bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovations in Antibody-Drug Conjugate (ADC) in the Treatment of Lymphoma
Authors: Al Sbihi Ali , Alasfour Maryam , Pongas Georgios
Published: February 2024

Chemoimmunotherapy and cellular therapy are the mainstay of the treatment of relapsed/refractory (R/R) lymphomas. Development of resistance and commonly encountered toxicities of these treatments limit their role in achieving desired response rates and durable remissions. The Antibody–Drug Conjugate (ADC) is a novel class of targeted therapy that has demonstrated significant efficacy in treating various cancers, including lymphomas. To date, three ADC agents have been approved for different lymphomas, marking a significant advancement in the field. In this article, we aim to review the concept of ADCs and their application in lymphoma treatment, provide an analysis of currently approved agents, and discuss the ongoing advancements of ADC development.
Prognostic Value of Inflammatory Burden Index in Advanced Gastric Cancer Patients Undergoing Multimodal Treatment
Authors: Pelc Zuzanna , Sędłak Katarzyna , Mlak Radosław , Leśniewska Magdalena , Mielniczek Katarzyna , Rola Piotr , Januszewski Jacek , Zhaldak Olena , Rekowska Anna , Gęca Katarzyna , Skórzewska Magdalena , Polkowski Wojciech P. , Pawlik Timothy M. , Rawicz-Pruszyński Karol
Published: February 2024

Since increasing evidence underlines the prominent role of systemic inflammation in carcinogenesis, the inflammation burden index (IBI) has emerged as a promising biomarker to estimate survival outcomes among cancer patients. The IBI has only been validated in Eastern gastric cancer (GC) patients; therefore, the aim of this study was to evaluate the IBI as a prognostic biomarker in Central European GC patients undergoing multimodal treatment. Ninety-three patients with histologically confirmed GC who underwent multimodal treatment between 2013 and 2021 were included. Patient recruitment started with the standardization of neoadjuvant chemotherapy (NAC). Blood samples were obtained one day prior to surgical treatment. The textbook outcome (TO) served as the measure of surgical quality, and tumor responses to NAC were evaluated according to Becker’s system tumor regression grade (TRG). A high IBI was associated with an increased risk of postoperative complications (OR 2.95, 95% CI 1.13–7.72). In multivariate analysis, a high IBI (HR = 2.56, 95% CI 1.28–5.13) and a high neutrophil-to-lymphocyte ratio (NLR, HR = 2.55, 95% CI 1.32–4.94) were associated with an increased risk of death, while NAC administration (HR = 0.40, 95% CI 0.18–0.90) and TO achievement (HR = 0.42, 95% CI 0.22–0.81) were associated with a lower risk of death. The IBI was associated with postoperative complications and mortality among GC patients undergoing multimodal treatment.
Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model
Authors: Araya Mariela , Sepúlveda Francisca , Villegas Jaime , Alarcón Luis , Burzio Luis O. , Burzio Verónica A. , Borgna Vincenzo
Published: February 2024

Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.
Identifying PLAUR as a Pivotal Gene of Tumor Microenvironment and Regulating Mesenchymal Phenotype of Glioblastoma
Authors: Fu Zaixiang , Chen Zihang , Ye Jingya , Ji Jianxiong , Ni Weifang , Lin Weibo , Lin Haopu , Lu Liquan , Zhu Ganggui , Xie Qin , Yan Feng , Chen Gao , Liu Fuyi
Published: February 2024

The mesenchymal (MES) phenotype of glioblastoma (GBM) is the most aggressive and therapy-resistant subtype of GBM. The MES phenotype transition during tumor progression results from both tumor-intrinsic genetic alterations and tumor-extrinsic microenvironmental factors. In this study, we sought to identify genes that can modulate the MES phenotype via both mechanisms. By integrating weighted gene co-expression network analysis (WGCNA) and the differential expression analysis of hypoxia-immunosuppression-related genes, we identified the plasminogen activator, urokinase receptor (PLAUR) as the hub gene. Functional enrichment analysis and GSVA analysis demonstrated that PLAUR was associated with the MES phenotype of glioma and the hypoxia-immunosuppression-related microenvironmental components. Single-cell sequencing analysis revealed that PLAUR mediated the ligand–receptor interaction between tumor-associated macrophages (TAMs) and glioma cells. Functional experiments in vitro with cell lines or primary glioma cells and xenograft models using BALB/c nude mice confirmed the role of PLAUR in promoting the MES phenotype of GBM. Our findings indicate that PLAUR regulates both glioma cells and tumor cell-extrinsic factors that favor the MES phenotype and suggest that PLAUR might be a potential target for GBM therapy.
Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors
Authors: Shimizu Takuto , Miyake Makito , Nishimura Nobutaka , Yoshida Takanori , Itami Yoshitaka , Tachibana Akira , Omori Chihiro , Oda Yuki , Kohashi Mikiko , Tomizawa Mitsuru , Onishi Kenta , Hori Shunta , Morizawa Yosuke , Dotoh Daisuke , Nakai Yasushi , Torimoto Kazumasa , Tanaka Nobumichi , Fujimoto Kiyohide
Published: February 2024

