bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheumatoid arthritis disease activity significantly impacts on the severity of interstitial lung disease.
Authors: Ito Yuhei , Ichikawa Yasutaka , Murashima Shuichi , Sakuma Hajime , Nakajima Ayako
Published: February 2024

Objectives: Rheumatoid arthritis (RA) related interstitial lung disease (ILD) impacts on the treatment strategy and its prognosis in patients with RA. However, the relationship between RA disease activity and the severity of comorbid ILD has not been fully investigated. This study aimed to investigate the impact of RA disease activity on the severity of comorbid ILD in detail based on currently established visual scoring method along with physiological severity.
Methods: Consecutive patients with RA visiting to our Rheumatology Centre between December 2020 and December 2023 were analysed. The radiological severity of ILD was evaluated by averaging the extent of the combined lesion of ground glass opacity, reticulation and honeycombing in 5% increments in six representative high-resolution computed tomography slices ranging from 0% (no involvement) to 100% (all lung fields affected) according to Goh and Walsh’s method. Associations between the radiological and physiological severity of ILD and patients’ features were investigated using linear regression analysis.
Results: Among 124 patients (32 men, 92 women), the median age was 70 years, and the median disease duration was 2.92 years. Radiological severity of ILD was 0% (without ILD) in 107 (86.2%), ILD with extent <10% in nine (7.2%), ILD with extent ³10% and <20% in three (2.4%), ILD with extent ³20% in five (4.0%). Both disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) (standardized coefficient = 0.199, P = 0.03) and rheumatoid factor titre (standardized coefficient = 0.247, P = 0.01) were significantly associated with the radiological quantitative severity of ILD in multivariate analysis adjusted for age, sex, disease duration, smoking status and anti-citrullinated peptide antibody titre. DAS28-ESR was significantly associated with forced vital capacity% predicted (standardized coefficient = -0.230, P = 0.047).
Conclusion: Disease activity of RA was significantly associated with the severity of RA-ILD both radiologically and physiologically.
Does Enterprise Digital Transformation Reduce Tax Compliance?
Authors: ren gaofei
Published: February 2024

In the era of the digital economy characterized by technologies such as artificial intelligence, big data, and cloud computing, digital transformation has become a key path for enterprises to enhance their competitiveness and achieve sustained growth. Existing research has not reached a consensus on the impact of corporate digital transformation on tax compliance behavior, and there is a lack of empirical evidence from a micro perspective on the level of an enterprise. This study explores the impact of enterprises' digital transformation on tax compliance behavior based on data from 2011–2022 Chinese listed companies. Results show that the digital transformation of enterprises can significantly reduce tax compliance behavior by reducing tax avoidance costs. Further research found that this negative effect has significant heterogeneity among enterprises of different ownership and size. Our findings not only expand the theoretical understanding of enterprise digital transformation and tax compliance but also provide theoretical support for governments to promote enterprise digital transformation and tax supervision.
Preferential Graphitic-Nitrogen Formation in Pyridine-Extended graphene Nanoribbons
Authors: Ruffieux Pascal , Bassi Nicolo , Xiushang Xu , Xiang Feifei , Krane Nils , Pignedoli Carlo Antonio , Narita Akimitsu , Fasel Roman
Published: February 2024

Graphene nanoribbons (GNRs), nanometer-wide strips of graphene, have garnered significant attention due to their tunable electronic and magnetic properties arising from quantum confinement. A promising approach to manipulate their electronic characteristics involves substituting carbon with heteroatoms, such as nitrogen, with different effects predicted depending on their position. In this study, we present the extension of the edges of 7-atom-wide armchair graphene nanoribbons (7-AGNRs) with pyridine rings, achieved on a Au(111) surface via on-surface synthesis. High-resolution structural characterization confirms the targeted structure, showcasing the predominant formation of carbon-nitrogen (C-N) bonds (over 90% of the units) during growth. This favored bond formation pathway is elucidated and confirmed through density functional theory (DFT) simulations. Furthermore, an analysis of the electronic properties reveals a reduction of the band gap of the GNR, accompanied by the presence of nitrogen-localized states. Our results underscore the successful formation of C-N bonds on the metal surface, providing insights for designing new GNRs that incorporate substitutional nitrogen atoms to precisely control their electronic properties.
RETRACTED: The Effect of Interactive Problem Solved Sleep Hygiene Education (Ips-she) on Sleep Quality and Affecting Factors, Randomized Controlled Trial
Authors: Bektaş Merve , Kurçer Mehmet Ali
Published: February 2024

The authors have requested that this preprint be removed from Research Square.
Acquired deforming hypertonia in French Caribbean people: a cross-sectional analysis in long-term care units
Authors: KERJEAN Nicolas , BANYDEEN Rishika , GLIZE Bertrand , BONNET Michel , RENE-CORAIL Patrick , TABUE Maturin , DRAME Moustapha , DEHAIL Patrick , BARNAY José-Luis
Published: February 2024

