bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin K supports TGF-β1 depended in vitro human Langerhans cell differentiation and function via Axl
Authors: Bauer Thomas , Richter-Eder Susanne , Yasmin Nighat , Jurkin Jennifer , Köffel René , Strobl Herbert
Published: February 2025

Introduction

On the outermost edge of the body a dense network of dendritic cells (DCs), the so-called Langerhans cells (LCs), represents the first immune barrier. The establishment and maintenance of this epidermal network is dependent on the cytokine transforming growth factor-β1 (TGF-β1) expressed by keratinocytes (KC) and LCs. We recently identified a crucial downstream effector of TGF-β1, the receptor tyrosine kinase Axl. Axl belongs to the TAM receptor family, which also includes Tyro3 and Mer, and is activated through the vitamin K-dependent ligands Gas6 and Protein S.

Methods

We have now established that TGF-β1 dependent in vitro human LC generation from CD34+ progenitor cells can be enhanced by Axl over-expression.

Results

Additionally, we supplemented vitamin K into serum-free human LC generation cultures in order to activate the endogenous ligands Gas6 and Protein S. Vitamin K exhibited supportive effects on LC differentiation and LC-associated gene expression. The vitamin K antagonist warfarin on the other hand, hindered efficient LC differentiation. Blocking antibodies against Axl abrogated the positive effect of vitamin K on LC differentiation. Lastly, vitamin K downregulated the immune activation marker CD86 during LC differentiation and blocked the upregulation of CD86 during LC activation in vitro, in an Axl independent manner.

Discussion

Taken together, we provide evidence for the supportive role of vitamin K in regulating skin immunity.
Recognition of MR1-antigen complexes by TCR Vγ9Vδ2
Authors: Loureiro José Pedro , Vacchini Alessandro , Berloffa Giuliano , Devan Jan , Schaefer Verena , Nosi Vladimir , Colombo Rodrigo , Beshirova Aisha , Montanelli Giulia , Meyer Benedikt , Sharpe Timothy , Chancellor Andrew , Recher Mike , Mori Lucia , De Libero Gennaro
Published: February 2025

The TCR-mediated activation of T cells expressing the TCR Vγ9Vδ2 relies on an innate-like mechanism involving the butyrophilin 3A1, 3A2 and 2A1 molecules and phospho-antigens, without the participation of classical antigen-presenting molecules. Whether TCR Vγ9Vδ2 cells also recognize complexes composed of antigens and antigen-presenting molecules in an adaptive-like manner is unknown. Here, we identify MR1-autoreactive cells expressing the TCR Vγ9Vδ2. This MR1-restricted response is antigen- and CDR3δ-dependent and butyrophilin-independent. TCR gene transfer reconstitutes MR1-antigen recognition, and engineered TCR Vγ9Vδ2 tetramers interact with soluble MR1-antigen complexes in an antigen-dependent manner. These cells are present in healthy individuals with low frequency and are mostly CD8+ or CD4-CD8 double negative. We also describe a patient with autoimmune symptoms and TCR γδ lymphocytosis in which ~10% of circulating T cells are MR1-self-reactive and express a TCR Vγ9Vδ2. These cells release pro-inflammatory cytokines, suggesting a possible participation in disease pathogenesis. Thus, MR1-self-antigen complexes can interact with some TCRs Vγ9Vδ2, promoting full cell activation and potentially contributing to diseases.
A cross-sectional study of risk factors associated with sarcopenia in patients with metabolic dysfunction-associated steatotic liver disease
Authors: Amer Johnny , Abdoh Qusay , Salous Zaina , Alsoud Eithar Abu , AbuBaker Sama , Salhab Ahmad , Badrasawi Manal
Published: February 2025

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease linked to several adverse health consequences that include metabolic disturbances affecting skeletal muscle. Sarcopenia, characterized by skeletal muscle loss, is commonly observed in individuals with MASLD. Our study aimed to identify modifiable lifestyle factors associated with sarcopenia in patients with MASLD.

Methods

This study was a cross-sectional study that was conducted in three clinics in Nablus. A total of 162 adults diagnosed with MASLD were recruited for the study. The patients were interviewed and instructed to provide the necessary information, such as sociodemographic factors, medical and surgical history, lifestyle information, MASLD-related data, and nutritional and functional status. Sarcopenia was defined using the Foundation for the National Institutes of Health (FNIH) criteria, which includes the weight-adjusted skeletal muscle index (wSMI) with the cut-off scores (male subjects: 35.7% and female subjects: 30.7%). Statistical analysis was conducted using SPSS v.21. A chi-squared or independent samples t-test was utilized to identify the factors linked to sarcopenia in the study sample.

Results

Our data found that 44% of MASLD patients had sarcopenia. This condition was significantly associated with female gender (p < 0.0001), older age (p < 0.0001), presence of chronic diseases (p < 0.035), and medication use (p < 0.05). Regarding nutritional factors, sarcopenia had a significant association with obesity, a higher body fat percentage, a high waist-to-hip ratio, a low mid-upper arm circumference, and a reduced calf circumference (p < 0.001). Sarcopenic individuals often exhibit reduced handgrip strength. Lifestyle factors such as a history of smoking and the type of smoking were found to be positively associated with sarcopenia (p < 0.0001).

