bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown SIK3 in hippocampal CA1 decreases seizure susceptibility in mice
Authors: Jiang Zhen-Fu , Xuan Li-Na , Sun Xiao-Wan , Liu Shao-Bo , Yin Jian 
Published: March 2023

Abstract
The imbalance between excitation and inhibition is an important cause of epilepsy. It has been found that SIK1 gene mutation can cause epilepsy. In this study, we first found that the expression of SIK3 is increased after epilepsy. Furthermore, the role of SIK3 in epilepsy is explored. In the cultured hippocampal neurons, we used Pterosin B, a selective SIK3 inhibitor, that could inhibit epileptiform discharges induced by the convulsant drug cyclothiazide (a positive allosteric modulator of AMPA receptors, CTZ). Knockdown SIK3 could also inhibit epileptiform discharges and increase the amplitude of mIPSC currents. In mice, knockdown SIK3 could reduce the epilepsy susceptibility in pentylenetetrazole (a GABAA receptor antagonist, PTZ) acute kindling experiment and increase the expression of GABAA receptor α1. In conclusion, our results suggest that blockade or knockdown SIK3 can inhibit epileptiform discharges, and SIK3 has the potential to be a novel target for epilepsy treatment.
JT002, a small molecule inhibitor of the NLRP3 inflammasome for the treatment of autoinflammatory disorders
Authors: Ambrus-Aikelin Geza , Takeda Katsuyuki , Joetham Anthony , Lazic Milos , Povero Davide , Santini Angelina M. , Pranadinata Rama , Johnson Casey D. , McGeough Matthew D. , Beasley Federico C. , Stansfield Ryan , McBride Christopher , Trzoss Lynnie , Hoffman Hal M. , Feldstein Ariel E. , Stafford Jeffrey A. , Veal James M. , Bain Gretchen , Gelfand Erwin W. 
Published: March 2023

Abstract
The NLRP3 inflammasome is an intracellular, multiprotein complex that promotes the auto-catalytic activation of caspase-1 and the subsequent maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome has been implicated in the pathophysiology of a number of inflammatory and autoimmune diseases, including neuroinflammation, cardiovascular disease, non-alcoholic steatohepatitis, lupus nephritis and severe asthma. Here we describe the preclinical profile of JT002, a novel small molecule inhibitor of the NLRP3 inflammasome. JT002 potently reduced NLRP3-dependent proinflammatory cytokine production across a number of cellular assays and prevented pyroptosis, an inflammatory form of cell death triggered by active caspase-1. JT002 demonstrated in vivo target engagement at therapeutically relevant concentrations when orally dosed in mice and prevented body weight loss and improved inflammatory and fibrotic endpoints in a model of Muckle-Wells syndrome (MWS). In two distinct models of neutrophilic airway inflammation, JT002 treatment significantly reduced airway hyperresponsiveness and airway neutrophilia. These results provide a rationale for the therapeutic targeting of the NLRP3 inflammasome in severe asthma and point to the use of JT002 in a variety of inflammatory disorders.
Molecular investigation in Orofacial Clefts with Microphthalmia-Anophthalmia-Coloboma spectrum
Authors: Gil-da-Silva-Lopes Vera Lúcia , Atique-Tacla Milena , Copelli Matheus , Pairet Eleonore , Monlleó Isabella , Ribeiro Erlane , Lustosa-Mendes Elaine , Helaers Raphael , Vieira Tarsis , Vikkula Miikka 
Published: March 2023

Abstract
Orofacial clefts (OC) are the most common birth defects in humans and approximately 30% of them form the group of syndromic orofacial clefts (SOCs). Microphthalmia/anophthalmia/coloboma spectrum (MAC) can be associated with OC, however the genetic etiologies of OC-MAC have been poorly characterized. This study describes genomic findings among individuals with OC-MAC recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole exome sequencing (WES) were performed in 17 individuals with OC-MAC. Genotype-phenotype correlation was based on clinical data available at the BDCA and on re-examination. No copy number variants (CNVs) classified as likely pathogenic or pathogenic were detected by CMA. WES allowed a conclusive diagnosis in six individuals (35.29%), two of them involving the CHD7 gene. Variant of uncertain significance (VUS) possibly associated to the phenotypes were found in six other individuals. Among the individuals with VUSes, three individuals presented variants in genes associated to defects of cilia structure and/or function. Investigation by WES seems to be the most effective method for diagnosis in OC-MAC. This study also reinforces the genetic heterogeneity of OC-MAC, highlights the presence of the CHD7 gene, and the importance of genes related to ciliopathies in this phenotype.
Research on building material design in circular economy based on improved neural network
Authors: Yi Teng 
Published: March 2023

