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Bioimpedance measurements are becoming important in probing the human body for diagnosis and monitoring. An age old 4-electrode technique called tetrapolar impedance measurement (TPIM), giving transfer impedance, cannot localize a specific zone besides having large zones of negative sensitivity. A new technique named the focused impedance method (FIM) from Dhaka University (DU), Bangladesh used the algebraic average of two concentric and orthogonal TPIMs, localizing a zone of interest and having reduced magnitudes of negative sensitivity. Earlier, this was implemented with electrodes applied from one side of the human body giving information to shallow depths only. To get information from deeper regions, specifically, of the thorax, the same DU group placed two electrodes of a 4-electrode version of FIM at the front and two at the back in a horizontal plane of the thorax, using physics-based visualization. This was followed by a few quantitative studies using point sensitivity, which supported the concept. However, more quantitative studies still need to be performed, particularly using objects of finite sizes, in order to establish the technique on a stronger footing. The present study was taken up with this objective. A simplified approach was used in which the volume conductor was a rectangular non-conducting container filled with saline of uniform conductivity with an embedded spherical object – first an insulator and then a conductor. Electrodes were placed at specific chosen positions following the above visualization. Percentage change in transfer impedance with the object placed at different internal positions, compared to that without the object was obtained first using COMSOL simulation and then through experimental measurements. These were performed for both TPIM and FIM. The new configuration of 4-electrode FIM gave good depth sensitivity supporting the effectiveness of the new placement of electrodes.

Lucy Gracen,1 Melanie Aikebuse,2,3 Babak Sarraf,2– 4 Steven M McPhail,5 Anthony W Russell,6 James O’Beirne,7 Katharine M Irvine,8 Suzanne Williams,9 Patricia C Valery,4,* Elizabeth E Powell2– 4,* 1Department of Gastroenterology and Hepatology, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia; 2Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia; 3Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia; 4QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; 5Australian Centre for Health Services Innovation School of Public Health, Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia; 6Endocrinology and Diabetes, the Alfred Hospital, Melbourne, VIC, Australia; 7Department of Gastroenterology and Hepatology, Sunshine Coast University Hospital, Birtinya, QLD, Australia; 8Mater Research, Translational Research Institute, Brisbane, QLD, Australia; 9Inala Primary Care General Practice, Inala, QLD, Australia*These authors contributed equally to this workCorrespondence: Elizabeth E Powell, Centre for Liver Disease Research, Faculty of Medicine, Translational, Research Institute, The University of Queensland, Level 5, West Wing, 37, Kent Street, Woolloongabba, Brisbane, QLD, 4102, Australia, Tel +61 412 014 337, Email e.powell@uq.edu.auBackground: Although clinical guidelines endorse screening for metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis in people with type 2 diabetes (T2D), the feasibility of and barriers and considerations relevant to implementing this approach in the community remain unclear.Methods: Sequential adults with T2D attending selected community clinics during 2021– 2023 were invited to receive a “liver health check” (n=543). A further 95 participants were referred directly from their general practitioner (GP) or self-referred to the study. A total of 302 participants underwent a point of care assessment of hepatic steatosis and stiffness (FibroScan) and were advised to see their GP to discuss the results. “Template” letters containing key results, their interpretation and advice about management of cardiometabolic risk, patient follow-up and referral criteria, were sent to participants’ GPs.Results: Referral to a tertiary liver clinic was advised in GP letters for 45 (15%) participants with an increased risk of clinically significant fibrosis (liver stiffness measurement ≥ 8), 15 participants with ‘red flags’ (eg splenomegaly, thrombocytopenia) and 2 with unsuccessful FibroScan examinations. A referral from GPs to the liver clinic was received for 27 (44%) of these 62 participants. Approximately 90% of GPs rated the “template” letters favourably on a Likert rating scale.Conclusion: The low rate of participation in the “liver health check” and liver clinic referral reflects a real-world scenario and may stem from societal under-recognition and engagement with MASLD, competing health priorities or under-appreciation of the link between liver fibrosis severity and mortality risk. Further studies need to address strategies to enhance participation in liver health assessments and determine their impact on liver-related morbidity/mortality and overall survival.Keywords: NAFLD, primary care, chronic liver disease, FibroScan

Qianhan Lin,1 Jiajia Li,1 Zulimire Abudousalamu,1 Yating Sun,1 Mengyang Xue,1 Liangqing Yao,2 Mo Chen1 1Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Gynecologic Oncology, Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Liangqing Yao; Mo Chen, Email yaoliangqing@163.com; chenmo_nicy@163.comAbstract: Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.Keywords: targeted drug delivery, ovarian cancer, drug conjugates, nanoparticle, hydrogel

Fengsong Chen,1 Yanhua Huang,1 Yayun Qian,2 Ya Zhao,2 Chiwen Bu,3 Dong Zhang3 1Department of Gastroenterology, Haimen People’s Hospital, Nantong, 226000, People’s Republic of China; 2Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Institute of Surgery, Guanyun People’s Hospital, Guanyun, 222200, People’s Republic of ChinaCorrespondence: Dong Zhang; Chiwen Bu, Email gyxrmyykjk@163.com; gyxrmyybcw@163.comBackground: Gastric lesions pose significant clinical challenges due to their varying degrees of malignancy and difficulty in early diagnosis. Early and accurate detection of these lesions is crucial for effective treatment and improved patient outcomes.Methods: This paper proposed a label-free and highly sensitive classification method for serum of patients with different degrees of gastric lesions by combining surface-enhanced Raman scattering (SERS) and machine learning analysis. Specifically, we prepared Au lotus-shaped (AuLS) nanoarrays substrates using seed-mediated and liquid–liquid interface self-assembly method for measuring SERS spectra of serum, and then the collected spectra were processed by principal component analysis (PCA) - multi-local means based nearest neighbor (MLMNN) model to achieve differentiation.Results: By employing this pattern analysis, AuLS nanoarray substrates can achieve fast, sensitive, and label-free serum spectral detection. The classification accuracy can reach 97.5%, the sensitivity is higher than 96.7%, and the specificity is higher than 95.0%. Moreover, by analyzing the PCs loading plots, the most critical spectral features distinguishing different degrees of gastric lesions were successfully captured.Conclusion: This discovery lays the foundation for combining SERS with machine learning for real-time diagnosis and recognition of gastric lesions.Keywords: surface-enhanced Raman scattering, gastric lesions, Au lotus-shaped nanoarrays, principal component analysis, multi-local means based nearest neighbor

Wenyu Zhang,1,* Linquan Li,1,* Yaguang Wu,1 Chengzhilin Li,1 Zi’ang Xu,1 Nianlei Zhang,1 Xinyu Wang,1 Yingchun Zhao,1 Tingjian Zu,1 Qingbin He,1 Jianwei Jiao,2 Runxiao Zheng1 1School of Clinical and Basic Medical Sciences, Medical Science and Technology Innovation Center, Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China; 2State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China*These authors contributed equally to this workCorrespondence: Runxiao Zheng, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, People’s Republic of China, Email zhengrunxiao@sdfmu.edu.cn Jianwei Jiao, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China, Email jwjiao@ioz.ac.cnIntroduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses.Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME).Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response.Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy. Keywords: metabolic immunotherapy, nanoparticles, reprograming, iron oxide, macrophages

Valeria Magarotto,1 Julien Thevenon,2 Kate Morgan,3 Silene ten Seldam,3 Wafae Iraqi,4 Xavier Guillaume,5 Marjorie Leclerc,5 Claire Graziani-Taugeron,5 Bleuenn Rault,5 Dahbia Horchi5 1MD, Janssen-Cilag, Cologno Monzese, MI, Italy; 2Medical Affairs, Janssen Pharmaceuticals, Issy-les-Moulineaux, France; 3Myeloma Patients Europe, Brussels, Belgium; 4Patient Engagement, Janssen Pharmaceuticals, Issy-les-Moulineaux, France; 5RWE Data & Analytics, Oracle Life Sciences, Paris, FranceCorrespondence: Xavier Guillaume; Claire Graziani-Taugeron, Oracle France, 198 Avenue de France, Paris, 75013, France, Email xavier.guillaume@oracle.com; claire.graziani-taugeron@oracle.comPurpose: To provide real-world data on patient perceptions and experiences with subcutaneous (SC) versus intravenous (IV) daratumumab.Patients and Methods: This was a cross-sectional, mixed-method (qualitative/quantitative) survey conducted in France, Germany, Spain and the United Kingdom involving multiple myeloma (MM) patients who switched from IV to SC daratumumab in the last 12 months (qualitative phase) or 24 months (quantitative phase [26 months in the UK]) prior to enrollment in the study.Results: Nine patients (mean age 65 years) participated in the qualitative phase and 113 patients (mean age 65.1 years) in the quantitative phase. Qualitative study results provided insights for the quantitative study and highlighted the benefits of switching from daratumumab IV to daratumumab SC as an improvement and a satisfactory change in patients’ treatment journey. Quantitative survey showed that patients were significantly less anxious, stressed and nervous before SC injections than IV infusions (mean score: 1.3, 1.1, 1.4 versus 2.1, 2.0, 2.0 respectively, p< 0.001), and significantly more reassured, ready/well-prepared, usual self and relieved (mean score: 3.8, 4.3, 3.7, 3.6 versus 3.0, 3.6, 3.1, 3.0 respectively, p< 0.001). Immediately after SC first injection, 96.5% patients were feeling well or very well versus 77.9% immediately after IV first infusion (p< 0.001). 97.3% patients were satisfied with their SC treatment versus 89.4% for the IV injection (p< 0.001). Patients spent significantly less time in hospital for an SC injection of daratumumab than for an IV infusion, 1.5 hours and 5.0 hours respectively (p< 0.001). In the UK, the differences between the two administration forms were less visible, likely because of confounding factors including a longer time passed since the switch from the IV to the SC form and administration of the survey.Conclusion: In line with results from other studies, the SC form of daratumumab had less impact on patients’ emotional burden than the IV form.Keywords: multiple myeloma, daratumumab, mode of administration, patients’ emotional burden, mixed method