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35–0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.
Modeling the Effect of Spatial Structure on Solid Tumor Evolution and Circulating Tumor DNA Composition
Authors: Rachman Thomas , Bartlett David , LaFramboise William , Wagner Patrick , Schwartz Russell , Carja Oana
Published: February 2024

Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones are over-represented in ctDNA, clonal diversity can appear elevated in the blood, and spatial bias in shedding can inflate subclonal variant allele frequencies (VAFs). Additionally, we find that tumors that are mostly quiescent can display similar biases but are far less detectable, and the extent of perceptible spatial bias strongly depends on sequence detection limits. Overall, we show that spatially structured shedding might cause liquid biopsies to provide highly biased profiles of tumor state. While this may enable more sensitive detection of expanding clones, it could also increase the risk of targeting a subclonal variant for treatment. Our results indicate that the effects and clinical consequences of spatially variable cell death on ctDNA composition present an important area for future work.
Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy
Authors: Nojima Hiroyuki , Shimizu Hiroaki , Murakami Takashi , Shuto Kiyohiko , Koda Keiji
Published: February 2024

The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.
Identification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD
Authors: Kanai Ryan , Norton Emily , Stern Patrick , Hynes Richard O. , Lamar John M.
Published: February 2024

Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early-phase clinical trials in cancer patients. However, a lack of a reliable way to identify tumors with YAP/TAZ-TEAD activation for most cancer types makes it difficult to determine which tumors will be susceptible to TEAD inhibitors. Here, we used a combination of RNA-seq and bioinformatic analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent in several melanoma cell lines, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be effective tools to predict tumor cell dependence upon YAP/TAZ-TEAD, and thus potentially provide a means to identify patients likely to benefit from TEAD inhibitors.
Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma
Authors: Codenotti Silvia , Sandrini Leonardo , Mandracchia Delia , Lorenzi Luisa , Corsetti Giovanni , Poli Maura , Asperti Michela , Salvi Valentina , Bosisio Daniela , Monti Eugenio , Mitola Stefania , Triggiani Luca , Guescini Michele , Pozzo Enrico , Sampaolesi Maurilio , Gastaldello Stefano , Cassandri Matteo , Marampon Francesco , Fanzani Alessandro
Published: February 2024

Identifying the molecular mechanisms underlying radioresistance is a priority for the treatment of RMS, a myogenic tumor accounting for approximately 50% of all pediatric soft tissue sarcomas. We found that irradiation (IR) transiently increased phosphorylation of Akt1, Src, and Cav1 in human RD and RH30 lines. Synthetic inhibition of Akt1 and Src phosphorylation increased ROS levels in all RMS lines, promoting cellular radiosensitization. Accordingly, the elevated activation of the Akt1/Src/Cav1 pathway, as detected in two RD lines characterized by overexpression of a myristoylated Akt1 form (myrAkt1) or Cav1 (RDCav1), was correlated with reduced levels of ROS, higher expression of catalase, and increased radioresistance. We found that treatment with cholesterol-lowering drugs such as lovastatin and simvastatin promoted cell apoptosis in all RMS lines by reducing Akt1 and Cav1 levels and increasing intracellular ROS levels. Combining statins with IR significantly increased DNA damage and cell apoptosis as assessed by γ histone 2AX (γH2AX) staining and FACS analysis. Furthermore, in combination with the chemotherapeutic agent actinomycin D, statins were effective in reducing cell survival through increased apoptosis. Taken together, our findings suggest that the molecularly linked signature formed by Akt1, Src, Cav1, and catalase may represent a prognostic determinant for identifying subgroups of RMS patients with higher probability of recurrence after radiotherapy. Furthermore, statin-induced oxidative stress could represent a treatment option to improve the success of radiotherapy.
Sex-Specific Differences in Nutrient Intake in Late Preterm Infants
Authors: Alur Pradeep , Ramarao Sumana , Hitt Addie , Vig Simmy , Alur Radha , Hussain Naveed
Published: February 2024

