bluuebunny/crossref_metadata_2025 huggingface dataset:
Unincreased mortality of patients with early rheumatoid arthritis compared to the general population in the past two decades: results from a Japanese prospective observational cohort: IORRA
Authors: Sugitani Naohiro , Tanaka Eiichi , Inoue Eisuke , Abe Mai , Sugano Eri , Saka Kumiko , Ochiai Moeko , Higuchi Yoko , Yamaguchi Rei , Sugimoto Naoki , Ikari Katsunori , Nakajima Ayako , Yamanaka Hisashi , Harigai Masayoshi
Published: July 2022

Background:The mortality of patients with rheumatoid arthritis (RA) has been reported to have reduced due to the improved treatment of RA in the last two decades. However, it has not yet been clarified whether the progress of RA treatment improves the prognosis of patients with early RA. We aimed to investigate the mortality rate of patients with early RA over the past two decades.Methods:Patients with RA who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort within two years of disease onset between 2001– 2012 were enrolled and classified into Group A (2001–2006) and B (2007–2012). The standardized mortality ratio (SMR) versus the Japanese general population and five-year survival rate were calculated. A multiple imputation method was employed for the sensitivity analysis of SMR. The five-year survival rates were evaluated using the Kaplan–Meier method.Results:Groups A and B had 1,609 and 1,608 patients, respectively, of which 167 (10.4%) and 178 (11.0%) patients were lost during follow-up, respectively. Overall, 47 and 45 deaths of patients were confirmed in Groups A and B, respectively. The SMR (95% confidence interval) for Groups A and B were 0.81 (0.59–1.08) and 0.78 (0.57–1.04), respectively, with the condition that all untraceable patients were alive for 5 years. Assuming that the mortality rate of patients lost to follow-up was twice as high as that of the general population, the SMR was 0.90 (0.68–1.19) for Group A and 0.92 (0.68–1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for groups A and B, respectively (P=0.83).Conclusions:The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population; the 5-year survival rate has been stable over the past two decades.
KW-2449 and VPA exert therapeutic effects on human neurons and cerebral organoids derived from MECP2-null hESCs
Authors: Xu Ya-Jie , Liu Pei-Pei , Yan Zhong-Ze , Wang Ying-Ying , Li Qian , Teng Zhao-Qian , Liu Chang-Mei
Published: July 2022

Background
Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MECP2), is one of the most prevalent neurodevelopmental disorders in girls. However, the underlying mechanism of MECP2 remains largely unknown and currently there is no effective treatments available for RTT.
Methods
We generated MECP2-KO human embryonic stem cells (hESCs), and differentiated them into neurons and cerebral organoids to investigate MECP2 loss-of-function phenotypes as well as potential therapeutic agents in human neuronal models, and the mechanism was verified after transcriptome sequencing.
Results
We found that MECP2 deletion caused reduced number of hESCs-derived neurons and simplified dendritic morphology. Moreover, MECP2-KO cortical organoids exhibited fewer neural progenitor cells and neurons at day 60. Transcriptome analysis of organoids identified an PI3K-AKT pathway downregulated following MECP2 deletion. Treatment with either KW-2449 or VPA, small molecules for the activation of PI3K-AKT signaling pathway, alleviated neuronal deficits and transcriptome impairment of MECP2-KO human neuronal models.
Conclusions
Together, these data suggest that KW-2449 and VPA might be promising drugs for RTT treatment.
Robust and Efficient Parameter Estimation for Discretely Observed Stochastic Processes
Authors: Hore Rohan , Ghosh Abhik
Published: July 2022

In various practical situations, we encounter data from stochastic processes which can be efficiently modelled by an appropriate parametric model for subsequent statistical analyses. Unfortunately, the most common estimation and inference methods based on the maximum likelihood (ML) principle are susceptible to minor deviations from assumed model or data contamination due to their well known lack of robustness. Since the alternative non-parametric procedures often lose significant efficiency, in this paper, we develop a robust parameter estimation procedure for discretely observed data from a parametric stochastic process model which exploits the nice properties of the popular density power divergence measure in the framework of minimum distance inference. In particular, here we define the minimum density power divergence estimators (MDPDE) for the independent increment and the Markov processes. We establish the asymptotic consistency and distributional results for the proposed MDPDEs in these dependent stochastic process setups and illustrate their benefits over the usual ML estimator for common examples like Poisson process, drifted Brownian motion and auto-regressive models.
Dysregulation of GYS1 and GYS2 correlated with poor prognosis and immune infiltrates in patients with hepatocellular carcinoma
Authors: Li Gong , Zhang Peng , Wei Bajin , Jiang Bin , Li Xuefeng , Li Huili , Xing Chunyang , Wan Yunyan , Ma Wei , Zhou Wuhua
Published: July 2022