Katherine S Monroe, Lindsey Amerson, William Bundy, Yulanda Greene, Gregory Jarvis, Jennifer Stever, Gaurav P Patel Department of Anesthesiology, Anesthesiologist Assistant Program, Emory University School of Medicine, Atlanta, GA, USACorrespondence: Gaurav P Patel, Department of Anesthesiology, Anesthesiologist Assistant Program, Emory University School of Medicine, 57 Executive Park South, Suite 300, Atlanta, GA, 30329, USA, Email gppatel@emory.eduBackground: The Anesthesiologist Assistant (AA) profession is gaining popularity, and as such, the number of applicants and the number of AA programs are also increasing. There is no published data on what makes a good AA student – multiple studies exist in this regard for anesthesiology residents and medical students. The Medical College Admissions Test (MCAT) and the Graduate Record Examination (GRE) have shown to have some correlation with student success in other health professions. There is no data to suggest that they can indicate potential success or academic problems during AA school. As such, this study evaluated the impact of these standardized test scores and student success in both the preclinical and clinical curricula at the Emory AA program.Methods: A retrospective analysis of MCAT scores and GRE scores was performed. 2-tailed Pearson coefficients were calculated to see if there was a relationship between higher MCAT and GRE scores and performance in our program.Results: 2- tailed Pearson coefficients showed a moderately strong correlation between MCAT scores and our AA program’s science curriculum. There was a weak correlation as well between GRE scores here. The correlation dropped slightly for the MCAT and performance during our clinical curriculum, and a similar drop was noted for the GRE.Discussion: Our study shows that the MCAT appears to more strongly correlated with better performance in both the science curriculum of our program and also with our clinical program. The study likely implies that the MCAT appears to be a better gauge as to how a student will do in an AA program in comparison to the GRE. Further studies are needed to understand how to appropriately admit students who will successfully complete the rigorous AA program curriculum both at Emory and beyond.Keywords: admission metrics, certified anesthesiologist assistant, anesthesia care team, student success, standardized test scores

Ghada H Naguib,1,2 Gamal S Abd El-Aziz,3 Abdulghani Mira,1 Rayyan A Kayal,4 Lulwa Al-Turki,5 Hisham Mously,5 Abeer Alnowaiser,6 Jumana Mazhar,7 Mohamed T Hamed5,8 1Department of Restorative Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Oral Biology, Cairo University School of Dentistry, Cairo, Egypt; 3Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Periodontology, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Oral and Maxillofacial Prosthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; ‬6Department of Pediatric Dentistry, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 7King Abdulaziz University, Jeddah, Saudi Arabia; 8Department of Fixed Prosthodontics, Cairo University School of Dentistry, Cairo, EgyptCorrespondence: Ghada H Naguib, Department of Restorative Dentistry, Faculty of Dentistry, King Abdulaziz University, P.O Box 80209, Jeddah, 21589, Saudi Arabia, Tel +966558190589, Email gnagieb@kau.edu.saBackground: Polymeric denture materials can be susceptible to colonization by oral microorganisms. Zein-coated magnesium oxide nanoparticles (zMgO NPs) demonstrate antimicrobial activity. The aim of this study was to investigate the antimicrobial effect and adherence of different oral microorganisms on hybrid polymeric denture materials incorporated with zMgO NPs.Methods: Five types of polymeric denture materials were used. A total of 480 disc-shaped specimens were divided by material type (n=96/grp), then subdivided by zMgO NPs concentration: control with no nanoparticles and other groups with zMgO NPs concentrations of 0.3%, 0.5% and 1% by weight. Characterization of the polymeric denture materials incorporating zMgO NPs was done, and the antimicrobial activity of all groups was tested against four types of microorganisms: 1) Streptococcus mutans, 2) Staphylococcus aureus, 3) Enterococcus faecalis and 4) Candida albicans. The samples underwent an adherence test and an agar diffusion test. Experiments were done in triplicates.Results: The characterization of the hybrid samples revealed variation in the molecular composition, as well as a uniform distribution of the zMgO NPs in the polymeric denture materials. All hybrid polymeric denture materials groups induced a statistically significant antimicrobial activity, while the control groups showed the least antimicrobial activity. The agar diffusion test revealed no release of the zMgO NPs from the hybrid samples, indicating the NPs did not seep out of the matrix.Conclusion: The zMgO NPs were effective in reducing the adherence of the tested microorganisms and enhancing the antimicrobial activity of the polymeric denture materials. This antimicrobial effect with the polymeric dentures could aid in resisting microbial issues such as denture stomatitis.Keywords: antimicrobial, nanoparticles, denture, magnesium oxide, biomaterial

Ying Shao,1,&ast; Qianfei Li,2,&ast; Meirong Bian,3 Yue Wang,1 Xiaohong Zhang4 1Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Nursing Department, Third hospital of Shanxi medical university, Shanxi Bethune hospital, Shanxi academy of medical sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Zhang, Nursing Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13453443366, Email zxhxb2013@126.comBackground: The “Key Points of the Core System of Medical Quality and Safety” (hereinafter referred to as the “Key Points”) was promulgated by the National Health Commission of China in 2018, requiring that nursing ward rounds should be carried out with reference to the three-level ward round system; In 2020 and 2022 editions of the “Evaluation Standards for Tertiary Hospitals”, which were implemented in China, required that nursing ward rounds should be carried out with reference to the “Key Points”. Additionally, the Action Plan for Comprehensively Improving Medical Quality (2023– 2025) also mentions the need to improve the quality of three-level ward rounds. However, there are no detailed guidelines regarding implementing “Nursing Three-level Ward Rounds”.Purpose: This study aimed to investigate the current situation of nursing three-level ward rounds in tertiary hospitals after the promulgation of the “Key Points of the Core System of Medical Quality and Safety” to provide insights and guidelines regarding relevant standards, so as to better implement of the requirements of “nursing ward rounds” in the “Evaluation Standards for Tertiary Hospitals” and “improving the quality of three-level ward rounds” in the “Action Plan”.Methods: A multi-center study was conducted in February 2024, including all tertiary public hospitals in the Shanxi Province, China. A questionnaire survey using the self-designed “Questionnaire on the Implementation of Nursing Three-level Ward Rounds” was carried out. The questionnaire included the basic information of the hospital and the implementation of the three-level (namely I, II, and III) rounds (including “five aspects”: ward round personnel, object, content, frequency, and record), which is expressed by quantity and composition ratio. Next is the text analysis method. First, the “five aspects” of the hospital that filled in the questionnaire survey with “nursing three-level ward rounds have been carried out” were assessed. Second, the five aspects of each hospital were assessed for consistency with the “Nursing Three-level Ward Rounds System” (hereinafter referred to as the “System”) of their respective hospitals.Third, the consistency of the “System” of the hospital with the “Key Points” was assessed. The results of the analysis of the former are expressed in terms of quantity and composition ratio; the results of the latter two were analyzed using Fisher’s exact test method to compare any differences.Results: Notably, 14 of the 67 tertiary public hospitals (20.9%) carried out nursing three-level ward rounds. There were 4– 10 situations in the five aspects of I, II, and III ward rounds filled in by the hospitals. The five aspects of the I, II, III ward rounds in 14 hospitals were significantly comparable with the “System”, which, in turn, was comparable with the “Key Points” (P < 0.05).Conclusion: Not all tertiary public hospitals in the Shanxi Province have not all carried out nursing three-level ward rounds. Furthermore, the five aspects of the hospitals that carried out nursing three-level ward rounds were not entirely consistent in terms of ward round personnel, object, content, frequency, and record. The filling in of the nursing three-level ward rounds carried out by the hospitals is inconsistent with the respective “System”; the “System” of the hospital is not in line with the “Key Points”.Impact on Nursing Work: Nursing administrators should be aware of the newly issued norms and requirements in their workplace, and revise the relevant systems in accordance with the norms and requirements in a timely manner. Additionally, the revision of the system should cover the core requirements of the norms and be practicable. The system should be supervised to ensure that 100% of the implementation is in accordance with the system.Keywords: nursing three-level ward rounds, tertiary hospitals, core system, current status of ward round, multi-center