Conclusion

Sarcopenia was prevalent in the study population and was linked to modifiable risk factors that can be managed to reduce its progression. Future research using different study designs, such as longitudinal design, is recommended to identify the determinants of sarcopenia. Intervention studies are also required to improve the nutritional and functional status of MASLD patients.
Fecal carriage and molecular characterization of carbapenem-resistant Enterobacteriaceae from hospitalized children in a tertiary hospital of Shandong, China
Authors: Deng Xia , Wang Shuyun , Hou Peibin , Sun Na , Yang Ying , Zeng Qian , Wang Juan , Wang Chunping , Lv Xin , Zhang Wenqiang , Fan Ruyue
Published: February 2025

Background

The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has emerged as a serious public health problem worldwide, and the data on the fecal carriage of CRE strains in hospitalized children remain limited. This study aimed to investigate the molecular characteristics of intestinal colonization of CRE in hospitalized children in Shandong, China.

Methods

A retrospective study was conducted from August to November 2023. Antimicrobial susceptibility testing was performed by the broth microdilution method. Carbapenemase genes, drug resistance genes, and plasmid replicon types were detected using multiplex real-time PCR and whole-genome sequencing. Multilocus sequence typing (MLST) was used to determine the genetic relationships between strains.

Results

A total of 20 CRE isolates were identified from 432 fecal samples, with a fecal carriage rate of 4.6%. The CRE isolates predominantly consisted of Escherichia coli (E. coli, n = 13) and Klebsiella strains (n = 6). CRE isolates showed a high resistance rate of 90–100% to seven β-lactam antibiotics. Resistance rates for other antibiotics such as trimethoprim-sulfamethoxazole, tetracycline, azithromycin, ciprofloxacin, chloramphenicol, nalidixic acid, and streptomycin were 90, 85, 85, 80, 75, 75, and 75%, respectively. CRE isolates showed low resistance to amikacin (20%), and none of the isolates were resistant to tigecycline. Additionally, the multidrug resistance rate of CRE isolates was 95%. All CRE strains carried sulfonamide antibiotic and β-lactamase resistance genes, of which the most common β-lactamase resistance genes were blaNDM-1 (n = 9), blaNDM-5 (n = 7) and blaOXA-1 (n = 7). Resistance genes to tetracycline and macrolide antibiotics were also widespread among the strains. The study found that IncFIB and IncFII series plasmids were present in 84 and 42% of the CRE strains, respectively. Additionally, Col, IncFIA, IncC, IncHI2, and IncX series plasmids were also detected. MLST analysis revealed diverse sequence types (STs) among CRE isolates, with ST167 being a common ST among E. coli isolates.

Conclusion

This study revealed blaNDME. coli were the dominant isolates in fecal samples of hospitalized children in Shandong Province, with a broad multidrug resistance to antibiotics, emphasizing that infection control measures need to be taken to limit the spread of these strains.
Cognitive impairment assessed by static and dynamic changes of spontaneous brain activity during end stage renal disease patients on early hemodialysis
Authors: Wu Yunfan , Li Rujin , Jiang Guihua , Yang Ning , Liu Mengchen , Chen Yanying , Chen Zichao , Yu Kanghui , Yin Yi , Xu Shoujun , Xia Bin , Meng Shandong
Published: February 2025

Background

Compared with the general population, patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (ESHD) exhibit a higher incidence of cognitive impairment. Early identification of cognitive impairment in these patients is crucial for reducing disability and mortality rates. Examining the characteristics of static and dynamic regional spontaneous activities in ESHD cases may provide insights into neuropathological damage in these patients.

Methods

Resting-state functional magnetic resonance images were acquired from 40 patients with early ESHD (3 or 4 times/week for more than 30 days but less than 12 months) and 31 healthy matched controls. Group differences in regional static and dynamic regional homogeneity (ReHo) were identified, and correlations examined with clinical variables, including neuropsychological scale scores, while controlling for covariates. Receiving operating characteristic (ROC) curve analyses were conducted to assess the accuracy of ReHo abnormalities for predicting cognitive decline among early ESHD.

Results

The ESHD group exhibited significantly reduced static and dynamic ReHo in the temporal and parietal lobes, including regions involved in basal ganglia–thalamus-cortex circuits, the default mode network, and ventral attentional network. Several static and dynamic ReHo abnormalities (including those in the right parietal and left middle temporal gyrus) were significantly correlated with neurocognitive scale scores. In addition, the dynamic ReHo value of the left superior temporal gyrus was positively correlated with depression scale scores. Comparing the ROC curve area revealed that numerous brain regions with altered ReHo can effectively distinguish between patients with ESHD and those without cognitive impairment.

Conclusion

Our study found that spontaneous activity alterations located in the basal ganglia-thalamus-cortex circuit, default mode network, and ventral attentional network are associated with the severity of cognitive deficits and negative emotion in early ESHD patients. These findings provide further insight into the relationship between cognitive impairment and underlying neuropathophysiological mechanisms underlying the interplay between the kidneys and the nervous system in ESRD patients, and provide further possibilities for developing effective clinical intervention measures.
Efficacy of three modern anti-diabetic drugs on survival outcomes of lung cancer patients with type 2 diabetes in China
Authors: Chen Zijia , Sun Ziyi , Zhang Zhongtao , Lei Chao , Ren Zhewen , Di Yupeng , Wang Zhifei
Published: February 2025

Background

Some anti-diabetic drugs have been proved to be a tumor suppressor or activator. The associations of three relatively new classes of anti-diabetic medications–glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP-4I), and sodium-glucose cotransporter 2 inhibitors (SGLT-2I) with lung cancer prognosis remain unclear.