Challenging the assumption of uniform nutritional needs in preterm feeding, this study identifies crucial sex-specific disparities in formula milk intake and growth among late preterm infants. Premature infants have difficulty regulating their oral intake during feeds, which is why clinicians prescribe feeding volume, calories, and protein via the nasogastric route. However, premature male and female infants have different body compositions at birth, and, subsequently, there is no evidence to suggest that male and female preterm infants differ in their nutritional consumption once they begin feeding ad libitum. This study investigates whether there are any differences in the volume and nutrient intake between the sexes when fed formula ad libitum. Methods: The study involved a retrospective analysis of preterm infants admitted to the NICU and evaluated between 34 0/7 and 36 6/7 weeks of corrected gestation. Late preterm infants appropriate for gestational age who were spontaneously fed formula milk ad-lib and free of any respiratory support for at least two days were included. The study excluded infants with short gut syndrome, severe chromosomal anomalies, or congenital heart conditions. We included 85 male and 85 female infants in this study. The data collected included sex, gestational age, birth weight, anthropometric data at birth, maternal data, nutritional intake, and neonatal morbidity. Results: This study found that female infants consumed more volume, protein, and calories than male infants. The mean formula intake in female and male infants was 145.5 ± 20.8 mL/kg/d and 135.3 ± 19.3 mL/kg/d, respectively, with p = 0.002. However, ad-lib feeding duration was not different between the sexes. Growth velocity was also higher in female infants. Conclusions: This study is the first to demonstrate differences in formula milk intake among late preterm infants fed ad libitum. Additional research is needed to confirm our findings and understand sex-specific differences in neonatal nutrition in extremely early preterm infants.
Modified Graphene Micropillar Array Superhydrophobic Coating with Strong Anti-Icing Properties and Corrosion Resistance
Authors: Zhang Wanyu , Liu Fuchun , Li Yushan , Chen Tao , Nwokolo Izuchukwu Kenneth , Ahmed Sharjeel , Han En-Hou
Published: February 2024

Ice accumulation on outdoor surfaces tends to cause a series of serious accidents in extreme climates. In recent years, superhydrophobic coatings have garnered significant interest in the passive anti-icing field owing to their exceptional ability to repel water. However, these superhydrophobic coatings displayed inadequate anti-icing properties in conditions of low temperature and high humidity, as well as poor corrosion resistance after prolonged immersion. Herein, we prepared a series of modified graphene micropillar array superhydrophobic coatings that have various micropillar widths based on simple physical embossing and spraying techniques. These coatings combined the graphene nanosheets modified by perfluorodecyl triethoxysilane (AC-FAS) and the fluorocarbon varnish coating with a micropillar array structure to gain great superhydrophobicity and anti-icing properties. Among these, the average freezing delay time of the Q200G coating increased over 500 times relative to the unmodified Al surface (about 10 s), and its average deicing shear force was as low as 0.1 N. Meanwhile, the corrosion resistance increased steadily as the micropillar width decreased, based on the electrochemical impedance spectroscopy test results. More importantly, such facile fabrication methods and multi-functionality make superhydrophobic coatings hold great application prospects.
Dynamic Numerical Simulation of Curved Surface Coating Trajectory Based on STL Slicing Algorithm
Authors: Xu Jiangmin , Cheng Haolan , Liu Jinhao , Jing Xuwen , Lin Haodong , Ji Jianbo
Published: February 2024

The thickness of the coating on the surface of a workpiece is an important factor in determining the quality of spraying. However, it is challenging to estimate the distribution of film thickness accurately before the actual spraying process. This lack of estimation hinders the optimization of spraying process parameters and trajectory. To overcome this, a numerical simulation of surface spray coating thickness was conducted to provide guidance for the actual coating process. The research consists of three main parts. Firstly, the spray trajectory of the spray gun is determined using the proposed Stereo Lithography (STL) model slicing algorithm. Secondly, a two-phase flow spray model and collision adhesion model are established to construct the spray film model. The surface mesh is determined, and the spraying process parameters are set. Finally, numerical simulation is conducted to analyze the dynamic spraying trajectory and the distribution of coating thickness. The results show that the coating thickness distribution on an arc surface is thicker in the middle and thinner on the edges. The distribution is symmetric with respect to both the transverse and longitudinal directions of the arc surface. The coating thickness distribution at both ends is not as uniform as in the middle section. The concave part of the free surface has the largest coating thickness, while the coating thickness distribution on the convex part is not as uniform as on the relatively flat part. This method of simulating the coating thickness distribution on complex surfaces provides a solid foundation for further optimization of spraying process parameters and trajectory, ultimately improving the qualification rate of workpiece spraying processing.
European Funding for Sustainable Transport Systems—Influencing Factor of Regional Economic Development in Romania
Authors: Bocaneala Ana Maria , Manole Daniel Sorin , Gherasim Elvira Alexandra , Motorga Bianca , Iliescu Livia Cristina
Published: February 2024

