bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Performance of the Optimized Dye CF583R in Direct Stochastic Optical Reconstruction Microscopy of Active Zones in Drosophila Melanogaster
Authors: Noß Marvin , Ljaschenko Dmitrij , Mrestani Achmed
Published: August 2024

Super-resolution single-molecule localization microscopy (SMLM) of presynaptic active zones (AZs) and postsynaptic densities contributed to the observation of protein nanoclusters that are involved in defining functional characteristics and in plasticity of synaptic connections. Among SMLM techniques, direct stochastic optical reconstruction microscopy (dSTORM) depends on organic fluorophores that exert high brightness and reliable photoswitching. While multicolor imaging is highly desirable, the requirements necessary for high-quality dSTORM make it challenging to identify combinations of equally performing, spectrally separated dyes. Red-excited carbocyanine dyes, e.g., Alexa Fluor 647 (AF647) or Cy5, are currently regarded as “gold standard” fluorophores for dSTORM imaging. However, a recent study introduced a set of chemically modified rhodamine dyes, including CF583R, that promise to display similar performance in dSTORM. In this study, we defined CF583R’s performance compared to AF647 and CF568 based on a nanoscopic analysis of Bruchpilot (Brp), a nanotopologically well-characterized scaffold protein at Drosophila melanogaster AZs. We demonstrate equal suitability of AF647, CF568 and CF583R for basal AZ morphometry, while in Brp subcluster analysis CF583R outperforms CF568 and is on par with AF647. Thus, the AF647/CF583R combination will be useful in future dSTORM-based analyses of AZs and other subcellularly located marker molecules and their role in physiological and pathophysiological contexts.
Additive Manufacturing: Experiments, Simulations, and Data-Driven Modelling
Authors: Mahmood Muhammad Arif , Ur Rehman Asif , Khraisheh Marwan , Salamci Metin U. , Ur Rehman Rashid , Sajjad Uzair , Ristoscu Carmen , Popescu Andrei C. , Oane Mihai , Mihailescu Ion N.
Published: August 2024

Additive manufacturing (AM) has profoundly impacted modern engineering and materials science by enabling unparalleled control over microstructures, customization, and material properties [...]
Adult Pancreatoblastoma: Clinical Insights and Outcomes Compared to Pancreatic Ductal Adenocarcinoma (PDAC)
Authors: Yin Han , Romero-Hernandez Fernanda , Ganjouei Amir Ashraf , Wang Jaeyun Jane , Brown Audrey , Hirose Kenzo , Maker Ajay V. , Nakakura Eric , Corvera Carlos , Kirkwood Kimberly S. , Wilhelm Alexander , Peng June S. , Alseidi Adnan , Adam Mohamed A.
Published: August 2024

Pancreatoblastoma is perceived to be aggressive in adults; however, data are limited due to the rarity of the disease. We benchmarked clinico-pathologic characteristics, outcomes, and survival of adult patients with pancreatoblastoma to a comparable PDAC cohort using the National Cancer Database (NCDB). This study included 301,204 patients: 35 with pancreatoblastoma and 301,169 PDAC patients. Pancreatoblastoma patients were younger than PDAC patients (56 vs. 69 years, p < 0.001). More pancreatoblastoma patients were managed at academic institutions (63.0% vs. 40.7%, p = 0.047). The most frequent primary site was the head and the neck of the pancreas. There were no differences in tumor size (4.2 cm vs. 3.7 cm, p = 0.828), lymph node positivity (14.3% vs. 26.4%, p = 0.103), or metastasis at time of diagnosis (31.4% vs. 46.1%, p = 0.081). The majority of pancreatoblastoma patients underwent resection compared to a minority of PDAC patients (69.7% vs. 15.5%, p < 0.001). Time from diagnosis to surgery was longer for pancreatoblastoma patients (33 vs. 14 days, p = 0.030). Pancreaticoduodenectomy was the most common type of resection in the pancreatoblastoma and PDAC groups (47.8% vs. 67.7%, p = 0.124). Among resected patients, pancreatoblastoma patients were less likely to receive radiation (4.8% vs. 37.0%, p = 0.002), but the use of chemotherapy was similar to PDAC patients (60.9% vs. 70.7%). After matching, median overall survival was longer for pancreatoblastoma than PDAC (59.8 months vs. 15.2 months, p = 0.014).
Focal Update on Immunotherapy and Liver Transplantation in the Era of Transplant Oncology
Authors: Abdelrahim Maen , Esmail Abdullah , Hibi Taizo , Mazzaferro Vincenzo
Published: August 2024

Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and “bridging” previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update’s utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance.
Unraveling the Predictive Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) on Survival Outcomes in Patients with Grade 4 Adult-Type Diffuse Gliomas
Authors: Aydin Asim Armagan , Yuceer Ramazan Oguz
Published: August 2024

