bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral hepatitis is associated with increased risk of decompensated cirrhosis or liver failure in patients positive for liver cytosol antibody type 1
Authors: Wang Rong , Jing Keying , Liu Yang , Zhao Huijuan , Cai Jun
Published: March 2023

Objective
Liver cytosol antibody type 1 (anti-LC1) is reported to be a marker of type 2 autoimmune hepatitis (AIH), a type of autoimmune liver disease (AILD). However, anti-LC1 is not entirely disease-specific, and its clinical value in other hepatic diseases has not been well elucidated. Our study aimed to explore the associations between the diagnoses and outcome of decompensated cirrhosis or liver failure (DC/LF) in patients positive for anti-LC1.
Methods
A total of 157 patients positive for anti-LC1 were included in our final analysis. DC/LF was defined as the outcome of patients positive for anti-LC1. The risk of DC/LF according to diagnosis was estimated using multivariable Cox proportional hazards models, while stratified Cox regression models were used in the subgroup analyses.
Results
The diagnoses of patients positive for anti-LC1 were found to be comprised of various liver disorders. Versus other diagnoses, viral hepatitis was associated with a 2.25-fold increased risk of DC/LF in these patients, independent of sex, age, disease course, treatment and drinking history. Additionally, the associations were more significant by subgroup analysis in male patients, younger patients, non-newly diagnosed patients, patients without treatment and patients without drinking history.
Conclusion
Anti-LC1 is not a disease-specific antibody, as it was found in multiple types of hepatic disease. Furthermore, viral hepatitis rather than AILD was associated with an increased risk of DC/LF in patients positive for anti-LC1. These findings emphasize the important role of viral hepatitis in the progression of DC/LF in patients positive for anti-LC1.
Programming Conformational Cooperativity to Regulate Allosteric Protein-Oligonucleotide Signal Transduction
Authors: Zhang Cheng , Liang Yuan , Qie Yunkai , Yang Jing , Cui Shuang , Zhao Yuliang , Anderson Greg J , Nie Guangjun , Li Suping
Published: March 2023

Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we developed a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generated a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implemented allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields.
Metrics of anterior sclera in normal Chinese adults: Anterior segment imaging using the swept-source optical coherence tomography Running
Authors: Lin Na , Sun Yunqi , Yang Maoyuan , Chen Bichi , Mao Jieli , Liu Yongshun , Deng Ruzhi
Published: March 2023

Background: To measure the corneoscleral limbus and anterior sclera parameters of normal Chinese adults by swept-source optical coherence tomography (OCT).
Methods: In this cross-sectional study, a total of 56 Chinese subjects with ametropia were evaluated in the Eye Hospital of Wenzhou Medical University from September 2020 to December 2020, including 26 (46.4%) men, with an average age of 24.7±1.8 years old, and a spherical equivalent of -2.05±0.46 D. The optical coherence tomograph SS-1000 (CASIA, Tomey, Tokyo, Japan) was used to measure the sagittal height, corneoscleral junction angle (CSJ), corneal angle, and scleral angle. One-way analysis of variance and least significant difference test were used to compare the differences in the four segment parameters.
Results: The mean sagittal heights of the right eyes at chord lengths of 10.0, 12.3, and 15.0 mm were 1756±72, 2658±110, and 3676±155 μm, respectively. The absolute values of the differences between horizontal and vertical meridians at chord lengths of 10.0, 12.3, and 15.0 mm were 54±40, 70±67, and 117±95 μm, respectively. The differences of CSJ and corneal angles at 12.3 mm chord and scleral angle at 15.0 mm chord in the four segments were statistically significant (F values were 32.01, 21.31, and 13.37, respectively, all P values < 0.001). The CSJ angles from low to high were 176.53±2.14° (nasal), 178.66±1.84° (inferior), 179.13±1.20° (temporal), and 179.31±1.68° (superior), and 87.5% of the nasal angles were less than 179°. The corneal angles at 12.3 mm chord from high to low were 40.31±2.80° (nasal), 39.46±2.41° (temporal), 37.20±2.26° (inferior), and 37.50±2.28° (superior). The scleral angles at 15.0 mm chord from high to low were 38.35±2.47° (temporal), 38.26±3.37° (superior), 35.37±3.10° (nasal), and 35.30±4.71° (inferior).
Conclusion: The morphology of corneoscleral limbus and anterior sclera is asymmetrical in normal Chinese adults. The nasal side of the corneoscleral limbus has the largest angle, and the superior and temporal sides of the scleral angle are larger. From the corneoscleral limbus to the anterior sclera, the superior side becomes steep and the other segments become flat.
Factor structure of the Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) in a clinical sample recruited from the community
Authors: Šipka Dajana , Brodbeck Jeannette , Schulz Ava , Stolz Timo , Berger Thomas
Published: March 2023

