bluuebunny/crossref_metadata_2025 huggingface dataset:
A Framework for the Human-Centered Design of Service Processes Enabled by Medical Devices: A Case Study of Wearable Devices for Parkinson’s Disease
Authors: Vannelli Sara , Visintin Filippo , Dosi Clio , Fiorini Laura , Rovini Erika , Cavallo Filippo
Published: October 2024

The successful introduction of medical devices (MDs) in real-world settings hinges on designing service processes that cater to stakeholders’ needs. While human-centered design (HCD) approaches have been widely applied to service process innovation, the literature lacks a methodology that leverages MDs’ key features to design service processes that meet stakeholders’ needs. This study aims to fill this gap by developing a framework for the HCD of service processes enabled by MDs. The proposed framework mixes and adapts methodological elements from HCD and technology-enabled design approaches and proposes four new tools. The five-phase framework was applied to the design of a new Parkinson’s disease diagnosis and treatment process (PD-DTP) enabled by two wearable MDs for the detection of motor symptoms. The case study lasted five months and involved 42 stakeholders in 21 meetings (interviews, focus groups, etc.). Thanks to the case study, the framework was tested, and a new PD-DTP that could benefit all stakeholders involved was identified. This study provides a framework that, in addition to contributing to theory, could assist MDs developers and healthcare managers in designing service processes that cater to stakeholders’ needs by leveraging MDs’ key features.
Single-Base Methylome Analysis of Sweet Cherry (Prunus avium L.) on Dwarfing Rootstocks Reveals Epigenomic Differences Associated with Scion Dwarfing Conferred by Grafting
Authors: Hong Yi , Wen Zhuang , Qiao Guang , Tian Tian , Wen Xiaopeng
Published: October 2024

Plant grafting using dwarfing rootstocks is one of the important cultivation measures in the sweet cherry (Prunus avium) industry. In this work, we aimed to explore the effects of the dwarfing rootstock “Pd1” (Prunus tomentosa) on sweet cherry ‘Shuguang2’ scions by performing morphological observations using the paraffin slice technique, detecting GA (gibberellin) and IAA (auxin) contents using UPLC-QTRAP-MS (ultra-performance liquid chromatography coupled with a hybrid triple quadrupole-linear ion trap mass spectrometer), and implementing integration analyses of the epigenome and transcriptome using whole-genome bisulfite sequencing and transcriptome sequencing. Anatomical analysis indicated that the cell division ability of the SAM (shoot apical meristem) in dwarfing plants was reduced. Pd1 rootstock significantly decreased the levels of GAs and IAA in sweet cherry scions. Methylome analysis showed that the sweet cherry genome presented 15.2~18.6%, 59.88~61.55%, 28.09~33.78%, and 2.99~5.28% methylation at total C, CG, CHG, and CHH sites, respectively. Shoot tips from dwarfing plants exhibited a hypermethylated pattern mostly due to increased CHH methylation, while leaves exhibited a hypomethylated pattern. According to GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, DMGs (differentially methylated genes) and DEGs (differentially expressed genes) were enriched in hormone-related GO terms and KEGG pathways. Global correlation analysis between methylation and transcription revealed that mCpG in the gene body region enhanced gene expression and mCHH in the region near the TSS (transcription start site) was positively correlated with gene expression. Next, we found some hormone-related genes and TFs with significant changes in methylation and transcription, including SAURs, ARF, GA2ox, ABS1, bZIP, MYB, and NAC. This study presents a methylome map of the sweet cherry genome, revealed widespread DNA methylation alterations in scions caused by dwarfing rootstock, and obtained abundant genes with methylation and transcription alterations that are potentially involved in rootstock-induced growth changes in sweet cherry scions. Our findings can lay a good basis for further epigenetic studies on sweet cherry dwarfing and provide valuable new insight into understanding rootstock–scion interactions.
Effects of Nitric Oxide on Bladder Detrusor Overactivity through the NRF2 and HIF-1α Pathways: A Rat Model Induced by Metabolic Syndrome and Ovarian Hormone Deficiency
Authors: Lin Hung-Yu , Lu Jian-He , Lin Rong-Jyh , Chueh Kuang-Shun , Juan Tai-Jui , Mao Jing-Wen , Lee Yi-Chen , Chuang Shu-Mien , Shen Mei-Chen , Sun Ting-Wei , Juan Yung-Shun
Published: October 2024

Metabolic syndrome (MetS) includes cardiovascular risk factors like obesity, dyslipidemia, hypertension, and glucose intolerance, which increase the risk of overactive bladder (OAB), characterized by urgency, frequency, urge incontinence, and nocturia. Both MetS and ovarian hormone deficiency (OHD) are linked to bladder overactivity. Nitric oxide (NO) is known to reduce inflammation and promote healing but its effect on bladder overactivity in MetS and OHD is unclear. This study aimed to investigate NO’s impact on detrusor muscle hyperactivity in rats with MetS and OHD. Female Sprague-Dawley rats were divided into seven groups based on diet and treatments involving L-arginine (NO precursor) and L-NAME (NOS inhibitor). After 12 months on a high-fat, high-sugar diet with or without OVX, a cystometrogram and tracing analysis of voiding behavior were used to identify the symptoms of detrusor hyperactivity. The MetS with or without OHD group had a worse bladder contractile response while L-arginine ameliorated bladder contractile function. In summary, MetS with or without OHD decreased NO production, reduced angiogenesis, and enhanced oxidative stress to cause bladder overactivity, mediated through the NF-kB signaling pathway, whereas L-arginine ameliorated the symptoms of detrusor overactivity and lessened oxidative damage via the NRF2/HIF-1α signaling pathway in MetS with or without OHD-induced OAB.
In Vitro Evaluation of New 5-Nitroindazolin-3-one Derivatives as Promising Agents against Trypanosoma cruzi
Authors: Pozo-Martínez Josué , Arán Vicente J. , Zúñiga-Bustos Matías , Parra-Magna Sebastián , Rocha-Valderrama Esteban , Liempi Ana , Castillo Christian , Olea-Azar Claudio , Moncada-Basualto Mauricio
Published: October 2024