Methods

The electronic medical data from the National Healthcare Big Data (East) Center was retrospectively analyzed. We included 11,357 newly diagnosed lung cancer patient with type 2 diabetes (T2D) between January 1st, 2020 and July 1st, 2023. Patients were categorized into eight groups according to the mono-or-combination therapy of GLP-1RA, DPP-4I and SGLT-2I. Disease progression and mortality risk were evaluated by cox proportional hazards analysis. Progression-free survival (PFS) and overall survival (OS) were assessed by the Kaplan-Meier (log-rank) method.

Results

Lung cancer patients with T2D who were treated with SGLT-2I & GLP-1RA exhibited the lowest progression (hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.18, 0.78) and mortality risks (HR: 0.34; 95% CI: 0.14, 0.82) as well as prolonged median PFS (1.55 years) and OS (1.62 years) among all groups. In contrast, DPP-4I monotherapy did not show benefit for progression (HR: 1.09; 95% CI: 0.98, 1.22. Median PFS: 1.41 years) and mortality risks (HR: 0.96, 95%CI: 0.84, 1.09. Median OS: 1.48 years). However, when DPP-4I was used in combination with SGLT-2I or GLP-1RA, it caused reductions in both progression and mortality risks.

Conclusion

SGLT-2I & GLP-1RA dual therapy is associated with improved prognosis for lung cancer patients with concurrent T2D. DPP-4I transits from a tumor activator to suppressor when combined with other anti-diabetic drugs. Future studies are needed to examine the underlying biological mechanisms.
Identification and functional characterization of m1A-related genes in colorectal cancer: implications for prognosis, immune infiltration, and therapeutic strategies
Authors: Sun Lan , Huangfu Liwei , Li Fang , Yan Yuhui , Kong Ruiping , Ji Kun , Li Jiachun
Published: February 2025

Introduction

Colorectal cancer (CRC), characterized by its complex genetic heterogeneity and varied responses to treatment, is a leading cause of cancer-related mortality worldwide. The role of N1-methyladenosine (m1A)-related genes in tumor biology remains underexplored. This study aimed to investigate the prognostic value of m1A-related genes in CRC, characterize their role in tumor molecular subtyping, and explore their influence on the tumor microenvironment (TME) and immune infiltration.

Methods

To identify prognostic markers, univariate Cox analysis was performed using multiple datasets, including TCGA and GEO, identifying 43 m1A-related genes. Four distinct molecular subtypes of CRC were defined based on the expression of these genes using non-negative matrix factorization (NMF). Immune infiltration analysis was conducted, and the TIDE algorithm was used to predict response to immune checkpoint inhibitors (ICIs). Furthermore, a prognostic model based on m1A-related genes was constructed and validated across multiple datasets.

Results

The results demonstrated that the four CRC molecular subtypes exhibited significant differences in survival outcomes and clinical characteristics. Stromal cells showed higher m1A scores, suggesting a regulatory role in the TME. There was a positive correlation between m1A-related gene expression and immune checkpoint genes. Moreover, the constructed prognostic model showed robust predictive performance and outperformed other recently published models.

Discussion

The findings suggest that m1A-related genes are not only valuable biomarkers for CRC prognosis but also have significant implications for the immune landscape and could serve as potential targets for therapeutic intervention, particularly in the context of immunotherapy. For instance, SLC12A2 was found to enhance invasion, proliferation, and migration of colorectal cancer cells while inhibiting apoptosis. Further studies are needed to understand the functional roles of m1A modifications across different cell types within the TME.
ASF1B promotes gastric cancer progression by modulating H2AC20 and activating PI3K/AKT and ERK1/2 pathways
Authors: Zhao Mengyuan , Zhang Junchang , He Yanjun , You Chongge
Published: February 2025

Background

Gastric cancer (GC) ranks among the most prevalent malignant neoplasms globally and is associated with a significant mortality rate. Despite the availability of various therapeutic interventions for GC, the overall prognosis for this disease remains unfavorable. This can be attributed to several factors, including delayed diagnosis and the inherent heterogeneity of the tumors. With the continuous enrichment of treatment methods, GC has entered an era of comprehensive treatment oriented toward precision and standardization.

Methods

Through the application of bioinformatics and assessments of tissue microarrays, this study has selected the histone chaperone Anti-Silencing Function 1B (ASF1B) for detailed analysis, including clinical specimens. We then constructed ASF1B knockout and overexpression cell lines, and conducted biological function tests on this basis, validated at mouse and organoid levels. Additionally, human immunereconstitution was performed in NOD-PrkdcscidIl2rgem1/Smoc (NSG) mice, followed by flow cytometry analysis of mouse blood. Mechanically, protein-protein interaction analyses were conducted utilizing Immunoprecipitation-Mass Spectrometry (IP-MS) and Tandem mass tagging (TMT) methodologies to identify protein clusters.

Results

The analysis demonstrated that ASF1B is significantly upregulated in GC tissues and correlates with unfavorable prognostic outcomes. Biological function tests provided that ASF1B contributes to tumor cell proliferation, colony formation, invasion and migration, and plays an important role in the progression of GC in vivo. These findings were validated at both the mouse and organoid levels. Additionally, we observed that ASF1B is involved in the tumor microenvironment, where ASF1B knockdown increases CD8+ T cell infiltration, indicating a negative correlation with immune activation. Mechanically, our investigation revealed that ASF1B emerged as a promoter of GC progression by downregulating H2A clustered histone 20 (H2AC20), thereby influencing the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinases (ERK)1/2 signaling pathways.

