bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear transient dynamic responses of a rotating composite blade with graphene coating layers
Authors: Bai Bin , Li Han
Published: January 2024

The higher demands on the performance and efficiency of rotating machinery have led to an urgent demand for advanced composite materials and new structures in recent years. In response to this requirement, a rotating sandwich plate model based on the first-order shear deformation theory is developed to investigate the nonlinear transient dynamic response of a rotating composite blade with graphene reinforced composite coating layers under the pulse load. In this work, three kinds of pulse loads, including the step load, sinusoidal load and air blast load, are considered. The material properties of graphene coating layers are estimated based on the modified Halpin-Tsai micromechanical model. Considering the geometric nonlinearity, the nonlinear partial differential governing equations of motion for the rotating composite blade are derived via the Hamilton principle. According to the Galerkin method, the nonlinear partial differential governing equations of motion are discretized into the nonlinear ordinary differential governing equations. A comprehensive parameter study is performed to explore the effects of the blade aspect ratio, graphene platelet (GPL) geometry, GPL weight fraction, rotating speed, damping, and excitation parameter on nonlinear transient dynamic responses of the rotating composite blade. In addition, the effect of the GPL weight fraction on nonlinear transient dynamic responses of the rotating composite blade at different rotational speeds is also discussed. The verification study demonstrates that the developed model can predict the nonlinear transient dynamic response of the rotating composite blade with graphene coating layers, which will be helpful for the design of the rotating blade with higher performance.
Agonist-selective activation of individual G-proteins by muscarinic receptors
Authors: Janouskova-Randakova Alena , Nelic Dominik , Chetverikov Nikolai , Hochmalova Martina , Diaz Christina , Doležal Vladimír , Boulos John , Jakubik Jan , Martemyanov Kirill
Published: January 2024

Selective activation of individual subtypes of muscarinic receptors is a promising way to safely alleviate a wide range of pathological conditions in the central nervous system and the periphery as well. The flexible G-protein interface of muscarinic receptors allows them to interact with several G-proteins with various efficacy, potency, and kinetics. Agonists biased to the particular G-protein mediated pathway may result in selectivity among muscarinic subtypes and, due to the non-uniform expression of individual G-protein alpha subunits, possibly achieve tissue specificity. Here, we demonstrate that novel tetrahydropyridine-based agonists exert specific signalling profiles in coupling with individual G-protein α subunits. These signalling profiles profoundly differ from the reference agonist carbachol. Moreover, coupling with individual Gα induced by these novel agonists varies among subtypes of muscarinic receptors which may lead to subtype selectivity. Thus, the novel tetrahydropyridine-based agonist can contribute to the elucidation of the mechanism of pathway-specific activation of muscarinic receptors and serve as a starting point for the development of desired selective muscarinic agonists.
Topical dorzolamide as adjunctive treatment with intravitreal bevacizumab in bilateral diabetic macular edema
Authors: Sadr Ata , Sargazi Meisam , Banaie Shahram , Asani Mahdi , Zamiri Seyedeh Sana , Mehrad-Majd Hassan , Mohammadi Seyed Omid , Maleki Ali-Reza
Published: January 2024

Background:
Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME.
Methods:
This randomized, double-blind, contralateral eye study included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first 3 months.
Results:
Among 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P>0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P>0.05). The present study showed a decrease in CMT in both study groups (P<0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P<0.001).
Conclusions:
The results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline but it did not have an additive effect on BCVA improvement Compared to IVB monotherapy.
Gender differences in the development of children’s conduct problems: A four-year longitudinal study
Authors: Álvarez-Voces María , Romero Estrella
Published: January 2024

Gender differences in the trajectories of conduct problems (CP) have received very little attention in the literature. The present four-year longitudinal study explores gender differences in CP trajectories through early childhood, assessing gender-specific predictors and outcomes. Gender-separated CP trajectories were identified in a sample of 2,246 young children (Mage=4.25; 48.53% girls) using latent class growth analyses (LCGA). Five trajectories were found in girls (i.e., low, average, downward, upward, and stable high) and four in boys (i.e., low, average, stable high, and upward). Low socioeconomic status was related to the most problematic trajectories only in boys, whereas the interpersonal psychopathic trait (grandiose-deceitful) was more pronounced in girls with higher CP scores relative to other psychopathic traits. Meanwhile, boys’ trajectories were more diverse in terms of negative outcomes (e.g., bullying, victimization) than those of girls. This study contributes to the body of work on heterogeneity in CP by identifying different trajectories according to gender, and shows the relevance of gender in understanding the predictors, development, and outcomes of CP.
Unlocking sustainable livestock production potential through paddock division and gender inclusivity
Authors: Castro Augusto , Buritica Alexander , Holmann Federico , Ngaiwi Mary , Quintero Marcela , Solarte Antonio , Gonzalez Carolina
Published: January 2024

