bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient Education on Exercise Prehabilitation Among Patients Receiving Neoadjuvant Therapy for Cancer Surgery in China: A Mixed-Methods Study
Authors: Xu Xiaohan , Zhang Jiao , Zhang Yuelun , Yang Tianxue , Yu Xuerong
Published: February 2025

Background/Objectives: Patients undergoing neoadjuvant therapy have ample time to engage in exercise prehabilitation. This study aimed to describe the current status, facilitators, and barriers of exercise prehabilitation among this population. Methods: This sequential explanatory mixed-methods evaluation was conducted at a general tertiary hospital in Beijing. It included a quantitative survey of patients who received neoadjuvant therapy before cancer surgery and qualitative semi-structured interviews with both patients and physicians. Thematic analysis was conducted using the Capability, Opportunity, and Motivation Behavior model. Results: A total of 269 patients participated in the survey, with a completion rate of 99.6%. Only 52.6% and 1.1% of patients met the standards for aerobic and muscle-strengthening activities, respectively. Fewer than 40% of patients reported learning about exercise prehabilitation from physicians. Patients’ knowledge was associated with meeting aerobic activity standards after adjusting for confounders (Level 1: odds ratio [OR] of 2.06, 95% confidence interval [CI] of 1.02–4.22; Level 2: OR of 2.56, 95% CI of 1.25–5.36). In total, 28 participants were interviewed. Facilitators of patient education on exercise prehabilitation included the surgeon’s ability to gain trust and patients’ prior commitment to exercise. Barriers included physicians’ lack of awareness of exercise benefits, insufficient knowledge or time for patient education, concerns about patients’ exercise ability, lack of referrals to rehabilitation clinics, challenges in follow-up, conflicts with cultural beliefs, and inadequate insurance coverage. Conclusions: This study revealed a lack of physician-led patient education on exercise prehabilitation. Efforts are needed to enhance physician education, implement collaborative clinics, and provide remote supervision.
Family Physicians’ Use of, Barriers to, and Attitudes Toward Remote Diagnosis and Treatment in China: A National Web-Based Survey
Authors: Tang Yao , Li Lianjun , Dong Wanyue , Xie Hong , Qiu Yiwei , Bai Ruhai
Published: February 2025

Background/Objectives: China has introduced a series of policies to encourage family physicians (FPs) to provide remote diagnosis and treatment (RDT) services, with the ultimate goal of providing more continuous, convenient, and efficient medical services for all residents, especially elderly patients and patients with chronic diseases. However, few studies have focused on this important issue. The aim of this study was to provide a comprehensive description of FPs’ use of, barriers to, and attitudes toward RDT in China. Methods: A cross-sectional survey was implemented for this study. The data were analyzed via basic descriptive statistics and are expressed as percentages. Additionally, a single-factor logistic regression was used to compare groups in terms of outcome measures. Results: Among the 682 respondents, 63.8% had participated in RDT, and 36.2% had never participated in RDT. Among the 435 respondents who participated in RDT, 19.1% were high-frequency users, and 80.9% were low-frequency users. The results of the single-factor logistic regression revealed that there were significant differences in the use of RDT among FPs in terms of age (p = 0.034), educational background (p < 0.001), hospital type (p = 0.008), income as a result of their work as an FP (p = 0.002), form of employment (p = 0.001), and general practitioner status (p < 0.001). Moreover, there were significant differences in the use frequency of RDT among FPs in terms of age (p = 0.009), years of practice as a health service provider (p = 0.001), years of practice as an FP (p = 0.003), educational background (p = 0.048), and working hours as an FP (p = 0.014). However, a lack of policy support (58.5%), technology support (55.3%), and information support (52.5%) were the top three factors hindering FPs from participating in RDT. Overall, FPs had positive attitudes toward RDT services, with more than half of the respondents expressing that they could benefit from such services and showing increasing interest in using them. Conclusions: The findings of this research can improve policymakers’ understanding of FPs’ use of, barriers to, and attitudes toward RDT. Our findings also provide suggestions, such as those for improving the promotion of RDT, optimizing relevant laws, and providing technical support for FPs to use RDT, which may help optimize related policies. There are also some limitations in our study; for example, the sample in this study included provincial administrative regions across China, but not all provinces were covered. In the future, research covering all provinces of the country could be carried out to make the research more nationally representative.
Saudi Electronic Caries Assessment Tool (SECAT) Development: Mixed Methods Feasibility Study
Authors: Alayadi Haya , Talakey Arwa , Alessa Tourkiah , Aldhalaan Abdulaziz
Published: February 2025