Background: This investigation evaluated the predictive and prognostic efficacy of the newly developed global immune-nutrition-inflammation index (GINI) in patients with grade 4 adult-type diffuse gliomas, comparing it with other established indices such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). Method: A retrospective cohort included 198 patients diagnosed with isocitrate dehydrogenase (IDH)-mutant gr4 (grade 4) astrocytoma and IDH-wt (wilde-type) glioblastoma (GBM) gr4 treated with surgical resection, radiotherapy, and temozolomide. Patients were stratified into two groups based on their GINI values: low GINI (<5815) and high GINI (≥5815). The primary endpoint was overall survival (OS). Results: High GINI was significantly associated with older age, poor performance status, multifocal tumors, and higher SII, SIRI, and PIV values (p < 0.005). The GINI demonstrated strong correlations with SII (r = 0.694), SIRI (r = 0.516), and PIV (r = 0.657) (p < 0.001). Patients with high GINI exhibited poorer OS (5.0 vs. 17.0 months) and PFS (5.0 vs. 13.0 months) in comparison to those with low GINI. Kaplan–Meier survival analysis revealed significantly prolonged OS and PFS among patients with low GINI (p < 0.001). Multivariate analysis identified high GINI as an independent negative risk factor for both PFS and OS. Conclusions: GINI is a robust predictor of clinical outcomes in IDH-mutant gr4 astrocytoma and IDH-wt GBM gr4, highlighting the crucial impact of nutrition and cancer cachexia. It shows superior prognostic value relative to the SII, SIRI, and PIV.
A Broken Duet: Multistable Dynamics in Dyadic Interactions
Authors: Medrano Johan , Sajid Noor
Published: August 2024

Misunderstandings in dyadic interactions often persist despite our best efforts, particularly between native and non-native speakers, resembling a broken duet that refuses to harmonise. This paper delves into the computational mechanisms underpinning these misunderstandings through the lens of the broken Lorenz system—a continuous dynamical model. By manipulating a specific parameter regime, we induce bistability within the Lorenz equations, thereby confining trajectories to distinct attractors based on initial conditions. This mirrors the persistence of divergent interpretations that often result in misunderstandings. Our simulations reveal that differing prior beliefs between interlocutors result in misaligned generative models, leading to stable yet divergent states of understanding when exposed to the same percept. Specifically, native speakers equipped with precise (i.e., overconfident) priors expect inputs to align closely with their internal models, thus struggling with unexpected variations. Conversely, non-native speakers with imprecise (i.e., less confident) priors exhibit a greater capacity to adjust and accommodate unforeseen inputs. Our results underscore the important role of generative models in facilitating mutual understanding (i.e., establishing a shared narrative) and highlight the necessity of accounting for multistable dynamics in dyadic interactions.
The Evaluation of Climate Change Competitiveness via DEA Models and Shannon Entropy: EU Regions
Authors: Karman Agnieszka , Banaś Jarosław
Published: August 2024

The purpose of this paper is to assess the efficiency of climate change competitiveness via a case study on EU regions by using the data envelopment analysis (DEA) model and Shannon entropy. First, on the same premise as similar composite indicators, we develop a DEA model to assess the relative performance of the regions in climate change competitiveness. Then, we extend our calculations with a DEA-like model and Shannon entropy to derive global estimates of a new competitiveness index by using common weights. Results show that the proposed DEA-Entropy model enables the construction of a regional climate change competitiveness index among all regions via a set of common weights. The proposed model’s common weight structure demonstrates more discriminative power compared to the weights obtained through pure DEA or DEA-like methods. In order to validate the proposed DEA-Entropy model, it was applied to 120 EU regions. The results are meaningful for the regions to improve their competitiveness.
Exploring Emotional Vulnerability and Sense of Agency in the Digital Realm: A Three-Year Case Study of an EFL Teacher in South Korea
Authors: Jang Jinsil
Published: August 2024

This study presents the findings from a longitudinal case study on a Korean English teacher’s experience of emotional vulnerability and professional development in online teaching. Grounded in an ecological perspective on teacher agency and emotional vulnerability, the study investigates how and why the teacher exercised agency in navigating her emotional challenges and adapting to the virtual teaching environment. Data were collected from various sources, including interviews, observations, field notes, and artifacts, for three years. The findings showed that the intricate connection between the teacher’s multiple and dynamic emotions, beliefs, and concurrent working environments significantly influences her engagement in digital teaching practices. Furthermore, the teacher’s emotional vulnerability in virtual teaching facilitated her engagement in reflective and action-oriented practices, leading to a more proactive approach to exploring and implementing alternative teaching methods online. The findings highlight the interplay between emotions, agency, and identity development, emphasizing the importance of experiencing, understanding, negotiating, and expressing emotions to discover potential alternative teaching resources and methods in ever-changing teaching environments. This study provides insights into how teachers can leverage their emotions and exercise teacher agency to enhance their professional growth and adaptability in digital learning environments.
Electronically Conductive Polymer Enhanced Solid-State Polymer Electrolytes for All-Solid-State Lithium Batteries
Authors: Smdani Md Gulam , Hasan Md Wahidul , Razzaq Amir Abdul , Xing Weibing
Published: August 2024