Low-emissions livestock production can be achieved through scaling production systems integrating trees, forages, and livestock within the same area. Such systems are known as silvopastoral production systems (SPS). However, despite SPS reported benefits, adoption rates globally remain low. This paper, therefore, aims to inform land use policy oriented towards increasing SPS adoption. This study intends to capture this by assessing SPS adoption benefits, identifying determinants of SPS adoption, and thus to contribute to policy for scaling low-emissions livestock production. Data was collected on socioeconomic status, livestock farming technical and economic indicators, and farm and paddock practices through farm-level surveys in four municipalities in the Amazon Piedmont of Colombia. Unlike previous studies that assume homogeneous farm management, when in fact, it is heterogeneous, this study assessed SPS adoption determinants using the paddock (n = 2,819) as the unit of analysis. This methodological approach is consistent with paddock-level land use decisions taken by farmers based on socioeconomic and biophysical factors such as soil financial resources, type, and topography. The methodological approach allows us to provide new insights into the determinant of adopting SPS and an understanding of intra-farm level land use decisions. The results show that the adoption of SPS at both paddocks and farm levels in Caquetá is low. The main factors associated with higher SPS adoption levels at the paddock level are framed in gender, resources, and knowledge. We observe that women are more motivated to conserve the environment. Cattle paddocks managed by women, smaller in size, and those with more SPS-related projects show a tendency for medium or high SPS adoption. Furthermore, the positive relationship between access to credit and SPS adoption emphasizes the importance of financial resources tailored to SPS projects. Enhancing gender roles, improving access to finance in land use, and providing training programs on SPS systems can contribute to low-emission livestock production in Colombia. This research paper highlights the significance of implementing diverse management strategies and reaching out to farmers not involved in SPS projects. It emphasizes investments in low-emission livestock production, especially for female heads of households. This approach recognizes the broader benefits of SPS, beyond production and financial gains, promoting the division of paddocks and the adoption of SPS.
Development of Low Smoke Environmental friendly Fire Retardant Intumescent Coatings for GI and Steel Structures
Authors: Mehta Charu , Kumar Aravind , Tiwari Mahesh Kumar , Kumar Rakesh , Shoeb Mohammad Ahmad
Published: January 2024

Steel begins to lose its mechanical strength above 500 ºC and tends to distort, leading to the collapse of building structures during fire accidents. Fire retardant intumescent coating can protect the steel structure as it swells upon exposure to fire several times its original thickness producing a carbonaceous protective char. The carbonaceous char acts as a heat transfer barrier and protects the structure of steel physically and thermally The objective of the experimental work is to develop the composition of fire retardant intumescent coating with low smoke emission on reaction to fire. Specific fire retardant intumescent coatings were formulated with various compositions using additives (acid source, carbon source, and blowing agent), binder (water-based), and fillers. All the formulations were examined with the non-luminous premixed flame gas torch preliminary test, and the thickness of the char layer formed at the end of the experiment was observed and measured. It was observed that the composition formulated with a water-based binder can form a char layer of a maximum of 70 times the coating thickness. Various standard tests were performed to examine the water-based coating formulations. The results showed that coating composed of a water-based binder with a 50% addition of epoxy and hardener achieved the criteria of ignitability evaluation as per BS 476 Part 5 as it was not easily ignitible. Fire propagation index BS 476 Part 6 showed a Fire propagation index value of less than 12 which signifies that the heat generation rate was low. According to the surface spread of flame of products as per BS 476-Part 7, the coating was classified as class 1 as no flame spread was observed on the surface. Specific optical density value at 1.5 min was found to be less than 100 and less than 200 at 4 min as per ASTM E 662 which was meeting the criteria as per NFPA 230. Sample IC3 was found to nearly meet Non-combustibility criteria. It can be concluded that an environmental friendly fire retardant intumescent coating can be achieved with a water-based binder, additives, and fillers.
Damage resistance of calcium sulfoaluminate cement-based engineered cementitious composites (CSA-ECC) under vehicle-bridge coupling vibration
Authors: Liu Sijia , Yu Long , Xu Biwan , Yang Ken , Wang Shunfeng , Xu Linglin , Yang Zhenghong
Published: January 2024

This study aims to develop the calcium sulfoaluminate cement-based engineered cementitious composites (CSA-ECC) to enhance the resistance of newly placed concrete against vibration-induced damage during highway bridge widening. The effects of vehicle-bridge coupled vibration on the mechanical properties of CSA-ECC including compressive strength, flexural strength and flexural toughness were investigated. The results indicate that the volume percentage of coarse air bubbles (> 1.0 mm3) decreases from 54.70–25.94%, and the volume percentage of micro air bubbles (0-0.2 mm3) increases from 30.89–54.19%. As a result, the microstructure of matrix and fiber/matrix interface are densified due to the redistribution of air bubbles caused by the coupling vibration. Therefore, the application of vibration significantly enhances the flexural strength and flexural toughness of CSA-ECC, ascribing to stronger matrix fracture toughness and fiber/matrix interfacial frictional bond. The digital image correlation (DIC) analysis also indicates that vibration delays the occurrence of main cracking and leads to more obvious multi-cracking characteristics. These indicate that the CSA-ECC has a promising application scenario in highway bridge widening projects with exceptional vibration-induced damage resistance ability.
Super-Enhancers Orchestrate Transcriptional Dysregulation and Metabolic Reprogramming in Uveal Melanoma
Authors: Zhuang Ai , Pan Hui , Shao Weihuan , Wang Huixue , Ge Shengfang , Zhang Lingyu , Xu Xiaofang
Published: January 2024