Chagas disease is a prevalent health problem in Latin America which has received insufficient attention worldwide. Current treatments for this disease, benznidazole and nifurtimox, have limited efficacy and may cause side effects. A recent study proposed investigating a wide range of nitroindazole and indazolone derivatives as feasible treatments. Therefore, it is proposed that adding a nitro group at the 5-position of the indazole and indazolone structure could enhance trypanocidal activity by inducing oxidative stress through activation of the nitro group by NTRs (nitroreductases). The study results indicate that the nitro group advances free radical production, as confirmed by several analyses. Compound 5a (5-nitro-2-picolyl-indazolin-3-one) shows the most favorable trypanocidal activity (1.1 ± 0.3 µM in epimastigotes and 5.4 ± 1.0 µM in trypomastigotes), with a selectivity index superior to nifurtimox. Analysis of the mechanism of action indicated that the nitro group at the 5-position of the indazole ring induces the generation of reactive oxygen species (ROS), which causes apoptosis in the parasites. Computational docking studies reveal how the compounds interact with critical residues of the NTR and FMNH2 (flavin mononucleotide reduced) in the binding site, which is also present in active ligands. The lipophilicity of the studied series was shown to influence their activity, and the nitro group was found to play a crucial role in generating free radicals. Further investigations are needed of derivatives with comparable lipophilic characteristics and the location of the nitro group in different positions of the base structure.
Characterization of EpCAM-Positive and EpCAM-Negative Tumor Cells in Early-Stage Breast Cancer
Authors: Perelmuter Vladimir M. , Grigoryeva Evgeniya S. , Alifanov Vladimir V. , Kalinchuk Anna Yu. , Andryuhova Elena S. , Savelieva Olga E. , Patskan Ivan A. , Bragina Olga D. , Garbukov Evgeniy Yu. , Vostrikova Mariya A. , Zavyalova Marina V. , Denisov Evgeny V. , Cherdyntseva Nadezhda V. , Tashireva Liubov A.
Published: October 2024

Most studies on CTCs have focused on isolating cells that express EpCAM. In this study, we emphasize the presence of EpCAM-negative and EpCAMlow CTCs, in addition to EpCAMhigh CTCs, in early BC. We evaluated stem cell markers (CD44/CD24 and CD133) and EMT markers (N-cadherin) in each subpopulation. Our findings indicate that all stemness variants were present in both EpCAMhigh and EpCAM-negative CTCs, whereas only one variant of stemness (nonCD44+CD24−/CD133+) was observed among EpCAMlow CTCs. Nearly all EpCAMhigh CTCs were represented by CD133+ stem cells. Notably, the hybrid EMT phenotype was more prevalent among EpCAM-negative CTCs. scRNA-seq of isolated CTCs and primary tumor partially confirmed this pattern. Therefore, further investigation is imperative to elucidate the prognostic significance of EpCAM-negative and EpCAMlow CTCs.
The Protective Role of Intermedin in Contrast-Induced Acute Kidney Injury: Enhancing Peritubular Capillary Endothelial Cell Adhesion and Integrity Through the cAMP/Rac1 Pathway
Authors: Gao Tingting , Gu Ruiyuan , Wang Heng , Li Lizheng , Zhang Bojin , Hu Jie , Tian Qinqin , Chang Runze , Zhang Ruijing , Zheng Guoping , Dong Honglin
Published: October 2024

Contrast-induced acute kidney injury (CIAKI) is a common complication with limited treatments. Intermedin (IMD), a peptide belonging to the calcitonin gene-related peptide family, promotes vasodilation and endothelial stability, but its role in mitigating CIAKI remains unexplored. This study investigates the protective effects of IMD in CIAKI, focusing on its mechanisms, particularly the cAMP/Rac1 signaling pathway. Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were assessed using CCK8 assay, flow cytometry, ELISA, and Western blotting. A CIAKI rat model was utilized to evaluate renal peritubular capillary endothelial cell injury and renal function through histopathology, immunohistochemistry, immunofluorescence, Western blotting, and transmission electron microscopy. In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway, with Rac1 inhibition attenuating these protective effects. In vivo, CIAKI caused severe damage to peritubular capillary endothelial cell junctions, impairing renal function. IMD treatment markedly improved renal function, an effect negated by Rac1 inhibition. IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, preserving peritubular capillary endothelial integrity and alleviating acute renal injury from contrast media. These findings suggest that IMD has therapeutic potential in CIAKI and highlight the cAMP/Rac1 pathway as a promising target for preventing contrast-induced acute kidney injury in at-risk patients, ultimately improving clinical outcomes.
A Map of Transcriptomic Signatures of Different Brain Areas in Alzheimer’s Disease
Authors: Ferrari Riccardo Rocco , Fantini Valentina , Garofalo Maria , Di Gerlando Rosalinda , Dragoni Francesca , Rizzo Bartolo , Spina Erica , Rossi Michele , Calatozzolo Chiara , Profka Xhulja , Ceroni Mauro , Guaita Antonio , Davin Annalisa , Gagliardi Stella , Poloni Tino Emanuele
Published: October 2024