Background: Dental caries is a significant public health challenge globally, particularly acute in Saudi Arabia’s remote areas with limited healthcare access. Traditional paper-based methods for recording epidemiological data have limitations in data collection, storage, and sharing, highlighting the need for mobile solutions to enhance dental surveillance in resource-limited settings. Objective: To develop and evaluate the Saudi Electronic Caries Assessment Tool (SECAT), a mobile application designed for collecting dental caries data in remote locations, following a user-centered design approach. Methods: This mixed-methods feasibility study was conducted in three stages: (1) requirement gathering through semi-structured interviews with 12 dental professionals to explore experiences and needs; (2) development of the SECAT application using Flutter frontend and Supabase backend; and (3) evaluation through usability testing with 18 clinicians and heuristic study with five domain experts. Results: The usability study revealed an 82% overall satisfaction rate among clinicians, with 78% strongly endorsing the application’s user-friendly features. Expert evaluation highlighted the application’s utility for remote areas and offline functionality. Key improvements implemented based on feedback included an automated tooth recognition system, enhanced visualization protocol, and integration of clinical metrics. Primary limitations identified included the need for improved color contrast and individual-level calculations of dental indices. Conclusions: The SECAT application demonstrated high satisfaction and acceptability among dental health providers for collecting examination data in remote locations. The preliminary evaluation identified both limitations and positive aspects, particularly regarding utility in areas with limited internet connectivity. The SECAT mobile application could be valuable aid for caries assessment in remote places and also in school and community-based dental health programs.
Patient Mobility in the Digital Era: How Online Service Information from Internet Hospitals Shapes Patients’ Cross-Regional Healthcare Choices
Authors: Lu Yingjie , Shi Luli , Wang Zimeng
Published: February 2025

Background/Objectives: Patients in medically underserved regions often seek cross-regional healthcare for high-quality medical services but face significant barriers due to limited information about providers. Internet hospitals address this gap by offering online consultations, remote diagnoses, and public service information. This study examines how such information shapes patients’ cross-regional healthcare choices. Methods: A binary logistic regression model using signaling theory was employed to evaluate the impact of platform-generated signals (e.g., hospital ratings) and patient-generated signals (e.g., review quantity and polarity) on patients’ cross-regional healthcare choices. The experimental data were sourced from a leading Chinese online medical platform, comprising 1901 hospitals and 273,884 patient feedback records. Among these, 216,793 patients (79.16%) sought cross-regional treatment, while 57,091 patients (20.84%) opted for local treatment. Results: Platform-generated signals, such as hospital ratings (B = 0.406, p < 0.01) and patient-generated signals, including review quantity (B = 0.089, p < 0.01) and polarity (B = 0.634, p < 0.01), significantly and positively influence patients’ cross-regional healthcare choices. Disease severity and local medical resource availability moderated these effects: Patients with severe conditions rely less on hospital ratings (B = −0.365, p < 0.01), while those in resource-limited areas depend more on hospital ratings (B = −0.138, p < 0.01) and review quantity (B = −0.029, p < 0.01) but less on review polarity (B = 0.273, p < 0.01). Conclusions: These findings offer actionable insights for policymakers and platform developers to optimize online healthcare services, facilitating informed cross-regional healthcare decisions and advancing healthcare equity in the digital era.
Assessment of Muscular Strength and Functional Capacity in Smoker Population Without Any Diagnosed Respiratory Disease: A Cross-Sectional Study
Authors: Thibon Christophe , Caty Gilles , Gohy Sophie , Aboubakar Nana Frank , Reychler Gregory
Published: February 2025

Introduction: Smoking is a risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. In addition to pulmonary damages, peripheral muscle impairments are present in this population. Pulmonary limitation is observed in smokers before disease diagnosis, but functional capacity limitations are uncertain, contrary to patients who have already been diagnosed. The aim of this study was to compare muscular strength and endurance between non-smoker and smoker populations without any diagnosed respiratory disease. Method: This cross-sectional study assessed subjects without diagnosed respiratory disease in terms of physical capacity using two tests (one-minute sit-to-stand test (STST) and Jamar dynamometer test (JDT)). Results: The sample consisted of 147 subjects. The number of repetitions and the muscle strength were lower in the smoker than in the non-smoker population (28.5 ± 8.7 vs. 33.5 ± 8.2 (p < 0.001), and 38.2 ± 10.1 vs. 42.4 ± 10.5 (p = 0.04), respectively). The relative change in heart rate during STST was lower in the smokers compared to the non-smokers (p = 0.01). No significant differences were found based on gender. Conclusions: Smokers without alcohol or drug dependence and without diagnosed lung disease exhibit non-clinically but statistically reduced muscular strength and endurance. Their heart rate response to exercise is also reduced.
Agronomic Strategies to Manipulate Kiwifruit Calcium Content to Understand Its Role in Fruit Physiology
Authors: Baldi Elena , Toselli Moreno , Bonora Alessandro , Boini Alexandra , Quartieri Maurizio , Germani Margherita , Polidori Greta , Corelli Grappadelli Luca
Published: February 2025

Calcium (Ca) is one of the most important nutrients involved in fruit quality and storability; therefore, its application in fruit trees is often used in pre- and post-harvest. The aims of this study were to manipulate soil Ca, K, and N availability, photosynthetic active radiation, and fruit transpiration rate to understand their implication on fruit Ca accumulation on green-flesh kiwifruit grown in calcareous soil. Our results show that Ca partitioning into the fruit is not affected by the applications of Ca, K, and N, as well as the increase of photosynthetic active radiation. However, the presence of reflective films reduced fruit firmness and increased soluble solid content at harvest and during cold storage, thus enhancing fruit quality. Fruit calcium accumulation is decreased by the reduction of fruit transpiration rate; however, it has the possibility to recover, even close to fruit harvest, when the fruit transpiration is restored. The presence of bags reduced fruit weight from 84 to 63 g even though bags were removed. Our data provide evidence of the inefficiency of calcium fertilization in kiwifruit in calcareous soils and demonstrate the extension of calcium transportation into the fruit, which seems to occur during the entire growing season.
Natural Diversity of Crataegus monogyna Jacq. in Northeastern Türkiye Encompassing Morphological, Biochemical, and Molecular Features
Authors: Erkek Bora , Yaman Mehmet , Sümbül Ahmet , Demirel Serap , Demirel Fatih , Çoşkun Ömer Faruk , Say Ahmet , Eren Barış , Aydin Adnan , Eroglu Ayten
Published: February 2025