Hany G Attia,1 Mai Abdelhalim Hamouda,2 Saeed Alasmari,3 Dalia F El-Telbany,4 Zaenah Zuhair Alamri,5 Safa H Qahl,5 Mohammad Y Alfaifi,6 Majid Mohammad Al-Sawahli,7 Sara Abd El Wahed8 1Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia; 2Department of Oral Pathology, Faculty of Dentistry, King Salman International University, El-Tur, Egypt; 3Department of Biology, College of Science and Arts, Najran University, Najran 1988, Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo, Egypt; 5Department of Biological Science, College of Science, University of Jeddah, Jeddah, Saudi Arabia; 6Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia; 7Department of Pharmaceutics, College of Pharmacy, The Islamic University, Najaf, Iraq; 8Department of Oral Pathology, Faculty of Dentistry, The British University in Egypt, Cairo, EgyptCorrespondence: Majid Mohammad Al-Sawahli, Department of Pharmaceutics, College of Pharmacy, The Islamic University, Najaf, Iraq, Tel +201119925299, Email majidalsawahli@gmail.com Hany G Attia, Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia, Tel +966555857605, Email hgattia@nu.edu.saPurpose: : Polyvinyl alcohol-capped silver nanostructures (cAgNSs) were investigated in order to enhance the cytotoxicity, pro-apoptotic, and oxidant patterns of in human laryngeal carcinoma Hep-2 cells by employing a 50 mT electromagnetic field (LEMF) for 30 min.Methods: Wet chemical reduction was used to synthesize the cAgNSs, and after they had been capped with polyvinyl alcohol, they were specifically examined for particle size analysis and structural morphology. To visualize how the silver may attach to the protein targets, a molecular docking study was conducted. Estimation of cytotoxicity, cell cycle progression supported by mRNA expression of three apoptotic-promoting genes and one apoptotic-resisting.Results: Particle size analysis results were a mean particle size of 157.3± 0.5 nm, zeta potential value of − 29.6 mV± 1.5 mV, and polydispersity index of 0.31± 0.05. Significantly reduction of IC50 against Hep-2 cells by around 6-fold was concluded. Also, we obtained suppression of the proliferation of Hep-2 cells, especially in the G0/G1 and S phases. Significant enhanced mRNA expression revealed enhanced induced CASP3, p53, and Beclin-1 mediated pro-apoptosis and induced NF-κB mediated autophagy in Hep-2 cells. Augmented levels of GR, ROS and MDA as oxidative stress biomarkers were also obtained. HE staining of Hep-2 cells exposed to cAgNSs and LEMF confirmed the enhanced apoptotic potential comparatively.Conclusion: By conclusion, the developed nano-sized structures with the aid of extremely-low frequency electromagnetic field were successful to fortify the anti-cancer profile of cAgNSs in Hep-2 cells. Keywords: electromagnetic field, silver nanoparticles, apoptosis, laryngeal carcinoma

Harini Sriraman, Saleena Badarudeen, Saransh Vats, Prakash Balasubramanian School of Computer Science and Engineering, Vellore Institute of Technology, Chennai, 600127, IndiaCorrespondence: Prakash Balasubramanian, School of Computer Science Engineering, Vellore Institute of Technology, Chennai, Tamil Nadu, India, Tel +91-044-39931228, Fax +91-044-39932555, Email Prakash.bala@vit.ac.inAbstract: Deep Learning (DL) drives academics to create models for cancer diagnosis using medical image processing because of its innate ability to recognize difficult-to-detect patterns in complex, noisy, and massive data. The use of deep learning algorithms for real-time cancer diagnosis is explored in depth in this work. Real-time medical diagnosis determines the illness or condition that accounts for a patient’s symptoms and outward physical manifestations within a predetermined time frame. With a waiting period of anywhere between 5 days and 30 days, there are currently several ways, including screening tests, biopsies, and other prospective methods, that can assist in discovering a problem, particularly cancer. This article conducts a thorough literature review to understand how DL affects the length of this waiting period. In addition, the accuracy and turnaround time of different imaging modalities is evaluated with DL-based cancer diagnosis. Convolutional neural networks are critical for real-time cancer diagnosis, with models achieving up to 99.3% accuracy. The effectiveness and cost of the infrastructure required for real-time image-based medical diagnostics are evaluated. According to the report, generalization problems, data variability, and explainable DL are some of the most significant barriers to using DL in clinical trials. Making DL applicable for cancer diagnosis will be made possible by explainable DL.Keywords: artificial intelligence, AI, machine learning, DL, CNN, healthcare, real-time diagnosis, classification, image processing, elastography, feedforward neural network

Jia-Xin Guan,1,2 Yan-Ling Wang,1,2,&ast; Jia-Lin Wang1,2,&ast; 1Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Institute of Ophthalmology, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Lin Wang; Yan-Ling Wang, Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China, Email wangjialin@bjmu.edu.cn; wangyanl@ccmu.edu.cnAbstract: Subretinal injection (SR injection) is a commonly used method of ocular drug delivery and has been mainly applied for the treatment of neovascular age-associated macular degeneration (nAMD) and sub-macular hemorrhage (SMH) caused by nAMD, as well as various types of hereditary retinopathies (IRD) such as Stargardt’s disease (STGD), retinitis pigmentosa (RP), and a series of fundus diseases such as Leber’s congenital dark haze (LCA), choroidal defects, etc. The commonly used carriers of SR injection are mainly divided into viral and non-viral vectors. Leber’s congenital amaurosis (LCA), choroidal agenesis, and a series of other fundus diseases are also commonly treated using SR injection. The commonly used vectors for SR injection are divided into two categories: viral vectors and non-viral vectors. Viral vectors are a traditional class of SR injection drug carriers that have been extensively studied in clinical treatment, but they still have many limitations that cannot be ignored, such as poor reproduction efficiency, small loading genes, and triggering of immune reactions. With the rapid development of nanotechnology in the treatment of ocular diseases, nanovectors have become a research hotspot in the field of non-viral vectors. Nanocarriers have numerous attractive properties such as low immunogenicity, robust loading capacity, stable structure, and easy modification. These valuable features imply greater safety, improved therapeutic efficacy, longer duration, and more flexible indications. In recent years, there has been a growing interest in nanocarriers, which has led to significant advancements in the treatment of ocular diseases. Nanocarriers have not only successfully addressed clinical problems that viral vectors have failed to overcome but have also introduced new therapeutic possibilities for certain classical disease types. Nanocarriers offer undeniable advantages over viral vectors. This review discusses the advantages of subretinal (SR) injection, the current status of research, and the research hotspots of gene therapy with viral vectors. It focuses on the latest progress of nanocarriers in SR injection and enumerates the limitations and future perspectives of nanocarriers in the treatment of fundus lesions. Furthermore, this review also covers the research progress of nanocarriers in the field of subretinal injection and highlights the value of nanocarrier-mediated SR injection in the treatment of fundus disorders. Overall, it provides a theoretical basis for the application of nanocarriers in SR injection.Keywords: nanoparticles, subretinal injection, drug delivery, non-viral vectors, nanomedicine, gene therapy

Chunjiao Lu,&ast; Xuewei Wu,&ast; Xin Meng,&ast; Yi Liu, Ting Yang, Yan Zeng, Yang Chen, Yishan Huang, Zhou Fang, Xiaojun Yang, Juanjuan Luo Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Yang; Juanjuan Luo, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, People’s Republic of China, Email yangx@stu.edu.cn; 15jjluo1@stu.edu.cnIntroduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood.Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h.Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish.Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.Keywords: AgNPs, focal adhesion, cardiac development, zebrafish

Henny Suzana Mediani,1,&ast; Fidy Randy Sada,2,&ast; Aan Nuraeni,3,&ast; Muhammad Arsyad Subu4,&ast; 1Department of Pediatric Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Faculty of Nursing, Universitas Katolik De La Salle Manado, Manado, Indonesia; 3Department of Critical Care of Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, Indonesia; 4Nursing Program, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates&ast;These authors contributed equally to this workCorrespondence: Henny Suzana Mediani, Department of Pediatric Nursing, Faculty of Nursing, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia, Tel +62 822-1739-1965, Email henny.mediani@unpad.ac.idBackground: In the Intensive Care Unit (ICU), it is vital to meticulously monitor symptoms and thoroughly understand the treatment objectives for critically ill patients. This highlights the necessity of integrating palliative care in this environment. Despite the potential advantages, several barriers impede the effective integration of palliative care in the ICU. Notably, many healthcare professionals (HCPs) in Indonesian ICUs have not fully leveraged the incorporation of palliative care.Purpose: This study aimed to investigate and clarify the experiences of healthcare providers (HCPs) involved in administering palliative care to ICU patients in Indonesia.Methods: This research employed a qualitative descriptive phenomenological approach. Semi-structured, in-depth individual interviews were conducted with four nurses and three doctors working in an Indonesian hospital. Colaizzi’s method was used for data analysis.Results: The analysis identified six themes from the interviews, reflecting the experiences of healthcare professionals in delivering palliative care in the ICU. These themes are: 1) Provide Professional Caring, 2) Caring and curing collaboration, 3) Quality Intensive Communication, 4) End-of-Life Care, 5) Controlling Feelings, and 6) Provide Holistic Caring.Conclusion: Providing care for ICU patients demands not only the expertise of HCPs but also compassion, communication skills, and a holistic approach to patient care. By offering comprehensive palliative care in the ICU, healthcare professionals can address the diverse needs of patients and their families, promoting comfort, respect, and an improved quality of life throughout the illness. This inclusive approach enhances the experience for both patients and their families while supporting healthcare providers in delivering empathetic and patient-centered care. It is recommended that hospitals develop policies to enhance palliative care services in Indonesia.Keywords: ICU patient, healthcare professionals, palliative care