Alzheimer’s disease (AD) is a neurodegenerative disorder that progressively involves brain regions with an often-predictable pattern. Damage to the brain appears to spread and worsen with time, but the molecular mechanisms underlying the region-specific distribution of AD pathology at different stages of the disease are still under-investigated. In this study, a whole-transcriptome analysis was carried out on brain samples from the hippocampus (HI), temporal and parietal cortices (TC and PC, respectively), cingulate cortex (CG), and substantia nigra (SN) of six subjects with a definite AD diagnosis and three healthy age-matched controls in duplicate. The transcriptomic results showed a greater number of differentially expressed genes (DEGs) in the TC (1571) and CG (1210) and a smaller number of DEGs in the HI (206), PC (109), and SN (60). Furthermore, the GSEA showed a difference between the group of brain areas affected early (HI and TC) and the group of areas that were subsequently involved (PC, CG, and SN). Notably, in the HI and TC, there was a significant downregulation of shared DEGs primarily involved in synaptic transmission, while in the PC, CG, and SN, there was a significant downregulation of genes primarily involved in protein folding and trafficking. The course of AD could follow a definite time- and severity-related pattern that arises from protein misfolding, as observed in the PC, CG, and SN, and leads to synaptic impairment, as observed in the HI and TC. Therefore, a map of the molecular and biological processes involved in AD pathogenesis may be traced. This could aid in the discovery of novel biological targets in order to develop effective and well-timed therapeutic approaches.
Molecular and Cellular Mechanisms of the Therapeutic Effect of Mesenchymal Stem Cells and Extracellular Vesicles in Corneal Regeneration
Authors: Kobal Nina , Marzidovšek Miha , Schollmayer Petra , Maličev Elvira , Hawlina Marko , Marzidovšek Zala Lužnik
Published: October 2024

The cornea is a vital component of the visual system, and its integrity is crucial for optimal vision. Damage to the cornea resulting from trauma, infection, or disease can lead to blindness. Corneal regeneration using mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) offers a promising alternative to corneal transplantation. MSCs are multipotent stromal cells that can differentiate into various cell types, including corneal cells. They can also secrete a variety of anti-inflammatory cytokines and several growth factors, promoting wound healing and tissue reconstruction. This review summarizes the current understanding of the molecular and cellular mechanisms by which MSCs and MSC-EVs contribute to corneal regeneration. It discusses the potential of MSCs and MSC-EV for treating various corneal diseases, including corneal epithelial defects, dry eye disease, and keratoconus. The review also highlights finalized human clinical trials investigating the safety and efficacy of MSC-based therapy in corneal regeneration. The therapeutic potential of MSCs and MSC-EVs for corneal regeneration is promising; however, further research is needed to optimize their clinical application.
Immp2l Deficiency Induced Granulosa Cell Senescence Through STAT1/ATF4 Mediated UPRmt and STAT1/(ATF4)/HIF1α/BNIP3 Mediated Mitophagy: Prevented by Enocyanin
Authors: Qu Xiaoya , Pan Pengge , Cao Sinan , Ma Yan , Yang Jinyi , Gao Hui , Pei Xiuying , Yang Yanzhou
Published: October 2024

Dysfunctional mitochondria producing excessive ROS are the main factors that cause ovarian aging. Immp2l deficiency causes mitochondrial dysfunction and excessive ROS production, leading to ovarian aging, which is attributed to granulosa cell senescence. The pathway controlling mitochondrial proteostasis and mitochondrial homeostasis of the UPRmt and mitophagy are closely related with the ROS and cell senescence. Our results suggest that Immp2l knockout led to granulosa cell senescence, and enocyanin treatment alleviated Immp2l deficiency-induced granulosa cell senescence, which was accompanied by improvements in mitochondrial function and reduced ROS levels. Interestingly, redox-related protein modifications, including S-glutathionylation and S-nitrosylation, were markedly increased in Immp2l-knockout granulosa cells, and were markedly reduced by enocyanin treatment. Furthermore, STAT1 was significantly increased in Immp2l-knockout granulosa cells and reduced by enocyanin treatment. The co-IP results suggest that the expression of STAT1 was controlled by S-glutathionylation and S-nitrosylation, but not phosphorylation. The UPRmt was impaired in Immp2l-deficient granulosa cells, and unfolded and misfolded proteins aggregated in mitochondria. Then, the HIF1α/BNIP3-mediated mitophagy pathway was activated, but mitophagy was impaired due to the reduced fusion of mitophagosomes and lysosomes. The excessive aggregation of mitochondria increased ROS production, leading to senescence. Hence, Enocyanin treatment alleviated granulosa cell senescence through STAT1/ATF4-mediated UPRmt and STAT1/(ATF4)/HIF1α/BNIP3-mediated mitophagy.
Identification of Reliable Reference Genes for Use in Gene Expression Studies in Rat Febrile Seizure Model
Authors: Kovalenko Anna A. , Zakharova Maria V. , Schwarz Alexander P. , Zubareva Olga E. , Zaitsev Aleksey V.
Published: October 2024

