bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescence‐associated transcriptional derepression in subtelomeres is determined in a chromosome‐end‐specific manner
Authors: Rey‐Millet Martin , Pousse Mélanie , Soithong Chan , Ye Jing , Mendez‐Bermudez Aaron , Gilson Eric 
Published: March 2023

AbstractAging is a continuous process leading to physiological deterioration with age. One of the factors contributing to aging is telomere shortening, causing alterations in the protein protective complex named shelterin and replicative senescence. Here, we address the question of the link between this telomere shortening and the transcriptional changes occurring in senescent cells. We found that in replicative senescent cells, the genes whose expression escaped repression are enriched in subtelomeres. The shelterin protein TRF2 and the nuclear lamina factor Lamin B1, both downregulated in senescent cells, are involved in the regulation of some but not all of these subtelomeric genes, suggesting complex mechanisms of transcriptional regulation. Indeed, the subtelomeres containing these derepressed genes are enriched in factors of polycomb repression (EZH2 and H3K27me3), insulation (CTCF and MAZ), and cohesion (RAD21 and SMC3) while being associated with the open A‐type chromatin compartment. These findings unveil that the subtelomere transcriptome associated with senescence is determined in a chromosome‐end‐specific manner according to the type of higher‐order chromatin structure.
Additional malignancies and mortality in uveal melanoma: A 20‐year follow‐up of a Norwegian patient cohort
Authors: Robsahm Trude E. , Falk Ragnhild S. , Eide Nils A. 
Published: March 2023

AbstractPurposeThe purpose of this study is to explore the frequency of additional primary malignancies in uveal melanoma (UM) patients and cause‐specific mortality, to help guide surveillance strategies after UM.MethodsAll patients diagnosed with UM at Oslo University Hospital during 1990–2017 were eligible for inclusion. Linkage to the Cancer Registry of Norway obtained information on additional malignancies and cause of death throughout 2019. UM patients were categorized according to timing of additional malignancy (prior/simultaneously or after UM) or no additional cancer, and by UM stage at diagnosis. Age‐adjusted mortality rates were presented per 1000 person‐years with 95% confidence intervals (CI).ResultsThe study population included 960 UM patients: 77% were diagnosed in stage and I/II and 56% were men. Mean age at diagnosis was 63 years. Additional malignancies were observed in 152 patients prior/simultaneous to UM, and in 120 patients >1 year after UM. Overall, mortality per 1000 person‐years was 3.5 (95% CI 3.1–3.9) for UM and 3.0 (2.6–3.4) for other causes. Lowest UM mortality [1.3 (0.60–2.1)] was seen in patients with a second malignancy after UM, regardless of stage. Highest UM mortality was seen for UM patients in stage III/IV, both without [16.1 (13.2–19.1)] and with any additional malignancy [16.9 (6.6–27.3)].ConclusionOur results support that UM patients frequently have additional malignancies, both before and after UM. Low‐UM mortality in patients with a primary malignancy after UM, might indicate less aggressive UM. The cumulative UM mortality flattens about 10 years after diagnosis and annual follow‐up of patients for 10 years seems adequate.
Longitudinal association between overweight years, polygenic risk and NAFLD, significant fibrosis and cirrhosis
Authors: Ajmera Veeral , Wang Na , Xu Hanfei , Liu Ching‐Ti , Long Michelle T. 
Published: March 2023