Andrej Jen&ccaron;a,1,&ast; David K Mills,2,&ast; Hadis Ghasemi,3,&ast; Elham Saberian,4,&ast; Andrej Jen&ccaron;a,1 Amir Mohammad Karimi Forood,5 Adriána Petrášová,1 Janka Jen&ccaron;ová,1 Zeinab Jabbari Velisdeh,2 Hadi Zare-Zardini,6 Meysam Ebrahimifar7 1Klinika of Stomatology and Maxillofacial Surgery Akadémia Košice Bacikova, UPJS LF, Kosice, Slovakia; 2Molecular Science and Nanotechnology, College of Engineering and Science, Louisiana Tech University, Ruston, LA, 71272, USA; 3Department of Chemistry, College of Art and Science, Southern Illinois University Edwardsville, Edwardsville, IL, USA; 4Pavol Jozef Šafárik University, Klinika and Akadémia Košice Bacikova, Kosice, Slovakia; 5Biomedical Engineering Department, University of Connecticut, Storrs, CT, USA; 6Department of Biomedical Engineering, Meybod University, Meybod, Iran; 7Department of Toxicology, Faculty of Pharmacy, Islamic Azad University, Shahreza Branch, Shahreza&ast;These authors contributed equally to this workCorrespondence: Hadi Zare-Zardini; Meysam Ebrahimifar, Email hzare@meybod.ac.ir; ebrahimifar67@gmail.comAbstract: Natural products have proven to be promising anti-cancer agents due to their diverse chemical structures and bioactivity. This review examines their central role in cancer treatment, focusing on their mechanisms of action and therapeutic benefits. Medicinal plants contain bioactive compounds, such as flavonoids, alkaloids, terpenoids and polyphenols, which exhibit various anticancer properties. These compounds induce apoptosis, inhibit cell proliferation and cell cycle progression, interfere with microtubule formation, act on topoisomerase targets, inhibit angiogenesis, modulate key signaling pathways, improve the tumor microenvironment, reverse drug resistance and activate immune cells. Herbal anti-cancer drugs offer therapeutic advantages, particularly selective toxicity against cancer cells, reducing the adverse side effects associated with conventional chemotherapy. Recent studies and clinical trials highlight the benefits of herbal medicines in alleviating side effects, improving tolerance to chemotherapy and the occurrence of synergistic effects with conventional treatments. For example, the herbal medicine SH003 was found to be safe and potentially effective in the treatment of solid cancers, while Fucoidan showed anti-inflammatory properties that are beneficial for patients with advanced cancer. The current research landscape on herbal anticancer agents is extensive. Numerous studies and clinical trials are investigating their efficacy, safety and mechanisms of action in various cancers such as lung, prostate, breast and hepatocellular carcinoma. Promising developments include the polypharmacological approach, combination therapies, immunomodulation and the improvement of quality of life. However, there are still challenges in the development and use of natural products as anti-cancer drugs, such as the need for further research into their mechanisms of action, possible drug interactions and optimal dosage. Standardizing herbal extracts, improving bioavailability and delivery, and overcoming regulatory and acceptance hurdles are critical issues that need to be addressed. Nonetheless, the promising anticancer effects and therapeutic benefits of natural products warrant further investigation and development. Multidisciplinary collaboration is essential to advance herbal cancer therapy and integrate these agents into mainstream cancer treatment.Keywords: herbal, anti-cancer, chemotherapy, cancer therapy, drug resistance

Formål: Å undersøke helsearbeidere ved et aktivitetssenter for personer med demens sine erfaringer med å delta på kunstverksted på en kulturinstitusjon sammen med personer som lever med en demenssykdom. Metode: En kvalitativ studie med deltagende observasjon, spørreskjema og fokusgruppeintervju. Tematisk analyse: To av de fire ledsagende helsearbeiderne som deltok i studien, deltok også i analysen av det empiriske materialet. Resultat: Helsearbeidernes erfaringer kan sammenfattes i to overordnede tema: «en styrket relasjon» og «en endret kompetanse». Det første temaet var et resultat av tre faktorer: For det første at de deltok i kunstnerisk samskaping med deltakerne med demens utenfor den vante omsorgssituasjonen. For det andre at samskapingen ga dem en felles erfaring som påvirket pleier-pasient-rollene. For det tredje at de på nye måter ble kjent med deltakerne med demenssykdom. At relasjonen til deltakerne ble styrket, førte også til at helsearbeiderne i etterkant prøvde ut aktiviteter de ikke hadde gjort før. Dette funnet beskrives som «en endret kompetanse». Originalitet: Artikkelen bidrar med kunnskap om helsearbeidernes utbytte av å delta i kunstnerisk samskaping sammen med personer med demens, noe som er underbelyst i forskningen. Resultatene viser hvilket potensial samskaping kan ha som metode når man planlegger kunst- og kulturtilbud hvor personer med demens og helsearbeidere deltar sammen.

Purpose. Sex determination in forensic anthropology is an essential step for medicolegal purposes and very important for identification, as the number of possible matches will be halved. A dental profile includes all the individual dental traits and dimensions which can provide significant information on such human biological problems as the genetic relationships between populations and human environmental adaptation. The purpose of this research was to determine the sex differences in dental measurements of canines, inter-canine width, and canine indices in Bulgarians. Material and Methods. The study included 169 subjects of Bulgarian origin in the age group of 20 – 40 years. Buccolingual, mesio-distal and cervicoincisal diameters of canines and inter-canine width were measured by Dentistry Sliding Vernier Caliper and analyzed with SPSS 28.0. Maxillary and mandibular canine indices were calculated. Results. Mesio-distal and cervicoincisal dimensions of upper canines, inter-canine width and mandibular canine index exhibited statistically significant differences with a high degree of significance between males and females in contrast with the maxillary canine index of Bulgarian males and females, which revealed no statistically significant differences. Conclusion. In accordance with similar odontometric studies, canines, inter-canine width, and mandibular canine index may differentiate both sexes successfully, and thus they can be reliable predictors in forensic identification.

Background: Studies have demonstrated that high-speed jaw-opening exercises are effective in improving swallowing function. However, there has been no objective tool available for monitoring jaw-opening pace. This study aimed to develop an objective tool for monitoring and validating jaw-opening pace and compare it between young and old ages from different age groups. Materials and methods: A load cell plug-in jaw pad connected to an automatic recording and analysis system was used to record jaw-opening motions for offline analysis. We recruited 58 healthy volunteers from different age groups (20–39 y/o; 40-59y/o; 60-79y/o). During a 2-min recording session, each participant was instructed to fully open and close their jaw as quickly as possible while wearing a sensor. Bland-Altman plot, paired t-test and Pearson's correlation test were used to compare the number of jaw-opening motions between manual counting and automatic software analysis. The number of jaw-opening motions during the 2-min recording was compared between the three age groups. Results: Automated analysis of jaw-opening pace was efficient and equally comparable with the traditional manual counting method across the three age groups. A declining trend in jaw-opening pace among the old age group was found but with no statistically significant difference. Conclusion: A jaw-opening motion monitoring tool with reliable automatic pace analysis software was validated in young and old ages The jaw-opening pace demonstrated a tendency to decline with age.

Background: Non-intubated video-assisted thoracoscopic surgery combines a minimally invasive technique with multimodal locoregional analgesia to enhance recovery. The mainstay sedation protocol involves propofol and fentanyl. Dexmedetomidine, given its opioid-sparing effect with minimal respiratory depression, facilitates sedation in non-intubated patients. This study aimed to evaluate the efficacy of dexmedetomidine during non-intubated video-assisted thoracoscopic surgery. Methods: A total of 114 patients who underwent non-intubated video-assisted thoracoscopic surgery between June 2015 and September 2017 were retrospectively evaluated. Of these, 34 were maintained with dexmedetomidine, propofol, and fentanyl, and 80 were maintained with propofol and fentanyl. After a 1:1 propensity score-matched analysis incorporating sex, body mass index, American Society of Anesthesiologists classification, pulmonary disease and hypertension, the clinical outcomes of 34 pairs of patients were assessed. Results: The dexmedetomidine group showed a significantly lower opioid consumption [10.3 (5.7–15.1) vs. 18.8 (10.0–31.0) mg, median (interquartile range); P = 0.001] on postoperative day 0 and a significantly shorter postoperative length of stay [3 (2–4) vs. 4 (3–5) days, median (interquartile range), P = 0.006] than the control group. During operation, the proportion of vasopressor administration was significantly higher in the dexmedetomidine group [18 (53) vs. 7 (21), patient number (%), P = 0.01]. On the other hand, the difference of the hypotension and bradycardia incidence, short-term morbidity and mortality rates between each group were nonsignificant. Conclusion: Adding adjuvant dexmedetomidine to propofol and fentanyl is safe and feasible for non-intubated video-assisted thoracoscopic surgery. With its opioid-sparing effect and shorter postoperative length of stay, dexmedetomidine may enhance recovery after surgery.

Background: Breast cancer-related lymphedema (BCRL) is one of the debilitating complications after breast cancer treatment. Several forms of patient-reported outcome measures (PROMs) were developed to evaluate the severity of BCRL based on the patients’ perspective. LYMPH-Q Upper Extremity Module is a newly developed questionnaire for BCRL. This study aimed to demonstrate the process of translation and cultural adaption from English to Mandarin Chinese. Methods and results: The translation process followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines for the translation and cultural adaption of PROM. The process included four steps: forward translation, back translation, back translation review, and patient interviews. In total, five patients with BCRL were recruited for patient interviews.The forward translation step involved two professional translators whose native language was Mandarin Chinese. A reconciled translated version was produced. In the back translation step, the reconciled translated version in Mandarin Chinese was sent to another professional translator whose native language was English. The back-translated version in English was sent back to the developer of LYMPH-Q for review. In this step, 22 items were revised. In the final step of patient interviews, 15 items were revised based on the patients’ feedback. Conclusion: The development of Mandarin Chinese version of LYMPH-Q Upper Extremity Module and its utilization in conjunction with the existing objective measures could provide a more well-rounded picture of the status of patients with BCRL worldwide.