Hawthorn (Cratageus monogyna Jacq.), one of the important wild fruit species in Turkey, is an important fruit species in many countries due to its use in traditional medicine, landscaping studies, and the food and beverage industry. In this study, morphological characterization revealed significant variation among genotypes, with fruit weight ranging from 0.55 g to 2.87 g, fruit width from 9.74 mm to 18.39 mm, and leaf width from 19.53 mm to 41.19 mm. Genotype-dependent variations were observed in the total phenolic content (151.34 mg–491.88 mg GAE 100 g−1 flesh), the total flavonoid content (16.74–48.13 mg CAE 100 g−1 flesh), the total anthocyanin content (26.34–79.79 mg cyn-3 gluc 100 g−1 flesh), and the antioxidant activity (29.20% to 56.70%). HPLC-based phenolic profiling identified substantial variations in key bioactive compounds, with the highest levels of chlorogenic acid (16.16 mg 100 g−1 fw), caffeic acid (10.21 mg 100 g−1 fw), epicatechin (13.83 mg 100 g−1 fw), rutin (74.05 mg 100 g−1 fw), and protocatechuic acid (2.00 mg 100 g−1 fw). ISSR marker-based molecular analysis revealed a high degree of genetic polymorphism (89.12%), with 55 out of 62 bands classified as polymorphic. The polymorphic information content values ranged from 0.34 to 0.44. The Jaccard similarity coefficient ranged from 0.04 (M9 and M16) to 0.63 (M17 and M3), indicating substantial genetic variability. The tanglegram analysis comparing genetic and morphological–biochemical dendrograms yielded an entanglement score of 0.714, indicating an alignment between molecular and phenotypic data. These findings show that hawthorn genotypes from the Kelkit Valley exhibit extensive genetic and biochemical diversity, which is critical for conservation efforts, breeding programs, and the development of high-value medicinal and functional food products.
Optimization of ‘Tainongyihao’ Mango Inflorescence-Cutting Technology
Authors: Jiang Chenyu , Gao Yijia , Jiao Jiabing , Wei Ling , Shi Shaopu , Hassam Tahir , Qian Minjie , Zhou Kaibing , Teng Yuanwen
Published: February 2025

Inflorescence cutting is a critical cultural practice that enhances yield and fruit quality in mango cultivation. This study evaluated four treatments with the “Tainongyihao” mango: no cutting (CK), 1/3, 1/2, and 2/3 cutting of the central inflorescence axis, classified as light (L), medium (M), and heavy (H) cutting, respectively. Inflorescences were categorized by length, and field experiments were conducted during the growth periods of autumn–winter and winter–spring fruit in under-regulated and conventional harvest systems. The measured indicators include yield efficiency per unit trunk circumference, average fruit weight, reduced sugar content, total soluble solids (TSS), total titratable acids (TA), vitamin C content (Vc), and the TSS/TA ratio. Results indicated that light cutting was optimal for yield efficiency of autumn–winter fruit, while medium and heavy cutting were most effective for winter–spring fruit. Comprehensive fruit quality improved most under heavy cutting across all inflorescences. Long inflorescences benefited from heavy or medium cutting, medium inflorescences benefited from heavy cutting, and short inflorescences benefited from medium cutting. Interactive effects were observed between inflorescence-cutting treatments and inflorescence length, with fruit quality consistently improving under inflorescence-cutting treatments. Heavy cutting is recommended for manual operations, and all the results of this paper provide a foundation for developing artificial intelligence (AI)-based inflorescence-cutting technologies that enable precise and efficient mango cultivation practices.
Flexible Passive IV Connector Safeguard Against Contact and Airborne Contamination to Prevent Central-Line Associated Bloodstream Infections
Authors: Walterspiel Juan N.
Published: February 2025

IV line connectors often become contaminated between infusions, which leads to line infections. A flexible shield was developed to prevent this by means of passive protection. It was tested in a simulated bedside environment and protected from touch contamination as well as airborne transmission of skin bacteria to the connector hub. This flexible shield can compensate for the unavoidable human factor infection control lapses that occur during IV line handling by healthcare workers.
Mapping the Vulnerability of Older-Adult Neighborhoods: An Ecological Study of New York State
Authors: Friedman Samantha , Fang Chunxu , Yang Tse-Chuan , Li Rui , Mithu Imran Hossain , Manganello Jennifer A. , Romeiko Xiaobo , Lin Shao
Published: February 2025

