bluuebunny/crossref_metadata_2025_split huggingface dataset:
14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice
Authors: Cho Eunsil , Park Jinsil , Hwang Eun Mi , Kim Hyung Wook , Park Jae-Yong 
Published: January 2023

AbstractThe 14-3-3 protein family with seven isoforms found in mammals is widely expressed in the brain and plays various roles in cellular processes. Several studies have reported that 14-3-3γ, one of the 14-3-3 protein isoforms, is associated with neurological and psychiatric disorders, but the role of 14-3-3γ in the pathophysiology of brain diseases is unclear. Although studies have been conducted on the relationship between 14-3-3γ protein and Parkinson’s disease (PD), a common neurodegenerative disorder with severe motor symptoms such as bradykinesia and rigidity, a direct connection remains to be elucidated. We recently showed that adult heterozygous 14-3-3γ knockout mice are hyperactive and exhibit anxiety-like behavior. In this study, we further characterized the molecular and behavioral changes in aged 14-3-3γ heterozygous mice to investigate the role of 14-3-3γ in the brain. We observed decreased dopamine levels and altered dopamine metabolism in the brains of these mice, including changes in the phosphorylation of proteins implicated in PD pathology. Furthermore, we confirmed that they displayed PD symptom-like behavioral deficits, such as impaired motor coordination and decreased ability to the nest-building activity. These findings suggest an association between 14-3-3γ dysfunction and PD pathophysiology.
KLF14 regulates the growth of hepatocellular carcinoma cells via its modulation of iron homeostasis through the repression of iron-responsive element-binding protein 2
Authors: Zhou Hui , Chen Junru , Fan Mingjie , Cai Huajian , Dong Yufei , Qiu Yue , Zhuang Qianqian , Lei Zhaoying , Li Mengyao , Ding Xue , Yan Peng , Lin Aifu , Zheng Shusen , Yan Qingfeng 
Published: January 2023

Abstract
Background
Hepatocellular carcinoma (HCC) is a multifactor-driven malignant tumor with rapid progression, which causes the difficulty to substantially improve the prognosis of HCC. Limited understanding of the mechanisms in HCC impedes the development of efficacious therapies. Despite Krüpple-Like factors (KLFs) were reported to be participated in HCC pathogenesis, the function of KLF14 in HCC remains largely unexplored.

Methods
We generated KLF14 overexpressed and silenced liver cancer cells, and nude mouse xenograft models for the in vitro and in vivo study. Luciferase reporter assay, ChIP-qPCR, Co-IP, immunofluorescence were performed for mechanism research. The expression of KLF14 in HCC samples was analyzed by quantitative RT-PCR, Western blotting, and immunohistochemistry (IHC) analysis.

Results
KLF14 was significantly downregulated in human HCC tissues, which was highly correlated with poor prognosis. Inhibition of KLF14 promoted liver cancer cells proliferation and overexpression of KLF14 suppressed cells growth. KLF14 exerts its anti-tumor function by inhibiting Iron-responsive element-binding protein 2 (IRP2), which then causes transferrin receptor-1(TfR1) downregulation and ferritin upregulation on the basis of IRP-IREs system. This then leading to cellular iron deficiency and HCC cells growth suppression in vitro and in vivo. Interestingly, KLF14 suppressed the transcription of IRP2 via recruiting SIRT1 to reduce the histone acetylation of the IRP2 promoter, resulting in iron depletion and cell growth suppression. More important, we found fluphenazine is an activator of KLF14, inhibiting HCC cells growth through inducing iron deficiency.

