bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Potentiality of Shikonin Derivatives Inhibiting SARS-CoV-2 Main Protease by Molecular Dynamic Simulation Studies
Authors: Das Raju , Habiba Sarmin Ummey , Dash Raju , Seo Yohan , Woo Joohan
Published: February 2023

Shikonin, a phytochemical present in the roots of Lithospermum erythrorhizon, is well-known for its broad-spectrum activity against cancer, oxidative stress, inflammation, viruses, and anti-COVID-19 agents. A recent report based on a crystallographic study revealed a distinct conformation of shikonin binding to the SARS-CoV-2 main protease (Mpro), suggesting the possibility of designing potential inhibitors based on shikonin derivatives. The present study aimed to identify potential shikonin derivatives targeting the Mpro of COVID-19 by using molecular docking and molecular dynamics simulations. A total of 20 shikonin derivatives were screened, of which few derivatives showed higher binding affinity than shikonin. Following the MM-GBSA binding energy calculations using the docked structures, four derivatives were retained with the highest binding energy and subjected to molecular dynamics simulation. Molecular dynamics simulation studies suggested that alpha-methyl-n-butyl shikonin, beta-hydroxyisovaleryl shikonin, and lithospermidin-B interacted with two conserved residues, His41 and Cys145, through multiple bonding in the catalytic sites. This suggests that these residues may effectively suppress SARS-CoV-2 progression by inhibiting Mpro. Taken together, the present in silico study concluded that shikonin derivatives may play an influential role in Mpro inhibition.
Genome-Wide Re-Identification and Analysis of CrRLK1Ls in Tomato
Authors: Ma Wenpeng , Liu Xin , Chen Kai , Yu Xinlong , Ji Dongchao
Published: February 2023

The Catharanthus roseus receptor-like kinase 1-like (CrRLK1L), which is a vital member of the plant receptor-like kinase family, plays versatile roles in plant growth, development, and stress response. Although the primary screening of tomato CrRLK1Ls has been reported previously, our knowledge of these proteins is still scarce. Using the latest genomic data annotations, a genome-wide re-identification and analysis of the CrRLK1Ls in tomatoes were conducted. In this study, 24 CrRLK1L members were identified in tomatoes and researched further. Subsequent gene structures, protein domains, Western blot analyses, and subcellular localization analyses all confirmed the accuracy of the newly identified SlCrRLK1L members. Phylogenetic analyses showed that the identified SlCrRLK1L proteins had homologs in Arabidopsis. Evolutionary analysis indicated that two pairs of the SlCrRLK1L genes had predicted segmental duplication events. Expression profiling analyses demonstrated that the SlCrRLK1L genes were expressed in various tissues, and most of them were up- or down-regulated by bacteria and PAMP treatments. Together, these results will lay the foundation for elaborating the biological roles of SlCrRLK1Ls in tomato growth, development, and stress response.
Tweaking the Small Non-Coding RNAs to Improve Desirable Traits in Plant
Authors: Halder Koushik , Chaudhuri Abira , Abdin Malik Z. , Datta Asis
Published: February 2023

Plant transcriptome contains an enormous amount of non-coding RNAs (ncRNAs) that do not code for proteins but take part in regulating gene expression. Since their discovery in the early 1990s, much research has been conducted to elucidate their function in the gene regulatory network and their involvement in plants’ response to biotic/abiotic stresses. Typically, 20–30 nucleotide-long small ncRNAs are a potential target for plant molecular breeders because of their agricultural importance. This review summarizes the current understanding of three major classes of small ncRNAs: short-interfering RNAs (siRNAs), microRNA (miRNA), and transacting siRNAs (tasiRNAs). Furthermore, their biogenesis, mode of action, and how they have been utilized to improve crop productivity and disease resistance are discussed here.
Eltrombopag Inhibits Metastasis in Breast Carcinoma by Targeting HuR Protein
Authors: Chen Yao , Zhang Rui , Yang Liuqing , Zhang Pei , Wang Feiyun , Lin Guoqiang , Zhang Jiange , Zhu Yuying
Published: February 2023

Eltrombopag is a small molecule TPO-R agonist that has been shown in our previous studies to inhibit tumor growth by targeting Human antigen R (HuR) protein. HuR protein not only regulates the mRNA stability of tumor growth-related genes, but it also regulates the mRNA stability of a variety of cancer metastasis-related genes, such as Snail, Cox-2, and Vegf-c. However, the role and mechanisms of eltrombopag in breast cancer metastasis have not been fully investigated. The purpose of this study was to investigate whether eltrombopag can inhibit breast cancer metastasis by targeting HuR. Our study first found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level. Secondly, eltrombopag was found to suppress 4T1 cell migration and invasion and inhibit macrophage-mediated lymphangiogenesis at the cellular level. In addition, eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of Snail, Cox-2, and Vegf-c in 4T1 cells and Vegf-c in RAW264.7 cells by targeting HuR. In conclusion, eltrombopag displayed antimetastatic activity in breast cancer in an HuR dependent manner, which may provide a novel application for eltrombopag, hinting at the multiple effects of HuR inhibitors in cancer therapy.
Methyl Donor Micronutrients: A Potential Dietary Epigenetic Target in Systemic Lupus Erythematosus Patients
Authors: Pesqueda-Cendejas Karen , Campos-López Bertha , Mora-García Paulina E. , Moreno-Ortiz José M. , De la Cruz-Mosso Ulises
Published: February 2023

