bluuebunny/crossref_metadata_2025 huggingface dataset:
First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti–PD-1 antibody budigalimab in patients with advanced solid tumors
Authors: Shimizu Toshio , Powderly John , Abdul Razak Albiruni , LoRusso Patricia , Miller Kathy D. , Kao Steven , Kongpachith Sarah , Tribouley Catherine , Graham Michelle , Stoll Brian , Patel Maulik , Sahtout Mohammad , Blaney Martha , Leibman Rachel , Golan Talia , Tolcher Anthony
Published: October 2024

Background

Transforming growth factor (TGF)-ß1 is a pleiotropic cytokine that can promote tumor growth and suppress antitumor immune responses. Latent TGF-ß1 associates with glycoprotein-A repetition predominant (GARP) on the surface of regulatory T cells prior to its activation and release. Livmoniplimab is a monoclonal antibody (mAb) that binds the GARP:TGF-ß1 complex to inhibit activation and release of TGF-ß1. It is in clinical development in combination with budigalimab, an anti-programmed cell death protein 1 Fc-modified mAb. The first-in-human, phase 1, dose-escalation results are presented herein (ClinicalTrials.gov: NCT03821935).

Methods

The dose-escalation phase enrolled adult patients with advanced solid tumors. Patients received escalating doses of livmoniplimab ranging from 3mg to 1500mg, once every 2 weeks (Q2W), as monotherapy or in combination with a 500mg fixed dose of budigalimab Q4W. The primary objective of the dose escalation was to determine the recommended phase 2 dose. Secondary objectives were to assess safety and pharmacokinetics (PK), and exploratory objectives included evaluating preliminary efficacy.

Results

Fifty-seven patients enrolled in the dose escalation: 23 in monotherapy cohorts and 34 in combination therapy cohorts. Dose-limiting toxicities were limited, no maximum tolerated dose was reached, and the maximum administered dose of 1500mg was selected for dose expansion. The most common adverse events reported in monotherapy-treated patients were fatigue, anemia, and nausea, and those in combination therapy-treated patients were pruritus, fatigue, nausea, and anemia. Livmoniplimab exhibited dose-proportional PK, and peripheral blood biomarker data demonstrated saturation of the GARP:TGF-ß1 complex on platelets at livmoniplimab doses within the linear PK range. No objective tumor responses were observed in the monotherapy dose escalation. However, the objective response rate was 15% in the combination dose escalation, with a median response duration of 8.4 months.

Conclusion

Livmoniplimab was well-tolerated as monotherapy and in combination with budigalimab in the dose-escalation phase. Encouraging preliminary efficacy was demonstrated in the combination dose escalation in heavily pretreated patients, supporting further development of this novel drug combination in patients with advanced solid tumors.
A national survey of first line antibiotic use in neonatal units – and the potential scope for iatrogenic sensorineural hearing loss prevention
Authors: Peterson J. , Muddiman L. , Groves F. , Booth N. , Newman W. G. , McDermott J. H. , Mahaveer A.
Published: October 2024

Objective

National Institute for Clinical Excellence (NICE) guidance for the management of neonatal sepsis recommends a first-line antibiotic regimen containing an aminoglycoside (gentamicin). Aminoglycoside exposure causes sensorineural hearing loss in individuals with a specific mitochondrial genetic variant (m.1555A>G). This variant can be detected promptly (in <30 min) by a point of care test. NICE does allow for variation in antibiotic regimes depending on local microbiology guidance. As practices can vary, this survey aimed to determine the current use of first-line antibiotic agents within neonatal units and postnatal wards across the UK.

Design and setting

A telephone survey was conducted across all neonatal units in the United Kingdom. Responses were requested from a member of the neonatal team experienced in neonatal septic screening processes. One response was recorded per unit.

Results

Of the 187 neonatal units, 186 (99%) responded to the survey. One unit declined to participate. The survey results show most neonatal units (93%) and postnatal wards (74%) across the United Kingdom use aminoglycosides as first-line antibiotic agents. Antibiotic regimes varied between different units and between different locations within the same hospital (NICU vs. postnatal wards). In cases where there was a contraindication to aminoglycosides, the most common alternative antibiotic was cefotaxime.

Conclusions

Most neonatal units in the UK use an aminoglycoside antibiotic as first-line agent for suspected sepsis. This places infants with the m.1555A>G genetic variant at risk of iatrogenic hearing loss. There needs to be integration of point-of-care genetic testing within the neonatal septic screening pathway.
JAK inhibitors: an evidence-based choice of the most appropriate molecule
Authors: Antonioli Luca , Armuzzi Alessandro , Fantini Massimo C. , Fornai Matteo
Published: October 2024

Janus kinase inhibitors (JAKis) represent a fundamental therapeutic tool for the treatment of patients with immune-mediated inflammatory diseases. Although JAKis are often considered a homogeneous class of drugs whose members are thought to be largely interchangeable, there are significant differences in their efficacy and safety profiles. This narrative review analyzes the pharmacokinetic and pharmacodynamic differences among JAKIs, highlighting their clinical relevance based on the most recent available evidence. The article aims to provide rheumatologists, gastroenterologists and dermatologists with practical guidance for choosing the most appropriate JAKi for each patient, given the lack of evidence-based recommendations on this topic, to improve clinical outcomes. Due to its preferential action on JAK1, intestinal metabolization and proven absence of impact on male fertility, filgotinib may be characterized by an improved benefit/risk ratio compared with other less selective JAKis.
Comparison of plant microbiota in diseased and healthy rice reveals methylobacteria as health signatures with biocontrol capabilities
Authors: Oeum Kakada , Suong Malyna , Uon Kimsrong , Jobert Léa , Bellafiore Stéphane , Comte Aurore , Thomas Emilie , Kuok Fidero , Moulin Lionel
Published: October 2024