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To ensure the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression levels were Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model.
Multi-Annual Study of Eriogaster catax (Linnaeus, 1758) (Lepidoptera, Lasiocampidae) Oviposition Strategy in Transylvania’s Largest Population: Key Insights for Species Conservation and Local Land Management
Authors: Sitar Cristian , Sitar Geanina Magdalena , Ionică Angela Monica , Hula Vladimír , Spitzer Lukáš , Rusu Alina Simona , Rakosy László
Published: October 2024

This study provides new insights into the oviposition strategy of Eriogaster catax (Linnaeus, 1758) (Lepidoptera, Lasiocampidae), an endangered species of moth found in semi-natural habitats within agricultural landscapes. Protected under various European directives and listed as Data Deficient by the IUCN, E. catax inhabits warmer regions of the Western Palearctic. Despite noted geographic variations in its ecological preferences, few studies have statistically significant data on its ecology. Our six-year study, conducted within the largest known population of E. catax. in Romania, reveals critical data on its oviposition preferences, including the species’ tendency to utilize Prunus spinosa L. and Crataegus monogyna Jacq. shrubs at an average height of 80.48 ± 34.3 cm, with most nests placed within the 41–80 cm range and containing an average of 186 ± 22 eggs. The study also addresses the species’ vulnerability to human activities such as bush trimming, agricultural burning, and uncontrolled grazing, particularly due to its low oviposition height. These findings underscore the negative impact of overgrazing and burning practices, particularly when conducted on a large scale, on the conservation of E. catax. The detailed ecological requirements identified in this study are essential for developing effective conservation strategies and habitat management practices. Furthermore, the study highlights the importance of local community involvement and public education in raising awareness about biodiversity and the conservation of endangered species.
Thioredoxin System in Insects: Uncovering the Roles of Thioredoxins and Thioredoxin Reductase beyond the Antioxidant Defences
Authors: Gřešková Andrea , Petřivalský Marek
Published: October 2024

Increased levels of reactive oxygen species (ROS) produced during aerobic metabolism in animals can negatively affect the intracellular redox status, cause oxidative stress and interfere with physiological processes in the cells. The antioxidant defence regulates ROS levels by interplaying diverse enzymes and non-enzymatic metabolites. The thioredoxin system, consisting of the enzyme thioredoxin reductase (TrxR), the redox-active protein thioredoxin (Trx) and NADPH, represent a crucial component of antioxidant defence. It is involved in the signalling and regulation of multiple developmental processes, such as cell proliferation or apoptotic death. Insects have evolved unique variations of TrxR, which resemble mammalian enzymes in overall structure and catalytic mechanisms, but the selenocysteine–cysteine pair in the active site is replaced by a cysteine–cysteine pair typical of bacteria. Moreover, the role of the thioredoxin system in insects is indispensable due to the absence of glutathione reductase, an essential enzyme of the glutathione system. However, the functions of the Trx system in insects are still poorly characterised. In the present review, we provide a critical overview of the current knowledge on the insect Trx system, focusing mainly on TrxR’s role in the antioxidant and immune system of model insect species.
Energy Reserve Allocation in the Trade-Off between Migration and Reproduction in Fall Armyworm
Authors: Xu Chuan-Feng , Liu Peng-Cheng , Chapman Jason W. , Wotton Karl R. , Qi Guo-Jun , Wang Yu-Meng , Hu Gao
Published: October 2024

Striking a trade-off between migration and reproduction becomes imperative during long-range migration to ensure proper energy allocation. However, the mechanisms involved in this trade-off remain poorly understood. Here, we used a takeoff assay to distinguish migratory from non-migratory individuals in the fall armyworm, which is a major migratory insect worldwide. Migratory females displayed delayed ovarian development and flew further and faster than non-migratory females during tethered flight. Transcriptome analyses demonstrated an enrichment of fatty acid genes across successive levels of ovarian development and different migratory behaviors. Additionally, genes with roles in phototransduction and carbohydrate digestion along with absorption function were enriched in migratory females. Consistent with this, we identified increased abdominal lipids in migratory females that were mobilized to supply energy to the flight muscles in the thorax. Our study reveals that the fall armyworm faces a trade-off in allocating abdominal triglycerides between migration and reproduction during flight. The findings provide valuable insights for future research on this trade-off and highlight the key energy components involved in this strategic balance.
Gender-Tailored Heart Team Decision Making Equalizes Outcomes for Female Patients after Aortic Valve Replacement through Right Anterior Small Thoracotomy (RAST)
Authors: Lavanchy Isabel , Passos Laina , Aymard Thierry , Grünenfelder Jürg , Emmert Maximilian Y. , Corti Roberto , Gaemperli Oliver , Biaggi Patric , Reser Diana
Published: October 2024

