bluuebunny/crossref_metadata_2025 huggingface dataset:
Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies
Authors: Gorji Leva , Aoun Hussein , Critchfield Jeffrey , Al Hallak Najeeb , Beal Eliza W.
Published: September 2023

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.
Reproducible Bioinformatics Analysis Workflows for Detecting IGH Gene Fusions in B-Cell Acute Lymphoblastic Leukaemia Patients
Authors: Thomson Ashlee J. , Rehn Jacqueline A. , Heatley Susan L. , Eadie Laura N. , Page Elyse C. , Schutz Caitlin , McClure Barbara J. , Sutton Rosemary , Dalla-Pozza Luciano , Moore Andrew S. , Greenwood Matthew , Kotecha Rishi S. , Fong Chun Y. , Yong Agnes S. M. , Yeung David T. , Breen James , White Deborah L.
Published: September 2023

B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection. Using Nextflow, we developed a simplified workflow containing the algorithms FusionCatcher, Arriba, and STAR-Fusion. We analysed samples from 35 patients harbouring IGH fusions (IGH::CRLF2 n = 17, IGH::DUX4 n = 15, IGH::EPOR n = 3) and assessed the detection rates for each caller, before optimizing the parameters to enhance sensitivity for IGH fusions. Initial results showed that FusionCatcher and Arriba outperformed STAR-Fusion (85–89% vs. 29% of IGH fusions reported). We found that extensive filtering in STAR-Fusion hindered IGH reporting. By adjusting specific filtering steps (e.g., read support, fusion fragments per million total reads), we achieved a 94% reporting rate for IGH fusions with STAR-Fusion. This analysis highlights the importance of filtering optimization for IGH gene fusion events, offering alternative workflows for difficult-to-detect high-risk B-ALL subtypes.
Recent Advances in Single-Cell RNA-Sequencing of Primary and Metastatic Clear Cell Renal Cell Carcinoma
Authors: Alchahin Adele M. , Tsea Ioanna , Baryawno Ninib
Published: September 2023

Over the past two decades, significant progress has been made in the treatment of clear cell renal cell carcinoma (ccRCC), with a shift towards adopting new treatment approaches ranging from monotherapy to triple-combination therapy. This progress has been spearheaded by fundamental technological advancements that have allowed a deeper understanding of the various biological components of this cancer. In particular, the rapid commercialization of transcriptomics technologies, such as single-cell RNA-sequencing (scRNA-seq) methodologies, has played a crucial role in accelerating this understanding. Through precise measurements facilitated by these technologies, the research community has successfully identified and characterized diverse tumor, immune, and stromal cell populations, uncovering their interactions and pathways involved in disease progression. In localized ccRCC, patients have shown impressive response rates to treatment. However, despite the emerging findings and new knowledge provided in the field, there are still patients that do not respond to treatment, especially in advanced disease stages. One of the key challenges lies in the limited study of ccRCC metastases compared to localized cases. This knowledge gap may contribute to the relatively low survival rates and response rates observed in patients with metastatic ccRCC. To bridge this gap, we here delve into recent research utilizing scRNA-seq technologies in both primary and metastatic ccRCC. The goal of this review is to shed light on the current state of knowledge in the field, present existing treatment options, and emphasize the crucial steps needed to improve survival rates, particularly in cases of metastatic ccRCC.
Adrenal Incidentalomas and Other Endocrine-Related Adenomas: How Much Does Cortisol Secretion Matter?
Authors: Herrera-Martínez Aura D. , Rebollo Román Ángel , Pascual Corrales Eider , Idrobo Cindy , Parra Ramírez Paola , Martín Rojas-Marcos Patricia , Robles Lázaro Cristina , Marginean Delia Lavinia , Araujo-Castro Marta
Published: September 2023

Background: Adrenal incidentalomas (AI) are frequent findings in clinical practice. About 40% of AIs are associated with hypercortisolism of variable severity. Although mild autonomous cortisol secretion (MACS) has been associated with the impaired clinical outcome of several diseases, its effect on the development of benign neoplasms is unknown. Aim: To compare the prevalence of adenomas (thyroid, parathyroid, pituitary and other locations) in patients with nonfunctioning AIs (NFAIs) and MACS. Methods: A multicenter, retrospective study of patients with AIs evaluated in four tertiary hospitals was performed. Results: A total of 923 patients were included. Most patients were male (53.6%), with a mean age at diagnosis of 62.4 ± 11.13 years; 21.7% presented with bilateral AIs. MACS was observed in 29.9% (n = 276) of patients, while 69.9% (n = 647) were NFAIs. Adenomas in locations other than the adrenal gland were observed in 36% of the studied population, with a similar distribution in patients with MACS and NFAIs (33% vs. 32%; p > 0.05). There were no statistically significant differences in the prevalence of pituitary, thyroid, parathyroid or other endocrine-related adenomas between both groups, but the prevalence of metabolic comorbidities and mortality was increased in patients with MACS, specifically in patients with thyroid and other endocrine-related adenomas (p < 0.05). Conclusions: Adenomas in locations other than the adrenal glands occur in one third of patients with AIs. Mild autonomous hypercortisolism does not affect the prevalence of other endocrine-related adenomas but is associated with increased metabolic comorbidities and mortality, especially in patients with thyroid adenomas and adenomas in other locations.
Current Issues in Molecular Biology Keep Evolving and Getting Better
Authors: Bhatia Madhav
Published: September 2023

