bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Potential Lead Compound from Magnolia officinalis for Alzheimer’s Disease through Pharmacokinetic Prediction, Molecular Docking, Dynamic Simulation, and Experimental Validation
Authors: Youn Kumju , Jun Mira
Published: September 2024

Amyloid β protein (Aβ) deposition has been implicated as the molecular driver of Alzheimer’s disease (AD) progression. The modulation of the formation of abnormal aggregates and their post-translational modification is strongly suggested as the most effective approach to anti-AD. Beta-site APP-cleaving enzyme 1 (BACE1) acts upstream in amyloidogenic processing to generate Aβ, which rapidly aggregates alone or in combination with acetylcholinesterase (AChE) to form fibrils. Accumulated Aβ promotes BACE1 activation via glycogen synthase kinase-3β (GSK-3β) and is post-translationally modified by glutaminyl cyclase (QC), resulting in increased neurotoxicity. A novel multi-target inhibitor as a potential AD agent was identified using an in silico approach and experimental validation. Magnolia officinalis, which showed the best anti-AD activity in our preliminary study, was subjected to analysis, and 82 compounds were studied. Among 23 compounds with drug-likeness, blood–brain barrier penetration, and safety, honokiol emerged as a lead structure for the inhibition of BACE1, AChE, QC, and GSK-3β in docking and molecular dynamics (MD) simulations. Furthermore, honokiol was found to be an excellent multi-target inhibitor of these enzymes with an IC50 of 6–90 μM, even when compared to other natural single-target inhibitors. Taken together, the present study is the first to demonstrate that honokiol acts as a multiple enzyme inhibitor with an excellent pharmacokinetic and safety profile which may provide inhibitory effects in broad-range areas including the overproduction, aggregation, and post-translational modification of Aβ. It also provides insight into novel structural features for the design and discovery of multi-target inhibitors for anti-AD.
Expanded Gene Regulatory Network Reveals Potential Light-Responsive Transcription Factors and Target Genes in Cordyceps militaris
Authors: Buradam Paradee , Thananusak Roypim , Koffas Mattheos , Chumnanpuen Pramote , Vongsangnak Wanwipa
Published: September 2024

Cordyceps militaris, a fungus widely used in traditional Chinese medicine and pharmacology, is recognized for its abundant bioactive compounds, including cordycepin and carotenoids. The growth, development, and metabolite production in various fungi are influenced by the complex interactions between regulatory cascades and light-signaling pathways. However, the mechanisms of gene regulation in response to light exposure in C. militaris remain largely unexplored. This study aimed to identify light-responsive genes and potential transcription factors (TFs) in C. militaris through an integrative transcriptome analysis. To achieve this, we reconstructed an expanded gene regulatory network (eGRN) comprising 507 TFs and 8662 regulated genes using both interolog-based and homolog-based methods to build the protein–protein interaction network. Aspergillus nidulans and Neurospora crassa were chosen as templates due to their relevance as fungal models and the extensive study of their light-responsive mechanisms. By utilizing the eGRN as a framework for comparing transcriptomic responses between light-exposure and dark conditions, we identified five key TFs—homeobox TF (CCM_07504), FlbC (CCM_04849), FlbB (CCM_01128), C6 zinc finger TF (CCM_05172), and mcrA (CCM_06477)—along with ten regulated genes within the light-responsive subnetwork. These TFs and regulated genes are likely crucial for the growth, development, and secondary metabolite production in C. militaris. Moreover, molecular docking analysis revealed that two novel TFs, CCM_05727 and CCM_06992, exhibit strong binding affinities and favorable docking scores with the primary light-responsive protein CmWC-1, suggesting their potential roles in light signaling pathways. This information provides an important functional interactive network for future studies on global transcriptional regulation in C. militaris and related fungi.
V2 Protein Enhances the Replication of Genomic DNA of Mulberry Crinkle Leaf Virus
Authors: Yin Zhen-Ni , Han Pei-Yu , Han Tao-Tao , Huang Ying , Yang Jing-Jing , Zhang Meng-Si , Fang Miao , Zhong Kui , Zhang Jian , Lu Quan-You
Published: September 2024

Mulberry crinkle leaf virus (MCLV), identified in mulberry plants (Morus alba L.), is a member of the genus Mulcrilevirus in the family Geminiviridae. The functions of the V2 protein encoded by MCLV remain unclear. Here, Agrobacterium-mediated infectious clones of a wild-type MCLV vII (MCLVWT) and two V2 mutant MCLV vIIs, including MCLVmV2 (with a mutation of the start codon of the V2 ORF) and MCLVdV2 (5′-end partial deletion of the V2 ORF sequence), were constructed to investigate the roles of V2 both in planta and at the cellular level. Although all three constructs (pCA-1.1MCLVWT, pCA-MCLVmV2, and pCA-MCLVdV2) were able to infect both natural host mulberry plants and experimental tomato plants systematically, the replication of the MCLVmV2 and MCLVdV2 genomes in these hosts was significantly reduced compared to that of MCLVWT. Similarly, the accumulation of MCLVmV2 and MCLVdV2 in protoplasts of Nicotiana benthamiana plants was significantly lower than that of MCLVWT either 24 h or 48 h post-transfection. A complementation experiment further confirmed that the decreased accumulation of MCLV in the protoplasts was due to the absence of V2 expression. These results revealed that MCLV-encoded V2 greatly enhances the level of MCLV DNA accumulation and is designated the replication enhancer protein of MCLV.
Nature of Charge Transfer Effects in Complexes of Dopamine Derivatives Adsorbed on Graphene-Type Nanostructures
Authors: Farcaş Alex-Adrian , Bende Attila
Published: September 2024