Background: Little is known about gender-dependent outcomes after aortic valve replacement (AVR) through right anterior thoracotomy (RAST). The aim of our study was to analyze the mid-term outcomes of our cohort. Methods: This study is a retrospective analysis of 338 patients (2013–2022). Subgroup analysis included a gender-dependent comparison of age groups ≤60 and >60 years. Results: Women were older (69.27 ± 7.98 vs. 64.15 ± 11.47, p < 0.001) with higher Euroscore II (1.25 ± 0.73 vs. 0.94 ± 0.45, p < 0.001). Bypass and cross-clamp time were shorter (109.36 ± 30.8 vs. 117.65 ± 33.1 minutes, p = 0.01; 68.26 ± 21.5 vs. 74.36 ± 23.3 minutes, p = 0.01), while ICU, hospital stay and atrial fibrillation were higher (2.48 ± 8.2 vs. 1.35 ± 1.4 days, p = 0.005; 11 ± 7.8 vs. 9.48 ± 2.3 days, p = 0.002; 6.7% vs. 4.4%, p = 0.024). Mortality was 0.9%, while stroke was 0.6%. Age subgroup analysis showed that women were older (p = 0.025) with longer ICU and hospital stays (p < 0.001, p = 0.007). On mid-term follow-up (4.52 ± 2.67 years) of 315 patients (94.3%), there was no significant difference in survival, MACCE and re-intervention comparing gender and age groups. Conclusions: Despite older age, higher Euroscore II, longer ICU and hospital stay in women, mortality, MACCE and reoperation were low and comparable in gender and age groups. We believe that our patient-tailored heart team decision making combined with RAST translates into gender-tailored medicine, which equalizes the widely reported negative outcomes of female patients after cardiac surgery.
Race, Sex, and Ejection Fraction-Based Differences in Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Risk Prediction
Authors: Chedid El Helou Michel , Gupta Mohak , Hussain Muzna , Hanna Mazen , Blumer Vanessa , William Preethi , Desai Milind Y. , Abadie Bryan Q. , Ives Lauren , Tang W. H. Wilson , Jaber Wael A. , Collier Patrick , Martyn Trejeeve
Published: October 2024

Background: The early detection of transthyretin cardiac amyloidosis (ATTR-CM) is essential, with Tc-99m pyrophosphate scintigraphy (PYP scan) being a key diagnostic tool. Although a previously validated score has shown promise in predicting PYP scan positivity among patients with HFpEF, further evaluation in diverse cohorts is necessary. Objectives: To assess the effectiveness of the ATTR-CM score in predicting PYP scan positivity within our patient population. Methods: We analyzed patients referred for PYP with SPECT at the Cleveland Clinic from January 2012 to January 2020, all of whom had undergone echocardiography within the previous year. The ATTR-CM score was determined using the following criteria: Age (60–69, +2; 70–79, +3; ≥80, +4), sex (male, +2), hypertension (present, −1), left ventricular ejection fraction (LVEF <60%, +1), posterior wall thickness (≥12 mm, +1), and relative wall thickness (>0.57, +2). A score of ≥6 indicated high risk. Results: Among the 540 patients (32% female, 33% black), 27% had an LVEF <40%. The score demonstrated good discrimination by AUC, with consistent performance across different racial groups, sexes, and LVEF categories. For scores ≥6, sensitivity was lower in women and black patients; however, lowering the cutoff to 5 markedly improved sensitivity. Conclusions: The ATTR-CM score displayed consistently good performance by AUC across our cohort, including patients with HFrEF. Nevertheless, its sensitivity was reduced in black patients and women. Efforts to scale ATTR-CM diagnosis tools should be mindful of demographic differences in risk prediction models.
The Abdominal Adiposity Index (A Body Shape Index) Predicts 10-Year All-Cause Mortality in Elderly Active Non-Obese Subjects
Authors: Nunnari Alessio , Di Girolamo Filippo Giorgio , Teraž Kaja , Fiotti Nicola , Šimunič Boštjan , Mearelli Filippo , Pišot Rado , Biolo Gianni
Published: October 2024

Background/Objectives: A Body Shape Index (ABSI), which accounts for waist circumference relative to mass and height, shows a robust association with mortality risk. The present study evaluates the effectiveness of ABSI as a predictor of 10-year all-cause mortality in physically active, non-obese elderly individuals. Methods: This prospective cohort study included 159 volunteers (94 women, aged 60–80 years), recruited in the frame of the “Physical Activity and Nutrition for Great Ageing” (PANGeA) Cross-border Cooperation Program Slovenia–Italy 2007–2013, and followed for 10 years. Baseline characteristics included anthropometric measurements, bioelectrical impedance analysis, and cardiovascular fitness tests (VO2max). Statistical analyses (Cox regression, Kaplan–Meier survival) were conducted to examine the relationship between ABSI and mortality. Results: During the 10-year follow-up, 10 deaths (6.7%) were recorded. ABSI (adjusted for age, smoking, comorbidities, and therapy) was an independent predictor of mortality (hazard ratio = 4.65, p < 0.001). Higher ABSI scores were linked to reduced VO2max (r = −0.190, p = 0.017) and increased systolic blood pressure (r = 0.262, p = 0.001). An ABSI-based predictive model showed strong discriminatory power (AUROC = 0.91). Conclusions: ABSI is a reliable predictor of 10-year mortality in active, non-obese elderly individuals and may improve risk stratification in clinical practice.
Soluble Urokinase Plasminogen Activator Receptor as a Predictor of All-Cause Death in Patients Undergoing Coronary Angiography at 10-Year Follow-Up
Authors: Kern Adam , Stompór Tomasz , Bojko Krystian , Sienkiewicz Ewa , Pawlak Sebastian , Pawlak Krystyna , Pawlak Dariusz , Poskrobko Grzegorz , Andrasz Ewa , Gromadziński Leszek , Jalali Rakesh , Onichimowski Dariusz , Piwko Grażyna , Zalewski Artur , Bil Jacek
Published: October 2024