Uveal melanoma (UM) is the most common intraocular malignancy which frequently metastasizes. Somatic mutations and chromatin aberrations have been identified in the pathogenesis of this deadly disease. Despite rapid progress in uveal melanoma genetic landscape, the epigenetic architecture in UM pathogenesis has not been fully clarified. Here, we describe a super enhancer-medicated epigenetic pipeline via genome-scale histone acetylation modification as well as transcriptional profiling. We first characterize an active landscape of super enhancer profiles in UM with ChIP-seq. We identify master transcription factors specifically driven by UM-specific super enhancers, and our pipeline unveils the transcription factor TFAP2A as the top essential regulator in UM, which is highly associated with metabolism and oncogenesis. TFAP2A occupies predicted super enhancers associated with the oncogene SLC7A8 in UM, thereby illuminating a mechanism for regulating oncogene expression. Collectively, our data illustrates epigenetic targeting of super enhancer-mediated oncogene addictions in UM, shedding light on an epigenetic vulnerability that can be targeted for precision therapy.
Athyrium yokoscense, a cadmium-hypertolerant fern, exhibits two cadmium stress mitigation strategies in its roots and aerial parts
Authors: Ukai Yuko , Taoka Hiroki , Kamada Manaka , Wakui Yuko , Goto Fumiyuki , Kitazaki Kazuyoshi , Abe Tomoko , Hokura Akiko , Yoshihara Toshihiro , Shimada Hiroaki
Published: January 2024

Athyrium yokoscense is hypertolerant to cadmium (Cd) and can grow normally under a high Cd concentration despite Cd being a highly toxic heavy metal. To mitigate Cd stress in general plant species, Cd is promptly chelated with a thiol compound and is isolated into vacuoles. Generated active oxygen species (ROS) in the cytoplasm are removed by reduced glutathione. However, we found many differences in the countermeasures in A. yokoscense. Thiol compounds accumulated in the stele of the roots, although a long-term Cd exposure induced Cd accumulation in the aerial parts. Synchrotron radiation-based X-ray fluorescence (SR-XRF) analysis indicated that a large amount of Cd was localized in the cell walls of the roots. Overexpression of AyNramp5a, encoding a representative Fe and Mn transporter of A. yokoscense, increased both Cd uptake and iron and manganese uptake in rice calli under the Cd exposure conditions. Organic acids were abundantly detected in A. yokoscense roots. Investigating the chemical forms of the Cd molecules by X-ray absorption fine structure (XAFS) analysis detected many compounds with Cd-oxygen (Cd-O) binding in A. yokoscense roots, whereas in the aerial parts, the ratio of the compounds with Cd-sulfur (Cd-S) binding was increased. Together, our results imply that the strong Cd tolerance of A. yokoscense is an attribute of the following two mechanisms: Cd-O compound formation in the cell wall is a barrier to reduce Cd uptake into aerial parts. Thiol compounds in the region of root stele are involved in detoxication of Cd by formation of Cd-S compounds.
Trends in the Geographic Inequality of Advanced Practice Nursing Workforce in Cancer Care in Japan from 1996 to 2022: A Panel Data Analysis
Authors: Tamaki Tomoko , Morioka Noriko , Machida Ako , Kashiwagi Masayo
Published: January 2024

Background

Cancer was ranked as the second leading cause of global mortality in 2019, with an increasing incidence. An adequate workforce of healthcare professionals with special skills and knowledge in cancer care is vital for addressing the disparities in cancer prognosis. This study aimed to elucidate the trends in the advanced practice nursing workforce (APNW) in cancer care, which included certified nurse specialists (CNSs) and certified nurses (CNs) in each prefecture of Japan from the system's inception to the present. Further, it sought to analyse the regional disparities and compare these trends with other healthcare resources to identifycontributing factors associated with the APNW in cancer care in each prefecture.

Methods

We performed a panel data analysis using publicly available data on the APNW in cancer care in each prefecture of Japan from 1996 to 2022. Gini coefficients were calculated to examine the trends in geographic equality. Univariate and multivariable fixed effect panel data regression models were used to examine regional factors associated with an APNW in cancer care.

