining of microbiome signatures in COVID-19 decedents that could be identified as taxonomic biomarkers effective for predicting the occurrence, the co-infections involved in its dysbiosis, and the evolution of the virus.
An artificial intelligence prediction model based on extracellular matrix proteins for the prognostic prediction and immunotherapeutic evaluation of ovarian serous adenocarcinoma
Authors: Geng Tianxiang , Zheng Mengxue , Wang Yongfeng , Reseland Janne Elin , Samara Athina 
Published: June 2023

Background: Ovarian Serous Adenocarcinoma is a malignant tumor originating from epithelial cells and one of the most common causes of death from gynecological cancers. The objective of this study was to develop a prediction model based on extracellular matrix proteins, using artificial intelligence techniques. The model aimed to aid healthcare professionals to predict the overall survival of patients with ovarian cancer (OC) and determine the efficacy of immunotherapy.Methods: The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) data collection was used as the study dataset, whereas the TCGA-Pancancer dataset was used for validation. The prognostic importance of 1068 known extracellular matrix proteins for OC were determined by the Random Forest algorithm and the Lasso algorithm establishing the ECM risk score. Based on the gene expression data, the differences in mRNA abundance, tumour mutation burden (TMB) and tumour microenvironment (TME) between the high- and low-risk groups were assessed.Results: Combining multiple artificial intelligence algorithms we were able to identify 15 key extracellular matrix genes, namely, AMBN, CXCL11, PI3, CSPG5, TGFBI, TLL1, HMCN2, ESM1, IL12A, MMP17, CLEC5A, FREM2, ANGPTL4, PRSS1, FGF23, and confirm the validity of this ECM risk score for overall survival prediction. Several other parameters were identified as independent prognostic factors for OC by multivariate COX analysis. The analysis showed that thyroglobulin (TG) targeted immunotherapy was more effective in the high ECM risk score group, while the low ECM risk score group was more sensitive to the RYR2 gene-related immunotherapy. Additionally, the patients with low ECM risk scores had higher immune checkpoint gene expression and immunophenoscore levels and responded better to immunotherapy.Conclusion: The ECM risk score is an accurate tool to assess the patient’s sensitivity to immunotherapy and forecast OC prognosis.
Development of a predictive risk stratification tool to identify the population over age 45 at risk for new-onset stroke within 7 years
Authors: Yang Kang , Chen Minfang , Wang Yaoling , Jiang Gege , Hou Niuniu , Wang Liping , Wen Kai , Li Wei 
Published: June 2023

Background and purposeWith the acceleration of the aging process of society, stroke has become a major health problem in the middle-aged and elderly population. A number of new stroke risk factors have been recently found. It is necessary to develop a predictive risk stratification tool using multidimensional risk factors to identify people at high risk for stroke.MethodsThe study included 5,844 people (age ≥ 45 years) who participated in the China Health and Retirement Longitudinal Study in 2011 and its follow-up up to 2018. The population samples were divided into training set and validation set according to 1:1. A LASSO Cox screening was performed to identify the predictors of new-onset stroke. A nomogram was developed, and the population was stratified according to the score calculated through the X-tile program. Internal and external verifications of the nomogram were performed by ROC and calibration curves, and the Kaplan-Meier method was applied to identify the performance of the risk stratification system.ResultsThe LASSO Cox regression screened out 13 candidate predictors from 50 risk factors. Finally, nine predictors, including low physical performance and the triglyceride-glucose index, were included in the nomogram. The nomogram's overall performance was good in both internal and external validations (AUCs at 3-, 5-, and 7-year periods were 0.71, 0.71, and 0.71 in the training set and 0.67, 0.65, and 0.66 in the validation set, respectively). The nomogram was proven to excellently discriminate between the low-, moderate-, and high-risk groups, with a prevalence of 7-year new-onset stroke of 3.36, 8.32, and 20.13%, respectively (P &lt; 0.001).ConclusionThis research developed a clinical predictive risk stratification tool that can effectively identify the different risks of new-onset stroke in 7 years in the middle-aged and elderly Chinese population.
Location estimation based on feature mode matching with deep network models
Authors: Bai Yu-Ting , Jia Wei , Jin Xue-Bo , Su Ting-Li , Kong Jian-Lei 
Published: June 2023

IntroductionGlobal navigation satellite system (GNSS) signals can be lost in viaducts, urban canyons, and tunnel environments. It has been a significant challenge to achieve the accurate location of pedestrians during Global Positioning System (GPS) signal outages. This paper proposes a location estimation only with inertial measurements.MethodsA method is designed based on deep network models with feature mode matching. First, a framework is designed to extract the features of inertial measurements and match them with deep networks. Second, feature extraction and classification methods are investigated to achieve mode partitioning and to lay the foundation for checking different deep networks. Third, typical deep network models are analyzed to match various features. The selected models can be trained for different modes of inertial measurements to obtain localization information. The experiments are performed with the inertial mileage dataset from Oxford University.Results and discussionThe results demonstrate that the appropriate networks based on different feature modes have more accurate position estimation, which can improve the localization accuracy of pedestrians in GPS signal outages.
Self-limited childhood epilepsies are disorders of the perisylvian communication system, carrying the risk of progress to epileptic encephalopathies—Critical review
Authors: Halász Péter , Szũcs Anna 
Published: June 2023

“Sleep plasticity is a double-edged sword: a powerful machinery of neural build-up, with a risk to epileptic derailment.”We aimed to review the types of self-limited focal epilepsies...“i.e. keep as two separate paragraphs” We aimed to review the types of self-limited focal epilepsies: (1) self-limited focal childhood epilepsy with centrotemporal spikes, (2) atypical Rolandic epilepsy, and (3) electrical status epilepticus in sleep with mental consequences, including Landau–Kleffner-type acquired aphasia, showing their spectral relationship and discussing the debated topics. Our endeavor is to support the system epilepsy concept in this group of epilepsies, using them as models for epileptogenesis in general. The spectral continuity of the involved conditions is evidenced by several features: language impairment, the overarching presence of centrotemporal spikes and ripples (with changing electromorphology across the spectrum), the essential timely and spatial independence of interictal epileptic discharges from seizures, NREM sleep relatedness, and the existence of the intermediate-severity “atypical” forms. These epilepsies might be the consequences of a genetically determined transitory developmental failure, reflected by widespread neuropsychological symptoms originating from the perisylvian network that have distinct time and space relations from secondary epilepsy itself. The involved epilepsies carry the risk of progression to severe, potentially irreversible encephalopathic forms.