Conclusion
KLF14 acts as a tumor suppressor which inhibits the proliferation of HCC cells by modulating cellular iron metabolism via the repression of IRP2. We identified Fluphenazine, as an activator of KLF14, could be a potential compound for HCC therapy. Our findings therefore provide an innovative insight into the pathogenesis of HCC and a promising therapeutic target.
The gut microbiota in multiple sclerosis varies with disease activity
Authors: Thirion Florence , Sellebjerg Finn , Fan Yong , Lyu Liwei , Hansen Tue H. , Pons Nicolas , Levenez Florence , Quinquis Benoit , Stankevic Evelina , Søndergaard Helle B. , Dantoft Thomas M. , Poulsen Casper S. , Forslund Sofia K. , Vestergaard Henrik , Hansen Torben , Brix Susanne , Oturai Annette , Sørensen Per Soelberg , Ehrlich Stanislav D. , Pedersen Oluf 
Published: January 2023

Abstract
Background
Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known.

Methods
Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity.

Results
We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-β, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages.

Conclusions
Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials.
Glucose metabolism tests and recurrent pregnancy loss: evidence from a systematic review and meta-analysis
Authors: Hantoushzadeh Sedigheh , Kohandel Gargari Omid , Shafiee Arman , Seighali Niloofar , Ghaemi Marjan 
Published: January 2023

Abstract
Objective
To synthesize the published citations to determine the association between glucose metabolism tests and recurrent pregnancy loss (RPL).

Method
The electronic databases including PubMed, Scopus and Web of Science were searched for the original articles that evaluated the correlation between glucose metabolism tests including fasting blood glucose (FBG), fasting insulin (FI), homeostatic model assessment for insulin resistance (HOMA-IR), the rate of individuals with HOMA-IR  > 4.5, insulin resistance, fasting glucose/fasting insulin (FG/FI) and FG/FI  > 4.5.and recurrent pregnancy loss with a combination of proper keywords.

Results
The database search led to finding 390 articles. Detailed screening of titles and abstracts for potential eligibility was performed, and after excluding the duplicated and irrelevant citations, finally, 8 studies were selected to be included in this study, 7 observational studies and one controlled clinical trial. A significant difference in the amount of FI, HOMA-IR, the rate of HOMA-IR  > 4.5, the rate of individuals with insulin resistance, fasting glucose/fasting insulin (FG/FI), and the rate of FG/FI  > 4.5 were found among RPL patients compared to controls. There was no difference when comparing FBG between the groups.

Conclusion
This study indicates an important link between abnormal glucose metabolism tests and a history of recurrent pregnancy loss. These data may encourage clinicians to request glucose metabolism tests other than FBG in women with recurrent pregnancy loss.
East African cichlid fishes
Authors: Santos M. Emília , Lopes João F. , Kratochwil Claudius F. 
Published: January 2023

AbstractCichlid fishes are a very diverse and species-rich family of teleost fishes that inhabit lakes and rivers of India, Africa, and South and Central America. Research has largely focused on East African cichlids of the Rift Lakes Tanganyika, Malawi, and Victoria that constitute the biodiversity hotspots of cichlid fishes. Here, we give an overview of the study system, research questions, and methodologies. Research on cichlid fishes spans many disciplines including ecology, evolution, physiology, genetics, development, and behavioral biology. In this review, we focus on a range of organismal traits, including coloration phenotypes, trophic adaptations, appendages like fins and scales, sensory systems, sex, brains, and behaviors. Moreover, we discuss studies on cichlid phylogenies, plasticity, and general evolutionary patterns, ranging from convergence to speciation rates and the proximate and ultimate mechanisms underlying these processes. From a methodological viewpoint, the last decade has brought great advances in cichlid fish research, particularly through the advent of affordable deep sequencing and advances in genetic manipulations. The ability to integrate across traits and research disciplines, ranging from developmental biology to ecology and evolution, makes cichlid fishes a fascinating research system.
Immune activation during pregnancy exacerbates ASD-related alterations in Shank3-deficient mice
Authors: Atanasova Ekaterina , Arévalo Andrea Pérez , Graf Ines , Zhang Rong , Bockmann Juergen , Lutz Anne-Kathrin , Boeckers Tobias M. 
Published: January 2023

Abstract
Background
Autism spectrum disorder (ASD) is mainly characterized by deficits in social interaction and communication and repetitive behaviors. Known causes of ASD are mutations of certain risk genes like the postsynaptic protein SHANK3 and environmental factors including prenatal infections.

