bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Risk Factors for Cognitive Decline Using Electronic Health Record Data: A Scoping Review
Authors: Wang Liqin , Yang Richard , Sha Ziqin , Kuraszkiewicz Anna Maria , Leonik Conrad , Zhou Li , Marshall Gad A.
Published: August 2024

Background: The data and information contained within electronic health records (EHR) provide a rich, diverse, longitudinal view of real-world patient histories, offering valuable opportunities to study antecedent risk factors for cognitive decline. However, the extent to which such records’ data have been utilized to elucidate the risk factors of cognitive decline remains unclear.
Methods: A scoping review was conducted following the PRISMA guideline, examining articles published between January 2010 and April 2023, from PubMed, Web of Science, and CINAHL. Inclusion criteria focused on studies using EHR to investigate risk factors for cognitive decline. Each article was screened by at least two reviewers. Data elements were manually extracted based on a predefined schema. The studied risk factors were classified into categories, and a research gap was identified.
Results: From 1,593 articles identified, 80 were selected. The majority (87.5%) were retrospective cohort studies, with 66.3% using datasets of over 10,000 patients, predominantly from the US or UK. Analysis showed that 48.8% of studies addressed medical conditions, 31.3% focused on medical interventions, and 17.5% on lifestyle, socioeconomic status, and environmental factors. Most studies on medical conditions were linked to an increased risk of cognitive decline, whereas medical interventions addressing these conditions often reduced the risk.
Conclusions: EHR data significantly enhanced our understanding of medical conditions, interventions, lifestyle, socioeconomic status, and environmental factors related to the risk of cognitive decline.
Structural and functional changes in the oral microbiome of the patients with craniofacial microsomia
Authors: ZANG TIANYING , TANG XIAOJUN , ZHANG Zhiyong , LIU WEI , YIN LIN , Zhao Shanbaga Zhao , Liu Bingyang , Ma LUNKUN , LI ZHIFENG
Published: August 2024

Background
Craniofacial microsomia (CFM), the second most common congenital craniofacial deformity, has manifold clinical manifestations and treatments that may interact with oral bacteria dysbiosis (OBD). However, studies exploring the relationship between CFM and OBD are scanty.
Methods
Saliva samples of 20 patients with CFM and 24 controls were collected, and oral microflora and gene function annotation were compared using 16S ribosomal RNA and metagenomics. The correlation between clinical phenotypes of CFM and microbiota community structure was also evaluated.
Results
The oral microflora of CFM patients exhibited higher richness and evenness. The dominant genera in CFM were mainly pathogenic and included Actinomyces, Fusobacterium, and Prevotella. The severity of CFM was significantly positively correlated with the abundance of Neisseria and Porphyromonas. The upregulated pathways were primarily enriched in biotin and amino acid metabolism, including Tryptophan metabolism, which positively correlated with the abundance of Neisseria.
Conclusion
This study suggests for the first time that patients with CFM exhibit distinct oral bacterial dysbiosis, characterized by an elevated prevalence of opportunistic pathogens and upregulated pathways associated with oral and systemic health. These findings provide evidence for corresponding preventions and therapeutic interventions of CFM.
Automated Radiographic Total Sharp Score (ARTSS) in Rheumatoid Arthritis: A Solution to Reduce Inter-Intra Reader Variation and Enhancing Clinical Practice
Authors: Moradmand Hajar , Ren Lei
Published: August 2024

The total Sharp-van der Heijde score (TSS) is crucial for assessing the joint damage severity in rheumatoid arthritis (RA). Manual scoring is often time-consuming and subjective, leading to variability. This study introduces an Automated Radiographic Sharp Scoring (ARTSS) framework that leverages deep learning to analyze full-hand X-ray images, aiming to reduce inter- and intra-observer variability. A key innovation is its ability to handle patients with joint disappearance and variable-length image sequenced. The framework involves four stages: image pre-processing with ResNet50, hand segmentation using UNet, joint identification via YOLOv7, and TSS prediction using models like VGG16, VGG19, ResNet50, DenseNet201, EfficientNetB0, and Vision Transformer (ViT). Evaluation metrics included Intersection over Union (IoU), Mean Average Precision (MAP), Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), and Huber loss. Training used 3-fold cross-validation with 970 patients, and external testing included 291 subjects. The joint identification model achieved 99% accuracy, with ViT showing a Huber loss of 0.87 for TSS prediction. The ARTSS addresses the challenge of joint disappearance and variable joint numbers, which lead to its generalizability and applicability to clinical. This approach preserves time, reduces inter- and intra-reader variability, improves radiologist accuracy, and aids rheumatologists in making more personalized treatments.
A meta-analysis of the risk of adverse cardiovascular events in patients with cancer treated with inhibitors of the PI3K/AKT/mTOR signaling pathway
Authors: Liang Xiao , Zhang Chengrong , Tang Yuyao , Li YongXin , Zhu Zijun , Qiu Tianlei , Zhao Jiuda
Published: August 2024