Continuing the investigation started for dopamine (DA) and dopamine-o-quinone (DoQ) (see, the light absorption and charge transfer properties of the dopamine zwitterion (called dopamine-semiquinone or DsQ) adsorbed on the graphene nanoparticle surface is investigated using the ground state and linear-response time-dependent density functional theories, considering the ωB97X-D3BJ/def2-TZVPP level of theory. In terms of the strength of molecular adsorption on the surface, the DsQ form has 50% higher binding energy than that found in our previous work for the DA or DoQ cases (−20.24 kcal/mol vs. −30.41 kcal/mol). The results obtained for electronically excited states and UV-Vis absorption spectra show that the photochemical behavior of DsQ is more similar to DA than that observed for DoQ. Of the three systems analyzed, the DsQ-based complex shows the most active charge transfer (CT) phenomenon, both in terms of the number of CT-like states and the amount of charge transferred. Of the first thirty electronically excited states computed for the DsQ case, eleven are purely of the CT type, and nine are mixed CT and localized (or Frenkel) excitations. By varying the adsorption distance between the molecule and the surface vertically, the amount of charge transfer obtained for DA decreases significantly as the distance increases: for DoQ it remains stable, for DsQ there are states for which little change is observed, and for others, there is a significant change. Furthermore, the mechanistic compilation of the electron orbital diagrams of the individual components cannot describe in detail the nature of the excitations inside the complex.
Study on the Thermal Condensation Mechanism of Dehydrogenated Polymer (DHP) and Glucuronic Acid
Authors: Wang Peng , Zhang Xu , Peng Wenyao , Chen Junjun , An Junjian , Zhang Guangyan , Xie Junxian
Published: September 2024

The preparation of traditional wood-based panels mostly uses adhesives such as urea-formaldehyde resin and phenolic resin, which not only consumes petrochemical resources but also releases formaldehyde, posing potential health risks to the human body. Lignin, a natural adhesive in plant cells, is characterized by high reactivity, and it is expected to aid in the development of a new generation of green formaldehyde-free adhesives. However, current studies of lignin adhesives have revealed that while strides have been made in reducing formaldehyde emissions, its residual presence remains a concern, an issue which is compounded by inadequate water resistance. Dehydrogenated Polymer (DHP) has a lignin-like structure and good water resistance, offering a new option for the development of formaldehyde-free adhesives. In this paper, DHP and glucuronic acid were reacted with each other in a simulated hot-pressing environment to obtain DHP-glucuronic acid complex, and then the structure of the complex was characterized by infrared nuclear magnetic resonance to verify whether DHP can be efficiently connected with hemicellulose components under hot-pressing conditions. The results showed that the thermal condensation reaction of DHP and glucuronic acid can generate ester bonds at the Cα position in a simulated hot-pressing environment. This paper explores the thermal condensation mechanism of DHP and glucuronic acid, which is helpful for understanding the bonding process between adhesives and components of wood-based panels in the hot-pressing process, and provides key theoretical support for the design of more sustainable lignin adhesives.
Inflammaging and Brain Aging
Authors: Jurcau Maria Carolina , Jurcau Anamaria , Cristian Alexander , Hogea Vlad Octavian , Diaconu Razvan Gabriel , Nunkoo Vharoon Sharma
Published: September 2024

Progress made by the medical community in increasing lifespans comes with the costs of increasing the incidence and prevalence of age-related diseases, neurodegenerative ones included. Aging is associated with a series of morphological changes at the tissue and cellular levels in the brain, as well as impairments in signaling pathways and gene transcription, which lead to synaptic dysfunction and cognitive decline. Although we are not able to pinpoint the exact differences between healthy aging and neurodegeneration, research increasingly highlights the involvement of neuroinflammation and chronic systemic inflammation (inflammaging) in the development of age-associated impairments via a series of pathogenic cascades, triggered by dysfunctions of the circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender differences in the susceptibility and course of neurodegeneration that appear to be mediated by glial cells emphasize the need for future research in this area and an individualized therapeutic approach. Although rejuvenation research is still in its very early infancy, accumulated knowledge on the various signaling pathways involved in promoting cellular senescence opens the perspective of interfering with these pathways and preventing or delaying senescence.
Extraction Condition Optimization, Quantitative Analysis, and Anti-AD Bioactivity Evaluation of Acorn Polyphenols from Quercus variabilis, Quercus aliena, and Quercus dentata
Authors: Du Jianing , Han Zhengkun , Ran Longyi , Zhang Taiyu , Li Junru , Li Huiying
Published: September 2024

In the present study, Quercus variabilis (Q. variabilis), Quercus aliena (Q. aliena), and Quercus dentata (Q. dentata) acorn kernels were taken as the research objects, and the free polyphenols and bound polyphenols in acorn kernels were extracted using improved ultrasound-assisted ethanolic and alkaline extraction methods, after which the contents of gallic acid, quercetin, azelaic acid, ellagic acid, and ferulic acid were quantified by LC-MC/MS. The results demonstrated that Q. variabilis and Q. aliena acorns were suitable as raw materials to extract ellagic acid, the contents of ferulic acid and bound gallic acid in them were different, and Q. aliena acorns were more suitable for the research of gallic acid, but not for azelaic acid. Results on APP/PS1 transgenic mice verified that five polyphenols significantly suppressed the progression of AD. This study provides a theoretical basis for the drug development of acorn polyphenols.
miR-21 and miR-145 as Prognostic Biomarkers for Radiotherapy Responses in Cervical Cancer Patients: A Preliminary Study
Authors: Putra Andi D. , Andrijono  , Winarto Hariyono , Prijanti Ani R. , Rachmadi Lisnawati , Pakasi Trevino A. , Gandamihardja Supriadi , Wirasugianto Jourdan , Amelia
Published: September 2024