Unlike hepatitis C virus (HCV) genotype (GT) 6, which is widely circulated in Southeast Asia and South China, GT 6 was not reported in Taiwan until 2006. GT 1b and 2a, also known as global HCV subtypes, have been reported as major GTs circulating in Taiwan. Because of improvement in genotyping kits and sequencing techniques for the subtyping of HCV, an increasing number of GT 6 subtypes have been reported, especially subtype 6a among intravenous drug users with human immunodeficiency virus infection after an outbreak since 2003. Thus, HCV GT 6 infection is regarded to be closely associated with injection drug use. However, recently, we found an unexpectedly high GT 6 prevalence in the general population in Tainan, southern Taiwan. Most of these GT 6 samples belonged to a putative novel subtype closely related to 6g and 6w instead of 6a. Phylogenetic analyses indicated that this putative 6g-related novel subtype and 6w could be indigenous in southern Taiwan for centuries. Southern Taiwan could be the origin of HCV subtype 6w. This finding might change the perspective of HCV epidemiology in Taiwan.

Background/purpose: Zirconia has been a popular material in dental implantology with good biocompatibility. But few research focused on its application in implant drills. This study aimed to investigate the physical, thermal, and biological effects on using the zirconia and stainless-steel drills for implant bone site preparation. Methods: We performed a series of experiments to evaluate the physical wearing properties of zirconia and stainless-steel drills of identical diameter and similar shape. During the implant site preparation thermal test, we subjected both drills onto a resin-embedded bone, utilizing a thermal couple device without irrigation. Moreover, we conducted a cell study by collecting bone cells in vivo while preparing the implant site with both tested drills. The cell activity was evaluated through cell proliferation colorimetric analysis (XTT) and alkaline phosphatase (ALP) activity measurements. Results: The zirconia drill outperforms the stainless-steel drill in terms of requiring less force, maintaining stability over repeated cutting tests, and generating lower temperatures during drilling (stainless-steel drill: 45.48 ± 1.31 °C; zirconia-coated drill: 32.98 ± 1.21 °C, P = 0.000247). Meanwhile, both types of drills show similar results in XTT colorimetric analysis and ALP activity test. Conclusion: The thermal effect study is more favorable for using the zirconia drill than the stainless-steel drill for bone preparation. Cytological analysis indicate that the zirconia drill produces a similar impact on bone cells activity as the stainless-steel drill. Therefore, we conclude that the zirconia drills offer a good cutting effect similar to currently available stainless-steel drills in various aspects.

Background: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. Methods: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. Results: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432–5p and miRNA-382–3p were upregulated in patients with abnormal SSS. Conclusion: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Background/Purpose: Human nerve development is vital, affecting trauma recovery and dental issues. Early embryonic clues link nerves to tooth development via factors like Wnt and Hedgehog pathways. Centrosomes play a role, and centriole issues can disrupt oral development, as in oral facial digital syndrome type 1. This study aimed to delve deeper into the role and influence of centrioles on the development of dental nerves. Methods: Cell migration assessed by co-culturing mouse neural tissue and human dental pulp stem cells (DPSCs). Centrioles were fluorescently stained, and their positions observed with confocal microscopy. Centrinone was employed to inhibit centriole activity, evaluating its impact on cell mobility under activity inhibition. Results: As the distance between nerve tissue and DPSCs decreased, more DPSCs had centrioles near nerve tissue. Co-culture with nerve tissue increased DPSCs migration toward it. In contrast, DPSCs cultured alone or with fibroblasts showed weaker migration, indicating neural tissue's attractive influence. The addition of 125 nM centrinone halted cell migration and centriole polymerization. After centrinone removal over two days, centrioles returned to normal, suggesting continued motility inhibition. Conclusion: Centrioles direct cell movement and polarization. There are two scenarios: centrioles at the cell center with the nucleus moving backward (as in NIH3T3 cells) and both cells and centrioles moving forward (as in DPSCs). DPSCs' attraction to neural tissue may shed light on nerve guidance by tooth germs, aiding embryonic cell differentiation into nerves. However, further in vivo and in vitro studies are needed to confirm the specific mechanism.

Background: To examine the efficacy and safety of patisiran, an RNA interference therapeutic, in patients from Taiwan with hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy. Methods: The APOLLO phase 3 trial included patients from Taiwan who received patisiran 0.3 mg/kg intravenously or placebo once every 3 weeks (q3w) for 18 months (18 M), followed by patisiran 0.3 mg/kg q3w in an ongoing global open-label extension (OLE) study. The primary endpoint was change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 18 M. Results: Eighteen Taiwanese patients were enrolled in APOLLO (patisiran, n = 8; placebo, n = 10; all A97S gene variant) and 14 continued in the global OLE. In this Taiwanese sub-population, beneficial treatment effects at 18 M were observed in mNIS+7 (least squares mean difference in change from baseline [patisiran-placebo], −26.5 points; 95% confidence interval: −45.5, −7.5). Patients who switched from placebo to patisiran demonstrated slowing of polyneuropathy progression at month 12 in the global OLE, while those who received patisiran in APOLLO maintained the beneficial treatment effects. Patisiran had an acceptable safety profile in the Taiwanese sub-population. Conclusion: This analysis suggests that patisiran is well tolerated and may provide a substantial clinical benefit for Taiwanese patients with hATTR amyloidosis with polyneuropathy. Trial registration information: The studies were registered on the ClinicalTrials.gov. The APOLLO study ClinicalTrials.gov identifier is NCT01960348 (https://clinicaltrials.gov/ct2/show/NCT01960348), with the registration date of October 10, 2013, and the first patient was enrolled on December 13, 2013. For the global OLE, the ClinicalTrials.gov identifier is NCT02510261 (https://clinicaltrials.gov/ct2/show/NCT02510261) with the registration date of July 29, 2015, and the first patient was enrolled on July 13, 2015. Classification of evidence: This study provides Class II evidence that treatment with patisiran is safe and efficacious in Taiwanese patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy.

Background: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. Methods: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Background/purpose: This study addresses the delicate balance between healthcare personnel burnout and medical accessibility in the context of endovascular thrombectomy (EVT) services in urban areas. We aimed to determine the minimum number of hospitals providing EVT on rotation each day without compromising patient access. Methods: Employing an optimization model, we developed shift schedules based on patient coverage rates and volumes during the pre-pandemic (2016–2018) and pandemic (2019–2021) periods. Starting with a minimum of two hospitals on duty per day, we gradually increased to a maximum of eight. Patient coverage rates, defined as the proportion of patients meeting bypass criteria and transported to rotating hospitals capable of EVT, were the primary outcomes. Sensitivity analyses explored the impact of varying patient transport intervals and accumulating patients over multiple years. Results: Results from 7024 patient records revealed patient coverage rates of 92.5% (standard deviation [SD] 2.8%) during the pre-pandemic and 91.4% (SD 2.8%) during the pandemic, with at least two rotating hospitals daily. No significant differences were observed between schedules based on the highest patient volume and coverage rate months. A patient coverage rate of 98.99% was achieved with four rotating hospitals per day during the pre-pandemic period, with limited improvement beyond this threshold. Changing patient transport intervals and accumulating patients over six years (p = 0.83) had no significant impact on coverage rates. Conclusion: Our optimization model supports reducing the number of daily rotating hospitals by half while preserving a balance between patient accessibility and alleviating strain on medical teams.

Background: This study aims to determine whether end-stage renal disease (ESRD) is a true contraindication for extracorporeal membrane oxygenation in adult patients. Materials and methods: Adult patients who received VA-ECMO at National Taiwan University Hospital between January 2010 and December 2021 were included. Patients who received regular dialysis before the index admission were included in the ESRD group. The primary outcome was in-hospital mortality. Results: 1341 patients were included in the analysis, 121 of whom had ESRD before index admission. The ESRD group was older (62.3 versus 56.8 years; P

Background: Acute myeloid leukemia (AML) is a hematological malignancy with a heterogeneous prognosis. Novel markers are required to accurately assess the prognosis and formulate treatment plans. Methods: The association of ARHGAP family genes with prognostic value in acute myeloid leukemia (AML) was assessed using public databases (CCLE, GEPIA, TCGA, and GEO). Results: Elevated expression of ARHGAP43 (SH3BP1) was associated with poor prognosis in patients with acute myeloid leukemia. ARHGAP43 (SH3BP1) expression was higher in the poor/adverse prognosis (P

Abstract Ischemic heart disease is the most prevalent cause of death worldwide affecting both the gender of all age groups. The high mortality rate is due to damage of myocardial tissue that emanates at the time of myocardial ischemia and re-oxygenation, thus averting reperfusion injury is recognized as a potential way to reduce acute cardiac injury and subsequent mortality. Flavonoids are polyphenol derivatives of plant origin and empirical shreds of evidence substantiate their numerous activities such as antioxidant, anti-inflammatory, anti-apoptotic, and anti-thrombotic activity, leading to their role in cardio protection. Recent investigations have unveiled the capacity of flavonoids to impede pivotal regulatory enzymes, signaling molecules, and transcription factors that orchestrate the mediators participating in the inflammatory cascade. The present comprehensive review, dwells on the preclinical studies on the effectiveness of flavonoids from the year 2007 to 2023, for the prevention and therapeutics for myocardial ischemia-reperfusion injury. Graphical Abstract

Abstract Background Vision impairment and blindness are significant global public health challenges, particularly in low- and middle-income countries, where access to eye care services remains limited. India has significantly reduced the prevalence of Blindness and Vision Impairment (VI) over the last two decades. This was achieved with the help of greater investments towards blindness control programs. The use of utility values helps in conducting economic evaluations of various eye health programs and empirically justify investing in these programs. This study aimed to estimate utility values for various childhood eye conditions in central India using the EuroQol-Five-Dimension-Youth (EQ-5D-Y) instrument. Methods This is a before and after study with data collected at two time points for few participants and at only one time point for others. This study was undertaken at Shri Sadguru Netra Chikitsalaya (SNC) and included children representing central and north India. Participants were randomly sampled in the hospital. After comprehensive eye examination, participants completed the EuroQol-Five-Dimension-Youth (EQ-5D-Y) questionnaire along with EuroQol Visual Analogue Scale (EQ VAS) measurement to elicit their health state for their condition which was repeated after six months post-intervention to measure the change in utility value. We have used Indonesian value set to analyze the preference scores of each dimension of EQ-5D-Y. Results Utility values of 16 eye conditions were estimated at baseline and seven conditions were followed up for post-intervention utility value estimation. There is a statistically significant improvement in the utility values post-intervention amongst six conditions. Blindness and Pediatric cataract had the greatest change (0.23 and 0.2 respectively) in utility value whereas mild Vision Impairment (VI) showed the least change (0.02) in the utility value post-intervention. Blindness had the lowest baseline (0.62) and post-intervention (0.85) utility value. Conclusion The utility values estimated in this study showed that generic measures such as EQ-5D-Y may be used to elicit health states for various eye conditions amongst children. These estimates are helpful in undertaking cost-utility analyses of eye health programs and interventions aimed at these eye conditions.