Background: With the increasing of PI3K/AKT/mTOR (PAM) inhibitors in cancer therapy, there is a growing need to understand the incidence of cardiovascular events (CVAEs) associated with PAM inhibitors.
Methods: A systematic search of all randomized clinical trials (RCTs) containing at least one PAM group in electronic databases such as PubMed, ClinicalTrials.gov registry, Embase, Medline, Cochrane Library, and major conferences was performed to extract available CVAEs. The cut-off date was January 31, 2024. Study heterogeneity was assessed using the I2 statistic. The risk of CVAEs associated with PAM inhibitors was calculated using Peto OR.
Main outcomes and measures:
The primary outcome was the incidence (95% CI) of PAM inhibitors cardiovascular adverse events in the total population and subgroups. The secondary outcome was the pooled risk of different CVAEs associated with PAM inhibitor exposure in the RCTs.
Results:
33 unique RCTs (n=12,351) were included. The incidence of PAM inhibitors CVAEs of any grade in the intervention group was 48.2%, yielding a combined OR of 2.52 (95% CI, 1.82 - 3.49). The incidence of severe adverse cardiovascular events (≥ grade 3) in the intervention group was estimated at 7.1%, yielding a combined Peto OR of 1.41 (95% CI,1.04 - 1.93). PAM inhibitors were associated with an increased risk of 5 CVAEs including peripheral edema, lymphoedema, hypercholesterolemia, hypertriglyceridaemia and hyperlipidemia, with higher risks for hypercholesterolemia (Peto OR:3.27,95% CI:2.61-4.11, P<0.01; I2 = 55.5%，P=0.06) and hyperlipidemia (Peto OR:3.53. 95%CI:1.70-7.32, P<0.01; I2 = 19.3%，P=0.29).
Conclusion:
This study identified an overall incidence of PAM inhibitors CVAEs and the increased risks associated with PAM inhibitor for five specific CVAEs, not confined to hypercholesterolemia and peripheral edema.
Diagnostic aspect of ferritin level in acquired heart failure in children: a retrospective study in Covid-19 patients
Authors: Hasabi Amir , Farrokhpour Sajjad , Fallahi Mahsa , Tavanayan Masome , Shahvari Samira Zakeri , Satarzadeh Mohammad
Published: August 2024

Background
More important than the issue of Covid is the management of its consequences on other vital organs. Many biomarkers change as a result of this respiratory infection, which depends on the function of vital organs such as the heart. This study aims to investigate the relationship between serum ferritin level and acquired heart diseases in children suffered from covid.
Method
This retrospective study started by examining ferritin levels measured in children with a positive PCR result. Children who underwent echocardiography from March 2019 to one year later were examined. We evaluated the age, gender, echocardiography results and ferritin level of these children.
Results
Out of a total of 116 examined covid patients, 62 (53.45%) were women and 54 (46.55%) were men. The highest level of ferritin based on the age of the examined patients was 6 months to 1 year and then 1 to 3 years, 90% of children were normal in terms of heart diseases, 4.3% MILD TR and 2.6% MILD TR & MR and 2.6 percent were MOD TR + SEVER MR + RV, LV HYPERTROPHY. Ferritin in children and infants with covid disease was lower in females and the statistical analysis of the data showed that there is a significant relationship between ferritin and heart diseases in female covid patients as opposed to males in covid patients in infants and children. Ferritin was significantly higher in covid patients under 6 months who had heart diseases, but this relationship is negligible in other categories.
Conclusion
Serum ferritin level is a predictive factor for acquired cardiovascular disorders, the increase of ferritin level has a high correlation with the severity of heart diseases, so it has a high prognostic potential in children suffered from covid.
A comprehensive treatment algorithm of hip replacement in patient with End-Stage renal disease: A Case Series
Authors: Yan Zhen-lin , Zhu Hong-xia , Xie Yu , Xie Lun-Li
Published: August 2024

Background
Considering the difficulties of femoral neck fractures in patient with end-stage renal disease associated with hemodialysis, it is important to formulate a comprehensive treatment algorithm providing a suitable individual protocol. Thus, the purpose of our study is to introduce a novel comprehensive treatment algorithm for these population.
Case presentation
This article retrospectively analyzed the data of six patients diagnosed with femoral neck fractures or femoral intertrochanteric fracture accompanying with end-stage renal disease associated and accepted regular hemodialysis. The subjects, comprising both males and a female, are of Asian ancestry and exhibit an age range from 66 years to 90 years. All patients accepted hemiarthroplasty of femoral intertrochanteric fracture or femoral neck fracture. Despite lack of large samples, the case series reveals an effective treatment algorithm.
Conclusions
Our study formulate a comprehensive treatment algorithm in patients with femoral neck fractures associated with End-Stage renal disease,and received regular hemodialysis.
Early-onset of Svalbard greening driven by sea ice loss and glacier retreat after the Little Ice Age
Authors: Ingrosso Gianmarco , Ceccarelli Chiara , Giglio Federico , Giordano Patrizia , Hefter Jens , Langone Leonardo , Miserocchi Stefano , Mollenhauer Gesine , Nogarotto Alessio , Sabino Mathia , Tesi Tommaso
Published: August 2024

Climate change is rapidly modifying tundra vegetation productivity and composition in the Arctic. However, empirical long-term evidence of this process is lacking due to field measurement limitations and problematic interpretation of the greening vs. browning from satellite data. Here, we measured plant-derived biomarkers from an Arctic fjord sediment core as proxies to reconstruct past changes in the tundra vegetation during the transition from the Little Ice Age to Modern Warming. Our findings reveal a rapid expansion of the tundra since the beginning of the twentieth century, largely coinciding with the decline of summer sea ice extent and glacier retreat. The greening trend inferred by biomarker analysis peaked significantly in the late 1990s, along with a shift in the tundra community toward a more mature successional stage. Most of this signal was consistent with the biomolecular fingerprint of vascular plant species more adapted to warmer conditions and widely expanding in proglacial areas during recent decades. Our results suggest that vegetation cover in Arctic fjords will drastically increase under the predicted warming scenario and sea ice loss, leading also to a significant change in tundra community structure.
How Does the eHealth Information Use Mitigate Cancer Fatalism in Family Cancer Histories Groups? A Study of Chain Mediation Effects Based on Social Cognitive Theory
Authors: Wang Jiazheng Zayn , Li Qingrui , Zhao Xinshu
Published: August 2024

