bluuebunny/crossref_metadata_2025 huggingface dataset:
Albendazole ameliorates aerobic glycolysis in myofibroblasts to reverse pulmonary fibrosis
Authors: Zeng Chenxi , Yue Huihui , Wang Congjian , Ju Xuetao , Wang Tianlai , Fu Xiangning , Zhou Qing , Zhang Huilan , He Long , Yu Jun , Wang Yi
Published: December 2023

Background
Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disorder for which effective treatments remain limited. Recent investigations revealed a potential link between altered glucose metabolism and the activation of fibroblasts, the key cells responsible for generating and depositing extracellular matrix proteins within the lung interstitium during IPF development.
Method
In this study, we aimed to investigate the potential therapeutic impact of albendazole on fibroblast to myofibroblast transition in IPF. We assess albendazole ‘s effectiveness in attenuating the activation of fibroblasts. We focused on elucidating the mechanism underlying albendazole's impact on TGF-β1-induced aerobic glycolysis in both lung tissues and fibroblasts obtained from patients with IPF and other lung fibrosis types. Furthermore, the antifibrotic effects of oral administration of albendazole were investigated in mouse models of pulmonary fibrosis induced by BLM or SiO2. Human precision-cut lung slices were employed to evaluate the impact of albendazole following TGF-β1 stimulation.
Result
In this work, we demonstrated that albendazole, a first-line broad-spectrum anthelmintic drug, effectively attenuated fibroblast to myofibroblast transition through alleviating TGF-β1-induced aerobic glycolysis dependent on the LRRN3/PFKFB3 signaling pathway. Additionally, LRRN3 expression was downregulated in both lung tissues and fibroblasts from patients with IPF and other types of lung fibrosis. Importantly, the levels of LRRN3 correlated with the progression of the disease. Notably, oral administration of albendazole exerted potent antifibrotic effects in mouse models of pulmonary fibrosis induced by BLM or SiO2, and in human precision-cut lung slices after TGF-β1 stimulation, as evidenced by improvements in lung morphology, reduced myofibroblast formation, and downregulation of α-SMA, collagen type 1 and FN expression in the lungs.
Conclusion
Our study implies that albendazole can act as a potent agonist of LRRN3 during fibroblast to myofibroblast differentiation and its oral administration shows potential as a viable therapeutic approach for managing IPF in clinical scenarios.
Noninvasive Evaluation of Myocardial Work in Hemodialysis Patients By Left Ventricular Pressure-Strain Loop Technique
Authors: Miao Yunxiang , Fan Lin , Zhou Bingyuan , Chen Fengling , Liao Yuping
Published: December 2023

Background Noninvasive left ventricular pressure-strain loop was used to evaluate the changes of myocardial work index in maintenance hemodialysis (MHD) patients.Methods We included 62 patients undergoing regular hemodialysis (HD) at the First Affiliated Hospital of Soochow University from July 2020 to October 2022. Left ventricular ejection fraction (LVEF) was measured by Simpson biplane method. Pulsed Doppler was used to calculate cardiac output (CO). Left ventricular longitudinal strain was obtained by two-dimensional speckle tracking imaging (2D-STI). Systolic blood pressure and diastolic blood pressure were input to obtain global work index (GWI), global constructive work (GCW), global wasted work (GEE) and global work efficiency (GWE). The differences of echocardiographic parameters before and after HD treatment were compared.Results After HD treatment, the size of cardiac chambers, LVEF and cardiac output decreased compared with those pre-HD (P < 0.05); Heart rate was faster than pre-HD (P < 0.05). Left ventricular diastolic function parameters (E-wave, A-wave, Septal e', Lateral e', E/e’ and PASP) were lower than pre-HD; GLS, GWI and GCW decreased after HD treatment (P < 0.05); There were no significant changes in GWW and GWE between HD sessions (P > 0.05).Conclusion Hemodialysis removed excessive fluids, the heart chambers became smaller. LVEF and CO declined, but remained within normal ranges. Left ventricular diastolic function was improved compared with pre-HD. PSL technique can effectively evaluate left ventricular myocardial work, and can provide a new approach for evaluating volume load and left ventricular myocardial function in HD patients. It is further verified that the myocardial work parameters have good repeatability.
Gene expression in metastatic breast cancer – patterns with prognostic potential in primary tumors and metastatic tissue
Authors: Tutzauer Julia , Larsson Anna-Maria , Aaltonen Kristina , Bergenfelz Caroline , Bendahl Pär-Ola , Rydén Lisa
Published: December 2023