Methods
To analyze the gene-environment interplay in ASD, we combined the Shank3Δ11−/− ASD mouse model with maternal immune activation (MIA) via an intraperitoneal injection of polyinosinic/polycytidylic acid (Poly I:C) on gestational day 12.5. The offspring of the injected dams was further analyzed for autistic-like behaviors and comorbidities followed by biochemical experiments with a focus on synaptic analysis.

Results
We show that the two-hit mice exhibit excessive grooming and deficits in social behavior more prominently than the Shank3Δ11−/− mice. Interestingly, these behavioral changes were accompanied by an unexpected upregulation of postsynaptic density (PSD) proteins at excitatory synapses in striatum, hippocampus and prefrontal cortex.

Limitations
We found several PSD proteins to be increased in the two-hit mice; however, we can only speculate about possible pathways behind the worsening of the autistic phenotype in those mice.

Conclusions
With this study, we demonstrate that there is an interplay between genetic susceptibility and environmental factors defining the severity of ASD symptoms. Moreover, we show that a general misbalance of PSD proteins at excitatory synapses is linked to ASD symptoms, making this two-hit model a promising tool for the investigation of the complex pathophysiology of neurodevelopmental disorders.
CDK8/19 inhibition plays an important role in pancreatic β-cell induction from human iPSCs
Authors: Sakuma Kensuke , Tsubooka-Yamazoe Noriko , Hashimoto Kiyohiro , Sakai Nozomu , Asano Shinya , Watanabe-Matsumoto Saori , Watanabe Takeshi , Saito Bunnai , Matsumoto Hirokazu , Ueno Hikaru , Ito Ryo , Toyoda Taro 
Published: January 2023

Abstract
Background
Transplantation of differentiated cells from human-induced pluripotent stem cells (hiPSCs) holds great promise for clinical treatments. Eliminating the risk factor of malignant cell transformation is essential for ensuring the safety of such cells. This study was aimed at assessing and mitigating mutagenicity that may arise during the cell culture process in the protocol of pancreatic islet cell (iPIC) differentiation from hiPSCs.

Methods
We evaluated the mutagenicity of differentiation factors used for hiPSC-derived pancreatic islet-like cells (iPICs). We employed Ames mutagenicity assay, flow cytometry analysis, immunostaining, time-resolved fluorescence resonance energy transfer-based (TR-FRET) cell-free dose–response assays, single-cell RNA-sequencing and in vivo efficacy study.

Results
We observed a mutagenic effect of activin receptor-like kinase 5 inhibitor II (ALK5iII). ALK5iII is a widely used β-cell inducer but no other tested ALK5 inhibitors induced β-cells. We obtained kinase inhibition profiles and found that only ALK5iII inhibited cyclin-dependent kinases 8 and 19 (CDK8/19) among all ALK5 inhibitors tested. Consistently, CDK8/19 inhibitors efficiently induced β-cells in the absence of ALK5iII. A combination treatment with non-mutagenic ALK5 inhibitor SB431542 and CDK8/19 inhibitor senexin B afforded generation of iPICs with in vitro cellular composition and in vivo efficacy comparable to those observed with ALK5iII.

Conclusion
Our findings suggest a new risk mitigation approach for cell therapy and advance our understanding of the β-cell differentiation mechanism.
Neuroblasts migration under control of reactive astrocyte-derived BDNF: a promising therapy in late neurogenesis after traumatic brain injury
Authors: Wu Na , Sun Xiaochuan , Zhou Chao , Yan Jin , Cheng Chongjie 
Published: January 2023

Abstract
Background
Traumatic brain injury (TBI) is a disease with high mortality and morbidity, which leads to severe neurological dysfunction. Neurogenesis has provided therapeutic options for treating TBI. Brain derived neurotrophic factor (BDNF) plays a key role in neuroblasts migration. We aimed to investigate to the key regulating principle of BDNF in endogenous neuroblasts migration in a mouse TBI model.