Background: We aimed to explore the predictive role of soluble urokinase plasminogen activator receptor (suPAR) in patients undergoing coronary angiography by systematically evaluating its association with adverse cardiovascular events at 10 years follow-up. Methods: The KORONEF study was a single-center, observational, prospective study with 492 subjects included. In the multivariable Cox regression model, we checked the impact of suPAR, neutrophil elastase, myeloperoxidase, and DNase 1 on long-term outcomes. Results: The mean study population age was 64.4 ± 9.9 years, and there were 37.2% women. We divided the population into tertiles of suPAR levels (T1 0.793–2.135 ng/mL; T2 2.136–2.868 ng/mL; and T3 2.872–8.677 ng/mL). Patients with higher suPAR concentrations were more often females (tertile 1 vs. tertile 3: 27.4% vs. 50.6%, p < 0.001) and older age (60.8 ± 8.7 years vs. 68.8 ± 9.5 years, p < 0.001). They also characterized higher incidence of diabetes (17.7% vs. 38.0%, p < 0.001), previous myocardial infarction (22% vs. 44.8%, p < 0.001), and chronic kidney disease (3% vs. 18.4%, p < 0.001), but lower incidence of dyslipidemia (54.3% vs. 35.6%). The 10-year all-cause death rates were 14.6% vs. 34.1%, HR 2.68, 95% CI 1.66–4.33, p < 0.001 for tertile 2, and 14.6% vs. 39.9%, HR 3.24, 95% CI 2.03–5.17, p < 0.001 for tertile 3. The optimal cut-off suPAR value of 2.39 ng/mL provided a sensitivity of 66.9% and a specificity of 54.6% in predicting all-cause death. Conclusions: The association of elevated suPAR with increased mortality risk suggests its potential relevance in predicting long-term outcomes and may help inform more individualized management strategies for high-risk patients.
Hemoincompatibility in Hemodialysis-Related Therapies and Their Health Economic Perspectives
Authors: Hornig Carsten , Bowry Sudhir K. , Kircelli Fatih , Kendzia Dana , Apel Christian , Canaud Bernard
Published: October 2024

Hemobiologic reactions associated with the hemoincompatibility of extracorporeal circuit material are an undesirable and inevitable consequence of all blood-contacting medical devices, typically considered only from a clinical perspective. In hemodialysis (HD), the blood of patients undergoes repetitive (at least thrice weekly for 4 h and lifelong) exposure to different polymeric materials that activate plasmatic pathways and blood cells. There is a general agreement that hemoincompatibility reactions, although unavoidable during extracorporeal therapies, are unphysiological contributors to non-hemodynamic dialysis-induced systemic stress and need to be curtailed. Strategies to lessen the periodic and direct effects of blood interacting with artificial surfaces to stimulate numerous biological pathways have focused mainly on the development of ‘more passive’ materials to decrease intradialytic morbidity. The indirect implications of this phenomenon, such as its impact on the overall delivery of care, have not been considered in detail. In this article, we explore, for the first time, the potential clinical and economic consequences of hemoincompatibility from a value-based healthcare (VBHC) perspective. As the fundamental tenet of VBHC is achieving the best clinical outcomes at the lowest cost, we examine the equation from the individual perspectives of the three key stakeholders of the dialysis care delivery processes: the patient, the provider, and the payer. For the patient, sub-optimal therapy caused by hemoincompatibility results in poor quality of life and various dialysis-associated conditions involving cost-impacting adjustments to lifestyles. For the provider, the decrease in income is attributed to factors such as an increase in workload and use of resources, dissatisfaction of the patient from the services provided, loss of reimbursement and direct revenue, or an increase in doctor–nurse turnover due to the complexity of managing care (nephrology encounters a chronic workforce shortage). The payer and healthcare system incur additional costs, e.g., increased hospitalization rates, including intensive care unit admissions, and increased medications and diagnostics to counteract adverse events and complications. Thus, hemoincompatibility reactions may be relevant from a socioeconomic perspective and may need to be addressed beyond just its clinical relevance to streamline the delivery of HD in terms of payability, future sustainability, and societal repercussions. Strategies to mitigate the economic impact and address the cost-effectiveness of the hemoincompatibility of extracorporeal kidney replacement therapy are proposed to conclude this comprehensive approach.
Whole-Body Perfusion in Neonates and Infants Undergoing Aortic Arch Surgery—Working Towards the New Standard
Authors: Sandoval Boburg Rodrigo , Doll Isabelle , Rustenbach Christian Jörg , Berger Rafal , Jost Walter , Magunia Harry , Nordmeyer Johannes , Michel Jörg , Schlensak Christian
Published: October 2024