Background
Metastatic breast cancer (MBC) is the main cause of breast cancer-related death. The outcome of MBC varies, and there is a lack of biomarkers to aid in prognostication. The primary aim of this study was to evaluate the prognostic value of gene expression (GEX) signatures in the primary tumor (PT) and distant metastasis (DM) for progression-free survival (PFS) and overall survival (OS). The secondary aim was to describe GEX changes through MBC evolution and to identify MBC subtypes.
Methods
RNA was extracted from the PT, lymph node metastases (LNM), and DM from MBC patients in a prospective observational study (n = 142; CTC-MBC NCT01322893) and was subjected to GEX analysis retrospectively using the NanoString Breast Cancer 360™ panel. 31 continuous GEX variables in DMs and PTs were analyzed for PFS and OS by Cox regression analysis and Kaplan-Meier estimates. Multivariable Cox regressions were adjusted for number of DM sites and CTCs, visceral metastasis, ECOG status, age at MBC diagnosis and, in additional analyses, PAM50 subtype. Differential GEX analyses and Euclidean distances were used to describe subgroup differences and visualize within-patient heterogeneity.
Results
Compared to DM GEX, GEX of the PT was at least equally useful for prognosticating MBC outcome. The strongest marker for a favorable PFS, both when expressed in the PT and the DM was AR, even after adjustment for prognostic markers including PAM50. GEX signatures related to hormone responsiveness, including ESR1, FOXA1, PGR, and AR were favorable prognostic markers, and the p53 signature was unfavorable for PFS when expressed in PT or DM. The previously published PAM50MET signature was prognostic for both PFS and OS. We established five distinct DM GEX profiles where two associated with liver and bone metastases, respectively. Finally, we identified four DM GEX profiles able to identify MBCs with poor OS in this cohort.
Conclusion
GEX of both DM and PT are useful in MBC prognostication. GEX of AR adds prognostic information for MBC. Our descriptive analyses illuminate the biological differences between MBCs in relation to outcome and metastatic site.
Proprioceptive Training Methods (PTM) in Female Soccer Players – A Systematic Review
Authors: Stanković Mima , Čaprić Ilma , Katanić Borko , Špirtović Omer , Maljanović Džejla , Nailovic Hamza , Mukovic Iso , Jelaska Igor , Trajković Nebojša
Published: December 2023

Background
Although previous studies have reported that proprioceptive training methods (PTM) have positive effects, there are a relatively small number of studies on the impact of PTM in women's soccer, and there is a need to systematize the given results. In this regard, this systematic review aimed to investigate the effect of proprioceptive training methods in female soccer players.
Methods
The studies' search and analysis were done according to the PRISMA guidelines. An electronic databases search (Google Scholar, PubMed Cochrane, ProQuest, and Research Gate), yielded 175 relevant studies conducted from 2000 to 2023.
Results
A total of 7 studies were included in the quantitative synthesis. Based on the analysis of previous research and detailed discussion, the main findings of the study resulted in the improvement of strength and muscle imbalance and the prevention and reduction of lower extremity injuries in female soccer players. PTM also improved agility, speed and accuracy in female soccer players.
Conclusion
The obtained results indicate the necessity of implementing proprioceptive training in female soccer training programs, in order to influence the prevention and reduction of injuries and improve balance and proprioceptive ability, and improve body control.
Water Quality Influences Cerrado Odonata Larval Assemblages
Authors: Melo Gabrielly Silva , Ferreira Victor Rennan Santos , Juen Leandro , Batista Joana Darc , Giehl Nubia França da Silva , Cabette Helena Soares Ramos , de Resende Bethânia Oliveira
Published: December 2023

Changes in water quality and stream habitats can significantly impact Odonata larvae dynamics as a result of their specific ecological requirements. This study investigated the effects of water quality and microhabitats on the structure of Odonata larval communities. During the same period, substrate types, water variables, and Odonata larvae were sampled. Our findings reveal that substrate type had no impact on community structure. However, the presence of ammonia and oxygen levels, among other water quality, influenced the abundance of Odonata larvae. While Odonata organisms are sensitive to the local environment, the intermittent flow of the creek and seasonal changes may be responsible for the lack of substrate influence on the Odonata community. Abiotic factors also play a critical role since Odonata larvae have limits to which they can tolerate. Variations in these factors can have a profound impact on the persistence and survival of the larvae. Additionally, the larvae's physiological responses, such as respiration, are influenced by these factors. Zygoptera larvae, which have branchial respiration, necessitate a water environment with low temperatures and high levels of dissolved oxygen. Therefore, the abiotic variables of the stream significantly affect the Odonata larvae community. Incorporating natural environmental changes and variations into monitoring and conservation programs is essential. By doing so, we can enhance our understanding of biodiversity and its distribution patterns, leading to more effective preservation efforts.
Exploring Patient Perspectives on EQ-5D-5L Data Visualization within an Individualized Decision Aid for Total Knee Arthroplasty (TKA) in Alberta, Canada
Authors: Johnson Jeffrey , Itiola Ademola , Rahman Shakib , Smith Christopher , Soprovich Allison , Wozniak Lisa , Marshall Deborah
Published: December 2023