Current Issues in Molecular Biology (CIMB) (https://www [...]
Efficient Two-Stage Max-Pooling Engines for an FPGA-Based Convolutional Neural Network
Authors: Hong Eonpyo , Choi Kang-A , Joo Jhihoon
Published: September 2023

This paper proposes two max-pooling engines, named the RTB-MAXP engine and the CMB-MAXP engine, with a scalable window size parameter for FPGA-based convolutional neural network (CNN) implementation. The max-pooling operation for the CNN can be decomposed into two stages, i.e., a horizontal axis max-pooling operation and a vertical axis max-pooling operation. These two one-dimensional max-pooling operations are performed by tracking the rank of the values within the window in the RTB-MAXP engine and cascading the maximum operations of the values in the CMB-MAXP engine. Both the RTB-MAXP engine and the CMB-MAXP engine were implemented using VHSIC hardware description language (VHDL) and verified by simulations. The implementation results demonstrate that the 16 CMB-MAXP engines achieved a remarkable throughput of about 9 GBPS (gigabytes per second) while utilizing only about 3% of the available resources on the Xilinx Virtex UltraScale+ FPGA XCVU9P. On the other hand, the 16 RTB-MAXP engines exhibited somewhat lower throughput and resource utilization, although they did offer a slightly better latency when compared to the CMB-MAXP engines. In the comparison with existing techniques, the CMB-MAXP engine exhibited comparable implementation results in terms of the resource utilization and maximum operating frequency. It is crucial to note that only the proposed engines provide the features of runtime window scalability and boundary padding capability, which are essential requirements for CNN accelerators. The proposed max-pooling engines were employed and tested in our CNN accelerator targeting the CNN model YOLOv4-CSP-S-Leaky for object detection.
Developing the Socio-Emotional Intelligence of Doctoral Students
Authors: Devis-Rozental Camila
Published: September 2023

Socio-emotional intelligence is the capacity to consider emotions, intuition, and cognition to identify, manage and express emotions and to respond to social situations with authenticity, openness and fairness. By doing so, individuals will achieve a sense of wellbeing and build meaningful relations whilst having a positive impact on the environment, others and themselves. The term doctoral student refers to a postgraduate researcher completing a doctoral degree. Supervisor is the term used in academia for an academic guiding and supporting the doctoral student. Doctoral supervisions usually include at least two academics as supervisors. A doctoral degree in the UK normally focuses on the in-depth study of a topic; these can be chosen by the doctoral student or sometimes be content-specific if a scholarship is attached.
Modeling 3D NAND Flash with Nonparametric Inference on Regression Coefficients for Reliable Solid-State Storage
Authors: Borghesi Michela , Zambelli Cristian , Micheloni Rino , Bonnini Stefano
Published: September 2023

Solid-state drives represent the preferred backbone storage solution thanks to their low latency and high throughput capabilities compared to mechanical hard disk drives. The performance of a drive is intertwined with the reliability of the memories; hence, modeling their reliability is an important task to be performed as a support for storage system designers. In the literature, storage developers devise dedicated parametric statistical approaches to model the evolution of the memory’s error distribution through well-known statistical frameworks. Some of these well-founded reliability models have a deep connection with the 3D NAND flash technology. In fact, the more precise and accurate the model, the less the probability of incurring storage performance slowdowns. In this work, to avoid some limitations of the parametric methods, a non-parametric approach to test the model goodness-of-fit based on combined permutation tests is carried out. The results show that the electrical characterization of different memory blocks and pages tested provides an FBC feature that can be well-modeled using a multiple regression analysis.
Multi-Antenna Jammer-Assisted Secure Short Packet Communications in IoT Networks
Authors: Chen Dechuan , Li Jin , Hu Jianwei , Zhang Xingang , Zhang Shuai
Published: September 2023

In this work, we exploit a multi-antenna cooperative jammer to enable secure short packet communications in Internet of Things (IoT) networks. Specifically, we propose three jamming schemes to combat eavesdropping, i.e., the zero forcing beamforming (ZFB) scheme, null-space artificial noise (NAN) scheme, and transmit antenna selection (TAS) scheme. Assuming Rayleigh fading, we derive new closed-form approximations for the secrecy throughput with finite blocklength coding. To gain further insights, we also analyze the asymptotic performance of the secrecy throughput in the case of infinite blocklength. Furthermore, we investigate the optimization problem in terms of maximizing the secrecy throughput with the latency and reliability constraints to determine the optimal blocklength. Simulation results validate the accuracy of the approximations and evaluate the impact of key parameters such as the jamming power and the number of antennas at the jammer on the secrecy throughput.
Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models
Authors: Chua Christianne J. , Morrissette-McAlmon Justin , Tung Leslie , Boheler Kenneth R.
Published: September 2023