Background: Cancer fatalism is the greatest obstacle to cancer prevention and treatment behavior and is particularly prevalent among people with a family history of cancer. While previous studies have shown that the use of eHealth information influences cancer fatalism beliefs in the general population, a deeper exploration of the underlying mechanisms is imperative. Using Social Cognitive Theory as a theoretical framework and targeting people with a family history of cancer, this study aimed to investigate whether eHealth information use can effectively alleviate cancer fatalism and elucidate the mechanisms driving this association.
Methods: Data for this study were obtained from the sixth iteration of the National Trends in Health Information Survey (HINTS6), using the survey sample of 3,131 individuals with a family history of cancer. Firstly, this study assesses the direct and indirect effects of eHealth information use on cancer fatalism beliefs; Secondly, exploring the mediating roles of cancer worry, frequency of doctor visits, and trust in cancer information from doctors; Finally, examining a chained mediation model to explain how individuals may change their inherent beliefs about cancer through the eHealth information use.
Results: The results showed that the direct effect (bp =-0.062, p<0.001) and the total effect (bp=-0.059, p<0.001) of eHealth information use were negatively correlated with cancer fatalism. Cancer worry, frequency of doctor visits, and trustin cancer information from doctors were mediating mechanisms and were positively correlated with eHealth information use. In addition, the study revealedthat trustin cancer information from doctors was negatively correlated with cancer fatalism (bp =-0.071, p < 0.001).
Conclusions: eHealth information use combinedwith interventions and offline communication with physicians plays a positive role in reducing cancer fatalism in the family cancer history, providing individuals with more health information and support. Public health departments should use eHealth information platforms to communicate correct cancer science knowledge and positive attitudes toward cancer and encourage people to trust health information from authoritative science, such as doctors, to reduce cancer fatalism and adopt positive health behaviors.
afthd: An R package for accelerated failure time model using MCMC for high dimensional time-to-event data
Authors: Bhattacharjee Atanu , Vishwakarma Gajendra K , Kumari Pragya , Tank Fatih
Published: August 2024

High-dimensional data, along with the time-to-event outcome analysis, is a challenging task. The accelerated failure time (AFT) model is an alternative to the Cox proportional hazard (CPH) model in survival analysis. However, there is a lack of available packages and functions to work on high-dimensional time-to-event data for the AFT model using Bayesian. We developed an R package 'afthd' that works with an advanced AFT model for high-dimensional time-to-event data under the Bayesian paradigm and also provides different diagnostics plots for univariate and multivariable Bayesian analysis. We attempted to present a computer code with open-source R software to work with high-dimensional data for the AFT model. The conventional AFT model has been extended for the Bayesian framework of log-normal, Weibull, and log-logistic AFT models for univariate and multivariable high-dimensional data contexts. The methodology is validated by performing the simulation technique, showing consistent results for parameters in all three types of parametric AFT models. The application part is also performed on two different real high-dimensional liver cancer datasets, which clearly reveals the proposed method’s significance by obtaining inferences for survival estimates for the disease. The developed package 'afthd' is competent to work with high-dimensional time-to-event data using the conventional AFT model and the Bayesian paradigm. Other aspects, like missing covariates in high-dimensional data and competing risks analysis, are also covered in this work.
Insecticide resistance status and mechanisms in Aedes aegypti and Aedes albopictus from different dengue endemic regions of Panama
Authors: Carrera Lorenzo Caceres , Piedra Luis , Torres-Cosme Rolando , Castillo Anakena M , Bruno Antonio , Martínez Dan , Rodríguez Maria Magdalena , Bisset Juan A
Published: August 2024

Background
Dengue is a serious public health problem worldwide, including Panama. During the last years the number of dengue cases have increased, this may be due to the presence of mosquito populations resistant to insecticides. The aim of this study was to characterize the resistance status, its enzymatic mechanisms and Kdr mutations in wild populations of Aedes aegypti and Aedes albopictus.
Methods
Standard WHO bioassays were performed using insecticide-treated filter papers to determine resistance in populations Ae. aegypti and Ae. albopictus to pyrethroids insecticides, organophosphates, to the carbamate propoxur and to the organochlorine DDT. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the Kdr mutations Val1016IIe and F1534C.
Results
The strains Ae. aegypti El Coco showed confirmed resistance to deltamethrin (78.5% mortality) and lambda-cyhalothrin (81%), Aguadulce to deltamethrin (79.3%), David to deltamethrin (74.8%) and lambda-cyhalothrin (87.5%) and Puerto Armuelles to permethrin (83%). Aedes aegypti El Empalme showed confirmed resistance to pirimiphos-methyl (62.3% mortality), chlorpyrifos-methyl (55.5%) and propoxur (85.3%). All strains of Ae. albopictus showed possible resistance to PYs and five strains to DDT. Only Ae. albopictus Canto del Llano showed confirmed resistance to pirimiphos-methyl (70% mortality) and malathion (62%). Esterase activity was variable across sites with the most frequent expression of α-EST compared to β-EST in Ae. aegypti populations. In Ae. albopictus the expressed enzymes were β-EST and MFOs. The Kdr Val1016IIe mutation was detected in Ae. aegypti Aguadulce, El Coco and David.
Conclusion
The presence of a varied and generalized resistance, enzymatic mechanisms and the Val1016IIe mutation may be associated with the intensive use and possibly misuse of the different insecticides applied to control Aedes populations. These results highlight the need to develop a program for resistance management. Also, alternative approaches to mosquito control that do not involve insecticides should be explored.
Golgi-derived extracellular vesicle production induced by Viral 2-E channels
Authors: Li Qiguang , Liu Qian , Li Shuangqu , Zuo Xiaoli , Zhou Hu , Gao Zhaobing , Xia Bingqing
Published: August 2024