Background
Decision aids can help patients set realistic expectations. In this study, we explored alternative presentations to visualise patient-reported outcomes (EQ-5D-5L) data within an online, individualized patient decision aid for total knee arthroplasty (TKA) to enhance usability prior to implementation into routine clinical practice.
Methods
We used data visualization techniques to modify the presentation of EQ-5D-5L outcomes data within the decision aid. The EQ-5D-5L data was divided into two parts allowing patients to compare themselves to similar individuals (1) pre-surgery and (2) 1-year post-surgery. We created 2 versions for each part and sought patient feedback on comprehension, usefulness, and visual appeal. Patients from an urban orthopedic clinic were recruited and their ratings and comments were recorded using a researcher-administered checklist. Data were managed using Microsoft Excel, R version 3.6.1 and ATLAS.ti V8 and analyzed using descriptive statistics and directed content analysis.
Results
A total of 24 and 25 patients participated in Parts 1 and 2, respectively. Overall, there was a slight preference for Version 1 in Part 1 (58.3%) and Version 2 in Part 2 (64%). Most participants demonstrated adequate comprehension for all versions (range 50–72%) and commented that the instructions were clear. While 50–60% of participants rated the content as useful, including knowing the possible outcomes of surgery, some participants found the information interesting only, were unsure how to use the information, or did not find it useful because they had already decided on a treatment. Participants rated visual appeal for all versions favorably but suggested improvements for readability, mainly larger font and image sizes and enhanced contrast between elements.
Conclusions
Based on the results, we will produce an enhanced presentation of EQ-5D-5L data within the decision aid. These improvements, along with further usability testing of the entire decision aid, will be made before implementation of the decision aid in routine clinical practice. Our results on patients’ perspectives on the presentation of EQ-5D-5L data to support decision making for TKA treatments contributes to the knowledge on EQ-5D-5L applications within healthcare systems for clinical care.
Differential expression and prognostic value of proliferation markers in different histological types of ovarian cancer
Authors: wang yurong , li xia
Published: December 2023

Purpose We will assess the expression of the Ki67 antigen in different histological types ofepithelial ovarian cancer and its correlation with pathological and clinical characteristics,and explore the clinical value of Ki67 antigen as a proliferation marker for diagnosis and prognosis.
Methods The GEPIA and GEO databases was used to assessed the mRNA expression of MKI67 in ovarian cancer. The expression of MKI67 in both normal and cancerous ovarian cells was assessed using qRT-PCR. Immunohistochemical staining was detected the expression of Ki67 protein in 104 ovarian cancers,general information was gathered,such as the age of each patient to analyze the connection between the expression of Ki67 and the clinicopathological features of the patients. Kaplan-Meier analysis examines the relationship between ovarian cancer patients' prognosis and Ki67 expression.
Results Ki67 was overexpressed in carcinoma ovarian cells and tissues compared with normal cells and tissues. Ki67 expression was significantly associated with FIGO stage (P<0.001), histologic subtype (P<0.001), involvement of unilateral/bilateral(P=0.007), and presence of lymph node metastasis(P=0.014). However, there was no association with other prognostic variables such age,tumor nature,or serum CA125. The expression of Ki67 was significantly different between serous carcinoma and endometrioid carcinoma (P=0.007) 、clear cell carcinoma (P <0.001). Moreover, its expression was significantly different between FIGO stage III and stages I (P=0.002) 、stage II (P=0.008). According to Kaplan-Meier analysis,the 3-year survival rate and PFS in the Ki67 high expression group were considerably poorer than in the low expression group (P<0.05).
Conclusions In the tissues of ovarian cancer, Ki67 was highly expressed, and its expression levels was closely correlated with clinicopathological features including tumor FIGO stage, histologic subtype, unilateral / bilateral involvement, and lymph node metastasis. Patients with high expression have a reduced survival rate and a worse prognosis. Inactivation of the proliferation marker Ki67 will lead to proliferative cell-specific death, therefore maybe a potential strategy for ovarian cancer.
Attitude, awareness, and understanding of Artificial Intelligence AI among medical and dental students in Jordan: a cross-sectional study
Authors: Abdallat Mahmoud , AlSamhori Jehad Feras , AlSamhori Abdel Rahman Feras , Shnekat Hala Hayel , AlSamhori Ahmad Feras , Abdallat Shahem , Murshidi Rand
Published: December 2023

Introduction:
The rapid growth of AI has transformed various sectors, including healthcare. AI aids medical diagnoses and treatment planning, but challenges such as privacy and ethical concerns exist. Understanding AI is crucial for medical and dental students in Jordan to enhance patient care. This study examines students' attitudes, awareness, and understanding of AI to inform effective education and better healthcare practices.
Methods:
A cross-sectional study was conducted in Jordan among medical and dental students from Nov 2022 to Mar 2023. Data were analyzed using descriptive statistics, Mann-Whitney U test, Kruskal-Wallis tests, and Spearman's correlation. Ethical approval was obtained, and SPSS was used for analysis.
Result:
A survey of 800 medical and dental students in Jordan revealed significant variations in AI awareness, understanding, and attitudes. Notably, 54.6% were female, average age 19.81. Only 38.8% had tech family background. 35.0% used social media for AI info. 28.0% believed AI would improve medical diagnosis. Correlation showed positive link between AI awareness and understanding (r: 0.491, p < 0.001).
Conclusion:
The younger generation of medical and dental professionals’ views AI as a collaborator in their practice. Strong interest and active engagement in AI-related courses highlight the importance of integrating AI education into medical curricula for innovative healthcare practices.
Physicians and midwives' perceptions and experiences of sexual health and right education and its influence on promoting women's empowerment: a qualitative content analysis study
Authors: Ghorbani Faeze , Latifnejad Robab , Khadivzadeh Talat , Mirzaii khadijeh
Published: December 2023