Introduction

Rice (Oryza sativa) is a staple food worldwide, but its production is under constant pressure from both abiotic and biotic stresses, resulting in high use of agrochemicals. The plant microbiome harbours microorganisms that can benefit plant health and provide alternatives to the use of agrochemicals. The composition of plant microbiomes depends on many factors (soil composition, age, and health) and is considered a primary driver of future plant health. To identify plant microbiomes that protect against disease, we hypothesised that asymptomatic rice plants in fields under high pathogen pressure (i.e., healthy islands of plants among predominantly diseased plants) might harbour a microbiota that protects them from disease.

Material and Methods

We sampled healthy and leaf-diseased plants in rice fields with high disease incidence in Cambodia and profiled their microbiota at leaf, root, and rhizosphere levels using 16S V3V4 and 18S V4 amplicon barcoding sequencing.

Results

Comparison of amplicon sequence variants (ASV) of the microbiota of healthy and diseased samples revealed both disease and healthy signatures (significant enrichment or depletion at ASV/species/genus level) in both fields. The genera Methylobacterium and Methylorubrum were identified health taxa signatures with several species significantly enriched in healthy leaf samples (Methylobacterium indicum, Methylobacterium komagatae, Methylobacterium aerolatum, and Methylorubrum rhodinum). A cultivation approach on rice samples led to the isolation of bacterial strains of these two genera, which were further tested as bioinoculants on rice leaves under controlled conditions, showing for some of them a significant reduction (up to 77%) in symptoms induced by Xanthomonas oryzae pv. oryzae infection.

Discussion

We validated the hypothesis that healthy plants in fields under high disease occurrence can host specific microbiota with biocontrol capacities. This strategy could help identify new microbes with biocontrol potential for sustainable rice production.
Diagnostic challenges in complicated case of glioblastoma
Authors: Aghova Tatiana , Lhotska Halka , Lizcova Libuse , Svobodova Karla , Hodanova Lucie , Janeckova Karolina , Vucinic Kim , Gregor Martin , Konecna Dora , Kramar Filip , Soukup Jiri , Netuka David , Zemanova Zuzana
Published: October 2024

Glioblastoma is the commonest primary malignant brain tumor, with a very poor prognosis and short overall survival. It is characterized by its high intra- and intertumoral heterogeneity, in terms of both the level of single-nucleotide variants, copy number alterations, and aneuploidy. Therefore, routine diagnosis can be challenging in some cases. We present a complicated case of glioblastoma, which was characterized with five cytogenomic methods: interphase fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, comparative genomic hybridization array and single-nucleotide polymorphism, targeted gene panel, and whole-genome sequencing. These cytogenomic methods revealed classical findings associated with glioblastoma, such as a lack of IDH and TERT mutations, gain of chromosome 7, and loss of chromosome 10. At least three pathological clones were identified, including one with whole-genome duplication, and one with loss of 1p and suspected loss of 19q. Deletion and mutation of the TP53 gene were detected with numerous breakends on 17p and 20q. Based on these findings, we recommend a combined approach to the diagnosis of glioblastoma involving the detection of copy number alterations, mutations, and aneuploidy. The choice of the best combination of methods is based on cost, time required, staff expertise, and laboratory equipment. This integrated strategy could contribute directly to tangible improvements in the diagnosis, prognosis, and prediction of the therapeutic responses of patients with brain tumors.
Experimental Analysis of Flow Separation Control by a Dielectric Barrier Discharge Plasma Actuator in Burst-in-Burst Actuation Mode
Authors: Viguera Rodrigo , Sasaki Yasuo , Nonomura Taku
Published: October 2024

This study investigated the effectiveness of a dielectric barrier discharge (DBD) plasma actuator operating in burst-in-burst (BIB) mode for flow separation control on a NACA 0015 airfoil. Time-resolved particle image velocimetry measurements were conducted at a Reynolds number of 66,000 and 13° angle of attack. Various BIB signal configurations were tested, with actuation periods of 70 ms and 150 ms, non-actuation periods ranging from 5 ms to 50 ms, and burst frequencies of 300 Hz and 600 Hz. Proper orthogonal decomposition was applied to analyze the flow field dynamics. The results showed that BIB actuation maintained flow attachment with reduced power consumption compared with continuous burst actuation. However, the effectiveness was highly sensitive to the BIB parameters, with some configurations failing to achieve consistent reattachment and becoming unstable. This study reveals complex interactions between actuation vortices and separation processes, highlighting both the potential and challenges of intermittent plasma actuation for efficient flow control.
Prevalence Rates and Predictors for Smoking Cigarettes Among Adolescents Attending School in Bissau, Guinea-Bissau
Authors: Gunnlaugsson Geir , Baldé Aladje , Jandi Zeca , Boiro Hamadou , Einarsdóttir Jónína
Published: October 2024