Extracellular vesicles (EVs) facilitate cell-to-cell communication, and some enveloped viruses utilize these vesicles as carriers to mediate viral transmission. SARS-CoV-2 envelope protein (2-E) forms a cation channel and overexpression of 2-E led to the generation of a distinct type of large extracellular vesicle (2-E-EV). Although 2-E-EV has been demonstrated to facilitate viral transmission in a receptor-independent way, the characteristics and biogenesis mechanism remained enigmatic. We identified 2-E-EV as a novel EV. Via lipidomics and proteomic analysis, we found 2-E-EV is distinct from endosome-derived exosomes. 2-E-EV is notably enriched in Golgi apparatus components, aligning with the observed fragmentation in Golgi morphology. Through live cell imaging, we established a connection between 2-E-EV formation, Golgi fragmentation, and channel activity, emphasizing the role of 2-E-EV as an ion channel-induced extracellular vesicle. Our work highlights 2-E-EVs as distinctive Golgi-derived vesicles, contributing to a deeper understanding of 2-E channel-mediated virus-host dynamics, with implications for therapeutic strategies and drug delivery.
GWSF-EuSWAP70 gene expression to enhance gray mold resistance in Arabidopsis thaliana
Authors: Huang Zhenchi , Ma Shengjian , Cai Fenglian , Li Lichun , Li Xiaoming , Wu Zhi hua
Published: August 2024

Background
Eucalyptus, a widely cultivated woody plant, is susceptible to a diverse array of pests and diseases, leading to reduced yields and economic losses. Traditional breeding methods are very time-consuming; therefore, plant genetic engineering has emerged as a promising approach for plant pathogen management. However, the genetic transformation system of eucalyptus is still in its early stages of development, while studies on transgenic eucalyptus and its disease-resistance genes are limited. The SWAP70 gene has been shown to play a crucial role in the defense response of Arabidopsis thaliana and rice. In this study, the model plant A. thalianawas selected for genetic transformation. The aim was to enhance the expression of the EuSWAP70 gene derived from Eucalyptus grandis, and other disease-resistance genes, by utilizing an artificial GWSF promoter.
Results
The results showed that the EuSWAP70 gene was successfully transformed into A. thaliana, and the PCR assay confirmed the presence of the EuSWAP70 gene in transgenic Arabidopsis plants. The gray mold resistance of the EuSWAP70 transgenic Arabidopsis plants under GWSF and CaMV35S promoters was evaluated against Botrytis cinerea infection. After gray mold infection, Arabidopsisplants were ranked by leaf pore area percentage: wild-type > CaMV35S-EuSWAP70 > GWSF-EuSWAP70. The transgenic plants showed stronger gray mold resistance, and the GWSF-EuSWAP70 transgenic plants were stronger than the CaMV35S-EuSWAP70 transgenic plants.
In two transgenic Arabidopsis plants treated with different inducers, the expression levels of ten disease-resistant genes were compared, and there was a significant difference between them. The expression levels of disease-resistance genes, particularly NPR1 and ChiB, were found to be higher in GWSF-EuSWAP70 transgenic Arabidopsis plants than those in CaMV35S-EuSWAP70transgenic plants. GWSF-EuSWAP70 transgenic Arabidopsis plants have stronger disease-resistance gene activity than CaMV35S-EuSWAP70plants under various inducers. The GWSF-EuSWAP70transgenic plants have minimal background expression and a wide range of plant inducer responses. Different inducer treatments had different effects on gene expression levels, B. cinerea treatment resulted in a significant increase in the expression levels of NPR1 and ChiB genes, whereas ethylene and salicylic acid (SA) pre-treatment reduced the expression levels of ChiB genes under B. cinerea treatment.
Conclusions
The EuSWAP70 gene can be effectively introduced into Arabidopsis plants, induced by two promoters, and potentially improve their B. cinerearesistance.
PET imaging of [ 52 Mn]Mn-DOTATATE and [ 52 Mn]Mn-DOTA-JR11
Authors: Omweri James M. , Houson Hailey A. , Lynch Shannon E. , Tekin Volkan , Sorace Anna G. , Lapi Suzanne E.
Published: August 2024