Background: The Social Phobia Scale (SPS) and the Social Interaction Anxiety Scale (SIAS) are widely used self-report questionnaires to assess symptoms of social anxiety. While SPS measures social performance anxiety, SIAS measures social interaction anxiety. They are mostly reported simultaneously, but there have not been consistent results of the joint factor structure and therefore no consistent recommendations on how to use and evaluate the questionnaires. The study aimed (1) to evaluate the underlying joint factor structure of the SPS and SIAS and (2) to test whether SPS and SIAS are reliable scales to assess two different aspects of social anxiety.
Methods: The one-factor, two-factor, and bifactor model were tested in a clinical sample recruited from the community and diagnosed with a social anxiety disorder. Exploratory and confirmatory factor analyses were conducted, bifactor specific indices were calculated, and the content of the less fitting items was examined.
Results: Confirmatory factor analyses showed that the best fitting model was the bifactor model with a reduced set of items. The bifactor-specific indices showed that the factor structure cannot be considered unidimensional and that SPS and SIAS are reliable subscales. A closer examination of the less fitting item content and implications for future studies are discussed.
Conclusions: In conclusion, SPS and SIAS can be reported together as an overall score of social anxiety and are separately reliable measures to assess different aspects of social anxiety.
Trial registration: not applicable.
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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Identification Of β-Glucan Polysaccharides In Hanjeli (Coix Lacryma Jobi) Using The Colorimetric Method
Authors: Mulyani Reni , mukmilah Lela
Published: March 2023

β-Glucan is a polysaccharide that the human body uses as a food fiber. Beta β-Glucan plays an important role in the human digestive process, slowing the rate at which food is digested. Hanjeli's β-Glucan content was investigated in this study (Coix lacryma jobi). Soft shell Hanjeli (Coix lacryma jobi var. ma-yuen) and hard shell Hanjeli were discovered (Coix lacryma jobi var. stenocarpa). Using Fourier-transform infrared spectroscopy, crude glucan solids from each Hanjeli variety were analyzed qualitatively for their functional groups (FTIR). The study's findings revealed that there is a specific structure of the -Dβ-Glucan compound at wave number 898 cm-1. The levels of β-Glucan in the hanjeli were analyzed using the Congo Red colorimetric method; the results of the analysis revealed that the β-Glucan levels in the hanjeli soft shell were 596,366 ppm (42% w/w), and in the hard shell hanjeli were 546,200 ppm (40.6% b/b). Hanjeli (Coix lacryma jobi) has good potential and prospects for development as a functional food because it contains an active compound β-Glucan, which functions as an immunomodulator, cholesterol lowering agent, and antioxidant.
WITHDRAWN: Investigation of Non-isolated Dual Inputstep-up Dc-dc Converter Using Sliding Mode Control for Ev Application
Authors: Subramaniyan J. , Balaji C.
Published: March 2023

This work investigates the design and implementation of a slide mode controller for a high step up dual input non-isolated dc-dc converter for Electric vehicle applications. The proposed high step up dual-input dc-dc non isolated converter comprises one inductor, one capacitor, two switches with anti parallel diodes, and two switches without diodes. The converter analysis is carried out using state space averaged model. The converter with the slide mode controller is analyzed by varying both the input voltage and the load. The performance characteristics of the proposed converter is compared against the conventional PID controller, and it is found that the high input step-up dual input dc-dc non-isolated converter with slide mode controller shows improved performance. The proposed converter is dynamic and exhibits a high-speed step-up conversion ratio. The slide mode controller is designed, analysed and it is simulated. The simulation results are validated by developing a prototype model. The proposed converter is simple in construction, highly reliable, and efficient. Further, the converter exhibits less input current ripple and low electromagnetic interference which makes it the best choice for Electric Vehicle applications.
Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Ankylosing spondylitis
Authors: Dong Tiantian , Li Xuhao , Lu Shiyou , Yang Jiguo , Liu Yuan-xiang
Published: March 2023