Conclusion

ASF1B, recognized as an oncogene, contributes to the initiation and progression of tumors, positioning it as a prospective target for therapeutic intervention in GC.
Monotropein inhibits epithelial–mesenchymal transition in chronic colitis via the mTOR/P70S6K pathway
Authors: Chen Yuanfan , Liu Jiaying , Zhong Shaowen , Zhang Tianwu , Yuan Jin , Zhang Jing , Chen Ying , Liang Jian , Chen Yonger , Hou Shaozhen , Huang Haiyang , Gao Jie
Published: February 2025

Introduction

Patients with chronic colitis are at risk of developing intestinal fibrosis through epithelial–mesenchymal transition (EMT). Monotropein (MON) is the main active ingredient in the traditional Chinese medicine Morinda officinalis How. It has been reported that monotropein can improve ulcerative colitis, but the mechanism remains unclear. However, whether monotropein can improve chronic colitis-associated intestinal fibrosis remains unknown. The study aimed to investigate the effect of monotropein on EMT in chronic colitis and its underlying mechanism.

Methods

The mice chronic colitis model was induced by dextran sodium sulfate (DSS). Cytokines were detected by ELISA. Concentrations of fluorescein isothiocyanate dextran (FITC-Dextran) in serum were detected using a fluorescein microplate analyzer. Intestinal tight junction proteins were detected by immunofluorescence. EMT marker proteins were detected by immunohistochemistry. Transforming growth factor-β1 (TGF-β1) was used to induce EMT in IEC-6 cells. Western blot, real-time quantitative PCR, and immunofluorescence were used to test the inhibitory effect of monotropein on the development of EMT and explore its mechanism.

Results

Results showed that monotropein significantly improved colonic injury and inhibited the expression of colonic tissue EMT marker protein. In addition, molecular docking and molecular dynamics (MD) simulation, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay validated monotropein targeting of mTOR. Monotropein inhibited TGF-β1-induced EMT in IEC-6 cells, inhibited the phosphorylation of mTOR and its downstream proteins, and increased the autophagy activity in chronic colitis mice and IEC-6 cells.

Discussion

The study indicates that monotropein inhibits the development of EMT in DSS-induced chronic colitis mice and TGF-β1-induced IEC-6 cells. Its inhibitory effect on EMT is associated with the mTOR/P70S6K pathway.
New insights into the transcription factor regulatory networks driving peel coloration under hormone induction analyzed by transcriptomics and metabolomics in tangor ‘Murcot’
Authors: Chen Yang , Yang Lei , Li Shuang , Wang Min , Yu Jianjun , Bai Wenqin , Hong Lin
Published: February 2025

Introduction

Fruit color is a crucial quality factor strongly influencing consumer preference for citrus. The coloration of citrus fruit is primarily determined by carotenoids, which produce a range of hues. Gibberellic acid (GA) and ethylene are critical in fruit coloration during the ripening process. Nevertheless, the underlying mechanisms remain poorly understood.

Methods

The present study utilized transcriptomic and metabolomic analyses to investigate the molecular regulatory mechanisms affecting peel pigment metabolism in tangors (Citrus reticulata Blanco×Citrus sinensis L. Osbeck) following GA and ethephon (ETH) treatments.

Results and discussion

Collectively, our findings indicated that GA inhibits chlorophyll degradation and the accumulation of numerous carotenoids, including five violaxanthin esters (violaxanthin palmitate, violaxanthin myristate–caprate, violaxanthin myristate–laurate, violaxanthin dilaurate, violaxanthin myristate) and two β-cryptoxanthin derivatives (β–cryptoxanthin laurate, β–cryptoxanthin myristate), while ETH promotes these processes. Furthermore, GA inhibited the downregulation of lutein, the predominant carotenoid in immature fruits. Notably, integrated transcriptomic and metabolomic analyses identified 33 transcription factors associated with pigment metabolism. Of these, two novel transcription factors, the ethylene-responsive transcription factor ABR1 and the HD-Zip transcription factor ATHB7, were uncovered through both transcriptomic analysis and weighted gene co-expression network analysis. These two transcription factors positively regulated the colouration process, as validated by transient overexpression assays in tobacco. Taken together, our findings elucidated the global carotenoid changes and transcriptional alterations in regulating citrus peel color under hormone induction, with significant implications for improving citrus production.
Effects of irrigation frequency on root growth, nutrients accumulation, yield, and water use efficiency of Panax notoginseng under micro-sprinkler irrigation
Authors: Huang Hui , Shi Yuzhe , Luo Anrong , Xiao Yanan , Liang Jiaping , He Zijian
Published: February 2025