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an aberrant immune response and persistent inflammation. Its pathogenesis remains unknown; however, a complex interaction between environmental, genetic, and epigenetic factors has been suggested to cause disease onset. Several studies have demonstrated that epigenetic alterations, such as DNA hypomethylation, miRNA overexpression, and altered histone acetylation, may contribute to SLE onset and the disease’s clinical manifestations. Epigenetic changes, especially methylation patterns, are modifiable and susceptible to environmental factors such as diet. It is well known that methyl donor nutrients, such as folate, methionine, choline, and some B vitamins, play a relevant role in DNA methylation by participating as methyl donors or coenzymes in one-carbon metabolism. Based on this knowledge, this critical literature review aimed to integrate the evidence in animal models and humans regarding the role of nutrients in epigenetic homeostasis and their impact on immune system regulation to suggest a potential epigenetic diet that could serve as adjuvant therapy in SLE.
Flavonoids from Hippophae rhamnoides Linn. Revert Doxorubicin-Induced Cardiotoxicity through Inhibition of Mitochondrial Dysfunction in H9c2 Cardiomyoblasts In Vitro
Authors: Zhou Wenna , Ouyang Jian , Hu Na , Wang Honglun
Published: February 2023

Doxorubicin (Dox) is one of the most frequently prescribed anti-cancer drugs. However, treatment with Dox is limited due to cumulative cardiotoxicity. 3-O-β-d-Sophorosylkaempferol-7-O-{3-O-[2(E)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl]}-α-L-rhamnoside (F-A), kaempferol 3-sophoroside 7-rhamnoside (F-B), and hippophanone (F-C) were successfully obtained by purification and separation of seabuckthorn seed residue in our previous research. This study was undertaken to investigate the protective effect of three flavonoids against Dox-induced H9c2 cell apoptosis. Cell proliferation was detected by MTT assay. 2′,7′-Dichlorofluorescein diacetate (DCFH-DA) was used to determine the production of intracellular reactive oxygen species (ROS). ATP content was measured using an assay kit. Transmission electron microscopy (TEM) was used to observe changes in mitochondrial ultrastructure. The expression levels of proteins (p-JNK, JNK, p-Akt, Akt, p-P38, P38, p-ERK, ERK, p-Src, Src, Sab, IRE1α, Mfn1, Mfn2, and cleaved caspase-3) were evaluated by Western blot. Molecular docking was performed using AutoDock Vina. The three flavonoids could significantly relieve Dox-induced cardiac injury and inhibit cardiomyocyte apoptosis. The mechanisms were mainly related to the stability of mitochondrial structure and function maintained by suppressing the production of intracellular ROS, p-JNK and cleaved caspase-3, and increasing ATP contents and protein expression of mitochondrial mitofusin (Mfn1, Mfn2), Sab and p-Src. Pretreatment with flavonoids from Hippophae rhamnoides Linn. can reduce Dox-induced H9c2 cell apoptosis based on the ‘JNK-Sab-Ros’ signal pathway.
Comparative Transcriptome Analysis Reveals OsBGs and OsGSLs Influence Sugar Transport through Callose Metabolism under Heat Stress in Rice
Authors: Luan Ruiwei , Liu Jingyang , Tao Longxing , Fu Guanfu , Zhang Caixia
Published: February 2023

Heat or high temperature stress have caused huge damage to many crops and have become the largest threat in terms of the future. Although a huge amount of research has been conducted to explore the mechanisms of heat tolerance and many achievements were accomplished, the mechanism by which how heat stress (HS) influences the yield is still unclear. In this study, RNA-seq analysis indicated that nine 1,3-β-glucanases (BGs) belonging to the carbohydrate metabolic pathway were expressed differently during heat treatment. Therefore, we identified the BGs and glucan-synthase-likes (GSLs) in three rice ecotypes and processed the analyses of gene gain and loss, phylogenetic relationship, duplication, and syntenic relationship. We found the possibility of an environmental adaption based on BGs and GSLs during evolution. Submicrostructure and dry matter distribution analysis confirmed that HS might block the endoplasmic sugar transport pathway by increasing callose synthesis, which may lead to decreased yield and quality in rice production. This study provides a new clue regarding rice yield and quality under HS and provides guidance to rice cultivation and heat tolerance breeding.
Fetuin-A: A Novel Biomarker of Bone Damage in Early Axial Spondyloarthritis. Results of an Interim Analysis of the SPACE Study
Authors: Favero Marta , Ometto Francesca , Belluzzi Elisa , Cozzi Giacomo , Scagnellato Laura , Oliviero Francesca , Ruggieri Pietro , Doria Andrea , Lorenzin Mariagrazia , Ramonda Roberta
Published: February 2023

