bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHOP-mediated IL-23 overexpression does not drive colitis in experimental spondyloarthritis
Authors: Navid Fatemeh , Gill Tejpal , Fones Lilah , Allbritton-King Jules D. , Zhou Kelly , Shen Isabel , Van Doorn Jinny , LiCausi Francesca , Cougnoux Antony , Randazzo Davide , Brooks Stephen R. , Colbert Robert A. 
Published: May 2024

AbstractHLA-B27 is a major risk factor for spondyloarthritis (SpA), yet the underlying mechanisms remain unclear. HLA-B27 misfolding-induced IL-23, which is mediated by endoplasmic reticulum (ER) stress has been hypothesized to drive SpA pathogenesis. Expression of HLA-B27 and human β2m (hβ2m) in rats (HLA-B27-Tg) recapitulates key SpA features including gut inflammation. Here we determined whether deleting the transcription factor CHOP (Ddit3−/−), which mediates ER-stress induced IL-23, affects gut inflammation in HLA-B27-Tg animals. ER stress-mediated Il23a overexpression was abolished in CHOP-deficient macrophages. Although CHOP-deficiency also reduced Il23a expression in immune cells isolated from the colon of B27+ rats, Il17a levels were not affected, and gut inflammation was not reduced. Rather, transcriptome analysis revealed increased expression of pro-inflammatory genes, including Il1a, Ifng and Tnf in HLA-B27-Tg colon tissue in the absence of CHOP, which was accompanied by higher histological Z-scores. RNAScope localized Il17a mRNA to the lamina propria of the HLA-B27-Tg rats and revealed similar co-localization with Cd3e (CD3) in the presence and absence of CHOP. This demonstrates that CHOP-deficiency does not improve, but rather exacerbates gut inflammation in HLA-B27-Tg rats, indicating that HLA-B27 is not promoting gut disease through ER stress-induced IL-23. Hence, CHOP may protect rats from more severe HLA-B27-induced gut inflammation.
Tuning pore size and density of rigid polylactic acid foams through thermally induced phase separation and optimization using response surface methodology
Authors: Ghorbandoust Morteza , Fasihi Mohammad , Norouzbeigi Reza 
Published: May 2024

AbstractRigid polylactic acid (PLA) foams fabricated via thermally induced phase separation (TIPS) utilizing a ternary solution of PLA, Tetrahydrofuran (THF), and water. The PLA gels were stabilized mechanically by the substituting of the THF/water solvent mixture with ethanol as non-solvent and subsequently vacuum dried. A comprehensive characterization of PLA foams was achieved by Scanning Electron Microscopy (SEM), X-ray Diffractometry (XRD) and Brunauer–Emmett–Teller (BET) analyses. The BET area obtained in the PLA foam is up to 18.76 m2/g. The Response Surface Methodology (RSM) was utilized to assess the impacts of four independent variables (polymer concentration, solvent composition, quench temperature, and aging time) on the pore size and density of PLA foam. The experimental findings demonstrated that the fabrication parameters could be fine-tuned to govern the morphology of the pores, comprising their size and density. The optimal values of parameters for cell size were identified by RSM to be 8.96 (wt%), 91.60 (w/w), 5.50 °C, and 3.86 h for the optimum cell size of 37.96 µm (37.78 by Genetic Algorithm). Optimum density by RSM 88.88 mgr/cm3 (88.38 mgr/cm3 by Genetic Algorithm) was obtained at 5.00 (wt%), 89.33 (w/w), 14.40 °C and 2.65 h.
The antipsychotic agent sulpiride microinjected into the ventral pallidum restores positive symptom-like habituation disturbance in MAM-E17 schizophrenia model rats
Authors: Péczely László , Dusa Daniella , Lénárd László , Ollmann Tamás , Kertes Erika , Gálosi Rita , Berta Beáta , Szabó Ádám , László Kristóf , Zagoracz Olga , Karádi Zoltán , Kállai Veronika 
Published: May 2024