We examined neighborhood-level demographic, economic, and social characteristics and food and health-services access to gauge the vulnerability of older-adult neighborhoods in New York State (NYS), which is understudied and is significant given the rapid aging of populations worldwide. We conducted descriptive ecological analyses using data from the American Community Survey, historical redlining maps, Social Capital Instruments, U.S. Department of Agriculture food access atlas, ESRI businesses, and Social Determinants of Health. We compared census tracts classified as having high and low levels of older-adult population; among those identified as high-older-adult neighborhoods, we then examined tracts with high and low levels of adult population living alone and in poverty. Our results showed that NYS neighborhoods with large shares of the older adult population are generally faring well in terms of their socioeconomic status, social capital, lack of social isolation, and health services access. However, the older-adult neighborhoods with larger shares of the population living alone and in poverty fare worse, living in areas with poorer socioeconomic status, lower social capital, and considered medically underserved. NYS older adult communities are projected to increase by 2030. Resources should be invested in such areas with vulnerable groups so populations may age in equitable and accessible communities.
Removal of Emerging Contaminants (Endocrine Disruptors) Using a Photocatalyst and Detection by High-Performance Liquid Chromatography (HPLC)
Authors: Santos Mayra Soares , Mourão Amanda Oliveira , Santos Thuanny Souza Xavier , Rodriguez Mariandry del Valle Rodriguez , Faria Márcia Cristina da Silva , Franco Elton Santos , Aguilar Núbia Aparecida de , Rodrigues Jairo Lisboa
Published: February 2025

Among several types of emerging contaminants, the endocrine disruptors 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) are particularly notable. These compounds are discharged into sewage systems and subsequently into water bodies, as conventional wastewater treatment processes are unable to effectively eliminate such pollutants. Therefore, the present study aimed to evaluate the possibility of removing the endocrine disruptors 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from water using the photocatalytic activity of the compound Ag3AsO4. Silver arsenate was synthesized and characterized, the quantification of the hormones E2 and EE2 was achieved by high-performance liquid chromatography with a fluorescence detector, and a validation process and some preliminary tests were performed on the photodegradation of the hormones using the Ag3AsO4 catalyst. Validation was performed, and satisfactory results were achieved: r = 0.9987 (E2), r = 0.9984 (EE2), a detection limit of 5.01 (E2) and 0.51 (EE2), a quantification limit of 15.19 (E2) and 1.54 (EE2), coefficients of variation for precision intraday and interday lower than 10.9725% and 11.3393%, respectively, and a recovery of 100.15% (E2) and 100.31% (EE2). In photodegradation studies, Ag3AsO4 showed different behavior in the presence of light for each hormone. In solution with E2, it reached a removal rate of 35% of the hormone under LED light, acting as a photocatalyst, while with EE2, it reached a removal rate of 96%; both results were obtained after 30 min of exposure to visible light. When this study is compared with other processes and materials, the high efficiency of the Ag3AsO4 photocatalyst in removing E2 and EE2, persistent emerging contaminants, becomes evident. This advancement has significant implications for wastewater treatment, offering a promising solution that can mitigate environmental impacts caused by endocrine disruptors.
MGST1 Protects Pancreatic Ductal Cells from Inflammatory Damage in Acute Pancreatitis by Inhibiting Ferroptosis: Bioinformatics Analysis with Experimental Validation
Authors: Zhang Ruoyi , Ling Xin , Guo Xianwen , Ding Zhen
Published: February 2025

Numerous animal experiments have implicated ferroptosis in the pathogenesis of acute pancreatitis (AP). Nonetheless, due to sampling constraints, the precise role of ferroptosis in the human body during AP remains elusive. Method: Peripheral blood sequencing data of patients with acute pancreatitis (GSE194331) were obtained from the Gene Expression Omnibus (GEO) database. We analyzed differentially expressed genes whose expression increased or decreased with increasing disease severity and intersected them with the ferroptosis gene set to identify ferroptosis-related driver genes for the disease. The hub genes were selected using machine learning algorithms, and a nomogram diagnosis model was constructed. Clinical samples, animal models, and an in vitro experiment were also used for validation. The investigation unveiled 22 ferroptosis-related driver genes, and we identified three hub genes, AQP3, TRIB2, and MGST1, by employing two machine learning algorithms. AQP3 and TRIB2 exhibit robust correlations with various immune cells. The disease diagnosis model constructed utilizing these three genes demonstrated high sensitivity and specificity (AUC = 0.889). In the in vitro experiments, we discovered for the first time that ferroptosis occurs in pancreatic duct cells during acute pancreatitis, and that MGST1 is significantly upregulated in duct cells, where it plays a crucial role in negatively regulating ferroptosis via the ACSL4/GPX4 axis. In addition, overexpression of MGST1 protects ductal cells from inflammatory damage. In our investigation, we explored the mechanisms of ferroptosis in immune cells and pancreatic duct cells in patients with AP. These results highlight a potential pathway for the early diagnosis and treatment of acute pancreatitis.
Evaluation of Metal Accumulation in Escherichia coli Expressing SPL2 by Single-Cell Inductively Coupled Plasma Mass Spectrometry
Authors: Fukumoto Yasunori , Li Enhui , Tanaka Yu-ki , Suzuki Noriyuki , Ogra Yasumitsu
Published: February 2025