Micro-sprinkler irrigation has been a promising irrigation method to promote Panax notoginseng (Burk) F. H. Chen production but their scientific irrigation frequency in improving yield and water use efficiency of P. notoginseng remains contradictory and inconclusive. The objective of this study was therefore to examine and propose a scientific irrigation frequency in water management of P. notoginseng cultivation considering their impact on soil water, soil available nutrients, root growth, yield, and water use efficiency (WUE). The micro-sprinkler irrigation experiment under shading and rain-shelter conditions was carried out in the growing season of P. notoginseng from 2017 to 2018.The treatments included four micro-sprinkler irrigation frequencies, such as IF1 (irrigation once every three days), IF2 (irrigation once every five days), IF3 (irrigation once every seven days), and IF4 (irrigation once every nine days) in 2017-2018. The results indicated that the IF3 treatment significantly increased the nitrogen accumulation of P. notoginseng (271.98 mg plant-1). In addition, the IF2 treatment enhanced the phosphorus accumulation (27.82 mg plant-1), potassium accumulation (408.38 mg plant-1), total root surface area (67.49 cm2 plant-1), total root volume (3.79 cm3 plant-1) and yield (702 kg ha-1). The IF2 treatment significantly increased WUE by 29.2%, 28.1%, and 37.7% compared with the IF1, IF3, and IF4 treatments, respectively. Our findings suggested that IF2 treatment increased the soil water content, reduced the soil nutrient content, increased the accumulation of phosphorus and potassium in P. notoginseng, promoted the root growth of P. notoginseng, and improved the quality and yield of P. notoginseng, providing a scientific theoretical basis for reasonable water control and green quality production in the cultivation of P. notoginseng under shade and rain shelter cultivation.
Perceived restorativeness and environment quality in relation to well-being, residential satisfaction, and sense of community: an analysis in Northeast Italy
Authors: Miola Laura , Pazzaglia Francesca
Published: February 2025

Introduction

Residential satisfaction consists of pleasure derived from living in a place according to one’s needs, expectations, and outcomes. The present study examines the role of sociodemographic variables, perceived residential quality indicators, and restorativeness in predicting i) well-being, ii) residential satisfaction, and iii) sense of communities in northeast Italy.

Methods

A total of 100 residents (47 women) in various cities in northeast Italy and 211 (112 women) residents in Piazzola sul Brenta (PD) took part in two studies. They answered demographic questions about self-reported restorativeness, residential environment quality, residential satisfaction, mental well-being, and sense of community.

Results

After accounting for age, gender, and income, the results showed that perceived restorativeness enhances sense of community in the Northeast and Piazzola sul Brenta samples and predicts psychological well-being and residential satisfaction in Piazzola sul Brenta. Architectural and functional aspects contribute, respectively, to residential satisfaction and sense of community in both samples, and functional factors predict residential satisfaction for the Northeast sample. Place attachment plays a positive role in residential satisfaction and sense of community in the Northeast and Piazzola sul Brenta.

Discussion

The study reveals a link between perceived restorativeness and residential satisfaction and well-being, providing insight for professionals and policy to improve urban quality.
Incorporating discrete choice experiments into long-term care insurance policy decisions: evidence from China
Authors: Chen Qian , Dong Yuting , Lyu Xinyue
Published: February 2025

Background

Rapid population aging has prompted most emerging economies to consider introducing long-term care insurance (LTCI) as part of a comprehensive social health protection scheme. China is also in the process of establishing its own LTCI framework. However, the details of the scheme are still being explored in pilot cities, and a long-term solution has yet to be finalized. This study aims to examine the insurance preferences of potential enrollees, providing insights to inform further adjustments to the existing framework.

Methods

We examine discrete choice experiment (DCE) evidence from LTCI and evaluate several relevant attributes, including the elimination period, maximum monthly benefit, out-of-pocket rate, and annual premium. The study uses a mixed logit model to elicit respondents’ preferences and willingness to pay (WTP) for these attributes of LTCI and uses physical health status to assess heterogeneity in responses to insurance choice.

Results

We found that most respondents would consider purchasing LTCI, with respondents most preferring the following attributes: (1) an out-of-pocket rate of 25%, (2) a maximum monthly benefit level of 2000 CNY (about 296 USD), and (3) a three-month elimination period. In addition, among the control variables, marital status, personal self-rated health, and the number of children were significant to varying degrees.

Conclusion

The study can provide a reference for further adjustments to the existing scheme, increasing residents’ willingness to participate in insurance and promoting the sustainable development of long-term care insurance.
The relevance of the real-world evidence in research, clinical, and regulatory decision making
Authors: Costa Valton , Custodio Marcelo Graziano , Gefen Eran , Fregni Felipe
Published: February 2025

The scientific method has been established as the optimal approach for systematically gathering and interpreting data on various human phenomena, mainly through the adoption of strict experimental methods, such as controlled randomized trials, which is relevant for clinical decision-making and research, but also weights the regulatory processes for approval of drugs and other medical products. However, a key factor in strict methods is the generalizability of findings that may be limited to specific settings and patient characteristics. This limitation can be addressed by non-experimental methods aimed at investigating populations in naturalistic routine clinical settings, which may offer a more representative reflection of the usage, effectiveness, and safety of healthcare interventions. These approaches can generate the so-called real-world data and the resulting real-world evidence. In this narrative review, we present these concepts, explore the potential applications and advantages of real-world evidence for clinical, research, and regulatory decision-making, and discuss the challenges of employing it, the solutions to improve its generation, and lastly the current level of evidence required for the integration of real-world evidence into regulatory decision-making. We concluded that the advantages of using it, when utilized in a balanced manner, overcome the challenges and, therefore, can offer a time- and cost-saving solution for researchers, the healthcare industry, regulatory agencies, policymakers, and payers towards the patient benefit. The knowledge generated by this approach provides valuable additional insights into medical interventions in real patients under realistic daily scenarios.
Enhancing surgical safety through surgical instruments repair technicians’ training: recent experience from Nigeria
Authors: Udeigwe-Okeke Chisom R. , Seyi-Olajide Justina O. , Obisesan Aderonke O. , Miles Keith , Obi Nkeiruka , Ameh Emmanuel A.
Published: February 2025

Background

Faulty or poorly maintained surgical instruments increase risks of complications, prolong operating times, and reduce efficiency, especially in low- and middle-income countries (LMICs). To address this, Nigeria introduced the Surgical Instruments Repair Technicians (SIRT) program, to improve instrument safety.

