bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumorigenic role of Pak4 in ovarian cancer and its correlation with immune infiltration
Authors: Tang Lan , Ye Hong , Chen Li , Dong Weiwei , Hu Xingyan , Yu Lan 
Published: May 2024

Abstract
Background
Ovarian cancer is the most common cause of gynecological cancer death. Pak4 has been proved to be tumorigenic in many types of cancers, but its role in ovarian cancer is still not clarified.

Methods
In this study, we used immunohistochemistry to investigate into Pak4 expression in different histological types of ovarian cancer. TIMER, TISCH2, GEPIA, ualcan, KM plotter, GSCA and GeneMANIA were used to identify the prognostic roles and gene regulation networks of Pak4 in ovarian cancer. Immune infiltration levels were investigated using TIMER database.

Results
Pak4 was highly expressed in ovarian cancers, regardless of different FIGO stages and histological grades. Single cell sequencing database proved that Pak4 was highly expressed in malignant ovarian cancer cells. Pak4 level was significantly correlated with different histological types of ovarian cancer. Pak4 expression was negatively connected with OS and PFS of ovarian cancer patients. Functions of Pak4 and its interacted genes were mainly involved in protein serine/threonine kinase activity, regulation of actin filament-based process and regulation of cytoskeleton organization. Pak4 level was negatively correlated with immune biomarkers of B cell infiltration (p = 2.39e-05), CD8 + T cell infiltration (p = 1.51e-04), neutrophil (p = 1.74e-06) and dendritic cell (p = 4.41e-08). Close correlation was found between Pak4 expression and T cell exhaustion (p < 0.05).

Conclusions
Our results demonstrated the expression level, gene interaction networks and immune infiltration levels of Pak4 in ovarian cancer. And the results revealed role of Pak4 in tumorigenesis and the possibility to be a potential immunotherapeutic target.
Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics
Authors: Ba Huixue , Guo Yingfan , Jiang Yujie , Li Ying , Dai Xuejing , Liu Yuan , Li Xiaohui 
Published: May 2024

AbstractPulmonary hypertension (PH) is regarded as cardiovascular disease with an extremely poor prognosis, primarily due to irreversible vascular remodeling. Despite decades of research progress, the absence of definitive curative therapies remains a critical challenge, leading to high mortality rates. Recent studies have shown that serious metabolic disorders generally exist in PH animal models and patients of PH, which may be the cause or results of the disease. It is imperative for future research to identify critical biomarkers of metabolic dysfunction in PH pathophysiology and to uncover metabolic targets that could enhance diagnostic and therapeutic strategies. Metabolomics offers a powerful tool for the comprehensive qualitative and quantitative analysis of metabolites within specific organisms or cells. On the basis of the findings of the metabolomics research on PH, this review summarizes the latest research progress on metabolic pathways involved in processes such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and nucleotide metabolism in the context of PH.
Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection
Authors: Zhang Yupei , Zhai Songhui , Huang Hai , Qin Shugang , Sun Min , Chen Yuting , Lan Xing , Li Guohong , Huang Zhiying , Wang Denggang , Luo Yaoyao , Xiao Wen , Li Hao , He Xi , Chen Meiwan , Peng Xingchen , Song Xiangrong 
Published: May 2024

AbstractThe signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.
Association of deletion polymorphism rs10573247 in the HMGA2 gene with the risk of breast cancer: bioinformatic and experimental analyses
Authors: Najibi Kolsoom , Moghanibashi Mehdi , Naeimi Sirous 
Published: May 2024

Abstract
Background
The high mobility group A2 (HMGA2) gene is expressed extensively during early embryonic development but is inactivated in adulthood, and it is also reactivated in various benign and malignant tumors, including breast cancer. We first assessed the potential functional significance of the unstudied deletion polymorphism rs10573247 at the 3′UTR of HMGA2 on miRNA binding using bioinformatic tools, and subsequently, the association between this polymorphism and breast cancer susceptibility was investigated.