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [68Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [68Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake. The goal of this study was to label both DOTATATE and DOTA-JR11 peptides with 52Mn in high radiochemical yields (RCY) and sufficient specific activity. A comparison of these two compounds was performed in in vitro and in vivo studies in animals with somatostatin receptor-positive xenografts to characterize differences in cell, tumor, and tissue uptake. Radiolabeling of DOTATATE and DOTA-JR11 was carried out by combining varying concentrations of the peptides with [52Mn]MnCl2. In vitro stability of the radiotracers was determined in mouse serum. In vitro cell uptake and internalization assays were performed in SSTR2 + AR42J cells and negative controls. In vivo biodistribution and longitudinal PET imaging was evaluated in mice bearing AR42J tumors. Both [52Mn]Mn-DOTATATE and [52Mn]Mn-DOTA-JR11showed affinity for SSTR2 in AR42J cells. However, the uptake of [52Mn]Mn-DOTATATE was higher (11.95 ± 0.71%/ mg) compared to [52Mn]Mn-DOTA-JR11 (7.31 ± 0.38%/ mg) after 2 h incubation. After 4 h incubation, 53.13 ± 1.83% of the total activity of [52Mn]Mn-DOTATATE was internalized, whereas only 20.85 ± 0.59% of the total activity of [52Mn]Mn-DOTA-JR11 was internalized. The PET images revealed similar biodistribution results, with [52Mn]Mn-DOTATATE showing a significant tumor uptake of 11.16 ± 2.97% ID/g, while [52Mn]Mn-DOTA-JR11 exhibited a lower tumor uptake of 2.11 ± 0.30% ID/g 4 h post-injection. The synthesis of both radiotracers was accomplished with high RCY and purity. The cell uptake and internalization of [52Mn]Mn-DOTATATE showed higher levels compared to [52Mn]Mn-DOTA-JR11. PET images of the radiotracers in AR42J tumor bearing mice demonstrated similar biodistribution in all organs except the tumor, with [52Mn]Mn-DOTATATE showing higher tumor uptake compared to [52Mn]Mn-DOTA-JR11. The variations in properties of these tracers could be used to guide further imaging and treatment studies.
Impact of encounters on patient app use: results of a tethered mobile personal health record usage pattern analysis
Authors: Tak Yae Won , Kim Jeong-Hoon , Lee Jae-Ho , Lee Yura
Published: August 2024

Introduction
The adoption of tethered mobile personal health records provides not only medical information to patients but also various convenience functions related to hospital use, thereby increasing accessibility to healthcare services and promoting patient engagement. We analyse the tethered mobile personal health records app’s usage logs to determine how it can contribute to improving medical service accessibility and patient engagement.
Methods
Log data, that comprised menu type, log time, and date, were collected from the mobile personal health records app of a tertiary referral hospital. Clinical information, including patients’ demographics and visit typeㅅ, was collected from the clinical research warehouse system. The usage log was analysed in terms of the type of visit, service function, and time period.
Results
Outpatients accounted for 34% of the total app usage and was the most app-accessed visit type. The most utilized menu functions were lab test and visit schedule for visits or non-visits. For Inpatient and Health check-ups, menu usage patterns showed a focus on lab test results. While investigations and other menu usage showed double peaks in the morning and afternoon, peak usage of lab test results correlated with inpatient blood sampling times, which was around 9 am.
Discussion
App menus to access health information, particularly blood tests, emerged as the most accessed menu. Hence, when compared with blood sampling times and hospital information system usage patterns, encounters occurring in the hospital majorly impacted patient app use. For improved patient engagement, improving lab test function should be the priority.
Effects of PD-L1 Inhibitors on Mitochondrial Function in Melanoma A375 Cells: Unveiling a Shielded Drug Resistance Mechanism
Authors: 张 宁 , Feng Fenglan , Dang Ruonan , Zhao Xiaoqing , Wang Xingrong , Yang Yuqi , Deng Jinjin , Meng Wei , Huang Xinglan , Zhang Shunying , Deng Yuqiong , Huang Caifeng , Yan Peng , Liu Zhongrong , Cheng Xiping
Published: August 2024

Background: Resistance to immune checkpoint inhibitors, particularly PD-L1 inhibitors, poses a significant challenge in cancer treatment by limiting patient survival. The intricate mechanisms underlying this resistance remain poorly understood, highlighting a critical gap in oncology research.
Objective: This study aimed to delve into the regulatory impacts of PD-L1 inhibitors on mitochondrial function within melanoma cells (A375) and explore the potential correlation between PD-L1 resistance and mitochondrial function.
Methods: 1. A375 cells were treated with PD-L1 inhibitors, and the effects on mitochondrial gene expression, respiratory chain complex IV activity, reactive oxygen species (ROS) levels, apoptosis-related genes (BAX and BCL-2) expression, tumor pathogenicity-related indicators (cell viability, migration, and invasion) were observed. 2. Fluorescently labeled mitochondria membrane, cell nucleus, and PD-L1 inhibitors were used in high-resolution confocal microscopy to determine whether PD-L1 inhibitors can enter mitochondria. 3. A375 cells treated with PD-L1 inhibitors were subjected to intervention with mitochondrial respiratory chain inhibitor, succinate carrier inhibitor, to observe the effects on apoptosis-related genes (BAX mRNA and BCL-2 expression), tumor pathogenicity-related indicators (cell viability, migration, and invasion).
Results: 1.Through high-resolution confocal microscopy, it was observed that PD-L1 inhibitors penetrated mitochondria, binding to the cristae of the inner mitochondrial membrane without entering the cell nucleus.2.Treatment with PD-L1 inhibitors resulted in increased mitochondrial gene expression and respiratory chain activity, reduced ROS levels, elevated BAX expression, decreased BCL-2 expression, and diminished tumor migration and invasion in A375 cells.3.Inhibition of mitochondrial respiratory chain function by succinate carrier inhibitors impeded the enhancement of mitochondrial function induced by PD-L1 inhibitors in A375 cells. This led to a sustained increase in BAX expression, a significant decrease in BCL-2 expression, and a notable reduction in cell viability, tumor migration, and invasion.
Conclusion: PD-L1 inhibitors exhibit the capability to penetrate mitochondria, exerting an inhibitory effect on tumor activity in melanoma cells while significantly enhancing mitochondrial function. Disrupting this enhancement of mitochondrial function by PD-L1 inhibitors reverses their overall anti-tumor efficacy, hinting at a novel mechanism of tumor resistance mediated through the regulation of the mitochondrial pathway by PD-L1 inhibitors.
Bee community response to multiple stressors along a tropical urban-peri urban gradient
Authors: Dutta Aditi , Samajpati Indranil , Basu Parthiba
Published: August 2024