Background: Osteoarticular deformities or contractures in institutionalized elderly individuals, described as acquired deforming hypertonia (ADH), have a multifactorial origin. The reported prevalence of ADH in French Caucasian patients in long-term care units (LTCUs) is 25.6%. To date, ADH in the Caribbean population has never been studied. We aimed to assess the prevalence and characteristics of ADH in such a population.
Methods: This was a cross-sectional observational study of a French Caribbean population in Martinique in which patients aged 75 years or older were institutionalized in LTCUs during the study period. Data extraction from the medical files of eligible LTCU patients was conducted to assess the prevalence, clinical characteristics and impact of ADH on patients’ daily care. The assessments were performed collaboratively between the patients’ geriatric team and a PM&R physician.
Results: In total, 81 patients were included, with an ADH prevalence of 77.8%. Reported ADH was bilateral (86%) or multiple (66% of patients had ≥ 5 ADH) and was responsible for major alterations in terms of hygiene, dressing, pain, and skin damage. ADH patients had a high level of dependence (GMP=924), and this level of dependence was significantly associated with the presence of at least one ADH (p<0.001) regardless of prior disease.
Conclusions: The incidence of ADH in our Caribbean population seems twice as high as that in Caucasian patients, underlining the necessity for this nosological framework to be better recognized, particularly in an insular context. Local campaigns for the prevention and recognition of ADH must be considered, and targeted multidisciplinary protocols need to be established for adapted care in all institutions receiving elderly people.
Insulin-like growth factor binding protein-3 (igfbp-3) and igfbp-5 in yellowtail kingfish (Seriola aureovittata): Molecular identification and expression under different nutritional status and stocking density
Authors: Zheng Jichang , Zhang Wenjing , Xu Yongjiang , Cui Aijun , Jiang Yan , Wang Bin
Published: February 2024

Insulin-like growth factor-binding proteins (IGFBPs) play an important role in regulating growth and development by binding to IGF, with IGFBP-3 and IGFBP-5 being the main binding carriers of IGF in circulation system. In the present study, the gene sequences of igfbp-3, igfbp-5a and igfbp-5b were cloned from the liver of yellowtail kingfish (Seriola aureovittata). The ORF sequences of igfbp-3, igfbp-5a and igfbp-5b were 888, 801 and 804 bp in length, which encoded 295, 266 and 267 amino acids, respectively. The above three genes were widely expressed in detected yellowtail kingfish tissues, with igfbp-3 being the most highly expressed in the heart, brain and gonads, while igfbp-5a and igfbp-5b were both most highly expressed in the liver and kidney. The gene expression of igfbp-3, igfbp-5a and igfbp-5b was detected throughout the embryonic and larval stages, suggesting their roles in early development and growth regulation of yellowtail kingfish. Besides, igfbp-3 and igfbp-5a were significantly up-regulated in liver under food deprivation and high-density rearing conditions, which was exactly opposite to the growth performance of yellowtail kingfish, identifying their typical growth inhibitory profile and implying that they may serve as biomarkers of adverse culture conditions. Overall, the above results initially identified the molecular characteristics of igfbp-3 and igfbp-5 in yellowtail kingfish and demonstrated that they play important roles in the growth and development, providing a basis for further research on underlying regulatory mechanisms.
A BLE-based communication network architecture for smart mobile devices to prevent rapid battery drain
Authors: Çetingöz Mustafa , Taşkın Deniz
Published: February 2024

Internet usage and user interaction on mobile smart devices have grown exponentially with technological advancements, leading to a major challenge: rapid battery depletion. This study addresses this issue by proposing a novel communication network designed to reduce power consumption on smart mobile devices during internet communication. The proposed architecture leverages Bluetooth Low Energy (BLE) technology, known for its energy efficiency. The system comprises two main components: a hardware unit that manages internet tasks via Wi-Fi and transmits notifications to the mobile device using BLE, and a new dedicated smartphone application that receives these notifications and alerts the user. To evaluate the system's effectiveness, a custom measurement system was developed. This system assessed the power consumption of the smartphone in standby mode, measured the power consumption of an email application selected for testing purposes while different connectivity options (3G, LTE and Wi-Fi) were active, and finally assessed the power consumption of the new mobile application using the developed communication methods. The findings demonstrate that the proposed architecture offers significant advantages in scenarios requiring frequent communication.
Radiographic Parameters and feasibility analysis of dual sacral-2 alar-iliac screw fixation using three-dimensional digital technology
Authors: Xie Mengqi , Chen Chao , Sun Xun , Dong Xiaoman , Wang Zhi , Zhao Dong , Liu Gang , Zhu Shan , Xu Baoshan , Zhao Yu , Ma Xinlong , Yang Qiang
Published: February 2024