Background: Neonatal aortic arch surgery remains one of the most challenging procedures in congenital cardiac surgery. In recent years, there has been a trend away from selective cerebral perfusion (SCP) and arrest of body circulation towards whole-body perfusion (WBP), a combination of SCP and lower-body perfusion (LBP), to facilitate arch surgery and preserve organ function. Methods: Retrospective, single-centre analysis was conducted of patients under one year of age undergoing aortic arch surgery from January 2014 until December 2022. SCP was used from January 2014—December 2017; WBP was implemented from January 2017—December 2022. Patients were separated according to the type of perfusion used during surgery, SCP or WBP. The cohort consisted of a total of 95 patients, 34 in the SCP group and 61 in the WBP group. Results: Patients in the WBP group showed significantly lower rates of intraoperative transfusions, namely red blood cells, fresh-frozen plasma and thrombocytes (p-value < 0.01, <0.01, and <0.01, respectively). The WBP group showed significantly lower creatinine and higher urine output values 24 and 72 h after surgery (p-value = 0.02, <0.01, respectively). The WBP group showed a significant lower incidence of major neurological complications (p-value 0.01). Binary logistic regression analyses showed favourable outcomes for the WBP group regarding 30-day mortality (OR = 0.03, CI = 0.003–0.391, p-value = <0.01), multiorgan failure (OR = 0.002, CI = 0–0.275, p-value = 0.01), neurological complications (OR = 0.994, CI = 0.998–1, p-value = 0.06) and postoperative renal replacement therapy (RRT) (OR = 0.989, CI = 0.983–0.995, p-value = <0.01). Conclusions: Patients with WBP received fewer intraoperative transfusions, showed improved postoperative renal function and suffered significantly fewer neurological complications.
Impact of Pelvic Calcification Severity on Renal Transplant Outcomes: A Prospective Single-Center Study
Authors: Žuža Iva , Dodig Doris , Brumini Ivan , Kutlić Mate , Đurić Robert , Katalinić Nataša , Gršković Antun , Jakšić Ante , Mavrinac Martina , Ćelić Tanja , Rački Sanjin , Orlić Lidija , Nekić Jasna , Markić Dean
Published: October 2024

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0–4), PCS Group 2 (PCS 5–19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management.
Geochemical and Physical Methods for Estimating the Saturation of Natural Gas Hydrates in Sediments: A Review
Authors: Xue Yuan , Lu Hailong , Yang Hailin , Cai Wenjiu , Zhan Linsen
Published: October 2024

The saturation of natural gas hydrates is a key parameter for characterizing hydrate reservoirs, estimating hydrate reserves, and developing hydrate as an energy resource. Several methods have been proposed to estimate hydrate saturation, although most of these studies rely on logging and seismic data. However, the methods for estimating hydrate saturation from recovered core sediments have not been thoroughly reviewed, which hinders a deeper understanding, proper application, and the use of these experimental data to integrate geophysical and numerical model results with the actual geological conditions. In this paper, the methods widely used for estimating natural gas hydrate saturation from core sediments, including those based on pore water chemistry (Cl− concentration, δD, and δ18O values), gas volumetric analysis, and temperature anomaly, have been summarized in terms of the principle, estimation strategy, and issues to be considered of each method. The applicability, advantages and disadvantages, and scope of application of each method are also compared and discussed. All methods for estimating gas hydrate saturation have certain limitations. A comprehensive application of results from multiple methods could lead to a better understanding of the amount of gas hydrate in sediments, although the chlorinity of pore water is the most commonly used method of estimation.
Development of an RPA-CRISPR/Cas12a Assay for Rapid and Sensitive Diagnosis of Plant Quarantine Fungus Setophoma terrestris
Authors: Zhao Peng , Feng Zhipeng , Cai Lei , Phurbu Dorji , Duan Weijun , Xie Fuhong , Li Xuelian , Liu Fang
Published: October 2024

Setophoma terrestris is an important phytopathogenic fungus listed by China as a harmful fungus subject to phytosanitary import control. This pathogen is a threat to a wide range of plants, particularly as the causal agent of onion pink root rot, one of the most severe diseases of onions. In order to provide rapid identification and early warning of S. terrestris and prevent its spread, we have developed a rapid, accurate, and visually intuitive diagnostic assay for this pathogen, by utilizing recombinase polymerase amplification (RPA), coupled with CRISPR/Cas12a cleavage and fluorescence-based detection systems or paper-based lateral flow strips. The developed RPA-CRISPR/Cas12a assay exhibited remarkable specificity for the detection of S. terrestris. Moreover, this protocol can detect the pathogen at a sensitivity level of 0.01 pg/μL, which significantly outperforms the 1 pg/μL sensitivity achieved by the existing qPCR-based detection method. The entire diagnostic procedure, including DNA extraction, the RPA reaction, the Cas12a cleavage, and the result interpretation, can be accomplished in 40 min. Furthermore, the successful application of the assay in infected plant samples highlighted its potential for rapid and accurate pathogen detection in agricultural settings. In summary, this RPA-CRISPR/Cas12a diagnostic method offers a potentially valuable technological solution for quarantine and disease management.
Application of Quantitative Magnetic Resonance Imaging (QMRI) to Evaluate the Effectiveness of Ultrasonic Atomization of Water in Truffle Preservation
Authors: Marino Alessia , Leonardi Marco , Zambonelli Alessandra , Iotti Mirco , Galante Angelo
Published: October 2024