Substance use is a growing problem among young people in sub-Saharan Africa who increasingly adopt the habit of smoking cigarettes. The aim was to analyse prevalence rates and identify predictors for cigarette smoking among school-attending adolescents in Bissau, Guinea-Bissau. In June 2017, a survey questionnaire was implemented in 16 schools in a class-based, random sample of 2039 adolescents aged 14–19 (52% girls). The chi-square (p < 0.05) and odds ratios (OR) were calculated with 95% confidence intervals (CI). Potential explanatory variables for the dependent variables were introduced into a multinomial logistic regression model, and p-values were transformed to LogWorth values. The prevalence rate for lifetime smoking experience was 14.8%, 4.0% for occasional smoking (<30 days), and 2.4% for daily smoking. The most significant predictors for cigarette smoking included having friends who smoke, being a boy, attending a private school, smoking initiation at a young age, other substance use, and violent behaviour. It is imperative to initiate preventive actions against smoking and other use of tobacco in Guinea-Bissau. Considering the significant impact of the peer group, policymakers need to engage young people in developing primary prevention strategies to curb the use of tobacco and other substances.
Aviation-BERT-NER: Named Entity Recognition for Aviation Safety Reports
Authors: Chandra Chetan , Ojima Yuga , Bendarkar Mayank V. , Mavris Dimitri N.
Published: October 2024

This work introduces Aviation-BERT-NER, a Named Entity Recognition (NER) system tailored for aviation safety reports, building on the Aviation-BERT base model developed at the Georgia Institute of Technology’s Aerospace Systems Design Laboratory. This system integrates aviation domain-specific data, including aircraft types, manufacturers, quantities, and aviation terminology, to identify named entities critical for aviation safety analysis. A key innovation of Aviation-BERT-NER is its template-based approach to fine-tuning, which utilizes structured datasets to generate synthetic training data that mirror the complexity of real-world aviation safety reports. This method significantly improves the model’s generalizability and adaptability, enabling rapid updates and customization to meet evolving domain-specific requirements. The development process involved careful data preparation, including the synthesis of entity types and the generation of labeled datasets through template filling. Testing on real-world narratives from the National Transportation Safety Board (NTSB) database highlighted Aviation-BERT-NER’s robustness, with a precision of 95.34%, recall of 94.62%, and F1 score of 94.78% when evaluated over 50 manually annotated (BIO tagged) paragraphs. This work addresses a critical gap in English language NER models for aviation safety, promising substantial improvements in the analysis and understanding of aviation safety reports.
Carbon and Nitrogen Mineralization of Common Organic Amendments in Olive Grove Soils
Authors: Domouso Pablo , Pareja-Sánchez Evangelina , Calero Julio , García-Ruiz Roberto
Published: October 2024

Cover crops (CC), pruning residues (PR), and olive mill pomace (OP) are common amendments to enhance soil quality in olive groves; however, there is limited information on the dynamics of carbon (C) and nitrogen (N) during their decomposition under varying conditions. In this laboratory decomposition experiment, we assessed the C and N mineralization of CC, PR, and OP at application rates of 2 and 5 mg C g−1 in soils with varying organic C levels, both with and without the addition of NO3−. The results indicated that C and N mineralization patterns varied significantly between amendments, although the predicted remaining C after one year was similar for CC and PR (46.7–48.9%) and slightly lower for OP (40.0%). Soil organic carbon level did not affect remaining amendment-C. The addition of N accelerated the decomposition rate of labile C by 15% but slowed down that of the recalcitrant C another 13%, with no significant effect on remaining C. Conversely, increasing the C dose led to a 13% overall reduction in amendment-C mineralization across all combinations of factors. CC decomposition released between −8 and 31% of the amendment-N by day 130, while PR and OP showed net N immobilization. Therefore, CC residues contribute to both C sequestration and N availability, while PR and OP residues can improve N retention in the olive groves while also contributing to C sequestration.
Solar Dryers: Technical Insights and Bibliometric Trends in Energy Technologies
Authors: Villagran Edwin , Espitia John Javier , Velázquez Fabián Andrés , Rodriguez Jader
Published: October 2024

This review article provides a comprehensive analysis of the technical advancements and research trends in solar drying technologies for agricultural products. The study encompasses various innovations in energy storage systems, including phase change materials (PCMs) and the use of computational fluid dynamics (CFD) for optimizing the drying process. Through a bibliometric analysis of 126 scientific papers published between 1984 and 2024, five major research clusters were identified: energy generation, heat transfer, thermal storage, simulation modeling, and the integration of hybrid systems. The results demonstrate a marked increase in scientific output over the past decade, emphasizing a growing interest in the sustainable use of solar energy for drying applications. Key findings highlight that while PCM-based storage solutions significantly enhance the thermal stability of dryers, the high implementation costs and technical complexities limit their adoption, especially in small-scale operations. Similarly, CFD models have proven effective in optimizing air and temperature distribution within dryers; however, their performance is hindered by real-world fluctuations in solar radiation and humidity levels. To address these limitations, future research should focus on the development of cost-effective PCM materials and the improvement of CFD models for dynamic environmental conditions. The review concludes by emphasizing the importance of interdisciplinary collaboration in the design and application of these technologies, recommending the inclusion of real-world case studies to better illustrate the practical implications and economic benefits of solar drying technologies for agricultural production.
Transcriptomic Analysis Reveals the Molecular Defense Mechanisms of Poa pratensis Against Powdery Mildew Fungus Blumeria graminis f. sp. Poae
Authors: Xu Zhiyu , Guo Zhanchao , Wu Fan , Zhang Yining , Zhao Yumin , Han Lingjuan , Gao Peng , Zhu Huisen , Xu Qingfang , Zhao Xiang , Liang Yinping
Published: October 2024