SummaryBackgroundAdiposity amplifies the genetic risk of non‐alcoholic fatty liver disease (NAFLD).AimWe evaluated the association between overweight‐years, a cumulative exposure based on the product of the duration and severity of excess body weight (body mass index (BMI) ≥ 25 kg/m2), and genetic risk on liver fat and fibrosis.MethodsThis is a longitudinal analysis derived from a prospective cohort of adults in the Framingham Heart Study who underwent genotyping and vibration‐controlled‐transient‐elastography with controlled attenuation parameter. Univariable and multivariable linear and logistic regression analyses were used to assess the association between overweight‐years and liver fat and fibrosis. The association between genetic variants of liver fat (PNPLA3, TM6SF2, GCKR) and fibrosis (PNPLA3, TM6SF2, HSD17B13) was also assessed using a polygenic risk score.ResultsOur sample included 2478 participants (54% women) with mean age and BMI of 40 (±8.5) years and 26.5(±5.1) kg/m2, respectively. The mean follow‐up was 14(±0.9) years, and each participant underwent three study visits. The prevalence of NAFLD was 28.3% (n = 700), and 207 (8.4%) had clinically significant fibrosis. In age‐, sex‐ and diabetes‐adjusted multivariable analyses, overweight‐years (per SD) had a strong association with NAFLD (aOR 3.53 [95% CI: 3.10–4.02], p < 0.001), clinically significant fibrosis (aOR 1.60 [95% CI: 1.40–1.84], p < 0.001) and cirrhosis (aOR 1.81 [95% CI: 1.38–2.37], p < 0.001). High‐polygenic risk was significantly associated with liver fat and clinically significant fibrosis (p < 0.05).ConclusionOverweight‐years is strongly associated with NAFLD and clinically significant fibrosis and combined with polygenic risk may assist in defining the trajectory of NAFLD.
Caveolae‐associated protein 3 promotes adipogenic differentiation of porcine preadipocytes by promoting extracellular signal‐regulated kinase phosphorylation
Authors: Shi Mingyue , Yang Shuai , Huang Xiaoyu , Wang Shouyuan , Li Wenxia , Yun Jiale , Lu Chang , Yang Yang , Cai Chunbo , Gao Pengfei , Guo Xiaohong , Li Bugao , Cao Guoqing 
Published: March 2023

AbstractFat deposition is one of the key factors affecting the economic development of pig husbandry. The aim of this study was to investigate the expression characteristics of caveolae‐associated protein 3 (CAVIN3) and to elucidate its effect and mechanism on adipogenic differentiation of porcine preadipocytes. Cell transfection, quantitative reverse transcription polymerase chain reaction (qRT‐PCR), western blot, and oil red O staining were used to detect the effect of CAVIN3 on the differentiation of porcine preadipocytes. The results showed that CAVIN3 was expressed in various tissues, with higher expression in adipose tissue, differentially expressed during cell adipogenic differentiation, and mainly distributed in the cytoplasm. Functional studies showed that, after CAVIN3 interference in preadipocytes, the expression of adipogenic factors and the content of lipid droplets were significantly decreased (p < 0.05). The results were reversed after CAVIN3 was overexpressed. The mechanism research showed that LY3214996 inhibited the extracellular signal‐regulated kinase (ERK) phosphorylation and further inhibited lipogenic factors expression. Overexpression of CAVIN3 attenuates the inhibitory effect of LY3214996 on ERK phosphorylation and attenuates its inhibitory effect on adipogenic differentiation. Therefore, this study demonstrated that CAVIN3 promotes the differentiation of porcine preadipocytes by promoting ERK phosphorylation. The present study can lay a theoretical foundation for further studying the molecular mechanism of porcine fat deposition.
Bifidobacterium promotes retinal ganglion cell survival by regulating the balance of retinal glial cells
Authors: Zhao Xiaohuan , Xu Mengqiao , Zhao Zhenzhen , Wang Yimin , Liu Yang , Zhang Ting , Wan Xiaoling , Jiang Mei , Luo Xueting , Shen Yao , Chen Lei , Zhou Minwen , Wang Feng , Sun Xiaodong 
Published: March 2023

AbstractIntroductionOptic nerve injury is a leading cause of irreversible blindness worldwide. The retinal ganglion cells (RGCs) and their axons cannot be regenerated once damaged. Therefore, reducing RGC damage is crucial to prevent blindness. Accordingly, we aimed to investigate the potential influence of the gut microbiota on RGC survival, as well as the associated action mechanisms.MethodsWe evaluated the effects of microbiota, specifically Bifidobacterium, on RGC. Optic nerve crush (ONC) was used as a model of optic nerve injury. Vancomycin and Bifidobacterium were orally administered to specific pathogen‐free (SPF) mice.ResultsBifidobacterium promoted RGC survival and optic nerve regeneration. The administration of Bifidobacterium inhibited microglia activation but promoted Müller cell activation, which was accompanied by the downregulation of inflammatory cytokines and upregulation of neurotrophic factors and retinal ERK/Fos signaling pathway activation.ConclusionsOur study demonstrates that Bifidobacterium‐induced changes in intestinal flora promote RGC survival. The protective effect of Bifidobacterium on RGC can be attributed to the inhibition of microglia activation and promotion of Müller cell activation and the secondary regulation of inflammatory and neurotrophic factors.
FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis
Authors: Zhang Qingxiang , Chen Zhiguo , Zhang Kaili , Zhu Jie , Jin Tao 
Published: March 2023