Objective

This study evaluated the SIRT program’s initial impact, sustainability, and scalability for improved surgical instrument maintenance in LMICs.

Methods

The program was deployed in two phases. Phase one involved online theoretical and hands-on training for biomedical technicians and operating room/central sterile supply department nurses from Smile Train partner and public hospitals across Nigeria’s six geopolitical zones. Participants were provided repair kits to establish institutional workbenches. Phase two focused on expanding training with a one-week hands-on program. Data on demographics, training feedback, and repair outcomes were collected.

Results

A total of 36 participants completed training (24 in phase one, 12 in phase two), evaluating 1,623 instruments with a 99.6% successful repair rate. Post-training surveys showed that 83.3% of participants felt more confident identifying faulty instruments, and 95.8% reported adequate repair skills. Institutional workbenches were established in 50% of hospitals, and repair drives were conducted within institutions and neighboring hospitals.

Conclusion

The program demonstrated significant potential for improving surgical instrument maintenance and enhancing safety in LMICs. Integrating the program into hospital budgets could support sustainable expansion.
Radon exhalation rate and natural radioactivity in the building materials used in metropolitan Jakarta and its surrounding areas, Indonesia
Authors: Nugraha Eka Djatnika , Modibo Oumar Bobbo , Wahyudi  , Pradana Radhia , Merdekawati Rima Agustin , Megagasri Kartini , Topandi Abdussalam , Rachman Agus Nur , Kurniawan Rusbani , Fajrianshah Evans Azka , Hidayati Nurahmah , Winarni Ilma Dwi , Rosianna Ilsa , Rixson Leons , Purnama Dikdik Sidik , Prasetio Heru , Tokonami Shinji
Published: February 2025

Introduction

Creating a safe living environment involves using healthy and sustainable building materials. Humans are exposed to natural radionuclides, such as 226Ra, 232Th, and 40K decay series, found in building materials that pose a radiological hazard. This study is aimed to investigate the radionuclides content of building materials used in Jakarta and its surrounding areas. The computer code RESRAD-BUILD was used to calculate the annual effective dose received by an adult living in a typical room constructed with the studied building materials.

Methods

Samples such as sand, cement, bricks, and Autoclaved Aerated Concrete (AAC) were collected. The 222Rn surface exhalation rate was determined using the closed chamber method using RAD7, while the activity concentration of natural radionuclide was measured using a gamma spectrometer.

Results and discussion

The 222Rn surface exhalation rate varies from 4 × 10−2 to 1.6 × 100 mBq m−2 s−1 with an average of 4 × 10−1 mBq m−2 s−1. The average 222Rn exhalation rate of the building materials studied was much lower than the global average value of 1.6 × 101 mBq m−2 s−1. The average activity concentration values of 232Th (21 Bq kg−1) and 40K (217 Bq kg−1) in all building materials studied are lower than the global average values of 45 and 412 Bq kg−1. In comparison, the average activity concentration of 226Ra (34 Bq kg−1) is similar to the global average value of 32 Bq kg−1. Furthermore, the assessed radiological hazard from the measured building material has an average activity index of 0.3, while the RESRAD-BUILD estimated total annual effective dose for a typical house constructed using a mixture of the building materials was 0.11 mSv, in which indoor 222Rn alone represents 92% of the total. From the assessment results, the building materials in Jakarta and its surrounding areas do not pose significant concerns regarding radiological hazards. However, the higher contribution of 222Rn suggests the need for a large-scale indoor 222Rn survey in the study area.
Effect of different load of shoulder external rotation exercises on changes in muscle activity and exerted torque
Authors: Saeki Yurika , Kubota Atsushi , Kishimoto Kohei , Inoue Mika , Inoue Takumi , Takazawa Yuji
Published: February 2025