Rare earth elements, comprising 17 elements including 15 lanthanides, are essential components in numerous high-tech applications. While physicochemical methods are commonly employed to remove toxic heavy metals (e.g., cadmium and mercury) from industrial wastewater, biological approaches offer increasingly attractive alternatives. Biomining, which utilizes microorganisms to extract valuable metals from ores and industrial wastes, and bioremediation, which leverages microorganisms to adsorb and transport metal ions into cells via active transport, provide eco-friendly solutions for resource recovery and environmental remediation. In this study, we investigated the potential of three recently identified lanthanide-binding proteins—SPL2, lanpepsy, and lanmodulin—for applications in these areas using single-cell inductively coupled plasma mass spectrometry (scICP-MS). Our results demonstrate that SPL2 exhibits superior characteristics for lanthanide and cadmium bioremediation. Heterologous expression of a cytosolic fragment of SPL2 in bacteria resulted in high expression levels and solubility. Single-cell ICP-MS analysis revealed that these recombinant bacteria accumulated lanthanum, cobalt, nickel, and cadmium, effectively sequestering lanthanum and cadmium from the culture media. Furthermore, SPL2 expression conferred enhanced bacterial tolerance to cadmium exposure. These findings establish SPL2 as a promising candidate for developing recombinant bacterial systems for heavy metal bioremediation and rare earth element biomining.
Antioxidant and Anti-Inflammatory Activities of Methanol Extract of Senna septemtrionalis (Viv.) H.S. Irwin & Barneby Through Nrf2/HO-1-Mediated Inhibition of NF-κB Signaling in LPS-Stimulated Mouse Microglial Cells
Authors: Lim Jae Sung , Li Xiangying , Lee Da Young , Yao Lulu , Yoo Guijae , Kim Yunyeong , Eum Sang Mi , Cho Young-Chang , Yoon Somy , Park Su-Jin
Published: February 2025

Botanical extracts are recognized in traditional medicine for their therapeutic potential and safety standards. Botanical extracts are viable and sustainable alternatives to synthetic drugs, being essential in drug discovery for various diseases. Senna septemtrionalis (Viv.) H.S. Irwin & Barneby is a medical plant traditionally used to treat inflammation. However, its antioxidant and anti-inflammatory properties and the molecular pathways activated in microglial cells require further investigation. Therefore, this study examines the antioxidant and anti-inflammatory properties of Senna septemtrionalis (Viv.) H.S. Irwin & Barneby methanol extracts (SMEs) in lipopolysaccharide (LPS)-stimulated mouse microglial cells. SMEs significantly inhibit LPS-induced nitric oxide (NO) and proinflammatory cytokine production, which are mediated through the dephosphorylation of mitogen-activated protein kinases and inhibition of nuclear factor kappa B (NF-κB) translocation into the nucleus. Additionally, SME treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO)-1, reducing oxidative stress, indicated by a decrease in reactive oxygen species and restoration of the total glutathione content in LPS-stimulated BV2 cells. The inhibitory effects of SMEs on inflammatory mediator production and NF-κB nuclear translocation were significantly reversed by Sn-protoporphyrin, a specific HO-1 inhibitor. These findings demonstrate that SME protects microglial cells by activating the Nrf2/HO-1 pathway and inhibiting NF-κB translocation.
Agomelatine Mitigates Kidney Damage in Obese Insulin-Resistant Rats by Inhibiting Inflammation and Necroptosis via the TNF-α/NF-ĸB/p-RIPK3 Pathway
Authors: Promsan Sasivimon , Pengrattanachot Nattavadee , Phengpol Nichakorn , Sutthasupha Prempree , Thongnak La-ongdao , Jaikumkao Krit , Lungkaphin Anusorn
Published: February 2025

Obesity is a risk factor for chronic kidney disease. The expansion of adipose tissues in obesity induces insulin resistance and low-grade systemic inflammation, promoting kidney damage. Our previous studies have demonstrated that agomelatine (AGOM) exerts renoprotective effects in experimental models of obesity and insulin resistance through various mechanisms, including the attenuation of ER stress and oxidative stress. This study aimed to further explore the effects of agomelatine on renal inflammation, insulin signaling, and necroptosis in obese, insulin-resistant rats. Obesity was induced in rats with a high-fat diet for 16 weeks, followed by 4 weeks of treatment with 20 mg kg−1 day−1 of AGOM or 10 mg kg−1 day−1 of pioglitazone (PIO). The results showed that insulin resistance was improved after treatment with AGOM and PIO, as demonstrated by the reduction in fasting plasma glucose, insulin, and HOMA-IR. Both treatments restored the levels of renal insulin signaling proteins. Moreover, AGOM inhibited TNFα, TNFR1, NF-ĸB, COX2, and IL1β, which attenuated the necroptosis-related proteins RIPK3 and MLKL. AGOM also prevented kidney DNA fragmentation, as detected by the TUNEL assay. In an obese condition, the level of the tight junction protein claudin-1 (CLDN1) was enhanced after being treated with AGOM. In conclusion, the novel mechanisms associated with AGOM and involved in limiting kidney injury were the inhibition of the TNFα/NF-ĸB/p-RIPK3 pathway and a reduction in inflammation and necroptosis. This suggested that AGOM could be an effective treatment for inhibiting kidney dysfunction in cases of obesity and insulin resistance. These findings open new avenues for the management of renal dysfunction, with implications for personalized medicine.
Genome-Wide Identification and Functional Analysis of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) in Three Populus Species
Authors: Li Zheng , Chen Feng-Xin , Li Ming-Ming , Tang Xian-Li , Liu Yu-Qi , Huang Meng-Bo , Niu Hao-Qiang , Liu Chao , Wang Hou-Ling , Xia Xin-Li , Yin Wei-Lun
Published: February 2025