Materials and methods
We applied the RNAhybrid tool to predict the functional effects of polymorphism rs10573247 located within the 3’ UTR of the HMGA2 gene on miRNA binding. Then, following DNA extraction, 141 breast cancer patients and 123 healthy controls were genotyped for polymorphism rs10573247 using RFLP-PCR with the restriction enzyme Eam1104I.

Results
Our bioinformatic data have shown that polymorphism rs10573247 is located in the region that serves as a potential target site for eight miRNAs binding. Among them, miR-3125 exhibited decreased binding affinity for the allele delTT (MFE = -21.8) when compared to the allele TT (MFE = -23.9), but miR-4476 increased binding affinity for the allele delTT (MFE = -22.4) compared to the allele TT (MFE = -22.2). In addition, our results showed that the genotype TT/delTT (p = 0.005) and the genotype delTT/delTT (p = 0.029) were significantly associated with an increased risk of developing breast cancer compared to the genotype TT/TT using RFLP-PCR.

Discussion and Conclusion
Our findings suggest that polymorphism rs10573247 may contribute to the risk of breast cancer through the functional effect of this polymorphism on miRNA binding.
What inhibits “speaking up” for patient safety among healthcare workers? A cross-sectional study in Malaysia
Authors: Kim Alex Ren Jye , Nishino Kimihiro , Bujang Mohamad Adam , Zulkifli Zubalqiah , Inthaphatha Souphalak , Yamamoto Eiko 
Published: May 2024

Abstract
Background
In healthcare, “speaking up” refers to when healthcare workers raise concerns regarding patient safety through questions, sharing information, or expressing their opinion to prevent harmful incidents and ensure patient safety. Conversely, withholding voice is an act of not raising concerns, which could be beneficial in certain situations. Factors associated with speaking up and withholding voices are not fully understood, especially in strong authoritarian societies, such as Malaysia. This study aimed to examine the factors associated with speaking up and withholding the voices of healthcare workers in Malaysia, thus providing suggestions that can be used in other countries facing similar patient safety challenges.

Methods
This cross-sectional study was conducted in a tertiary hospital in Sarawak State, Malaysia. Data were collected from 474 healthcare workers from 43 departments using a self-administered questionnaire for speaking up and withholding voices measures in 4 weeks prior to data analysis as well as socio-demographic factors of healthcare workers (sex, age group, profession, department, weekly work hours for patient care, years of employment in the hospital, and the hierarchical level) and speaking up related climate of the working environment were recorded. Data were analyzed using descriptive statistics. Logistic regression was performed to find out (adjusted) odds ratio of frequent speaking up and withholding voices.

Results
Nurse compared to doctors and healthcare workers with short weekly working hours were more likely to speak up. Healthcare workers in emergency and intensive care department, those with short years of employment, and those who worked at low hierarchical levels were less likely to speak up. Healthcare workers in discouraging environment towards speaking up were more likely to withhold their voices.

Conclusions
This study demonstrates the characteristics of healthcare workers who speak up and those who withhold their voices in Malaysia. To ensure patient safety and prevent harm, it is essential to establish an encouraging environment that promotes speaking up and prevents withholding voices among healthcare worker, especially in circumstances where multiple types of healthcare workers with different socio-demographic backgrounds work together.
Medical insurance, livelihood capital and public health in China
Authors: Sheng Wang , Fuchong Liao 
Published: May 2024

Abstract
Background
Medical insurance stands as a pivotal component within the overarching framework of public service systems. The intricate interplay between the extent of healthcare coverage and the overall well-being of the populace remains a pivotal research question within the academic sphere.

Methods
Drawing from the comprehensive dataset of the Chinese Household Livelihood Survey, this article employs a rigorous data model to delve into the profound implications of medical coverage on population health.

Results
The descriptive analysis revealed that areas with broader medical coverage tend to exhibit higher levels of overall population health. This initial observation provided a foundation for further quantitative exploration using multiple regression analysis. The regression analysis demonstrated a statistically significant positive relationship between medical coverage and population health. This finding is particularly noteworthy as it suggests that expanding access to healthcare services has tangible benefits for improving the overall health of a population.