Cardiomyopathies (CMPs) represent a significant healthcare burden and are a major cause of heart failure leading to premature death. Several CMPs are now recognized to have a strong genetic basis, including arrhythmogenic cardiomyopathy (ACM), which predisposes patients to arrhythmic episodes. Variants in one of the five genes (PKP2, JUP, DSC2, DSG2, and DSP) encoding proteins of the desmosome are known to cause a subset of ACM, which we classify as desmosome-related ACM (dACM). Phenotypically, this disease may lead to sudden cardiac death in young athletes and, during late stages, is often accompanied by myocardial fibrofatty infiltrates. While the pathogenicity of the desmosome genes has been well established through animal studies and limited supplies of primary human cells, these systems have drawbacks that limit their utility and relevance to understanding human disease. Human induced pluripotent stem cells (hiPSCs) have emerged as a powerful tool for modeling ACM in vitro that can overcome these challenges, as they represent a reproducible and scalable source of cardiomyocytes (CMs) that recapitulate patient phenotypes. In this review, we provide an overview of dACM, summarize findings in other model systems linking desmosome proteins with this disease, and provide an up-to-date summary of the work that has been conducted in hiPSC-cardiomyocyte (hiPSC-CM) models of dACM. In the context of the hiPSC-CM model system, we highlight novel findings that have contributed to our understanding of disease and enumerate the limitations, prospects, and directions for research to consider towards future progress.
Bioengineered Hybrid Rep 2/6 Gene Improves Encapsulation of a Single-Stranded Expression Cassette into AAV6 Vectors
Authors: Tejero Marcos , Duzenli Ozgun F. , Caine Colin , Kuoch Hisae , Aslanidi George
Published: September 2023

The production of clinical-grade recombinant adeno-associated viral (AAV) vectors for gene therapy trials remains a major hurdle in the further advancement of the gene therapy field. During the past decades, AAV research has been predominantly focused on the development of new capsid modifications, vector-associated immunogenicity, and the scale-up vector production. However, limited studies have examined the possibility to manipulate non-structural components of AAV such as the Rep genes. Historically, naturally isolated, or recombinant library-derived AAV capsids have been produced using the AAV serotype 2 Rep gene to package ITR2-flanked vector genomes. In the current study, we mutated four variable amino acids in the conservative part of the binding domain in AAV serotype 6 Rep to generate a Rep2/6 hybrid gene. This newly generated Rep2/6 hybrid had improved packaging ability over wild-type Rep6. AAV vectors produced with Rep2/6 exhibited similar in vivo activity as standard AAV6 vectors. Furthermore, we show that this Rep2/6 hybrid also improves full/empty capsid ratios, suggesting that Rep bioengineering can be used to improve the ratio of fully encapsulated AAV vectors during upstream manufacturing processes.
Chromosome Microarray Analysis and Exome Sequencing: Implementation in Prenatal Diagnosis of Fetuses with Digestive System Malformations
Authors: Wang You , Liu Liyuan , Fu Fang , Li Ru , Lei Tingying , Huang Ruibin , Li Dongzhi , Liao Can
Published: September 2023

(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA) and exome sequencing (ES) analysis in fetuses with digestive system malformations (DSMs). (2) Methods: In total, 595 women with fetal DSMs who underwent prenatal diagnosis were enrolled. We analyzed the diagnostic yields of CMA and ES and evaluated pregnancy outcomes. Copy number variants (CNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. (3) Results: Pathogenic CNVs were detected in 11/517 (2.12%) fetuses, and variants of unknown significance (VUS) were identified in 69 (13.35%) fetuses using CMA. ES detected 29 pathogenic/likely pathogenic variants in 23/143 (16.08%) fetuses and 26/143 (18.2%) VUS. In those with other ultrasound abnormalities, the detection rate of multiple system structural malformations was 41.2%, followed by skeletal (33.3%), cardiovascular (25.4%), and central nervous system (18.6%) malformations. Of the 391 surviving children, 40 (10.2%) exhibited varying degrees of mental retardation. (4) Conclusion: A correlation exists between DSMs and chromosomal abnormalities. When combined with other systemic abnormalities, the incidence of chromosomal abnormalities increases significantly. Patients with congenital DSM are at risk of developing neurodevelopmental disorders. Combined CMA and ES detection of fetal DSM has good clinical application potential.
BioChainReward: A Secure and Incentivised Blockchain Framework for Biomedical Data Sharing
Authors: Elkhodr Mahmoud , Gide Ergun , Darwish Omar , Al-Eidi Shorouq
Published: September 2023