Methods
In this study, controlled cortical impact (CCI) mice (C57BL/6J) model was established to mimic TBI. The sham mice served as control. Immunofluorescence staining and enzyme-linked immunosorbent assay were performed on the CCI groups (day 1, 3, 7, 14 and 21 after CCI) and the sham group. All the data were analyzed with Student’s t-test or one-way or two-way analysis of variance followed by Tukey’s post hoc test.

Results
Our results revealed that neuroblasts migration initiated as early as day 1, peaking at day 7, and persisted till day 21. The spatiotemporal profile of BDNF expression was similar to that of neuroblasts migration, and BDNF level following CCI was consistently higher in injured cortex than in subventricular zone (SVZ). Reactive astrocytes account for the major resource of BDNF along the migrating path, localized with neuroblasts in proximity. Moreover, injection of exogenous CC chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1, at random sites promoted neuroblasts migration and astrocytic BDNF expression in both normal and CCI mice (day 28). These provoked neuroblasts can also differentiate into mature neurons. CC chemokine ligand receptor 2 antagonist can restrain the neuroblasts migration after TBI.

Conclusions
Neuroblasts migrated along the activated astrocytic tunnel, directed by BDNF gradient between SVZ and injured cortex after TBI. CCL2 might be a key regulator in the above endogenous neuroblasts migration. Moreover, delayed CCL2 administration may provide a promising therapeutic strategy for late neurogenesis post-trauma.
Analysis of financial development and open innovation oriented fintech potential for emerging economies using an integrated decision-making approach of MF-X-DMA and golden cut bipolar q-ROFSs
Authors: Mikhaylov Alexey , Dinçer Hasan , Yüksel Serhat 
Published: January 2023

AbstractThe purpose of the paper is to identify the factors of financial development that have the greatest impact on open innovation in 7 emerging countries. The analysis was performed featuring the MF-X-DMA method, as well as its further verification for autocorrelation and heteroscedasticity. The time period covers years from 2002 to 2020. The article states that the main indicators to improve financial development should enhance the process of bank lending and equity market development. An important area is the development of competition by providing equal access to information to all market participants in a continuously refining technical infrastructure. Regression analysis with the MF-X-DMA method confirms the statistical significance of this influence. The article fills the knowledge gap into the link between open innovations and the relatively low capitalization of the modern emerging countries’ financial market, low liquidity in small cap stocks at the financial market and concentration of the banking sector, as well as risks arising in the process of globalization. Another analysis has also been conducted by generating a novel fuzzy decision-making model. In the first stage, the determinants of open innovation-based fintech potential are weighted for the emerging economies. For this purpose, M-SWARA methodology is taken into consideration based on bipolar q-ROFSs and golden cut. The second stage of the analysis includes evaluating the emerging economies with the determinants of open innovation-based fintech potential. In this context, emerging seven countries are examined with ELECTRE methodology. It found the most significant factor is the open innovation-based fintech potential.
Asymmetric relationship between global and national factors and domestic food prices: evidence from Turkey with novel nonlinear approaches
Authors: Kartal Mustafa Tevfik , Depren Özer 
Published: January 2023