Background: Training of sexual assertiveness, which is the knowledge and skill of defense of sexual rights and sexual identity, would enhance marital satisfaction and adjustment. It is necessary to have a deep understanding of this concept in order to achieve strategies to promote sexual assertiveness to empower women. The purpose of this study was to explore perceptions and experiences of midwives and physicians towards the concept of sexual assertiveness training and its promotion in line with women's empowerment.Methods: This qualitative study was conducted from July to November 1401 in the hospitals and health centers of Mashhad, Iran. The data was collected by conducting semi-structured and individual interviews (telephone and virtual) by 14 participants, who were selected through purposive sampling until data saturation was reached. Data analysis was done using conventional content analysis with MAXQda software.Results::Three main categorieswas emerged from analysis of qualitative data including: 1) the concept of sexual assertiveness (the meaning of sexual rights in life, the effects of sexual rights), 2) complications of sexual rights violation (psychological side effects, physical side effects) and 3) strategies for empowering women (not having a gender bias on women, participation of women in social life, comprehensive sex education) was obtained.Conclusion:In order to empower women in sexual rights, midwives and physicians should use strategies such as comprehensive sex education for women, and also eliminating the gender bias on women's issues and encouraging women to participate and negotiate in their sexual life.
Application of exercise therapy in patients with chronic kidney disease-induced muscle atrophy: A scoping review
Authors: Yin Jiawei , Zhang Xiaotu , Wang Zilin , Sun Xuefeng , Qu Zihan , Song Yuqing , Zhang Hongshi
Published: December 2023

Objective: To conduct a systematic analysis of existing research on the application of exercise intervention in the nursing care of patients suffering from chronic kidney disease (CKD)-induced muscle atrophy and identify the specific exercise modalities, contents, outcome indicators, and application effects associated with this intervention.
Methods:According to the method of a scoping review, nine databases (Cochrane, PubMed, EMBASE, Web of Science, ProQuest, Ovid, CNKI, Wanfang Data, and VIP) were searched until September 28, 2023. The included literature was screened, summarized, and analyzed.
Results: A total of 20 pieces of literature were included. Some types include aerobic exercise, resistance exercise, and aerobic combined resistance exercise. The exercise intensity primarily falls within the mild to moderate range, with a recommended frequency of 2-3 times a week, lasting 30-60 min each time. The types of outcomes encompassed in this study include body composition, functional testing, strength measurements, laboratory examinations, cardiopulmonary function assessments, and patient-reported outcomes. To varying degrees, exercise intervention positively impacts the subjects' physical activity ability, body composition, and skeletal muscle status. Currently, resistance training is the primary type of intervention used for preventing and treating CKD patients induced by muscle atrophy.
Conclusion: Exercise intervention can improve muscle strength, physical function, and quality of life in patients with CKD muscle atrophy. Therefore, patients should be fully informed of the effect of exercise intervention in the treatment of chronic kidney disease-induced muscle atrophy in future, so as to promote the standardized implementation of exercise intervention.
Research on the privacy protection technology of blockchain spatiotemporal big data
Authors: Zhou Bao , Zhao Junsan , Chen Guoping , Yin Ying
Published: December 2023

At present, the fast-paced development of big data technology and the Internet of Things has led to the generation of spatiotemporal data streams on a large scale. In this circumstance, data holders often choose the cloud storage of their data to alleviate with the pressure of local storage and computing overhead. However, this is a centralized mode of storage, and the data is susceptible to the risk of tampering and leakage in the absence of physical control over spatio-temporal big data. Therefore, a blockchain-based space-time big data privacy protection scheme is devised in this paper. To begin with, in order to ensure data privacy, the scheme adopts a storage mode in which the public chain are coordinated with the side chain. The former stores various information such as keys and security authentication parameters, while the latter stores private data. Then, the irreversible SHA256 algorithm is applied to authenticate the access nodes. Finally, AES and RSA hybrid encryption is performed to encrypt the collected spatio-temporal big data for the security of private data to be further enhanced. The security performance of the system is evaluated by comparing the success rate of attacks on the blockchain under different circumstances. Also, the system throughput of this scheme is analyzed through simulation, the results of which show that the service life of this system reaches a minimum of 13.79 years when 100 nodes are use. In this context, the system throughput reaches 1607 transactions/s, each node contains 1.2×107 blocks, and the time taken to query specific spatio-temporal data is less than 2 seconds.
Blood cadmium concentrations and risk of all-cause mortality among adults with chronic pruritic dermatoses: A prospective cohort study
Authors: Xiao Yu , Li Shan , Yang Wanying , Zhang Tianyi , Liu Chao
Published: December 2023