Radioresistance poses a significant challenge in the effective treatment of cervical cancer, often leading to poor patient outcomes. MicroRNA-21 (miR-21) and MicroRNA-145 (miR-145) are oncogenic micro-RNAs associated with various cancers, including cervical cancer, but their potential as predictive biomarkers for radioresistance remains underexplored. This study aimed to investigate the association between miR-21 and miR-145 expressions and the response to radiation therapy in cervical cancer patients. An analytical cross-sectional study was conducted on 140 subjects with cervical cancer stages IIIB and IVA who received definitive radiotherapy. miR-21 and miR-145 expressions were measured using real-time reverse transcriptase–polymerase chain reaction (RT-qPCR). A total of 102 subjects (72.9%) were classified as having stage III cervical cancer, and 38 subjects (27.1%) were classified as having stage IV cervical cancer. Disease progression occurred in 60.7% of subjects. The cut-off value for miR-21 expression was 0.00088 nmol/(mg/mL) (AUC 0.676, sensitivity 70.8%, specificity 50.8%), and a higher expression was significantly associated with radioresistance (p = 0.010). miR-145, with a cut-off of 0.0239 nmol/(mg/mL) (AUC 0.612, sensitivity 67.5%, specificity 45.5%), showed no significant association with treatment response (p = 0.132). Combining miR-21 and miR-145 (AUC 0.639, sensitivity 68.6%, specificity 46.9%, p = 0.063) did not significantly improve the predictive accuracy. This study suggests that an elevated miR-21 expression is significantly associated with radioresistance in cervical cancer patients, while miR-145 expression shows no significant correlation with treatment response. Additionally, combining miR-21 and miR-145 does not enhance the predictive power.
Novel CD44-Targeted Albumin Nanoparticles: An Innovative Approach to Improve Breast Cancer Treatment
Authors: Cirillo Giuseppe , Cappello Anna Rita , Curcio Manuela , Fiorillo Marco , Frattaruolo Luca , Avena Paola , Scorzafave Ludovica , Dolce Vincenza , Nicoletta Fiore Pasquale , Iemma Francesca
Published: September 2024

This study introduces novel CD44-targeted and redox-responsive nanoparticles (FNPs), proposed as doxorubicin (DOX) delivery devices for breast cancer. A cationized and redox-responsive Human Serum Albumin derivative was synthesized by conjugating Human Serum Albumin with cystamine moieties and then ionically complexing it with HA. The suitability of FNPs for cancer therapy was assessed through physicochemical measurements of size distribution (mean diameter of 240 nm), shape, and zeta potential (15.4 mV). Nanoparticles possessed high DOX loading efficiency (90%) and were able to trigger the drug release under redox conditions of the tumor environment (55% release after 2 h incubation). The use of the carrier increased the cytotoxic effect of DOX by targeting the CD44 protein. It was shown that, upon loading, the cytotoxic effect of DOX was enhanced in relation to CD44 protein expression in both 2D and 3D models. DOX@FNPs significantly decrease cellular metabolism by reducing both oxygen consumption and extracellular acidification rates. Moreover, they decrease the expression of proteins involved in the oxidative phosphorylation pathway, consequently reducing cellular viability and motility, as well as breast cancer stem cells and spheroid formation, compared to free DOX. This new formulation could become pioneering in reducing chemoresistance phenomena and increasing the specificity of DOX in breast cancer patients.
Genome-Wide Analysis Elucidates the Roles of AhLBD Genes in Different Abiotic Stresses and Growth and Development Stages in the Peanut (Arachis hypogea L.)
Authors: Wu Cuicui , Hou Baoguo , Wu Rilian , Yang Liuliu , Lan Gang , Xia Zhi , Cao Cairong , Pan Zhuanxia , Lv Beibei , Li Pengbo
Published: September 2024

The lateral organ boundaries domain (LBD) genes, as the plant-specific transcription factor family, play a crucial role in controlling plant architecture and stress tolerance. However, the functions of AhLBD genes in the peanut plant (Arachis hypogea L.) remain unclear. In this study, 73 AhLBDs were identified in the peanut plant and divided into three groups by phylogenetic tree analysis. Gene structure and conserved protein motif analysis supported the evolutionary conservation of AhLBDs. Tandem and segment duplications contributed to the expansion of AhLBDs. The evolutionary relationship analysis of LBD gene family between A. hypogaea and four other species indicated that the peanut plant had a close relationship with the soybean plant. AhLBDs played a very important role in response to growth and development as well as abiotic stress. Furthermore, gene expression profiling and real-time quantitative qRT-PCR analysis showed that AhLBD16, AhLBD33, AhLBD67, and AhLBD72 were candidate genes for salt stress, while AhLBD24, AhLBD33, AhLBD35, AhLBD52, AhLBD67, and AhLBD71 were candidate genes for drought stress. Our subcellular localization experiment revealed that AhLBD24, AhLBD33, AhLBD67, and AhLBD71 were located in the nucleus. Heterologous overexpression of AhLBD33 and AhLBD67 in Arabidopsis significantly enhanced tolerance to salt stress. Our results provide a theoretical basis and candidate genes for studying the molecular mechanism for abiotic stress in the peanut plant.
A Novel Newborn Screening Program for Sickle Cell Disease in Nigeria
Authors: Galadanci Aisha A. , Ibrahim Umma A. , Carroll Yvonne , Jobbi Yusuf D. , Farouk Zubaida L. , Mukaddas Aisha , Hussaini Nafiu , Sani Musa Bilya , Klein Lauren J. , DeBaun Michael R.
Published: September 2024