AbstractDysfunction of subcortical D2-like dopamine receptors (D2Rs) can lead to positive symptoms of schizophrenia, and their analog, the increased locomotor activity in schizophrenia model MAM-E17 rats. The ventral pallidum (VP) is a limbic structure containing D2Rs. The D2R antagonist sulpiride is a widespread antipsychotic drug, which can alleviate positive symptoms in human patients. However, it is still not known how sulpiride can influence positive symptoms via VP D2Rs. We hypothesize that the microinjection of sulpiride into the VP can normalize hyperactivity in MAM-E17 rats. In addition, recently, we showed that the microinjection of sulpirid into the VP induces place preference in neurotypical rats. Thus, we aimed to test whether intra-VP sulpiride can also have a rewarding effect in MAM-E17 rats. Therefore, open field-based conditioned place preference (CPP) test was applied in neurotypical (SAL-E17) and MAM-E17 schizophrenia model rats to test locomotor activity and the potential locomotor-reducing and rewarding effects of sulpiride. Sulpiride was microinjected bilaterally in three different doses into the VP, and the controls received only vehicle. The results of the present study demonstrated that the increased locomotor activity of the MAM-E17 rats was caused by habituation disturbance. Accordingly, larger doses of sulpiride in the VP reduce the positive symptom-analog habituation disturbance of the MAM-E17 animals. Furthermore, we showed that the largest dose of sulpiride administered into the VP induced CPP in the SAL-E17 animals but not in the MAM-E17 animals. These findings revealed that VP D2Rs play an important role in the formation of positive symptom-like habituation disturbances in MAM-E17 rats.
Improved ACOM pattern matching in 4D-STEM through adaptive sub-pixel peak detection and image reconstruction
Authors: Folastre Nicolas , Cao Junhao , Oney Gozde , Park Sunkyu , Jamali Arash , Masquelier Christian , Croguennec Laurence , Veron Muriel , Rauch Edgar F. , Demortière Arnaud 
Published: May 2024

AbstractThe technique known as 4D-STEM has recently emerged as a powerful tool for the local characterization of crystalline structures in materials, such as cathode materials for Li-ion batteries or perovskite materials for photovoltaics. However, the use of new detectors optimized for electron diffraction patterns and other advanced techniques requires constant adaptation of methodologies to address the challenges associated with crystalline materials. In this study, we present a novel image-processing method to improve pattern matching in the determination of crystalline orientations and phases. Our approach uses sub-pixel adaptive image processing to register and reconstruct electron diffraction signals in large 4D-STEM datasets. By using adaptive prominence and linear filters, we can improve the quality of the diffraction pattern registration. The resulting data compression rate of 103 is well-suited for the era of big data and provides a significant enhancement in the performance of the entire ACOM data processing method. Our approach is evaluated using dedicated metrics, which demonstrate a high improvement in phase recognition. Several features are extracted from the registered data to map properties such as the spot count, and various virtual dark fields, which are used to enhance the handling of the results maps. Our results demonstrate that this data preparation method not only enhances the quality of the resulting image but also boosts the confidence level in the analysis of the outcomes related to determining crystal orientation and phase. Additionally, it mitigates the impact of user bias that may occur during the application of the method through the manipulation of parameters.
Influences of muscle mass loss and exercise habits and personality traits on lower limb motor function among university students
Authors: Sano Nobuyuki , Enoki Haruto , Syutou Reita , Furukawa Ayumu 
Published: May 2024

AbstractSecondary sarcopenia, a risk factor even for young people, has attracted attention because of the deterioration of physical activity and nutritional status due to lifestyle change among university students. However, studies on the factors affecting motor function and their involvement are lacking. This cross-sectional study aimed to examine the influences of muscle mass loss and exercise and sleep habits on lower limb motor function, as well as the involvement of personality traits, in 101 university students. Approximately 6% of the participants had low skeletal muscle mass index, similar to previous reports, and that only exercise habits in high school were responsible for muscle mass loss (direct effect =  − 0.493; p < 0.05), wherease low skeletal muscle mass (direct effect =  − 0.539; p < 0.01) and current exercise habits (direct effect = 0.410; p < 0.01) were responsible for lower limb motor function. Additionaly, only the personality trait of high intellectual curiosity was involved in the establishment of exercise habits in high school, but no other personality traits showed a significant effect. In the prevention of secondary sarcopenia, encouraging sustained exercise habits while considering the influence of different personality traits is expected to prevent the decline in muscle mass and motor function.
A novel strategy to facilitate uniform epithelial cell maturation using liquid–liquid interfaces
Authors: Sonoi Rie , Kamihira Masamichi 
Published: May 2024

