bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimally invasive approaches for the early detection of endometrial cancer
Authors: Shen Yufei , Yang Wenqing , Liu Jiachen , Zhang Yu 
Published: March 2023

AbstractEndometrial cancer (EC) is one of the most common gynecologic cancers and its incidence is rising globally. Although advanced EC has a poor prognosis; diagnosing EC at an earlier stage could improve long-term patient outcomes. However, there is no consensus on the early detection strategies for EC and the current diagnostic practices such as transvaginal ultrasound, hysteroscopy and endometrial biopsy are invasive, costly and low in specificity. Thus, accurate and less invasive screening tests that detect EC in women with early stages of the disease are needed. Current research has revolutionized novel EC early detection methodologies in many aspects. This review aims to comprehensively characterizes minimally invasive screening techniques that can be applied to EC in the future, and fully demonstrate their potential in the early detection of EC.
Effects of needle puncturing on re-vascularization and follicle survival in xenotransplanted human ovarian tissue
Authors: Olesen Hanna Ørnes , Pors Susanne Elisabeth , Adrados Cristina Subiran , Zeuthen Mette Christa , Mamsen Linn Salto , Pedersen Anette Tønnes , Kristensen Stine Gry 
Published: March 2023

Abstract
Background
Ovarian tissue transplantation can restore fertility in young cancer survivors, however the detrimental loss of follicles following transplantation of cryopreserved ovarian tissue is hampering the efficiency of the procedure. This study investigates whether needle puncturing prior to transplantation can enhance revascularization and improve follicle survival in xenotransplanted human ovarian cortex.

Methods
Cryopreserved human ovarian cortex pieces (N = 36) from 20 women aged 24–36 years were included. During the thawing process, each piece of tissue was cut in halves; one half serving as the untreated control and the other half was punctured approximately 150–200 times with a 29-gauge needle. The cortex pieces were transplanted subcutaneously to immunodeficient mice for 3, 6 and 10 days (N = 8 patients) and for 4 weeks (N = 12 patients). After 3, 6 and 10 days, revascularization of the ovarian xenografts were assessed using immunohistochemical detection of CD31 and gene expression of angiogenic factors (Vegfα, Angptl4, Ang1, and Ang2), and apoptotic factors (BCL2 and BAX) were performed by qPCR. Follicle density and morphology were evaluated in ovarian xenografts after 4 weeks.

Results
A significant increase in the CD31 positive area in human ovarian xenografts was evident from day 3 to 10, but no significant differences were observed between the needle and control group. The gene expression of Vegfα was consistently higher in the needle group compared to control at all three time points, but not statistically significant. The expression of Ang1 and Ang2 increased significantly from day 3 to day 10 in the control group (p < 0.001, p = 0.0023), however, in the needle group this increase was not observed from day 6 to 10 (Ang2 p = 0.027). The BAX/BCL2 ratio was similar in the needle and control groups. After 4-weeks xenografting, follicle density (follicles/mm3, mean ± SEM) was higher in the needle group (5.18 ± 2.24) compared to control (2.36 ± 0.67) (p = 0.208), and a significant lower percentage of necrotic follicles was found in the needle group (19%) compared to control (36%) (p = 0.045).

Conclusions
Needle puncturing of human ovarian cortex prior to transplantation had no effect on revascularization of ovarian grafts after 3, 6 and 10 days xenotransplantation. However, needle puncturing did affect angiogenic genes and improved follicle morphology.
METTL3 promotes chemoresistance in small cell lung cancer by inducing mitophagy
Authors: Sun Yueqin , Shen Weitao , Hu Shulu , Lyu Qiong , Wang Qiongyao , Wei Ting , Zhu Weiliang , Zhang Jian 
Published: March 2023

Abstract
Background
Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Although most patients are initially sensitive to first-line combination chemotherapy with cisplatin and etoposide, chemotherapy drug resistance easily develops and quickly leads to tumour progression. Therefore, understanding the mechanisms of chemotherapy drug resistance and how to reverse it is key to improving the prognosis of patients with SCLC. Moreover, N6-methyladenosine (m6A) is the most abundant mRNA modification and is catalysed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit.