BackgroundWith millions of victims worldwide, multiple sclerosis is the second most common cause of disability among young adults. Although formidable advancements have been made in understanding the disease, the neurodegeneration associated with multiple sclerosis is only partially counteracted by current treatments, and effective therapy for progressive multiple sclerosis remains an unmet need. Therefore, new approaches are required to delay demyelination and the resulting disability and to restore neural function by promoting remyelination and neuronal repair.AimsThe article reviews the latest literature in this field.Materials and methodsThe fibroblast growth factor (FGF) signaling pathway is a promising target in progressive multiple sclerosis.DiscussionFGF signal transduction contributes to establishing the oligodendrocyte lineage, neural stem cell proliferation and differentiation, and myelination of the central nervous system. Furthermore, FGF signaling is implicated in the control of neuroinflammation. In recent years, interventions targeting FGF, and its receptor (FGFR) have been shown to ameliorate autoimmune encephalomyelitis symptoms in multiple sclerosis animal models moderately.ConclusionHere, we summarize the recent findings and investigate the role of FGF/FGFR signaling in the onset and progression, discuss the potential therapeutic advances, and offer fresh insights into managing multiple sclerosis.
The impact of share‐pledging purposes on firm performance and innovation
Authors: Jia Xiao , Jiang Ellen Jin , Wang Rui 
Published: March 2023

AbstractResearch questionShare pledging by controlling shareholders can be motivated by business or personal purposes. We investigate whether the firm performance and innovation outputs are different for firms with controlling shareholders pledging shares to support their firm's financing (business‐pledging firms) and those pledging shares for increasing personal wealth (individual‐pledging firms).Research findingsUsing data from publicly listed Chinese firms, we find that business‐pledging firms are associated with higher changes in Tobin's Q and more patent outputs compared with individual‐pledging firms. In additional tests, we show that the impact of share‐pledging purposes on firm performance and innovative outputs is more pronounced for Chinese non‐state‐owned enterprises, which have relatively limited access to traditional bank loans.Theoretical implicationsIn this study, we bring new empirical evidence to agency theory, especially the “principal–principal” problem. We identify two inherently different purposes in share‐pledging cases—business pledging and individual pledging. We show that in business‐pledging cases, pledgers' interests become more aligned with outside shareholders, and pledgers have higher incentives to enhance firm value and innovation productivity, relative to individual pledging. This paper adds to the evidence on the bright side of share pledges.Practitioner implicationsThis paper sheds light on the recent policy debate regarding the costs and benefits of share pledging and has implications for regulators and investors. Thus, it may be vital for publicly listed firms to disclose the purposes of share pledging.
Cytomegalovirus serology in young to mid‐adult life and decline of lung function
Authors: Nenna Raffaella , Zhai Jing , Spangenberg Amber , Sherrill Duane L. , Martinez Fernando D. , Halonen Marilyn , Guerra Stefano 
Published: March 2023

AbstractIntroductionCytomegalovirus (CMV) seropositivity has been recently linked to severity and progression of asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). To date, no longitudinal study has addressed the relation of CMV serology to levels and decline of lung function in the general adult population.MethodsWe evaluated 403 participants from the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD) who at enrollment were aged 28–55 years and completed lung function tests. During follow‐up, the 403 participants completed on average 7.2 lung function tests per subject for a total of 2908 observations over a mean period of 14.7 years. We tested CMV serology in serum samples from enrollment and categorized participants into low, medium, and high CMV serology based on tertiles. The relation of CMV serology at enrollment to lung function levels and decline during follow‐up was tested in multivariate random coefficients models.ResultsAfter full adjustment, participants in the highest CMV serology tertile had faster declines of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) compared with subjects in the lowest tertile (by −7.9 ml/year 95% confidence interval [−13.9 ml/year, −1.93 ml/year], and by −0.13%/year [−0.23%/year, −0.026%/year], respectively). These CMV effects were additive with those of cigarette smoking. No associations were found between CMV serology and FVC, indicating specific effects of CMV seropositivity on airflow limitation.ConclusionHigh CMV serology in young to mid‐adult life may be linked to increased COPD risk through an accelerated decline of lung function.
Conservation prioritisation through genomic reconstruction of demographic histories applied to two endangered suids in the Malay Archipelago
Authors: Schleimer Anna , Frantz Alain C. , Richart Lorraine , Mehnert Jörg , Semiadi Gono ,   Wirdateti, Rode‐Margono Johanna , Mittelbronn Michel , Young Stuart , Drygala Frank 
Published: March 2023