Kentucky bluegrass (Poa pratensis L.) is a valuable cool-season turfgrass widely utilized for forage, turf, and ecological purposes; however, its productivity and ornamental value are significantly compromised by powdery mildew, caused by Blumeria graminis f. sp. Poae, which negatively affects turf quality. In the present study, we examined the interactions between P. pratensis varieties and B. graminis, focusing on primary haustorium formation at 24 h post-inoculation and the formation of germ tubes at 48 h post-inoculation. We explored the molecular mechanisms underlying the response of different P. pratensis varieties at 48 h post-inoculation via transcriptomic techniques. Our results revealed that the primary haustorium formation rate in ‘Taihang’ at 24 h after B. graminis inoculation was significantly lower than that in ‘Explorer’ and ‘Black Jack’. The conidia of B. graminis could form two to five germ tubes, and the proportion of conidia that formed five germ tubes in ‘Taihang‘ at 48 h post-inoculation was significantly lower than that in the other two varieties. Transcriptome analysis revealed 680,765 transcripts as unigenes. A total of 9983 unigenes were identified as differentially expressed genes in one or more varieties of P. pratensis after inoculation with powdery mildew compared with the control. In total, 6284 differentially expressed genes were upregulated in ‘Taihang’, which was substantially greater than those in ‘Black Jack’ (4530) and ‘Explorer’ (4666). Moreover, 2843 differentially expressed genes were specific to ‘Taihang’, whereas 1644 and 1590 unique differentially expressed genes were specific to ‘Explorer’ and ‘Black Jack’, respectively. The specifically expressed genes play crucial roles in determining the disease resistance of powdery mildew. Notably, the expression of genes encoding chitinase, gamma-glutamyltranspeptidase 1, UDP-arabinopyranose mutase 1, oxalate oxidase 2, mitogen-activated protein kinase kinase 1-like, tryptophan decarboxylase, and aromatic L-amino acid decarboxylase was closely related to powdery mildew resistance in ‘Taihang’, making them promising candidate genes for studying resistance to powdery mildew in P. pratensis. This study identified critical genes involved in powdery mildew resistance in P. pratensis, providing a basis for future gene mining and molecular breeding to increase disease resistance in P. pratensis.
Hybrid Artificial Intelligence Strategies for Drone Navigation
Authors: San-Segundo Rubén , Angulo Lucía , Gil-Martín Manuel , Carramiñana David , Bernardos Ana M.
Published: October 2024

Objective: This paper describes the development of hybrid artificial intelligence strategies for drone navigation. Methods: The navigation module combines a deep learning model with a rule-based engine depending on the agent state. The deep learning model has been trained using reinforcement learning. The rule-based engine uses expert knowledge to deal with specific situations. The navigation module incorporates several strategies to explain the drone decision based on its observation space, and different mechanisms for including human decisions in the navigation process. Finally, this paper proposes an evaluation methodology based on defining several scenarios and analyzing the performance of the different strategies according to metrics adapted to each scenario. Results: Two main navigation problems have been studied. For the first scenario (reaching known targets), it has been possible to obtain a 90% task completion rate, reducing significantly the number of collisions thanks to the rule-based engine. For the second scenario, it has been possible to reduce 20% of the time required to locate all the targets using the reinforcement learning model. Conclusions: Reinforcement learning is a very good strategy to learn policies for drone navigation, but in critical situations, it is necessary to complement it with a rule-based module to increase task success rate.
The Analyst’s Hierarchy of Needs: Grounded Design Principles for Tailored Intelligence Analysis Tools
Authors: Girona Antonio E. , Peters James C. , Wang Wenyuan , Crouser R. Jordan
Published: October 2024

Intelligence analysis involves gathering, analyzing, and interpreting vast amounts of information from diverse sources to generate accurate and timely insights. Tailored tools hold great promise in providing individualized support, enhancing efficiency, and facilitating the identification of crucial intelligence gaps and trends where traditional tools fail. The effectiveness of tailored tools depends on an analyst’s unique needs and motivations, as well as the broader context in which they operate. This paper describes a series of focus discovery exercises that revealed a distinct hierarchy of needs for intelligence analysts. This reflection on the balance between competing needs is of particular value in the context of intelligence analysis, where the compartmentalization required for security can make it difficult to group design patterns in stakeholder values. We hope that this study will enable the development of more effective tools, supporting the well-being and performance of intelligence analysts as well as the organizations they serve.
Joint Genomic and Transcriptomic Analysis Reveals Candidate Genes Associated with Plumage Color Traits in Matahu Ducks
Authors: Ren Pengwei , Yang Liu , Khan Muhammad Zahoor , Jing Yadi , Zhang Meixia , Qi Chao , Zhang Xin , Liu Xiang , Liu Zhansheng , Zhang Shuer , Zhu Mingxia
Published: October 2024