Abstract

Material management technology has always been the basic and core technology of traditional construction projects. But now, because traditional material management consumes more resources and has low efficiency, it has gradually been replaced by modern material management systems represented by computer technology, thus saving a lot of enterprise input costs and reducing the impact of traditional material management technology on enterprise operating income. Based on this background, this paper introduces improved neural network technology to adapt to the circular economy environment, so as to complete the construction and improvement of the building materials data management system. The system can be used to complete building materials management, basic data management, etc., and can be optimized for the system itself. Through network technology, the client can be connected to the server switch, and Ajax technology and JSP programming language can be used for compatibility processing, so that the system can run better in the Windows environment. According to the simulation experiment designed for the system, the output sample value of the system is close to the measured value, with good prediction accuracy, small error and high stability. Therefore, the application of AdaBoost ANN algorithm can effectively realize the prediction of building materials. In addition, other functions of the system, such as interactive page design, operation interface and database, can better adapt to the circular economy environment and actual user needs. In this paper, the improved neural network is applied to the field of building materials design under the environment of circular economy, thus completing the system optimization.
Tumor Intrinsic Mechanisms of Antigen Escape to Anti-BCMA and Anti-GPRC5D Targeted Immunotherapies in Multiple Myeloma
Authors: Bahlis Nizar , Lee Holly , Ahn Sungwoo , Maity Ranjan , Leblay Noémie , Ziccheddu Bachisio , Chojnacka Monika , Cirrincione Anthony , Durante Michael , Barakat Elie , Tilmont Remi , Sinha Sarthak , Truger Marietta , Kyman Shari , Krishnan Amrita , Landgren Ola , Walter Wencke , Meggendorfer Manja , Haferlach Claudia , Haferlach Torsten , Einsele Hermann , Kortüm K. , Knop Stefan , Alberge Jean-Baptiste , Keats Jonathan , Rasche Leo , Maura Francesco , Neri Paola 
Published: March 2023

Abstract
B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G protein coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T. To examine the tumor intrinsic factors that promote MM antigen escape, we performed combined bulk and single cell whole genome sequencing/ copy number variation analysis of 25 patients treated with anti-BCMA and/ or -GPRC5D CAR T/ TCE. In two cases, MM relapse post TCE/CAR T was driven by BCMA negative clones harboring focal biallelic deletions at the TNFRSF17 locus at relapse or by selective expansion of pre-existing subclones with biallelic TNFRSF17 loss. In another three cases of MM relapse, we identified non-truncating missense mutations or in-frame deletions in the extracellular domain of BCMA which negates the efficacies of anti-BCMA TCEs, despite detectable surface BCMA protein expression. With respect to GPRC5D, we report the first four cases of MM relapse with biallelic mutations of GPRC5D following anti-GPRC5D TCE, including two cases with convergent evolution where multiple subclones lost GPRC5D through different somatic events. Our data support that immunoselection of BCMA or GPRC5D negative or mutant clones post CAR T/ TCE therapies may be more prevalent than currently perceived. The engineering and selection of immunotherapies in MM should account for target antigen structural and extracellular domain mutations.
A Novel Hermit Crab optimization algorithm
Authors: Guo Jia , Zhou Guoyuan , Di Yi , Ke Yan , Sato Yuji , Shi Binghua 
Published: March 2023

Abstract
The minimax problem in continuous high-dimensional spaces has been a challenge in optimization. Traditional optimization algorithms cannot balance well between depth search and breadth search in high dimensional search spaces. A new hermit crab optimization algorithm (HCOA) is introduced in this paper to address these problems. Inspired by the population behavior of hermit crabs, the hermit crab optimization algorithm introduces the optimal crab memory and the backtracking search around the memory. Compared with other metaheuristic algorithms, the hermit crab optimization algorithm does not require advanced training or parameter correction and thus can be more quickly employed for different optimization problems. To explore the capabilities of HCOA, the simulation experiment selected CEC2017 as the test function and five well-known optimization algorithms as the control group. Among the 29 benchmark features in the CEC2017, HCAO ranks first in the number of features with 23, and second, third and fifth with two each. Experimental results demonstrate that HCOA present highly accurate and robust results for high-dimensional optimization problems.
Clinical Outcomes and Prognostic Factors in Triple-Negative Invasive Lobular Carcinoma of the Breast
Authors: Joshi Utsav , Budhathoki Pravash , Gaire Suman , Yadav Sumeet K. , Shah Anish , Adhikari Anurag , Choong Grace , Couzi Rima , Giridhar Karthik , Leon-Ferre Roberto , Boughey Judy C. , Hieken Tina J. , Mutter Robert , Ruddy Kathryn J. , Haddad Tufia C. , Goetz Matthew P. , Couch Fergus J. , Yadav Siddhartha 
Published: March 2023