All-solid-state lithium batteries (ASSLBs) have gained enormous interest due to their potential high energy density, high performance, and inherent safety characteristics for advanced energy storage systems. Although solid-state ceramic (inorganic) electrolytes (SSCEs) have high ionic conductivity and high electrochemical stability, they experience some significant drawbacks, such as poor electrolyte/electrode interfacial properties and poor mechanical characteristics (brittle, fragile), which can hinder their adoption for commercialization. Typically, SSCE-based ASSLBs require high cell stack pressures exerted by heavy fixtures for regular operation, which can reduce the energy density of the overall battery packages. Polymer–SSCE composite electrolytes can provide inherently good interfacial contacts with the electrodes that do not require high cell stack pressures. In this study, we explore the feasibility of incorporating an electronically and ionically conducting polymer, polypyrrole (PPy), into a polymer backbone, polyvinylidene fluoride-co-hexafluoropropylene (PVDF-HFP), to improve the ionic conductivity of the resultant polymer–SSCE composite electrolyte (SSPE). The electronically conductive polymer-incorporated composite electrolyte showed superior room temperature ionic conductivity and electrochemical performance compared to the baseline sample (without PPy). The PPy-incorporated polymer electrolyte demonstrated a high resilience to high temperature operation compared with the liquid-electrolyte counterpart. This performance advantage can potentially be employed in ASSLBs that operate at high temperatures. In our recent development efforts, SSPEs with optimal formulations showed room temperature ionic conductivity of 2.5 × 10−4 S/cm. The data also showed, consistently, that incorporating PPy into the polymer backbone helped boost the ionic conductivity with various SSPE formulations, consistent with the current study. Electrochemical performance of ASSLBs with the optimized SSPEs will be presented in a separate publication. The current exploratory study has shown the feasibility and benefits of the novel approach as a promising method for the research and development of next-generation solid composite electrolyte-based ASSLBs.
Predicting Industrial Electricity Consumption Using Industry–Geography Relationships: A Graph-Based Machine Learning Approach
Authors: Zhan Xiangpeng , Qian Xiaorui , Liu Wei , Liu Xinru , Chen Yuying , Zhang Liang , Hong Huawei , Shen Yimin , Xiao Kai
Published: August 2024

Accurately predicting industrial electricity consumption is of paramount importance for optimizing energy management and operational efficiency. Traditional forecasting approaches face significant challenges in capturing the complex factors influencing industrial electricity consumption, often due to the inadequate representation of correlations, thus limiting their predictive capabilities. To overcome these limitations, we propose a novel graph-based forecasting model termed Industry–Geography Time Series Forecasting Model (IG-TFM). Our approach leverages historical electricity consumption data and geographical information relevant to similar industries to construct an industry–geography relationship graph. This graph serves as the foundation of a comprehensive network that encompasses all industries of interest, allowing us to identify sectors closely associated with the target industry. The structured graph data are then processed within a graph convolutional neural network framework, which effectively captures the impact of geographical location, industry similarities, and inter-industry relationships on electricity consumption patterns. Utilizing this enriched representation, we develop our IG-TFM for accurate time series forecasting of industrial electricity consumption. Experiments conducted on real-world data, including 31 industries across 9 cities in a southern province of China, demonstrate the significant advantages of our proposed method across key performance indicators such as the Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), and Mean Absolute Percentage Error (MAPE). These findings underscore the importance and efficacy of employing complex networks to encode sequence-related information, thereby substantially improving prediction accuracy in industrial electricity consumption forecasting.
Performance of a Methanol-Fueled Direct-Injection Compression-Ignition Heavy-Duty Engine under Low-Temperature Combustion Conditions
Authors: Treacy Mark , Xu Leilei , Fatehi Hesameddin , Kaario Ossi , Bai Xue-Song
Published: August 2024