Sustainable development is a core concept in regional development. Sustainability is characterized by supporting the building of resilient infrastructure and promoting the sustainable industry. In this context, sustainable transport is particularly important as it represents an opportunity for regional development. This research aims to quantify the impact of investments through structural instruments, specifically EU funds, on promoting a sustainable transport system and eliminating barriers from large-scale transport networks. This study focuses on the impact of these investments on regional economic development in Romania. The analysis used data from all eight development regions of the Romanian economy between 2014 and 2020. Panel data regression models, including the generalized difference method of moments (Dif-GMM) and the system GMM method (Sys GMM), were employed. This study confirms the idea that European structural and investment funds (ESIFs) play a positive role in promoting sustainable transport for regional economic development. Additionally, the quality of regional governance is identified as a key factor in economic development. This study, therefore, reveals a convergence effect between regions. Regions with a lower initial GDP per capita develop quicker compared to regions with a higher initial GDP per capita, indicating a “catch-up” effect. From a policy perspective, these issues can guide decision making and resource allocation.
Analysis of Vegetation NDVI Changes and Driving Factors in the Karst Concentration Distribution Area of Asia
Authors: Yang Shunfu , Zhao Yuluan , Yang Die , Lan Anjun
Published: February 2024

Due to the special nature of karst landforms, quantification of their vegetation dynamics and their underlying driving factors remains a formidable challenge. Based on the NDVI dataset, this study uses principal component analysis to extract comprehensive factors and utilizes an optimized parameter-based geographical detector and geographically weighted regression models to assess the explanatory capacity of comprehensive factors concerning the spatial differentiation of vegetation change. The results of this study revealed the following: (1) In terms of temporal and spatial vegetation changes, the Asian karst concentrated distribution area (AKC) displayed overall stability and an increasing trend between 2000 and 2020. Notably, the northern (Southwest China) karst region experienced the most substantial vegetation increase, with increased areas exceeding 70%, primarily concentrated in the provinces of Guizhou and Guangxi. In contrast, the southern (Indochina Peninsula) karst region, particularly in Cambodia, Laos, and Vietnam (CLV), exhibited a significant decreasing trend, with decreased areas exceeding 30%. (2) By analyzing the driving factors affecting vegetation change, vegetation changes exhibited distinct spatial differentiations, along with positive and negative effects. Human factors, including human activity intensity, urban economic development, and agricultural economic development (explanatory power and local R2 were both greater than 0.2), exerted a more significant impact on vegetation change in the AKC than natural factors such as thermal conditions, water conditions, and soil conditions. This impact was positive in Southwest China but inhibited in the Indochina Peninsula, particularly within the CLV karst area. Notably, the interaction between natural and human factors greatly enhanced their impacts on vegetation changes. These results provide valuable insights into vegetation changes and their driving mechanisms, which are crucial for preserving the stability of delicate karst ecosystems and facilitating vegetation recovery.
Correction: Wang et al. Estimation of Aboveground Biomass for Different Forest Types Using Data from Sentinel-1, Sentinel-2, ALOS PALSAR-2, and GEDI. Forests 2024, 15, 215
Authors: Wang Chu , Zhang Wangfei , Ji Yongjie , Marino Armando , Li Chunmei , Wang Lu , Zhao Han , Wang Mengjin
Published: February 2024

In the original publication [...]
Do Mature Quercus aliena Primarily Use Deep Soil Water?
Authors: Ren Ranran , Zhang Beibei , Xu Qing , Gao Deqiang , Xu Wenbin , Zuo Haijun , Zhang Ying , Diao Ke
Published: February 2024