Objective
The purpose of this study was to evaluate the feasibility and the trajectories of dual sacral-2 alar-iliac (S2AI) screw fixation with three-dimensional digital technology simulation analysis.
Methods
The pelvic computed tomography scan data of 60 (30 men and 30 women, age: 25–86 years) individuals were selected and reconstructed. The trajectories of dual S2AI screws were plotted using three-dimensional reconstruction software. A cylinder with a radius of 5 mm was selected to simulate screw placement. If screw placement based on the cylinder with 5 mm radius failed, selected a cylinder with a radius of 4.5 mm or 4 mm. Dual S2AI trajectories were simulated, the maximum length and width of the trajectories were ensured, and their parameters were precisely measured. All parameters were measured in the three-dimensional image, including distance parameters, radius and angles.
Results
The placement of dual S2AI screws on the same side could be achieved in all individuals. No significant differences were found between the male and female regarding the head inclination angle, abduction angle, and total length or thread length of screws in the same position (P > 0.05). LH(the shortest distance from the greater sciatic notch to the cross-section of the screw trajectory)were17.52 ± 3.96 mm and 14.18 ± 2.92 mm in L1,28.19 ± 2.58 mm and 25.54 ± 4.15 mm in L2, 16.09 ± 4.08 mm and 14.71 ± 3.94 mm in R1, 26.90 ± 3.76 mm and 24.59 ± 2.85 mm in R2 in male and female models, respectively. The shortest distance from the greater sciatic notch to the cross-section of the screw trajectory differed significantly between the sexes (P < 0.05).
Conclusion
Using a radius of 4 mm (minimum diameter of S2AI screw) as a standard, it is feasible to place two S2AI screws on the same side for the Chinese adult. Screw placement can be achieved by trisecting the lateral process of S1-S2, with one screw inserted in the bottom third and the other in the upper third. Furthermore, preoperative three-dimensional digital technology simulation analysis can effectively simulate the dual S2AI screws trajectories on the same side, and they can provide accurate data for clinical applications.
Electric Field Measurements at Aragats Observatory: How to Make the Physical Inferences From the Multivariate Correlated Information
Authors: Chilingarian Ashot , Karapetyan T. , Sargsyan B. , Khanikyanc Y. , Chilingaryan S.
Published: February 2024

To make transformational scientific progress in Space science and geophysics, the Sun, heliosphere, magnetosphere, and different layers of the atmosphere must be studied as a coupled system. The presented paper describes how information on complicated physical processes in the atmosphere can be immediately assessable for researchers via an advanced multivariate visualization system with a simple statistical analysis package. Research of the high-energy phenomena in the atmosphere and the atmospheric discharges is of special importance. The relationship between thundercloud electrification, lightning activity, wideband radio emission, and particle fluxes has not yet been established. One of the most intriguing opportunities opened by observation of the high-energy processes in the atmosphere is their relation to lightning initiation. Investigations of the accelerated structures in the geospace plasmas can also shed light on particle acceleration up to much higher energies in the similar structures of space plasmas in the distant objects of the Universe. For example, we demonstrate how to infer the physical inferences from time series of the surges of particle flux intensity, near-surface electric field strength, records of wideband field, and interferometer antenna signals.
Risk Management of Venous Thromboembolism in Inpatients at Tertiary Hospitals in China: A Retrospective Longitudinal Study
Authors: Shi Ziyue , Yu Yaqian , Hou Yifang , Duan Jun , Hu Yonghuan , Huang Chengzhang , Jiang Enshe , Deng Xiaomei
Published: February 2024

Background
While it is recognized that racial differences in the risk of venous thromboembolism (VTE) exist between Asian and Western populations, comprehensive data on VTE risk, bleeding risk, and prevention strategies among large-scale hospitalized patients in China remain limited.
Materials and Methods
A retrospective longitudinal study was conducted on 85,366 adult inpatients, hospitalized for more than 24 hours at a tertiary comprehensive hospital in China from May 1, 2021 to April 30, 2022. Standardized assessment tools recommended by the 9th edition of the CHEST guidelines were used to assess the patient’s VTE and bleeding risks. An analysis was performed on their demographic characteristics, risk factors, use of prevention measures, and VTE incidence.
Results
The study found that among surgical and medical inpatients, the proportions of patients at high risk for VTE were 4.97% (95%CI: 4.77%-5.18%) and 11.23% (95%CI: 10.93%-11.53%), respectively. The highest proportions of high-risk patients were observed in diseases of the circulatory system (9.90%, 95%CI: 8.83%-11.08%) and certain infectious and parasitic diseases (19.31%, 95%CI: 16.36%-22.64%). Among those assessed for bleeding risk, the proportions of surgical and medical inpatients at high risk were 3.47% and 16.69% (95 CI: 15.57%-17.87%), respectively. However, the proportion of patients receiving different types of preventive measures did not reach 80% in both surgical and medical groups. The VTE incidence rates during hospitalization for surgical and medical patients were 0.65% (95%CI:0.58%-0.73%) and 2.24% (95 CI: 2.1%-2.39%), respectively, with the highest VTE rates observed in patients with diseases of the circulatory system both. The study also found significant differences in VTE risk among different diseases and between surgical and medical inpatients.
Conclusion
Despite most patients undergoing VTE and bleeding risk assessments, adherence to guideline-recommended prevention strategies was not optimal. This underscores the need for healthcare professionals to raise awareness and take proactive measures to reduce the disease burden and improve patient outcomes.
The effect of Center-Perforated tapered twisted tape insert in tube on the performance of heat exchanger: A numerical approach
Authors: Yadav Ajeet , Gupta Rajesh , Mohit Manish Kumar
Published: February 2024