Conclusion
From the lens of familial sustenance, this article delves into the intricate health implications of medical coverage, thereby introducing a novel theoretical lens to the evolving discourse surrounding medical insurance healthcare systems and their impact on public health. This approach aims to enrich the current understanding of this complex relationship and contribute to the scholarly dialogue.
Barriers and facilitators to medical care retention for pediatric systemic lupus erythematosus in South Africa: a qualitative study
Authors: Ikram Naira , Lewandowski Laura B. , Watt Melissa H. , Scott Christiaan 
Published: May 2024

Abstract
Background
Systemic lupus erythematosus (SLE) is a life-threatening, chronic, autoimmune disease requiring long term subspecialty care due to its complex and chronic nature. Childhood-onset SLE (cSLE) is more severe than adult-onset, and the cSLE population in South Africa has been reported to have an even higher risk than patients elsewhere. Therefore, it is critical to promptly diagnose, treat, and manage cSLE. In this paper, we aim to describe and evaluate barriers and enablers of appropriate long-term care of cSLE South Africa from the perspective of caregivers (parents or family members).

Methods
Caregivers (n = 22) were recruited through pediatric and adult rheumatology clinics. Individuals were eligible if they cared for youth (≤ 19 years) who were diagnosed with cSLE and satisfied at least four of the eleven ACR SLE classification criteria. Individual in-depth, semi-structured interviews were conducted between January 2014 and December 2014, and explored barriers to and facilitators of ongoing chronic care for cSLE. Data were analyzed using applied thematic analysis.

Results
Four barriers to chronic care engagement and retention were identified: knowledge gap, financial burdens, social stigma of SLE, and complexity of the South African medical system. Additionally, we found three facilitators: patient and caregiver education, robust support system for the caregiver, and financial support for the caregiver and patient.

Conclusion
These findings highlight multiple, intersecting barriers to routine longitudinal care for cSLE in South Africa and suggest there might be a group of diagnosed children who don’t receive follow-up care and are subject to loss to follow-up. cSLE requires ongoing treatment and care; thus, the different barriers may interact and compound over time with each follow-up visit. South African cSLE patients are at high risk for poor outcomes. South African care teams should work to overcome these barriers and place attention on the facilitators to improve care retention for these patients and create a model for other less resourced settings.
Assistance force-line of exosuit affects ankle multidimensional motion: a theoretical and experimental study
Authors: Zhang Xinyue , Li Ying , Sun Ronglei 
Published: May 2024

Abstract
Background
The talocrural joint and the subtalar joint are the two major joints of the ankle-joint complex. The position and direction of the exosuit force line relative to these two joint axes can influence ankle motion. We aimed to understand the effects of different force-lines on ankle multidimensional motion.

Methods
In this article, three assistance force line schemes for ankle exosuits were proposed: perpendicular to the talocrural joint axis (PT), intersecting with the subtalar joint axis (IS), and parallel to the triceps surae (PTS). A theoretical model was proposed to calculate the exosuit’s assistance moment. Seven participants completed four experimental tests of ankle plantarflexion, including three passive motions assisted by the PT, PTS and IS schemes, and one active motion without exosuit assistance (Active).

Results
The simulation results demonstrated that all three exosuits were able to produce significant moments of ankle plantarflexion. Among these, the PT scheme exhibited the highest moments in all dimensions, followed by the PTS and IS schemes. The experimental findings confirmed the effectiveness of all three exosuit schemes in assisting ankle plantarflexion. Additionally, as the assistive force lines approached the subtalar joint, there was a decrease in ankle motion assisted by the exosuits in non-plantarflexion directions, along with a reduction in the average distance of ankle angle curves relative to active ankle motion. Furthermore, the linear correlation coefficients between inversion and plantarflexion, adduction and plantarflexion, and adduction and inversion gradually converged toward active ankle plantarflexion motion.