Cadmium (Cd) accumulates in the human body over time, posing significant health risks. This study focused on the relationship between blood Cd concentrations and all-cause mortality in adults suffering from chronic pruritic dermatoses (CPD). Data utilized in our study was collected from the National Health and Nutrition Examination Survey for the 2005–2006 cycle in the United States. To assess the hazard ratio (HR) for mortality, a weighted multivariable Cox regression analysis was conducted, considering age, sex, race, body mass index, waist circumference, hay fever, and allergy. The restricted cubic spline analyses were adopted to explore the dose-response association. Additionally, subgroup and sensitivity analyses were implemented to estimate the stability of the findings. In this study, 323 participants were collected from 10,348 individuals. Compared with the lowest quantile of blood Cd concentrations group, individuals in the highest quantile had an adjusted HR of 3.35 (95% CI: 1.46, 7.73) for all-cause mortality. The restricted cubic spline analyses of multivariate adjustment revealed a significant linear dose-response relationship between ln-transformed blood Cd concentrations (ranging from 0.46 to 3.96µg/g ) and the risk of all-cause mortality. In addition, no significant interactions were observed between strata variables and blood Cd (all Pinteraction > 0.05). Sensitivity analyses also yielded similar results to those obtained in our study. Cd exposure serves as a critical risk factor for all-cause mortality in adults suffering from CPD. Our data substantiate a linear relationship between blood Cd concentrations and mortality risk. These findings underscore the imperative for policy makers and the general public to mitigate Cd exposure, thereby reducing long-term adverse health outcomes.
NSUN7 gene polymorphisms increase the risk of neuroblastoma in Chinese children
Authors: Xu Yile , Zhang Weixin , Hu Yaofang , Guo Huiqin , Li Meng , Li Di , Lin Lei , He Jing , Miao Lei
Published: December 2023

Purpose
Neuroblastoma (NB) is the most common childhood solid tumor, exhibiting significant genetic variability. This study aims to assess the impact of NSUN7 gene polymorphisms (rs55690540 T > G, rs2437323 G > T, rs4861311 A > G, and rs11724316 T > C) on the susceptibility and prognosis of NB in a Chinese cohort. It focuses on elucidating the role of NSUN7 expression correlation with NB progression and outcomes, leveraging public databases and bioinformatics analysis.
Methods
A case-control study comprising 398 NB patients and 473 healthy controls was conducted, utilizing TaqMan assays for genotyping NSUN7 polymorphisms. Multivariate logistic regression determined the association between these polymorphisms and NB risk. The GTEx database was used to assess gene expression impact. Kaplan–Meier analysis and bioinformatics tools, including GSEA and KEGG pathway analysis, were employed to evaluate the prognostic implications of NSUN7 expression in datasets GSE49710 and GSE45547.
Results
Certain NSUN7 polymorphisms, particularly rs11724316 CC and rs2437323 TT genotypes, showed a significant association with increased NB susceptibility. Stratification analysis revealed age and stage-specific correlations. Elevated NSUN7 expression, correlated with poor prognosis in NB, was linked to significant metabolic shifts and involvement in key pathways like KRAS signaling, E2F targets, and G2M checkpoint.
Conclusion
NSUN7 polymorphisms emerge as potential biomarkers for NB susceptibility and prognosis. High NSUN7 expression is associated with adverse outcomes, highlighting its critical role in NB pathogenesis and as a promising target for therapeutic intervention. This study provides a foundation for future research in neuroblastoma genetics and treatment strategies.
Impact of Large-Scale Disasters on Breast Cancer Care: A Qualitative Analysis of Patient Experiences During the 2011 Triple Disaster in Fukushima, Japan
Authors: Kaneda Yudai , Ozaki Akihiko , Murakami Michio , Saito Hiroaki , Sawano Toyoaki , Yamashiat Erika , Gonda Kenji , Tachibana Kazunoshin , Ohtake Tohru , Tsubokura Masaharu , Ohira Hiromichi
Published: December 2023

Background Large-scale disasters can severely affect breast cancer care, leading to treatment disruption and delay. Although few empirical studies have explored these effects, analyzing patients’ narratives can help bridge this gap. This study aimed to explore treatment continuity and medical access among patients with breast cancer during the 2011 triple disaster using qualitative research methods. Methods This qualitative study focused on 21 patients with breast cancer diagnosed before the disaster and were affected by it. Upon receiving consent, semi-structured interviews were conducted, lasting between 20 min to 1 h. Inductive thematic analysis was used for data interpretation. Results Five key themes emerged in the present study, ranging from immediate response to long-term recovery: medical challenges faced after the disaster, family roles and burdens, information access and communication, mental health effects of disasters, and challenges faced during evacuation. These themes covered a range of challenges, including infrastructure damage, treatment disruptions, substantial constraints arising from familial roles that could overburden the family support, importance of reliable medical and nonmedical information sources, psychological impacts of the disaster, and unique difficulties experienced in evacuation shelters. Conclusions This analysis highlights the critical need for ongoing care and addresses the key challenges faced by breast cancer patients during disasters. Future research should aim to develop practical and prompt solutions to address these issues in disaster settings.
Fast recovery of COVID-19-induced acute respiratory distress syndrome after hyperbaric oxygen treatment and changes in endoplasmic reticulum (ER) stress response in peripheral monocytes – A randomized-controlled trial
Authors: Kjellberg Anders , Zhao Allan , Lussier Anna , Hassler Adrian , Al-Ezerjawi Sarah , Boström Emil , Catrina Sergiu-Bogdan , Bergman Peter , Rodriguez-Wallberg Kenny Alexandra , Lindholm Peter
Published: December 2023