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the axial skeleton. Meanwhile, copper is a mineral nutrient involved in cell proliferation and death pathways and has been observed in various diseases.
Methods: The purpose of this study was to identify potential new biomarkers of ankylosing spondylitis through biomarker analysis and explore its immune cell infiltration analysis. Gene expression profiles of GSE73754, GSE25101 and GSE18781 datasets were retrieved from the GEO database. Three machine learning algorithms, i.e., minimum absolute shrinkage and selection operator ( LASSO ), random forest ( RF ) and support vector machine recursive feature elimination ( SVM-RFE ), were used to screen cuprotosis-related genes ( CRGs ) of ankylosing spondylitis. Besides, ankylosing spondylitis specimens were classified using the consensus clustering method. The three machine learning results were intersected with the CRGs obtained by difference analysis and the differential CRGs obtained by clustering to obtain key genes. Additionally, the infiltration of immune cells was detected by ssGSEA, and the cuprotosis-related genes related to immune cells and immune function were detected by spearman correlation analysis. The nomogram model was established, and the accuracy of cuprotosis-related genes in predicting the development of AS disease was verified by external data sets.
Result: The two AS libraries in the GEO database were merged after removing the batch effect. Through the difference analysis, 6 CRGs were obtained, 9 CRGs were obtained by LASSO algorithm, 4 CRGs were obtained by SVM-RFE, and 13 CRGs were obtained by RF. It was also found by clustering the consistency of AS samples that they could be divided into 2 subtypes, and 5 CRGs were obtained as well. Finally, two key genes of SLC31A1 and PDHB were obtained by VENN intersection. The immune infiltration and GSEA analysis showed that PDHB had the strongest positive correlation with T cells CD8, followed by T cells CD4 memory resting, and had the strongest negative correlation with Neutrophils. Besides, SLC31A1 had the strongest positive correlation with NK cells resting and the strongest negative correlation with T cells CD8. By establishing a nomogram model, it was found that the two genes could better predict the development of AS, and the verification of the external data set GSE18781 indicated the stronger predictive ability of PDHB.
Conclusion: In summary, the present study revealed several newly discovered cuprotosis-related genes that interfered with the progression of ankylosing spondylitis through immune infiltration, and found the large research space of PDHB.
Establishment of a lipopolysaccharide-induced inflammation model of human fetal colon cells
Authors: YU KEQI , LIAO SHENGTAO , LI CHUANFEI , SONG YA , MEI ZHECHUAN , lin LV
Published: March 2023

AIM: To culture a human fetal colon (FHC) cell line in vitro and establish an FHC cell inflammation model that meets the requirements for high expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).
Methods: FHC cells were cultured with various concentrations of Escherichia coli lipopolysaccharide (LPS) in appropriate media for 0.5, 1, 2, 4, 8, 16 and 24 h to stimulate an inflammatory reaction. The viability of FHC cells was detected by a Cell Counting Kit-8 (CCK-8) assay. The transcriptional levels of IL-6 and tumor necrosis factor-α and the protein expression changes in FHC cells were detected by PCR and ELISA, respectively. Appropriate stimulation conditions were selected (i.e., LPS concentration and treatment time), based on changes in cell survival rate, and IL-6 and TNF-α expression levels.
Results: An LPS concentration higher than 100 μg/mL or a treatment time longer than 24 h resulted in morphological changes and decreased cell survival. By contrast, expression levels of IL-6 and TNF-α significantly increased within 24 h when LPS concentration lower than 100 μg/mL and peaked at 2 h, whilst maintaining cell morphology and viability in FHC cells.
Conclusion: The treatment of FHC cells with 100 μg/mL LPS within 24h was optimal. was optimal in terms of stimulating IL-6 and TNF-α expression.
Relapse EBV-HLH and ANKL in an 8-Year-Old Patient:a Case report
Authors: Huang Cheng shuang , Le Qu , Huang Jia , Sun Shu wen , Zhou Yan
Published: March 2023