Conclusions
Our research indicates that the position of the exosuit force line to the subtalar joint has a significant impact on ankle inversion and adduction. Among all three schemes, the IS, which has the closest distance to the subtalar joint axes, has the greatest kinematic similarity to active ankle plantarflexion and might be a better choice for ankle assistance and rehabilitation.
Comparative analysis of arthroscopic technique for anterior talofibular and calcaneofibular ligament reconstruction versus open modified brostrom-gould procedure in chronic lateral ankle instability management
Authors: Hong Gang , Kong XiaoChuan , Zhang Le , Zheng YinFeng , Fan Ning , Zang Lei 
Published: May 2024

Abstract
Background
Chronic Lateral Ankle Instability (CLAI) is a common condition treated using either Anterior Talofibular and Calcaneofibular Ligament (ATFL and CFL) reconstruction or Modified Brostrom Procedure (MBP). However, the comparative efficacy of these approaches is not well-studied.

Methods
In this study, clinical data were retrospectively collected from 101 patients diagnosed with CLAI who underwent either ATFL and CFL reconstruction (n = 51) or the MBP (n = 50). Patients were comparable in terms of age, sex, Body Mass Index (BMI), post-injury duration, preoperative American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson score, Visual Analog Score (VAS), Anterior Talar Translation, and Talar Tilt Angle.

Results
The post-operative measures showed no significant differences in AOFAS Score, Karlsson Score, and VAS between both treatment groups. However, patients who underwent ATFL and CFL reconstruction showed significantly lower follow-up Anterior Talar Translation (mean = 4.1667 ± 1.3991 mm) and Talar Tilt Angle (mean = 5.0549 ± 1.6173°) compared to those who underwent MBP. Further, patients treated with ATFL and CFL reconstruction experienced a significantly longer postoperative recovery time (median = 6 weeks) compared to MBP (median = 3 weeks).

Conclusions
Although both therapeutic techniques were generally effective in treating CLAI, the ATFL and CFL reconstruction approach delivered superior control of Anterior Talar Translation and Talar Tilt Angle. However, its longer recovery time merits further study to optimize the balance between therapeutic efficacy and recovery speed.
Five recommendations to advance implementation science for humanitarian settings: the next frontier of humanitarian research
Authors: Falb Kathryn , Kullenberg Sheree , T Yuan Christina , Blackwell Alexandra 
Published: May 2024

AbstractChallenges in delivering evidence-based programming in humanitarian crises require new strategies to enhance implementation science for better decision-making. A recent scoping review highlights the scarcity of peer-reviewed studies on implementation in conflict zones. In this commentary, we build on this scoping review and make five recommendations for advancing implementation science for humanitarian settings. These include (1) expanding existing frameworks and tailoring them to humanitarian dynamics, (2) utilizing hybrid study designs for effectiveness-implementation studies, (3) testing implementation strategies, (4) leveraging recent methodological advancements in social and data science, and (5) enhancing training and community engagement. These approaches aim to address gaps in understanding intervention effectiveness, scale, sustainability, and equity in humanitarian settings. Integrating implementation science into humanitarian research is essential for informed decision-making and improving outcomes for affected populations.
Nonthermal biocompatible plasma in stimulating osteogenic differentiation by targeting p38/ FOXO1 and PI3K/AKT pathways in hBMSCs
Authors: Akter Khadija , Kim Youngsun , Choi Eun Ha , Han Ihn 
Published: May 2024