Methods
The effects of METTL3 on chemoresistance in SCLC cells were determined using qRT–PCR, Western blotting, immunohistochemistry, cell counting kit (CCK-8) assays, flow cytometry, and tumorigenicity experiments. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), MeRIP qPCR, immunofluorescence, and drug inhibitor experiments were performed to confirm the molecular mechanism of Decapping Protein 2 (DCP2), which is involved in the chemoresistance of SCLC.

Results
In the present study, we found that METTL3 is a marker for poor SCLC prognosis, and it is highly expressed in chemoresistant SCLC cells. METTL3 promotes SCLC chemoresistance by positively regulating mitophagy. METTL3 induces m6A methylation of DCP2 and causes the degradation of DCP2, which promotes mitochondrial autophagy through the Pink1-Parkin pathway, leading to chemotherapy resistance. We also found that STM2457, a novel METTL3 inhibitor, can reverse SCLC chemoresistance.

Conclusions
The m6A methyltransferase METTL3 regulates Pink1-Parkin pathway-mediated mitophagy and mitochondrial damage in SCLC cells by targeting DCP2, thereby promoting chemotherapy resistance in patients with SCLC.
Impact of a multifaceted early mobility intervention for critically ill children — the PICU Up! trial: study protocol for a multicenter stepped-wedge cluster randomized controlled trial
Authors: Azamfirei Razvan , Mennie Colleen , Dinglas Victor D. , Fatima Arooj , Colantuoni Elizabeth , Gurses Ayse P. , Balas Michele C. , Needham Dale M. , Kudchadkar Sapna R. ,   on behalf of the PICU Up! ﻿Investigators, Alqahtani Mashael , Azar Justin , Berkenbosch John W. , Bjorklund Ashley R. , Corbett Kelly L. , Dorfman Molly V. , Kiragu Andrew W. , Musick Matthew A. , Porter Melissa B. , Rothschild Charles B. , Scarlett Elizabeth E. , Walker Tracie C. , Wright Melvin L. 
Published: March 2023

Abstract

Background
Over 50% of all critically ill children develop preventable intensive care unit-acquired morbidity. Early and progressive mobility is associated with improved outcomes in critically ill adults including shortened duration of mechanical ventilation and improved muscle strength. However, the clinical effectiveness of early and progressive mobility in the pediatric intensive care unit has never been rigorously studied. The objective of the study is to evaluate if the PICU Up! intervention, delivered in real-world conditions, decreases mechanical ventilation duration (primary outcome) and improves delirium and functional status compared to usual care in critically ill children. Additionally, the study aims to identify factors associated with reliable PICU Up! delivery.

Methods
The PICU Up! trial is a stepped-wedge, cluster-randomized trial of a pragmatic, interprofessional, and multifaceted early mobility intervention (PICU Up!) conducted in 10 pediatric intensive care units (PICUs). The trial’s primary outcome is days alive free of mechanical ventilation (through day 21). Secondary outcomes include days alive and delirium- and coma-free (ADCF), days alive and coma-free (ACF), days alive, as well as functional status at the earlier of PICU discharge or day 21. Over a 2-year period, data will be collected on 1,440 PICU patients. The study includes an embedded process evaluation to identify factors associated with reliable PICU Up! delivery.

Discussion
This study will examine whether a multifaceted strategy to optimize early mobility affects the duration of mechanical ventilation, delirium incidence, and functional outcomes in critically ill children. This study will provide new and important evidence on ways to optimize short and long-term outcomes for pediatric patients.

Trial registration
ClinicalTrials.gov NCT04989790. Registered on August 4, 2021.
A comparison of different physical stimulation combined with platelet-rich plasma for the treatment of knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Liu Yan , Xiang Xiao-Na , Wang Qian , He Hong-Chen 
Published: March 2023