Glycogen synthase encoding genes GYS1 and GYS2 are aberrantly expressed and play a vital role in progression of multiple malignancies. However, the clinical significance and biological function of GYS1 and GYS2 in hepatocellular carcinoma remain little known. The present study aims to evaluate the relationship of GYS1 and GYS2 expression with clinicopathologic characteristics, prognostic pattern and immune infiltration in hepatocellular carcinoma (HCC) using the data from The Cancer Genome Atlas (TCGA). The expression of GYS1 and GYS2 in HCC and normal liver tissues were primarily compared using TCGA data and further validated by another independent cohort from the gene expression omnibus (GEO) database and human protein atlas (HPA). Wilcoxon rank sum test, Chi-square test and logistical regression analysis were used to examine the relationship of GYS1 and GYS2 expression with clinicopathological features. Gene ontology (GO) term analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were conducted to explain the enrichment pathways and underlying molecular mechanism for GYS1 and GYS2. Kaplan-meier analysis, Cox regression and nomograms were used to evaluate the predictive value of GYS1 and GYS2 expression on clinical outcomes in HCC. Receive operating characteristic (ROC) curve was performed to illustrate the correlation of GYS1 and GYS2 expression with the risk of HCC. In addition, the relationship of GYS1 and GYS2 expression with immune infiltrate cells and immune checkpoint related genes were analyzed. Higher GYS1 expression and lower GYS2 expression were examined in HCC than in normal liver tissue and prominently associated with AFP level, tumor stage, histologic grade, pathologic stage and unfavorable overall survival (OS). ROC analysis showed that GYS1 and GYS2 may serve as reasonable diagnostic biomarkers for HCC patients. Moreover, GYS1 expression and GYS2 expression were significantly correlated with abundance of immune infiltrate cells and level of immune checkpoint related genes. Function annotation disclosed that both GYS1 and GYS2 were probably involved in synapse membrane, potassium ion transport, passive transmembrane transporter activity, channel activity, synaptic membrane, transport complex, neuroactive ligand-receptor interaction, allograft rejection, E2F targets, epithelial mesenchymal transition, G2M checkpoint and KRAS signaling pathway. The current study demonstrated that GYS1 upregulation and GYS2 downregulation might reshape tumor immune microenvironment and contribute progression of HCC. Both GYS1 and GYS2 were identified as promising biomarkers associated with diagnosis, prognosis and immune infiltration in HCC.
Closed-loop chemical recycling of cross-linked polymeric materials based on reversible amidation chemistry
Authors: Qin Bo , Liu Siyuan , Huang Zehuan , Zeng Lingda , Xu Jiang-Fei , Zhang Xi
Published: July 2022

Closed-loop chemical recycling provides a solution to the end-of-use problem of synthetic polymers. However, it remains a major challenge to design dynamic bonds, capable of effective bonding and reversible cleaving, for preparing chemically recyclable cross-linked polymers. Herein, we report a new dynamic maleic acid tertiary amide bond based upon reversible amidation reaction between maleic anhydrides and secondary amines. This dynamic bond allows for the construction of polymer networks with tailorable and robust mechanical properties, covering strong elastomers with a tensile strength of 22.3 MPa and rigid plastics with a yield strength of 38.3 MPa. Impressively, these robust polymeric materials can be completely depolymerized in an acidic aqueous solution at ambient temperature, leading to efficient monomer recovery with > 94% separation yields. This work unveils a general approach to design polymer networks with tunable mechanical performance and closed-loop recyclability, which will open a new avenue for sustainable polymeric materials.
The correlation between fat-soluble vitamin levels and inflammatory factors in pediatric community-acquired pneumonia : a retrospective study.
Authors: Wang Qing-tai , Wei Jian-wei , Jiang Hua , Chen Gang-xin
Published: July 2022

Objective: To analyze the correlation between vitamin A, D, E levels and tumor necrosis factor (TNF-a), interleukin-1 (IL-1), interleukin-10 (IL-10), neutrophil, C-reactive protein (CRP) levels in pediatric community-acquired pneumonia (CAP). Methods: 110 children with CAP and 100 normal children were collected.The concentrations of fat-soluble vitamin A, D, E, the proportion of leukocytes and subtypes, the concentration of CRP, and the concentration of cytokines TNF-a, IL-1, and IL-10 were tested. Differences between vitamin levels and inflammatory factor levels were compared between the two groups.The correlation between vitamin levels and inflammatory factor levels was analyzed in children with CAP. Results: The hemoglobin, leukocyte concentration, neutrophils, monocytes and CRP concentration in the CAP group showed significant differences (P <0.05).The levels of vitamin A, D and E in the CAP group were lower than those in the control group, and the levels of TNF-a and IL-1 were higher than those in the control group, and the difference was statistically significant (P<0.05). IL-10 levels have no significant between 2 groups (P>0.05).The Pearson analysis showed that the vitamin A, D, and E levels were all correlated with the TNF-a, IL-10, and CRP levels (P <0.05). Conclusion: The vitamin A, D, E levels of CAP children were lower than normal children. The content of fat-soluble vitamins are somewhat correlated with the secretion of TNF-a and IL-10 .
Road Anomaly Segmentation Based on Pixel-wise Logit Variance with Iterative Background Highlighting
Authors: Lee Dongkun , Kim Han-Gyu , Choi Ho-Jin
Published: July 2022