Low-temperature combustion (LTC) concepts, such as homogeneous charge compression ignition (HCCI) and partially premixed combustion (PPC), aim to reduce in-cylinder temperatures in internal combustion engines, thereby lowering emissions of nitrogen oxides (NOx) and soot. These LTC concepts are particularly attractive for decarbonizing conventional diesel engines using renewable fuels such as methanol. This paper uses numerical simulations and a finite-rate chemistry model to investigate the combustion and emission processes in LTC engines operating with pure methanol. The aim is to gain a deeper understanding of the physical and chemical processes in the engine and to identify optimal engine operation in terms of efficiency and emissions. The simulations replicated the experimentally observed trends for CO, unburned hydrocarbons (UHCs), and NOx emissions, the required intake temperature to achieve consistent combustion phasing at different injection timings, and the distinctively different combustion heat release processes at various injection timings. It was found that the HCCI mode of engine operation required a higher intake temperature than PPC operation due to methanol’s low ignition temperature in fuel-richer mixtures. In the HCCI mode, the engine exhibited ultra-low NOx emissions but higher emissions of UHC and CO, along with lower combustion efficiency compared to the PPC mode. This was attributed to poor combustion efficiency in the near-wall regions and engine crevices. Low emissions and high combustion efficiency are achievable in PPC modes with a start of injection around a crank angle of 30° before the top dead center. The fundamental mechanism behind the engine performance is analyzed.
A GIS-Based Approach for Urban Building Energy Modeling under Climate Change with High Spatial and Temporal Resolution
Authors: Chen Liang , Zheng Yuanfan , Yu Jia , Peng Yuanhang , Li Ruipeng , Han Shilingyun
Published: August 2024

The energy demand and associated greenhouse gas (GHG) emissions of buildings are significantly affected by the characteristics of the building and local climate conditions. While energy use datasets with high spatial and temporal resolution are highly needed in the context of climate change, energy use monitoring data are not available for most cities. This study introduces an approach combining building energy simulation, climate change modeling, and GIS spatial analysis techniques to develop an energy demand data inventory enabling assessment of the impacts of climate change on building energy consumption in Shanghai, China. Our results suggest that all types of buildings exhibit a net increase in their annual energy demand under the projected future (2050) climate conditions, with the highest increase in energy demand attributed to Heating, Ventilation, and Cooling (HVAC) systems. Variations in building energy demand are found across building types. Due to the large number of residential buildings, they are the main contributor to the increases in energy demand and associated CO2 emissions. The hourly residential building energy demand on a typical hot summer day (29 July) under the 2050 climate condition at 1 p.m. is found to increase by more than 40%, indicating a risk of energy supply shortage if no actions are taken. The spatial pattern of total annual building energy demand at the individual building level exhibited high spatial heterogeneity with some hotspots. This study provides an alternative method to develop a building energy demand inventory with high temporal resolution at the individual building scale for cities lacking energy use monitoring data, supporting the assessment of building energy and GHG emissions under both current and future climate scenarios at minimal cost.
Forest Products Trade and Sustainable Development in China and the USA: Do Bioenergy and Economic Policy Uncertainty Matter?
Authors: Mi Li , Huang Yongjun , Sohail Muhammad Tayyab , Ullah Sana
Published: August 2024

The United Nations Agenda 2030 for Sustainable Development has induced the empirics to find the factors that can contribute to sustainable development. However, limited empirical evidence has estimated the impact of forest trade, bioenergy, and economic policy uncertainty on sustainable development. This study fills the gap by analyzing the impact of forest trade, bioenergy, and economic policy uncertainty on sustainable development in China and the USA using the ARDL and QARDL approaches. The findings of the ARDL model suggest that forest trade helps boost both short- and long-run sustainable development in China and the USA, while bioenergy fosters sustainable development in the short and long run only in China and in the USA, bioenergy improves sustainable development only in the long run. In contrast, economic policy uncertainty hurts sustainable development in the short and long run in China, while in the USA, only the long-run negative association between the two variables is observed. Thus, policymakers in China and the USA need to focus on enhancing trade in forest products, fostering bioenergy generation, and reducing uncertainties in economic policy to promote sustainable development.
Multi-Scenario Ecological Network Conservation Planning Based on Climate and Land Changes: A Multi-Species Study in the Southeast Qinghai–Tibet Plateau
Authors: Li Chuang , Su Kai , Yu Sufang , Jiang Xuebing
Published: August 2024