Newborn screening for sickle cell disease (SCD) is sparse in sub-Saharan Africa. The leadership of the Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria, with the support of local religious authorities, established a groundbreaking SCD newborn screening program that has become the standard of care for pregnant women and their newborns. Our program includes (1) prenatal genetic counseling for all pregnant women in the antenatal clinic, (2) newborn screening, (3) postnatal genetic counseling for parents of newborns diagnosed with SCD and SCT, and (4) referral of newborns with SCD for follow-up in the SCD Comprehensive Care Clinic by 3 months of age. From September 2020 to December 2023, the team screened 7530 infants for SCD at the AKTH, identifying 126 (1.7%) infants with SCD and 1546 (20.5%) with SCT. Of these, 93 (73.8%) newborns with SCD received individualized genetic counseling, and 43 (46%) were referred to the SCD Comprehensive Care Clinic before 3 months. Group genetic counseling was provided to the parents of 778 (50.3%) of newborns identified with SCT. The SCD newborn screening at the AKTH is now standard care, indicating the viability of sustaining an SCD newborn screening program that provides pre- and postnatal genetic counseling and comprehensive SCD care within a low-income setting.
Analysis of Effects on Scientific Impact Indicators Based on Coevolution of Coauthorship and Citation Networks
Authors: Xue Haobai
Published: September 2024

This study investigates the coevolution of coauthorship and citation networks and their influence on scientific metrics such as the h-index and journal impact factors. Using a preferential attachment mechanism, we developed a model that integrated these networks and validated it with data from the American Physical Society (APS). While the correlations between reference counts, paper lifetime, and team sizes with scientific impact metrics are well-known, our findings demonstrate how these relationships vary depending on specific model parameters. For instance, increasing reference counts or reducing paper lifetime significantly boosts both journal impact factors and h-indexes, while expanding team sizes without adding new authors can artificially inflate h-indexes. These results highlight potential vulnerabilities in commonly used metrics and emphasize the value of modeling and simulation for improving bibliometric evaluations.
Social Networks and Digital Influencers in the Online Purchasing Decision Process
Authors: Gonçalves Maria José Angélico , Oliveira Adriana , Abreu António , Mesquita Anabela
Published: September 2024

Social networks have become a significant part of people’s daily lives, particularly in the purchasing process. In this context, digital influencers have played an essential role in shaping consumers’ opinions. In this sense, studying the role of social networks and influencers in the online product purchase decision process was considered pertinent. We selected two technology adoption models to fulfill this purpose: the Technology Acceptance Model (TAM) and the Unified Theory of Acceptance and Use of Technology (UTAUT). We conducted an exploratory study using a quantitative approach, with data being collected through a questionnaire distributed online. The statistical analysis of the empirical model employed a partial least squares structural equation modeling (PLS-SEM) technique. Analyzing the 135 responses allowed us to conclude that social networks are relevant in consumers’ purchase decision process. This research highlights the importance of the credibility of influencers, emotional connections with audiences, and the dynamics of the media in shaping consumer behavior. It highlights the strong influence of digital influencers on purchasing decisions and makes a methodological contribution with a rigorous empirical model. This study also suggests avenues for future research in order to deepen the understanding of influencer and social media marketing strategies.
Antibacterial Biocomposite Based on Chitosan/Pluronic/Agarose Noncovalent Hydrogel: Controlled Drug Delivery by Alginate/Tetracycline Beads System
Authors: Abdollahi Hossein , Amiri Saber , Amiri Farzaneh , Moradi Somayeh , Zarrintaj Payam
Published: September 2024

Designing a wound dressing with controlled uptake, antibacterial, and proper biocompatibility is crucial for the appropriate wound healing process. In this study, alginate/tetracycline (Alg/TC) beads were produced and embedded into chitosan/pluronic/agarose semi-interpenetrating polymer network hydrogel, which serves as a potential biocompatible dressing for treating skin wounds. The effect of pluronic content on the porosity, swelling, mechanical characteristics, and degradation of the hydrogel was investigated. Furthermore, the impact of Alg beads on TC release was subsequently examined. In the absence of Alg beads, faster release was observed. However, after incorporating beads into the hydrogels, the release was sustained. Particularly, the hydrogel containing Alg beads exhibited a nearly linear release, reaching 74% after 2 days in acidic media. The antimicrobial activity and biocompatibility of the hydrogel were also evaluated to assess the capability of the TC-loaded hydrogels for wound dressing applications. The hydrogel demonstrated efficient antibacterial features against Gram-positive and Gram-negative bacteria. Additionally, the sample behavior was evaluated against exposure to yeast. Furthermore, based on biocompatibility studies using HFF2 cells, the TC-loaded hydrogel exhibited remarkable biocompatibility. Overall, this novel composite hydrogel shows remarkable biocompatibility and antibacterial activities which can be used as a great potential wound dressing to prevent wound infections due to its effective inhibition of bacterial growth.
Chemically Pretreated Densification of Juniper Wood for Potential Use in Osteosynthesis Bone Implants
Authors: Andze Laura , Nefjodovs Vadims , Andzs Martins , Skute Marite , Zoldners Juris , Kapickis Martins , Dubnika Arita , Locs Janis , Vetra Janis
Published: September 2024