AbstractEpithelial tissue forms and maintains a critical barrier function in the body. A novel culture design aimed at promoting uniform maturation of epithelial cells using liquid materials is described. Culturing Madin–Darby canine kidney (MDCK) cells at the liquid–liquid interface yielded reduced migration and stimulated active cell growth. Similar to solid–liquid interfaces, cells cultured on a fibronectin-coated liquid–liquid interface exhibited active migration and growth, ultimately reaching a confluent state. These cells exhibited reduced stress fiber formation and adopted a cobblestone-like shape, which led to their even distribution in the culture vessel. To inhibit stress fiber formation and apoptosis, the exposure of cells on liquid–liquid interfaces to Y27632, a specific inhibitor of the Rho-associated protein kinase (ROCK), facilitated tight junction formation (frequency of ZO-2-positive cells, FZ = 0.73). In Y27632-exposed cells on the liquid–liquid interface, the value obtained by subtracting the standard deviation of the ratio of nucleus densities in each region that compartmentalized a culture vessel from 1, denoted as HLN, was 0.93 ± 0.01, indicated even cell distribution in the culture vessel at t = 72 h. The behavior of epithelial cells on liquid–liquid interfaces contributes to the promotion of their uniform maturation.
Dysregulated Wnt and NFAT signaling in a Parkinson’s disease LRRK2 G2019S knock-in model
Authors: Wetzel Andrea , Lei Si Hang , Liu Tiansheng , Hughes Michael P. , Peng Yunan , McKay Tristan , Waddington Simon N. , Grannò Simone , Rahim Ahad A. , Harvey Kirsten 
Published: May 2024

AbstractParkinson’s disease (PD) is a progressive late-onset neurodegenerative disease leading to physical and cognitive decline. Mutations of leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of PD. LRRK2 is a complex scaffolding protein with known regulatory roles in multiple molecular pathways. Two prominent examples of LRRK2-modulated pathways are Wingless/Int (Wnt) and nuclear factor of activated T-cells (NFAT) signaling. Both are well described key regulators of immune and nervous system development as well as maturation. The aim of this study was to establish the physiological and pathogenic role of LRRK2 in Wnt and NFAT signaling in the brain, as well as the potential contribution of the non-canonical Wnt/Calcium pathway. In vivo cerebral Wnt and NFATc1 signaling activity was quantified in LRRK2 G2019S mutant knock-in (KI) and LRRK2 knockout (KO) male and female mice with repeated measures over 28 weeks, employing lentiviral luciferase biosensors, and analyzed using a mixed-effect model. To establish spatial resolution, we investigated tissues, and primary neuronal cell cultures from different brain regions combining luciferase signaling activity, immunohistochemistry, qPCR and western blot assays. Results were analyzed by unpaired t-test with Welch’s correction or 2-way ANOVA with post hoc corrections. In vivo Wnt signaling activity in LRRK2 KO and LRRK2 G2019S KI mice was increased significantly ~ threefold, with a more pronounced effect in males (~ fourfold) than females (~ twofold). NFATc1 signaling was reduced ~ 0.5-fold in LRRK2 G2019S KI mice. Brain tissue analysis showed region-specific expression changes in Wnt and NFAT signaling components. These effects were predominantly observed at the protein level in the striatum and cerebral cortex of LRRK2 KI mice. Primary neuronal cell culture analysis showed significant genotype-dependent alterations in Wnt and NFATc1 signaling under basal and stimulated conditions. Wnt and NFATc1 signaling was primarily dysregulated in cortical and hippocampal neurons respectively. Our study further built on knowledge of LRRK2 as a Wnt and NFAT signaling protein. We identified complex changes in neuronal models of LRRK2 PD, suggesting a role for mutant LRRK2 in the dysregulation of NFAT, and canonical and non-canonical Wnt signaling.
Adverse effects of excessive dietary arachidonic acid on survival, PUFA-derived enzymatic and non-enzymatic oxylipins, stress response in rainbow trout fry
Authors: Cardona Emilie , Segret Emilien , Heraud Cécile , Roy Jerome , Vigor Claire , Gros Valérie , Reversat Guillaume , Sancho-Zubeldia Battitte , Oger Camille , Durbec Anaelle , Bertrand-Michel Justine , Surget Anne , Galano Jean-Marie , Corraze Geneviève , Cachelou Yoann , Marchand Yann , Durand Thierry , Cachelou Frederic , Skiba-Cassy Sandrine 
Published: May 2024