Results

From 1996 to 2012, the APNW in cancer care increased from four to 6,982 staff, while their Gini coefficients decreased from 0.79 to 0.43. However, from 2012 to 2022, the Gini coefficientsdecreased slightly from 0.43 to 0.41. The coefficient value was comparable to that for the disparity between hospital doctors (0.43) but more pronounced compared to those for other medical resources, such as hospitals (0.34), hospital nurses (0.37), and designated cancer care hospitals (0.29). The APNW in cancer care in each prefecture was significantly associated with a higher number of hospital nurses (coefficient: 0.63, 95% confidence interval (CI): 0.23-1.03), a higher number of designed cancer care hospitals in the previous year (see first quartile, the coefficient for second quartile:0.31, 95% CI: 0.21–0.40), and a fewer number of hospital doctors (-1.89, 95%CI: -2.70 to -1.09).

Conclusions

The size of the APNW in cancer care has increased since the system was established in 1996 up till 2022. With the increase in numbers, geographic inequality narrowed until 2012 and has since then remained stagnant.
Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers
Authors: Chiarle Roberto , Cheong Taek-Chin , Jang Ahram , Wang Qi , Leonardi Giulia , Ricciuti Biagio , Alessi Joao , Federico Alessandro Di , Awad Mark , Lehtinen Maria , Harris Marian
Published: January 2024

Tyrosine kinase (TK) fusions are frequently found in cancers, either as initiating events or as a mechanism of resistance to targeted therapy. Partner genes and exons in most TK fusions are typical and recurrent, but the underlying mechanisms and clinical implications of these patterns are poorly understood. Here, we investigated structures of > 8,000 kinase fusions and explore their generative mechanisms by applying newly developed experimental framework integrating high-throughput genome-wide gene fusion sequencing and clonal selection called Functionally Active Chromosomal Translocation Sequencing (FACTS). We discovered that typical oncogenic TK fusions recurrently seen in patients are selected from large pools of chromosomal rearrangements spontaneously occurring in cells based on two major determinants: active transcription of the fusion partner genes and protein stability. In contrast, atypical TK fusions that are rarely seen in patients showed reduced protein stability, decreased downstream oncogenic signaling, and were less responsive to inhibition. Consistently, patients with atypical TK fusions were associated with a reduced response to TKI therapies, as well as a shorter progression-free survival (PFS) and overall survival (OS) compared to patients with typical TK fusions. These findings highlight the principles of oncogenic TK fusion formation and their selection in cancers, with clinical implications for guiding targeted therapy.
Cryosphere tipping elements decisive for tipping risks and cascading effects in the Earth system
Authors: Rosser Jonathan , Winkelmann Ricarda , Wunderling Nico
Published: January 2024

The Earth's climate system is a complex system that includes key components such as the Arctic Summer Sea Ice or the El Niño Southern Oscillation as well as climate tipping elements like the continental-scale ice sheets or the Amazon rainforest. Crossing warming thresholds of these elements can lead to a qualitatively different climate state, endangering the stability of human societies. Particularly, the cryosphere elements are vulnerable at current levels of global warming (1.2°C) while also having long response times and large structural uncertainties. Investigating a network of interacting Earth system components using an established conceptual model, we systematically assess which uncertainties of key Earth system component have the largest impacts on tipping risks. We find that the cryosphere tipping elements (the Greenland and the West Antarctica ice sheets) are most decisive for tipping risks and cascading effects within our model. At a global warming level of 1.5°C, neglecting the large cryosphere tipping elements can reduce the mean number of disintegrated Earth system components by as much as 56%. This is concerning as overshooting 1.5°C of global warming is fast becoming inevitable, while current state-of-the-art IPCC-type global circulation models do not (yet) include dynamic ice sheets. Our results suggest that urgent integrated Earth system model development and Earth observation efforts including the large polar ice sheets are necessary and a precautionary measure of meeting stringent climate targets is crucial to limit tipping risks.
Detection of viruses in special stands of common ash reveals insights into the virome of Fraxinus excelsior
Authors: Rehanek Marius , Kubrusli Rim Al , Köpke Kira , von Bargen Susanne , Büttner Carmen
Published: January 2024

We report the results of a virus screening conducted on selected special stands of common ash (Fraxinus excelsior) within the FraxVir project. This project among others deals with the recording and assessment of the virus diversity in common ash and the impact of the ash virome on ash dieback diseased trees. Ash dieback, a fungal disease caused by the invasive fungus Hymenoscyphus fraxineus is a major threat to Fraxinus excelsior populations across Europe. Over three consecutive years, ash trees from different origins were tested including leaf material from mother trees and seedlings from the natural regeneration as well as fruits to gain insight into possible modes of virus transmission. Using RT-PCR, we screened for five viruses, including the generalist species arabis mosaic virus and cherry leaf roll virus, as well as newly discovered viruses in ash including an emaravirus, an idaeovirus and viruses of the cytorhabdovirus group. Amplification and comparison of PCR amplicons comprising the nucleocapsid region revealed sequence diversities that confirm two distinct cytorhadovirus species present in different populations of common ash. Signatures of novel viruses from different families have been identified by high-throughput sequencing. Together our results provide insights into the virus diversity and distribution of viruses in ash and expand our knowledge about the virome of this endangered tree species.
Routing Networking Technology Based on Improved Ant Colony Algorithm in Space-Air-Ground Integrated Network
Authors: Nie Wuzhou , Chen Yong , Wang Yuhao , Wang Peizheng , Li Meng , Ning Lei
Published: January 2024