Seasonal drought events induced by climate change have exacerbated the water deficit in trees. This is particularly pronounced in mature trees with considerable heights and extensive branches, where the long water transport distance leads to a reduction in hydraulic transportation efficiency. Therefore, investigating the water uptake patterns of mature trees is essential to enhance their growth and resilience to climate change. However, previous studies have predominantly focused on trees aged 10–60 years, with limited research on the water uptake patterns of trees over 60 years old. In this study, we employed hydrogen and oxygen stable isotopes coupled with the MixSIAR model to determine the water uptake patterns of mature Quercus aliena var. acuteserrata (40–60 years, 60–90 years, 120–150 years, >150 years) during the growing seasons of 2021 and 2022 in Baotianman Nature Reserve, Henan Province, China. Additionally, we utilized a random forest model to quantify the relative contributions of vegetation (fine root biomass) and soil properties (soil moisture, bulk density, total porosity, field capacity, and soil texture) to the water uptake patterns of Q. aliena. Our findings demonstrate that most mature Q. aliena predominantly extracted deep soil water (60–100 cm) in the early growing season, but shifted towards utilizing shallow soil water (0–40 cm) in the late growing season. The water uptake pattern of mature Q. aliena was primarily regulated by soil moisture. These results reveal that mature Q. aliena trees exhibit a flexible water use strategy, enabling them to cope with seasonal drought by altering the soil depth from which they extract water. In the future, in the process of the cultivation and conservation of mature oak trees, surface soil irrigation can be increased to prevent tree mortality resulting from water deficit during drought conditions.
Energy-Efficient De-Duplication Mechanism for Healthcare Data Aggregation in IoT
Authors: Khan Muhammad Nafees Ulfat , Cao Weiping , Tang Zhiling , Ullah Ata , Pan Wanghua
Published: February 2024

The rapid development of the Internet of Things (IoT) has opened the way for transformative advances in numerous fields, including healthcare. IoT-based healthcare systems provide unprecedented opportunities to gather patients’ real-time data and make appropriate decisions at the right time. Yet, the deployed sensors generate normal readings most of the time, which are transmitted to Cluster Heads (CHs). Handling these voluminous duplicated data is quite challenging. The existing techniques have high energy consumption, storage costs, and communication costs. To overcome these problems, in this paper, an innovative Energy-Efficient Fuzzy Data Aggregation System (EE-FDAS) has been presented. In it, at the first level, it is checked that sensors either generate normal or critical readings. In the first case, readings are converted to Boolean digit 0. This reduced data size takes only 1 digit which considerably reduces energy consumption. In the second scenario, sensors generating irregular readings are transmitted in their original 16 or 32-bit form. Then, data are aggregated and transmitted to respective CHs. Afterwards, these data are further transmitted to Fog servers, from where doctors have access. Lastly, for later usage, data are stored in the cloud server. For checking the proficiency of the proposed EE-FDAS scheme, extensive simulations are performed using NS-2.35. The results showed that EE-FDAS has performed well in terms of aggregation factor, energy consumption, packet drop rate, communication, and storage cost.
Investigating the Wound-Healing Potential of a Nanoemulsion–Gel Formulation of Pituranthos tortuosus Essential Oil
Authors: Bahloul Badr , Ben Bnina Enis , Hamdi Assia , Castillo Henríquez Luis , Baccar Dhaou , Kalboussi Nesrine , Abbassi Aïmen , Mignet Nathalie , Flamini Guido , Vega-Baudrit José Roberto
Published: February 2024

This study explores a nanoemulsion (NE)-based gel incorporating Tunisian Pituranthos tortuosus essential oil, with a focus on its wound-healing potential. The essential oil, extracted via hydrodistillation, underwent GC-MS analysis for compositional verification. The physicochemical characterization included dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential measurement, pH, and viscosity. The gelification of the NE facilitated topical application. The results revealed an average extraction yield of 0.45% and identified 38 compounds in the essential oil. The NE exhibited a particle size of 27 ± 0.4 nm, a polydispersity index (PDI) of 0.3, and a zeta potential of −22.8 ± 1.4 mV. The stability of the gelified preparation was confirmed through thermodynamic stability studies, TEM observations, and zeta and size results. In vivo experiments confirmed significant wound-healing effects, highlighting the promising role of the NE-based gel in healthcare advancements. This research underscores the potential of novel phyto-based delivery systems in wound care.
Disulfide Cross-Linked Polymeric Redox-Responsive Nanocarrier Based on Heparin, Chitosan and Lipoic Acid Improved Drug Accumulation, Increased Cytotoxicity and Selectivity to Leukemia Cells by Tumor Targeting via “Aikido” Principle
Authors: Zlotnikov Igor D. , Ezhov Alexander A. , Dobryakova Natalia V. , Kudryashova Elena V.
Published: February 2024