AbstractAimThe biodiversity of the Malay Archipelago is the product of the region's rich biogeographical history with periods of island connectivity and isolation during the Pleistocene glacial cycles. Here, the case of two endemic suid species, the Javan (Sus verrucosus) and Bawean (S. blouchi) warty pigs, was used to illustrate how biogeographic processes and recent anthropogenic pressures can shape demographic histories with significant implications for species conservation.LocationMalay Archipelago, with focus on Bawean and Java.MethodsWe employed genome‐wide single nucleotide polymorphisms from the Porcine SNP60 v2 BeadChip to assess interspecific genetic differentiation, to estimate divergence times and to perform demographic model selection.ResultsIn contrast to the hypothesis of recent divergence during the last glacial maximum, S. blouchi was found to have diverged from S. verrucosus at least 166 k years ago following a founder event. The contemporary S. blouchi population was characterised by a recent bottleneck that reduced the effective population size to less than 20. The genomic assessment supports the single species status of S. blouchi, as was previously proposed based on morphometrics. The demographic history of S. verrucosus showed evidence of secondary contact with the sympatric banded pig (S. scrofa vittatus) that colonised Java 70 k years ago.Main ConclusionsWhile the Javan and Bawean warty pigs have persisted throughout the Pleistocene climatic oscillations, contemporary pressures from human activities threaten their survival and immediate action should be taken to grant legal protection to both S. verrucosus and S. blouchi. This study highlighted the use of demographic history modelling using genomic data to identify evolutionary significant units and inform conservation.
Teaching Honesty and Improving Democracy in the Post‐Truth Era
Authors: Stitzlein Sarah 
Published: March 2023

AbstractIn this paper, Sarah Stitzlein considers the consequences of honesty on our democracy, especially for citizens' ability to engage in civic inquiry together as they face shared problems. Honesty is a key component of a well‐functioning democracy; it develops trust and fosters the sorts of relationships among citizens that enable civic dialogue and reasoning. Post‐truth attitudes and truth decay pose serious obstacles to good civic reasoning as citizens struggle to draw clear distinctions between fact and opinion, weigh personal beliefs and emotions over facts, and increasingly distrust traditionally respected sources of information. Stitzlein employs a Deweyan pragmatist account of truth and a distinctly social account of democracy to build a case for foregrounding honesty in the development of citizens. She describes how schools can employ communities of inquiry to cultivate habits of honesty within citizenship education. She explains how a better democracy — one grounded in a wider understanding of social life and relationships — might head off the temptation to be dishonest for self‐serving reasons, focusing on how dishonesty jeopardizes our relationships to each other as citizens and our ability to engage in civic reasoning together to fulfill shared goals.
Unlocking the genome of perch – From genes to ecology and back again
Authors: Vasemägi Anti , Ozerov Mikhail , Noreikiene Kristina , López María‐Eugenia , Gårdmark Anna 
Published: March 2023