Inserts of twisted tapes in tubes with a large number of variations have long been used to enhance heat transfer rate and improve heat exchanger performance. Although, this improved the heat transfer rate but tends to increase the friction factor simultaneously. This paper primarily focuses on the investigation of inserts of twisted tapes with varying widths instead of constant ones to improve thermos-hydraulic performance with an adequate reduction in friction factor. Further perforated twisted tape insert is expected to provide a reduction in the wetted area of the tube and reduce pressure drop. A numerical investigation using the ANSYS FLUENT is carried out to analyze the performance of the center-perforated tapered twisted tape with water as working fluid under laminar flow conditions i.e. 500 ≤ Re ≤ 1750. In addition to this, twin tapered TT configuration is also analyzed; a total of 36 cases are evaluated. The computational results revealed that the flow resistance is reduced with the proposed twisted tape configuration as compared to the plain twisted tape; however, thermal performance is affected only marginally. In the optimization study, it is advised to use the tapered twisted tape arrangement because it results in a significant reduction of pressure drop, about 65 percent, as well as the power input for the marginal reduction in thermal performance.
Third(fourth) order accurate method for one dimensional local fractional Viscous Burgers’ and diffusion-convection equations
Authors: Pandey Ankit , Mohanty R. K.
Published: February 2024

A Singular fractal boundary value problem whose order term is a Hausdroff Fractal derivative of order δ ∈ (0, 1] is considered. In this article, using three grid points, we discuss the variable mesh method of order three that requires only three function evaluations on some regularity conditions. we give importance to solve a singular problem in our scheme and prove that the recommended scheme is significant. We also discussed the convergence analysis of our method and proved that the method is reliable, like classical numerical methods. Special numerical illustrations for solving linear and nonlinear fractal differential equations are provided to demonstrate the accurate outcome of the recommended method, which has been discussed in convergence analysis.
Pulmonary function, genetic predisposition, and the risk of cirrhosis: A prospective cohort study
Authors: Guo Rongchang , Wang Lanbo , Liu Tiancong , Li Shiwen , Liu Yashu , Yang Honghao , Chen Liangkai , Ji Chao , Xia Yang
Published: February 2024

Background
Pulmonary function is known to be associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis modifies these associations.
Methods
A total of 308,678 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk.
Results
During a median follow-up of 12.0 years, 2,725 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.30 [1.16, 1.45]) and airflow obstruction (HR [95%CI]: 1.19 [1.08, 1.32]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.68 [1.41, 2.00]).
Conclusion
Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition.
The prognosis and immune repertoire characteristics of HBsAg and anti-HBs double positivity chronic hepatitis B patients
Authors: Liang Huijun , Wang Haifang , Liang Minfeng , Zhang Xiaobin , Dai Meifen , Li Haixia , Li Xin , Yin Xiaofeng , Liu Xinyao , Guan Ziyun , Qiu Yurong
Published: February 2024

Background: Coexistence of HBsAg and anti-HBs has been observed in some chronic hepatitis B patients, but the clinical outcomes and comprehensive characterization of immune microenvironmental changes for this specific population remain inconclusive.
Methods: A retrospective analysis of 305 patients in Foshan City, Guangdong Province, China, was conducted to investigate the prognosis. Molecular immunology changes of HBsAg and anti-HBs dual-positive chronic HBV patients (DP) and recovery patients (RP) were detected using TCR and BCR immune repertoire sequencing technology.
Results: Our findings revealed that 22.30% of the dual-positive patients in Foshan district, Guangdong province, were diagnosed with severe liver disease. Furthermore, immune repertoire sequencing demonstrated significant skewing in the diversities of TRB and BCR in the DP group compared to the RP group. V(D)J combinations, such as IGHV1-18/IGHD3-22/IGHJ5, IGHV1-8/IGHD6-13/IGHJ3, and IGHV1-8/IGHD6-19/IGHJ3, along with TRBV12-3/TRBD1/TRBJ1-5 and TRBV11-2/TRBD2/TRBJ2-1, emerged as potential biomarkers for diagnosing the DP group. Additionally, distinct amino acid motifs in the TCR CDR3 of DP and HC groups, compared to the RP group, were identified. Notably, motifs "xxxYDSSGYx" and "AREx" in the BCR were selectively prevalent in the DP group, suggesting their potential to specifically identify the DP group from the RP group.
Conclusions:These findings provide evidence for the poor clinical prognosis of dual-positive chronic HBV patients, offer new insights for the study of immune microenvironmental changes and pathogenesis, and may contribute to the development of potential diagnostic biomarkers and therapeutic targets for the DP group.
Specification for Light Rare Earth Concentrates Prepared from Egyptian Crude Monazite Spectrophotometrically
Authors: Shehata SH. B. , El-Ghany M. S. Abd , Helaly O. S. , Abo-Aly M. M.
Published: February 2024