Background:
Hemophagocytic Lymphohistiocytosis (HLH) often arises as a hematologic complication of acute and chronic diseases. Identification of underlying disease is crucial for determining HLH prognosis. The global incidence of aggressive natural killer cell leukemia (ANKL), which is rare, aggressive, and lacks a distinctive immunophenotypic or molecular hallmark characteristic, is much rarer in children. Approximately 60–90% of ANKL co-occurs with HLH. The diagnosis of HLH may ignore the presence of ANKL. Therefore, identifying and treating ANKL in children with HLH is difficult.
Case presentation:
The case reports an 8-year-old male initially diagnosed with EBV-HLH and consented to the HLH-2004 regimen, but EBV-HLH returned. We found that the NK cell fraction increased in EBV-HLH. Finally, peripheral blood flow cytometry (FCM) was performed to diagnose ANKL. We strengthened the L-DEP regimen for EBV-HLH with methylprednisolone; and the SMILE regimen for ANKL. After haplo-HSCT, the patient endured for more than four years.
Conclusions:
It serves as a reminder that the increased NK cell fraction is an important clue for identifying ANKL in EBV-HLH; peripheral blood FCM is superior to bone marrow and other tissue sites with restricted laboratory testing for the diagnosis of ANKL.
FOXO3a Negatively Regulates miR-155-5p Expression to impact the proliferation and invasion of Renal Cell Carcinoma
Authors: Wan Rui , Chen Li , Bai Peide , Huang Haichao , Wang Xuegang , Wu Zhun , Sun Anran , Shao Zhiqiang , Chen Yuedong , Wang Huiqiang , Chen Bin , Xing Jinchun , Wang Tao
Published: March 2023

The development of targeted therapy and biotherapy drug resistance is the major barrier in terminal Renal Cell Carcinoma (RCC) therapy. Emerging evidence revealed that FOXO3a could be regulated to suppress RCC. In this study, the regulatory mechanism of FOXO3a on miR-155 and their specific effects in the development of RCC were investigated. We found that FOXO3a was down-regulated in RCC tissues and cell lines, whereas miR-155-5p was highly expressed. Furthermore, the expression of FOXO3a was negatively correlated to miR-155-5p, while FOXO3a was clinically correlated with TNM stages and lymphatic metastasis. The mechanism study showed that FOXO3a transcriptionally regulates miR-155-5p expression by binding to the miR-155 Host gene promoter to regulate the biosynthesis of pre-miR-155. In addition, FOXO3a suppressed the proliferation and migration of RCC cells by regulating miR-155-5p expression. In searching for the downstream targets of miR-155-5p, we found that miR-155-5p suppressed the expression of DUSP-14. Furthermore, FOXO3a up-regulated DUSP-14 expression by down-regulating miR-155-5p. The findings suggest that FOXO3a negatively regulates miR-155-5p expression to impact the proliferation and invasion of renal cell carcinoma.
Clinicopathologic Characteristics of Second Primary Squamous Cell Carcinoma in Patients with Nasopharyngeal Carcinoma after Intensity-modulated Radiotherapy
Authors: Wang Xi , Wang Shunlan , Cao Yang , Li Chunqiao , Fang Caishan , He Weiping , Guo Zhuming
Published: March 2023

Objective
To compare the clinicopathologic characteristics of second primary squamous cell carcinoma (SPSCC) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT) with that after radiotherapy (RT).
Methods
From 49,021 patients with NPC who treated by definitive RT, we were able to identify 15 male patients with SPSCC after IMRT, and 23 male patients with SPSCC after RT. We examined the difference between groups.
Results
In IMRT group, 50.33% developed SPSCC within 3 years, whereas 56.52% developed SPSCC after more than 10 years in RT group. Receiving IMRT was related positively to an increased risk of SPSCC (HR = 4.25; P < 0.001). There was no significant correlation between receiving IMRT and the survival of SPSCC (P = 0.051).
Conclusion
Receiving IMRT was related positively to an increased risk of SPSCC, and the latency was much shorter. A follow-up protocol, especially in the first three years, should be designed for NPC patients with IMRT.
Precipitation Nowcasting using CNN-RNN - Use case: North of Algeria
Authors: HACHEMI Hayat , HAMDAD Leila , DOUBA Oussama
Published: March 2023

