bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA-targeted therapy corrects neuronal deficits in PACS1 syndrome mice
Authors: Thomas Gary , Villar-Pazos Sabrina , Thomas Laurel , Yang Yunhan , Chen Kun , Lyles Jenea , Deitch Bradley , Ochaba Joseph , Ling Karen , Powers Berit , Gingras Sebastien , Kordasiewicz Holly , Grubisha Melanie , Huang Yanhua 
Published: January 2023

Abstract
Neurodevelopmental disorders (NDDs) are frequently associated with dendritic abnormalities in pyramidal neurons that affect arbor complexity, spine density, and synaptic communication 1,2. The underlying genetic causes are often complex, obscuring the molecular pathways that drive these disorders 3. Next-generation sequencing has identified recurrent de novo missense mutations in a handful of genes associated with NDDs, offering a unique opportunity to decipher the molecular pathways 4. One such gene is PACS1, which encodes the multi-functional trafficking protein PACS1 (or PACS-1); a single recurrent de novo missense mutation, c607C>T (PACS1R203W), causes developmental delay and intellectual disability (ID) 5,6. The processes by which PACS1R203W causes PACS1 syndrome are unknown, and there is no curative treatment. We show that PACS1R203W increases the interaction between PACS1 and the α-tubulin deacetylase HDAC6, elevating enzyme activity and appropriating control of its posttranscriptional regulation. Consequently, PACS1R203W reduces acetylation of α-tubulin and cortactin, causing the Golgi to fragment and enter developing neurites, leading to increased dendrite arborization. The dendrites, however, are beset with diminished spine density and fewer functional synapses, characteristic of ID pathology. Treatment of PACS1 syndrome mice with PACS1- or HDAC6-targeting antisense oligonucleotides restores neuronal structure and synaptic transmission, suggesting PACS1R203W/HDAC6 may be targeted for treating PACS1 syndrome neuropathology.
Clinical and Biochemical Assessment of the Effect of Topical Use of Coenzyme Q10 Versus Topical Corticosteroid in Management of Symptomatic Oral Lichen Planus: Randomized Controlled Clinical Trial
Authors: Abdelsamie Mostafa , Zahran Fat’heya M. , Hussine Amal A. , Shaker Olfat , Al-mahallawi Abdulaziz Mohsen 
Published: January 2023

Abstract
Background: Oral lichen planus (OLP) is a chronic mucocutaneous immunologically mediated condition that has a great adverse effect on oral functions.Corticosteroids are still the first drugs of choice used in the treatment of OLP, however, they have extensive medical side effects. The present study was carried out to assess the clinical therapeutic effect of topical use of coenzyme Q10 (coQ10 or ubiquinol) versus topical corticosteroids in the management of symptomatic OLP and to determine whether the effect, if any, was due to the powerful antioxidant activity of coQ10.
Subjects and Methods: We performed a randomized, double blinded controlled trial at the Faculty of Dentistry, Cairo University, Egypt. The study was conducted on 34 patients suffering from symptomatic OLP. Patients were randomly divided into two groups, intervention group (I), who received topical CoQ10 in the form of mucoadhesive tablets (40% CoQ10) 3 times daily for one month and control group (II), who received topical corticosteroid (kenacort in Orabase: triamcinolone acetonide 0.1% 5 gram adhesive paste – dermapharm), 4 times daily for one month. Patients were evaluated at one-week intervals using the clinical parameters (score) of pain (VAS) and lesion size. Additionally, salivary levels of malondialdehyde (MDA) were assessed in both groups before and after treatment using ELISA. All recorded data wereanalysed using independent t test, ANOVA followed by Bonferroni post hoc test for lesion size and salivary level of MDA data and Mann-Whitney U test and Friedman test for VAS data.
Results: Both groups showed a significant reduction in pain and size of the lesions (p ≤ 0.05) with no statistically significant difference between them (p>0.05) and this clinical improvement was associated with a reduction in the salivary levels of MDA in both groups.
Conclusions: The topical use of CoQ10 mucoadhesive tablets was as effective as the topical use of triamcinolone acetonide, and its clinical effect was associated with reduction in the salivary level of MDA.
Trial registration: The study protocol was registered at www.clinicaltrial.gov (NCT04091698) and registration date: 17/9/2019.
Identification of endoplasmic reticulum stress-related biomarkers in idiopathic pulmonary fibrosis based on machine learning
Authors: Huang Haishan , Wang Zhiqi , Liu Tianyang 
Published: January 2023