The aim of the study was to perform treatment of juniper wood to obtain wood material with a density and mechanical properties comparable to bone, thus producing a potential material for use in osteosynthesis bone implants. In the first step, partial delignification of wood sample was obtained by Kraft cooking. The second step was extraction with ethanol, ethanol–water mixture, saline, and water to prevent the release of soluble compounds and increase biocompatibility. In the last step, the thermal densification at 100 °C for 24 h was implemented. The results obtained in the dry state are equivalent to the properties of bone. The swelling of chemically pre-treated densified wood was reduced compared to chemically untreated densified wood. Samples showed no cytotoxicity by in vitro cell assays. The results of the study showed that it is possible to obtain noncytotoxic wood samples with mechanical properties equivalent to bones by partial delignification, extraction, and densification. However, further research is needed to ensure the material’s shape stability, water resistance, and reduced swelling.
Cognitive Ability, Personality, and Psychopathology: A Stormy Relationship
Authors: Colom Roberto , Shih Ma Pei-Chun
Published: September 2024

Cognitive and non-cognitive traits are frequently analyzed in isolation. However, there is an increasing acknowledgment that their interplay should be considered for enhancing our understanding of human psychological differences. Testing both traits in the same sample of individuals is desirable when addressing their relationships. Here, for that purpose, 299 university students from Spain (mean age = 18.5 years., 83% female) completed a cognitive ability battery comprised by nine tests, the NEO-FFI for assessing the big five personality traits, and the SCL-90-R for evaluating a range of subjective psychopathological symptoms. This resulted in 23 cognitive and non-cognitive variables that were submitted to a data reduction providing four factors: (1) neuroticism/p, (2) cognitive ability/g, (3) agreeableness/A, and (4) introversion/I. Summary factor scores revealed a positive correlation between p and I (0.47), along with negative correlations of A with p (−0.26) and with g (−0.24), and a negative correlation between A and I (−0.16). These factors were related to some degree even when the assessment of the cognitive and non-cognitive variables cannot be considered straightforwardly comparable because the former was performance based, whereas the later was based on self-reports. Conceptual and methodological implications are discussed regarding the three-way relationship among cognitive ability, personality, and subjective psychopathological symptoms.
A Causal Inference Approach to Mediation Analysis in Vitreomacular Traction: How Much Does Traction Resolution Mediate Functional Outcomes?
Authors: Lescrauwaet Benedicte , Vansteelandt Stijn , Jackson Timothy L. , Sadda SriniVas R. , Duchateau Luc
Published: September 2024

Modern mediation analysis techniques supplement the primary intention-to-treat analysis with the aim to shed light onto the treatment mechanism. We investigate to what extent the anatomic marker vitreomacular adhesion resolution (VMAR) mediates vision benefits, comparing ocriplasmin vs. a sham regimen. A causal mediation analysis is applied to randomized trial data including 218 participants with vitreomacular traction. Logistic regression models are used to estimate the total treatment effect (TTE) on binary outcomes. Outcomes, assessed at month 24, included visual acuity improvement (VA-I): ≥2-line increase in VA; visual function questionnaire improvement (VFQ-I): ≥5-point increase in the 25-item visual function questionnaire composite score (VFQ-25cs); visual function improvement (VF-I): defined as either a VA-I or a clinically meaningful improvement in the VFQ-25cs. Quantity of interest is the breakdown of TTE into an indirect (through VMAR) and direct effect to estimate the extent to which the TTE is transmitted through the mediating variable (VMAR) vs. other pathways. Causal effects are expressed as risk differences. Indirect effects for VFQ-I, VA-I, and VF-I are 5.7%, 11.8%, and 5.2%, respectively, representing the increase in the probability of a vision improvement if VMAR status were changed for each participant to the extent that it is affected by ocriplasmin. The direct effects are 8.3%, 12.1%, and 24.1% respectively, capturing the effect of treatment on the probability of a vision improvement if ocriplasmin left each participant’s VMAR status unchanged. The relative treatment effect of ocriplasmin on the functional outcome VA-I is to a large extent the result of its effect on VMAR, while an improvement in the patient-reported outcomes VFQ-I or VF-I was only partially mediated by VMAR.
A Step beyond Reliability in the Industry 4.0 Era: Operator-Leveraged Manufacturing
Authors: Muro Belloso Alejandro , López de Calle Etxabe Kerman , Garate Perez Eider , Arnaiz Aitor
Published: September 2024

Avoiding downtime is one of the major concerns of manufacturing industries. In the era of connected industry, acquiring data has become cheaper than ever; however, turning that data into actionable insights for operators is not always straightforward. In this work, we present a manufacturing scenario involving a circular blade rubber cutting machine, where the goal is to minimize downtime. Historical cutting data are available, and the aim is to provide the machine operators with an intuitive tool that helps them reduce this downtime. This work demonstrates how, in an Industry 4.0 environment, data can be leveraged to minimize downtime. To achieve this, different survival model approaches are compared, a Health Index (HI) is developed, and the model deployment is analysed, highlighting the importance of understanding the model as a dynamic system in which the operator plays a key role.
Overlapping Gene Expression and Molecular Features in High-Grade B-Cell Lymphoma
Authors: Faißt Katharina D. , Husemann Cora C. , Kleo Karsten , Twardziok Monika , Hummel Michael
Published: September 2024