Anomaly segmentation on the urban landscape scene is an important task in autonomous driving. This process exploits a pre-trained semantic segmentation network to estimate anomalous regions. The anomaly segmentation approaches implemented with extra requirements such as out-of-domain data, extra network, or network retraining might increase computational cost or degradation of segmentation performance. In this research, to exploit information from the segmentation network for more robust anomaly segmentation, we propose the use of pixel-wise logit variance, which tends to be small for anomalies as network outputs even logits without confidence. Additionally, to detect anomalous objects on the background robustly, iterative background highlighting is also proposed, which is implemented by feeding the logits back into the linear classifier of the network. We achieved state-of-the-art performance among anomaly segmentation approaches without extra requirements, reaching relative average precision improvements of 21.7% on Fishyscapes Lost&Found and 17.4% on Fishyscapes Static compared to the state-of-the-art method.
WITHDRAWN: Learning to Optimize Decision Boundary for One-Shot One-Class Image Recognition
Authors: Chen Linkai , Zhu Hongjin , You Congzhe , Fan Honghui , Ruan Yaduan
Published: July 2022

In this paper, we study One-Shot One-Class classification (OSOC), where the aim is to identify the objects of a specific class amongst all objects by using only one single sample of that class as training data. The key challenge of this task is how to learn a robust decision boundary to distinguish a class in such an extreme case. Towards this goal, we propose a novel meta-learning strategy to meta learn a mapping function from the exemplar image of a target class to the categorical classifier as well as a reference score for this class. The classifier is applied to a testing sample to predict the classification score, which will be compared against the reference score to decide whether this sample belongs to the target class or not. To realize this idea, in the meta training phase, we propose a ranking loss that employs the reference score as the threshold to distinguish samples both from the target class and other non-target classes. On top of this basic loss function, we develop another two terms: a fidelity term to ensure the learned classifier has high fidelity to the exemplar and a learnable slack term to adaptively adjust the reference score on the fly. These two terms compete against each other and consequently seek a balance to optimize the decision boundary. Comprehensive experimental results on five OSOC datasets demonstrate the proposed method can obviously outperform state-of-the-art
Clinically unsuspected orthopedic implants during S. aureus bacteremia do not require additional diagnostic work-up
Authors: Kouijzer Ilse , Speijker Lydia , Aarntzen Erik , Rijnen Wim , Somford Matthijs , Maat Ianthe , Meer Maurits van , Oever Jaap ten , Gisolf Jet
Published: July 2022

Purpose
To assess the likelihood of occult infection in patients with clinically unsuspected orthopedic implants during Staphylococcus aureus bacteremia (SAB).
Methods
In a retrospective study in two Dutch hospitals, we included all patients with SAB between 2013 and 2020 with one or more orthopedic implants in whom [18F]FDG-PET/CT was performed. The primary outcome was the percentage of patients who had an infected orthopedic implant by S. aureus. Also, we compared the clinical parameters of infected and uninfected orthopedic implants.
Results
Fifty-five of 191 (29%) orthopedic implants in 118 SAB patients included had clinical signs of infection. Of all 136 unsuspected implants, 5 (3%, all arthroplasties), showed increased [18F]FDG uptake around the prosthesis on [18F]FDG-PET/CT. The clinical course of these patients without clinically overt infection or relapse of bacteremia during follow-up of a median of 48 months (range 0–48), however, argued against prosthetic joint infection.
Conclusion
Although orthopedic implants are evidently a risk factor for metastatic infection during SAB, the absence of clinical symptoms obviate the need of additional investigations or prolonged antibiotic treatment.
Place, position and pedagogy: Using collaborative autoethnography to explore the teaching of qualitative research methods in health and medicine
Authors: Ibrahim Kinda , Weller Susie , Elvidge Elissa , Tavener Meredith
Published: July 2022

This article explores experiences of teaching qualitative research (QR) methods in health and medicine, highlighting the challenges faced, and offering suggestions for overcoming them. Using collective online interviews, collaborative autoethnography (CAE) was employed to generate data comprising educator’s reflective accounts of teaching QR in medical schools across two continents. Three main themes were identified through collaborative thematic analysis: making meaningful contributions from a marginalized position; finding our pedagogical feet; and recognizing the translational applicability and value of qualitative research. We reflected on the marginalized positioning of QR methods in medical and health sciences teaching and the under estimation of the value and contribution of QR to such disciplines. Analysis revealed a lack of formal training for educators and curriculum space for QR methods. Our teaching pedagogies, developed through our own research experiences, self-reflection and student feedback, were primarily student-centred employing a range of novel approaches aimed at "retraining” students’ minds from a quantitative-dominant perspective to introduce greater curiosity and an appreciation of the significance of QR to health and medical sciences. Future curriculum development should aim to break down the perception of competing/ opposing qualitative and quantitative methodologies and instead emphasise the place and value of different approaches, methods and data to health and medicine. CAE allowed us to reflect and identify some key recommendations that could help educators plan their QR methods teaching in these disciplines.
Comparison of 3D Quantitative Osteoarthritis Imaging Biomarkers from Paired CT and MR Images: data from the IMI-APPROACH study
Authors: Brett Alan , Bowes Michael A , Conaghan Philip G
Published: July 2022