Background: Many questions remain unanswered regarding the scientific understanding of SARS-CoV-2 and host interaction. There is an established need to develop anti-inflammatory agents with the potential to prevent or mitigate the development of severe COVID-19, targeting viral replication and/or the immune response. To address these unmet needs, we investigated the effects of oxygen treatment (HBOT) on clinical inflammatory markers, peripheral blood cells and transcriptional changes in patients with severe COVID-19.
Methods: In this pre-defined sub-study of a randomized controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome (ARDS) at one Swedish university hospital were enrolled and randomly assigned (1:1) to HBOT plus best practice or best practice (Control) and followed up on nine visits for 30 days. HBOT was administered with five treatments at 2.4 atmospheres absolute (ATA) for 80 min each, the first seven days. Clinical inflammatory markers, lymphocyte phenotyping with flow cytometry, and bulk RNA sequencing (RNAseq) were analyzed on peripheral blood monocytes (PBMCs).
Results: Between December 3rd 2020, and May 17th 2021, 23 patients were randomized, and 17 were analyzed. RNAseq revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed unique decreases of the unfolded protein response (UPR) and inflammatory response in the HBOT group. The HBOT group recovered faster. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F(8, 120) = 3.817, p < 0.001) and PaO2/FiO2 was higher in the HBOT group (Mixed effects model, F(8, 94) = 2.900, p < 0.01). The HBOT group had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99% CI -16-0), p=0.045, saving ~300.000 USD.
Conclusions: Pathways related to viral-induced ER stress with downregulation of the UPR and inflammatory response in critical COVID-19 patients treated with HBOT was significantly different compared to controls and associated with faster recovery and reduced HLoS.
Trial registration: NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020)
Inborn error of WAS presenting with SARS-CoV-2-related multisystem inflammatory syndrome in children
Authors: Drago Enrico , Fioredda Francesca , Penco Federica , Prigione Ignazia , Bertoni Arinna , Zotto Genny Del , Bocca Paola , Massaccesi Erika , Lanciotti Marina , Moratto Daniele , Thurner Lorenz , Caorsi Roberta , Gattorno Marco , Volpi Stefano
Published: December 2023

Multisystem inflammatory syndrome in children (MIS-C) has been reported in patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case of MIS-C in a child affected by Wiskott-Aldrich syndrome (WAS) gene mutation, elucidating underlying predisposing factors and the involved inflammatory pathways. Genetic analysis revealed a frameshift truncating variant in the WAS gene, resulting in WAS protein expression between mild and severe forms, despite a clinical phenotype resembling X-linked thrombocytopenia (XLT). IL-1β secretion by LPS-stimulated peripheral blood mononuclear cells from patient during MIS-C was lower compared to healthy subjects but increased during follow-up. Conversely, the percentage ASC (apoptosis-associated speck-like protein containing a CARD) specks in the patient's circulating monocytes during the acute phase was higher than in healthy subjects. The type I interferon (IFN) score during MIS-C was normal, in contrast to the raised IFN signature measured far from the acute event. This case confirms the association of IEI with MIS-C, potentially linked to delayed immune responses to SARS-CoV-2. The XLT phenotype underlies a subclinical immunodysregulation involving the NLRP3 inflammasome and the type-I IFN response.
Fingertip Tactile Sensation via Piezoelectric Micromachined Ultrasonic Transducers with an Amplified Interface
Authors: Sone Junji
Published: December 2023

Tactile devices are often used in the field of robotics; however, the development of compact high-resolution tactile devices remains challenging. In this study, we developed a haptic device for force presentation using a DC motor and a tactile sensation device to simultaneously present haptic and tactile stimuli. A microelectromechanical system was selected to maintain the compactness of the tactile device. Piezoelectric micromachined ultrasonic transducers are known for high-power stimulation, and we selected lanthanum-doped lead zirconate titanate as the high-power amplified actuator. A finger mount structure that transfers force for amplifying ultrasonic waves was considered to combine acoustic pressure and aeroacoustics by attaching silicone rubber. The device was fabricated, and the performance of the tactile sensations was evaluated. The developed device uses the novel concept of combining acoustic pressure and aeroacoustics, and its compactness renders it suitable for wearable systems.
Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts
Authors: Hu Tingju , Gao Hong , Duan Rui , Bai Xue , Huang Xiang , Yan Xu , An Li , Ma Yanyan , Chen Rui , Hong Sen , Gan Mi
Published: December 2023

Myocardial ischemia-reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia-reperfusion hearts. Myocardial ischemia-reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia-reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immunofluorescence and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemia-reperfusion.
Regeneration of alveolar bone defects in the experimental pig model. A systematic review and meta-analysis
Authors: Shanbhag Siddharth , Kampleitner Carina , Sanz-Esporrin Javier , Lie Stein Atle , Gruber Reinhard , Mustafa Kamal , Sanz Mariano
Published: December 2023