Abstract Introduction This study comprehensively investigates the changes in healthcare utilization among chronic patients with regular outpatient visits to hospitals after the occurrence of Covid-19. The research examines whether patients altered their originally regular medical attendance frequencies due to the pandemic and explores potential negative impacts on the health conditions of those irregular attendees post-pandemic. Methods Data for this study were sourced from a database at a medical center in Taiwan. The subjects were chronic patients with regular hospital outpatient visits before the Covid-19 outbreak. The study tracked medical utilization patterns from 2017 to 2022 for different patient characteristics and outpatient behaviors, employing statistical methods such as Repeated Measures ANOVA and Generalized Estimating Equation to analyze changes in healthcare utilization and health status during the post-pandemic period. Results The results reveal that, compared to the regular group, chronic patients with irregular outpatient visits during the post-pandemic period exhibited a decrease of 5.85 annual outpatient visits, a reduction of NT$20,290.1 in annual medical expenses, and a significantly higher abnormality rate in average biochemical test results by 0.9%. Conclusions The findings contribute to understanding the impact of the Covid-19 pandemic on healthcare utilization and health conditions among outpatient chronic disease populations. In response to the new medical landscape in the post-pandemic era, proactive suggestions are made, including providing telemedicine outpatient services and referral-based medical care to meet the needs of the target population, ensuring a continuous and reassuring healthcare model for chronic patients, and mitigating the operational impacts of public health emergencies on hospitals.

Abstract Objective To estimate the economic impact for the society, generated as a consequence of the onset of loss of vision and irreversible legal blindness, for the main ophthalmologic diseases in Spain: glaucoma, diabetic retinopathy (DR), diabetic macular edema (DME), age-related macular degeneration (AMD) and high myopia (HM). Methods A cost analysis model was developed to estimate the economic burden of glaucoma, DR, DME, AMD and HM over a 10-year time horizon (2021-2030), from a societal perspective in Spain. The epidemiological and economic parameters used in the model were obtained through a literature review. Prevalence, incidence, and progression stages were used to establish the epidemiological flows. Annual costs per patient from publications were included and classified into direct healthcare, direct non-healthcare and indirect costs. Costs from other countries were converted based on purchasing-power-parity (€EUR, PPP). Epidemiological parameters about population and cost results were validated by a panel of experts. All costs were adjusted to euros, 2021 (€, 2021), and using the Consumer Price Index (CPI) of the last 10 years, extrapolated to 2030 euros (€, 2030). Results It was estimated that the total population of patients with the main diseases pathologies (glaucoma, DR, DME, AMD and HM) will increase to 7.99 million patients by 2030, representing an increase of 103%. The total cost by 2030 of all pathologies would amount to 99.8 billion euros. Direct non-healthcare costs account for the largest item (44%), followed by loss of productivity costs (38%), and direct healthcare costs (18%). The pathologies with the highest cumulative costs will be glaucoma (€33.6 billion) and DME (€19.8 billion).The greatest increment costs compared to 2021 will likely be generated by pathologies related to diabetes mellitus, such as DR (703%) and DME (317%). Conclusions Knowing the costs associated with the pathologies that generate loss of vision and irreversible legal blindness is essential to understand the socioeconomic impact associated with these pathologies. Furthermore, the high cost of treating these diseases makes necessary to coordinate efforts between administrations, together with the support of patient associations, to meet their needs.

Abstract We investigate the factors that influence the variance in hospital charges and inpatient care for kidney transplant cases in the US. Using the AHRQ’s (Agency for Healthcare Research and Quality) HCUP’s (Hospital Cost and Utilization Project) NIS (National Inpatient Sample) database, we find that variance in hospital charges and inpatient care is driven by patient demographics and hospital variables. We find that variance in hospital charges and inpatient care is determined by patient-specific factors including age, gender, race, and income, and hospital factors such as size, type, and location. Our results provide a deeper understanding of the non-clinical factors that impact hospital charges and inpatient care for kidney transplant patients.

Abstract Background Rape is one of the trauma incidents with the highest risk of subsequent post-traumatic stress disorder. Early interventions, such as prolonged exposure therapy (PE), have shown promise in preventing PTSD following a sexual assault. The primary objective of this internal pilot trial was to examine the feasibility of the EIR study protocol, which used modified prolonged exposure therapy (mPE) as a preventive intervention after rape. Methods This parallel two-arm clinical pilot study involved three sexual assault centers (SACs) in Trondheim, Oslo, and Vestfold, with data collected between June 2022 and March 2023. Women seeking assistance at one of these three SACs within 72 h after rape or attempted rape received acute medical treatment and forensic examinations. Women who wanted further psychosocial treatment were, if eligible and consenting, recruited to complete baseline assessments and a clinical interview before being randomized to one of two study arms. The intervention group prescribed up to five sessions of modified PE (mPE) in addition to treatment as usual (TAU), starting within the first 14 days after the rape incident, followed by weekly sessions. The other group received TAU. The present pilot evaluation is based on 22 participants, i.e., nine mPE + TAU and 13 TAU alone. Primary outcomes were predefined progression criteria regarding recruitment, retention, intervention implementation, a harm reporting system, and applying biological measurements and actigraphy. Results During the 6-month recruitment period, 235 women visited the three SACs. After eligibility screening and consent, 22 (9.4%) women were randomized. Three months later, 14 (63.6%) participants completed the final assessments. Intervention implementation was successful using trained SAC personnel to deliver mPE. The harm reporting system was used according to the study’s plan, and adverse and serious adverse events were detected during the trial. The biological measurements and actigraphy had substantial missing data but were still considered usable for statistical analyses. Conclusion It may be feasible to conduct a full-scale RCT of early intervention after rape by comparing mPE + TAU to TAU alone. Minor design refinements were made to the protocol to enhance the main study outcome. Trial registration ClinicalTrials.gov Identifier: NCT05489133. Registered on 15 July 2022, retrospectively.

Abstract Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs). These small membrane-bound particles can modulate immune responses within the inflammatory microenvironment of damaged cartilage. To launch the clinical potential of EVs, they can be isolated from various cell types through several techniques. EVs can carry various bioactive molecules and anti-inflammatory or pro-regenerative drugs, deliver them directly to the affected joints, and affect the behavior of injured cells, making them a compelling choice for targeted therapy and drug delivery in RA patients. However, there are still several challenges and limitations associated with EV-based therapy, including the absence of standardized protocols for EV isolation, characterization, and delivery. This review provides a comprehensive overview of the cellular sources of EVs in RA and delves into their therapeutic potential and the hurdles they must overcome.

Abstract Background Primary human hepatocytes (PHHs) are highly valuable for drug-metabolism evaluation, liver disease modeling and hepatocyte transplantation. However, their availability is significantly restricted due to limited donor sources, alongside their constrained proliferation capabilities and reduced functionality when cultured in vitro. To address this challenge, we aimed to develop a novel method to efficiently expand PHHs in vitro without a loss of function. Methods By mimicking the in vivo liver regeneration route, we developed a two-step strategy involving the de-differentiation/expansion and subsequent maturation of PHHs to generate abundant functional hepatocytes in vitro. Initially, we applied SiPer, a prediction algorithm, to identify candidate small molecules capable of activating liver regenerative transcription factors, thereby formulating a novel hepatic expansion medium to de-differentiate PHHs into proliferative human hepatic progenitor-like cells (ProHPLCs). These ProHPLCs were then re-differentiated into functionally mature hepatocytes using a new hepatocyte maturation condition. Additionally, we investigated the underlying mechanism of PHHs expansion under our new conditions. Results The novel hepatic expansion medium containing hydrocortisone facilitated the de-differentiation of PHHs into ProHPLCs, which exhibited key hepatic progenitor characteristics and demonstrated a marked increase in proliferation capacity compared to cells cultivated in previously established expansion conditions. Remarkably, these subsequent matured hepatocytes rivaled PHHs in terms of transcriptome profiles, drug metabolizing activities and in vivo engraftment capabilities. Importantly, our findings suggest that the enhanced expansion of PHHs by hydrocortisone may be mediated through the PPARα signaling pathway and regenerative transcription factors. Conclusions This study presents a two-step strategy that initially induces PHHs into a proliferative state (ProHPLCs) to ensure sufficient cell quantity, followed by the maturation of ProHPLCs into fully functional hepatocytes to guarantee optimal cell quality. This approach offers a promising means of producing large numbers of seeding cells for hepatocyte-based applications.