Introduction: MRI bone surface area and femoral bone shape (B-score) measures have been employed as quantitative endpoints in DMOAD clinical trials. Computerized Tomography (CT) imaging is more commonly used for 3D visualization of bony anatomy due to its high bone-soft tissue contrast. We aimed to compare CT and MRI assessments of 3D imaging biomarkers. Methods: We used baseline and 24-month image data from the IMI-APPROACH 2-year prospective cohort study. Femur and tibia were automatically segmented using active appearance models to measure 3D bone shape, area and 3D joint space width (3DJSW). Linear regression was used to test for correlation between measures. Limits of agreement and bias were tested using Bland-Altman analysis. Results: CT-MR pairs of the same knee were available from 434 participants (78% female). B-scores from CT and MR were strongly correlated (R2 = 0.938) with minimal bias of 0.1. Area measures were also correlated but showed a consistent bias (MR smaller). 3DJSW showed different bias (MR larger) in lateral and medial sides. Discussion: The strong correlation and small B-score bias suggests that B-score may be measured reliably using either modality. It is likely that the bone surface identified using MR and CT will be at slightly different positions within the bone/cartilage boundary. The negative bone area bias suggests the MR bone boundary is inside the CT boundary producing smaller areas for MR, consistent with the positive 3DJSW bias. The lateral-medial 3DJSW difference is possibly due to a difference in knee pose during acquisition (fully extended for CT, flexed for MR).Trial registration number: NCT03883568
Potential neuroprotective capacity of L-glutamic acid attached to silica nanoparticles on behavioral disturbances, neural oxidative stress,and neural damage induced by hydrogen peroxide in rats
Authors: Hamdi Essia , Muniz-Gonzalez Ana-Belén , Hidouri Slah , Bermejo Alberto Marcos , Sakly Mohsen , Venero César , Amara Salem
Published: July 2022

Exposure to certain environmental factors and xenobiotic agents can lead to an excess of reactive oxygen species and free radical formation that can damage neuronal cells and affect cognitive function. Silica nanoparticles, as probes for genes or proteins, are already used in nanomedicine as a nanocarrier for several drugs. In the present study, SiO2 NPs were functionalized with glutamate to fight the oxidative-induced stress following chronic exposure to hydrogen peroxide (H2O2). This study aims to investigate whether Glutamate-functionalized Silica Nanoparticles can prevent the neurobehavioral and functional modifications displayed by adult male rats exposed to hydrogen peroxide (H2O2). We observed that subchronic exposure (21 days)to H2O2 induced an anxious state and a decrease in locomotor activity in the animals compared to controls. It the Morris water maze task, rats exposed to H2O2 showed impaired spatial learning and memory abilities. In addition, we observed that compared to controls, H2O2 exposed animals showed an imbalance in the redox status and disturbances of the enzyme’s activities-acetylcholinesterase (AChE) and Monoamine Oxidase (MAO) that were prevented by concomitant SiO2 NPs administration. Furthermore, H2O2 treatment enhanced the occurrence of necrotic and degenerative cell changes in several brain areas (hippocampus, subiculum, caudate-putamen and frontal cortex), that were ameliorated by SiO2 NPs treatment. In summary, the supplementation of L-glutamic acid-functionalized silica Nanoparticles corrected enzymatic activities, reduced behavioral disturbances and diminished histological alterations induced by H2O2. Our results suggest that SiO2 NPs are useful to prevent or ameliorate behavioral impairment, as well as antioxidant enzymatic disturbances and neural damage induced by oxidative stress in the hippocampus and frontal cortex.
Spatial-Temporal Meta-path Guided Explainable Crime Prediction
Authors: Sun Yuting , Chen Tong , Yin Hongzhi
Published: July 2022

Exposure to crime and violence can harm individuals’ quality of life and the economic growth of communities. In light of the rapid development in machine learning, there is a rise in the need to explore automated solutions to prevent crimes. With the increasing availability of both fine-grained urban and public service data, there is a recent surge in fusing such cross-domain information to facilitate crime prediction. By capturing the information about social structure, environment, and crime trends, existing machine learning predictive models have explored the dynamic crime patterns from different views. However, these approaches mostly convert such multi-source knowledge into implicit and latent representations(e.g., learned embeddings of districts), making it still a challenge to investigate the impacts of explicit factors on the occurrences of crimes behind the scenes. In this paper, we present a Spatial-Temporal Meta-path guided Explainable Crime prediction (STMEC) framework to capture dynamic patterns of criminal behaviors and explicitly characterize how the environmental and social factors mutually interact to produce forecasts. Extensive experiments show the superiority of STMEC compared with other SOTA spatiotemporal models, especially in predicting felonies (e.g., robberies and assaults with dangerous weapons).
Peroxisome Proliferator Activated Receptors Gamma Serum levels and Gene Polymorphism in Frontal Fibrosing Alopecia: A Case Control Study
Authors: Farag Assem Mohamed , Adawy Dina EL , Abdelrahman Amira Mohamed Noureldin , Ibrahim Shady Mahmoud Attia , Salem Rehab Mohammed
Published: July 2022