Objective
Pigs are emerging as a preferred experimental in vivo model for bone regeneration. The study objective was to answer the focused PEO question: in the pig model (P), what is the capacity in experimental alveolar bone defects (E) for spontaneous regeneration in terms of new bone formation (O)?
Methods
Following PRISMA guidelines, electronic databases were searched for studies reporting experimental bone defect- or extraction socket-healing in the maxillae or mandibles of pigs. The main inclusion criteria were presence of a control group of untreated defects/sockets and assessment of regeneration via 3D tomography [radiographic defect fill (RDF)] or 2D histomorphometry [new bone formation (NBF)]. Random effects meta-analyses were performed for the outcomes RDF and NBF.
Results
Overall, 45 studies were included reporting on alveolar bone defects or extraction sockets, most frequently in the mandibles of minipigs. Based on morphology, defects were broadly classified as “box-defects” (BD) or “cylinder-defects” (CD) with a wide range of healing times (10 days to 52 weeks). Meta-analyses revealed pooled estimates (with 95% confidence intervals) of 50% RDF (36.87–63.15%) and 43.74% NBF (30.47–57%) in BD, and 44% RDF (16.48–71.61%) and 39.67% NBF (31.53–47.81%) in CD, which were similar to estimates of socket-healing [48.74% RDF (40.35–57.13%) and 38.73% NBF (28.57–48.89%)]. Heterogeneity in the meta-analysis was high (I2 > 90%).
Conclusion
A substantial body of literature revealed a high capacity for spontaneous regeneration in experimental alveolar bone defects of (mini)pigs, which should be considered in future studies of bone regeneration in this animal model.
Undaria pinnatifida extract attenuates allergic airway inflammation by the modulation of epithelial cell dysfunction and oxidative stress
Authors: Yu Zhen Nan , Fan Yan Jing , Nguyen Thi , Piao Chun Hua , Lee Byung-Hoo , Lee So-Young , Shin Hee Soon , Song Chang Ho , Chai Ok Hee
Published: December 2023

Background: Combinative allergic rhinitis and asthma syndrome (CARAS) is a novel uniform airway inflammation composed of inflammation in the upper and lower respiratory tracts.Undaria pinnatifida (U. pinnatifida), a brown alga commonly grown in the oceans of East Asia, has long been a part of human diet and medicine. Though U. pinnatifida has been reported to have immunomodulatory, anti-inflammatory, anti-oxidant, anti-diabetic and anti-bacterial activities, its specific effect on combined allergic rhinitis and asthma syndrome (CARAS) has not been clarified.
Methods:In this study, the anti-allergic and anti-inflammatory effects of U. pinnatifida extract (UPE) were investigated in a mouse model of ovalbumin (OVA)-induced CARAS. ELISA was performed using serum samples, NALF and BALF to detect OVA-specific immunoglobulins and inflammatory cytokines. In addition, we checked the levels of MAPKs using western blotting, and we checked the levels of E-cadherin and ST2 using immunohistochemistry.
Results:The oral administrations of UPE inhibited allergic responses by reducing OVA-specific immunoglobulin levels; accordingly, symptoms in early reactions were also significantly improved. UPE inhibited the accumulation of inflammatory cells in both nasal and bronchoalveolar lavage fluid and tissues. UPE also attenuated the expression of Th2 cytokines (IL-4, IL-5, IL-13) and up-regulated the secretion of Th1 cytokines (IL-12, IFN-γ) in nasal and bronchoalveolar lavage fluid. Furthermore, UPE treatment inhibited the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathway in lung homogenates. Also, UPE treatment protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa. In addition, UPE ameliorated the dysfunction of the nasal epithelial barrier by enhancing antioxidant properties. UPE attenuated epithelial cell damage and thus down-regulated the expression of the inflammatory factor IL-33.
Conclusions:These results suggest that UPE may potentially treat CARAS by modulating epithelial cell dysfunction and oxidative stress, thereby attenuating the release of IL-33.
Illuminating HLA-DPA1 and HSH2D as Potential Prognostic Biomarkers by Weighted Gene Co-Expression Network Analysis for NRAS-Mutant Skin Cutaneous Melanoma
Authors: Dodin Yasmeen , Dodein Razan , Seetan Khaled
Published: December 2023