Plumage color is a key trait for identifying waterfowl breeds with significant economic importance. A white-feathered group has recently emerged within the native Matahu duck population, presenting an opportunity for breeding new lines. However, the genetic basis for this plumage variation is still unknown, necessitating further research. This study aims to identify the genetic mechanisms underlying the emergence of white-feathered individuals in the Matahu duck population through combined genome and transcriptome analysis, providing insights for selective breeding and the development of new white-feathered lines. In this study, a total of 1344 selected genes and 1406 significantly differentially expressed genes were identified through selection signal analysis and transcriptomic analysis, respectively. The functional enrichment of these genes revealed several key signaling pathways, including those related to cGMP-PKG, cAMP, PI3K-Akt, and MAPK. Furthermore, important candidate genes involved in melanin biosynthesis, such as MITF, MC1R, TYR, TYRP1, and ABCB6, were identified. Notably, 107 genes were detected by both methods, and, among these, DGKI, GPRC5B, HMX1, STS, ADGRA1, PRKAR2B, and HOXB9 are suggested to play a role in melanin formation and potentially influence plumage traits. Through the integrative approach combining genomic selection signals and transcriptomic analyses, we identified several candidate genes directly associated with plumage color, including MITF, TYR, TYRP1, and MC1R, along with multiple signaling pathways linked to melanin formation. We hypothesize that the expression of DGKI, GPRC5B, HMX1, STS, ADGRA1, PRKAR2B, and HOXB9, detected by both methods, may be closely related to the regulation of plumage color traits. These findings provide a foundational basis for further research aimed at elucidating the genetic mechanisms governing plumage color variation in ducks.
The Adoption Potential of Extended Lactation as a Strategy to Reduce Excess Calf Numbers in Dairy Farming
Authors: Gresham Josephine , Reiber Christoph , Chagunda Mizeck G. G.
Published: October 2024

Dairy production relies predominantly on a few, selectively bred, high-yielding dairy breeds, resulting in a surplus of low-value male offspring. This situation leads to a conflict between a growing demand for milk and low appreciation for dairy calves. Extending lactation could reduce the number of calves born. This study aimed to assess the current use of extended lactation in dairy production in Southern Germany, identify the perceived potential, and determine the biological potential extended lactation has to reduce calf numbers. A survey from 2020 with 310 farmers was analysed. A total of 145 (46.8%) farmers used extended lactation. The use of extended lactation on farms correlated significantly with breed, milk yield, interest in continuing or implementing the use of extended lactation, and the indicated feasibility of extended lactation. The perceived potential was assessed by 39.8% of farmers as “high” to “very high”. A total of 17 (12.8%) farmers currently not using extended lactation were identified as potential adopters. Together with existing adopters, this could result in 52.3% of farms using extended lactation, which could biologically reduce calf numbers by 7.3% or 14.1% p.a., when extended by three or six months, respectively. This adoption potential shows that extended lactation can reduce calf numbers considerably, addressing both ethical and economic concerns in dairy farming and benefiting farmers as well as society.
Behavioral Nudges to Encourage Appropriate Antimicrobial Use Among Health Professionals in Uganda
Authors: Ross Allison , Meacham Philip J. , Waswa J. P. , Joshi Mohan P. , Hafner Tamara , Godby Sarah , Johnson Courtney , Londhe Shilpa , Aibo Dorothy , Kwikiriza Grace , Kasujja Hassan , Kiggundu Reuben , Cho Michelle , Kovar Sarah , Kitutu Freddy Eric
Published: October 2024

Background/Objectives: Antimicrobial resistance (AMR) is a global public health concern exacerbated by inappropriate antimicrobial prescribing practices, particularly in low-resource settings such as Uganda. The research aimed to develop a culturally sensitive behavioral intervention, leveraging a “nudge” strategy, to improve healthcare provider adherence to the 2016 Uganda Clinical Guidelines (UCG 2016) in five Ugandan hospitals. This intervention formed part of broader antimicrobial stewardship initiatives led by the United States Agency for International Development Medicines, Technologies, and Pharmaceutical Services Program. Methods: This study employed a mixed-methods approach, combining formative research and behavioral intervention. Guided by the Deloitte Behavioral Insights Framework, the research team conducted key informant interviews to identify prescribing barriers and motivators and developed three suitable behavioral interventions: perceived monitoring, ward leaderboards, and educational workshops. The study evaluated the interventions’ impact through point prevalence surveys (PPS), using the World Health Organization PPS methodology at three stages: pre-intervention, immediate post-intervention, and one-month post-intervention. Results: Key behavioral themes across individual, social, environmental, and organizational elements informed the intervention design and implementation. The behavioral intervention package increased antimicrobial prescription compliance with the UCG 2016 from 27% at baseline to 50% immediately post-intervention, though these effects diminished at one-month post-intervention. Conclusions: Our study addresses an existing gap in behavioral nudges-based operational research on antimicrobial prescribing in low- and middle-income countries. These results showed an immediate improvement in adherence to the UCG 2016 among healthcare providers in Ugandan hospitals, though the effect was attenuated at one-month follow-up. Despite the attenuation, behavior change presents a feasible, cost-effective, and sustainable approach to improving antimicrobial prescribing practices and addressing AMR.
Synthesis and Antibacterial Activity of Alkylamine-Linked Pleuromutilin Derivatives
Authors: Hainsworth Kerrin , Cadelis Melissa M. , Rouvier Florent , Brunel Jean Michel , Copp Brent R.
Published: October 2024