Abstract Background Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms. Methods This prospective, self-controlled clinical study was conducted at Henan Provincial People’s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation. Results Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy. Conclusion UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines. Trial registration The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.

Abstract Background Atrial fibrillation has an estimated prevalence of 1.5–2%, making it the most common cardiac arrhythmia. The processes that cause and sustain the disease are still not completely understood. An association between atrial fibrillation and systemic, as well as local, inflammatory processes has been reported. However, the exact mechanisms underlying this association have not been established. While it is understood that inflammatory macrophages can influence cardiac electrophysiology, a direct, causative relationship to atrial fibrillation has not been described. This study investigated the pro-arrhythmic effects of activated M1 macrophages on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes, to propose a mechanistic link between inflammation and atrial fibrillation. Methods Two hiPSC lines from healthy individuals were differentiated to atrial cardiomyocytes and M1 macrophages and integrated in an isogenic, pacing-free, atrial fibrillation-like coculture model. Electrophysiology characteristics of cocultures were analysed for beat rate irregularity, electrogram amplitude and conduction velocity using multi electrode arrays. Cocultures were additionally treated using glucocorticoids to suppress M1 inflammation. Bulk RNA sequencing was performed on coculture-isolated atrial cardiomyocytes and compared to meta-analyses of atrial fibrillation patient transcriptomes. Results Multi electrode array recordings revealed M1 to cause irregular beating and reduced electrogram amplitude. Conduction analysis further showed significantly lowered conduction homogeneity in M1 cocultures. Transcriptome sequencing revealed reduced expression of key cardiac genes such as SCN5A, KCNA5, ATP1A1, and GJA5 in the atrial cardiomyocytes. Meta-analysis of atrial fibrillation patient transcriptomes showed high correlation to the in vitro model. Treatment of the coculture with glucocorticoids showed reversal of phenotypes, including reduced beat irregularity, improved conduction, and reversed RNA expression profiles. Conclusions This study establishes a causal relationship between M1 activation and the development of subsequent atrial arrhythmia, documented as irregularity in spontaneous electrical activation in atrial cardiomyocytes cocultured with activated macrophages. Further, beat rate irregularity could be alleviated using glucocorticoids. Overall, these results point at macrophage-mediated inflammation as a potential AF induction mechanism and offer new targets for therapeutic development. The findings strongly support the relevance of the proposed hiPSC-derived coculture model and present it as a first of its kind disease model.

Abstract Background The immunomodulatory oligodeoxynucleotide (ODN) IMT504 might harbor antifibrotic properties within the liver. Methods Fibrosis models were induced in mice through thioacetamide (TAA) administration and bile-duct ligation. Cre-loxP mice were utilized to identify GLAST + Wnt1 + bone marrow stromal progenitors (BMSPs) and to examine their contribution with cells in the liver. In vivo and in vitro assays; flow-cytometry, immunohistochemistry, and qPCR were conducted. Results IMT504 demonstrated significant inhibition of liver fibrogenesis progression and reversal of established fibrosis. Early responses to IMT504 involved the suppression of profibrogenic and proinflammatory markers, coupled with an augmentation of hepatocyte proliferation. Additionally, this ODN stimulated the proliferation and mobilization of GLAST + Wnt1 + BMSPs, likely amplifying their contribution with endothelial- and hepatocytes-like cells. Moreover, IMT504 significantly modulated the expression levels of Wnt ligands and signaling pathway/target genes specifically within GLAST + Wnt1 + BMSPs, with minimal impact on other BMSPs. Intriguingly, both IMT504 and conditioned media from IMT504-pre-treated GLAST + Wnt1 + BMSPs shifted the phenotype of fibrotic macrophages, hepatic stellate cells, and hepatocytes, consistent with the potent antifibrotic effects observed. Conclusion In summary, our findings identify IMT504 as a promising candidate molecule with potent antifibrotic properties, operating through both direct and indirect mechanisms, including the activation of GLAST + Wnt1 + BMSPs.

Abstract Background Understanding the lineage differentiation of human prostate not only is crucial for basic research on human developmental biology but also significantly contributes to the management of prostate-related disorders. Current knowledge mainly relies on studies on rodent models, lacking human-derived alternatives despite clinical samples may provide a snapshot at certain stage. Human embryonic stem cells can generate all the embryonic lineages including the prostate, and indeed a few studies demonstrate such possibility based on co-culture or co-transplantation with urogenital mesenchyme into mouse renal capsule. Methods To establish a stepwise protocol to obtain prostatic organoids in vitro from human embryonic stem cells, we apply chemicals and growth factors by mimicking the regulation network of transcription factors and signal transduction pathways, and construct cell lines carrying an inducible NKX3-1 expressing cassette, together with three-dimensional culture system. Unpaired t test was applied for statistical analyses. Results We first successfully generate the definitive endoderm, hindgut, and urogenital sinus cells. The embryonic stem cell-derived urogenital sinus cells express prostatic key transcription factors AR and FOXA1, but fail to express NKX3-1. Therefore, we construct NKX3-1-inducible cell line by homologous recombination, which is eventually able to yield AR, FOXA1, and NKX3-1 triple-positive urogenital prostatic lineage cells through stepwise differentiation. Finally, combined with 3D culture we successfully derive prostate-like organoids with certain structures and prostatic cell populations. Conclusions This study reveals the crucial role of NKX3-1 in prostatic differentiation and offers the inducible NKX3-1 cell line, as well as provides a stepwise differentiation protocol to generate human prostate-like organoids, which should facilitate the studies on prostate development and disease pathogenesis.

Abstract Background Periodontal ligament stem cells (PDLSCs) are important seed cells in tissue engineering and clinical applications. They are the priority receptor cells for sensing various mechanical stresses. Yes-associated protein (YAP) is a recognized mechanically sensitive transcription factor. However, the role of YAP in regulating the fate of PDLSCs under tension stress (TS) and its underlying mechanism is still unclear. Methods The effects of TS on the morphology and fate of PDLSCs were investigated using fluorescence staining, transmission electron microscopy, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). Then qRT-PCR, western blotting, immunofluorescence staining and gene knockdown experiments were performed to investigate the expression and distribution of YAP and its correlation with PDLSCs proliferation. The effects of cytoskeleton dynamics on YAP nuclear translocation were subsequently explored by adding cytoskeleton inhibitors. The effect of cytoskeleton dynamics on the expression of the LINC complex was proved through qRT-PCR and western blotting. After destroying the LINC complex by adenovirus, the effects of the LINC complex on YAP nuclear translocation and PDLSCs proliferation were investigated. Mitochondria-related detections were then performed to explore the role of mitochondria in YAP nuclear translocation. Finally, the in vitro results were verified by constructing orthodontic tooth movement models in Sprague-Dawley rats. Results TS enhanced the polymerization and stretching of F-actin, which upregulated the expression of the LINC complex. This further strengthened the pull on the nuclear envelope, enlarged the nuclear pore, and facilitated YAP’s nuclear entry, thus enhancing the expression of proliferation-related genes. In this process, mitochondria were transported to the periphery of the nucleus along the reconstructed microtubules. They generated ATP to aid YAP’s nuclear translocation and drove F-actin polymerization to a certain degree. When the LINC complex was destroyed, the nuclear translocation of YAP was inhibited, which limited PDLSCs proliferation, impeded periodontal tissue remodeling, and hindered tooth movement. Conclusions Our study confirmed that appropriate TS could promote PDLSCs proliferation and periodontal tissue remodeling through the mechanically driven F-actin/LINC complex/YAP axis, which could provide theoretical guidance for seed cell expansion and for promoting healthy and effective tooth movement in clinical practice.

Abstract Background Chronic lung disease of prematurity, called bronchopulmonary dysplasia (BPD), lacks effective therapies, stressing the need for preclinical testing systems that reflect human pathology for identifying causal pathways and testing novel compounds. Alveolar organoids derived from human pluripotent stem cells (hPSC) are promising test platforms for studying distal airway diseases like BPD, but current protocols do not accurately replicate the distal niche environment of the native lung. Herein, we investigated the contributions of cellular constituents of the alveolus and fetal respiratory movements on hPSC-derived alveolar organoid formation. Methods Human PSCs were differentiated in 2D culture into lung progenitor cells (LPC) which were then further differentiated into alveolar organoids before and after removal of co-developing mesodermal cells. LPCs were also differentiated in Transwell® co-cultures with and without human fetal lung fibroblast. Forming organoids were subjected to phasic mechanical strain using a Flexcell® system. Differentiation within organoids and Transwell® cultures was assessed by flow cytometry, immunofluorescence, and qPCR for lung epithelial and alveolar markers of differentiation including GATA binding protein 6 (GATA 6), E-cadherin (CDH1), NK2 Homeobox 1 (NKX2-1), HT2-280, surfactant proteins B (SFTPB) and C (SFTPC). Results We observed that co-developing mesenchymal progenitors promote alveolar epithelial type 2 cell (AEC2) differentiation within hPSC-derived lung organoids. This mesenchymal effect on AEC2 differentiation was corroborated by co-culturing hPSC-NKX2-1+ lung progenitors with human embryonic lung fibroblasts. The stimulatory effect did not require direct contact between fibroblasts and NKX2-1+ lung progenitors. Additionally, we demonstrate that episodic mechanical deformation of hPSC-derived lung organoids, mimicking in situ fetal respiratory movements, increased AEC2 differentiation without affecting proximal epithelial differentiation. Conclusion Our data suggest that biophysical and mesenchymal components promote AEC2 differentiation within hPSC-derived distal organoids in vitro.