Aggressive B-cell lymphoma encompasses Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and, as per the 2016 WHO classification, high-grade B-cell lymphoma (HGBL) not otherwise specified (NOS) and HGBL double/triple hit (DH/TH). However, the diagnostic distinction of HGBL from BL and DLBCL is difficult by means of histology/immunostaining in a substantial number of patients. This study aimed to improve subtyping by the identification of molecular features of aggressive B-cell lymphomas, with a specific focus on HGBL. To this end, we performed a comprehensive gene expression and mutational pattern analysis as well as the detection of B-cell clonality of 34 cases diagnosed with BL (n = 4), DLBCL (n = 16), HGBL DH (n = 8), and HGBL NOS (n = 6). Three distinct molecular subgroups were identified based on gene expression, primarily influenced by MYC expression/translocation and cell proliferation. In HGBL, compared to BL, there was an upregulation of PRKAR2B and TERT. HGBL DH exhibited elevated expression of GAMT and SMIM14, while HGBL NOS showed increased expression of MIR155HG and LZTS1. Our gene mutation analysis revealed MYC, ARID1A, BCL2, KMT2D, and PIM1 as the most affected genes in B-cell lymphoma, with BCL2 and CREBBP predominant in HGBL DH, and MYC and PIM1 in HGBL NOS. Clonality analysis of immunoglobulin heavy and light chain rearrangements did not show distinguishable V- or J-usage between the diagnostic subgroups.
A Numerical Investigation of the Influence of the Wake for Mixed Layout Wind Turbines in Wind Farms Using FLORIS
Authors: Tian Wenxin , Wei Fulong , Zhao Yuze , Wan Jiawei , Zhao Xiuyong , Liu Langtong , Zhang Lidong
Published: September 2024

A common retrofitting method for wind farms is the replacement of low-power turbines with high-power ones. The determination of the optimal replacement sequence for the purpose of maximizing revenue is a significant challenge. This paper employs a combination of FLORIS and a sequencing algorithm to simulate the power output resulting from the replacement of 1.5 MW small turbines with 5 MW large turbines. This study demonstrates that the optimal strategy for maximizing the overall power output is to replace the turbines in the first column. When the turbines situated in the first column have already undergone replacement or are unable to be replaced due to the characteristics of the terrain, it would be prudent to prioritize those in the final column. In the case of staggered arrangements, priority should be given to diagonal points that do not have turbines situated behind them. In the case of replacing the same number of large wind turbines, the preferred replacement option has a minimal impact on the power output of the existing small wind turbines, with an estimated reduction of 0.67%. This effectively enhances the economic efficiency of wind farm renovation.
An Improved Convolutional Neural Network for Pipe Leakage Identification Based on Acoustic Emission
Authors: Xu Weidong , Huang Jiwei , Sun Lianghui , Yao Yixin , Zhu Fan , Xie Yaoguo , Zhang Meng
Published: September 2024

Oil and gas pipelines are the lifelines of the energy market, but due to long-term use and environmental factors, these pipelines are prone to corrosion and leaks. Offshore oil and gas pipeline leaks, in particular, can lead to severe consequences such as platform fires and explosions. Therefore, it is crucial to accurately and swiftly identify oil and gas leaks on offshore platforms. This is of significant importance for improving early warning systems, enhancing maintenance efficiency, and reducing economic losses. Currently, the efficiency of identifying leaks in offshore platform pipelines still needs improvement. To address this, the present study first established an experimental platform to simulate pipeline leaks in a marine environment. Laboratory leakage signal data were collected, and on-site noise data were gathered from the “Liwan 3-1” offshore oil and gas platform. By integrating leakage signals with on-site noise data, this study aimed to closely mimic real-world application scenarios. Subsequently, several neural network-based leakage identification methods were applied to the integrated dataset, including a probabilistic neural network (PNN) combined with time-domain feature extraction, a Backpropagation Neural Network (BPNN) optimized with simulated annealing and particle swarm optimization, and a Long Short-Term Memory Network (LSTM) combined with Mel-Frequency Cepstral Coefficients (MFCC). Corresponding models were constructed, and the effectiveness of leak detection was validated using test sets. Additionally, this paper proposes an improved convolutional neural network (CNN) leakage detection technology named SART-1DCNN. This technology optimizes the network architecture by introducing attention mechanisms, transformer modules, residual blocks, and combining them with Dropout and optimization algorithms, which significantly enhances data recognition accuracy. It achieves a high accuracy rate of 99.44% on the dataset. This work is capable of detecting pipeline leaks with high accuracy.
Evaluating Two Fungicides, Prochloraz–Manganese Chloride Complex and Seboctylamine Acetate, to Control Cobweb Disease in White Button Mushroom Caused by Cladobotryum mycophilum
Authors: Chen Qiqi , Yuan Yazhen , Chen Gang , Li Ning , Li Xinrong , Lan Yufei , Wang Hongyan
Published: September 2024