Abstract
Background
Endoplasmic reticulum stress (ERS) is critical in the development and progression of idiopathic pulmonary fibrosis (IPF). The aim of this study was to explore ERS-related biomarkers in IPF using a bioinformatics approach and to further investigate their relationship with immune cells. Three IPF datasets (GSE10667, GSE24206 as the training set and GSE53845 as the validation set) were obtained based on the Gene Expression Omnibus (GEO). In the training set, ERS-related differentially expressed genes(DEGs) between IPF and normal tissues were screened and subjected to GO and KEGG enrichment analysis. Key ERS-related DEGs were further screened using Weighted Gene Co-expression Network Analysis (WGCNA) and three machine learning algorithms (Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Support Vector Machine - Recursive Feature Elimination with Local Feature Selection (SVM-RFE)) and validated in a validation set. Then the CIBERSORT method was used to calculate the immune cell infiltration abundance and investigate the relationship between immune cells and key markers.
Results
we obtained 65 ERS-related DEGs from the training set, and 2 key ERS-related DEGs (COMP, GPX8) were screened by WGCNA and machine learning and validated in the validation set. COMP and GPX8 showed high diagnostic value (AUC > 0.8). The results of immune cell infiltration studies showed substantial associations between these two key markers and T-cell CD8, neutrophils, monocytes, macrophage M2 and plasma cells.
Conclusion
COMP and GPX8 are valuable potential biomarkers for IPF and provide a basis for future studies on the early diagnosis and treatment of IPF.
Divergent indicator changes in different exercise states in non-hypertensive individuals and patients with hypertension
Authors: Zhang Hui , Xu Youlong , Gao Junqing , Li Min , Fa Jingjing , Ding Xinyue , Yang Chenhao , Zhang Lingxiao , Luan Yuling , Xia Yinjuan , Wang Mingyu , Li Qingli , Xing Lina , Liu Zongjun 
Published: January 2023

AbstractBackgroundHypertension is a kind of clinical syndrome, characterized by the increase of systemic arterial pressure. There is a lack of identifiable triggers and predictors of hypertensive disease in response to treatment at rest and during exercise. In this study, a mathematical model was used to screen and compare the indicators and related changes at rest and during exercise between normotensive and hypertensive individuals.MethodsBlood pressure and ultrasound-related indicators, blood biochemical indicators and metabolic compounds were collected and logistic regression model and Principal component analysis (PCA) were used to explore the differences of indexes at rest and in different exercise states in healthy and hypertensive patients. An indicator change map for hypertension is established.ResultsThe results reveal that hypertension is not only related to oxidative stress, inflammatory reaction and fatty acid oxidation, but also involves various amino acid metabolism. The defined mathematical models and indicators changes during exercise might be helpful for early screening of hypertension and future studies are needed to explore their value on prevention and control of hypertension.ConclusionThe research shows that the main regulation indicators at different exercise states differ significantly in the normal group and the hypertensive group. The key indicators of the normal group are blood pressure and ultrasound related indicators, while those of the hypertensive group are metabolites related to lactic acid metabolism, glycolysis, aerobic oxidation and lipid metabolism.
Clinical and Psychosocial Factors associated with Quality of Life in Patients with Head and Neck Cancer: An Analytical Cross-Sectional Study from a Lower-Middle-Income Country
Authors: Zahid Nida , Martins Russell Seth , Dawood Zaiba , Zahid Wajeeha , Azam Iqbal , Ikram Mubasher , Hassan Aneesa , Bhamani Shireen Shehzad , Asad Nargis , Jabbar Adnan Abdul , Akhtar Shabbir , Siddiqui Moghira Iqbaluddin , Awan Mohammad Sohail , Ahmad Khabir 
Published: January 2023