AbstractBackgroundPlatelet-rich plasma (PRP) contains various growth factors and inflammatory regulators, which can effectively reduce inflammation in joints and promote tissue repair. Multiple studies have proved its effectiveness in the treatment of knee osteoarthritis (KOA). Low-intensity focused ultrasound (LIFU) and transcutaneous electrical nerve stimulation (TENS) are non-invasive and safe physical therapy methods for KOA. This study is the first to propose the treatment of KOA with physical stimulation after PRP treatment, and to observe the clinical efficacy of the treatment method.MethodsThis is a protocol paper that outlines a randomized controlled trial, patients will be assigned randomly to the PRP group, PRP+LIFU group, PRP+TENS group, and PRP+LIFU combined TENS group. The patients will be followed at 12-week and 24-week time points to evaluate the primary and secondary outcomes of the study. The primary outcome is the VAS pain score. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Knee Documentation Committee scores (IKDC). After baseline examination, all patients will sign a written informed consent for study participation after a full explanation of the treatment protocol. We have planned a total of 120 patients (30 patients per group).DiscussionThe objective of this clinical trial is to evaluate the effect of different physical stimulation after PRP treatment for KOA. The data will be published after the completion of the study.Trial registrationThis study has been registered with the Chinese Clinical Trials Registry. Registration number: ChiCTR2200065119 (registered date: 10/28/2022).
spSeudoMap: cell type mapping of spatial transcriptomics using unmatched single-cell RNA-seq data
Authors: Bae Sungwoo , Choi Hongyoon , Lee Dong Soo 
Published: March 2023

AbstractSince many single-cell RNA-seq (scRNA-seq) data are obtained after cell sorting, such as when investigating immune cells, tracking cellular landscape by integrating single-cell data with spatial transcriptomic data is limited due to cell type and cell composition mismatch between the two datasets. We developed a method, spSeudoMap, which utilizes sorted scRNA-seq data to create virtual cell mixtures that closely mimic the gene expression of spatial data and trains a domain adaptation model for predicting spatial cell compositions. The method was applied in brain and breast cancer tissues and accurately predicted the topography of cell subpopulations. spSeudoMap may help clarify the roles of a few, but crucial cell types.
Maternal hyperglycemia inhibits pulmonary vasculogenesis during mouse fetal lung development by promoting GβL Ubiquitination-dependent mammalian target of Rapamycin assembly
Authors: Luo Qingqing , Chai Xinqun , Xin Xiaoyan , Ouyang Weixiang , Deng Feitao 
Published: March 2023

Abstract
Background
Gestational diabetes mellitus (GDM) is associated with retarded lung development and poor lung health in offspring. Mammalian target of rapamycin (mTOR) is a key regulator of vasculogenesis and angiogenesis. The aim of this study was to investigate the role mTOR plays in pulmonary vasculogenesis during fetal lung development under maternal hyperglycemia.

Methods
First, GDM was induced via streptozotocin injection in pregnant C57BL/6 mice before the radial alveolar count (RAC) in the fetal lungs was assessed using hematoxylin and eosin staining. The angiogenic ability of the cultured primary mouse fetal lung endothelial cells (MFLECs) was then assessed using the tube formation assay technique, while western blot and real-time polymerase chain reaction were performed to determine the expression of mTOR, regulatory-associated protein of mTOR (Raptor), rapamycin-insensitive companion of mTOR (Rictor), stress-activated protein kinase interacting protein 1 (Sin1), G protein beta subunit-like protein (GβL), Akt, tumor necrosis receptor associated factor-2 (TRAF2), and OTU deubiquitinase 7B (OTUD7B) in both the fetal lung tissues and the cultured MFLECs. Immunoprecipitation assays were conducted to evaluate the status of GβL-ubiquitination and the association between GβL and mTOR, Raptor, Rictor, and Sin1 in the cultured MFLECs.

Results
The GDM fetal lungs exhibited a decreased RAC and reduced expression of von Willebrand factor, CD31, and microvessel density. The high glucose level reduced the tube formation ability in the MFLECs, with the mTOR, p-mTOR, p-Raptor, and TRAF2 expression upregulated and the p-Rictor, p-Sin1, p-Akt, and OTUD7B expression downregulated in both the GDM fetal lungs and the high-glucose-treated MFLECs. Meanwhile, GβL-ubiquitination was upregulated in the high-glucose-treated MFLECs along with an increased GβL/Raptor association and decreased GβL/Rictor and GβL/Sin1 association. Furthermore, TRAF2 knockdown inhibited the high-glucose-induced GβL-ubiquitination and GβL/Raptor association and restored the tube formation ability of the MFLECs.