AbstractArachidonic acid (C20: 4n-6, AA) plays a fundamental role in fish physiology, influencing growth, survival and stress resistance. However, imbalances in dietary AA can have detrimental effects on fish health and performance. Optimal AA requirements for rainbow trout have not been established. This study aimed to elucidate the effects of varying dietary AA levels on survival, growth, long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic capacity, oxylipin profiles, lipid peroxidation, and stress resistance of rainbow trout fry. Over a period of eight weeks, 4000 female rainbow trout fry at the resorptive stage (0.12 g) from their first feeding were fed diets with varying levels of AA (0.6%, 1.1% or 2.5% of total fatty acids) while survival and growth metrics were closely monitored. The dietary trial was followed by an acute confinement stress test. Notably, while the fatty acid profiles of the fish reflected dietary intake, those fed an AA-0.6% diet showed increased expression of elongase5, highlighting their inherent ability to produce LC-PUFAs from C18 PUFAs and suggesting potential AA or docosapentaenoic acidn-6 (DPAn-6) biosynthesis. However, even with this biosynthetic capacity, the trout fed reduced dietary AA had higher mortality rates. The diet had no effect on final weight (3.38 g on average for the three diets). Conversely, increased dietary AA enhanced eicosanoid production from AA, suggesting potential inflammatory and oxidative consequences. This was further evidenced by an increase in non-enzymatic lipid oxidation metabolites, particularly in the AA-2.5% diet group, which had higher levels of phytoprostanes and isoprostanes, markers of cellular oxidative damage. Importantly, the AA-1.1% diet proved to be particularly beneficial for stress resilience. This was evidenced by higher post-stress turnover rates of serotonin and dopamine, neurotransmitters central to the fish's stress response. In conclusion, a dietary AA intake of 1.1% of total fatty acids appears to promote overall resilience in rainbow trout fry.
PRSS3/mesotrypsin as a putative regulator of the biophysical characteristics of epidermal keratinocytes in superficial layers
Authors: Kida Moeko , Abe Junya , Hori Haruna , Hirai Yohei 
Published: May 2024

AbstractMesotrypsin, encoded by the PRSS3 gene, is a distinctive trypsin isoform renowned for its exceptional resistance to traditional trypsin inhibitors and unique substrate specificity. Within the skin epidermis, this protein primarily expresses in the upper layers of the stratified epidermis and plays a crucial role in processing pro-filaggrin (Pro-FLG). Although prior studies have partially elucidated its functions using primary cultured keratinocytes, challenges persist due to these cells' differentiation-activated cell death program. In the present study, HaCaT keratinocytes, characterized by minimal endogenous mesotrypsin expression and sustained proliferation in differentiated states, were utilized to further scrutinize the function of mesotrypsin. Despite the ready degradation of the intact form of active mesotrypsin in these cells, fusion with Venus, flanked by a peptide linker, enables evasion from the protein elimination machinery, thus facilitating activation of the Pro-FLG processing system. Inducing Venus-mesotrypsin expression in the cells resulted in a flattened phenotype and reduced proliferative capacity. Moreover, these cells displayed altered F-actin assembly, enhanced E-cadherin adhesive activity, and facilitated tight junction formation without overtly influencing epidermal differentiation. These findings underscore mesotrypsin's potentially pivotal role in shaping the characteristic cellular morphology of upper epidermal layers.
In-layer inhomogeneity of molecular dynamics in quasi-liquid layers of ice
Authors: Yasuda Ikki , Endo Katsuhiro , Arai Noriyoshi , Yasuoka Kenji 
Published: May 2024