Our study aimed to evaluate the association between fetuin-A levels and the presence of radiographic sacroiliitis and syndesmophytes in patients with early axial spondyloarthritis (axSpA) and to identify potential predictors of radiographic damage in the sacroiliac joints (SIJs) after 24 months. Patients diagnosed with axSpA in the Italian cohort of the SpondyloArthritis-Caught-Early (SPACE) study were included. Physical examinations, laboratory tests (including fetuin-A), SIJ,+ and spinal X-rays and MRIs at T0 (diagnosis) and at T24 were considered. Radiographic damage in the SIJs was defined according to the modified New York criteria (mNY). Fifty-seven patients were included in this analysis (41.2% male, median (interquartile range), chronic back pain [CBP] duration of 12 (8–18) months). Fetuin-A levels were significantly lower in patients with radiographic sacroiliitis compared to those without at T0 (207.9 (181.7–215.9) vs. 239.9 (217.9–286.9), respectively, p < 0.001) and at T24 (207.6 (182.5–246.5) vs. 261.1 (210.2–286.6) µg/mL, p = 0.03). At T0, fetuin-A levels were significantly higher in non-smokers, in patients with heel enthesitis and in those with a family history of axSpA; fetuin-A levels at T24 were higher in females, in patients with higher ESR or CRP at T0 and in those with radiographic sacroiliitis at T0. Fetuin-A levels at T0 were independently negatively associated with the likelihood of radiographic sacroiliitis (OR = 0.9 per 10-unit increase (95% CI 0.8, 0.999), p = 0.048); but not with the presence of syndesmophytes. After adjustment for confounders, fetuin-A levels at T0 and T24 were also negatively associated with mNY at T0 (β −0.5, p < 0.001) and at T24 (β −0.3, p < 0.001), respectively. Among other variables at T0, fetuin-A levels did not achieve statistical significance in predicting mNY at T24. Fetuin-A levels were negatively associated with radiographic damage of the SIJs, but not of the spine, in early axSpA and after 2 years of follow-up. Our findings suggest that fetuin-A levels may serve as a biomarker to identify patients with a higher risk of developing severe disease and early structural damage.
Echocardiographic Parameters to Predict Malignant Events in Arrhythmic Mitral Valve Prolapse Population
Authors: Vairo Alessandro , Desalvo Paolo , Rinaudo Andrea , Piroli Francesco , Tribuzio Anna , Ballatore Andrea , Marcelli Gianluca , Pistelli Lorenzo , Dusi Veronica , Montali Nicolò , Alunni Gianluca , Barbero Cristina , Salizzoni Stefano , Pocar Marco , Rinaldi Mauro , Gaita Fiorenzo , De Ferrari Gaetano Maria , Giustetto Carla
Published: February 2023

Bileaflet Mitral Valve Prolapse (bMVP) has been linked to major arrhythmic events and sudden cardiac death (SCD). Consistent predictors in this field are still lacking. Echocardiography is the best tool for the analysis of the prolapse and its impact on the ventricular mechanics. The aim of this study was to find new echocardiographic predictors of malignant events within an arrhythmic MVP population. We evaluated 22 patients with arrhythmic bMVP with a transthoracic echocardiogram focused on mitral valve anatomy and ventricular contraction. Six of them had major arrhythmic events that required ICD implantation (ICD-MVP group), while sixteen presented with a high arrhythmic burden without major events (A-MVP group). The best predictors of malignant events were the Anterior Mitral Leaflet (AML) greater length and greater Mechanical Dispersion (MD) of basal and mid-ventricular segments, while other significant predictors were the larger mitral valve annulus (MVA) indexed area, lower MVA anteroposterior diameter/AML length ratio, higher inferolateral basal segment S3 velocity.
Short-Term Outcomes of Surgery and Rehabilitation on Activities of Daily Living after Displaced Femoral Neck Fractures: Structural Equation Modeling
Authors: Yokoyama Kazutaka , Katoh Hiroyuki , Bito Seiji , Fujita Yoshinari , Yamauchi Keita
Published: February 2023

In order to explore the factors affecting patients’ level of activities of daily living (ADL) on discharge after undergoing bipolar hemiarthroplasty or total hip arthroplasty for displaced femoral neck fractures at an acute care hospital, patient data were analyzed with the following statistical tools: multiple regression analysis (MRA), structural equation modeling (SEM), and simultaneous analysis of several groups (SASG). The Barthel Index (BI) on discharge was set as the objective variable, while age, sex, degree of dementia, BI on admission, number of days from admission to surgery, surgical option, and number of rehabilitation units per day were set as explanatory variables. Factors such as age, sex, degree of dementia, BI on admission, and number of rehabilitation units per day were significant in MRA. While not significant in MRA, the number of days from admission to surgery was significant in SEM. According to the SASG, the number of rehabilitation units per day was significant for patients without dementia but not for patients with dementia. Analysis of real-world data suggests that early surgery and rehabilitation affect ADL on discharge to a greater degree than the surgical method. For patients without dementia, longer daily rehabilitation was significantly associated with better ADL on discharge.
Does Post-COVID-19 Erectile Dysfunction Improve over Time?
Authors: Gök Alper , Altan Mehmet , Doğan Ahmet Emin , Eraslan Aşır , Uysal Fahrettin Şamil , Öztürk Ufuk , Saguner Ardan Muammer , İmamoğlu Muhammet Abdurrahim
Published: February 2023