Conclusion
Maternal hyperglycemia inhibits pulmonary vasculogenesis during fetal lung development by promoting GβL-ubiquitination-dependent mTORC1 assembly.
The relationship of insulin resistance and diabetes to tau PET SUVR in middle-aged to older adults
Authors: Ennis Gilda E. , Betthauser Tobey J. , Koscik Rebecca Langhough , Chin Nathaniel A. , Christian Bradley T. , Asthana Sanjay , Johnson Sterling C. , Bendlin Barbara B. 
Published: March 2023

AbstractBackgroundInsulin resistance (IR) and type 2 diabetes have been found to increase the risk for Alzheimer’s clinical syndrome in epidemiologic studies but have not been associated with tau tangles in neuropathological research and have been inconsistently associated with cerebrospinal fluid P-tau181. IR and type 2 diabetes are well-recognized vascular risk factors. Some studies suggest that cardiovascular risk may act synergistically with cortical amyloid to increase tau measured using tau PET. Utilizing data from largely nondemented middle-aged and older adult cohorts enriched for AD risk, we investigated the association of IR and diabetes to tau PET and whether amyloid moderated those relationships.MethodsParticipants were enrolled in either the Wisconsin Registry for Alzheimer’s Prevention (WRAP) or Wisconsin Alzheimer’s Disease Research Center (WI-ADRC) Clinical Core. Two partially overlapping samples were studied: a sample characterized using HOMA-IR (n=280 WRAP participants) and a sample characterized on diabetic status (n=285 WRAP andn=109 WI-ADRC). IR was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Tau PET employing the radioligand18F-MK-6240 was used to detect AD-specific aggregated tau. Linear regression tested the relationship of IR and diabetic status to tau PET standardized uptake value ratio (SUVR) within the entorhinal cortex and whether relationships were moderated by amyloid assessed by amyloid PET distribution volume ratio (DVR) and amyloid PET positivity status.ResultsNeither HOMA-IR nor diabetic status was significantly associated with tau PET SUVR. The relationship between IR and tau PET SUVR was not moderated by amyloid PET DVR or positivity status. The association between diabetic status and tau PET SUVR was not significantly moderated by amyloid PET DVR but was significantly moderated by amyloid PET positivity status. Among the amyloid PET-positive participants, the estimated marginal tau PET SUVR mean was higher in the diabetic (n=6) relative to the nondiabetic group (n=88).ConclusionFindings indicate that IR may not be related to tau in generally healthy middle-aged and older adults who are in the early stages of the AD clinicopathologic continuum but suggest the need for additional research to investigate whether a synergistic relationship between type 2 diabetes and amyloid is associated with increased tau levels.
Cloud-edge data encryption in the internet of vehicles using Zeckendorf representation
Authors: Wu Yun , Wu Liangshun , Cai Hengjin 
Published: March 2023

AbstractCloud-edge data security is a key issue in the internet of vehicles (IoV), as the potential for data breaches increases as more vehicles are connected. As vehicles become smarter and more connected, the risk of unauthorized access to the data generated by the vehicles also increases. Data encryption is a highly effective security measure that is widely used to protect the IoV from malicious actors. By encrypting data, it becomes virtually impossible for unauthorized individuals to access the information. This ensures that only the intended parties can access the data, allowing for secure communication between cloud and edge. Data encryption is a cost-effective and reliable security measure that is essential for any organization that relies on the IoV. The IoV is characterized by the large volume of data that is exchanged between devices in cloud and edge. This necessitates the use of a strong encryption method, such as stream ciphering, which is particularly well-suited to this type of environment. Stream ciphering provides the highest levels of security, making it the ideal choice for securing data transmission in the IoV. Many stream ciphering algorithms use bitwise exclusive or (XOR) to encrypt the data stream, so the core is the generation of a pseudo-random key stream. This paper proves that the probability of the number 1 appearing in the middle part of the Zeckendorf representation is constant, which can be used to generate pseudo-random key stream sequences. The pseudo-random sequence generated by the linear feedback shift register (LSFR) is periodic, and the key sequence will be duplicated. The logistic chaos (LC) sequence is too sensitive to the disturbance of initial value, and its stability is poor. In this paper, our proposed ZPKG (key generator based on Zeckendorf presentation) algorithm solves these two main problems in stream ciphering. The generated key sequence not only has strong randomness, but also is infinitely long, and it is robust to the minor disturbance of the initial value.Graphical Abstract
A study of COVID anxiety, spiritual well-being and resilience levels in patients with cancer undergoing chemotherapy during the COVID-19 pandemic: a cross-sectional study in the south of Iran
Authors: Khiyali Zahra , Naderi Zeinab , Vakil Mohammadkazem , Ghasemi Hajar , Dehghan Azizallah , Bijani Mostafa 
Published: March 2023

Abstract
Background
Patients with cancer are at higher risk of contracting COVID-19 with poor prognosis. Therefore, the present study was conducted to investigate anxiety, spiritual well-being, and resilience levels in patients with cancer undergoing chemotherapy during the COVID-19 pandemic in the south of Fars Province, Iran.

