bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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 &amp; 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.