Urbanization in tropical landscapes is a complex phenomenon that can lead to community shift rather than simple species extinction in response to multiple stressors in peri-urban and urban settings. We have investigated impacts of different stressors along a tropical urban-peri-urban gradient on the bee community, the health of which is a global conservation concern. Several stressors such as, increased built-up area, pesticide application and air pollution may effectively regulate bee community composition and corresponding functional diversity along urban-peri urban gradients. We investigated the changes in bee community structure in response to associated stressors in 20 locations including parks and gardens along an urban-peri urban gradient surrounding the megacity of Kolkata. Bee community structure differed significantly between urban and peri urban sites with urban sites showing lower value of nestedness. Network analysis also revealed thatApis floreaandLasioglosssumsp. 1 were the most important species in the urban and peri-urban areas respectively. Functional diversity increased with urbanization and decreased with pesticide toxicity. Functional redundancy decreased with urbanization. Individual stressor impacted the bee assemblage differentially along the urbanization gradient. SO2and pesticide toxicity negatively influenced bee abundance and diversity. Urban sites sustained more specialized species and therefore are more vulnerable to shocks while peri-urban sites had a more functionally redundant community making it comparatively more resilient.
“Being a round square in an extremely challenging situation”—Healthcare professionals’ experiences of palliative care during the COVID-19 pandemic – A deductive and inductive qualitative study
Authors: Melin-Johansson Christina , Olsson Cecilia , Larsson Maria , Tillfors Maria , Granrud Marie Dahlen , Grøndahl Vigdis Abrahamsen , Helgesen Ann Karin , Sandsdalen Tuva , Bååth Carina , Osterlind Jane
Published: August 2024

Background
The COVID-19 pandemic has highlighted the importance of healthcare systems that can deliver high-quality palliative care during extreme challenges. During the pandemic, professionals across all healthcare contexts confronted enormous pressure due to a lack of pandemic readiness, practical and emotional challenges, and an increased number of dying patients. To support equitable high-quality palliative care for all people in future pandemics, it is crucial to learn from the nurses on the front lines during the COVID-19 pandemic.
Aim
To explore nurses’ experiences of providing end-of-life care in general and specialized palliative care settings to patients during the COVID-19 pandemic.
Methods
This qualitative study is part of a larger Swedish–Norwegian multi-center project called Palliative Quality Care COVID-19 (PaQC-C19). Data were collected in autumn 2021 and spring 2022 using qualitative individual interviews with 20 registered nurses and assistant nurses in general and specialized palliative care. A stepwise deductive and inductive qualitative content analysis was utilized in the search for domains and subthemes following the method of Elo and Kyngäs (2008).
Results
Three domains, one overarching theme, and nine subthemes were developed. The domains described positive and negative aspects as well as strategies used when providing modified palliative care, the challenges concerning contamination, and how the nurses experienced guidance from managers during the pandemic. The overarching theme “being a round square in an extremely challenging situation” summarizes how the nurses safeguarded the patients’ dignity and provided support to the next of kin in extremely challenging situations during the COVID-19 pandemic.
Conclusions
The results of this study suggest that the prerequisites for nurses and the palliative care approach they use change during a pandemic; they felt inadequate and insecure and struggled very hard throughout the seemingly never-ending pandemic. These findings can be used as a basis for reflection in collaborative learning interventions within palliative care and as a guide for teachers in educational palliative care programs.
Differences in the epidemiology, clinical characteristics, distribution of microorganisms and outcomes between COVID-19 patients and non-COVID-19 patients with ICU- associated BSIs: a one-center retrospective study
Authors: Sarıtaş Çağla Keskin , Özsüt Halit , Benli Aysun , Başaran Seniha
Published: August 2024