Abstract
Introduction
The disease course of head and neck (H&N) cancers can severely impair patients’ quality of life (QoL). In Pakistan, a South Asian lower-middle-income country (LMIC), psychosocial factors may be associated with QoL. Thus, we aimed to assess QoL and associated factors amongst patients with H&N cancers in Pakistan.
Methods
An analytical cross-sectional study was conducted amongst adult (≥ 18 years) patients with H&N cancer who were ≥ 4 weeks post-initiation of treatment. The survey assessed QoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaires), mental health outcomes (Hospital Anxiety and Depression Scale), and social support (Enriched Social Support Instrument). Multivariable linear regression was used for analysis.
Results
A total of 250 patients (mean age: 51.6 years) were included. The majority of patients were married (87%) and living with multigenerational/extended family households (53%). On multivariable linear regression, ongoing cancer treatment (beta coefficient: -13.93), having a tracheostomy (-10.02), and receiving adjuvant chemoradiotherapy (-8.17) were significantly associated with poorer global QoL. Additionally, poorer QoL was associated with depression (-24.37) and anxiety (-13.34). However, having more household family member was associated with better global QoL (0.34).
Conclusion
The QoL of patients with H&N cancer in Pakistan is affected by both the nature of cancer treatment as well as sociocultural factors such as household size. Given that poorer QoL is associated with poorer mental health outcomes, there is a need to develop and implement psychosocial interventions to improve QoL of patients with H&N cancer in Pakistan, particularly during active treatment.
Heat extremes in Western Europe are increasing faster than simulated due to missed atmospheric circulation changes
Authors: Vautard Robert , Cattiaux Julien , Happé Tamara , Singh Jitendra , Bonnet Rémy , Cassou Christophe , Coumou Dim , D'Andrea Fabio , Faranda Davide , Fischer Erich , Ribes Aurélien , Sippel Sebastian , Yiou Pascal 
Published: January 2023

Abstract
Over the last 70 years, extreme heat has been increasing at global scale [1,2], with a rapid rate in several regions including Western Europe [3]. Climate models broadly capture heat trends globally [1], but exhibit systematically weaker extreme heat trends than observations in Western Europe [4-6], together with a weaker summer warming [7,8]. The causes of this mismatch, confirmed here by the analysis of 273 latest generation coupled climate simulations, among which only a handful of them overpass observed trends, are not well understood. Here we use a circulation analogue approach [9,10] to identify the dynamical contribution to temperature trends [11-12], and show that a substantial fraction (1.0°C [0.4°-1.6°C] of 3.4°C per global warming degree) of the trend is due to circulation changes, largely due to increases in southerly flows over Western Europe. Their rapid increase in frequency (+63% [20%-106%] since 1950) and persistence (+45% [12%-77%]) are not captured by any of the 32 climate model flow simulations analyzed. The few simulations reaching the observed warming trends in extreme heat have weak dynamical changes, with a decrease in occurrence of southerly flows, indicating that they capture the warming trend for the wrong reasons. These model biases in circulation trends can be due to a systematically underestimated or erroneous representation of the circulation response to external forcing, or to a systematic underestimation of interdecadal variability, or both. The former implies that projections are too conservative, the latter that we are left with deep uncertainty regarding the pace of future summer heat in Europe: the current strong recent trend could weaken or increase in future decades. This calls for caution when interpreting climate projections of heat extremes over Western Europe, in particular in view of adaptation to heat waves.
Single-cell multi-omics analysis identifies two distinct phenotypes of newly-onset microscopic polyangiitis
Authors: Nishide Masayuki , Nishimura Kei , Matsushita Hiroaki , Edahiro Ryuya , Inukai Sachi , Shimagami Hiroshi , Kawada Shoji , Kato Yasuhiro , Kawasaki Takahiro , Tsujimoto Kohei , Kamon Hokuto , Omiya Ryusuke , Okada Yukinori , Hattori Kunihiro , Narazaki Masashi , Kumanogoh Atsushi 
Published: January 2023