In the era of digital healthcare, biomedical data sharing is of paramount importance for the advancement of research and personalised healthcare. However, sharing such data while preserving user privacy and ensuring data security poses significant challenges. This paper introduces BioChainReward (BCR), a blockchain-based framework designed to address these concerns. BCR offers enhanced security, privacy, and incentivisation for data sharing in biomedical applications. Its architecture consists of four distinct layers: data, blockchain, smart contract, and application. The data layer handles the encryption and decryption of data, while the blockchain layer manages data hashing and retrieval. The smart contract layer includes an AI-enabled privacy-preservation sublayer that dynamically selects an appropriate privacy technique, tailored to the nature and purpose of each data request. This layer also features a feedback and incentive mechanism that incentivises patients to share their data by offering rewards. Lastly, the application layer serves as an interface for diverse applications, such as AI-enabled apps and data analysis tools, to access and utilise the shared data. Hence, BCR presents a robust, comprehensive approach to secure, privacy-aware, and incentivised data sharing in the biomedical domain.
Development of the Refugees and Asylum Seekers Occupational Satisfaction (RASOS) Assessment Tool
Authors: Psychouli Pavlina , Louta Ioulia , Christodoulou Constantina
Published: September 2023

The objective of this study was to develop an occupation-centered and client-centered assessment tool for refugees and asylum seekers. A preliminary tool outline was produced based on a literature review, while considering previous published tools’ strengths and limitations. A qualitative study was undertaken via focus groups to improve on the tool’s design and adequacy for its purpose, resulting in the creation of a pilot version of the tool. Convenience sampling included 8 Greek and Cypriot professional and student occupational therapists with experience in the field, 8 international expert occupational therapists, 4 laypeople, 4 humanitarian professionals, and 5 refugees and asylum seekers. Basic qualitative content and thematic analysis led to topics regarding tool modifications that concerned categorization, formation/structure, wording, administration, and assessment scale. Corresponding tool revisions ensued. This study led to the development of the pilot version of the Refugees and Asylum Seekers Occupational Satisfaction (RASOS), which can also be used to identify underlying personal and environmental factors that contribute to self-perceived low satisfaction. A future quantitative study is required to establish the psychometric properties of the tool.
Substance Use among Emerging Adults during the COVID-19 Pandemic: A Review through the Lens of Sustainable Development Goals
Authors: Remesan Ajith K. , Sekaran Varalakshmi Chandra , Jothikaran Teddy Andrews Jaihind , Ashok Lena
Published: September 2023

Public health initiatives, including lockdowns to reduce the spread of COVID-19, have resulted in societal stressors like loneliness, job loss, and economic collapse linked to worsening mental health outcomes, such as depression, anxiety, and coping-related substance use. The various psychosocial stressors caused by the pandemic have potentially led to the increased use of substances across the globe, particularly among emerging adults. The current study summarises the literature on substance use among emerging adults during the COVID-19 pandemic. The terms “coronavirus”, “COVID-19”, “substance use”, “substance abuse”, “drug use”, drug abuse”, “emerging adults”, and “young adults” were all used in different combinations throughout the search, using the Scopus, PubMed, and JSTOR databases. Using this method, a total of 28 English-language citations published between 2020 and 2023 were obtained. Following a study of the articles mentioned above, 16 papers were removed. The remaining 12 papers were included in this review. Even though substance use dropped when COVID-19 lockdowns began, it rose when restrictions were removed, particularly among those with prior substance use. Studies related to mental health need to assess substance use, as many emerging adults use substances to cope with distress, including isolation and loneliness, which are part of the current mental health crisis among emerging adults.
Results from a Nationwide Evaluation Study of Labor Market-Integrative Health Promotion for the Unemployed: Impact of the JOBS Program Germany
Authors: Hollederer Alfons , Jahn Heiko J.
Published: September 2023

Compared to the employed, the unemployed suffer from poorer health, especially in terms of mental health. At the same time, health promotion rarely reaches unemployed people. The “JOBS Program” is an intervention to promote health and labor market integration and has shown positive effects in the USA and Finland. In this confirmatory study, we investigated whether the JOBS Program achieves similar effects in Germany. We applied a randomized controlled trial to compare an intervention group (IVG) with a waiting control group (WCG) before (T0; N = 94) and shortly after (T1; n = 65) the intervention. Concerning our primary outcomes, the JOBS Program Germany was beneficial: Compared to the WCG, the regression estimated that the IVG had (1) a 2.736 scale point higher level of life satisfaction (p = 0.049), (2) a 0.337 scale point higher level of general health (p = 0.025), and (3) a 14.524 scale point higher level of mental well-being (p = 0.004). Although not statistically significant, job search-specific self-efficacy also appeared to be positively associated with the intervention. This study provides evidence of the effectiveness of JOBS Program on the abovementioned outcomes, including for older and long-term unemployed people, supporting the benefits of regular implementation of this program for a wide range of unemployed people in Germany.
NOD-like Receptor Signaling Pathway in Gastrointestinal Inflammatory Diseases and Cancers
Authors: Zhou Yujie , Yu Songyan , Zhang Wenyong
Published: September 2023