The Qinghai–Tibet Plateau ecosystem is fragile, experiencing rapid changes in land cover driven by both climate change and human activities, leading to habitat fragmentation and loss and resulting in biodiversity decline. Habitat ecological networks (HA-ENs) are considered effective solutions for habitat connectivity and biodiversity conservation in response to these dual drivers. However, HA-EN studies typically rely on current or historical landscape data, which hinders the formulation of future conservation strategies. This study proposes three future scenarios—improvement, deterioration, and baseline scenarios—focused on the southeastern Qinghai–Tibet Plateau (SE-QPT). The habitats of 10 species across three classes are extracted, integrating land use and climate change data into habitat ecological network modeling to assess the long-term dynamics of HA-ENs in the SE-QPT. Finally, conservation management strategies are proposed based on regional heterogeneity. The results show the following: Climate change and human activities are expected to reduce the suitable habitat area for species, intensifying resource competition among multiple species. By 2030, under all scenarios, the forest structure will become more fragmented, and grassland degradation will be primarily concentrated in the southeastern and western parts of the study area. Compared to 1985 (71,891.3 km2), the habitat area by 2030 is projected to decrease by 12.9% (62,629.3 km2). The overlap rate of species habitats increases from 25.4% in 1985 to 30.9% by 2030. Compared to the HA-EN control in 1985, all scenarios show a decrease in connectivity and complexity, with only the improvement scenario showing some signs of recovery towards the control network, albeit limited. Finally, based on regional heterogeneity, a conservation management strategy of “two points, two cores, two corridors, and two regions” is proposed. This strategy aims to provide a framework for future conservation efforts in response to climate change and human activities.
Genetic Evidence of SpGH9A3 in Leaf Morphology Variation of Spathiphyllum ‘Mojo’
Authors: Yang Songlin , Hu Minghua , Wu Runxin , Hou Zhiwen , Zhang Huan , He Wenying , Gao Lili , Liao Feixiong
Published: August 2024

Leaves play a crucial role as ornamental organs in Spathiphyllum, exhibiting distinct differences across various Spathiphyllum varieties. Leaf development is intricately linked to processes of cell proliferation and expansion, with cell morphology often regulated by plant cell walls, primarily composed of cellulose. Alterations in cellulose content can impact cell morphology, subsequently influencing the overall shape of plant organs. Although cellulases have been shown to affect cellulose levels in plant cells, genetic evidence linking them to the regulation of leaf shape remains limited. This study took the leaves of Spathiphyllum ‘Mojo’ and its somatic variants as the research objects. We screened four cellulase gene family members from the transcriptome and then measured the leaf cellulose content, cellulase activity, and expression levels of cellulase-related genes. Correlation analysis pinpointed the gene SpGH9A3 as closely associated with leaf shape variations in the mutant. Green fluorescent fusion protein assays revealed that the SpGH9A3 protein was localized to the cell membrane. Notably, the expression of the SpGH9A3 gene in mutant leaves peaked during the early spread stage, resulting in smaller overall leaf size and reduced cellulose content upon overexpression in Arabidopsis.
Epidermal Differentiation Genes of the Common Wall Lizard Encode Proteins with Extremely Biased Amino Acid Contents
Authors: Holthaus Karin Brigit , Sachslehner Attila Placido , Steinbinder Julia , Eckhart Leopold
Published: August 2024

The epidermal differentiation complex (EDC) is a cluster of genes that code for protein components of cornified cells on the skin surface of amniotes. Squamates are the most species-rich clade of reptiles with skin adaptations to many different environments. As the genetic regulation of the skin epidermis and its evolution has been characterized for only a few species so far, we aimed to determine the organization of the EDC in a model species of squamates, the common wall lizard (Podarcis muralis). By comparative genomics, we identified EDC genes of the wall lizard and compared them with homologs in other amniotes. We found that the EDC of the wall lizard has undergone a major rearrangement leading to a unique order of three ancestral EDC segments. Several subfamilies of EDC genes, such as those encoding epidermal differentiation proteins containing PCCC motifs (EDPCCC) and loricrins, have expanded by gene duplications. Most of the EDPCCC proteins have cysteine contents higher than 50%, whereas glycine constitutes more than 50% of the amino acid residues of loricrin 1. The extremely biased amino acid compositions indicate unique structural properties of these EDC proteins. This study demonstrates that cornification proteins of the common wall lizard differ from homologous proteins of other reptiles, illustrating the evolutionary dynamics of diversifying evolution in squamates.
COVID-19 Vaccination Acceptance and Hesitancy in Healthcare Workers and the General Population: A Systematic Review and Policy Recommendations
Authors: Pereira da Silva Alessandra , Castaneda Luciana Ribeiro , Cavalcante de Oliveira Ana Paula , Fronteira Inês , Craveiro Isabel , Maia Leila Senna , Chança Raphael , Boniol Mathieu , Ferrinho Paulo , Dal Poz Mario Roberto
Published: August 2024