Background
We aimed to study the differences between patients with COVID-19 and non-COVID-19 ICU-associated BSIs in terms of epidemiological, clinical, microbiological and outcome data.
Methods
Patients who developed BSI >48 hours after admission to the ICU among patients with COVID-19 and non-COVID-19 who were followed during a two-year pandemic period at a university hospital in the ICU were selected.
Descriptive statistics were used for differences between patients with COVID-19 and without COVID-19. Logistic regression analysis was used to determine mortality risk factors in BSI patients.
Results
Infection of the lower respiratory tract was much more common in COVID-19 patients (43.3% to 26%, p =0,000). The abundance of Acinetobacter baumanii, a microorganism causing BSI was significantly greater in COVID-19 patients than in non-COVID-9 patients (5.6% to 24.4%; p = 0.000), and the prevalence of Gram-negative MDR bacteria (61.7 to 81.7%, p = 0.020) was greater.
The duration of antibiotic use in the hospital was associated with the BSI, where Gram-negative MDR bacteria are active (p = 0,000), and the appropriateness of empirical treatment (p = 0.031) was more common in the COVID-19 group.
In our study, we discovered that patients with COVID-19 had lower levels of acute-phase reagents commonly used for BSI but more severe clinical symptoms during BSI.
COVID-19 survivors had shorter survival times after BSI (p = 0.032) than non-COVID-19 survivors.
Conclusions
The increased use of antibiotics in hospitals for patients with severe COVID-19 and deficiencies in infection control measures have led to an increase in MDR microorganisms.
Evaluation of the validity of pancreatoduodenectomy in older patients with distal cholangiocarcinoma in terms of recurrence
Authors: Izumo Wataru , Kawaida Hiromichi , Saito Ryo , Nakata Yuki , Amemiya Hidetake , Higuchi Yudai , Nakayama Takashi , Takahashi Kazunori , Maruyama Suguru , Takiguchi Koichi , Shoda Katsutoshi , Shiraishi Kensuke , Furuya Shinji , Kawaguchi Yoshihiko , Ichikawa Daisuke
Published: August 2024

Background This retrospective study investigated the validity of pancreatoduodenectomy (PD) with regard to recurrence in older patients with distal cholangiocarcinoma (DC). Methods We compared 32 patients aged ≥ 75 years and 68 patients aged < 75 years who underwent PD for DC, and evaluated the relationship between age, clinicopathological factors, and outcomes. Results Postoperative mortality and morbidity rates did not differ between the groups. Although there were no significant differences in 5-year recurrence, disease-specific survival, and overall survival rates between the groups (44.5, 61.5, and 55.0% in patients ≥ 75 years and 48.7%, 63.0%, and 58.5% in patients < 75 years; P = 0.82, 0.57, and 0.34, respectively), the median time from recurrence to death (RTD) in older patients was significantly shorter than that in younger patients (0.6 years vs 1.3 years, P = 0.020). In multivariate analysis, age ≥ 75 years (hazard ratio [HR]: 3.5), controlling nutritional status (CONUT) score ≥ 4 (HR: 4.7), poorly-differentiated adenocarcinoma or adenosquamous carcinoma (HR: 4.7), and failure to implement treatment after recurrence (HR: 5.8) were independent risk factors for a short time from RTD. Furthermore, at the time of recurrence, older patients had significantly poorer serum albumin levels, prognostic nutrition index, Glasgow prognostic score, and CONUT score. Age ≥ 75 years (odds ratio: 0.24) was an independent risk factor for implementation of treatment after recurrence. Conclusions PD in older patients may be acceptable; however, the median time from RTD was shorter owing to lower nutritional status and rates of treatment implementation after recurrence.
The Pathway Relationship Between Physical Activity Levels and Depressive Symptoms in University Students Mediated by Cognitive Flexibility
Authors: Yu Fen , Jia Shuqi , Liu Qin , Guo Zhaohui , Li Pan
Published: August 2024

Objective
To explore the mediating pathway of cognitive flexibility in the relationship between physical activity and depressive symptoms among university students.
Methods
A cross-sectional design was used to survey 2,537 university students using the Physical Activity Rating Scale-3, Patients′ Health Questionnaire, and Cognitive Flexibility Inventory. Data analysis was conducted using independent samples t-test, chi-square test, correlation analysis, one-way ANOVA, and mediation analysis.
Results
There was a significant negative correlation between physical activity levels and depressive symptoms scores (r = 0.063, P < 0.059), a significant positive correlation between physical activity levels and controllability scores (r = 0.064, P < 0.05), and a significant negative correlation between depressive symptoms and controllability scores (r=-0.367, P < 0.01). The total effect of physical activity intensity on depressive symptoms was − 0.3542, 95% CI: -0.5439~-0.1645, the direct effect of physical activity intensity on depressive symptoms was − 0.3542, 95% CI: -0.5439~-0.1645, and the mediating effect of controllability was − 0.1343, 95% CI: -0.2145~-0.0630.
Conclusion
The more physical activity university students engage in, the lower their depressive symptoms scores. Controllability mediates the relationship between physical activity and depressive symptoms in university students.
SRT3025-loaded cell membrane hybrid liposomes enhanced anti-carcinoma activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase
Authors: Wang Xiaobin , Li Shulin , Li Zichen , Lin Zhuona , Wang Zhifeng
Published: August 2024