Intercellular communication mediated by CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) peptides and their receptors is crucial for plant development and environmental adaptation. In this study, 45 and 89 CLEs were identified in Populus tomentosa and Populus alba × Populus glandulosa, respectively, and, together with the 52 CLEs in Populus trichocarpa, the chromosome localization, gene and protein characteristics, collinearity and gene duplication events, cis-acting regulatory elements in promoters and evolutionary relationships of CLEs in these three poplar species were analyzed. The CLEs of three poplar species were divided into four subfamilies. Among them, the CLEs in subfamilies I, II and IV were A-type CLEs, while those in subfamily III were B-type CLEs. During the evolutionary process of poplar, the selection pressure faced by whole-genome duplication or segmental duplication was purifying selection, and the duplication events led to the expansion of the CLE family in poplar. The exogenous addition of a certain concentration of poplar CLE13 peptides inhibits the root growth of Arabidopsis thaliana and poplar and simultaneously reduces the expression levels of ARFs and LBDs in the roots. In addition, drought stress induces the expression of PtrCLE13A. The overexpression of preCLE13A significantly enhances the osmotic and drought tolerance in Populus tomentosa. These results have provided valuable information for further research on the molecular mechanisms of CLE peptide signaling pathways in the woody model plant poplar regarding plant growth and stress resistance.
SERPINA3: A Novel Therapeutic Target for Diabetes-Related Cognitive Impairment Identified Through Integrated Machine Learning and Molecular Docking Analysis
Authors: An Yu , Cao Zhaoming , Du Yage , Xu Guangyi , Wang Jingya , Ma Yinchao , Wang Ziyuan , Zheng Jie , Lu Yanhui
Published: February 2025

Diabetes-related cognitive impairment (DCI) is a severe complication of type 2 diabetes mellitus (T2DM), with limited understanding of its molecular mechanisms hindering effective therapeutic development. This study identified SERPINA3 as a potential therapeutic target for DCI through integrated machine learning and molecular docking analyses. Transcriptomic data from cortical neuronal samples of T2DM patients were analysed using support vector machine recursive feature elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, revealing SERPINA3 as a significantly upregulated gene in DCI. Experimental validation via Western blot confirmed elevated SERPINA3 protein levels in DCI patient plasma. Molecular docking demonstrated the stable binding of sulfonylurea hypoglycaemic agents, such as gliclazide and glimepiride, to SERPINA3, with binding energies of −6.8 and −6.6 kcal/mol, respectively. These findings suggest that SERPINA3 plays a pivotal role in DCI pathogenesis and that sulfonylurea drugs may exert neuroprotective effects through SERPINA3-mediated pathways. This study provides novel insights into the molecular mechanisms of DCI and highlights the potential of SERPINA3-targeted therapies for early intervention and treatment. Further research is warranted to validate these findings in larger cohorts and explore their clinical applicability.
Trends in Precision Medicine and Pharmacogenetics as an Adjuvant in Establishing a Correct Immunosuppressive Therapy for Kidney Transplant: An Up-to-Date Historical Overview
Authors: Belardi Riccardo , Pacifici Francesca , Baldetti Matteo , Velocci Silvia , Minieri Marilena , Pieri Massimo , Campione Elena , Della-Morte David , Tisone Giuseppe , Anselmo Alessandro , Novelli Giuseppe , Bernardini Sergio , Terrinoni Alessandro
Published: February 2025

Kidney transplantation is currently the treatment of choice for patients with end-stage kidney diseases. Although significant advancements in kidney transplantation have been achieved over the past decades, the host’s immune response remains the primary challenge, often leading to potential graft rejection. Effective management of the immune response is essential to ensure the long-term success of kidney transplantation. To address this issue, immunosuppressives have been developed and are now fully integrated into the clinical management of transplant recipients. However, the considerable inter- and intra-patient variability in pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs represents the primary cause of graft rejection. This variability is primarily attributed to the polymorphic nature (genetic heterogeneity) of genes encoding xenobiotic-metabolizing enzymes, transport proteins, and, in some cases, drug targets. These genetic differences can influence drug metabolism and distribution, leading to either toxicity or reduced efficacy. The main objective of the present review is to report an historical overview of the pharmacogenetics of immunosuppressants, shedding light on the most recent findings and also suggesting how relevant is the research and investment in developing validated NGS-based commercial panels for pharmacogenetic profiling in kidney transplant recipients. These advancements will enable the implementation of precision medicine, optimizing immunosuppressive therapies to improve graft survival and kidney transplanted patient outcomes.
Association of Genes TRH, PRL and PRLR with Milk Performance, Reproductive Traits and Heat Stress Response in Dairy Cattle
Authors: Fang Qianhai , Zhang Hailiang , Gao Qing , Hu Lirong , Zhang Fan , Xu Qing , Wang Yachun
Published: February 2025