AbstractEurasian perchPerca fluviatilishas been a popular model species for decades in the fields of aquatic ecology, community dynamics, behaviour, physiology and ecotoxicology. Yet, despite extensive research, the progress of integrating genomic perspective into existing ecological knowledge in perch has been relatively modest. Meanwhile, the emergence of high‐throughput sequencing technologies has completely changed the methods for genetic variation assessment and conducting biodiversity and evolutionary research. During the last 5 years, three genome assemblies ofP. fluviatilishave been generated, allowing substantial advancement of our understanding of the interactions between ecological and evolutionary processes at the whole‐genome level. We review the past progress, current status and potential future impact of the genomic resources and tools for ecological research in Eurasian perch focusing on the utility of recent whole‐genome assemblies. Furthermore, we demonstrate the power of genome‐wide approaches and newly developed tools and outline recent cases where genomics have contributed to new ecological and evolutionary knowledge. We explore how the availability of reference assembly enables the efficient application of various statistical tools, and how genomic approaches can provide novel insights into resource polymorphism, host–parasite interactions and to genetic and phenotypic changes associated with climate change and harvesting‐induced evolution. In summary, we call for increased integration of genomic tools into ecological research for perch, as well as for other fish species, which is likely to yield novel insights into processes linking the adaptation and plasticity to ecosystem functioning and environmental change.
Topical application of imatinib mesylate ameliorated psoriasis‐like skin lesions in imiquimod‐induced murine model via angiogenesis inhibition
Authors: Hayakawa Kazuma , Maeda Tatsuo , Egusa Chizu , Okubo Yukari , Harada Kazutoshi 
Published: March 2023

AbstractPsoriasis is a chronic skin disorder characterized by a skin rash with scaly patches. Microvascular abnormalities are a characteristic feature of psoriasis and play a crucial role in the pathogenesis of psoriatic lesions. Angiogenic factors are upregulated in psoriatic skin lesions and are thought to induce angiogenesis. Platelet‐derived growth factor (PDGF) induces vascular endothelial growth factor (VEGF), and PDGF is upregulated in keratinocytes in psoriatic skin lesions. The present study aimed to investigate the effect of topical imatinib mesylate (IMT) in inhibiting the activation of PDGF signalling in the pathogenesis of psoriasis. When topically applied to the skin of mice with imiquimod (IMQ)‐induced psoriasis, IMT ameliorated skin symptoms similar to those of human psoriasis. Hyperproliferation of keratinocytes, hyperkeratosis, inflammatory cell infiltration and hypervascularity were histologically suppressed by topical IMT. The expression of angiogenic factors including fibroblast growth factor (FGF) and VEGF was decreased. The expression of FGF and VEGF in a PDGF‐stimulated fibroblast cell line was inhibited by IMT. PDGF is required for the signalling pathway producing angiogenic factors in fibroblast. Thus, topically applied IMT inhibits PDGFR activation in fibroblast and suppresses the production of angiogenic factors, thereby mitigating the symptoms of psoriasis. The inhibitory effect of IMT on angiogenesis suggests that topical application IMT may be a viable treatment option for psoriasis.
A novel prediction approach of polymer gear contact fatigue based on a WGAN‐XGBoost model
Authors: Jia Chenfan , Wei Peitang , Lu Zehua , Ye Mao , Zhu Rui , Liu Huaiju 
Published: March 2023

AbstractPolymer gears have long been used on power transmissions with the fundamental durability data, including fatigue S‐N curves, yielding important data informing reliable and compact designs. This paper proposed a prediction method for polyformaldehyde (POM) gear fatigue life based on the innovative WGAN‐XGBoost algorithm. The findings generated herein revealed that the proposed method performs well in terms of prediction accuracy. The predicted fatigue lives, analyzed under different loading conditions, were within 1.5 times dispersion band compared with experimental results. Furthermore, based upon the enhanced fatigue dataset, a thermo‐mechanical coupled prediction formula for POM gear contact fatigue life was proposed. These findings offered a new approach for high‐power density design of polymer gears.
The consequences of non‐trading institutional investors
Authors: Irani Mohammad (Vahid) , Kim Hugh Hoikwang 
Published: March 2023

AbstractWe document that institutional investors do not trade a single share, on average, in one of five stocks in their portfolio for an extended period. Investors with high inaction are likely to underperform in the future. Our results show a similar underperformance for stocks with a high non‐trading level of institutional investors. We investigate several behavioral biases as potential drivers of the non‐trades and find no evidence of distraction, overconfidence, and disposition effects. Institutional investors’ tendency to sell stocks with salient price movements and recency bias best explains their inactions. Overall, the non‐trading behavior of institutional investors serves as a unique predictor for their future performance and potential behavioral biases are driving this predictability.