Introduction: The COVID-19 pandemic challenged the scientific community to find and develop a vaccine to fight the disease. However, problems with achieving high vaccine coverage have emerged, even among high-risk groups such as healthcare workers (HCWs). Objective: The objective of this study is to examine factors that influence HCW’s and the general population’s adherence to COVID-19 vaccination and national policies to vaccinate HCWs and other target groups. Methods: This study implemented a systematic review. The eligibility criterion for inclusion was being a HCW, target population for COVID-19 vaccination, or general population. Vaccination was the target intervention, and the COVID-19 pandemic was the context. We selected publications published between 1 January 2020 and 31 March 2022. Qualitative synthesis used a meta-aggregation approach. Results: Nineteen articles were included in the review, with study samples varying from 48 to 5708 participants. Most of the evidence came from cross-sectional and qualitative studies. The main findings were related to vaccine hesitancy rather than acceptance. Factors associated with HCW vaccine hesitancy included subjective feelings such as safety concerns, rapid vaccine development, and insufficient testing. Countries have adopted few public policies to address this problem, and the main concern is whether to enforce vaccination and the extent to which measures are legal. Conclusion: The quality of the evidence base remains weak. Skepticism, mistrust, and hesitancy toward vaccination are global issues that can jeopardize vaccination coverage.
Effects of Local Vasodilators and the Autonomic Nervous System on Microcirculation and Mitochondrial Function in Septic Rats
Authors: Marcus Carsten , Hansen Claudia , Schlimgen Charlotte , Eitner-Pchalek Jeanne , Schulz Jan , Hof Stefan , Kuebart Anne , Truse Richard , Vollmer Christian , Bauer Inge , Picker Olaf , Herminghaus Anna
Published: August 2024

Systemic vasodilating agents like nitroglycerin (NG) or iloprost (Ilo) show beneficial effects on intestinal microcirculation during sepsis, which could be attenuated by activation of the sympathetic nervous system or systemic side effects of vasodilating agents. This exploratory study aimed to investigate the effects of topically administered vasodilators and the parasympathetic drug carbachol on colonic microcirculatory oxygenation (µHbO2), blood flow (µFlow) and mitochondrial respiration. A total of 120 male Wistar rats were randomly assigned to twelve groups and underwent either colon ascendens stent peritonitis (CASP) or sham surgery. After 24 h, animals received the following therapeutic regimes: (1) balanced full electrolyte solution, (2) carbachol, (3) NG, (4) Ilo, (5) NG + carbachol, and (6) Ilo + carbachol. Mitochondrial respiration was measured in colon homogenates by respirometry. In sham animals, NG (−13.1%*) and Ilo (−10.5%*) led to a decrease in µHbO2. Additional application of carbachol abolished this effect (NG + carbachol: −4.0%, non-significant; Ilo + carbachol: −1.4%, non-significant). In sepsis, carbachol reduced µHbO2 when applied alone (−10.5%*) or in combination with NG (−17.6%*). Thus, the direction and degree of this effect depend on the initial pathophysiologic condition.
Genome-Wide Association Study of Cuticle and Lipid Droplet Properties of Cucumber (Cucumis sativus L.) Fruit
Authors: Rett-Cadman Stephanie , Weng Yiqun , Fei Zhangjun , Thompson Addie , Grumet Rebecca
Published: August 2024

The fruit surface is a critical first line of defense against environmental stress. Overlaying the fruit epidermis is the cuticle, comprising a matrix of cutin monomers and waxes that provides protection and mechanical support throughout development. The epidermal layer of the cucumber (Cucumis sativus L.) fruit also contains prominent lipid droplets, which have recently been recognized as dynamic organelles involved in lipid storage and metabolism, stress response, and the accumulation of specialized metabolites. Our objective was to genetically characterize natural variations for traits associated with the cuticle and lipid droplets in cucumber fruit. Phenotypic characterization and genome-wide association studies (GWAS) were performed using a resequenced cucumber core collection accounting for >96% of the allelic diversity present in the U.S. National Plant Germplasm System collection. The collection was grown in the field, and fruit were harvested at 16–20 days post-anthesis, an age when the cuticle thickness and the number and size of lipid droplets have stabilized. Fresh fruit tissue sections were prepared to measure cuticle thickness and lipid droplet size and number. The collection showed extensive variation for the measured traits. GWAS identified several QTLs corresponding with genes previously implicated in cuticle or lipid biosynthesis, including the transcription factor SHINE1/WIN1, as well as suggesting new candidate genes, including a potential lipid-transfer domain containing protein found in association with isolated lipid droplets.
Exploring the Effects and Potential Mechanisms of Hesperidin for the Treatment of CPT-11-Induced Diarrhea: Network Pharmacology, Molecular Docking, and Experimental Validation
Authors: Shu Xinyao , Xu Ruitong , Xiong Peiyu , Liu Junyu , Zhou Zubing , Shen Tao , Zhang Xiaobo
Published: August 2024