Background: Some studies have shown that there may be an increase in the frequency of erectile dysfunction after COVID-19. However, no long-term study has investigated whether this is permanent or temporary. In this study, we aimed to examine whether there was an increase in the frequency of erectile dysfunction among individuals with a history of COVID-19, and, if there was, whether their condition improved over time. Materials and methods: In this study, a total of 125 healthy male healthcare workers, 95 with and 30 without a history of COVID-19, were evaluated in terms of erectile function. Four study groups were formed. The first three groups consisted of individuals with a history of COVID-19 confirmed by the polymerase chain reaction (PCR) test at different times, who recovered from the disease (time elapsed since COVID-19 positivity: <6 months for Group 1, 6 to 12 months for Group 2, and >12 months for Group 3). The individuals in Group 4 did not have a history of COVID-19 diagnosis. In order to evaluate the erectile function of the participants, they were asked to complete the five-item International Index of Erectile Function questionnaire (IIEF-5). Then, statistical analyses were performed to evaluate whether there was a difference between the groups in terms of the IIEF-5 scores. Results: There was a statistically significant difference between the groups in terms of the IIEF-5 scores (p < 0.001), and this difference was determined to be caused by the significantly higher IIEF-5 scores of Groups 3 and 4 compared to Group 1 (p = 0.004 and p < 0.001, respectively). In addition, the IIEF-5 score of Group 4 was statistically significantly higher than that of Group 2 (p < 0.001). However, the IIEF-5 scores did not statistically significantly differ between Groups 1 and 2, Groups 2 and 3, and Groups 3 and 4 (p > 0.999, p = 0.204, and p = 0.592, respectively). Conclusion: There may be deterioration in erectile function after COVID-19; however, this tends to improve over time, especially from the first year after active infection. Given that vascular, hormonal, and/or psychogenic factors may lead to the development of erectile dysfunction after COVID-19, we consider that in order to easily manage this process, it is important to determine the underlying cause, initiate appropriate treatment, and inform couples that this situation can be temporary.
Diminishing the Gender-Related Disparity in Survival among Chemotherapy Pre-Treated Patients after Radical Cystectomy—A Multicenter Observational Study
Authors: Kaczmarek Krystian , Lemiński Artur , Małkiewicz Bartosz , Gurwin Adam , Lisiński Janusz , Słojewski Marcin
Published: February 2023

There is a well-documented problem of inferior outcome of muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC) in women. However, previous studies were conducted before neoadjuvant chemotherapy (NAC) was widely adopted to multidisciplinary management of MIBC. In our study, we assessed the gender-related difference in survival between patients who received NAC and those who underwent upfront RC, in two academic centers. This non-randomized, clinical follow-up study enrolled 1238 consecutive patients, out of whom 253 received NAC. We analyzed survival outcome of RC according to gender between NAC and non-NAC subgroups. We found that female gender was associated with inferior overall survival (OS), compared to males (HR, 1.234; 95%CI 1.046–1.447; p = 0.013) in the overall cohort and in non-NAC patients with ≥pT2 disease (HR, 1.220 95%CI 1.009–1.477; p = 0.041). However, no gender-specific difference was observed in patients exposed to NAC. The 5-year OS in NAC-exposed women in ≤pT1 and ≥pT2 disease, was 69.333% 95%CI (46.401–92.265) and 36.535% (13.134–59.936) respectively, compared to men 77.727% 95%CI (65.952–89.502) and 39.122% 95%CI (29.162–49.082), respectively. The receipt of NAC not only provides downstaging and prolongs patients’ survival after radical treatment of MIBC but may also help to diminish the gender specific disparity.
Radiation Recall Pneumonitis Anticipates Bilateral Immune-Induced Pneumonitis in Non-Small Cell Lung Cancer
Authors: Torresan Sara , Zussino Gaia , Cortiula Francesco , Follador Alessandro , Fasola Gianpiero , Girometti Rossano , Cereser Lorenzo
Published: February 2023

Radiation recall pneumonitis (RRP) is a rare inflammatory reaction that occurs in previously irradiated fields, and it may be caused by various triggering agents. Immunotherapy has been reported to potentially be one of these triggers. However, precise mechanisms and specific treatments have not been explored yet due to a lack of data in this setting. Here, we report a case of a patient who received radiation therapy and immune checkpoint inhibitor therapy for non-small cell lung cancer. He developed first radiation recall pneumonitis and subsequently immune-checkpoint inhibitor-induced pneumonitis (IIP). After presenting the case, we discuss the currently available literature on RRP and the challenges of differential diagnosis between RRP, IIP, and other forms of pneumonitis. We believe that this case is of particular clinical value since it highlights the importance of including RRP in a differential diagnosis of lung consolidation during immunotherapy. Furthermore, it suggests that RRP might anticipate more extensive ICI-induced pneumonitis.
Elevated Circulating Endocan Levels Are Associated with Increased Levels of Endothelial and Inflammation Factors in Postprandial Lipemia
Authors: Ozer Yaman Serap , Balaban Yucesan Fulya , Orem Cihan , Vanizor Kural Birgul , Orem Asım
Published: February 2023

Background: Postprandial lipemia (PPL) causes endothelial dysfunction by causing endothelial damage to lipoproteins that remain rich in triglycerides. Endocan is a proteoglycan with increased tissue expression, endothelial activation, and neovascularization. The aim of the study was to examine circulating endocan levels in PPL subjects by considering the degree of PPL response according to a high-fat test meal. The other aim was to determine the association between endocan levels and endothelial and inflammatory factors. Method: Fifty-four hyperlipidemic subjects and 28 normolipidemic subjects consumed the high-fat meal. Endocan, sICAM-1, sVCAM-1, and VEGFA as endothelial factors and IL-6 and LFA-1α as inflammatory factors were evaluated. Results: Fasting serum endocan, VEGFA, sICAM-1, sVCAM-1 IL-6, and LFA-1α levels were increased in the PPL group compared to the control group. The PPL group was divided into tertiles based on mean AUC levels. Endocan levels in tertile 3 were at the highest and were increased significantly compared to tertiles 1 and 2. AUC and endocan levels were positively correlated with other endothelial and inflammation factors. ROC analysis showed endocan levels to be one of the highest values. Conclusions: Circulating endocan is seen at significantly higher levels and independently associated with endothelial and inflammatory factors in postprandial lipemia and dyslipidemia.
Artificial Intelligence-Assisted Transcriptomic Analysis to Advance Cancer Immunotherapy
Authors: Gui Yu , He Xiujing , Yu Jing , Jing Jing
Published: February 2023