In our previous study, we found that changes in plasma prolactin (PRL) concentration were significantly associated with heat stress in dairy cows, and that PRL plays an important role in milk performance. Microarray sequencing revealed that thyrotropin releasing hormone (TRH) and prolactin receptor (PRLR), two genes important for PRL expression or function, may affect milk performance, reproduction, and heat stress response in dairy cattle. In this study, we further validated the genetic effects of the three genes in Chinese Holsteins. The potential variants within the three genes were first detected in 70 Chinese Holstein bulls and then screened in 1152 Chinese Holstein cows using the KASP (Kompetitive allele-specific PCR) method. In total, 42 variants were identified. Further, 13 SNPs were retained for KASP genotyping, including 8 in TRH, 3 in PRL, and 2 in PRLR. Using SNP-based association analyses, the multiple significant (p < 0.05) associations of these 13 SNPs with milk performance, reproduction, and heat stress response traits were found in the Holstein population. Furthermore, linkage disequilibrium analysis found a haplotype block in each of the TRH and PRL genes. Haplotype-based association analyses showed that haplotype blocks were also significantly (p < 0.05) associated with milk performance, reproduction, and heat stress response traits. Collectively, our results identified the genetic associations of TRH, PRL, and PRLR with milk performance, reproduction, and heat stress response traits in dairy cows, and found the important roles of SNP g.55888602A/C and g.55885455A/G in TRH in all traits, providing important molecular markers for genetic selection of high-yielding dairy cows.
Five-Year Outcomes of Patients with Pompe Disease Identified by the Pennsylvania Newborn Screen
Authors: Ron Hayley A. , Kane Owen , Guo Rose , Menello Caitlin , Engelhardt Nicole , Pressley Shaney , DiBoscio Brenda , Steffensen Madeline , Cuddapah Sanmati , Ng Kim , Ficicioglu Can , Ahrens-Nicklas Rebecca C.
Published: February 2025

Pennsylvania started newborn screening for Pompe disease (PD) in 2016. As a result, the prevalence of PD has increased with early detection, primarily of late-onset Pompe disease (LOPD). No clear guidelines exist regarding if and when to initiate enzyme replacement therapy (ERT) in patients identified through a newborn screen (NBS). To help define the natural history and indications for starting ERT, we present the long-term follow-up data of 45 patients identified through NBS from 2016 to 2021. These patients were evaluated at regular intervals through our multi-disciplinary clinic at the Children’s Hospital of Philadelphia (CHOP) with physical examinations, physical therapy evaluations, muscle biomarkers including creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hexosaminidase 4 levels (Hex4), as well as cardiac evaluation at certain points in time. We found that newborn screening of acid alpha-glucosidase (GAA) enzyme detected primarily LOPD. One case of infantile-onset PD (IOPD) was detected. Muscle biomarkers in LOPD were elevated at birth and showed a general downward trend over time. NBS GAA levels and initial CK levels helped to differentiate LOPD cases from unaffected infants (carriers, pseudodeficiency alleles), while Hex4 was not a meaningful discriminator. On repeat NBS, there was a significant difference between mean GAA levels for the unaffected vs. compound heterozygote groups and unaffected vs. homozygote groups for the common splice site pathogenic variant (c.-32-13T>G). Echocardiogram and electrocardiogram (EKG) are essentially normal at the first evaluation in LOPD. One LOPD patient was started on ERT at age 4.5 months. Continued data collection on these patients is critical for developing management guidelines, including timing of ERT and improved genotype–phenotype correlation.
Vehicle Exhaust Estimation Using YOLOv7 and Support Vector Regression with Image Features
Authors: Lin Yun-Sin , Chen Ting-Yu , Liaw Jiun-Jian , Yang Hsi-Hsien , Hsieh Cheng-Hsiung
Published: February 2025

Vehicle exhaust is a major source of air pollution that contributes to environmental degradation and poses risks to public health. This paper presents an image-based method to estimate opacity (OP) and particulate matter (PM) from vehicle exhaust. In the proposed method, YOLOv7 was used to identify vehicles and, thus, the region of interest (ROI). Then, a support vector regression was trained, with four image features extracted from the ROI as the input vectors, while OP or PM was used as the output. The proposed method was verified by experiments where moving and static scenarios with three ROIs were considered. The ROIs used in the experiments were exhaust pipe area (EPA), vehicle bounding box (VBB), and white background (WBG). In the moving scenario, the EPA and VBB ROIs were considered. For the VBB ROI, the average R2 values for OP and PM in the given examples were 0.834 and 0.894, respectively. For the EPA ROI, the average R2 values for OP and PM were 0.838 and 0.910, respectively. In the static scenario, the EPA and WBG ROIs were considered. For the EPA ROI, the average R2 values for OP and PM were 0.619 and 0.612, respectively. For the WBG ROI, the average R2 values for OP and PM were 0.748 and 0.732, respectively. The results suggest that the EPA ROI is preferable in the moving scenario and the WBG ROI in the static scenario to estimate OP and PM from vehicle exhaust. The proposed method is promising in the estimation of OP and PM from vehicle exhaust because satisfactory R2 values were achieved.
Associations Between Soluble Cell Adhesion Molecules and Cardiovascular Comorbidities in Systemic Sclerosis: Implications for Insulin Resistance
Authors: Ferraz-Amaro Iván , Ibrahim-Achi Zeina , de Vera-González Antonia , González-Delgado Alejandra , Renuncio-García Mónica , Vicente-Rabaneda Esther F. , Ocejo-Vinyals J. Gonzalo , Castañeda Santos , González-Gay Miguel Á.
Published: February 2025