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K–Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.
Novel Magnesium- and Silver-Loaded Dressing Promotes Tissue Regeneration in Cutaneous Wounds
Authors: Pan Shin-Chen , Huang Ying-Jhen , Wang Chong-Han , Hsu Chao-Kai , Yeh Ming-Long
Published: August 2024

Wound healing is a dynamic process involving a complex interaction between many cells and mediators. Magnesium (Mg) is an essential element for cell stabilization. Mg was reported to stimulate the proliferation and migration of endothelial cells in angiogenesis in vitro. However, the function of Mg in wound healing is not known. We observed that the expression level of Mg in human wound tissue fluid was only 10% of that found in human blood serum. To confirm whether Mg is a suitable wound dressing material, we fabricated a Mg- or Mg-silver (Ag)-based polyethylene dressing to study its effect on wound healing. We observed that Mg and Ag were stably preserved in the constructed material and were able to be rapidly released in the moist environment. We also observed that the Mg-based dressing had good cellular compatibility without harmful extractables. Furthermore, Mg enhanced the antibacterial activity of Ag. In line with the observed increase in fibroblast migration in vitro, the Mg-Ag-based dressing improved acute and chronic wound repairs via an increase in neovascularization and basal cell proliferation. The present results show that a Mg-Ag-based coating can be manufactured as an optimal dressing for adjuvant wound therapy.
Effect of Levetiracetam on Oxidant–Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats
Authors: Ignacio-Mejía Iván , Contreras-García Itzel Jatziri , Pichardo-Macías Luz Adriana , García-Cruz Mercedes Edna , Ramírez Mendiola Blanca Alcira , Bandala Cindy , Medina-Campos Omar Noel , Pedraza-Chaverri José , Cárdenas-Rodríguez Noemí , Mendoza-Torreblanca Julieta Griselda
Published: August 2024

Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant–antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant–antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups’ oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.
Molecular Sex Differences and Clinical Gender Efficacy in Opioid Use Disorders: From Pain Management to Addiction
Authors: Concato Monica , Giacomello Emiliana , Al-Habash Ibrahim , Alempijevic Djordje , Kolev Yanko Georgiev , Buffon Maria , Radaelli Davide , D’Errico Stefano
Published: August 2024

Opioids have been utilized for both medical and recreational purposes since their discovery. Primarily recognized for their analgesic properties, they are also associated with the development of tolerance and dependence, contributing to a significant public health concern worldwide. Sex differences in opioid use disorder reveal that while men historically exhibit higher rates of abuse, women may develop dependence more quickly and are more susceptible to the addictive nature of opioids. This narrative review explores sex differences in opioid response in both clinical and experimental models, focusing on opioid receptor mechanisms, pain modulation, and hormonal influences. Additionally, it discusses the complexities of opioid addiction and withdrawal, highlighting sex-specific responses and the role of opioid replacement therapies. Diverse experimental outcomes, together with observational data, underscore the need for further research into sex-specific opioid biological mechanisms in a wider context, including demographic, cultural, and health-related factors. A comprehensive understanding of these complexities holds the potential to enhance personalized opioid therapies.
Gold Nanoparticles for Retinal Molecular Optical Imaging
Authors: Park Sumin , Nguyen Van Phuc , Wang Xueding , Paulus Yannis M.
Published: August 2024

The incorporation of gold nanoparticles (GNPs) into retinal imaging signifies a notable advancement in ophthalmology, offering improved accuracy in diagnosis and patient outcomes. This review explores the synthesis and unique properties of GNPs, highlighting their adjustable surface plasmon resonance, biocompatibility, and excellent optical absorption and scattering abilities. These features make GNPs advantageous contrast agents, enhancing the precision and quality of various imaging modalities, including photoacoustic imaging, optical coherence tomography, and fluorescence imaging. This paper analyzes the unique properties and corresponding mechanisms based on the morphological features of GNPs, highlighting the potential of GNPs in retinal disease diagnosis and management. Given the limitations currently encountered in clinical applications of GNPs, the approaches and strategies to overcome these limitations are also discussed. These findings suggest that the properties and efficacy of GNPs have innovative applications in retinal disease imaging.
Role of Nitric Oxide Synthases in Respiratory Health and Disease: Insights from Triple Nitric Oxide Synthases Knockout Mice
Authors: Ogoshi Takaaki , Yatera Kazuhiro , Mukae Hiroshi , Tsutsui Masato
Published: August 2024