Determination of several light and medium REEs individually such as lanthanum, neodymium, praseodymium, samarium and gadolinium in high-grade concentrates prepared from Egyptian crude Monazite are achieved. These concentrates were firstly specified using SCAN-EDX analysis to identify the constituents of the analyzed rare earth elements. Complex formation study was carried out spectrophotometrically between disodium ethylene diaminetetraacetic acid (EDTA) and these trivalent rare earth elements “REEs” as Ln-EDTA for light and middle REEs. Different factors have been investigated including, EDTA-REEs molar ratio, pH of the LREEs / EDTA medium; time required for complex formation and initial concentrations of rare earth elements.
Subtractive Genome mining in Xanthomonas citri pv. Citri strain 306 for identifying novel drug target proteins coupled with in-depth protein-protein interaction and coevolution analysis - A leap towards prospective drug design
Authors: Mahato Tumpa , Mandal Jayanta , Chatterjee Eilita , Bhattacharya Satyabrata , Sinha Sangram
Published: February 2024

Citrus canker (CC) poses a serious threat to a highly significant citrus fruit crop, this disease caused by one of the most destructive bacterial plant pathogens Xanthomonas citri pv. citri. Bacterial plant diseases cause substantial global losses in crop production. Reducing crop yield losses is necessary to meet growing global food demands with a rising population. High rates of antibiotic resistance to conventional pesticides and antibiotics among Xanthomonas citri pv. citri (XCC) strains the effectiveness of current control methods is diminishing, have rendered treatment management more challenging and highlighted the need for novel therapeutic targets or new approaches to combat the rising antimicrobial resistance trend. Utilizing OMICS data offers an appealing alternative to experimental methods, propelling drug discovery and reducing the risk of later-stage drug failures. Using an innovative hierarchical computational method, the goal of this present study was to identify and characterize potential drug targets against the pathogen XCC strain 306. The study involved retrieving the XAC proteome from the UniProt database, eliminating paralogous proteins using CD-HIT (80% identity cutoff), and selecting nonhomologous proteins through BLASTp (e-value < 0.005). Essential proteins were identified using BLAST against the DEG (e-value cutoff 0.00001). Subsequent analyses included metabolic pathway assessment, subcellular localization prediction, and druggability analysis. Protein network analysis, coevolution analysis (CoeViz server), protein active site identification (CastP 3.0), and centrality betweenness graph plotting (ProsNex) were performed. In conclusion, this study identified eight drug targets (GlmU, CheA, RmlD, GspE, FleQ, RpoN, Shk, SecB), highlighting RpoN, FleQ, and SecB as unprecedented targets for XCC. These findings may contribute to the development of novel antimicrobial agents in the future that can efficiently control citrus canker disease.
Stress boundary layers for the Phan-Thien–Tanner fluid at the static contact line in extrudate swell
Authors: Evans Jonathan D. , Evans Morgan L.
Published: February 2024

The method of matched asymptotic expansions is used to examine the behaviour of the Phan-Thien–Tanner (PTT) fluid in the neighbourhood of the contact line singularity in extrudate swell. The solution structure for this shear-thinning viscoelastic fluid model, has solvent stresses that dominate the polymer stresses, but requires stress boundary layers to fully resolve the solution at the die wall and free surface. The sizes and mechanism of the boundary layers at the two surfaces are different. We derive and present a similarity solution for the boundary layer at the die wall and an exact solution for the boundary layer at the free-surface. An expression for the local behaviour of the free-surface is also derived. The results for the boundary layers completes the preliminary asymptotic results for the PTT model presented in previous work.
Utility of an untargeted metabolomics approach using a 2D GC-GC‒MS platform to distinguish relapsing and progressive multiple sclerosis
Authors: Datta Indrani , Zahoor Insha , Ata Nasar , Rashid Faraz , Cerghet Mirela , Rattan Ramandeep , Pisson Laila M , Giri Shailendra
Published: February 2024

Introduction:
Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS and may progress to the progressive form (PPMS).
Objectives
There is a gap in knowledge regarding whether the relapsing form can be distinguished from the progressive course or healthy subjects (HS) based on an altered serum metabolite profile. In this study, we performed global untargeted metabolomics with the 2D GCxGC-MS platform to identify altered metabolites between RRMS, PPMS, and HS.
Methods
We profiled 235 metabolites in the serum of patients with RRMS (n = 41), PPMS (n = 31), and HS (n = 91). A comparison of RRMS and HS patients revealed 22 significantly altered metabolites at p < 0.05 (false discovery rate [FDR] = 0.3). The PPMS and HS comparisons revealed 28 altered metabolites at p < 0.05 (FDR = 0.2).
Results
Pathway analysis using MetaboAnalyst revealed enrichment of four metabolic pathways in both RRMS and PPMS (hypergeometric test p < 0.05): 1) galactose metabolism; 2) amino sugar and nucleotide sugar metabolism; 3) phenylalanine, tyrosine, and tryptophan biosynthesis; and 4) aminoacyl-tRNA biosynthesis. The Qiagen IPA enrichment test identified the sulfatase 2 (SULF2) (p = 0.0033) and integrin subunit beta 1 binding protein 1 (ITGB1BP1) (p = 0.0067) genes as upstream regulators of altered metabolites in the RRMS vs. HS groups. However, in the PPMS vs. HS comparison, valine was enriched in the neurodegeneration of brain cells (p = 0.05), and heptadecanoic acid, alpha-ketoisocaproic acid, and glycerol participated in inflammation in the CNS (p = 0.03).
Conclusion
Overall, our study suggested that RRMS and PPMS may contribute metabolic fingerprints in the form of unique altered metabolites for discriminating MS disease from HS, with the potential for the construction of a metabolite panel for progressive autoimmune diseases such as MS.
COVID-related Constrictive Pericarditis Requiring Pericardiectomy: A Case Report
Authors: Boyles Rachel , Lu Joseph , Yoo Joseph , Samuels Louis
Published: February 2024