Abstract Background Reduction of adult hippocampal neurogenesis is an early critical event in Alzheimer’s disease (AD), contributing to progressive memory loss and cognitive decline. Reduced levels of the nucleoporin 153 (Nup153), a key epigenetic regulator of NSC stemness, characterize the neural stem cells isolated from a mouse model of AD (3×Tg) (AD-NSCs) and determine their altered plasticity and gene expression. Methods Nup153-regulated mechanisms contributing to NSC function were investigated: (1) in cultured NSCs isolated from AD and wild type (WT) mice by proteomics; (2) in vivo by lentiviral-mediated delivery of Nup153 or GFP in the hippocampus of AD and control mice analyzing neurogenesis and cognitive function; (3) in human iPSC-derived brain organoids obtained from AD patients and control subjects as a model of neurodevelopment. Results Proteomic approach identified Nup153 interactors in WT- and AD-NSCs potentially implicated in neurogenesis regulation. Gene ontology (GO) analysis showed that Nup153-bound proteins in WT-NSCs were involved in RNA metabolism, nuclear import and epigenetic mechanisms. Nup153-bound proteins in AD-NSCs were involved in pathways of neurodegeneration, mitochondrial dysfunction, proteasomal processing and RNA degradation. Furthermore, recovery of Nup153 levels in AD-NSCs reduced the levels of oxidative stress markers and recovered proteasomal activity. Lentiviral-mediated delivery of Nup153 in the hippocampal niche of AD mice increased the proliferation of early progenitors, marked by BrdU/DCX and BrdU/PSANCAM positivity and, later, the integration of differentiating neurons in the cell granule layer (BrdU/NeuN+ cells) compared with GFP-injected AD mice. Consistently, Nup153-injected AD mice showed an improvement of cognitive performance in comparison to AD-GFP mice at 1 month after virus delivery assessed by Morris Water Maze. To validate the role of Nup153 in neurogenesis we took advantage of brain organoids derived from AD-iPSCs characterized by fewer neuroepithelial progenitor loops and reduced differentiation areas. The upregulation of Nup153 in AD organoids recovered the formation of neural-like tubes and differentiation. Conclusions Our data suggest that the positive effect of Nup153 on neurogenesis is based on a complex regulatory network orchestrated by Nup153 and that this protein is a valuable disease target.

Abstract Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

Abstract Background Burn trauma is one of the major causes of morbidity and mortality worldwide. The standard management of burn wounds consists of early debridement, dressing changes, surgical management, and split-thickness skin autografts (STSGs). However, there are limitations for the standard management that inclines us to find alternative treatment approaches, such as innovative cell-based therapies. We aimed to systematically review the different aspects of cell-based treatment approaches for burn wounds in clinical trials. Methods A systematic search through PubMed, Medline, Embase, and Cochrane Library databases was carried out using a combination of keywords, including “Cell transplantation”, “Fibroblast”, “Keratinocyte”, “Melanocyte”, or “Stem Cell” with “Burn”, “Burn wound”, or “Burn injury”. Firstly, titles and abstracts of the studies existing in these databases until “February 2024” were screened. Then, the selected studies were read thoroughly, and considering the inclusion and exclusion criteria, final articles were included in this systematic review. Moreover, a manual search was performed through the reference lists of the included studies to minimize the risk of missing reports. Results Overall, 30 clinical trials with 970 patients were included in our study. Considering the type of cells, six studies used keratinocytes, nine used fibroblasts, eight used combined keratinocytes and fibroblasts, one study used combined keratinocytes and melanocytes, five used combined keratinocytes and fibroblasts and melanocytes, and one study used mesenchymal stem cells (MSCs). Evaluation of the preparation type in these studies showed that cultured method was used in 25 trials, and non-cultured method in 5 trials. Also, the graft type of 17 trials was allogeneic, and of 13 other trials was autologous. Conclusions Our study showed that employing cell-based therapies for the treatment of burn wounds have significant results in clinical studies and are promising approaches that can be considered as alternative treatments in many cases. However, choosing appropriate cell-based treatment for each burn wound is essential and depends on the situation of each patient.

Abstract Background Inflammation-induced testicular damage is a significant contributing factor to the increasing incidence of infertility. Traditional treatments during the inflammatory phase often fail to achieve the desired fertility outcomes, necessitating innovative interventions such as cell therapy. Methods We explored the in vivo properties of intravenously administered Sertoli cells (SCs) in an acute lipopolysaccharide (LPS)-induced inflammatory mouse model. Infiltrating and resident myeloid cell phenotypes were assessed using flow cytometry. The impact of SC administration on testis morphology and germ cell quality was evaluated using computer-assisted sperm analysis (CASA) and immunohistochemistry. Results SCs demonstrated a distinctive migration pattern, importantly they preferentially concentrated in the testes and liver. SC application significantly reduced neutrophil infiltration as well as preserved the resident macrophage subpopulations. SCs upregulated MerTK expression in both interstitial and peritubular macrophages. Applied SC treatment exhibited protective effects on sperm including their motility and kinematic parameters, and maintained the physiological testicular morphology. Conclusion Our study provides compelling evidence of the therapeutic efficacy of SC transplantation in alleviating acute inflammation-induced testicular damage. These findings contribute to the expanding knowledge on the potential applications of cell-based therapies for addressing reproductive health challenges and offer a promising approach for targeted interventions in male infertility.

Abstract Background In 2016, a voluntary National Healthy Food and Drink Policy was released to improve the healthiness of food and drinks for sale in New Zealand health sector organisations. The Policy aims to role model healthy eating and demonstrate commitment to health and well-being of hospital staff and visitors and the general public. This study aimed to understand the experiences of hospital food providers and public health dietitians/staff in implementing the Policy, and identify tools and resources needed to assist with the implementation. Methods A maximum variation purposive sampling strategy (based on a health district’s population size and food outlet type) was used to recruit participants by email. Video conference or email semi-structured interviews included 15 open-ended questions that focused on awareness, understanding of, and attitudes towards the Policy; level of support received; perceived customer response; tools and resources needed to support implementation; and unintended or unforeseen consequences. Data was analysed using a reflexive thematic analysis approach. Results Twelve participants (eight food providers and four public health dietitians/staff) were interviewed; three from small ( 300,000 people) health districts. There was agreement that hospitals should role model healthy eating for the wider community. Three themes were identified relating to the implementation of the Policy: (1) Complexities of operating food outlets under a healthy food and drink policy in public health sector settings; (2) Adoption, implementation, and monitoring of the Policy as a series of incoherent ad-hoc actions; and (3) Policy is (currently) not achieving the desired impact. Concerns about increased food waste, loss of profits and an uneven playing field between food providers were related to the voluntary nature of the unsupported Policy. Three tools could enable implementation: a digital monitoring tool, a web-based database of compliant products, and customer communication materials. Conclusions Adopting a single, mandatory Policy, provision of funding for implementation actions and supportive tools, and good communication with customers could facilitate implementation. Despite the relatively small sample size and views from only two stakeholder groups, strategies identified are relevant to policy makers, healthcare providers and public health professionals.

Abstract Background Food insecurity has involved more than 750 million individuals worldwide. The association of food insecurity with socio-economic factors is also undeniable demand more consideration. Food insecurity will become a global priority by 2030. This systematic review and meta-analysis examined current literature concerning the association between food insecurity and psychological distress. Methods Relevant researches were identified by searching databases including PubMed, EMBASE, Scopus, and Web of Science, ProQuest, and Cochrane Library up to June 2024 without language limitation. Then a snowball search was conducted in the eligible studies. The quality assessment was made through Newcastle–Ottawa Scale. Results Data were available from 44 cross-sectional articles for systematic review and 17 eligible articles for meta-analysis with 2,267,012 and 1,953,636 participants, respectively. Findings support the growing segment of literature on the association between food insecurity and psychological distress. The highly represented groups were households with low income. Psychological and diabetic distress was directly associated with food insecurity as it increased the odds of distress to 329% (OR: 3.29; 95% CI: 2.46–4.40). Sleep problems, anxiety, depression, lower life satisfaction, obesity, and a higher rate of smoking were among the secondary outcomes. Conclusion Food insecurity was a common stressor that can have a negative impact on psychological well-being and even physical health. The findings should be considered in the public health and making policy-making process.

Abstract Background People living with obesity receive treatment services from health professionals for their weight or other health needs. In order for the students of the Faculty of Health Sciences, who will be a member of the health team in the future, to raise awareness of the society, it is necessary to first determine their obesity prejudices and eating habits. Methods The study is a cross-sectional and descriptive research. The study data were collected from 406 students studying at the Faculty of Health Sciences by online questionnaire method using a personal characteristics identification form, GAMS 27-Obesity Bias Scale and University Students Eating Behavior Scale (USEBS). The data were analyzed with SPSS 26 statistical software. Results In this study, all students were found to be prone to prejudice according to the mean total score of the Obesity Bias Scale and Obesity Bias Scale was higher in female students studying in perfusion department. In the sub-dimensions of the University Students Eating Behavior Scale, the enjoyment of food score was found to have the highest mean score. Conclusion According to the results of the study, there is a need to develop educational planning that will both increase the awareness of university students about the relationship between eating behaviors and obesity and eliminate obesity prejudice tendencies due to the fact that they are educated to provide services in the field of health.