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are intracellular proteins with a central role in innate and adaptive immunity. As a member of pattern recognition receptors (PRRs), NLRs sense specific pathogen-associated molecular patterns, trigger numerous signaling pathways and lead to the secretion of various cytokines. In recent years, cumulative studies have revealed the significant impacts of NLRs in gastrointestinal (GI) inflammatory diseases and cancers. Deciphering the role and molecular mechanism of the NLR signaling pathways may provide new opportunities for the development of therapeutic strategies related to GI inflammatory diseases and GI cancers. This review presents the structures and signaling pathways of NLRs, summarizes the recent advances regarding NLR signaling in GI inflammatory diseases and GI cancers and describes comprehensive therapeutic strategies based on this signaling pathway.
Identification of Potential miRNA Biomarkers to Detect Hydrocortisone Administration in Horses
Authors: Kikuchi Mio , Ishige Taichiro , Minamijima Yohei , Hirota Kei-ichi , Nagata Shun-ichi , Tozaki Teruaki , Kakoi Hironaga , Ishiguro-Oonuma Toshina , Kizaki Keiichiro
Published: September 2023

Circulating microRNAs (miRNAs) are stable in bodily fluids and are potential biomarkers of various diseases and physiological states. Although several studies have been conducted on humans to detect drug doping by miRNAs, research on drugs and miRNAs in horses is limited. In this study, circulating miRNAs in horses after hydrocortisone administration were profiled and variations in miRNAs affected by hydrocortisone administration during endogenous hydrocortisone elevation were examined. The miRNAs were extracted from thoroughbred horse plasma before and after hydrocortisone administration and subjected to small RNA sequencing and reverse transcription quantitative PCR (RT-qPCR). RT-qPCR validation was performed for the 20 miRNAs that were most affected by hydrocortisone administration. The effects of elevated endogenous hydrocortisone levels due to exercise and adrenocorticotropic hormone administration were also confirmed. The validation results showed that approximately half of the miRNAs showed the same significant differences as those obtained using small RNA sequencing. Among the twenty miRNAs, two novel miRNAs and miR-133a were found to vary differently between exogenous hydrocortisone administration and endogenous hydrocortisone elevation. This study provides basic knowledge regarding the circulating miRNA profile of horses after hydrocortisone administration and identifies three miRNAs that could potentially be used as biomarkers to detect hydrocortisone administration.
Analysis of Functional Single-Nucleotide Polymorphisms (SNPs) and Leaf Quality in Tea Collection under Nitrogen-Deficient Conditions
Authors: Samarina Lidiia , Fedorina Jaroslava , Kuzmina Daria , Malyukova Lyudmila , Manakhova Karina , Kovalenko Tatyana , Matskiv Alexandra , Xia Enhua , Tong Wei , Zhang Zhaoliang , Ryndin Alexey , Orlov Yuriy L. , Khlestkina Elena K.
Published: September 2023

This study discusses the genetic mutations that have a significant association with economically important traits that would benefit tea breeders. The purpose of this study was to analyze the leaf quality and SNPs in quality-related genes in the tea plant collection of 20 mutant genotypes growing without nitrogen fertilizers. Leaf N-content, catechins, L-theanine, and caffeine contents were analyzed in dry leaves via HPLC. Additionally, the photochemical yield, electron transport efficiency, and non-photochemical quenching were analyzed using PAM-fluorimetry. The next generation pooled amplicon–sequencing approach was used for SNPs-calling in 30 key genes related to N metabolism and leaf quality. The leaf N content varied significantly among genotypes (p ≤ 0.05) from 2.3 to 3.7% of dry mass. The caffeine content varied from 0.7 to 11.7 mg g−1, and the L-theanine content varied from 0.2 to 5.8 mg g−1 dry leaf mass. Significant positive correlations were detected between the nitrogen content and biochemical parameters such as theanine, caffeine, and most of the catechins. However, significant negative correlations were observed between the photosynthetic parameters (Y, ETR, Fv/Fm) and several biochemical compounds, including rutin, Quercetin-3-O-glucoside, Kaempferol-3-O-rutinoside, Kaempferol-3-O-glucoside, Theaflavin-3′-gallate, gallic acid. From our SNP-analysis, three SNPs in WRKY57 were detected in all genotypes with a low N content. Moreover, 29 SNPs with a high or moderate effect were specific for #316 (high N-content, high quality) or #507 (low N-content, low quality). The use of a linear regression model revealed 16 significant associations; theaflavin, L-theanine, and ECG were associated with several SNPs of the following genes: ANSa, DFRa, GDH2, 4CL, AlaAT1, MYB4, LHT1, F3′5′Hb, UFGTa. Among them, seven SNPs of moderate effect led to changes in the amino acid contents in the final proteins of the following genes: ANSa, GDH2, 4Cl, F3′5′Hb, UFGTa. These results will be useful for further evaluations of the important SNPs and will help to provide a better understanding of the mechanisms of nitrogen uptake efficiency in tree crops.
The Protective Role of Oleuropein Aglycone against Pesticide-Induced Toxicity in a Human Keratinocytes Cell Model
Authors: Leri Manuela , Vasarri Marzia , Barletta Emanuela , Schiavone Nicola , Bergonzi Maria Camilla , Bucciantini Monica , Degl’Innocenti Donatella
Published: September 2023