Background : Frontal fibrosing alopecia (FFA) is a scarring alopecia with a complex pathogenesis that is not completely clear yet. Objective : The aims of the study were to evaluate serum PPAR gamma levels and gene polymorphism in a sample of Egyptian FFA patients.Methods : The case-control study included 93 FFA female patients, and 157 matching apparently healthy control subjects. Patients were subjected to clinical and trichoscopic examinations to diagnose FFA according to the updated diagnostic criteria. FFA severity was evaluated using FFA severity index (FFASI). Serum PPARγ levels and gene polymorphisms were assessed in all participants using ELISA and PCR techniques respectively.Results : Serum PPARγ levels in patients’ group were significantly lower than that of control subjects’ group. PPARG (Pro12Ala) gene polymorphism was significantly predominant in FFA patients when compared to the control subjects. Patients carrying polymorphic genotypes showed significantly reduced serum PPARγ levels when compared to patients carrying the wild genotype. Limitations : Compliance of patients didn’t allow to evaluate PPARγ agonist therapeutic efficacy and safety on FFA.Conclusion : PPARγ may play an important role in FFA development. It might have a potential utility as biomarker in FFA.
M2 macrophage-derived exosomes inhibit ferroptosis via regulating circ_TNFRSF21/ miR-451a/SLC7A11 axis in cutaneous squamous cell carcinoma
Authors: Ma Jun , Huang Lei , Gao Yan-Bin , Li Min-Xiong , Chen Liang-Long , Yang Lei
Published: July 2022

Background: Cutaneous squamous cell carcinoma (cSCC) is a malignant proliferation of cutaneous epithelium. Ferroptosis is a new type of cell death involved in cancer progression. M2 macrophage derived exosomes promote cancer proliferation and progression. We intended to investigate the role of M2 macrophages derived exosomes on ferroptosis in cSCC and explore the underlying mechanism. Methods: cSCC samples and adjacent normal tissues were obtained from cSCC patients. Exosomes were isolated from M2 macrophages differentiated from human mononuclear macrophage (THP-1) cells by flow cytometry. Cell viability, iron level, Malondialdehyde (MDA), Lipid ROS, mitochondrial superoxide, mitochondrial membrane potential (MMP) were detected for the validation of ferroptosis. RNAs and proteins were measured using RT-qPCR and western blot. Binding relationships between miR-451a and circ_TNFRSF21 or SLC7A11 were revealed by dual luciferase assay.Results: M2 macrophages were increased in cSCC tissues. M2 macrophages inhibited erastin-induced ferroptosis, which was reversed by exosome inhibitor GW4869. SLC7A11 was up-regulated in cSCC tissues. Erastin treatment reduced cell viability, increased the level of iron and Fe2+, upregulated MDA, lipid-ROS, mitochondrial superoxide, and declined MMP, which were reversed by M2 exosomes. Interestingly, circ_TNFRSF21 knockdown antagonized these effects of M2 exosomes. Circ_TNFRSF21 targeted miR-451a to regulate SLC7A11. Erastin-induced ferroptosis was promoted by miR-451a mimics, which was reversed after SLC7A11 overexpression. M2 exosomes inhibited erastin-induced ferroptosis in cSCC cells, which was antagonized by SLC7A11 downregulation or miR-451a upregulation. Conclusion: M2 macrophage exosomes inhibited ferroptosis in cSCC through circ_TNFRSF21/miR-451a/SLC7A11 axis. It is contributed to cSCC progression and may providing a novel target for therapy.
Defining the timeline of periostin upregulation in cardiac fibrosis following acute myocardial infarction in mice
Authors: Gil Hadas , Goldshtein Matan , Etzion Sharon , Elyagon Sigal , Hadad Uzi , Etzion Yoram , Cohen Smadar
Published: July 2022

After myocardial infarction (MI), the heart's reparative response to the ischemic insult and the related loss of cardiomyocytes involves cardiac fibrosis, in which the damaged tissue is replaced with a fibrous scar. Although the scar is essential to prevent ventricular wall rupture in the infarction zone, it expands over time to remote, non-infarct areas, significantly increasing the extent of fibrosis and markedly altering cardiac structure. Cardiac function in this scenario deteriorates, thereby increasing the probability of heart failure and the risk of death. Recent works have suggested that the matricellular protein periostin, known to be involved in fibrosis, is a candidate therapeutic target for the regulation of MI-induced fibrosis and remodeling. Different strategies for the genetic manipulation of periostin have been proposed previously, yet those works did not properly address the time dependency between periostin activity and cardiac fibrosis. Our study aimed to fill that gap in knowledge and fully elucidate the explicit timing of cellular periostin upregulation in the infarcted heart to enable the safer and more effective post-MI targeting of periostin-producing cells. Surgical MI was performed in C57BL/6J and BALB/c mice by ligation of the left anterior descending coronary artery. Flow cytometry analyses of cells derived from the infarcted hearts and quantitative real-time PCR of the total cellular RNA revealed that periostin expression increased during days 2–7 and peaked on day 7 post-infarct, regardless of mouse strain. The established timeline for cellular periostin expression in the post-MI heart is a significant milestone toward the development of optimal periostin-targeted gene therapy.
Treatment outcomes in primary pulmonary angiosarcoma: an analysis based on the SEER database
Authors: Li Zhishu , Zeng Jia , Zheng Dong , Dong Lixia
Published: July 2022