Precipitation nowcasting is very important to secure individuals and property against adverse events that may be triggered, as well as to optimize the management of water resources and so-called weather-sensitive economic activities. Achieving effective temporal and spatial nowcasting resolution poses additional challenges to the meteorological community due to the chaotic dynamics that characterize the atmosphere as well as the spatio-temporal variability of this phenomenon. In this work, we aim to use deep learning architectures as Convolutional Neural Network or/and Recurrent Neural Network for the prediction of precipitation to better capture the spatio-temporal variability of meteorological data which are complex. We are particularly interested in rainfall data from northeastern Algeria, where the previously prediction was based on Numerical Weather Prediction. Two types of meteorological data will be used. Firstly, we predict precipitations on synoptic data and secondly, we predict precipitation using synoptic data and previous numerical predicted data obtained by Numerical Weather Prediction. The results were evaluated according to several metrics and a comparison between different approaches was conducted showing the effectiveness of Deep Learning in this field.
APT Encrypted Traffic Detection Method based on Two-Parties and Multi-Session for IoT
Authors: Xu Junfeng , Lin Weiguo , Fan Wenqing , Sun Yunchuan
Published: March 2023

The rise of IoT devices has led to an increase in network endpoints, making Advanced Persistent Threat (APT) attacks a significant concern. APT attacks typically use encrypted communication protocols, making traditional detection methods less effective. Machine learning-based APT encrypted traffic detection methods have been proposed but are limited in their efficacy. In this paper, we propose a novel APT encrypted traffic detection method based on two parties and multi-session analysis. The method extracts a limited set of features from network traffic, including session sequence, session time interval, upstream and downstream data size, which are then transformed into images. These images are subsequently fed into a convolutional neural network (CNN) to recognize patterns and identify network traffic. The proposed method was evaluated through five experiments, demonstrating significant success in detecting APT attacks. The use of multi-session analysis provided a comprehensive view of network traffic, enabling more accurate APT attack detection. The proposed method offers potential for deployment in enterprise security, with implications for the development of more effective APT detection methods.
ALG13 as a prognostic biomarker of prostate cancer associated with tumor immune infiltration and mediated by upstream ncRNA
Authors: Xiao Maolin , Xiao Yunfeng , Liu Wanlan , Xiao Xiao , Yang Zongke
Published: March 2023

Asparagine-linked glycosylation 13 (ALG13) is a highly conserved protein in most eukaryotes, which belongs to the OTU family. It plays a role in neuroblastoma and non-small cell lung cancer. However, the role of ALG13 in prostate cancer (Pca) and its correlation with tumor-infiltrating immune cells remain unclear. Thus, in this study, we extracted and analyzed The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER), and Human Protein Atlas (HPA) data sets to study the potential carcinogenic mechanism of ALG13, including ALG13 expression, prognosis and the correlation of ALG13 expression in immune cell infiltration in Pca. Furthermore, the potential biological signaling pathway of ALG13 in Pca was studied by using Gene set enrichment analysis (GSEA). Upstream microRNA and lncRNA related to ALG13 were found through the prediction of miRWalk and starBase. Results showed that ALG13 was highly expressed in Pca tissues and associated with poor overall survival (OS) and disease-specific survival (DSS). ALG13 expression was correlated with immune cell infiltration. In addition, ALG13 was co-expressed with most immune-related genes, and the high-expression of ALG13 was effective for immune-checkpoint blockade treatment. ALG13 may regulate the pathogenesis of Pca through tumor and immune-related pathways. Finally, AL390728.6/hsa-miR-381-3p axis is considered as a potential upstream ncRNA-related pathway of ALG13 in Pca. Our results demonstrate that the ncRNA-mediated upregulation of ALG13 is associated with poor OS in Prostate adenocarcinoma (PRAD) and tumor immune infiltration. ALG13 may be a new potential prognostic biomarker.
­­­Sense of time is slower following exhaustive cycling exercise
Authors: Moore Andrew , Olson Maddie
Published: March 2023

Subjective perception of time is altered during vigorous exercise. This could be due in part to the fatigue associated with physical activity at high intensities. The aim of this study was to determine the effect of fatigue, specifically, on subjective time perception. Twenty-six healthy, untrained subjects (17 men/9 women; age = 26.0 ± 4.3 years; V̇O2peak = 38.13 ± 5.62 mL/kg/min) completed a maximal aerobic exercise test on a cycle ergometer. Time perception was assessed before (PRE) and after (POST) the exercise test using a time production task. Relative error of the timing task was significantly higher for POST (0.112 ± 0.260) than for PRE (0.028 ± 0.173),p = .032,η2 = .178. Subjects produced ~ 8.4% more time than the target intervals when fatigued, which is indicative of a slower sense of time perception. A shift in attentional focus from timing to the sensations associated with fatigue is a possible factor to explain this result. Future studies which investigate the effects of exercise on time perception should consider the impact of fatigue experienced during exercise.