Space-Air-Ground Integrated networks comprise a multi-level heterogeneous integrated network that combines satellite-based, aerial, and terrestrial networks. With the increasing human exploration of space and growing demands for internet applications, Space-Air-Ground Integrated networks have gradually emerged as the direction for communication network development. These networks face various challenges such as extensive coverage, diverse communication node types, low-quality communication links, and simultaneous operation of multiple network protocols. However, the rapid development and widespread application of artificial intelligence and machine learning technologies in recent years have offered new perspectives and solutions for the communication architecture and routing algorithm research within Space-Air-Ground Integrated networks. In these networks, not all nodes can typically communicate directly with satellites; instead, a specific set of specialized communication nodes facilitates data communication between aerial and satellite networks due to their superior communication capabilities. Consequently, in contrast to traditional communication architectures, Space-Air-Ground Integrated networks, particularly in the terrestrial layer, often need to address challenges related to the diversity of communication node types and low-quality communication links. A well-designed routing approach becomes crucial in addressing these issues.
Therefore, this paper proposes an AODV routing network protocol based on an Improved Ant Colony Algorithm (AC-AODV), specifically designed for the terrestrial layer within the Space-Air-Ground Integrated networks. By integrating information such as the type, energy, and location of communication nodes, this protocol aims to facilitate network communication. The objective is to guide information flow through nodes that are more suitable for communication, either by relaying communication or by connecting with satellites through specialized nodes. This approach alleviates the burden on ordinary nodes within the terrestrial communication network, thereby enhancing the overall network performance. In this protocol, specialized nodes hold a higher forwarding priority than regular nodes. When a source node needs to transmit data, it enters the route discovery phase, utilizing its own type, location, and energy information as heuristic data to calculate forwarding probabilities. Subsequently, it broadcasts route request (RREQ) messages to find the path. Upon receiving the RREQ message, the destination node sends an RREP message for updating information elements and selects the optimal path based on these information elements. Compared to AODV, AC-AODV shows significant improvements in performance metrics such as transmission latency, throughput, energy conversion rate, and packet loss rate.
Preventive effect of Lactobacillus johnsonii YH1136 against uric acid accumulation and renal damages
Authors: Zhang Xingting , Sun Ning , Xin Jinge , Jiang Junliang , Gan Baoxing , Jiang Yi , Gong Xuemei , Zhao Zhifang , Chen Yu , Li Hao , Ma Hailin , Ni Xueqin , Bai Yang , Wang Hesong
Published: January 2024

Hyperuricemia (HUA) is a prevalent metabolic disorder globally, and its development is increasingly associated with intestinal microbiota. Therefore, probiotics have emerged as a potential and safe approach for lowering uric acid (UA) levels. However, effective probiotic strains and the underlying mechanism remain unknown. Therefore, this study aims to investigate microbiota alterations in each intestinal segment during HUA to identify the most affected segment and potential probiotic strains. Whole intestinal diversity was significantly decreased in the model group than in the control, with the most significant decrease in the cecum and colon. Firmicutes, Bacteroidota, and Actinobacteriota were the dominant phyla common to the control and model groups, whereas Bacteroidota was more dominant in the colon of the model group than in the control group. In the RDA analysis, Lactobacillus in the colon and the model group exhibited a strong correlation, suggesting that Lactobacillus may play an important role in HUA. Consequently, Lactobacillus johnsonii YH1136 was used to assess its preventive effects against HUA. The results showed that Lactobacillus johnsonii YH1136 administration effectively reduced serum UA levels in vivo, mainly inhibiting hepatic xanthine oxidas(XOD) activity and promoting renal ABCG2 transporter expression.Moreover, increased colonization using Lactobacillus johnsonii YH1136 significantly ameliorated pathological damage in the kidney and liver, causing UA accumulation. These findings highlight the potential significance of Lactobacillus as a connection between HUA and the gut microbiota, providing compelling evidence for Lactobacillus johnsonii YH1136 as a potential treatment for HUA.
The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates
Authors: Liddle Karen , Kriukelis Rebecca , Gabbett Michael , Beswick Rachael , McInerney-Leo Aideen , Driscoll Carlie
Published: January 2024