Background: To determine the risk of death and factors associated with survival in patients with primary pulmonary angiosarcoma(PPA).Methods: All patients diagnosed with small cell lung cancer (SCLC) or PPA between 1975 and 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. A further analysis of the PPA patient cohort was performed to assess the effect of surgery, chemotherapy, and radiotherapy on overall survival (OS). A multivariable analysis using the Cox proportional methods and a survival analysis using the Kaplan-Meier method were adopted.Results: A total of 127,126 patients with SCLC and 117 patients with PPA were identified. The majority of PPA patients were older than 60 years (64.1%), were more male (59.0%), and were predominantly white race (77.8%). The median survival time of PPA was 3.0 months (1.88-4.12 months), which was significantly lower than that of SCLC at 7.0 months (6.94-7.06 months, p < 0.01). The median survival with PPA surgery was 4.0 months (2.37-5.63 months), which was higher than that without surgery but not statistically different (4.0 months vs 3.0 months, aHR,0.80; 95% CI: 0.43-1.47; p = 0.46). Median survival with radiotherapy was higher but not statistically different (6.0 months vs 2.0 months, aHR, 0.79; 95% CI: 0.30-2.09; p = 0.63). Median survival with chemotherapy was significantly higher than in those without chemotherapy (9.0 months vs 1.0 month, aHR, 0.43; 95% CI: 0.23-0.80; p < 0.01).Conclusion: PPA is associated with poor outcomes, it has the same predilection site as SCLC, and chemotherapy significantly improves PPA survival outcomes.
Structural and Biochemical Insight into a Modular β-1,4-Galactan Synthase in Plants
Authors: Prabhakar Pradeep , Pereira Jose , Taujale Rahil ,   Wanchen Shao5, Bharadwaj Vivek , Chapla Digantkumar , Yang Jeong-Yeh , Bomble Yannick , Moremen Kelley , Kannan Natarajan , Hammel Michal , Adams Paul , Scheller Henrik , Urbanowicz Breeanna
Published: July 2022

Rhamnogalacturonan I (RGI) is a structurally complex pectic polysaccharide with a backbone of alternating rhamnose and galacturonic acid residues substituted with arabinan and galactan side chains. Galactan synthase 1 (GalS1), transfers galactose and arabinose to either extend or cap the β-1,4 galactan side chains of RGI, respectively. Here we report the structure of GalS1 from Populus trichocarpa, showing a modular protein consisting of an N-terminal domain that represents the founding member of a new family of carbohydrate-binding module, CBMXX (number denoted as ‘XX” assigned upon publication), and a C-terminal glycosyltransferase family 92 (GT92) catalytic domain that adopts a GT-A fold. GalS1 exists as a dimer in vitro, with stem domains interacting across the chains in a 'handshake' orientation that is essential for maintaining stability and activity. In addition to understanding the enzymatic mechanism of GalS1, we gained insight into the donor and acceptor substrate binding sites using deep evolutionary analysis, molecular simulations, and biochemical studies. Combining all the results, a mechanism for GalS1 catalysis and a new model for pectic galactan side chain addition are proposed.
Modelling forces in milling screw rotors
Authors: Wang Xi , Ahmadi Keivan
Published: July 2022

The deflections of screw rotors under machining forces cause mismatch between the male and female rotors and, consequently, accelerated wear and suboptimal efficiency in their performance. Optimizing the machining process to minimize the generated forces and accounting for the resulting mismatch in the design of the rotor profile requires accurately computing the machining forces in computer simulations. Virtual machining systems combine graphics-based computation of the Cutter-Workpiece Engagement (CWE) with the physics-based models of machining mechanics to simulate the forces during complex machining processes. However, because of the high computational load of graphical simulations, virtual machining is not suitable for the repetitive force simulations that are required for optimizing the design and manufacturing of rotors. In this work, we present a new method that simulates screw milling forces based on the process kinematics instead of graphical simulations. The semi-analytical nature of the presented method allows for computing the forces with arbitrary resolution within a reasonable time. The accuracy and efficiency of the presented method is verified by comparing the simulated forces against a dexel-based virtual machining system.
Changes in Retinal Vascular Bifurcation in Eyes with Myopia
Authors: Sun Caixia , Chen Tingli , Cong Jing , Wu Xinyuan , Wang Jing , Yuan Yuanzhi
Published: July 2022

Objective: To evaluate the effect of myopia on retinal vascular bifurcation. Methods: A cross-sectional study that retrospectively analyzed the fundus photographs and clinical data of 493 people who participated in routine physical examinations in Huadong Sanatorium. One eye of each subject was included in the analysis. Retinal vascular bifurcation measurements were extracted by using a validated computer program. One-way ANOVA and analysis of covariance were performed to compare the measurements across high myopia, low to moderate myopia, and non-myopia groups. Results: The mean age was 41.83 ± 10.43 years and 63.49% were women. The mean spherical equivalent refraction (SER) was -4.59 ± 3.07 D. Ninety-nine (20.08%) eyes met the definition of high myopia (SER ≤ -6.0 D), along with 234 (47.46%) low to moderate myopia (-6.0 D< SER <-0.5 D), and 160 (32.45%) non-myopia (SER ≥ -0.5 D). The differences in the arteriolar branching angle, venular branching coefficient, venular asymmetry ratio, venular angular asymmetry, and venular junctional exponent among the three groups remained significant (p<0.05) after multivariate adjustment. Pairwise comparisons showed arteriolar branching angle and venular angular asymmetry in high myopia were significantly lower than low to moderate myopia (p<0.001, p=0.014 respectively) and non-myopia (p=0.007, p=0.048 respectively). Venular asymmetry ratio and venular branching coefficient in high myopia were significantly higher than low to moderate myopia (p=0.029, p=0.001 respectively) and non-myopia (p=0.041, p=0.043 respectively). There was a significant difference in venular junctional exponent between high myopia and low to moderate myopia (p=0.031). Conclusion: The vascular bifurcation differs in dependence of the myopic refractive error and a significant increase in the difference can be observed in high myopic eyes.
Patient reported outcomes and joint tenderness at three months-follow up better predict long term pain than baseline characteristics – an early rheumatoid arthritis cohort study
Authors: Eberhard Anna , Bergman Stefan , Mandl Thomas , Olofsson Tor , Sharma Ankita , Turesson Carl
Published: July 2022