The extensive use of agricultural pesticides to improve crop quality and yield significantly increased the risk to the public of exposure to small but repeated doses of pesticides over time through various routes, including skin, by increasing the risk of disease outbreaks. Although much work was conducted to reduce the use of pesticides in agriculture, little attention was paid to prevention, which could reduce the toxicity of pesticide exposure by reducing its impact on human health. Extra virgin olive oil (EVOO), a major component of the Mediterranean diet, exerts numerous health-promoting properties, many of which are attributed to oleuropein aglycone (OleA), the deglycosylated form of oleuropein, which is the main polyphenolic component of EVOO. In this work, three pesticides with different physicochemical and biological properties, namely oxadiazon (OXA), imidacloprid (IMID), and glyphosate (GLYPHO), were compared in terms of metabolic activity, mitochondrial function and epigenetic modulation in an in vitro cellular model of human HaCaT keratinocytes to mimic the pathway of dermal exposure. The potential protective effect of OleA against pesticide-induced cellular toxicity was then evaluated in a cell pre-treatment condition. This study showed that sub-lethal doses of OXA and IMID reduced the metabolic activity and mitochondrial functionality of HaCaT cells by inducing oxidative stress and altering intracellular calcium flux and caused epigenetic modification by reducing histone acetylation H3 and H4. GLYPHO, on the other hand, showed no evidence of cellular toxicity at the doses tested. Pretreatment of cells with OleA was able to protect cells from the damaging effects of the pesticides OXA and IMID by maintaining metabolic activity and mitochondrial function at a controlled level and preventing acetylation reduction, particularly of histone H3. In conclusion, the bioactive properties of OleA reported here could be of great pharmaceutical and health interest, as they could be further studied to design new formulations for the prevention of toxicity from exposure to pesticide use.
Knocking Out OsRLK7-1 Impairs Rice Growth and Development but Enhances Its Resistance to Planthoppers
Authors: Han Shanjie , Shen Zhifan , Gao Qing , Jin Nuo , Lou Yonggen
Published: September 2023

Leucine-rich repeat receptor-like kinases (LRR-RLKs) are an important subfamily of receptor-like kinases (RLKs) in plants that play key roles in sensing different biotic and abiotic stress. However, the role of LRR-RLKs in herbivore-induced plant defense remains largely elusive. Here, we found that the expression of a rice gene, OsRLK7-1, was induced by mechanical wounding, but was slightly suppressed by the infestation of gravid females of brown planthopper (BPH, Nilaparvata lugens) or white-backed planthopper (WBPH, Sogatella furcifera). Through targeted disruption of OsRLK7-1 (resulting in the ko-rlk lines), we observed an augmentation in transcript levels of BPH-induced OsMPK3, OsWRKY30, OsWRKY33, and OsWRKY45, alongside heightened levels of planthopper-induced jasmonic acid, JA-isoleucine, and abscisic acid in plant tissues. These dynamic changes further facilitated the biosynthesis of multiple phenolamides within the rice plants, culminating in an enhanced resistance to planthopper infestations under both lab and field conditions. In addition, knocking out OsRLK7-1 impaired plant growth and reproduction. These results suggest that OsRLK7-1 plays an important role in regulating rice growth, development, and rice-planthopper interactions.
Prediction of Crack Width in RC Piles Exposed to Local Corrosion in Chloride Environment
Authors: Shao Wei , He Xiaoqing , Shi Danda , Zhu Wenjin
Published: September 2023

A novel prediction model for crack development of reinforced concrete (RC) piles with localized chloride corrosion in the marine environment is proposed. A discrete method is used to solve the corrosion pit radius model and a crack extension model is developed to investigate the initiation and extension of cracks. The maximum corrosion degree of the reinforced concrete pile is predicted according to the limit crack criterion, and finally, a sensitivity analysis is carried out on the important parameters of crack extension. The results show that the radius of the corrosion pit, the depth corrosion pit, and the cross-sectional area loss of reinforcement gradually increase as the corrosion level increases. The loss of the local reinforcement section at crack initiation increases with the increase in the ratio of concrete cover to initial diameter and increases with the increase in the pitting factor. The required pit depth for reinforcement cracking increases with the increase in the ratio of concrete cover thickness to diameter. The loss of the cross-sectional area of reinforcement and the radius of the corrosion pit increase with the increase in the initial diameter of reinforcement. Increasing the pitting factor can reduce the pit depth and make the crack width develop faster before reaching the limit crack width. Increasing the concrete cover thickness can provide an improvement in the propagation of cracks. A comparative analysis shows that the localized corrosion pattern is more in conformity with marine engineering practice.
Computational Analysis on the Performance of Elongated Liquid Crystal Biosensors
Authors: Shadkami Reza , Chan Philip K.
Published: September 2023