The emergence of immunotherapy has dramatically changed the cancer treatment paradigm and generated tremendous promise in precision medicine. However, cancer immunotherapy is greatly limited by its low response rates and immune-related adverse events. Transcriptomics technology is a promising tool for deciphering the molecular underpinnings of immunotherapy response and therapeutic toxicity. In particular, applying single-cell RNA-seq (scRNA-seq) has deepened our understanding of tumor heterogeneity and the microenvironment, providing powerful help for developing new immunotherapy strategies. Artificial intelligence (AI) technology in transcriptome analysis meets the need for efficient handling and robust results. Specifically, it further extends the application scope of transcriptomic technologies in cancer research. AI-assisted transcriptomic analysis has performed well in exploring the underlying mechanisms of drug resistance and immunotherapy toxicity and predicting therapeutic response, with profound significance in cancer treatment. In this review, we summarized emerging AI-assisted transcriptomic technologies. We then highlighted new insights into cancer immunotherapy based on AI-assisted transcriptomic analysis, focusing on tumor heterogeneity, the tumor microenvironment, immune-related adverse event pathogenesis, drug resistance, and new target discovery. This review summarizes solid evidence for immunotherapy research, which might help the cancer research community overcome the challenges faced by immunotherapy.
Association between Inflammatory Bowel Disease and Iridocyclitis: A Mendelian Randomization Study
Authors: Meng Yang , Tan Zongbiao , Liu Chuan , Dong Weiguo , Chen Changzheng
Published: February 2023

Background: Iridocyclitis (IC) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Observational studies showed patients with ulcerative colitis (UC) and Crohn’s disease (CD) both have a higher risk of IC. However, due to the inherent limitations of observational studies, the association and its directionality between the two forms of IBD and IC remain undiscerned. Methods: Genetic variants for IBD and IC were selected as instruments from genome-wide association studies (GWAS) and FinnGen database as instrumental variables, respectively. A bidirectional Mendelian randomization (MR) and multivariable MR were performed successively. Three different MR methods were performed to determine the causal association, including inverse-variance weighted (IVW), MR Egger, and weighted median, whereas IVW was used as the main analysis. Different methods for sensitivity analysis were used, including MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, Cochran’s Q test, and leave-one-out analysis. Results: Bidirectional MR suggested both UC and CD were positively associated with IC as a whole, acute and subacute IC, and chronic IC. However, in the MVMR analysis, only the association from CD to IC remained stable. In the reverse analysis, no association was observed from IC to UC or CD. Conclusions: Both UC and CD are associated with an increased risk of IC compared with healthy individuals. However, the association between CD and IC is stronger. In the reverse direction, patients with IC do not suffer a higher risk of UC or CD. We emphasize the importance of ophthalmic examinations for IBD patients, especially for CD patients.
The Effects of Orthoptic Therapy on the Surgical Outcome in Children with Intermittent Exotropia: Randomised Controlled Clinical Trial
Authors: Xu Meiping , Peng Yiyi , Zheng Fuhao , Yu Huanyun , Zhou Jiawei , Zheng Jingwei , Wang Yuwen , Hou Fang , Yu Xinping
Published: February 2023

Background: To assess the clinical effectiveness of orthoptic therapy in the postoperative stabilisation and rehabilitation of binocular function in children with intermittent exotropia (IXT) after surgery. Methods: This was a prospective, parallel, randomised controlled trial. A total of 136 IXT patients (aged from 7 to 17 years) who had been successfully corrected at 1 month after surgery were enrolled in this study, and 117 patients (58 controls) completed the 12-month follow-up visit. The primary outcome was established as the proportion of patients with suboptimal surgical outcomes, which were defined as: (1) exodeviation ≥10 prism diopters (PD) at distance or near using the simultaneous prism and cover test (SPCT), or (2) constant esotropia ≥6 PD at distance or near using SPCT, or (3) loss of 2 or more octaves of stereopsis from baseline. The secondary outcomes were the exodeviation at distance and near using the prism and alternate cover test (PACT), stereopsis, fusional exotropia control and convergence amplitude. Results: The cumulative probability of suboptimal surgical outcome by 12 months was 20.5% (14/68) in the orthoptic therapy group and 42.6% (29/68) in the control group. There was a significant difference between these two groups (χ2 = 7.402, p = 0.007). Improvements in stereopsis, fusional exotropia control and fusional convergence amplitude were found in the orthoptic therapy group. A smaller exodrift was found in the orthoptic therapy group at near fixation (t = 2.26, p = 0.025). Conclusions: Early postoperative orthoptic therapy can effectively improve the surgical outcome as well as stereopsis and fusional amplitude.
Artificial Intelligence Based Analysis of Corneal Confocal Microscopy Images for Diagnosing Peripheral Neuropathy: A Binary Classification Model
Authors: Meng Yanda , Preston Frank George , Ferdousi Maryam , Azmi Shazli , Petropoulos Ioannis Nikolaos , Kaye Stephen , Malik Rayaz Ahmed , Alam Uazman , Zheng Yalin
Published: February 2023