We have developed a micellar formulation of anticancer drugs based on chitosan and heparin grafted with lipoic and oleic acids that can release the cytotoxic cargo (doxorubicin) in response to external stimuli, such as increased glutathione concentration—a hallmark of cancer. Natural polysaccharides (heparin and chitosan) provide the pH sensitivity of the nanocarrier: the release of doxorubicin (Dox) is enhanced in a slightly acidic environment (tumor microenvironment). Fatty acid residues are necessary for the formation of nanoparticles (micelles) and solubilization of cytostatics in a hydrophobic core. Lipoic acid residues provide the formation of a labile S-S cross-linking between polymer chains (the first variant) or covalently attached doxorubicin molecules through glutathione-sensitive S-S bridges (the second variant)—both determine Redox sensitivity of the anticancer drugs carriers stable in blood circulation and disintegrate after intracellular uptake in the tumor cells. The release of doxorubicin from micelles occurs slowly (20%/6 h) in an environment with a pH of 7.4 and the absence of glutathione, while in a slightly acidic environment and in the presence of 10 mM glutathione, the rate increases up to 6 times, with an increase in the effective concentration up to 5 times after 7 h. The permeability of doxorubicin in micellar formulations (covalent S-S cross-linked and not) into Raji, K562, and A875 cancer cells was studied using FTIR, fluorescence spectroscopy and confocal laser scanning microscopy (CLSM). We have shown dramatically improved accumulation, decreased efflux, and increased cytotoxicity compared to doxorubicin control with three tumor cell lines: Raji, K562, and A875. At the same time, cytotoxicity and permeability for non-tumor cells (HEK293T) are significantly lower, increasing the selectivity index against tumor cells by several times.
FecB Was Associated with Litter Size and Follows Mendel’s Laws of Inheritance When It Transited to Next Generation in Suhu Meat Sheep Breeding Population
Authors: Su Pengwei , Gu Yifei , Wang Shanhe , Cao Xiukai , Lv Xiaoyang , Getachew Tesfaye , Li Yutao , Song Zhenghai , Yuan Zehu , Sun Wei
Published: February 2024

In order to investigate the effect of FecB on litter size and growth and development traits of Suhu meat sheep and the inheritance patterns of FecB between parents and offspring in the population. In this experiment, 2241 sheep from the Suhu meat sheep population were tested for FecB using capillary electrophoresis. We combined the lambing records of 473 ewes, the growth trait records of 881 sheep at both the birth and weaning (2-month-old) stages, and the complete genealogical records of 643 lambs to analysis the distribution of FecB in the Suhu meat sheep breeding population, its effect on litter size of ewes, growth and development of lambs, and the inheritance patterns of FecB. The results showed that there were three genotypes of FecB in the Suhu meat sheep population, namely the AA genotype, AG genotype, and GG genotype. FecB in this population has a moderate polymorphism (0.25 < PIC < 0.5), and deviates from Hardy–Weinberg disequilibrium (p < 0.05). The litter size of GG genotype ewes was significantly higher than that with the AG and AA genotypes (p < 0.01). A Chi-square test showed that the inheritance patterns of FecB follows Mendel’s Laws of Inheritance (p > 0.05). An association analysis of different genotypes of FecB with body weight and body size of Suhu meat sheep at birth and weaning revealed that FecB adversely affects the early growth and development of Suhu meat sheep. In summary, FecB can improve the litter size of ewes but it has negative effects on the early growth and survival rate of lambs in sheep. Therefore, FecB test results and feeding management measures should be comprehensively applied to improve the reproductive performance of ewes, the survival rate and production performance of lambs in sheep production, and thus improve the economic benefits of sheep farms.
Antibiotic-Free Gene Vectors: A 25-Year Journey to Clinical Trials
Authors: Marie Corinne , Scherman Daniel
Published: February 2024

Until very recently, the major use, for gene therapy, specifically of linear or circular DNA, such as plasmids, was as ancillary products for viral vectors’ production or as a genetic template for mRNA production. Thanks to targeted and more efficient physical or chemical delivery techniques and to the refinement of their structure, non-viral plasmid DNA are now under intensive consideration as pharmaceutical drugs. Plasmids traditionally carry an antibiotic resistance gene for providing the selection pressure necessary for maintenance in a bacterial host. Nearly a dozen different antibiotic-free gene vectors have now been developed and are currently assessed in preclinical assays and phase I/II clinical trials. Their reduced size leads to increased transfection efficiency and prolonged transgene expression. In addition, associating non-viral gene vectors and DNA transposons, which mediate transgene integration into the host genome, circumvents plasmid dilution in dividing eukaryotic cells which generate a loss of the therapeutic gene. Combining these novel molecular tools allowed a significantly higher yield of genetically engineered T and Natural Killer cells for adoptive immunotherapies due to a reduced cytotoxicity and increased transposition rate. This review describes the main progresses accomplished for safer, more efficient and cost-effective gene and cell therapies using non-viral approaches and antibiotic-free gene vectors.
Modeling within and between Sub-Genomes Epistasis of Synthetic Hexaploid Wheat for Genome-Enabled Prediction of Diseases
Authors: Cuevas Jaime , González-Diéguez David , Dreisigacker Susanne , Martini Johannes W. R. , Crespo-Herrera Leo , Lozano-Ramirez Nerida , Singh Pawan K. , He Xinyao , Huerta Julio , Crossa Jose
Published: February 2024