Elongated ellipsoidal liquid crystal microdroplet reorientation dynamics are discussed in this paper for biosensor applications. To investigate the effect of elongated droplets on nematic liquid crystal droplet biosensors, we simulated a model of a liquid crystal droplet using ellipse geometry. Director reorientation is examined in relation to the elongated droplet shape. In addition, we examined aspect ratio as a factor affecting biosensor response time in relation to surface viscosity and anchoring energy. Finally, the findings suggest that the aspect ratio should be taken into account when designing biosensors. These results can be used to develop more effective biosensors for a variety of applications. This model then predicts the director reorientation angle, which is dependent on the anchoring energy and surface viscosity. This model further suggests that both surface viscosity and homeotropic anchoring energy play an important role when it comes to the director reorientation angle. We developed and applied a nonlinear unsteady-state mathematical model utilizing torque balance and Frank free energy according to the Leslie–Ericksen continuum theory for simulating elongated nematic liquid crystal biosensor droplets with aqueous interfaces. Using the Euler–Lagrange equation, a transient liquid crystal–aqueous interface realignment is modeled by changing the easy axis when surfactant molecules are added to the interface. The realignment at the surface of the droplet is assumed to be driven by the effect of the surfactant, which causes an anchoring transition. According to the results, the response time of the biosensor depends on the aspect ratio. Therefore, the elongation has the potential to control biosensing response time. The result of our study provides a better understanding of director reorientation in elongated liquid crystal droplets in biosensing applications through the numerical results which are presented in this paper.
Total Ionizing Dose Effects on the Threshold Voltage of GaN Cascode Devices
Authors: Wu Hao , Fu Xiaojun , Luo Jun , Yang Manlin , Yang Xiaoyu , Huang Wei , Zhang Huan , Xiang Fan , Pu Yang , Wang Ziwei
Published: September 2023

GaN devices are nowadays attracting global attention due to their outstanding performance in high voltage, high frequency, and anti-radiation ability. Research on total ionizing dose and annealing effects on E-mode GaN Cascode devices has been carried out. The Cascode device consists of a low-voltage MOSFET and a high-voltage depletion-mode GaN MISHEMT. Cascode devices of both conventional processed MOSFET and radiation-hardened MOSFET devices are fabricated to observe the TID effects. Experiment results indicate that, for the Cascode device with conventional processed MOSFET, the VTH shifts to negative values at 100 krad(Si). For the Cascode device with radiation-hardened MOSFET, the VTH shifts by −0.5 V at 100 krad(Si), while shifts to negative values are 500 krad(Si). The annealing process, after the TID experiment, shows that it can release trapped charges and help VTH recover. On one hand, the VTH shift and recover trends are similar to those of a single MOSFET device, suggesting that the MOSFET is the vulnerable part in the Cascode which determines the anti-TID ability of the device. On the other hand, the VTH shift amount of the Cascode device is much larger than that of a previously reported p-GaN HEMT device, indicating that GaN material shows a better anti-TID ability than Si.
Fast and Accurate Prediction of Refractive Index of Organic Liquids with Graph Machines
Authors: Duprat François , Ploix Jean-Luc , Aubry Jean-Marie , Gaudin Théophile
Published: September 2023

The refractive index (RI) of liquids is a key physical property of molecular compounds and materials. In addition to its ubiquitous role in physics, it is also exploited to impart specific optical properties (transparency, opacity, and gloss) to materials and various end-use products. Since few methods exist to accurately estimate this property, we have designed a graph machine model (GMM) capable of predicting the RI of liquid organic compounds containing up to 16 different types of atoms and effective in discriminating between stereoisomers. Using 8267 carefully checked RI values from the literature and the corresponding 2D organic structures, the GMM provides a training root mean square relative error of less than 0.5%, i.e., an RMSE of 0.004 for the estimation of the refractive index of the 8267 compounds. The GMM predictive ability is also compared to that obtained by several fragment-based approaches. Finally, a Docker-based tool is proposed to predict the RI of organic compounds solely from their SMILES code. The GMM developed is easy to apply, as shown by the video tutorials provided on YouTube.
Therapeutic Potential of Natural Products in the Treatment of Schistosomiasis
Authors: Azevedo Carine Machado , Meira Cássio Santana , da Silva Jaqueline Wang , Moura Danielle Maria Nascimento , de Oliveira Sheilla Andrade , da Costa Cícero Jádson , Santos Emanuelle de Souza , Soares Milena Botelho Pereira
Published: September 2023