Abstract
Purpose:
Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined.
Methods:
Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy.
Results:
The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001).
Conclusion:
Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.
Association between psychological stress, anxiety and oral health status among college students during the Omicron wave: a cross-sectional study
Authors: Cao Rongkai , Lai Junyu , Fu Xiaoxin , Qiu Piaopiao , Chen Jinghong , Liu Weicai 
Published: March 2023

Abstract
Background
Within 3 years of the COVID-19 pandemic, increasing interest has been given to its potential influence on health status due to lockdowns caused by the pandemic. However, the impact is inadequately understood, especially for college students. This study aimed to investigate the potential association between psychological stress, anxiety and oral health status of college students during the Omicron wave of the COVID-19 pandemic.
Methods
An online survey with measurements of psychological stress, anxiety and oral health was completed by 1770 Chinese college students. The Perceived Stress Scale-14 (PSS-14) and Generalized Anxiety Disor-der-7 (GAD-7) were used to measure psychological stress and anxiety, respectively. Oral health status was self-reported including toothache, gingival bleeding, and oral ulcer. Multivariable logistic regressions were per-formed to determine underlying associations for outcome variables. Structural equation modeling (SEM) was conducted to confirmed the relationship between mental and oral health status.
Results
Of the 1770 subjects, 39.2% presented high psychological stress and only 41.2% expressed no anxiety. A significant association was found between psychological stress, anxiety and oral health status. Anxiety has significant impacts on toothache (OR = 0.358, p < 0.01), gingival bleeding (OR = 0.431, p < 0.01), and oral ulcer (OR = 0.535, p < 0.01). Anxiety also significantly mediated the relationship between psychological stress and self-reported oral symptoms.
Conclusions
COVID-19 may be a significant risk indicator for mental health among college students and shows a significant correlation with the occurrence of self-reported oral symptoms. Maintaining good mental health is favorably associated with self-reported oral health status.
Efficacy of customized corneal crosslinking versus standard corneal crosslinking in patients with progressive keratoconus (C-CROSS study): study protocol for a randomized controlled trial
Authors: Vandevenne Magali M.S. , Berendschot Tos T.J.M. , Winkens Bjorn , Biggelaar Frank J.H.M. van den , Visser Nienke , Dickman Mor M. , Wisse Robert P.L. , Wijdh Robert-Jan H.J. , Roy Abhijit Sinha , Shetty Rohit , Nuijts Rudy M.M.A. 
Published: March 2023

Abstract
Background
Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea.
Methods
We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking.
Discussion
The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient’s cornea may stop the progression of keratoconus and result in flattening of the cornea.
Trial registration
This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.
Prevalence and factors associated of metabolic syndrome in first- treatment drug-naïve schizophrenia patients: a large-scale cross- sectional study
Authors: Zhang Lin , Dai Xiaoyan , Li Yi , Zhang Yanting , Ma Jun 
Published: March 2023

Abstract
Background: Patients with schizophrenia are at high risk of developing metabolic disorders, even prior to exposure to antipsychotic medication. The aim of this paper is to report on the prevalence of MetS in first-treatment drug-naïve schizophrenia patients and to further analyze the factors influencing of the MetS.
Methods: A total of 668 patients with first-treatment drug-naïve schizophrenia were included in the present study. We report the prevalence of metabolic syndrome in the target population, compare the differences in demographic and general clinical information between two clinical subgroups with and without MetS, and analyze factors influencing MetS and its severity.
Results: The prevalence of MetS in the target population was 10.93%. Univariate analysis showed significant differences in demographic and general clinical characteristics between the two clinical subgroups of MetS and non-MetS. The higher onset age of schizophrenia, female, total cholesterol (TC), red blood cell count (RBC) and white blood cell count (WBC) were risk factors for Mets, while free tetraiodothyronine (FT4) and the Clinical Global Impression Inventory-Severity of Illness (CGI-SI) were protective factors. Finally, we found that higher onset age of schizophrenia was a risk factor for MetS scores.
Conclusion: The prevalence of MetS in primary treatment drug naïve patients with schizophrenia is not high, and many factors influence MetS in this group, with higher onset age of schizophrenia being an influential factor in MetS severity. We need to further investigate the overlapping effects of the schizophrenia illness itself and age on the effects of MetS.
String-like brane splitting in the context of f(T, B) gravity
Authors: Moreira Allan , Almeida Carlos Alberto 
Published: March 2023