The system of nitric oxide synthases (NOSs) is comprised of three isoforms: nNOS, iNOS, and eNOS. The roles of NOSs in respiratory diseases in vivo have been studied by using inhibitors of NOSs and NOS-knockout mice. Their exact roles remain uncertain, however, because of the non-specificity of inhibitors of NOSs and compensatory up-regulation of other NOSs in NOS-KO mice. We addressed this point in our triple-n/i/eNOSs-KO mice. Triple-n/i/eNOSs-KO mice spontaneously developed pulmonary emphysema and displayed exacerbation of bleomycin-induced pulmonary fibrosis as compared with wild-type (WT) mice. Triple-n/i/eNOSs-KO mice exhibited worsening of hypoxic pulmonary hypertension (PH), which was reversed by treatment with sodium nitrate, and WT mice that underwent triple-n/i/eNOSs-KO bone marrow transplantation (BMT) also showed aggravation of hypoxic PH compared with those that underwent WT BMT. Conversely, ovalbumin-evoked asthma was milder in triple-n/i/eNOSs-KO than WT mice. These results suggest that the roles of NOSs are different in different pathologic states, even in the same respiratory diseases, indicating the diversity of the roles of NOSs. In this review, we describe these previous studies and discuss the roles of NOSs in respiratory health and disease. We also explain the current state of development of inorganic nitrate as a new drug for respiratory diseases.
Inflammation and Fibrosis in Progeria: Organ-Specific Responses in an HGPS Mouse Model
Authors: Krüger Peter , Schroll Moritz , Fenzl Felix , Lederer Eva-Maria , Hartinger Ramona , Arnold Rouven , Cagla Togan Deniz , Guo Runjia , Liu Shiyu , Petry Andreas , Görlach Agnes , Djabali Karima
Published: August 2024

Hutchinson–Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder that causes accelerated aging, due to a pathogenic variant in the LMNA gene. This pathogenic results in the production of progerin, a defective protein that disrupts the nuclear lamina’s structure. In our study, we conducted a histopathological analysis of various organs in the LmnaG609G/G609G mouse model, which is commonly used to study HGPS. The objective of this study was to show that progerin accumulation drives systemic but organ-specific tissue damage and accelerated aging phenotypes. Our findings show significant fibrosis, inflammation, and dysfunction in multiple organ systems, including the skin, cardiovascular system, muscles, lungs, liver, kidneys, spleen, thymus, and heart. Specifically, we observed severe vascular fibrosis, reduced muscle regeneration, lung tissue remodeling, depletion of fat in the liver, and disruptions in immune structures. These results underscore the systemic nature of the disease and suggest that chronic inflammation and fibrosis play crucial roles in the accelerated aging seen in HGPS. Additionally, our study highlights that each organ responds differently to the toxic effects of progerin, indicating that there are distinct mechanisms of tissue-specific damage.
RT-qPCR Testing and Performance Metrics in the COVID-19 Era
Authors: Bustin Stephen A.
Published: August 2024

The COVID-19 pandemic highlighted the crucial role of diagnostic testing in managing infectious diseases, particularly through the use of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tests. RT-qPCR has been pivotal in detecting and quantifying viral RNA, enabling the identification and management of SARS-CoV-2 infections. However, despite its widespread use, there remains a notable gap in understanding fundamental diagnostic metrics such as sensitivity and specificity among many scientists and healthcare practitioners. This gap is not merely academic; it has profound implications for interpreting test results, making public health decisions, and affecting patient outcomes. This review aims to clarify the distinctions between laboratory- and field-based metrics in the context of RT-qPCR testing for SARS-CoV-2 and summarise the global efforts that led to the development and optimisation of these tests during the pandemic. It is intended to enhance the understanding of these fundamental concepts among scientists and healthcare professionals who may not be familiar with the nuances of diagnostic test evaluation. Such knowledge is crucial for accurately interpreting test results, making informed public health decisions, and ultimately managing infectious disease outbreaks more effectively.
One-Shot Learning from Prototype Stock Keeping Unit Images
Authors: Kowalczyk Aleksandra , Sarwas Grzegorz
Published: August 2024

This paper highlights the importance of one-shot learning from prototype Stock Keeping Unit (SKU) images for efficient product recognition in retail and inventory management. Traditional methods require large supervised datasets to train deep neural networks, which can be costly and impractical. One-shot learning techniques mitigate this issue by enabling classification from a single prototype image per product class, thus reducing data annotation efforts. We introduce the Variational Prototyping Encoder (VPE), a novel deep neural network for one-shot classification. Utilizing a support set of prototype SKU images, VPE learns to classify query images by capturing image similarity and prototypical concepts. Unlike metric learning-based approaches, VPE pre-learns image translation from real-world object images to prototype images as a meta-task, facilitating efficient one-shot classification with minimal supervision. Our research demonstrates that VPE effectively reduces the need for extensive datasets by utilizing a single image per class while accurately classifying query images into their respective categories, thus providing a practical solution for product classification tasks.