Abstract
Patients with autoimmune vasculitis present with diverse organ-threatening symptoms, but the underlying immunological basis of the clinical heterogeneity remains poorly understood. We conducted single-cell transcriptome and surface proteome analyses using CITE-seq on 109,350 peripheral blood mononuclear cells (PBMCs) and CyTOF on 737,794 PBMCs from newly-onset patients with microscopic polyangiitis (MPA) and age-matched healthy donors. Increased proportions of activated CD14+ monocytes, CD14+ monocytes expressing interferon signature genes (ISGs), cytotoxic CD8+ T cells, and killer immunoglobulin-like receptor (KIR)+ CD8+ T cells were distinctive features of MPA. Patient-specific analysis classified MPA into two groups characterized by CD14+ monocyte signature gene expression (MPA-MONO) and ISG expression (MPA-IFN). The MPA-MONO group was characterized by a high proportion of activated CD14+ monocytes, which persisted before and after immunosuppressive therapy. Patients in this group had a high rate of relapse and were clinically defined by increased monocyte ratio in the total PBMC count and high C-reactive protein titers. The MPA-IFN group was characterized by a high proportion of ISG+ CD14+ monocytes, which significantly decreased following treatment. Patients in this group showed good response to immunosuppressive therapy and were clinically defined by high serum interferon-alpha concentrations, renal symptoms, and high myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers. Our findings identify the immunological phenotypes of MPA and provide clinical recommendations for personalized treatment based on accurate prognostic prediction.
Combined cerium and zinc oxide nanoparticles induced hepato-renal damage in rats through oxidative stress mediated inflammation
Authors: Adeniyi Olola Esther , Adebayo Olayinka Anthony , Akinloye Oluyemi , ADARAMOYE Oluwatosin Adekunle 
Published: January 2023

Abstract
The toxicity profiles of nanoparticles (NPs) used in appliances nowadays remain unknown. In this study, we investigated the toxicological implications of cerium oxide (CeO2) and zinc oxide (ZnO) NPs given singly or in combination on the integrity of liver and kidney of male Wistar rats. Twenty rats were assigned equally into four groups and treated as: Control (normal saline), CeO2NPs (50µg/kg), ZnONPs (80µg/kg) and [CeO2NPs (50µg/kg) + ZnONPs (80µg/kg)]. The NPs were administered intraperitoneally thrice weekly for four consecutive weeks. Results showed that administration of CeO2 and ZnO NPs (Singly) increased serum AST and ALT by 29% & 57%; 41% & 18%, and co-administration by 53% and 23%, respectively. CeO2 and ZnO NPs increased hepatic and renal malondialdehyde (MDA) by 33% and 30%; 38% and 67%, respectively, while co-administration increased hepatic and renal MDA by 43% and 40%, respectivelyThe combined NPs increased hepatic NO by 28%. Also, CeO2 and ZnO NPs, and combined increased BAX, interleukin-1β and TNF-α by 45, 38, 52%; 47, 23, 82% and 41, 83, 70%, respectively. Histology revealed hepatic necrosis and renal haemorrhagic parenchymal in NPs-treated rats. Overall, NPs elicited oxidative stress and inflammation in the liver and kidney of the rats.
Hierarchical structures of hematopoietic stem cells and their bone marrow niches are measured via immune privilege
Authors: Furuhashi Kazuhiro , Kakiuchi Miwako , Ueda Ryosuke , Reizis Boris , Owens David , Frangos John , Robson Simon , Fujisaki Joji 
Published: January 2023

Abstract

Stem cells reside in specialized regulatory microenvironments, termed niches, at several different locations within tissues1-3. The differential functions of heterogeneous stem cells and niches are important given increasing clinical application of stem cell transplantation and cancer immunotherapy. It remains unknown whether hierarchical arrangements amongst stem cells and distinct niches exist, and are responsible for aspects of immune tolerance. Here, we propose novel hierarchical arrangements within hematopoietic stem cells (HSCs) and bone marrow (BM) niches, that dictate both regenerative potential and immune privilege. High level nitric oxide-generating (NOHi) HSCs are refractory to immune attack; and exhibit “delayed” but robust long-term reconstitution. Such highly immune-privileged, primitive NOHi HSCs are present at distinct capillaries, characterized by primary cilia and high levels of the immune-checkpoint molecule CD200. These capillaries regulate regenerative functions of NOHi HSCs through cilia/CD200/eNOS/autophagy signals, further mediating immune-protection. Notably, described niche constituents, sinusoidal cells and Type H vessels2-10, co-localize with less immune-privileged and less potent NOLow HSCs. Therefore, we have identified highly immune-privileged, “late-rising” primitive HSCs and characterized immune-protective niches constituted of specialized vascular domains. Our studies suggest the niche may orchestrate stem cell hierarchy with immune tolerance, delineating future immunotherapeutic targets.
Site-directed placement of three-dimensional DNA origami
Authors: Martynenko Irina , Erber Elisabeth , Ruider Veronika , Dass Mihir , Yin Xin , Posnjak Gregor , Altpeter Philipp , Liedl Tim 
Published: January 2023