In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines 16, 17, 18, and 22, as well as two unusual amine-linked bis-pleuromutilin examples 20 and 23, displayed variable levels of activity towards Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus, but with no detectable activities towards Gram-negative bacteria. Fortunately, the incorporation of a longer-chain triamine or polyamine (spermine) at C-22 did afford analogues (30, 31) that exhibited activity towards both S. aureus ATCC 25923 and Escherichia coli ATCC 25922 with MIC 6.1–13.4 µM. Spermine–pleuromutilin analogue 31 was also able to enhance the action of doxycycline towards Pseudomonas aeruginosa ATCC 27853 by eight-fold, highlighting it as a useful scaffold for the development of new antibacterial pleuromutilin analogues that exhibit a broader spectrum of activity.
The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity
Authors: Kowalczyk Adam , Tuberoso Carlo Ignazio Giovanni , Jerković Igor
Published: October 2024

Rosmarinic acid (RA), a polyphenolic compound found in herbs, such as rosemary, basil, and mint, has garnered significant attention due to its potent antioxidant and anticancer properties. This review examined the molecular mechanisms underlying these properties and their potential application in cancer prevention and therapy. It focuses specifically on RA’s role in modulating cancer-related pathways and presents a detailed analysis of recent advancements in this area. A systematic review of PubMed, Scopus, and Web of Science databases was conducted in accordance with PRISMA (Reporting Items for Systematic Reviews and Meta-Analysis) guidelines, focusing on studies published between 2019 and 2024. A total of 25 articles providing evidence from in vitro, in vivo, and in silico studies were selected. These findings elucidate the role of RA in inhibiting tumor cell proliferation, inducing apoptosis, and preventing metastasis in various types of cancer through diverse mechanisms, including its antioxidant properties. Despite these promising results, RA’s bioavailability challenges limit its therapeutic efficacy, underscoring the necessity for improved delivery methods. This review concludes that RA exhibits significant potential as a natural agent for cancer prevention and treatment, although further clinical trials are warranted.
Effects of Nitrite Stress on the Antioxidant, Immunity, Energy Metabolism, and Microbial Community Status in the Intestine of Litopenaeus vannamei
Authors: Duan Yafei , Zhong Guowei , Nan Yuxiu , Yang Yukai , Xiao Meng , Li Hua
Published: October 2024

Nitrite is the main environmental pollutant that endangers shrimp culture. Intestinal health is essential for the disease resistance of shrimp. In this study, Litopenaeus vannamei shrimps were separately exposed to 1 and 5 mg/L of nitrite stress for 48 h, and then the variations in intestinal health were investigated from the aspects of histology, antioxidant, immunity, energy metabolism, and microbial community status. The results showed that nitrite stress damaged intestinal mucosa, and 5 mg/L of nitrite induced more obvious physiological changes than 1 mg/L. Specifically, the relative expression levels of antioxidant (ROMO1, Nrf2, SOD, GPx, and HSP70), ER stress (Bip and XBP1), immunity (proPO, Crus, ALF, and Lys), inflammation (JNK and TNF-α), and apoptosis (Casp-3 and Casp-9) genes were increased. Additionally, intestinal energy metabolism was activated by inducing glucose metabolism (HK, PK, PDH, and LDH), lipid metabolism (AMPK and FAS), tricarboxylic acid cycle (MDH, CS, IDH, SDH, and FH), and electron transfer chain (NDH, CytC, COI, CCO, and AtpH) gene transcription. Further, the homeostasis of intestinal microbiota composition was also disturbed, especially the abundance of some beneficial genera (Clostridium sensu stricto 1, Faecalibacterium, Romboutsia, and Ruminococcaceae UCG-010). These results reveal that nitrite stress could damage the intestinal health of L. vannamei by destroying mucosal integrity, inducing oxidation and ER stress, interfering with physiological homeostasis and energy metabolism, and disrupting the microbial community.
Hyperbaric Oxygen Improves Cognitive Impairment Induced by Hypoxia via Upregulating the Expression of Oleic Acid and MBOAT2 of Mice
Authors: Li Zhen , Fu Jun , Jiang Kaiyuan , Gao Jie , Guo Yuejun , Li Chen , Zhao Liangcai , Nam Jutaek , Gao Hongchang
Published: October 2024

Cognitive impairment (CI) causes severe impairment of brain function and quality of life of patients, which brings a great burden to society. Cerebral hypoxia is an important factor in the pathogenesis of CI. Hyperbaric oxygen (HBO) therapy may mitigate hypoxia-induced CI, but its efficacy and mechanisms are not fully understood. In this study, a mice model of CI induced by hypoxia environment was established, then behavioral tests, pathological examination, metabolomic and lipidomic analyses, and molecular biology were used to assess the impact of HBO on hypoxia-induced CI. HBO was found to alleviate CI and pathological damage of hypoxia mice. Metabolomic, lipidomic, and molecular biology analyses showed that HBO increased the levels of oleic acid (OA) and membrane-bound O-acyltransferase 2 (MBOAT2), thereby altering the composition of membrane phospholipids (PLs) and reducing hypoxia-induced neuronal ferroptosis (FPT) to interfere with cognitive function in mice. In vitro experiments confirmed that OA and MBOAT2 led to membrane PL remodeling in a mutually dependent manner, affecting cell resistance to hypoxia-FPT. The results emphasized the combined effect value of OA and MBOAT2 in HBO for hypoxia-induced CI, and provided a novel perspective for the treatment of CI by HBO.
Concurrent Access Performance Comparison Between Relational Databases and Graph NoSQL Databases for Complex Algorithms
Authors: Lupu Elena , Olteanu Adriana , Ionita Anca Daniela
Published: October 2024