Background
Bladder cancer is one of the most common malignancies of the urinary system, and despite significant advances in diagnosis and treatment, oxaliplatin resistance remains a major clinical challenge. Thus, developing a novel delivery system is required to overcome oxaliplatin resistance and improve patient outcomes.
Methods
Bladder cancer cell lines, T24 and 5637, were cultured in McCoy’s 5A and RPMI 1640 medium, respectively. The phospholipids and cell membranes were used to formulate the hybrid liposomes. Cell Counting Kit-8 assay was used to determine the cell viability and proliferation. Cell death and apoptosis were quantified by trypan blue, calcein-AM/PI double staining, and Annexin V-APC/PI apoptosis assay. Western blot analysis was used to determine the proteins level.
Results
The present study demonstrated that SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhance the chemosensitivity to oxaliplatin (OXA). 3025@ML monotherapy as well as the combination therapy, 3025@ML plus OXA significantly enhanced the anti-carcinoma activity of OXA. In mechanistic studies, 3025@ML inhibited the PI3K/AKT/mTOR signaling pathway and reduced the expression of key metabolic regulators PKM2 and FASN. Furthermore, this study demonstrated that targeting lipid metabolism and inhibiting FASN can effectively overcome oxaliplatin resistance.
Conclusion
The study demonstrated that SRT3025-loaded cell membrane hybrid liposomes significantly enhance the anti-tumor activity of OXA. This novel drug delivery system inhibits key metabolic pathways, increasing DNA damage and tumor cell apoptosis. The results suggest that 3025@ML is a promising therapeutic strategy for overcoming oxaliplatin resistance and improving cancer treatment outcomes.
The application of augmented reality navigation combined with fluorescence laparoscopy in the resection of tumors in the middle lobe of the liver
Authors: Shen Zhengchao , Xi Shihang , Jiang Bin , Chen Zhiyuan , Pan Xuan , Wang Xiaoming
Published: August 2024

Objective
To investigate the application value of augmented reality (AR) navigation combined with fluorescence laparoscopy in the resection of tumors in the middle lobe of the liver.
Methods
The clinical data of 10 patients who underwent hepatectomy for middle hepatic lobe tumors and AR combined with fluorescence laparoscopy at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wannan Medical College, from May 2023 to January 2024 were retrospectively analyzed. The implementation method of AR was as follows: the preoperative 3D model was projected into the created 3D space, and the collected real-time laparoscopic images were fused into the 3D space background to create an interactive environment. For the fluorescence imaging method, according to the results of ICG-15, the appropriate operation time was determined to achieve the best fluorescence imaging effect.
Results
A total of 10 patients were successfully treated without conversion to open surgery. (1) Intraoperative situations: All the tumors were located in the middle lobe of the liver; the intraoperative fluorescence imaging rate was 100%; the average tumor length was 5[4–7] cm; the average operation time was 262.5 ± 24.8 min; and the average amount of intraoperative blood loss was 440.0 ± 58.1 ml. In the technical application of AR, the average registration error was 6.3 ± 0.6 mm; the average intraoperative verification of the number of blood vessels was 5.6 ± 0.6; and the average intraoperative prediction of the number of blood vessels was 4 [2–5]. (2) Postoperative situation: the average postoperative hospital stay was 9.1 ± 1.6 days. The postoperative pathological diagnosis was hepatic cell carcinoma (HCC) in eight cases and metastatic hepatic carcinoma (MHC) in two patients.
Conclusion
In complex hepatectomy, the application of AR combined with fluorescence laparoscopy can help verify and predict important anatomical structures, which has broad clinical application prospects.
Complex shape markers can detect alterations in the spatial distribution of cell nuclei in human lung squamous cell carcinoma: a useful tool for automatic analysis?
Authors: Santos Ana Vitoria Ferreira dos , Ferreira Renan Gabriel da Silva , Tenorio Fernanda das Chagas Angelo Mendes , Maia Carina Scanoni , Junior Valdemiro Amaro da Silva , Nogueira Romildo de Albuquerque , Tenorio Bruno Mendes
Published: August 2024

Lung cancer is the leading cause of cancer deaths. The use of computational methods to quantify changes not perceptible to the human eye is growing in digital pathology imaging, improving detection rates quickly and at low cost. Therefore, the present study aims to use computational complex shape markers as tools for automated analysis of the spatial distribution of cells in microscopic images of squamous cell lung carcinoma (SqCC). Photomicrographs from pathology glass slides in the database LC25000 were used. The fractal dimension and lacunarity of the lung cell nuclei statistically changed in SqCC compared to the control. The multifractal analysis showed a significant difference in Dq, α, and f(α) for all values of q (-10 to + 10), with a greater increase for more positive q values. The number of cells, circularity, area, and perimeter also changed in SqCC images. However, the parameters aspect ratio, roundness, and solidity did not show statistical differences between the SqCC and benign tissue. The complex shape markers with the greatest changes in this study were the f(α) value in multifractality (53%) and lacunarity (41%). In conclusion, the automated quantification of the spatial distribution of cell nuclei can be a fast, low-cost tool for evaluating the microscopic characteristics of SqCC; therefore, the complex shape markers could be useful methods for software and artificial intelligence to detect lung carcinoma.
Study on the operating parameter optimization based on the temperature characteristics of fuel cell
Authors: Feng Yong , He Miaomiao , Wang Kaiqiong , Chen Juexiao , Jiang Qian , Shi Lei , Gu Ziheng , Ding Wei
Published: August 2024

The performance of fuel cells is influenced by many factors, among which operating temperature is crucial. Therefore, this study focuses on analyzing the performance of fuel cells at different temperatures and optimizing operational parameters at the optimum temperature condition to enhance the performance and lifespan of fuel cells. The research finds that the optimal temperature for fuel cells is 69.9°C, with an efficient operating temperature range of 60–80°C, and the optimal flow rate range is 1000–1600 ml/min. The influence of back pressure on fuel cell performance becomes less significant when it exceeds 2.5 bar. Furthermore, this study utilizes a Gaussian process regression model to optimize the performance of fuel cells under different temperature, flow rate, and back pressure combinations. Regression analysis model predictions suggest that the optimum operating temperature is 71°C, with an optimal back pressure range of 0.9–1.4 bar and a flow rate range of 1310–1600 ml/min.