The effects of shoulder external rotation exercises on the EMG amplitude of the infraspinatus, and teres minor, and torque in healthy individuals remain uncertain. In this study, we aimed to determine the effects of varying loads during shoulder external rotation exercises on exerted torque and muscle activity of the infraspinatus, teres minor, and deltoid. Twenty-four upper limbs from 12 healthy adult males (22.5 ± 1.9 years) were included. Participants performed shoulder external rotation exercises with low-, medium-, and high-load conditions using elastic bands of three different tensions. The number of exercises was set so that the total workload during the exercise was equal for each loading condition. The torque of the shoulder external rotation and electromyography (EMG) amplitude of the infraspinatus, teres minor, and the posterior deltoid were measured during the concentric shoulder external rotation task, before and after the exercise. In addition, the muscle activity ratio of the three muscles was calculated. Analysis divided into 30° intervals, under the low-load condition, shoulder external rotation torque and EMG amplitude of the infraspinatus and teres minor did not change; However, the EMG amplitude of the posterior deltoid increased significantly. The muscle activity ratio in the posterior deltoid showed exercise range × time interaction, with a significant increase from pre-exercise (Pre) (13.59 ± 5.70%) to 20 min after the exercise (15.40 ± 6.03%) in the 61°–90° external rotation range. In the medium- and high-load conditions, the EMG amplitude significantly increased for all muscles. However, under the medium-load condition, significant differences were observed between 0–30° (Pre: 25.4 Nm, 20 min: 26.0 Nm), 31–60° (Pre: 24.3 Nm, 20 min: 25.4 Nm), and 61–90° (Pre: 23.7 Nm, 20 min: 24.6 Nm). There was also an increase in the muscle activity ratio in the posterior deltoid, with a main effect on time in the medium load condition (p < 0.05). The changes in torque, EMG amplitude, and muscle activity ratio after the shoulder external rotation exercises were not uniform across different exercise loads. Therefore, it is necessary to use different tensions depending on the purpose of the exercise.
Limiting tourniquet use during total knee arthroplasty improves short-term postoperative outcomes in patients with hypertension
Authors: Zhang Lei , Ning Yuhui , Yang Cheng , He Tao
Published: February 2025

Introduction

Tourniquets are commonly used during total knee arthroplasty (TKA) to reduce intraoperative bleeding. However, information on the optimal tourniquet usage strategy in patients with hypertension are lacking.

Methods

A retrospective analysis of 90 patients with knee osteoarthritis and hypertension who underwent primary TKA was conducted. Patients were divided into three groups: Group A (tourniquet applied before skin incision and released after wound closure), Group B (tourniquet applied before prosthesis placement and released after wound closure), and Group C (tourniquet applied before prosthesis placement and released after bone cement solidification). Outcomes measured included intraoperative and postoperative blood loss, swelling rate, visual analog scale scores, perioperative complications, and Knee Society Scores.

Results

Group A exhibited the lowest intraoperative blood loss volume (239.26 ± 53.83 ml), but this group had significantly higher hidden blood loss, total blood loss, and transfusion volumes than Groups B and C (P < 0.05). The swelling rate and visual analog scores on postoperative day 3 were also significantly higher in Group A than in Groups B and C, as was the incidence of complications, including anemia, deep vein thrombosis, and anterior knee pain. Knee Society Scores at 4 weeks postoperatively were significantly lower in Group A than in Groups B and C.

Discussion

Tourniquet application before prosthesis placement and release after wound closure or bone cement solidification were associated with better short-term outcomes, reduced complications, and improved rehabilitation compared to tourniquet use during the entire procedure in patients with hypertension undergoing TKA.
Case report: Renal malformations in wild roe deer (Capreolus capreolus) in Central Poland
Authors: Kliczkowska Katarzyna , Bielecki Wojciech , Kloch Marta , Świątek Marcin , Klich Daniel
Published: February 2025

Kidney diseases are observed in various wild animal species, more often noted in captive than in free-ranging animals. There are few reports in roe deer (Capreolus capreolus). Two kidney malformations were encountered while reviewing and collecting the roe deer samples. Kidney malformations were found in samples from two roe deer in Central Poland, one in 5-year-old female near Węgrów (50 km northeast of Warsaw) and one in 7-year-old male near Rawa Mazowiecka (75 km southwest of Warsaw). The female had a smaller (5 cm long and weighed 20 g) shrunken kidney (no prominent histopathological changes) and compensatory hypertrophy of the other kidney (weighting 85.8 g). A diagnosis of renal hypoplasia was made. The male had a smaller kidney (4.5 cm long and weighed 15.3 g) and normal-sized the other kidney (7.5 cm and 55.6 g). Massive mononuclear infiltrates composed mainly of lymphocytes and plasma cells in the renal interstitium, with hyperplasia of the connective tissue and multifocal glomerular sclerosis, were found in both kidneys. Diagnosis of chronic interstitial nephritis was made.
Contribution of Acid Additive to Co-Composting of Chicken Manure: Gas Emission Reduction and Economic Assessment
Authors: Xue Wentao , Li Mao , Zhang Ling , Sun Qinping , Liu Shanjiang , Sun Hao , Wu Rong , Zou Guoyuan , Duan Na
Published: February 2025

Acidic additives have garnered significant attention due to their ability to reduce ammonia (NH3) emissions, enhance nitrogen retention, and balance function with cost-effectiveness. This study aimed to investigate the potential of oxalic acid (OA) in reducing gas emissions, promoting compost humification, and enhancing nutrient retention during the co-composting of chicken manure. Moreover, the comparative analysis of the effects and the economic benefits was conducted among OA groups with varying concentrations (OA1: 0.03 mol·kg−1, OA2: 0.10 mol·kg−1, and OA3: 0.15 mol·kg−1) and a sulfuric acid (SA) group (SA1: 0.03 mol·kg−1). The results indicated that the addition of OA can extend the thermophilic phase to some extent and achieve the required composting maturity. As the amount of OA increased, the NH3 emissions (p < 0.05) and the total nitrogen loss rate was decreased; however, this also increased the cost. No significant difference in the total nitrogen loss rate was observed between SA1 and OA1 (p < 0.05). It is worth noting that the addition of SA increased the SO42− content, leading to an increase of 113.52% in H2S emissions. In contrast, the addition of OA resulted in a reduction in H2S emissions by 29.92–45.90%. In terms of economic analysis, OA1 was the most effective (OA1 > OA2 > OA3 > SA1). Thereby, OA was proved to be a good alternative for SA in the co-composting of chicken manure, and 0.03 mol·kg−1 OA is recommended.
Multimodal Retrieval Method for Images and Diagnostic Reports Using Cross-Attention
Authors: Sata Ikumi , Amagasaki Motoki , Kiyama Masato
Published: February 2025