Common wheat (Triticum aestivum) is a hexaploid crop comprising three diploid sub-genomes labeled A, B, and D. The objective of this study is to investigate whether there is a discernible influence pattern from the D sub-genome with epistasis in genomic models for wheat diseases. Four genomic statistical models were employed; two models considered the linear genomic relationship of the lines. The first model (G) utilized all molecular markers, while the second model (ABD) utilized three matrices representing the A, B, and D sub-genomes. The remaining two models incorporated epistasis, one (GI) using all markers and the other (ABDI) considering markers in sub-genomes A, B, and D, including inter- and intra-sub-genome interactions. The data utilized pertained to three diseases: tan spot (TS), septoria nodorum blotch (SNB), and spot blotch (SB), for synthetic hexaploid wheat (SHW) lines. The results (variance components) indicate that epistasis makes a substantial contribution to explaining genomic variation, accounting for approximately 50% in SNB and SB and only 29% for TS. In this contribution of epistasis, the influence of intra- and inter-sub-genome interactions of the D sub-genome is crucial, being close to 50% in TS and higher in SNB (60%) and SB (60%). This increase in explaining genomic variation is reflected in an enhancement of predictive ability from the G model (additive) to the ABDI model (additive and epistasis) by 9%, 5%, and 1% for SNB, SB, and TS, respectively. These results, in line with other studies, underscore the significance of the D sub-genome in disease traits and suggest a potential application to be explored in the future regarding the selection of parental crosses based on sub-genomes.
Discovery, Pathogenesis, and Complete Genome Characterization of Lates calcarifer Herpesvirus
Authors: Simmelink Bartjan , Coolen Jordy P. M. , Vogels Wannes , Deijs Martin , van der Last-Kempkes Jessica L. M. , Ng Kah Sing , Chang Siow Foong , Gevers Koen , Harkema Liesbeth , van der Hoek Lia , de Groof Ad
Published: February 2024

In 2015 and 2016, two Barramundi (Lates calcarifer) farms in Singapore reported a disease outbreak characterized by lethargic behavior, pronounced inappetence, generalized skin lesions, erosions of the fins and tail, and ultimately high mortality in their fish. Next-generation sequencing and PCR confirmed presence of a novel virus belonging to the Alloherpesviridae family, Lates calcarifer herpesvirus (LCHV), which was subsequently isolated and cultured. We characterize, for the first time, the complete genome of two cultured LCHV isolates. The genome contains a long unique region of approximately 105,000 bp flanked by terminal repeats of approximately 24,800 bp, of which the first 8.2 kb do not show any similarity to described genomes in the Alloherpesviridae family. The two cultured isolates share 89% nucleotide identity, and their closest relatives are the viruses belonging to the genus Ictalurivirus. Experimental infections using one of the cultured LCHV isolates resulted in identical clinical signs as originally described in the index farm, both in intraperitoneal-injection infected fish and cohabitant fish, with mortality in both groups. Histopathological analysis showed pronounced abnormalities in the gills. Virus culture and PCR analysis confirmed the replication of LCHV in the infected fish, and thus Koch’s postulates were fulfilled.
Effects of Lifestyle Interventions on the Improvement of Chronic Non-Specific Low Back Pain: A Systematic Review and Network Meta-Analysis
Authors: Herrero Pablo , Val Paula , Lapuente-Hernández Diego , Cuenca-Zaldívar Juan Nicolás , Calvo Sandra , Gómez-Trullén Eva María
Published: February 2024