Guidelines recommend GJB2 (connexin 26) and GJB6 (connexin 30) testing for bilateral non-syndromic sensorineural hearing loss (SNHL). However, associated audiological phenotypes vary. There is limited Australian data on GJB2 variant frequency and associated phenotypes. Audiograms from a paediatric cohort with SNHL, predominantly identified through newborn hearing screening and carrying GJB2 variants and/or a GJB6 deletion (GJB6-D13S11830) were retrospectively reviewed (n = 127). Two thirds were homozygous or compound heterozygous for pathogenic or likely pathogenic variants of GJB2 and/or GJB6 (n = 80). The most frequent variant, c.109G > A, occurred in homozygous (n = 32), compound heterozygous (n = 8) and heterozygous (n = 5) states. Compared to homozygous/compound heterozygous carriage of other GJB2 variants, c.109G > A positive individuals (homozygous/compound heterozygous) were more likely to have mild HL at their initial (p = 0.00004) and latest audiograms (p = 0.0004). Homozygous/compound heterozygous carriage of c.35delG was associated with moderately-severe or greater HL at both initial (p = 0.007) and latest (p = 0.007) audiograms. The c.101T > C variant presented with milder HL and U-shaped audiograms (p = 0.02). In this agnostically identified cohort, mild HL predominated in GJB2/GJB6 carriers in contrast to previous studies targeting individuals with significant loss. Consequently, c.109G > A, associated with milder phenotypes, was the most frequent. This data provides valuable, balanced prognostic information for preconception, prenatal and paediatric counselling of couples and families carrying these variants.
Ceratocystis fimbriata causing canker and wilt disease on West Indian mahogany trees in Indonesia
Authors: MUSLIM A , Suwandi Suwandi , Pratama Rahmat , Gunawan Bambang
Published: January 2024

Between 2021 and 2023, a new disease affecting West Indian mahogany plants emerged in South Sumatra, Indonesia. The disease's incidence steadily increased, particularly in Palembang (Jakabaring), where it rose from 0.27–0.46%, and in Bukit Siguntang, increasing from 0–0.73%. In Ogan Ilir Regency (Universitas Sriwijaya), the incidence increased from 2.07–4.71%, and in Ogan Komering Ilir Regency (Celika) the incidence rose from 6.77–15.25%. Initial symptoms of this disease on the plant's stem included canker formation, gum exudation, vascular tissue discoloration, leaf wilting, and eventual plant death. The fungus was isolated from symptomatic vascular tree tissue and confirmed as a pathogen following Koch's postulates. Pathogen identification used a polyphasic approach, combining morphological and molecular characteristics from specific genomic regions (ITS and β-tubulin). Morphological traits and phylogenetic analysis identified the isolate as Ceratocystis fimbriata. Genomic sequences based on ITS revealed that the MHC2 isolate belonged to haplotype ITS7b, while the other four isolates (MHC1, MHC3, MHC4, and MHC5) were in haplotype ITS5. Thus far, C. fimbriata has not been identified as the cause of cankers and wilting in West Indian mahogany trees in Indonesia. Pathogenicity tests have demonstrated that the pathogen causes death in mahogany trees, as well as in Acacia, bullet wood, and jackfruit plants, indicating its potential to affect other agroforestry plants and pose a threat to the biodiversity of indigenous plants in South Sumatra, Indonesia.
A new model-based participatory approach to resolve land use competition in the energy transition: A case study of ground-mounted photovoltaics in a German municipality
Authors: Rösch Christine , Fakharizadehshirazi Elham
Published: January 2024

The German government requires states to set aside at least 2% of their land for renewable energy. Despite public support, the specific location of renewable energy installations is often debated. The study presents a new approach to resolving land use competition in the context of energy system transformation. Ground-mounted photovoltaics (GM PV) in a German municipality serves as a case study. Its methodology goes beyond standard socio-scientific methods. The innovation is the model-based spatial assessment of GM PV scenarios with different constraints and suitability criteria based on stakeholder values. The scenarios are a tool for dialogue between renewable energy producers, farmers and environmentalists. To the surprise of stakeholders, even in scenarios with strict constraints, GM PV has considerable potential within the municipal administrative boundaries. There was a consensus that GM PV should be used to achieve the energy transition, preferably after the potential of roofs and sealed surfaces has been exploited, except for a few farmers. The innovative participatory modelling approach, the results and the recommendations allow for a systematic, transparent and fair assessment of the GM PV projects at the community level. It enables responsible land-use planning and improves public acceptance by incorporating stakeholder values into the siting of GM PV projects. The new approach helps to defuse emotionally charged debates and promotes positive public attitudes towards genetically modified crops. It has already attracted considerable interest in other municipalities.
Multifaceted activation of STING axis upon Nipah and Measles virus-induced syncytia formation
Authors: Amurri Lucia , Dumont Claire , Pelissier Rodolphe , Reynard Olivier , Mathieu Cyrille , Spanier Julia , Pályi Bernadett , Deri Daniel , Karkowski Ludovic , Skerra Jennifer , Kis Zoltán , Kalinke Ulrich , Horvat Branka , Iampietro Mathieu
Published: January 2024