Background: Conventional medical image retrieval methods treat images and text as independent embeddings, limiting their ability to fully utilize the complementary information from both modalities. This separation often results in suboptimal retrieval performance, as the intricate relationships between images and text remain underexplored. Methods: To address this limitation, we propose a novel retrieval method that integrates medical image and text embeddings using a cross-attention mechanism. Our approach creates a unified representation by directly modeling the interactions between the two modalities, significantly enhancing retrieval accuracy. Results: Built upon the pre-trained BioMedCLIP model, our method outperforms existing techniques across multiple metrics, achieving the highest mean Average Precision (mAP) on the MIMIC-CXR dataset. Conclusions: These results highlight the effectiveness of our method in advancing multimodal medical image retrieval and set the stage for further innovation in the field.
Feasibility Evaluation of Dried Whole Egg Powder Application in Tadpole (Lithobates catesbeianus) Feed: Effects on Growth, Metamorphosis Rate, Lipid Metabolism and Intestinal Flora
Authors: Li Quan , Shao Chuang , Hu Yi , Chen Kaijian , Zhang Junzhi
Published: February 2025

At present, studies on tadpole nutrition and metabolism are scarce. This study aimed at comparing the influence of two protein sources, fishmeal (FM) and dried whole egg powder (DWEP), on tadpoles from the perspective of growth, the metamorphosis rate, lipid metabolism, antioxidant properties and the intestinal flora. In this experiment, the control diet was set to contain no FM or DWEP. Based on the control diet, 5% and 10% FM or DWEP were included, respectively. The results of the experiment indicated that FM or DWEP inclusion significantly enhanced the growth performance and metamorphosis rate (p < 0.05); activated hepatic lipid metabolism, as manifested by enhanced LPL and HL activity; upregulated lipid metabolism-related gene expression (fasn, acc, acadl and cpt1α) (p < 0.05); and distinctly elevated the activity of SOD, CAT and GPX (p < 0.05), suggesting improved antioxidant capabilities (p < 0.05). Moreover, the inclusion of FM or DWEP elevated the relative abundance of Actinobacteria and Actinomyces and reduced the relative abundance of Proteobacteria. Unexpectedly, no significant differences were observed between the FM and DWEP groups regarding the above detected indices. This indicates that using DWEP to replace FM is a viable option.
Optimization of Antimicrobial Use for Sepsis in Calves: Bayesian Evaluation of Existing and Novel Sepsis Scores
Authors: Pas Mathilde Laetitia , Bokma Jade , Boyen Filip , Chantillon Laurens , Castelain Donatienne , Clinquart Justine , Jourquin Stan , Pardon Bart
Published: February 2025

Early recognition and rapid appropriate antimicrobial treatment is essential for survival of sepsis. To date, it is unclear which sepsis score should be used for an early diagnosis in calves. The objective of this study was to evaluate two existing scores (Trefz and Fecteau), three novel calf sepsis screening models (CSS, CSSA, CSSB), and blood culture as diagnostic test for sepsis, using Bayesian latent class evaluation. A total of 131 sick calves were included in this study. Sepsis prevalence was 45%, 27%, 56%, 47%, and 55%, when using the Trefz score, Fecteau score, CSS, CSSA, and CSSB, respectively, and 22% had a relevant positive blood culture. The newly established models CSS (including ≥2 SIRS-criteria and abnormal mental state) and CSSB (alternative model CSS for practice, substituting abnormal leukocyte count with mucosae) had the highest sensitivity, with 86% and 84%, respectively, and could be interesting screening tests for sepsis. Sensitivity of the existing Trefz and Fecteau score was 70% and 35–39%, respectively. The presented new sepsis scoring systems have potential as screening tests to identify calves at risk, after which a calf-side diagnostic test is advised to confirm the diagnosis. Its use might aid in the rationalization of antimicrobial use in critically ill calves.
CAE Artificial Neural Network Applied to the Design of Incrementally Launched Prestressed Concrete Bridges
Authors: Goričan Tomaž , Kuhta Milan , Peruš Iztok
Published: February 2025

Bridges are typically designed by reputable, specialized engineering and design companies with years of experience. In these firms, experienced engineers share and pass on their knowledge to younger colleagues. However, when these experts retire, some of the knowledge is lost forever. As a subset of artificial intelligence methods, artificial neural networks (ANNs) can solve the problem of acquiring, transferring, and preserving specialized expert knowledge. This article describes the possible application of CAE ANN to acquire knowledge and to assist in the design of incrementally launched prestressed concrete bridges. Therefore, multidimensional graphs in the form of iso-curves of equal values were created, allowing practicing engineers to understand complex relationships between design parameters. The graphs also contain information about the reliability of the results, which is defined by an estimated parameter. The general rule is that results based on a larger number of actual data points are more reliable. Finally, an ANN BD assistant is proposed as an application that assists engineers and designers in the early stages of design and/or established engineers and designers in variant studies and design parameter optimization.