Cobweb disease in white button mushroom (Agaricus bisporus) is a newly identified disease caused by Cladobotryum mycophilum in China. Currently, there are few highly effective and safe fungicides for controlling this disease in the field. This study assessed the fungicidal effect of prochloraz–manganese chloride complex and seboctylamine acetate against C. mycophilum, as well as their ability to control cobweb disease. Additionally, the residues of these fungicides in the mycelium and the mushroom were evaluated. The extent of the fungicidal effect against the pathogen was determined based on the efficiency of crop production. The results revealed that, in addition to the potent inhibitory effect of prochloraz–manganese chloride complex on the hyphae of C. mycophilum, the domestically developed seboctylamine acetate exhibited high toxicity, inhibiting both mycelial growth and spore germination of C. mycophilum, with EC50 values of 0.990 mg/L and 0.652 mg/L, respectively. Furthermore, the application of the two chemical agents had no adverse effects on the mycelial growth and fruiting body growth of A. bisporus, and the residual amount of chemical agent was lower than the maximum residue limit standard. The field application results showed that 400 mg/L of prochloraz–manganese chloride complex and 6 mg/L of seboctylamine acetate resulted in 61.38% and 81.17% disease control respectively. This study presents efficient and safe fungicides for controlling cobweb disease in white button mushroom. Additionally, a residue determination analysis of the fungicide seboctylamine acetate in mushroom crops is described.
Morphological and Phylogenetic Analyses Reveal Dictyostelids (Cellular Slime Molds) Colonizing the Ascocarp of Morchella
Authors: Hu Wen-Shu , Jiang Lin-Lin , Liu Pu , Zhang Xiao-Yan , Wei Wei , Du Xi-Hui
Published: September 2024

Morchella spp. (true morels) are precious edible mushrooms consumed around the world, with a delicious taste, rich nutritional value, and unique healthcare effects. Various fungi and bacteria have been reported to colonize the ascocarps of Morchella, damaging their fruiting bodies and leading to serious economic losses in cultivation. The species identification of these colonizing organisms is crucial for understanding their colonization mechanisms on morels. Slime molds, which have characteristics of both “fungi” and “animals”, can occasionally colonize crops and edible fungi. However, there have been no reports of dictyostelid cellular slime molds (dictyostelids) colonizing plants and fungi to date. In this study, we discovered that dictyostelids colonized the surface of one wild ascoma of Morchella in the forest of Chongqing, China, with the tissues being black and rotten. Macro- and micro-morphological observations, along with molecular phylogenetic analyses, identified the specimens investigated in this study as Dictyostelium implicatum and Morchella sp. Mel-21. The results provide new knowledge of dictyostelid colonization on organisms and contribute to the diversity of species colonizing true morels. Moreover, this is also the first report of dictyostelids distributed in Chongqing, China. This study enhances our insights into the life history and potential ecological significance of dictyostelids and updates their distribution area in China. Further research will be conducted to uncover the mechanisms behind the colonization observed in this study.
Tracking Candidemia Trends and Antifungal Resistance Patterns across Europe: An In-Depth Analysis of Surveillance Systems and Surveillance Studies
Authors: Odoj Karin , Garlasco Jacopo , Pezzani Maria Diletta , Magnabosco Cristina , Ortiz Diego , Manco Federica , Galia Liliana , Foster Sarah K. , Arieti Fabiana , Tacconelli Evelina
Published: September 2024

Background: The WHO fungal priority list classifies Candida species as critical and high-priority pathogens, and the WHO GLASS fungi initiative seeks to establish a standardised global framework for antifungal resistance monitoring. We aimed to review resistance rates and antifungal resistance patterns across European surveillance systems and studies in response to these recent calls for action. Methods: A systematic review of national and international surveillance systems and peer-reviewed surveillance studies available up to June 2024 was conducted. Descriptive and trend analyses were performed on surveillance data reporting resistance to different antifungals in Candida spp. Results: In total, 6 national surveillance systems and 28 studies from 13 countries provided candidemia resistance data, mostly about the C. albicans, C. glabrata and C. parapsilosis complex. Azole resistance was most frequently reported (6/6 surveillance systems and 27/28 studies) with the highest resistance rate, especially for C. glabrata, in Croatia (100%, 28/28 isolates) and Slovenia (85.7%, 82/96) and C. parapsilosis in Croatia (80.6%, 54/67) and Italy (72.6%, 106/146). Echinocandin and polyene resistance rates were nearly zero. The number of isolates included in the surveillance systems increased over the years, particularly for C. albicans (+40–60 isolates/year), C. glabrata, and C. parapsilosis (+15–30 isolates/year). No surveillance system or study reported resistance data for C. auris. Pooled data from national surveillance revealed a decreasing trend in azole resistance in C. albicans and C. glabrata. The increasing azole-resistance trend in C. parapsilosis disappeared after adjusting for between-country heterogeneity. Overall, echinocandin and polyene resistance trends appeared relatively stable. Conclusions: Awareness of antifungal resistance is growing, but further actions are needed to strengthen surveillance capacity and knowledge-sharing networks across Europe.
Multidrug-Resistant Fungi
Authors: de Moraes Daniel Clemente , Ferreira-Pereira Antônio
Published: September 2024

Multidrug resistance in fungi is a growing challenge to global public health, resulting in ineffective treatments and thus high mortality rates [...]
Identification of Homeobox Transcription Factors in a Dimorphic Fungus Talaromyces marneffei and Protein-Protein Interaction Prediction of RfeB
Authors: Pongpom Monsicha , Khamto Nopawit , Sukantamala Panwarit , Kalawil Thitisuda , Wangsanut Tanaporn
Published: September 2024