Methods
This is a descriptive study with a cross-sectional design conducted on the patients undergoing chemotherapy at Dr. Ali Shariati Hospital in Fasa from November 2021 to February 2022. Cancer patients undergoing chemotherapy were included in the study by census method. Out of 210 patients, 155 participated in the study. Data were collected electronically using the standard instruments of Ellison’s Spiritual Well-being Scale, COVID-19 anxiety questionnaire, and Connor-Davidson resilience scale. The collected data were analyzed in SPSS 22 using descriptive statistics, Pearson correlation tests, T-test, ANOVA and multivariate linear regression at a level of significance of P < 0.05.

Results
The participants’ resilience mean score was 46.35 ± 26.51 and their spiritual well-being mean score was 69.58 ± 9.32. In addition, their COVID anxiety mean, score was found to be 16.85 ± 10.51. The results showed a significant direct correlation between the patients’ spiritual well-being and resilience (r = 0.47, P < 0.001) and a significant inverse correlation between the patients’ spiritual well-being and COVID-19-related anxiety (r = − 0.275, P < 0.001). In addition, there was a significant inverse correlation between the variables of resilience and COVID-19-related anxiety (r = − 0.637, P < 0.001). Based on multivariate linear regression, the most common predictors in resilience were age and history of infection with COVID-19, and in spiritual health and anxiety, was a history of infection with COVID-19.

Conclusion
Enhancement of spiritual well-being and resilience in patients should be an integral part of care as these qualities are valuable resources in fighting cancer and lowering patients’ anxiety, especially during the COVID-19 pandemic.
Comparison of gene expression between human and mouse iPSC-derived cardiomyocytes for stem cell therapies of cardiovascular defects via bioinformatic analysis
Authors: Bellman Ryan , Chen Jishizhan , Chen Lidan , Nomikou Nikolitsa , Tsui Janice , Hamilton George , Song Wenhui 
Published: March 2023

Abstract
Background
Preclinical studies have demonstrated the potential use of induced pluripotent stem cells (iPSCs) to treat cardiovascular disease (CVD). In vivo preclinical studies conducted on animal models (murine, porcine, guinea pig, etc.) have employed either syngeneic or human-derived iPSCs. However, no study has been carried out to investigate and report the key genetic differences between the human and animal-derived iPSCs. Our study analysed the gene expression profile and molecular pathway patterns underlying the differentiation of both human and mouse iPSCs to iPSC-cardiomyocytes (iPSC-CMs), and the differences between them via bioinformatic analysis.

Method
Data sets were downloaded from the Gene Expression Omnibus (GEO) database and included both human and mouse models, and the data for undifferentiated iPSCs and iPSC-CMs were isolated from each. Differentially expressed genes (DEGs) were screened and then analysed. The website g:Profiler was used to obtain the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) networks of the DEGs were constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. The subclusters were then extracted from the PPI network for further analysis.

Results
iPSC-derived cardiomyocytes expressed many genes related to vascular, endothelial, and smooth muscle repair in the human iPSC-CMs, and prevention of calcification in the mouse iPSC-CMs with clear differences in gene expression, which will affect how iPSCs act in research. Especially in the human iPSC-CMs, and also prevention of calcification processes in the mouse data. The identified differences in gene expression of iPSCs derived from the two species suggests that in vivo studies using mouse iPSC-CMs may not reflect those in humans.

Conclusion
The study provides new insights into the key genes related to the iPSCs, including genes related to angiogenesis, calcification, and striated muscle, endothelium, and bone formation. Moreover, the clear differences between both mouse and human-derived iPSCs have been identified, which could be used as new evidence and guidance for developing novel targeted therapy strategies to improve the therapeutic effects of iPSC treatment in cardiovascular defects.