Abstract
In this work, the influence of the boundary term B is analyzed in a string-like thick brane scenario in the gravity context f(T, B). For that, three models of f(T, B) are proposed, i. e., f1(T, B) = T + kBn, f2(T, B) = T + k(−T + B)n and f3(T, B) = T + k1T2 + k2B2, where n, k and k1,2 are parameters that control the deviation from the usual teleparallelism. The first relevant result obtained was the appearance of a super-located tower in the core for energy density. Furthermore, the greater the influence of the boundary term, the new maximums and minimums appear in the energy density. All this indicates the emergence of capable structures from split to the brane. The second relevant result was obtained by analyzing the gravitational perturbations, where the effective potential presents the supersymmetric form of quantum mechanics, leading to well-localized massless modes.
Three Genes Expressed in Relation to Lipid Metabolism Considered as Potential Biomarkers for the Diagnosis and Treatment of Diabetic Nephropathy
Authors: Yang Ye , Wang Qin 
Published: March 2023

Abstract
Objective: Diabetic neuropathy is one of the most common chronic complications and is present in approximately 50% of diabetic patients. A bioinformatic approach was used to analyze candidate genes involved in diabetic distal symmetric polyneuropathy and their potential mechanisms.
Methods: GSE95849 was downloaded from the Gene Expression Omnibus database (GEO) for differential analysis, together with the identified diabetic peripheral neuropathy-associated genes and the three major metabolism-associated genes in the CTD database to obtain overlapping Differentially Expressed Genes (DEGs). Gene Set Enrichment Analysis (GSEA) and Functional Enrichment Analysis were performed. Protein-Protein Interaction (PPI) and hub gene networks were constructed using the STRING database and Cytoscape software. The expression levels of target genes were evaluated using GSE24290 samples, followed by (Receiver operating characteristic, ROC) curve analysis. And Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the target genes. Finally, mRNA-miRNA networks were constructed.
Results: A total of 442 co-expressed DEGs were obtained through differential analysis, of which 353 expressed up-regulated genes and 89 expressed down-regulated genes. The up-regulated DEGs were involved in 742 GOs and 10 KEGG enrichment results, mainly associated with lipid metabolism-related pathways, TGF-β receptor signaling pathway, lipid transport, and PPAR signaling pathway. A total of 4 target genes (CREBBP, EP300, ME1, CD36) were identified. Analysis of subject operating characteristic curves indicated that CREBBP (AUC=1), EP300 (AUC=0.917), ME1 (AUC=0.944) and CD36 (AUC=1) may be candidate serum biomarkers for DPN.
Conclusion: Diabetic peripheral neuropathy pathogenesis and progression is caused by multiple pathways, which also provides clinicians with potential therapeutic tools.
Resting-state EEG measures cognitive impairment in Parkinson’s disease
Authors: Anjum Md Fahim , Espinoza Arturo , Cole Rachel , Singh Arun , May Patrick , Uc Ergun , Dasgupta Soura , Narayanan Nandakumar 
Published: March 2023

Abstract
Background: Cognitive dysfunction is common in Parkinson’s disease (PD) and is diagnosed by complex, time-consuming psychometric tests which are affected by language and education, subject to learning effects, and not suitable for continuous monitoring of cognition.
Objectives: We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG.
Methods: We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from the National Institutes of Health (NIH) Toolbox using cross-validation schemes, regression models, and randomization tests.
Results: We observed cognition-related changes in EEG activities over multiple spectral rhythms. Utilizing only 8 best-performing EEG electrodes, our proposed index strongly correlated with cognition (rho = 0.68, p value < 0.001 with MoCA; rho ≥ 0.56, p value < 0.001 with cognitive tests from the NIH Toolbox) outperforming traditional spectral markers (rho = -0.30 – 0.37). The index showed a strong fit in regression models (R2 = 0.46) with MoCA, yielded 80% accuracy in detecting cognitive impairment, and was effective in both PD and control participants.
Conclusions: Our approach is computationally efficient for real-time indexing of cognition across domains, implementable even in hardware with limited computing capabilities, making it potentially compatible with dynamic therapies such as closed-loop neurostimulation, and will inform next-generation neurophysiological biomarkers for monitoring cognition in PD and other neurological diseases.