Talaromyces marneffei is a thermally dimorphic fungus that can cause life-threatening systemic mycoses, particularly in immunocompromised individuals. Fungal homeobox transcription factors control various developmental processes, including the regulation of sexual reproduction, morphology, metabolism, and virulence. However, the function of homeobox proteins in T. marneffei has not been fully explored. Here, we searched the T. marneffei genome for the total homeobox transcription factors and predicted their biological relevance by performing gene expression analysis in different cell types, including conidia, mycelia, yeasts, and during phase transition. RfeB is selected for further computational analysis since (i) its transcripts were differentially expressed in different phases of T. marneffei, and (ii) this protein contains the highly conserved protein-protein interaction region (IR), which could be important for pathobiology and have therapeutic application. To assess the structure-function of the IR region, in silico alanine substitutions were performed at three-conserved IR residues (Asp276, Glu279, and Gln282) of RfeB, generating a triple RfeB mutated protein. Using 3D modeling and molecular dynamics simulations, we compared the protein complex formation of wild-type and mutated RfeB proteins with the putative partner candidate TmSwi5. Our results demonstrated that the mutated RfeB protein exhibited increased free binding energy, elevated protein compactness, and a reduced number of atomic contacts, suggesting disrupted protein stability and interaction. Notably, our model revealed that the IR residues primarily stabilized the RfeB binding sites located in the central region (CR). This computational approach for protein mutagenesis could provide a foundation for future experimental studies on the functional characterization of RfeB and other homeodomain-containing proteins in T. marneffei.
Analysis of 2-Year Survival Outcomes of Japanese Older Populations on Hemodiafiltration: A Propensity Score-Matched Study Based on Insurance Claims Data
Authors: Jamal Aziz , Babazono Akira , Liu Ning , Fujita Takako , Kim Sung-a , Li Yunfei
Published: September 2024

Despite the lack of evidence that suggests hemodiafiltration (HDF) offers a better survival outcome than standard hemodialysis (HD), the number of patients initiating HDF in Japan continues to rise. This study examined the temporal change in the number of HDF incidents, evaluated factors associated with all-cause mortality, and compared the mortality risk and survival time of patients on HDF with patients receiving standard HD in three sets of 2-year cohorts. The primary analyses included the insurance claims data of 460 HDF patients and propensity score-matched 903 standard HD patients who initiated dialysis therapy between 1 April 2012 and 31 March 2018. Patient follow-up was censored at the time of death or the end of the 2-year study period. The number of patients who initiated HDF and the proportion of all-cause mortality cases were evaluated. Additionally, the survival outcomes between propensity score-matched HDF and standard HD patient groups were compared throughout cohorts. The number of HDF patients increased throughout cohorts, but the proportions of mortality cases across cohorts slowly decreased. Adjusting for all study covariates, we observed that HDF patients had a lower mortality risk and longer survival time than patients on standard HD. This study supports the notion that HDF lowers all-cause mortality compared with standard HD in an incident dialysis population in Fukuoka Prefecture, Japan.
Construction of Landscape Ecological Risk Collaborative Management Network in Mountainous Cities—A Case Study of Zhangjiakou
Authors: Li Mu , Zhang Lingli , Chen Yuanyuan , Liu Shuangliang , Cai Mingyao , Sun Qiangqiang
Published: September 2024

The prevention of ecological risks is a critical determinant influencing sustainable development. Driven by rapid socio-economic development, the ecosystems of mountainous cities within agro-pastoral transition zones are increasingly vulnerable to complex disturbances, constituting a significant threat to sustainable development and human well-being. To help achieve sustainable development, it is essential to conduct research on addressing and mitigating ecological risks from the perspective of collaborative management networks in mountainous cities. Taking Zhangjiakou as the study area, this paper employed the land use transfer matrix and standard deviation ellipse methods to analyze the dynamic land use changes. Additionally, using Fragstats 4,2 to calculate the landscape indices with land use data, this paper evaluated the landscape ecological risk (LER) from 2000 to 2020. Furthermore, the social network analysis (SNA) method was utilized to explore the spatial correlation characteristics of the LER. The findings indicate that: (1) Cultivated land and grassland were the predominant land use types in Zhangjiakou. During 2000–2020, Zhangjiakou experienced significant changes in land use, dominated by the transfer among cultivated land, forestland, and grassland. It indicated that the issue of unstable ecological land use continued to exist. Affected by human activities, construction land showed a consistent upward trend, primarily concentrated in the urban built-up areas and areas along the Jing-Zhang Railway. (2) The LER of Zhangjiakou was predominantly characterized by low risk, medium risk, and high risk levels. In the transitional areas and foothills, the LER was relatively higher. During 2000–2020, Zhangjiakou showed a declining trend of LER. This suggested that the ecological protection policies in Zhangjiakou were effective, leading to an improvement in the local ecological environment. (3) The LER in Zhangjiakou demonstrated a spatial clustering pattern that exhibited an upward trend, which was supported by both spatial autocorrelation and the SNA analysis. In the LER collaborative management network, Xuanhua, Qiaodong, Qiaoxi, Wanquan and Zhangbei consistently upheld pivotal roles. Based on the number of inward and outward connections, 16 counties in Zhangjiakou were classified into four categories and three zones accompanied by corresponding recommendations. The findings of this study can serve as a valuable reference for subsequent landscape pattern optimization and ecological restoration in Zhangjiakou.