Background
NRAS-mutant skin cutaneous melanoma (NRAS-MT SKCM) poses clinical challenges due to its aggressive progression and unfavorable outcomes compared to other subtypes. NRAS mutations, present in around 26% of cases, play a significant role in cutaneous melanoma. However, targeted therapies tailored to NRAS mutations are currently lacking, highlighting an unmet need. Our study aimed to identify hub/key genes specifically associated with NRAS-MT SKCM prognosis. The identification of prognostic biomarkers for survival prediction is essential to enhance patient care and facilitate the development of personalized treatment strategies.
Methods
We comprehensively analyzed RNA-seq data from The Cancer Genome Atlas-Skin Cutaneous Melanoma (TCGA-SKCM) and Genotype-Tissue Expression (GTEx) for NRAS-MT SKCM and normal skin tissues. Our analyses included weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, functional enrichment analysis, construction of a protein-protein interaction (PPI) network, identification of hub genes, survival analysis, and external validation using the microarray dataset GSE65904 from the Gene Expression Omnibus (GEO) database.
Results
The analysis of differential gene expression revealed 6,577 differentially expressed genes (DEGs) with significant changes in NRAS-mutant SKCM, including 3,823 up-regulated and 2,754 down-regulated genes. WGCNA highlighted a noteworthy blue module consisting of 248 genes strongly correlated with NRAS-mutant SKCM. An intersection analysis identified 211 genes common to both the DEGs and the blue module. Through PPI network analysis and survival analysis, key hub genes within the blue module were identified, including HLA-DPA1, SIGLEC1, HSH2D, and TNFSF8. Survival analysis indicated that lower expression of these genes was associated with poorer overall survival in NRAS-mutant SKCM patients. External validation confirmed the prognostic significance of two survival-related hub genes, namely HLA-DPA1 and HSH2D.
Conclusion
Our study identified HLA-DPA1 and HSH2D as potential prognostic biomarkers in NRAS-MT SKCM. These findings contribute to a better understanding of the disease's molecular mechanisms and have implications for personalized treatment strategies.
Metal mixture exposure and the risk of osteopenia or osteoporosis: Baseline Data from the Chinese Multi-Ethnic Cohort (CMEC) Study
Authors: zhang yuxin , Chen Cheng , Wu Shenyan , Nie Chan , Hu Yuxin , Zhong Jianqin , Hong Feng
Published: December 2023

Osteoporosis is emerging as a growing public health concern worldwide due to the aging population, and metal exposure is widely recognized as a risk factor for human health. However, studies on the relationship between metal exposure and bone health yield inconsistent results. Limited epidemiological research exists on the associations of metal mixtures with osteopenia and osteoporosis, particularly among ethnic minorities in China. We conducted a study on 9206 ethnic Chinese (Dong and Miao) aged 30–79 years using data from the Chinese Multi-Ethnic Cohort Study (CMCS) baseline survey database. We utilized inductively coupled plasma mass spectrometry (ICP-MS) to measure the concentrations of 11 metals in urine and quantitative ultrasound to measure bone mineral density (BMD). Multivariate logistic regression model, Quantile g-computation and Principal component analysis were used to explore the correlation between single-metal exposure and metal mixture exposure with osteopenia and osteoporosis. In the single-metal exposure model, urinary concentrations of As, Cd, Cr, Fe, Hg and Mn were positively associated with the risk of osteopenia. Conversely, urinary Co and Zn were negatively associated with the risk of osteopenia. Urinary As, Cd, Cr and Mn were positively associated with the risk of osteoporosis, while urinary V was negatively associated with the risk of osteoporosis. In addition, Quantile g-comptation showed that exposure to metal mixtures was positively associated with osteopenia and osteoporosis. Principal component analysis identified principal component 1, characterized by Fe and Mn, and principal component 3, characterized by Hg and Cd, as positively associated with osteopenia and osteoporosis. These findings suggest that the co-exposure of polymetals affects the occurrence and development of osteoporosis, warranting further investigation into the complex mechanisms involved.
Surgical Cholecystectomy Score (SCS) for grading the difficulty of laparoscopic cholecystectomy
Authors: S Kruthika , Asuri Krishna , Singh Deepti , Prakash Om , Rai Sanjeet , Ramachandran Rashmi , Kumar Subodh , Bansal Virinder Kumar
Published: December 2023

Background: Laparoscopic cholecystectomy (LC) is the standard of care for symptomatic gall stone disease. A good scoring system is necessary to standardize the reporting. Our aim was to develop and validate an objective scoring system, the Surgical Cholecystectomy Score (SCS) to grade the difficulty of LC.
Methods:The study was conducted in a single surgical unit at a tertiary care hospital in two phases from January 2017 to April 2021. Retrospective data was analysed and the difficulty of each procedure was graded according to the modified Nassar’s scoring system. Significant preoperative and intraoperative data obtained was given a weightage score. In phase II, these scores were validated on a prospective cohort. Each procedure was classified either as easy, moderately difficult or difficult.
Statistical analysis: A univariate analysis was performed on the data followed by a multivariate regression analysis. Bidirectional stepwise selection was done to select the most significant variables. The Beta /Schneeweiss scoring system was used to generate a rounded risk score.
Results: Data of 800 patients was retrieved and graded. 10 intraoperative parameters were found to be significant. Each variable was assigned a rounded risk score. The final SCS range for intraoperative parameters was 0-15. The scoring system was validated on a cohort of 249 LC.
In the final scoring, cut off SCS of >8 was found to correlate with difficult procedures. Score of < 2 was equivalent to easy LC. A score between 2 and 8 indicated moderate difficulty. The area under ROC curve was 0.98 and 0.92 for the intraoperative score indicating that the score was an excellent measure of the difficulty level of LCs.
Conclusion: The scoring system developed in this study has shown an excellent correlation with the difficulty of LC. It needs to be validated in different cohorts and across multiple centers further.