Diabetic peripheral neuropathy (DPN) is the leading cause of neuropathy worldwide resulting in excess morbidity and mortality. We aimed to develop an artificial intelligence deep learning algorithm to classify the presence or absence of peripheral neuropathy (PN) in participants with diabetes or pre-diabetes using corneal confocal microscopy (CCM) images of the sub-basal nerve plexus. A modified ResNet-50 model was trained to perform the binary classification of PN (PN+) versus no PN (PN−) based on the Toronto consensus criteria. A dataset of 279 participants (149 PN−, 130 PN+) was used to train (n = 200), validate (n = 18), and test (n = 61) the algorithm, utilizing one image per participant. The dataset consisted of participants with type 1 diabetes (n = 88), type 2 diabetes (n = 141), and pre-diabetes (n = 50). The algorithm was evaluated using diagnostic performance metrics and attribution-based methods (gradient-weighted class activation mapping (Grad-CAM) and Guided Grad-CAM). In detecting PN+, the AI-based DLA achieved a sensitivity of 0.91 (95%CI: 0.79–1.0), a specificity of 0.93 (95%CI: 0.83–1.0), and an area under the curve (AUC) of 0.95 (95%CI: 0.83–0.99). Our deep learning algorithm demonstrates excellent results for the diagnosis of PN using CCM. A large-scale prospective real-world study is required to validate its diagnostic efficacy prior to implementation in screening and diagnostic programmes.
Clinical Outcomes of XEN45®-Stent Implantation after Failed Trabeculectomy: A Retrospective Single-Center Study
Authors: Weber Constance , Hundertmark Sarah , Petrak Michael , Ludwig Elisabeth , Brinkmann Christian Karl , Holz Frank G. , Mercieca Karl
Published: February 2023

Background: The implantation of a collagen gel micro-stent (XEN45®) as a minimally invasive form of glaucoma surgery (MIGS) after a failed trabeculectomy (TE) may be an effective option with few risks. This study investigated the clinical outcome of XEN45® implantation after a failed TE, with follow-up data of up to 30 months. Materials and Methods: In this paper, we present a retrospective review of patients undergoing XEN45® implantation after a failed TE at the University Eye Hospital Bonn, Germany, from 2012 to 2020. Results: In total, 14 eyes from 14 patients were included. The mean follow-up time was 20.4 months. The mean time duration between the failed TE and XEN45® implantation was 110 months. The mean intraocular pressure (IOP) decreased from 17.93 mmHg to 12.08 mmHg after one year. This value increased again to 17.63 mmHg at 24 months and 16.00 mmHg at 30 months. The number of glaucoma medications decreased from 3.2 to 0.71, 2.0, and 2.71 at 12, 24, and 30 months, respectively. Conclusions: XEN45® stent implantation after a failed TE did not lead to an effective long-term decrease in IOP and glaucoma medications in many patients in our cohort. Nevertheless, there were cases without the development of a failure event and complications, and others in whom further, more invasive surgery was delayed. XEN45® implantation in some failed trabeculectomy cases may, therefore, be a good option, especially in older patients with multiple comorbidities.
Infrared Macrothermoscopy Patterns—A New Category of Dermoscopy
Authors: Ferrari Flavio Leme , Brioschi Marcos Leal , Dalmaso Neto Carlos , Medeiros Carlos Roberto de
Published: February 2023

(1) Background: The authors developed a new non-invasive dermatological infrared macroimaging analysis technique (MacroIR) that evaluates microvascular, inflammatory, and metabolic changes that may be dermoscopy complimentary, by analyzing different skin and mucosal lesions in a combined way—naked eye, polarized light dermatoscopy (PLD), and MacroIR—and comparing results; (2) Methods: ten cases were evaluated using a smartphone coupled with a dermatoscope and a macro lens integrated far-infrared transducer into specific software to capture and organize high-resolution images in different electromagnetic spectra, and then analyzed by a dermatologist; (3) Results: It was possible to identify and compare structures found in two dermoscopic forms. Visual anatomical changes were correlated with MacroIR and aided skin surface dermatological analysis, presenting studied area microvascular, inflammatory, and metabolic data. All MacroIR images correlated with PLD, naked eye examination, and histopathological findings; (4) Conclusion: MacroIR and clinic dermatologist concordance rates were comparable for all dermatological conditions in this study. MacroIR imaging is a promising method that can improve dermatological diseases diagnosis. The observations are preliminary and require further evaluation in larger studies.
Predicted Changes in the Biogeographical Range of Gracilaria vermiculophylla under Present and Future Climate Scenarios
Authors: Mendoza-Segura Clara , Fernández Emilio , Beca-Carretero Pedro
Published: February 2023