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni, S. japonicum, and S. haematobium, each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.
Dietary Patterns and Association with Anemia in Children Aged 9–16 Years in Guangzhou, China: A Cross-Sectional Study
Authors: Ma Jie , Huang Jie , Zeng Chunzi , Zhong Xuexin , Zhang Weiwei , Zhang Bo , Li Yan
Published: September 2023

Anemia affects 1.8 billion people worldwide, and diet is one of the key modifiable factors for treating anemia in children. The dietary pattern has changed rapidly in recent decades, but its effect on childhood anemia has not been reported. This study aimed to identify dietary patterns among children in rural areas of Guangzhou, China, and explore their association with anemia. A total of 1476 children aged 9–16 years old were included in this study. Demographics, lifestyle, and anthropometric and dietary information were collected. Factor analysis was used to identify dietary patterns, and anemia was diagnosed based on hemoglobin levels. Robust Poisson regression and subgroup analysis were used to analyze the association between dietary patterns and anemia. The prevalence of anemia in children was 10.4%, with 6.1% in boys and 15.4% in girls. Four dietary patterns were identified, including a fast food pattern, a vegetarian pattern, a meat and egg pattern, and a rice and wheat pattern. A high score in the fast food pattern was positively associated with risk of anemia in children entering puberty (PR = 1.767, 95% CI: 1.026~3.043, p = 0.039), especially in girls after menarche, with marginal significance (PR = 1.740, 95% CI: 0.977~3.097, p = 0.059). A high score in the meat and egg pattern was negatively associated with risk of anemia in children entering puberty (PR = 0.498, 95% CI: 0.286~0.866, p = 0.013), especially in boys after spermatorrhea (PR = 0.237, 95% CI: 0.031~0.590, p = 0.007). The fast food pattern was a risk factor for anemia in children, and the meat and egg pattern was a protective factor for anemia in children entering puberty. The findings of this study could be used to guide the strategies of evidence-based preventive nutrition interventions to curb anemia in children.
High Nutritional Risk Is Associated with Poor Functional Status and Prognostic Biomarkers in Stroke Patients at Admission to a Rehabilitation Unit
Authors: Di Vincenzo Olivia , Pagano Ermenegilda , Cervone Mariarosaria , Natale Raffaele , Morena Annadora , Esposito Alessandra , Pasanisi Fabrizio , Scalfi Luca
Published: September 2023

Considering that malnutrition (undernutrition) is common in stroke patients and may negatively impact body function, the aim of this study was to determine the relationship between nutritional risk and functional status in stroke patients at admission to a rehabilitation unit. Nutritional risk was assessed using the Geriatric Nutritional Risk Index (GNRI), the Prognostic Nutritional Index (PNI) and the Controlling Nutritional Status (CONUT) score. Functional status was assessed using the Barthel Index, the modified Rankin Scale, the Trunk Control Test and the Sitting Balance Scale, and cognitive function was assessed using the Short Portable Mental Status Questionnaire. C-reactive protein, fibrinogen and D-dimer were also evaluated as established prognostic biomarkers. Stroke patients (n = 245; age 69.7 ± 12.8 years; 47%, women; 82% ischemic stroke) at admission to a rehabilitation unit were included in this study. A high prevalence of nutritional risk was detected with each tool and was found to be greater using the GNRI and in patients aged ≥75 years. Multiple logistic regression analysis showed that age and dysphagia were independent predictors of high nutritional risk. High risk groups performed worse on all functional tests compared to the low-risk groups (p < 0.05). Nutritional risk with each tool was associated with functional and cognitive statuses (with the highest correlation being with the Trunk Control Test). Significant associations were also found with C-reactive protein, fibrinogen and D-dimer. In conclusion, a high nutritional risk, as evaluated with the GNRI, the PNI and the CONUT score, was detected in stroke patients at admission to a rehabilitation unit. High nutritional risk was associated with functional status and with predictors of clinical outcomes (and specifically in older patients).
Anthocyanins as Immunomodulatory Dietary Supplements: A Nutraceutical Perspective and Micro-/Nano-Strategies for Enhanced Bioavailability
Authors: Ijinu Thadiyan Parambil , De Lellis Lorenza Francesca , Shanmugarama Santny , Pérez-Gregorio Rosa , Sasikumar Parameswaran , Ullah Hammad , Buccato Daniele Giuseppe , Di Minno Alessandro , Baldi Alessandra , Daglia Maria
Published: September 2023

Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells, such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute towards maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome, enhancing their immunomodulatory effects. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages across varied populations. Incorporating these natural compounds into functional foods or supplements could revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies may be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying the actions of their components. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.