AbstractThis study investigates the asymmetric relationship between global and national factors and domestic food prices in Turkey, considering the recent rapid and continuous increase in domestic food prices. In this context, six global and three national explanatory variables were included, and monthly data for the period from January 2004 to June 2021 were used. In addition, novel nonlinear time-series econometric approaches, such as wavelet coherence, Granger causality in quantiles, and quantile-on-quantile regression, were applied for examination at different times, frequencies, and quantiles. Moreover, the Toda-Yamamoto (TY) causality test and quantile regression (QR) approach were used for robustness checks. The empirical results revealed that (i) there is a significant relationship between domestic food prices and explanatory variables at different times and frequencies; (ii) a causal relationship exists in most quantiles, excluding the lowest quantile, some middle quantiles, and the highest quantile for some variables; (iii) the power of the effect of the explanatory variables on domestic food prices varies according to the quantiles; and (iv) the results were validated by the TY causality test and QR, which show that the results were robust. Overall, the empirical results reveal that global and national factors have an asymmetric relationship with domestic food prices, highlighting the effects of fluctuations in global and national variables on domestic food prices. Thus, the results imply that Turkish policymakers should consider the asymmetric effects of global and national factors on domestic food prices at different times, frequencies, and quantiles.
Mixed reality for extraction of maxillary mesiodens
Authors: Koyama Yu , Sugahara Keisuke , Koyachi Masahide , Tachizawa Kotaro , Iwasaki Akira , Wakita Ichiro , Nishiyama Akihiro , Matsunaga Satoru , Katakura Akira 
Published: January 2023

Abstract

Background
Mesiodentes are the most common supernumerary teeth. The cause is not fully understood, although proliferations of genetic factors and the dental lamina have been implicated. Mesiodentes can cause delayed or ectopic eruption of permanent incisors, which can further alter occlusion and appearance. Careful attention should be paid to the position and direction of the mesiodentes because of possible damage to adjacent roots in the permanent dentition period, errant extraction in the deciduous and mixed dentition periods, and damage to the permanent tooth embryo. To avoid these complications, we applied mixed reality (MR) technology using the HoloLens® (Microsoft, California). In this study, we report on three cases of mesiodentes extraction under general anesthesia using MR technology.

Results
The patients ranged in age from 6 to 11 years, all three were boys, and the direction of eruption was inverted in all cases. The extraction approach was palatal in two cases and labial in one case. The average operative time was 32 min, and bleeding was minimal in all cases. No intraoperative or postoperative complications occurred. An image was shared preoperatively with all the surgeons using an actual situation model. Three surgeons used Microsoft HoloLens® during surgery, shared MR, and operated while superimposing the application image in the surgical field.

Conclusions
The procedure was performed safely; further development of MR surgery support systems in the future is suggested.
Hip fracture or not? The reversed prevalence effect among non-experts’ diagnosis
Authors: Zhang Hanshu , Hung Shen-Wu , Chen Yu-Pin , Ku Jan-Wen , Tseng Philip , Lu Yueh-Hsun , Yang Cheng-Ta 
Published: January 2023

AbstractDespite numerous investigations of the prevalence effect on medical image perception, little research has been done to examine the effect of expertise, and its possible interaction with prevalence. In this study, medical practitioners were instructed to detect the presence of hip fracture in 50 X-ray images with either high prevalence (Nsignal = 40) or low prevalence (Nsignal = 10). Results showed that compared to novices (e.g., pediatricians, dentists, neurologists), the manipulation of prevalence shifted participant’s criteria in a different direction for experts who perform hip fracture diagnosis on a daily basis. That is, when prevalence rate is low (pfracture-present = 0.2), experts held more conservative criteria in answering “fracture-present,” whereas novices were more likely to believe there was fracture. Importantly, participants’ detection discriminability did not vary by the prevalence condition. In addition, all participants were more conservative with “fracture-present” responses when task difficulty increased. We suspect the apparent opposite criteria shift between experts and novices may have come from medical training that made novices to believe that a miss would result in larger cost compared to false positive, or because they failed to update their prior belief about the signal prevalence in the task, both would suggest that novices and experts may have different beliefs in placing the optimal strategy in the hip fracture diagnosis. Our work can contribute to medical education training as well as other applied clinical diagnosis that aims to mitigate the prevalence effect.