Objective: To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA.Methods: A cohort of 275 patients with early RA, recruited in 2012-2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain >40 based on the patient acceptable symptom state (PASS), and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain with or without low inflammation, respectively, were evaluated using logistic regression analysis. Results: Mean pain improved significantly from inclusion to 3 months, but was thereafter essentially unchanged. After 2 years, 32% had unacceptable pain. Out of these patients 81% had low inflammation. More and stronger associations were found for 3-month predictors of unacceptable pain with or without low inflammation at 1 and 2 years, compared with baseline predictors. Three-month predictors of these pain states at 1 and 2 years were higher pain, higher patient global assessment, higher score for the health assessment questionnaire, and having at least 2 more tender joints than swollen joints. No significant associations were found for objective inflammatory measures. Conclusion: A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. This emphasizes the non-inflammatory pain spectrum in early RA. Three months after diagnosis is a good time-point for assessing the risk of long-term pain. Worse patient reported outcomes at 3-months follow-up were associated with increased risk of long-lasting pain, whereas no such associations were found for objective inflammatory measures, further strengthening the uncoupling between pain and inflammation in RA. Having at least 2 more tender joints than swollen joints was associated with future unacceptable pain, supporting this measure as a tool for predicting long-term pain.
Will Transition Services in Psychiatry be an added value? Perspective of Child & Adolescent and Adult psychiatrists in Portugal (A qualitative study)
Authors: Serra Helena Maria Rocha , Xavier Fernando Miguel Teixeira , Salgado José António Costa
Published: July 2022

Background: The transition from paediatric health to adult services is not a simple process, it has several vicissitudes that often compromise its success, breaking the continuity of care. Although common in many medical specialties, this issue is particularly important in mental health, and the literature tell us that there is not enough research on it. This study aims to characterize the perceptions about this subject of Portuguese physicians who most directly intervene in the process (C&A and adult psychiatrists), the associated difficulties and the possibilities of improvement to be introduced into the system. Methods: A qualitative methodology was used, through semi-structured interviews, allowing for the approach of topics not anticipated by the interviewer. A convenience sample was evaluated, consisting of psychiatrists from public health sector, in the Lisbon region; the number of physicians to be interviewed was not established at the outset, which was determined by the "Saturation", a point from which no opinions different from those that have already emerged.Results: The data collected shows that two thirds of the interviewees consider that it would be useful to have transition services, while the others think that these services would be useless, not bringing improvement in the quality of care. All agree that it would be advantageous to have transition strategies that would improve communication between paediatric and adult services. Informal transfer was the one that produced the best results, given the lack of transition protocols.Conclusions: Many young people move to an adult service informally, depending on the success of the commitment of doctors, family, and patients. Another way often used is the clinical discharge for GP’s, who decides on referral to Psychiatry. Formal and standardized service transitions were not found. The importance of a transition without rupture in the continuity of care is recognized by all participants. Some of them acknowledged that this was an issue on which they had not previously reflected. This shows that the reality in Portugal is similar to other countries, with not enough awareness of the importance of this process in the patient's prognosis.
Net-zero emissions aviation
Authors: Bergero Candelaria , Gosnell Greer , Gielen Dolf , Kang Seungwoo , Bazilian Morgan , Davis Steven
Published: July 2022

International climate goals imply reaching net-zero global carbon dioxide (CO2) emissions by roughly mid-century. Among the most difficult emissions to avoid will be those from modern aviation given the industry’s need for energy-dense liquid fuels and the lack of commercially competitive substitutes. Here, we systematically assess pathways to net-zero emissions aviation, exploring the potential contribution of different approaches as well as their social, technical, and economic limits. We find that ambitious reductions in demand for air transport and improvements in the energy efficiency of aircraft might avoid up to 62% and 26%, respectively, of projected business-as-usual aviation emissions in 2050. However, further reductions will depend on replacing fossil jet fuel with very large quantities of net-zero emissions biofuels or synthetic fuels (2.5-21 EJ)—which are currently much more expensive. Our results may inform investments and priorities for innovation by highlighting plausible pathways to net-zero emissions aviation, including the relative potential and trade-offs of changes in behavior, technology, and energy sources.
Exploring Teaching Reform in Medical English Courses with a Questionnaire Survey under the Background of "New Medicine"
Authors: Wang Jiao , Pei Jiao , Chen Xiangdong , Luo Ting , Zhou Shaoyan , Ai Lu , Fan Li , Chen Huabo , Gan Yunbo
Published: July 2022