Background: Soluble cell adhesion molecules such as sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and P-selectin have been implicated in cardiovascular disease pathogenesis in the general population. Cardiovascular disease is prevalent among patients with systemic sclerosis (SSc). This study aims to investigate potential associations between the serum levels of these adhesion molecules and specific cardiovascular comorbidities in SSc patients. Methods: This cross-sectional study encompassed 81 individuals with SSc. All SSc patients underwent a complete clinical evaluation. Serum sICAM-1, sVCAM-1, and P-selectin levels, lipid profiles and insulin resistance indices, and carotid ultrasound were assessed. Multivariable linear regression analyses were employed to investigate potential associations between adhesion molecule levels (sICAM, sVCAM, and P-selectin) and both SSc-specific manifestations and cardiometabolic parameters. Results: The associations of disease-related parameters with sICAM-1, sVCAM-1, and P-selectin levels were limited. Notably, only the modified Rodnan skin score exhibited a significant positive association with sVCAM-1 levels, while no such associations were observed for sICAM-1 and P-selectin. Regarding cardiovascular disease-related data, sVCAM-1 significantly correlated with higher values of insulin resistance and beta-cell function indices. In the case of P-selectin, although a trend was observed, statistical significance was not reached. Conclusions: In patients with SSc, serum values of sVCAM-1 independently correlate with insulin resistance. The assessment of CAMs in patients with SSc could serve as a valuable clinical tool for identifying individuals with increased insulin resistance and a higher risk of cardiovascular disease.
Challenges in Saving Trauma Patients in Seoul Based on the 2016–2020 Community-Based Severe Trauma Survey
Authors: Park Hoonsung , Baik Seung Min , Cho Hangjoo , Kim Maru , Lee Jae-Myeong
Published: February 2025

Background/Objectives: The preventable trauma death rate (PTDR) reflects the quality of trauma management systems. In the Republic of Korea, the PTDR in Seoul, the capital city, decreased from 30.8% in 2015 to 20.4% in 2019. However, it remains the highest in the country. In contrast, Gyeonggi-Incheon, which includes Gyeonggi Province and Incheon Metropolitan City surrounding Seoul, had the lowest nationwide PTDR (27.4% in 2015 to 13.1% in 2019). This study aimed to investigate the characteristics and in-hospital mortality risk factors for patients with trauma in Seoul and Gyeonggi-Incheon. Methods: This retrospective cohort study used data from a 2016 to 2020 Community-Based Severe Trauma Survey. Among 237,616 patients, 24,448 were included in the study after applying the inclusion and exclusion criteria. Results: The proportions of the population with motor vehicle and workers’ compensation insurance increased with increasing injury severity in both regions. The injury severity score (ISS) was significantly higher in Gyeonggi-Incheon in the ISS < 9 and ISS 9–15 groups. Across all hospital levels, the proportion of patients who visited regional trauma centers in Seoul was low across all three ISS groups (0.2%[n = 26], 0.6%[n = 23], and 1.9%[n = 56] for ISS < 9, ISS 9–15, and ISS > 15, respectively). Conversely, in Gyeonggi-Incheon, the proportion of patients who visited regional trauma centers increased as injury severity increased across all three ISS groups (37.3%[n = 1404], 50.6%[n = 732], and 64.4%[n = 856] for ISS < 9, ISS 9–15, and ISS > 15, respectively). In Seoul, the identified in-hospital mortality risk factors included age, National Health Insurance (NHI) loss, other insurance, ISS, regional and local emergency centers or institutes, and the number of angioembolizations. In Gyeonggi-Incheon, the in-hospital mortality risk factors included age, ISS, falls and slippage, and the number of angioembolizations. Conclusions: The unique in-hospital mortality risk factors in Seoul compared with those in Gyeonggi-Incheon include transfers to regional emergency centers (ISS > 15), local emergency centers or institutes (ISS > 15), NHI loss (ISS 9–15 and ISS > 15), and the use of other insurance (ISS > 15).
Comparison Between Intravitreal Anti-Vascular Endothelial Growth Factor Monotherapy and Vitrectomy in Age-Related Macular Degeneration with Large Submacular Hemorrhages
Authors: Miyazato Misa , Maruyama-Inoue Maiko , Tanaka Shin , Inoue Tatsuya , Yanagi Yasuo , Kadonosono Kazuaki
Published: February 2025

Objectives: To compare the 1-year visual outcomes of patients treated with intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy or vitrectomy for large submacular hemorrhages (SMHs) due to neovascular age-related macular degeneration (nAMD). Methods: We retrospectively studied 31 eyes with severe SMHs exceeding 3 disc areas (DAs) secondary to nAMD treated with anti-VEGF agents or a vitrectomy. Patients undergoing anti-VEGF monotherapy received three monthly loading doses of intravitreal injections of aflibercept or brolucizumab followed by as-needed injections or proactive treatment (anti-VEGF group); those undergoing vitrectomies underwent a 25-gauge vitrectomy and a submacular injection of tissue plasminogen activator (25 μg) and 0.4 mL of air with a microneedle having an outer diameter of 50 μm. The best-corrected visual acuities (BCVAs) were compared before and 6 and 12 months after initial treatment. Factors affecting the visual acuity (VA) at 12 months and VA improvements were determined. Results: A total of 17 eyes from 16 patients (54.8%) received anti-VEGF treatment and 14 eyes from 14 patients (45.2%) underwent vitrectomy. The baseline and 12-month mean logarithm of the minimum angle of resolution BCVAs in all eyes after treatment were 0.78 and 0.82, respectively, which were not significantly different (p = 0.661). The lens status, central foveal thickness (CFT) height, and baseline VA were associated significantly with the 12-month BCVA (p = 0.028, p = 0.008, and p = 0.021, respectively) and VA improvement (p = 0.015, p = 0.002, and p = 0.003, respectively). Conclusions: Anti-VEGF monotherapy and vitrectomy maintained functionality in patients with large SMHs due to nAMD. Greater CFT was associated with worse 12-month BCVA and less BCVA improvement despite the treatment modality.