Activation of the DNA-sensing STING axis by RNA viruses plays a role in antiviral response through mechanisms that remain poorly understood. Here, we show that the STING pathway regulates Nipah virus (NiV) replication in vivo in mice. Moreover, we demonstrate that following both NiV and measles virus (MeV) infection, IFNγ-inducible protein 16 (IFI16), an alternative DNA sensor in addition to cGAS, induces the activation of STING, leading to the phosphorylation of NF-κB p65 and the production of IFNβ and interleukin 6. Finally, we found that paramyxovirus-induced syncytia formation is responsible for loss of mitochondrial membrane potential and leakage of mitochondrial DNA in the cytoplasm, the latter of which is further detected by both cGAS and IFI16. These results contribute to improve our understanding about NiV and MeV immunopathogenesis and provide potential paths for alternative therapeutic strategies.
A relationship between progesterone, maternal body weight, and offspring sex following the frozen/thawed single embryo transfer.
Authors: Ciepiela Przemyslaw , Czech Robert , Wójcik Dariusz , Skweres Tomasz , Śliwiński Wojciech , Zamkowska Dorota
Published: January 2024

Background/Objectives: to investigate a possible relationship between women’s age, serum progesterone concentration (PRG), and body weight expressed by body mass index (BMI) on the day of embryo frozen/thawed transfer (FET), and the sex of the newborn baby.
Subjects/Methods: A retrospective cohort study concerning children born after FET cycles conducted in one fertility clinic between January 2018 and September 2022. Out of 2,502 FET cycles, a group of 928 patients who underwent the transfer of the first best embryo from all frozen embryos, was extracted. All patients aged 23–46 qualified for FET during the study period were considered eligible. Cases where two embryos were transferred, and cycles where no data on progesterone concentration or embryos frozen at the cleavage stage were excluded from the study.
Results: Odds ratio (OR) of maternal age (OR: 0.97; 95% CI: 0.94–1.00; p = 0.064), PRG (OR: 1.00; 95% CI: 0.77–1.30; p = 0.988), and BMI (OR: 1.01; 95% CI: 0.98–1.05; p = 0.478) were not found to be associated with childbirth. Moreover, the maternal age did not have a statistically significant effect on the likelihood of giving birth to a female child (OR: 0.99, 95% CI: 0.95–1.02; p = 0.495) or a male child (OR: 0.97, 95% CI: 0.94–1.01; p = 0.128). However, the study found that increased levels of PRG over 20 ng/ml (OR: 1.38, 95% CI: 1.01–1.89; p = 0.044) and increased maternal BMI (OR: 1.06, 95% CI: 1.01–1.10; p = 0.007) significantly raised the chance of giving birth to a girl. Conversely, PRG levels less than 20 ng/ml are associated with lower odds of male birth (OR: 0.72, 95% CI: 0.53–0.99; p = 0.044), and higher maternal BMI is associated with an almost statistically-significant lower chance of male birth (OR = 0.96, 95% CI: 0.92–1.00; p = 0.067).
Conclusion: Higher BMI and PRG levels positively predicted female childbirth; conversely, elevated levels negatively predicted male delivery.
Digital Twins in Healthcare: A Global Perspective on Adoption Trends, Challenges, and Impacts across Public and Private Hospital
Authors: Marino Alfonso , Pariso Paolo , Picariello Michele
Published: January 2024

The authors have requested that this preprint be removed from Research Square.
Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride
Authors: Popović-Nikolić Marija R. , Čakar Mira , Todorović Nina , Nikolić Katarina , Popović Gordana
Published: January 2024

The acid-base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1=7.21±0.02, pKa2=7.86±0.02, pKa3=9.97±0.04) defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10-3 M HP-β-CD which was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of 10-3 M β-CD.
Human endogenous retroviruses are upregulated in Frontotemporal Dementia-MAPT mutation carriers
Authors: Fort-Aznar Laura , Borrego-Écija Sergi , Molina-Porcel Laura , Comas Aina , Puey Roger , Gómez Alba , Balasa Mircea , Lladó Albert , Antonell Anna , Sánchez-Valle Raquel
Published: January 2024