Background: In 2017, the School of Basic Medicine at Hubei University of Arts and Science offered a course in English for Medical Purposes (EMP) for the first time. Under the background of new medical science, the EMP curriculum and teaching at medical schools should focus on cultivating composite interdisciplinary medical talent in the new era. According to the feedback of teachers and students, the need for EMP teaching reform is urgent.Methods: Based on our design and investigation of electronic questionnaires, the curriculum suggestions and evaluations of students in different majors and stages were continuously counted to put forward reform measures and explore segmented teaching reform. Pearson chi-square analysis and a two-sample T-test were used to determine whether student performance has shown significant improvement before and after the extant and proposed reforms. Meanwhile, multiple logistic regression analysis was performed to reveal the impact of teaching factors on the teaching effect of the outcome variables.Results: The pre-reform curriculum problems were mainly the closeness of teaching content and the cultivation of ability objectives, the fit between teachers' professional knowledge and their teaching content, and the lack of scientificity in the assessment methods. Therefore, the teaching content and form adjustment implemented from 2016 to 2018 and during 2019 have focused on the reform of comprehensive ability evaluation, based on the previous stage. With the progress of this process, students' EMP learning attitude has become positive, and students' performance levels have significantly improved compared with those from before the reform. The second stage of the reform has also achieved significantly better results than those before the reform. Teaching content, form, class hours, and comprehensive ability indicators are positively correlated with students' excellent results.Conclusions: This course has been reformed and achieved remarkable results via the following: reducing class hours, increasing the integration and application of professional knowledge, placing students at the centre of the participatory teaching method, applying the situational, heuristic, and project-driven teaching methods, flipping classrooms, etc. These measures have students' abilities through the application of the comprehensive evaluation model, significantly augmenting the teaching effect.
The fabrication processes and simple micro-cavity size adjustment of fiber Mach-Zehnder interferometer by laser-induced micro-plasma
Authors: Shuhao Cai , Sergeev Maksim , Petrov Andrey , Varzhel Sergey , Li Li
Published: July 2022

The detailed fabrication processes of fiber Mach-Zehnder interferometers (FMZIs) by nanosecond laser-induced micro-plasma and its simple micro-cavity size adjustment are proposed and demonstrated. The fabrication can be divided into 4 processes: (1) heat transfer, (2) micro-plasma formation, (3) micro-plasma expansion and ablation, (4) cooling down and micro-structure formation. The simple micro-cavity size adjustment is proposed based on the above understanding, instead of the “point processing” of femtosecond laser, here only the focus position is required to be moved. The fabricated FMZI exhibits a high sensitivity of -15811 nm/RIU (refractive index unit) for the index sensing application.
Systemic Lupus Erythematosus due to Gain-of-Function Mutation in UNC93B1
Authors: Wolf Christine , Kind Barbara , Lim Ee Lyn , Dückers Gregor , Koss Sarah , Engel Kerstin , Lara-Villacanas Eusebia , Siepermann Kathrin , Niehues Tim , Mann Carina C. de Oliveira , Latz Eicke , Majer Olivia , Lee-Kirsch Min Ae
Published: July 2022

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the loss of tolerance to nuclear antigens. Activation of type I interferon (IFN) induced by immune recognition of self-nucleic acids by endosomal Toll-like receptors (TLR) is central to SLE pathogenesis. In two siblings with early-onset SLE, we identified a homozygous mutation in UNC93B1, encoding a multi-transmembrane protein required for trafficking and maturation of endosomal nucleic acid-sensing TLRs. The mutation alters the interaction of UNC93B1 with TLR7 leading to TLR7 hyperactivation with constitutive type I IFN signaling. Moreover, we demonstrate that treatment with the Janus kinase inhibitor ruxolitinib is of therapeutic value.
Comparing the Effects of Swimming and Running Wheel on Clinical Symptoms and Myelin Basic Protein in Mice with Experimental Autoimmune Encephalomyelitis
Authors: Karimian Maryam , karimian Razieh , Xirouchaki Chrisa Eleni , Ghanbarzadeh Mohsen , Habibi Abdolhamid
Published: July 2022

Background
Degradation of Myelin Basic Protein (MBP) is among the causes of Multiple Sclerosis (MS); MBP plays a vital role in the myelination in the nervous system.
Purpose
The present study was conducted to compare the effects of aerobic swimming and running wheel on clinical symptoms and brain MBP in mice with Experimental Autoimmune Encephalomyelitis (EAE).
Methods
The samples of this study consisted of 96 female C57BL/6 mice; after the EAE induction, Mice were divided into two groups of swimming and running wheel and in each protocol into 8 groups (healthy and EAE). The animals implemented two protocols. Then, the brain tissue was isolated and levels of the mentioned variables were measured via ELISA method. The data were analyzed statistically through one-way ANOVA (P ≤ 0.05).
Results
Results showed lesion scores, in both exercise protocols RW = 0/857, SW = 0/420 were lower in EAE mice than those in the control groups, con = 5/00 (p < 0.001); swimming and receiving interferon-beta-1 reduced MBP degradation, but the decrease was not significant (p = 0.09); running wheel reduced MBP degradation, which was statistically significant (p = 0.001).
Conclusion
Results suggested that the utilization of voluntary running wheel might be a more effective exercise method than swimming in preventing MBP degradation in the brain tissues of mice with EAE.