Chronic non-specific low back pain (CNSLBP) is a highly prevalent musculoskeletal condition that has a great socioeconomic impact on health systems. Instead of focusing on mechanical causes and direct workload in the development of CNSLBP, genetics, psychosocial environment, lifestyle and quality of life are coming to the forefront in its approach. The main objective was to analyze whether interventions aimed at modifying lifestyle can be effective in improving pain intensity and functional disability in CNSLBP. A search in PubMed, Web of Science, Scopus and SportDiscus databases was performed. Both a univariate and a multivariate network meta-analysis were applied with the difference pre/post-treatment. A total of 20 studies were included for qualitative analysis, of which 16 were randomized clinical trials with a moderate–high methodological quality and were part of the quantitative analysis. The interventions that had the greatest effect in reducing pain intensity were cognitive therapy combined with functional exercise programs, lumbar stabilization exercise and resistance exercise; meanwhile, for functional disability, they were functional exercise programs, aerobic exercise and standard care. In conclusion, a multimodal intervention aimed at changing one’s lifestyle that encompasses cognitive, behavioral, and physical aspects seems to be highly effective in improving pain intensity and functional disability caused by CNSLBP; however, it is not yet known if these improvements are maintained in the long term.
Professional Perspectives on Children’s Health Assets: A Delphi Study
Authors: Vidal-Sánchez María Isabel , Cantero-Garlito Pablo A. , Gasch-Gallén Ángel
Published: February 2024

This study aims to describe a local community expert’s perspective on the identification of and access to children’s health assets and to gather proposals to promote children’s health and well-being within their community. The health asset approach is essential for health promotion, and there is evidence of its benefits to individuals’ or communities’ health when this approach is observed. Children’s health assets are gaining increasing interest, but the literature that captures the perception of professionals working with children is scarce. Qualitative research designed with Delphi methodology was carried out with the participation of 25 professionals working in a neighbourhood with children and families. The participants stated that this neighbourhood was a good environment for the healthy and happy growth of children but pointed out that there were inequities. They emphasised the importance of economic and physical security and feeling loved. The absolute best aspects of the neighbourhood according to these experts were its support networks, mutual help, educational and health services, and green spaces, and the most deficient aspects were the possibility of a hopeful future and emotional support within the family unit. Poverty and/or the scarcity of economic resources were identified as the main barriers to accessing health assets. Special difficulties in access to health for migrant and Roma children were also identified. The panel of experts made concrete action proposals. It was recommended to support resources and services that already exist in their community. The experts prioritised work with families, education, working in conjunction with vulnerable groups, community participation, and networking.
Serious Games for Developing Social Skills in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review
Authors: Carneiro Tânia , Carvalho António , Frota Sónia , Filipe Marisa G.
Published: February 2024

Serious games represent a promising avenue for intervention with children diagnosed with autism spectrum disorder, a neurodevelopmental disorder marked by persistent challenges in social communication and the presence of restricted, repetitive behaviors. Despite this potential, comprehensive reviews on this subject are scarce. This systematic review aims to evaluate the effectiveness of serious games and their specific characteristics in enhancing social skills among children and adolescents with autism. Employing PICO strategies and adhering to PRISMA guidelines, we screened 149 studies initially identified through PubMed and EBSCOhost databases. Nine studies met inclusion criteria and found a positive influence of serious games on social skills and related domains, encompassing emotion recognition/encoding/decoding, emotional regulation, eye gaze, joint attention, and behavioral skills. Nevertheless, despite these promising results, the limited available evidence underscores the need for rigorous study designs to consolidate findings and integrate evidence-based intervention strategies.
Artificial Intelligence: A Promising Tool for Application in Phytopathology
Authors: González-Rodríguez Victoria E. , Izquierdo-Bueno Inmaculada , Cantoral Jesús M. , Carbú María , Garrido Carlos
Published: February 2024

Artificial intelligence (AI) is revolutionizing approaches in plant disease management and phytopathological research. This review analyzes current applications and future directions of AI in addressing evolving agricultural challenges. Plant diseases annually cause 10–16% yield losses in major crops, prompting urgent innovations. Artificial intelligence (AI) shows an aptitude for automated disease detection and diagnosis utilizing image recognition techniques, with reported accuracies exceeding 95% and surpassing human visual assessment. Forecasting models integrating weather, soil, and crop data enable preemptive interventions by predicting spatial-temporal outbreak risks weeks in advance at 81–95% precision, minimizing pesticide usage. Precision agriculture powered by AI optimizes data-driven, tailored crop protection strategies boosting resilience. Real-time monitoring leveraging AI discerns pre-symptomatic anomalies from plant and environmental data for early alerts. These applications highlight AI’s proficiency in illuminating opaque disease patterns within increasingly complex agricultural data. Machine learning techniques overcome human cognitive constraints by discovering multivariate correlations unnoticed before. AI is poised to transform in-field decision-making around disease prevention and precision management. Overall, AI constitutes a strategic innovation pathway to strengthen ecological plant health management amidst climate change, globalization, and agricultural intensification pressures. With prudent and ethical implementation, AI-enabled tools promise to enable next-generation phytopathology, enhancing crop resilience worldwide.