Previous studies have identified an upregulation of human endogenous retroviruses (HERVs) in several disorders, but little is known about their role in neurodegenerative dementias. In this study, we investigate a possible role of HERVs in the pathogenesis of sporadic and genetic frontotemporal dementia (FTD) and Alzheimer’s disease (AD). We measured HERVs transcripts using quantitative reverse transcription PCR (qRT-PCR) in post-mortem prefrontal cortex tissue samples from individuals with sporadic FTD (sFTD), genetic FTD (gFTD), sporadic AD (sAD), genetic AD (gAD) and healthy controls and then analysed RNA from whole blood from individuals with gFTD and controls. We also evaluated HERVK-env protein levels by an enzyme-linked immunosorbent assay (ELISA) in post-mortem brain FTD-MAPT mutation carriers and controls. We further analysed DNA methylation microarrays data from sFTD and gFTD patients looking for alterations in HERV-interacting genes. We show that in FTD-MAPT post-mortem brain tissue, HERVK (pol, gag, env and env3), HERVR-env and HERVW-env transcripts were upregulated with a fold-change (FC) > 2. In the other groups, HERVK-pol and HERVR-env transcripts were significantly upregulated in sFTD with tau deposits, sAD, and gAD patients, compared to controls, but the fold-change (FC) was lower than 2. HERVK-env protein was significantly elevated in FTD-MAPT brain compared to controls. We found several differentially methylated CpGs in interacting-HERVs genes (NUPR1, PGBD5, CBX1, CBX3, and ARC) in FTD-MAPT carriers compared to healthy subjects. In contrast, RNA from whole blood displayed decreased expression of HERVK-pol, HERVK-gag, HERVK-env3 and HERVW-env in FTD-MAPT compared to controls. These results strongly suggest that brain HERVs upregulation is associated with FTD-MAPT pathology. We hypothesize that HERV activity could serve as a potential target for antiviral drug administration in human FTD-MAPT carriers.
Impact of Internet Usage and Video Gaming on the Academic Performance of Postgraduate Students in a Prestigious Taiwanese University
Authors: Chen Gu Yun
Published: January 2024

The influence of technology usage on the growth and academic achievements of children, teenagers, and young adults is still a topic of ongoing discussion and debate. This study investigates the intricate relationship between internet usage, video gaming, and the academic performance of postgraduate students at a prestigious Taiwanese university. With a diverse sample of master's and Ph.D. students, research objectives guided a comprehensive analysis blueprint. According to the results, descriptive statistics provided nuanced insights into academic and lifestyle factors, revealing diverse engagement patterns in internet use and gaming. Correlation analyses explored relationships between Grade Point Average (GPA) and lifestyle factors, with modest associations noted, though statistical significance was not achieved. The regression model indicated that study hours, gaming hours, internet usage, and sleeping hours did not significantly predict GPA. The Chi-square test revealed a meaningful association between video game addiction and academic performance, emphasizing the need for further exploration. Friedman tests delved into negative impacts, coping mechanisms, and alternative leisure activities, offering valuable insights into students' experiences. Notably, female Ph.D. students exhibited a slightly higher GPA, and age-related variations in gaming habits were observed. These findings contribute to the discourse on digital well-being, shedding light on the multifaceted recreational landscape and academic challenges faced by postgraduate students. This study underscores the importance of addressing these concerns to foster balanced lifestyles and promote holistic well-being in the evolving digital landscape of postgraduate education.
Assessment of the occurrence and cause of bloody urine in cattle and management practices in Cheliya, Jibat, and Dire Inchini districts of the West Shewa Zone, Oromia, Ethiopia
Authors: Borena Bizunesh Mideksa , Sarba Edilu Jorga , Eteya Waktole Terfa , Feyissa Negassa , Bayu Morka Dandecha , Kebede Birhanu , Tola Getachew Kebebew
Published: January 2024

Background
A study was conducted to assess the causes of bloody urine and management practices in cattle from the Cheliya, Jibat, and Dire Inchini districts of the West Shoa Zone, Oromia, Ethiopia.
Materials and methods
Two kebeles from each of the three districts were selected based on bloody urine case reports, and a total of 215 cattle-owning households were selected for the questionnaire survey. Field observations were performed to screen for possible causes of bloody urine in the study areas. Six animals with symptoms of bloody urine were clinically examined, followed by postmortem and histopathological examinations.
Results
The questionnaire survey results showed that 72.1% (n = 155) of the households had at least one bloody urine case in their cattle herd. Among the three districts, more bloody urine cases were reported in the Cheliya district (95.0%), compared to 67.4% in Jibat and 53.5% in Dire Inchini. About 33.0% of the households reported the death of at least one cattle due to bloody urine; 58.8% of which were from the households in Cheliya, while 40.8% in Jibat, and 4.7% in Dire Inchini district. The occurrence of bloody urine was related to the dry season, feed shortage, access to bracken fern-infested pasture, and a known history of eating bracken fern. There was a high infestation rate of bracken fern (Pteridium aquilinum) in the grazing areas. All six suspected cattle exhibited chronic wasting and hematuria. Centrifugation of the urine samples revealed hematuria. Postmortem examination revealed petechial hemorrhage, papillomatous formations, thickened areas of mucosa, and white/red nodules on the urinary bladder.
Conclusions
Severe infestation of the bracken fern in the study areas, chronic hematuria, and wasting and postmortem findings in the bladder were all suggestive of bracken fern poisoning. Therefore, an immediate and integrated approach should be implemented to prevent cattle from accessing infested areas, remove this plant from grazing areas, and replace it with appropriate forage.