Databases are a fundamental element of contemporary software applications. The most widely used and recognized type in practice is the relational database, valued for its ability to store and organize data in tabular structures, its emphasis on data consistency and integrity, and its use of a standardized query language, SQL. However, with the rapid increase in both the volume and complexity of data, relational databases have recently encountered challenges in effectively modeling this expanding information. To address performance challenges, new database systems have emerged, offering alternative approaches to data modeling—these are known as NoSQL databases. In this paper, we present an indoor navigation application designed to operate on both a relational database, Microsoft SQL Server, and a graph-based NoSQL database, Neo4j. We describe the algorithms implemented for testing and the performance metrics analyzed to draw our conclusions. The results revealed Neo4j’s strength in managing data with complex relationships but also exposed its limitations in handling concurrent access, where SQL Server demonstrated significantly greater stability.
Topological Defect Evolutions Guided by Varying the Initial Azimuthal Orientation
Authors: Shen Yanchun , Wu Jinbing , Wang Jingge , Wu Saibo , Hu Wei
Published: October 2024

Topological defects are a key concern in numerous branches of physics. It is meaningful to exploit the topological defect evolutions during the phase transitions of condensed matter. Here, via varying the initial azimuthal orientation of the square alignment lattice in a hybrid cell, the topological defect evolution of liquid crystal during the nematic (N)–smectic A (SmA) phase transition is investigated. The director fields surrounding ±1 point defects are manipulated by predesigning the initial azimuthal orientation. When further cooled to the SmA phase, spiral toric focal conic domain (TFCD) arrays are formed as a result of twisted deformation suppression and unique symmetry breaking after the phase transition. The variation in the azimuthal orientation causes the TFCDs to degenerate from infinite rotational symmetry to quadruple rotational symmetry, thus releasing new textures for the SmA phase. Landau–de Gennes numerical modeling is adopted to reproduce the director distributions in the N phase and reveal the evolution of the topological defects. This work enriches the knowledge on the self-organization of soft matter, enhances the capability for the manipulations of topological defects, and may inspire new intriguing applications.
WGAN-Based Realization Process of Gravel Soil for Hydraulic Property Simulation
Authors: Zhu Bin , Hu Xiang-Gang
Published: October 2024

Gravel soil faces significant engineering challenges such as leakage erosion and soil flow due to its complex composition and susceptibility to groundwater effects. This study integrates the entire machine learning process, including pre- and post-processing of images, WGAN implementation, and validation of hydraulic and morphological properties. Obtaining intact gravel soil samples is difficult and costly due to their erodible nature in the Li River, China. A μ-CT scanning series is employed to capture detailed images with three microstructural characteristics of gravel soil, forming the basis for training datasets using WGANs. This approach allows the generation of similar 3D realizations that replicate the microstructural characteristics and hydraulic behaviors of a prototype of gravel soils. Through computational fluid dynamics (CFD) simulations, the effectiveness of the realizations in hydraulic behavior within reconstructed porous structures is verified. This process indirectly validates the consistency between the realization′s microstructure and the prototype. This integrated methodology not only enhances understanding but also aids in the optimization of engineering designs and applications in geotechnical and materials science disciplines.
Catalytic Hydrothermal Treatment for the Recycling of Composite Materials from the Aeronautics Industry
Authors: Vázquez-Fernández José M. , Abelleira-Pereira José M. , García-Jarana Belén , Cardozo-Filho Lucio , Sánchez-Oneto Jezabel , Portela-Miguélez Juan R.
Published: October 2024

Epoxy resin composite matrices reinforced with carbon fibers are highly demanded by certain industries such as the aeronautics industry because of their exceptional mechanical properties. Unfortunately, the use of reinforcing carbon fibers makes these composite materials hard to recycle by conventional methods. Therefore, in this study, specific hydrothermal treatments have been employed to recover carbon fibers from the offcuts of composite parts from the aeronautics industry. The resin decomposition rates (DRs) achieved by different settings of the operating parameters, such as the use of alkaline catalysts (KOH, NaOH, or K2CO3), the application of mechanical stirring, the use of different reaction times, the solvent volume/composite mass ratio, the specific surface area (surface area/mass) of the composite pieces, and the operating temperature and pressure (subcritical or supercritical conditions), have been examined and assessed. Under the conditions that have been evaluated, resin decomposition rates nearly as high as 98% have been achieved, while the recycled fibers retained over 95% of their original tensile strength (TS).
A Privacy-Preserving Scheme for a Traffic Accident Risk Level Prediction System
Authors: Marcillo Pablo , Suntaxi Gabriela , Hernández-Álvarez Myriam
Published: October 2024