AbstractOsteoporosis is manifested by decreased bone density and deterioration of bone architecture, increasing the risk of bone fractures Human bone marrow mesenchymal stem cells (hBMSCs)-based tissue engineering serves as a crucial technique for regenerating lost bone and preventing osteoporosis. Non-thermal biocompatible plasma (NBP) is a potential new therapeutic approach employed in several biomedical applications, including regenerative medicine. NBP affects bone remodeling; however, its role in the regulation of osteogenic differentiation in hBMSCs remains largely unexplored. This study aimed to explore the efficiency of NBP in promoting osteogenic differentiation, and the molecular pathways through which these responses occurred in hBMSCs. We found that NBP facilitated osteogenic differentiation through the upregulation of the bone morphogenic protein signal (BMPs) cascade, which in turn induced the expression of p38 and inhibited the forkhead box protein O1 (FOXO1). To further gain insight into the mechanism through which NBP extensively triggers the initiation of osteogenic differentiation in hBMSCs, PI3K/AKT pathway was also analyzed. Overall, these results highlight that NBP enhances osteogenic differentiation in hBMSCs by the stimulation of the p38/FOXO1 through PI3K/AKT signaling pathways. Therefore, the application of NBP in hBMSCs may offer tremendous therapeutic prospects in the treatment of bone regeneration and osteoporosis prevention.
Reproductive isolation arises during laboratory adaptation to a novel hot environment
Authors: Hsu Sheng-Kai , Lai Wei-Yun , Novak Johannes , Lehner Felix , Jakšić Ana Marija , Versace Elisabetta , Schlötterer Christian 
Published: May 2024

Abstract
Background
Reproductive isolation can result from adaptive processes (e.g., ecological speciation and mutation-order speciation) or stochastic processes such as “system drift” model. Ecological speciation predicts barriers to gene flow between populations from different environments, but not among replicate populations from the same environment. In contrast, reproductive isolation among populations independently adapted to the same/similar environment can arise from both mutation-order speciation or system drift.

Results
In experimentally evolved populations adapting to a hot environment for over 100 generations, we find evidence for pre- and postmating reproductive isolation. On one hand, an altered lipid metabolism and cuticular hydrocarbon composition pointed to possible premating barriers between the ancestral and replicate evolved populations. On the other hand, the pronounced gene expression differences in male reproductive genes may underlie the postmating isolation among replicate evolved populations adapting to the same environment with the same standing genetic variation.

Conclusion
Our study confirms that replicated evolution experiments provide valuable insights into the mechanisms of speciation. The rapid emergence of the premating reproductive isolation during temperature adaptation showcases incipient ecological speciation. The potential evidence of postmating reproductive isolation among replicates gave rise to two hypotheses: (1) mutation-order speciation through a common selection on early fecundity leading to an inherent inter-locus sexual conflict; (2) system drift with genetic drift along the neutral ridges.
Educational telerehabilitation program for women with pelvic floor dysfunctions after gynecological pelvic cancer treatment: protocol study for a randomized and controlled clinical trial
Authors: Bem Fretta Tatiana de , Dacanal Gabriela Dassie , de Souza Mendes Pauliana Carolina , Dias Mirella , Jorge Cristine Homsi 
Published: May 2024

Abstract
Background
Educational and self-care measures are important for women after gynecological pelvic cancer treatment. Pelvic floor muscle training exercises (PFMT) are a conservative treatment for pelvic floor (PF) dysfunction. The purpose is to evaluate the impact of a telerehabilitation and self-care program on PF dysfunctions, reports of urinary incontinence (UI), and physical–emotional factors of participants post-treatment for gynecological pelvic cancer.

Methods
Two-arm randomized clinical trial: an intervention group (IG) will evaluate the effect of a telerehabilitation program on women undergoing clinical practice of radiotherapy for the treatment of gynecological pelvic cancer and a control group (CG) will maintain the routine. Primary outcome is the prevalence of reports of UI, which will be assessed using the International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF). The secondary outcomes will be the severity and impact of UI on quality of life, location and perception of pain intensity, presence and intensity of dyspareunia, vaginal stenosis, fecal incontinence (FI), and levels of physical activity. Statistical analysis will be performed by intention-to-treat, and multivariate mixed effects analysis will be used to compare results.

Discussion
Activities in the context of telerehabilitation using PFMT and self-care can represent a viable and effective solution to minimize the side effects of gynecological cancer treatment and improve women’s quality of life.