Abstract
Assembling hybrid substrates with nanometer-scale precision and molecular addressability enables advances in such distant fields as material research and biosensing. As such, the combination of lithographic methods with 2D DNA origami self-assembly has led, among others, to the development of photonic crystal cavity arrays and the exploration of sensing nanoarrays where molecular devices are patterned on the sub-micron scale. Here we extend this concept to the third dimension through mounting 3D DNA origami onto nano-patterned substrates followed by silicification to provide mechanical and chemical stability. Our versatile and scalable method relying on self-assembly at ambient temperatures offers the potential to 3D-position any inorganic and organic components that are compatible with DNA architectures. This way, complex and 3D-patterend surfaces designed on the molecular level while reaching macroscopic dimensions could supersede energy-intensive manufacturing steps in substrate processing.
Microglial P2X4 receptors promote ApoE degradation and contribute to memory deficits in Alzheimer disease
Authors: Hua Jennifer , de Paco Elvira Garcia , Linck Nathalie , Maurice Tangui , Desrumaux Catherine , Manoury Bénédicte , Rassendren François , Ulmann Lauriane 
Published: January 2023

Abstract
Numerous evidence support that microglia contributes to the progression of Alzheimer’s disease. P2X4 receptors are ATP-gated channels with high calcium permeability, which are de novo expressed in a subset of reactive microglia associated to various pathological contexts, contributing to microglial functions. P2X4 receptors trafficking to the plasma membrane is tightly regulated and are mainly localized in lysosomes. Here, we investigated the role of P2X4 in the context of Alzheimer disease (AD). Using proteomic, we identified ApoE as a specific P2X4 interacting protein. We found that P2X4 regulates lysosomal cathepsin B activity promoting ApoE degradation; P2rx4 deletion results in higher amount of intracellular and secreted ApoE in both BMDM and microglia from APPswe/PSEN1dE9 brain. In both human AD brain and APP/PS1 mice, P2X4 and ApoE are almost exclusively expressed in plaque associated microglia. In 12 months old APP/PS1 mice, genetic deletion of p2rx4 reverses topographical and spatial memory impairment and reduces amount of soluble small aggregates of Aß1-42 peptide, while no obvious alteration of plaque associated microglia characteristics is observed. Our results support that microglial P2X4 promotes lysosomal ApoE degradation, indirectly altering Aß peptide clearance, which in turn might promote synaptic dysfunctions and cognitive deficits. Our findings uncover a specific interplay between purinergic signaling, microglial ApoE, sAß species and cognitive deficits associated with AD.
Optimization of diesel engine performance and emission using waste plastic pyrolytic oil by ANN and its thermo economic assessment
Authors: Panda Achyut Kumar , Rout Saroj Kumar , DAS AMAR KUMAR 
Published: January 2023

Abstract
The current study focuses on the engine performance and emission analysis of a 4 stroke compression ignition engine powered by medical waste plastic oil (WPO) followed by their optimization study and economic analysis. Engine tests were conducted using WPO blended diesel at various proportions to acquire required data for training the ANN model, which enables better prediction for the engine performance by making use of the standard back-propagation algorithm.Considering supervised data obtained from repeated engine tests, an artificial intelligence-based model of ANN was designed to select different parameters of performance and emission as output layers, at the same time engine loading and different blending ratio of the test fuels were taken as the input layers. The ANN model was built up making use of 80% of testing outcomes for training. The ANN model forecasted engine performance and exhaust emission with regression coefficients (R) at 0.989–0.998 intervals and a mean relative error from 0.002% to 0.348%. Such results illustrated the effectiveness of the ANN model for estimating emissions and the performance of diesel engines. This study demonstrates the use of artificial neural networks (ANNs) to forecast a multi-component fuel mixture, which is novel and reduces the amount of experimental effort required to determine the engine output characteristics. Moreover, the economic viability of the use of 20WPO as an alternative to diesel was justified by thermo-economic analysis.