Truffles of the Tuber genus (Pezizales, Ascomycetes) are among the most valuable and expensive foods, but their shelf life is limited to 7–10 days when stored at 4 °C. Alternative preservation methods have been proposed to extend their shelf life, though they may alter certain quality parameters. Recently, a hypogeal display case equipped with an ultrasonic humidity system (HDC) was developed, extending the shelf life to 2–3 weeks, depending on the truffle species. This study assesses the efficacy of HDC in preserving Tuber melanosporum and Tuber borchii ascomata over 16 days, using quantitative magnetic resonance imaging (QMRI) to monitor water content and other parameters. Sixteen T. melanosporum and six T. borchii ascomata were stored at 4 °C in an HDC or a static fridge (SF) as controls. QMRI confirmed that T. borchii has a shorter shelf life than T. melanosporum under all conditions. HDC reduced the rate of shrinkage, water, and mass loss in both species. Additionally, the Apparent Diffusion Coefficient (ADC), longitudinal relaxation time (T1), and transverse relaxation time (T2), which reflect molecular changes, decreased more slowly in HDC than SF. QMRI proves useful for studying water-rich samples and assessing truffle preservation technologies. Further optimization of this method for industrial use is needed.
On the Energy Behaviors of the Bellman–Ford and Dijkstra Algorithms: A Detailed Empirical Study
Authors: Alamoudi Othman , Al-Hashimi Muhammad
Published: October 2024

The Single-Source Shortest Paths (SSSP) graph problem is a fundamental computation. This study attempted to characterize concretely the energy behaviors of the two primary methods to solve it, the Bellman–Ford and Dijkstra algorithms. The very different interactions of the algorithms with the hardware may have significant implications for energy. The study was motivated by the multidisciplinary nature of the problem. Gaining better insights should help vital applications in many domains. The work used reliable embedded sensors in an HPC-class CPU to collect empirical data for a wide range of sizes for two graph cases: complete as an upper-bound case and moderately dense. The findings confirmed that Dijkstra’s algorithm is drastically more energy efficient, as expected from its decisive time complexity advantage. In terms of power draw, however, Bellman–Ford had an advantage for sizes that fit in the upper parts of the memory hierarchy (up to 2.36 W on average), with a region of near parity in both power draw and total energy budgets. This result correlated with the interaction of lighter logic and graph footprint in memory with the Level 2 cache. It should be significant for applications that rely on solving a lot of small instances since Bellman–Ford is more general and is easier to implement. It also suggests implications for the design and parallelization of the algorithms when efficiency in power draw is in mind.
TCEDN: A Lightweight Time-Context Enhanced Depression Detection Network
Authors: Yan Keshan , Miao Shengfa , Jin Xin , Mu Yongkang , Zheng Hongfeng , Tian Yuling , Wang Puming , Yu Qian , Hu Da
Published: October 2024

The automatic video recognition of depression is becoming increasingly important in clinical applications. However, traditional depression recognition models still face challenges in practical applications, such as high computational costs, the poor application effectiveness of facial movement features, and spatial feature degradation due to model stitching. To overcome these challenges, this work proposes a lightweight Time-Context Enhanced Depression Detection Network (TCEDN). We first use attention-weighted blocks to aggregate and enhance video frame-level features, easing the model’s computational workload. Next, by integrating the temporal and spatial changes of video raw features and facial movement features in a self-learning weight manner, we enhance the precision of depression detection. Finally, a fusion network of 3-Dimensional Convolutional Neural Network (3D-CNN) and Convolutional Long Short-Term Memory Network (ConvLSTM) is constructed to minimize spatial feature loss by avoiding feature flattening and to achieve depression score prediction. Tests on the AVEC2013 and AVEC2014 datasets reveal that our approach yields results on par with state-of-the-art techniques for detecting depression using video analysis. Additionally, our method has significantly lower computational complexity than mainstream methods.
An Adapted Physical Activity Program for Adolescents with an Intellectual Disability: An International Classification of Functioning, Disability, and Health Perspective
Authors: Shen Xin , Huang Peiying , Nie Bing , Su Maolin , Liu Dan , Guo Yin , Zheng Lan
Published: October 2024

The International Classification of Functioning, Disability, and Health (ICF) offers a comprehensive bio-psycho-social model for evaluating the multifaceted needs of individuals with disabilities. While its adoption in healthcare settings is widespread, its utilization within the domain of physical activity interventions, particularly for adolescents with intellectual disabilities (IDs), remains insufficiently explored. This study rigorously examines the efficacy of a 6-month ICF-based Adaptive Physical Activity (APA) intervention on the development of fundamental motor skills (FMSs), improvements in physical fitness (PF), and enhancements in quality of life (QoL) among adolescents with ID. A total of thirty-eight adolescents were randomly allocated into either an intervention group (IG), which participated in the tailored APA program, or a control group (CG), which received standard physical education. The findings demonstrated statistically significant improvements in the IG’s test of gross motor development (TGMD) total, locomotor, object control, and QOL scores relative to the CG (p < 0.001, η² = 0.330, 0.249, 0.224, and 0.439, respectively). Furthermore, substantial gains were observed in PF measures, including upper and lower limb strength as well as cardiorespiratory fitness (p < 0.001, η² = 0.254, 0.351, 0.176). Strong positive correlations were noted between FMS, PF, and QoL (r = 0.34–0.71, p < 0.05). This study underscores the importance of tailoring physical activity programs for adolescents with ID, offering insights into the relationships between FMS, PF, and QoL, and guidance for future interventions aimed at improving health outcomes in this population.