Background
The COVID-19 pandemic was primarily considered a respiratory malady in the early phases of the outbreak. However, as more patients suffer from this illness, a myriad of symptoms emerge in organ systems separate from the lungs. Among those patients with cardiac involvement, myocarditis, pericarditis, myocardial infarction, and arrhythmia were among the most common manifestations. Pericarditis with pericardial effusion requiring medical or interventional treatments has been previously reported in the acute setting. Notably, chronic pericarditis with pericardial thickening resulting in constriction requiring sternotomy and pericardiectomy has not been published to date.
Case Presentation
A patient with COVID-19-associated constrictive pericarditis three years after viral infection requiring pericardiectomy was reported. The COVID-19 infection originally manifested as anosmia and ageusia. Subsequently, the patient developed dyspnea, fatigue, right-sided chest pressure, bilateral leg edema, and abdominal fullness. Following recurrent right pleural effusions and a negative autoimmune work-up, the patient was referred for cardiothoracic surgery for pericardiectomy when radiographic imaging and hemodynamic assessment were consistent with constrictive pericarditis. Upon median sternotomy, the patient’s pericardium was measured to be 8 mm thick. Descriptions of the clinical, diagnostic, and therapeutic features are provided. Within the first week after the operation, the patient’s dyspnea resolved; one month later, leg edema and abdominal bloating were relieved.
Conclusions
Although an association between COVID-19 and cardiac complications has been established, this case adds another element of virus severity and chronic manifestations. The need for sternotomy and pericardiectomy to treat COVID-19-related constrictive pericarditis is believed to be the first reported diagnosis.
Integrative analysis of genomic and epigenomic regulation reveals microRNA regulatory network mediated tumor heterogeneity and immune evasion in lower grade glioma
Authors: Yang Zhen , Liu Xiaocen , Xu Hao , Teschendorff Andrew E. , Xu Lingjie , Li Jingyi , Fu Minjie , Liu Jun , Zhou Hanyu , Wang Yingying , Zhang Licheng , He Yungang , Lv Kun , Yang Hui
Published: February 2024

Background
Lower grade glioma (LGG) is the most frequent primary tumors of the central nervous system and has been a major healthcare burden, however, the specific molecular mechanism underlying its initiation and progression remains to be elucidated. Although it is known that microRNAs (miRNAs) are widely involved in the regulation of malignant phenotypes of glioma, the underling mechanism for miRNA dysregulation remains largely unanswered.
Methods
In the present work, we developed a novel strategy to obtain the genome wide copy number variation (CNV) and promoter DNA methylation (DNAm) data of miRNAs and performed a systematic integrative study for the multi-omics data to identify mechanisms underlying miRNA dysregulation molecular subtyping in LGG. The relationship between LGG subtypes, prognosis, molecular features, tumor immune microenvironment and response to immune therapy was further analyzed. We also developed a prognostic model based on immune-related miRNAs that were differentially expressed between LGG samples. Then, the influence of the prognostic model on the immune microenvironment in LGG was comprehensively analyzed.
Results
We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis of the copy number and methylation related miRNAs revealed four subtypes with differing prognoses, which were validated with independent cohort data. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. We further screened immune-related miRNAs through investigation of their correlation with immune cell infiltrations and immune microenvironment. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to glioma immunotherapy. We finally evaluated the associations between prognosis related miRNAs and immune regulation. Among them, miR-155-5p, miR-196a-5p, miR-196b-5p, miR-200a-3p, miR-503-5p, and miR-15b-5p were validated as immunoevasive biomarkers and to promote cell migration, invasion and proliferation for glioma through in vitro experiments.
Conclusions
Our study systematically reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of novel biomarkers for immunotherapy approaches.
KDM6B enhances anti-PD-L1 immunotherapy efficacy by increasing CD8+ T-cell infiltration in colorectal cancer
Authors: Xun Jing , Liu Zehan , Liu Bin , Jiang Xiaolin , Liu Jinjin , Wang Botao , Gao Ruifang , Zhang Aimin , Wu Xueliang , Wang Ximo , Yu Xiangyang , Zhang Qi
Published: February 2024