AbstractQuasi-liquid layers (QLLs) are present on the surface of ice and play a significant role in its distinctive chemical and physical properties. These layers exhibit considerable heterogeneity across different scales ranging from nanometers to millimeters. Although the formation of partially ice-like structures has been proposed, the molecular-level understanding of this heterogeneity remains unclear. Here, we examined the heterogeneity of molecular dynamics on QLLs based on molecular dynamics simulations and machine learning analysis of the simulation data. We demonstrated that the molecular dynamics of QLLs do not comprise a mixture of solid- and liquid water molecules. Rather, molecules having similar behaviors form dynamical domains that are associated with the dynamical heterogeneity of supercooled water. Nonetheless, molecules in the domains frequently switch their dynamical state. Furthermore, while there is no observable characteristic domain size, the long-range ordering strongly depends on the temperature and crystal face. Instead of a mixture of static solid- and liquid-like regions, our results indicate the presence of heterogeneous molecular dynamics in QLLs, which offers molecular-level insights into the surface properties of ice.
Hippo–YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass
Authors: Choi Sungwoo , Kang Ju-Gyeong , Tran Yen T. H. , Jeong Sun-Hye , Park Kun-Young , Shin Hyemi , Kim Young Hoon , Park Myungsun , Nahmgoong Hahn , Seol Taejun , Jeon Haeyon , Kim Yeongmin , Park Sanghee , Kim Hee-joo , Kim Min-Seob , Li Xiaoxu , Bou Sleiman Maroun , Lee Eries , Choi Jinhyuk , Eisenbarth David , Lee Sang Heon , Cho Suhyeon , Moore David D. , Auwerx Johan , Kim Il-Young , Kim Jae Bum , Park Jong-Eun , Lim Dae-Sik , Suh Jae Myoung 
Published: May 2024

AbstractAdipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ–TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo–YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.
Identifying multi-resolution clusters of diseases in ten million patients with multimorbidity in primary care in England
Authors: Beaney Thomas , Clarke Jonathan , Salman David , Woodcock Thomas , Majeed Azeem , Aylin Paul , Barahona Mauricio 
Published: May 2024

Abstract
Background
Identifying clusters of diseases may aid understanding of shared aetiology, management of co-morbidities, and the discovery of new disease associations. Our study aims to identify disease clusters using a large set of long-term conditions and comparing methods that use the co-occurrence of diseases versus methods that use the sequence of disease development in a person over time.

Methods
We use electronic health records from over ten million people with multimorbidity registered to primary care in England. First, we extract data-driven representations of 212 diseases from patient records employing (i) co-occurrence-based methods and (ii) sequence-based natural language processing methods. Second, we apply the graph-based Markov Multiscale Community Detection (MMCD) to identify clusters based on disease similarity at multiple resolutions. We evaluate the representations and clusters using a clinically curated set of 253 known disease association pairs, and qualitatively assess the interpretability of the clusters.

Results
Both co-occurrence and sequence-based algorithms generate interpretable disease representations, with the best performance from the skip-gram algorithm. MMCD outperforms k-means and hierarchical clustering in explaining known disease associations. We find that diseases display an almost-hierarchical structure across resolutions from closely to more loosely similar co-occurrence patterns and identify interpretable clusters corresponding to both established and novel patterns.

Conclusions
Our method provides a tool for clustering diseases at different levels of resolution from co-occurrence patterns in high-dimensional electronic health records, which could be used to facilitate discovery of associations between diseases in the future.
Comprehensive review on dynamic state estimation techniques with cybersecurity applications
Authors: Zhou Zhuoran , Zhang Xin , Zhang Jinning , Taylor Gareth 
Published: May 2024

AbstractThe role of cybersecurity in cyber‐physical power systems (CPPS) is reviewed, focusing on the applications of dynamic state estimation (DSE) techniques. These DSE techniques are particularly relevant with the integration of phasor measurement units (PMUs) and advanced communication infrastructure. A comprehensive review on DSE techniques and applications to efficiently protect CPPS against cyberattacks is classified into three cyber resilience phases including prevention, detection, and mitigation. The DSE techniques in the prevention phase are surveyed to improve the observability of the CPPS by the robust design of the Kalman filter and optimal protection of PMUs. The DSE techniques in the detection phase are surveyed to improve the adaptability of CPPS in various attack detection scenerios and optimise the detection accuracy. The DSE techniques in the mitigation phase are surveyed to enhance the flexibility of CPPS resource utilisation with compensation‐based, isolation‐based, and scheduling‐based strategies. Finally, the benefits and limitations of each DSE technique are summarised with potential suggestions on research directions for enhancing the cyber resilience of CPPS.