Due to the expansion of Artificial Intelligence (AI), especially Machine Learning (ML), it is more common to face confidentiality regulations about using sensitive data in learning models generally hosted in cloud environments. Confidentiality regulations such as HIPAA and GDPR seek to guarantee the confidentiality and privacy of personal information. Input and output data of a learning model may include sensitive data that must be protected. Adversaries could intercept and exploit this data to infer more sensitive data or even to determine the structure of the prediction model. To guarantee data privacy, one option could be encrypting data and making inferences over encrypted data. This strategy would be challenging for learning models that now must receive encrypted data, make inferences over encrypted data, and deliver encrypted data. To address this issue, this paper presents a privacy-preserving machine learning approach using Fully Homomorphic Encryption (FHE) for a model that predicts risk levels of suffering a traffic accident. Despite the limitations of experimenting with FHE on machine learning models using a low-performance computer, limitations that are undoubtedly overcome by using high-performance computational infrastructure, we built some encrypted models. Among the encrypted models based on Decision Trees, Random Forests, XGBoost, and Fully Connected Neural Networks (FCNN), the model based on FCNN reached the highest accuracy (80.1%) for the lowest inference time (8.476 s).
A Comparative Analysis of Active Control vs. Folding Wing Tip Technologies for Gust Load Alleviation
Authors: Toffol Francesco
Published: October 2024

As part of the Ultra High Aspect Ratio Wing Advanced Research and Designs (U-HARWARD) project, funded by CS2JU, various gust load alleviation (GLA) technologies have been developed and studied. GLA plays a crucial role in the development of new generation ultra-high aspect ratio wings (UHARWs), as it reduces gust loads, thereby decreasing the structural weight of the wing and, consequently, the entire aircraft. This weight reduction enhances overall aircraft efficiency, enabling a higher aspect ratio. GLA technologies are categorized into passive systems, which require no active intervention, and active systems, where control surfaces redistribute the aerodynamic loads. In this study, passive GLA was implemented using a folding wing tip (FWT) developed by the University of Bristol, while active GLA employed a Static Output Feedback controller developed by Politecnico di Milano. Both approaches were compared against a baseline aircraft configuration. A flutter assessment confirmed that FWT does not introduce aeroelastic instabilities, ensuring the aircraft remains flutter-free across its flight envelope. A thorough comparison of load envelopes, based on nearly 2000 load cases across different flight points and mass configurations, was conducted in compliance with CS25 regulations, examining both positive and negative gust conditions. The results show a possible 15% reduction in the dynamic load envelope for both passive and active solutions. Using NeOPT, a hybrid finite element (FE) model was developed, with a detailed global FEM (GFEM) for the wingbox and stick elements for other components. Linear gust analyses in Nastran, with the hinge locked and released, provided high-fidelity results, comparing wing failure indexes and demonstrating the effectiveness of the FWT solution.
Environmental Pollution and Oxidative Stress: Health Effects During Pregnancy: A Review
Authors: Itziou Aikaterini , Balis Vasileios , Lakioti Evangelia , Karayannis Vayos , Tsanaktsidis Constantinos
Published: October 2024

Oxidative stress is an imbalance between reactive oxygen species production and antioxidant defense that can lead to reproductive disorders and poor pregnancy outcomes. Environmental pollution under climate change is involved in reactive oxygen species formation and may cause various dysfunctions of the reproductive system. Oxidative stress is a widespread factor that affects the physiology of the male and female reproductive systems, leading to high levels of DNA damage and infertility. Miscarriage, preeclampsia, and premature birth are all linked to oxidative stress. Environmental pollution induces excesses of oxidative stress by expanding ROS generation or overwhelming the physiological responses of the antioxidant defense system. This increases cellular damage, inflammation, and the development of numerous diseases. Here, we present a brief outline of the physiological and developmental roles that oxidative stress plays during pregnancy. We also offer some insights into the underlying mechanisms that have been put forth, which culminate in a summary of the harmful effects of oxidative stress that have an environmental origin in pregnancy-related complications. The current work may motivate the design of more focused wellbeing measures in order to prevent and promote human health and anticipate unfavorable pregnancy outcomes.
Analysis of 3D Printed Dielectric Resonator Antenna Arrays for Millimeter-Wave 5G Applications
Authors: Li Siyu , Sanz Izquierdo Benito , Gao Steven , Chen Zhijiao
Published: October 2024

This paper explores the potential use of fused deposition modeling (FDM) technology for manufacturing microwave and millimeter-wave dielectric resonator antennas (DRAs) for 5G and beyond communication systems. DRAs operating at microwave and millimeter-wave (mmWave) frequency bands were simulated, fabricated, and analyzed in terms of manufacturing quality and radio frequency (RF) performance. Samples were manufactured using a 3D printer and PREPERM® ABS1000 filament, which offers a stable dielectric constant (εr = 10 ± 0.35) and low losses (tan δ = 0.003) over wide frequency and temperature ranges. Surface profile tests and microscope measurements revealed discrepancies in the dimensions in the xy-plane and along the z-axis, consistent with the observed shift in resonant frequency. Despite these variations, reasonably good agreement between RF-simulated and measured results was achieved, and the DRA array successfully covered the intended mmWave band. However, challenges in achieving high precision may restrict applications at higher mmWave bands. Nevertheless, compared with conventional methods, FDM techniques offer a highly accessible and flexible solution with a wide range of materials for home and micro-manufacturing of mmWave DRAs for modern 5G systems.