Background: CD8+ T cells in the tumor microenvironment are crucial for antitumor effects. Boosting their infiltration can significantly enhance the efficacy of antitumor immunotherapy. However, the precise contribution of the epigenetic regulator lysine-specific demethylase 6B (KDM6B) to colorectal cancer (CRC) immunity remains elusive.
Methods: KDM6B expression was detected in adjacent and CRC tissues or normal and cancer cells. Mouse models of CRC were established to assess the impact of KDM6B on tumor progression. The infiltration of CD8+ T cells was detected by IHC and a transwell assay. RT-qPCR, western blotting or flow cytometry were used to detect the effect of KDM6B on PD-L1, CD8+ T-cell-attracting chemokines and p-STAT3 expression. ChIP-qPCR was performed to determine the H3K27me3 enrichment in the promoter regions of target genes PD-L1 and CD8+ T-cell-attracting chemokines. Finally, paricalcitol was combined with anti-PD-L1 antibodies to evaluate their anti-CRC effects.
Results: KDM6B was downregulated in CRC tissues and cells, but its overexpression successfully hindered CRC growth and liver metastasis. Mechanistically, the activation of demethylase activity and STAT3 signaling, leading to increased expression of CD8+ T-cell-attracting chemokines CCL5, CXCL9, and CXCL10, as well as enhanced PD-L1 expression in CRC cells. This ultimately resulted in increased infiltration of CD8+ T cells. Paricalcitol and anti-PD-L1 antibody therapy work together to achieve superior tumor elimination efficiency. Paricalcitol, combined with anti-PD-L1 antibodies, offered superior tumor elimination efficiency.
Conclusion: These findings suggest that KDM6B plays a positive role in regulating the immune microenvironment in CRC, potentially offering a theoretical basis for CRC immunotherapy.
Generalized Coupled Matrix Tensor Factorization Method Based on Normalized Mutual Information for Simultaneous EEG-fMRI Data Analysis
Authors: Rabiei Zahra , Kordy H. Montazery
Published: February 2024

Through the fusion of electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) data, the complementary properties of both modalities can be exploited. Thus, joint analysis of both modalities can be utilized in brain studies to estimate their shared and unshared components in brain activities. In this study, a comprehensive approach was proposed to jointly analyze EEG and fMRI datasets based on the advanced coupled matrix tensor factorization (ACMTF) method. The similarity of the components based on normalized mutual information (NMI) was defined to overcome the restrictive equality assumption of shared components in the common dimension of the ACMTF method. Because the mutual information (MI) measure is capable of identifying both linear and nonlinear relationships between the components, the proposed method can be viewed as a generalization of the ACMTF method; thus, it is called the generalized coupled matrix tensor factorization (GCMTF). The proposed GCMTF method was applied to simulated data, in which there was a nonlinear relationship between the components. The results demonstrate that the average match score increased by 23.46% compared to the ACMTF model, even with different noise levels. Furthermore, by applying this method to real data from an auditory oddball paradigm, it was demonstrated that three shared components with frequency responses in the alpha and theta bands were identified. The proposed MI-based method is not only capable of extracting shared components with any nonlinear or linear relationship but it is also able to identify more active brain areas corresponding to an auditory oddball paradigm compared to the ACMTF and other similar methods.
Genetic variability in Iranian sainfoin (Onobrychis viciifolia Scop.) landraces by morphological characteristics
Authors: Sabaghnia Naser , Ahadnezhad Amin , Moayed Farid Normand , Janmohammdi Mohsen
Published: February 2024

The sainfoin (Onobrychis viciifolia Scop.) is an ancient fodder crop traditionally cultivated in Mediterranean climates, yet its cultivation has dwindled in favor of other forage options across many regions. We investigated the diversity among 32 sainfoin landraces sourced from various parts of Iran, analyzing 18 distinct traits over two seasons (2022 and 2023) using a randomized complete block scheme. Notable variations were observed across the majority of measured characteristics, whereas the coefficient of variation ranged from 10.5–6.8% (for days to seed filling initiation) to as high as 63.2% and 70.8% (for inflorescence dry weight) in the first and second years, respectively. Principal Component Analysis (PCA) highlighted significant variability, with the first four components explaining 83% of the variance in 2022 and 78% in 2023. When plotting PCA1 against PCA2 for both years, distinct groups emerged, revealing three discernible groups of sainfoin landraces. Notably, certain landraces consistently grouped together across both years, including G1 (Bonab), G3 (Marand), and G11 (Urmia) from the northwest, G23 (Khomeyn), G24 (Arak), and G30 (Khansar) from the central region, and G26 (Asadabad) from the western, alongside G28 (Damavand) from the north. These landraces, originating from diverse geographical locations, were identified as particularly promising due to their distinct traits. Our findings underscore the rich morphological diversity present in current sainfoin landraces, suggesting ample opportunities for genetic improvement initiatives. These insights hold relevance for future breeding efforts aimed at enhancing specific traits through strategic crossbreeding of parent plants.
Factors Affecting Student Learning Experience: The Case of Arabic Calligraphy and Morphology Subjects in MSU KFCIAAS During Online Modality
Authors: Mama Jasmin Jeanette C. , Vistal Jogie A. , Maruhom Jenan Shahri A.
Published: February 2024