Global change effects have favoured the introduction of new species in marine ecosystems in recent years. Gracilaria vermiculophylla, a red seaweed native from the north-eastern Pacific, has successfully colonised large regions in the Northern Hemisphere. In this research, we implemented species distribution models (SDMs) to (i) examine which were the most important environmental factors defining the presence of G. vermiculophylla at a global scale, and (ii) determine the potential current and future distribution of G. vermiculophylla based on two climate scenarios (representative concentration pathways (RCP 2.6 and RCP 8.5)). Our results suggest that temperature and salinity were the most important variables explaining the distribution of the target species. Additionally, the SDMs for present climate settings showed a potential wider distribution than is recorded to date. In addition, a subtle habitat expansion of 2.9° into higher latitudes was reported under the RCP 2.6 scenario by the end of this century. The high-carbon-emission scenario (RCP 8.5) delivered a potential large habitat expansion (6.0°), even reaching arctic latitudes, and a remarkable habitat loss of 11° in its southern distribution range. SMDs also forecasted suitable areas for this species in the Southern Hemisphere, pointing toward a potential global expansion in the coming decades.
How Clinicians Conceptualize “Actionability” in Genomic Screening
Authors: Owens Kellie , Sankar Pamela , Asfaha Dina M.
Published: February 2023

Over the last decade, the concept of actionability has become a primary framework for assessing whether genetic data is useful and appropriate to return to patients. Despite the popularity of this concept, there is little consensus about what should count as “actionable” information. This is particularly true in population genomic screening, where there is considerable disagreement about what counts as good evidence and which clinical actions are appropriate for which patients. The pathway from scientific evidence to clinical action is not straightforward—it is as much social and political as it is scientific. This research explores the social dynamics shaping the integration of “actionable” genomic data into primary care settings. Based on semi-structured interviews with 35 genetics experts and primary care providers, we find that clinicians vary in how they define and operationalize “actionable” information. There are two main sources of disagreement. First, clinicians differ on the levels and types of evidence required for a result to be actionable, such as when we can be confident that genomic data provides accurate information. Second, there are disagreements about the clinical actions that must be available so that patients can benefit from that information. By highlighting the underlying values and assumptions embedded in discussions of actionability for genomic screening, we provide an empirical basis for building more nuanced policies regarding the actionability of genomic data in terms of population screening in primary care settings.
Building Trusted Federated Learning: Key Technologies and Challenges
Authors: Chen Depeng , Jiang Xiao , Zhong Hong , Cui Jie
Published: February 2023

Federated learning (FL) provides convenience for cross-domain machine learning applications and has been widely studied. However, the original FL is still vulnerable to poisoning and inference attacks, which will hinder the landing application of FL. Therefore, it is essential to design a trustworthy federation learning (TFL) to eliminate users’ anxiety. In this paper, we aim to provide a well-researched picture of the security and privacy issues in FL that can bridge the gap to TFL. Firstly, we define the desired goals and critical requirements of TFL, observe the FL model from the perspective of the adversaries and extrapolate the roles and capabilities of potential adversaries backward. Subsequently, we summarize the current mainstream attack and defense means and analyze the characteristics of the different methods. Based on a priori knowledge, we propose directions for realizing the future of TFL that deserve attention.
The Morphology of Case and Possession in Balkar: Evidence that Oblique Cases Contain Accusative
Authors: Davis Colin
Published: February 2023

This paper uses facts about case allomorphy and possessive morphology in Balkar, a Turkic language spoken in southern Russia, to contribute to the examination of the internal structure of case. A number of recent findings in morpho-syntactic research indicate that case markers have a richer internal structure than their surface appearance typically suggests. Specifically, many works in this vein argue based on cross-linguistic facts about phenomena such as suppletion and syncretism that case features are organized into an implicational containment hierarchy. In this hierarchy, accusative case contains the features of the nominative, and the accusative is itself a sub-part of oblique cases. Many arguments for case containment have relied on diagnostics that are less direct than surface-level morpho-syntactic analysis. In this paper, I argue that there is a part of Balkar grammar that shows the containment of accusative case by obliques in a surface-evident way. While such containment is not normally evident in Balkar, I argue that in certain possessed oblique NPs we see an overt expression of the accusative, except when phonological factors interfere. I go on to discuss other related topics about Balkar and the case containment hypothesis more generally.
State-of-the-Art in Sustainable Machining of Different Materials Using Nano Minimum Quality Lubrication (NMQL)
Authors: Kumar Avinash , Sharma Anuj Kumar , Katiyar Jitendra Kumar
Published: February 2023

In the manufacturing industry, during machining, the conventional cutting fluid plays a vital role; however, extravagant use of cutting fluids due to its disposal affects the environment badly. Nowadays, due to these advantages of conventional cutting fluids, alternative methods of conventional cutting fluids or alternative methods are preferred. One of the most preferred methods may be the minimum quantity lubrication technique with conventional or nanoparticle-enriched cutting fluids. The present paper has a compilation of the investigations based on MQL application in different machining processes such as turning, milling, grinding, and drilling. The machining also involves hard-to-machine alloys. The paper discusses cryogenic MQL in brief and opens the domain for work in future. The purpose of this paper is to provide a quick reference for researchers working on the practical use of MQL lubricants with nanopowders dissolved and their application in machining for different materials.
Wire Arc Additive Manufacturing (WAAM) for Aluminum-Lithium Alloys: A Review
Authors: Rodríguez-González Paula , Ruiz-Navas Elisa María , Gordo Elena
Published: February 2023