During the pandemic, educational institutions worldwide were forced to shift to online modalities for safety reasons, affecting not only English subjects but also Arabic subjects. This shift posed challenges for Arabic subjects, as the standard online learning infrastructure often did not adequately support these specialized courses. Students found it more difficult to adjust compared to traditional face-to-face classes. Hence, this study aims to investigate the factors influencing students’ learning experiences in Arabic subjects during online modality using Structural Equation Modelling. Key elements were identified as influential on students’ learning outcomes on these subjects, such as self-regulation, technology literacy and competency, technological sufficiency, technology complexity, and learning resources. On the other hand, the study explores the factors contributing to students’ successful completion of Arabic Calligraphy and Morphology subjects during online learning such as imitating, consolidation, deep mastery, tamrin, and ijazah. The study was conducted on a sample size of 100 students who were enrolled in Arabic Calligraphy and Arabic Morphology subjects during the online modality. The instrument comprised 52 questions designed to collect data on the factors affecting students’ learning experiences during the online modality. The findings shed light on the implications of teaching and learning Arabic subjects within online education.
Binding predictions and molecular docking as a computational approach to identify human T CD4 epitopes from Leishmania proteins
Authors: Martínez Magda Melissa Flórez , Larios Dariannis , Martínez Wilson David , Rojas Karel , Uribe Yajaira , Torres Francy Elaine
Published: February 2024

Leishmaniasis is an important public health problem caused by a protozoan parasite and distributed in 98 countries worldwide. Leishmania can causes from skin ulcers to complex visceral involvement, and treatment options available for humans have high toxicity and prolonged application schemes, therefore low treatment adhesion. So far there are not licensed vaccines for humans so is necessary to develop a strategy that can improve treatment options or that can prevent the onset of the disease. To eliminate intracellular Leishmania amastigotes inside macrophage, a cellular immune response of CD4+ Th1 profile is essential, therefore the identification of sequences that binds strong to HLA class II pockets are good candidates to induce a protective immune response against Leishmania spp.
The aim of this study was to identify T CD4+ epitopes from immunogenic Leishmania proteins.
Methodology: First, three prediction tools were used as screening comparing the 15mer sequences along the complete protein sequence against 25 HLA-DR alleles employing NH, SMT, CPA, CPB, and CPC proteins. Second, molecular docking was run for the best candidates.
Results: 6 peptides were identified as HLA-DR strong binders simultaneously from the three bioinformatic prediction tools: NH69-83, SMT133-148, CPA39-54, CPA301-316, CPB42-57, and CPC37-52. After alignment and molecular docking analysis, the most promising sequences were SMT113-148 and CPA39-54.
Conclusion: This bioinformatic strategy allowed a sequential screening from 1 857 possible peptides to 2 promising candidates, raising the probability of these sequences being natural T CD4+ Leishmania spp. epitopes in humans, therefore good candidates to be evaluated in further studies.
Subcision with and without suction for acne scars: A split-faced, rater-blinded randomized control trial
Authors: Shi Victoria J. , Ma Melissa S. , Koza Eric , Haq Misha , Ahmed Areeba , Yi Michael D. , Dirr McKenzie A. , Anvery Noor , Christensen Rachel E. , Pagdhal Kapila , Geisler Amelia , Nodzenski Michael , Roongpisuthipong Wanjarus , Brieva Joaquin C. , Cahn Brian A. , Yoo Simon S. , Lucas Jennifer , Poon Emily , West Dennis P. , Fife Douglas , Alam Murad
Published: February 2024

Objectives: Therapeutic options for acne scars include subcision and suction with microdermabrasion, but these treatment modalities have not been studied in conjunction.
To compare effectiveness of subcision alone versus subcision with suction for the treatment of facial acne scars.
Methods: Randomized, split-faced, evaluator-blinded control trial. Participants underwent one subcision treatment on both sides of the face followed by 10 sessions of suction to one side. Photographs at baseline, 1-month, and 4-months were assessed. Primary outcome measures were the validated Acne Scar Severity Scale (ASSS) (0=no acne scarring, 4=severe), Acne Scar Improvement Grading Scale (ASIGS) (-100% to 100%), and modified Quantitative Global Scarring Grades (QGSG) (point-based questionnaire instrument), as well as subject preference.
Results: Twenty-eight treatment areas and 154 treatments were analyzed. Dermatologist raters found no differences between subcision alone and subcision-suction at 1-month or 4-months. Mean subject-assessed percent improvement for subcision-suction was higher than that for subcision alone at 1-month (37% versus 24%, p=0.04) but not at 4-months (p=0.37). Subjects preferred combination therapy to monotherapy at 1 month (50% vs 21%) and 4 months (43%, 21%).
Conclusions: While blinded raters did not detect significant differences, subjects perceived combination treatment as working more quickly than monotherapy, and preferred combination treatment at all time points.
Clinical trial registration: NCT01696513 on Clinicaltrials.gov