Out of all the metal additive manufacturing (AM) techniques, the directed energy deposition (DED) technique, and particularly the wire-based one, are of great interest due to their rapid production. In addition, they are recognized as being the fastest technique capable of producing fully functional structural parts, near-net-shape products with complex geometry and almost unlimited size. There are several wire-based systems, such as plasma arc welding and laser melting deposition, depending on the heat source. The main drawback is the lack of commercially available wire; for instance, the absence of high-strength aluminum alloy wires. Therefore, this review covers conventional and innovative processes of wire production and includes a summary of the Al-Cu-Li alloys with the most industrial interest in order to foment and promote the selection of the most suitable wire compositions. The role of each alloying element is key for specific wire design in WAAM; this review describes the role of each element (typically strengthening by age hardening, solid solution and grain size reduction) with special attention to lithium. At the same time, the defects in the WAAM part limit its applicability. For this reason, all the defects related to the WAAM process, together with those related to the chemical composition of the alloy, are mentioned. Finally, future developments are summarized, encompassing the most suitable techniques for Al-Cu-Li alloys, such as PMC (pulse multicontrol) and CMT (cold metal transfer).
Identification Modelling and Fault-Tolerant Predictive Control for Industrial Input Nonlinear Actuator System
Authors: Dong Shijian , Zhang Yuzhu
Published: February 2023

Industrial actuator systems play an important role in mechanical manufacture, chemical production and other industrial processes. There is important theoretical research significance and engineering application value in accurately modeling and accurately controlling for an industrial actuator system with dead-zone input nonlinearity. The structure and order of the system are determined by the mechanism relationship of the system. Based on sampled data, an identification algorithm is proposed to describe the main dynamic characteristics of the system output. The convergence property of the proposed identification algorithm is also analyzed. Process faults may reduce the tracking control accuracy of the industrial actuator system. By using an intermediate observer to estimate the faults, a fault-tolerant synchronous control feedback rate is designed to compensate faults. The input dead-zone block may weaken the feedback control performance of the input signal and reduce the control precision. According to the dead-zone input nonlinearity model parameter, a compensator is introduced to transform the dead-zone function into a linear function passing through the origin of coordinates. The transformed and dynamic linear segment of the system constitute the generalized linear system. The model predictive control (MPC) strategy is designed to achieve robust and precise control by eliminating the effects of measurement noise. The results of numerical simulation and experimental test verify the superiority and merit of the modeling and fault-tolerant control strategy. The research results of this paper can provide a good reference and guidance for other complex systems in theoretical research and engineering applications.
Fault Diagnosis of Rotating Machinery Based on Two-Stage Compressed Sensing
Authors: You Xianglong , Li Jiacheng , Deng Zhongwei , Zhang Kai , Yuan Hang
Published: February 2023

Intelligent on-site fault diagnosis and professional vibration analysis are essential for the safety and stability of rotating machinery operation. This paper represents a fault diagnosis scheme based on two-stage compressed sensing for triaxial vibration data, which realizes fault diagnosis for rotating machinery based on compressed data and data reconstruction for professional vibration analysis. In the 1st stage, the triaxial vibration signals are compressed using a pre-designed hybrid measurement matrix; these compressed data can be used both for time-frequency transform and for vibration data reconstruction. In the 2nd stage, the frequency spectra of the triaxial vibration signals are fused and further compressed using another pre-designed joint measurement matrix, which inhibits the high-frequency noises simultaneously. Finally, the fused spectra are employed as feature vectors in sparse-representation-based classification, where the proposed batch matching pursuit (BMP) algorithm is utilized to calculate the sparse vectors. The two-stage compression scheme and the BMP algorithm minimize the computational cost of on-site fault diagnosis, which is suitable for edge computing platforms. Meanwhile, the compressed vibration data can be reconstructed, which provides evidence for professional vibration analysis. The method proposed in this study is validated by two practical case studies, in which the accuracies are 99.73% and 96.70%, respectively.
Understanding the Parameter Influence on Lesion Growth for a Mechanobiology Model of Atherosclerosis
Authors: Hernández-López Patricia , Martínez Miguel A. , Peña Estefanía , Cilla Myriam
Published: February 2023

In this work, we analyse the influence of the parameters of a mathematical model, previously proposed by the authors, for reproducing atheroma plaque in arteries. The model uses Navier–Stokes equations to calculate the blood flow along the lumen in a transient mode. It also uses Darcy’s law, Kedem–Katchalsky equations, and the three-pore model to simulate plasma and substance flows across the endothelium. The behaviours of all substances in the arterial wall are modelled with convection–diffusion–reaction equations, and finally, plaque growth is calculated. We consider a 2D geometry of a carotid artery, but the model can be extrapolated to other geometries or arteries, such as the coronaries or the aorta. A mono-variant sensitivity analysis of the model parameters was performed, with values of ±25% and ±10%, with respect to the values of the previous model. The results were analysed with respect to the volume in the plaque of foam cells (FC), synthetic smooth muscle cells (SSMC), and collagen fibre. It was observed that the volume in the plaque of the different substances (FC, SSMC, and collagen) has a strong influence on the results, so it could be used to analyse the vulnerability of plaque. The stenosis ratio of the plaque was also analysed, showing a strong influence on the results as well. Parameters that influence all the results considered when ranged ±10% are the rate of LDL degradation and the diffusion coefficients of LDL and monocytes in the arterial wall. Furthermore, it was observed that the change in the volume of foam cells in the plaque has a greater influence on the stenosis ratio than the change of synthetic smooth muscle cells or collagen fibre.