Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

Newborn screening (NBS) is hailed as a public health success, but little is known about long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Diseases pose a significant and pressing concern for the sustainable development of the aquaculture sector, particularly as their impact continues to grow due to climatic shifts such as rising water temperatures. While various approaches, ranging from biosecurity measures to vaccines, have been devised to combat infectious diseases, their efficacy is disease- and species-specific and contingent upon a multitude of factors. The field of genetics and genomics offer effective tools to control and prevent disease outbreaks in aquatic animal species. In this study, we present the key findings from our recent research, focusing on the genetic resistance to three specific diseases: White Spot Syndrome Virus WSSV) in white shrimp, Bacterial Necrotic Pancreatitis (BNP) in striped catfish and skin fluke (a parasitic ailment) in yellowtail kingfish. Our investigations reveal that all three species possess substantial heritable genetic components for disease resistant traits, indicating their potential responsiveness to artificial selection in genetic improvement programs tailored to combat these diseases. Also, we observed a high genetic association between disease traits and survival rates. Through selective breeding aimed at enhancing resistance to these pathogens, we achieved substantial genetic gains, averaging 10% per generation. These selection programs also contributed positively to the overall production performance and productivity of these species. Although the effects of selection on immunological traits or immune responses were not significant in white shrimp, they yielded favourable results in striped catfish. Furthermore, our genomic analyses, including shallow genome sequencing of pedigreed populations, enriched our understanding of the genomic architecture underlying disease resistance traits. These traits are primarily governed by a polygenic nature, with numerous genes or genetic variants, each with small effects. Leveraging a range of advanced statistical methods, from mixed models to machine and deep learning, we developed prediction models that demonstrated moderate to high levels of accuracy in forecasting these disease-related traits. In addition to genomics, our RNA-seq experiments identified several genes that undergo upregulation in response to infection or viral loads within the populations. Preliminary microbiome data, while offering limited predictive accuracy for disease traits in one of our studied species, underscore the potential for combining such data with genome sequence information to enhance predictive power for disease traits in our populations. Lastly, this paper briefly discusses the roles of precision agriculture systems, AI algorithms, and outlines the path for future research to expedite the development of disease-resistant genetic lines tailored to our target species. In conclusion, our study underscores the critical role of genetics and genomics in fortifying the aquaculture sector against the threats posed by diseases, paving the way for more sustainable and resilient aquaculture development.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

In 2023, the Bureau of Land Management (BLM) estimated that there were 68,928 mustangs living on United States public lands in 10 western states. The agency uses Appropriate Management Levels to determine the number of mustangs who need to be removed from the land. Once removed and processed, mustangs are sent to adoptions or sales events or retained in short-or long-term holding facilities. Adoptions and sales are the leading avenues for rehoming mustangs; however, the number of horses the BLM can place fluctuates annually and never approaches the greater number removed from the range. To explore opportunities for increasing the number of mustang adoptions, we conducted in-depth interviews with 23 horse trainers located on the U.S. East Coast, asking about participants’ training programs, relationships with horses, perceptions of mustangs, and challenges that mustangs face in the dressage and eventing industries. Participants had varying experiences with mustangs; however, all were willing to work with a mustang in some capacity. Participants voiced the need for more satellite adoption locations on the East Coast to decrease barriers to acquiring a mustang, notably cost and time, and for expanding existing training programs to include eventing and dressage.

In recent years, more and more health data are being generated. These data come not only from professional health systems, but also from wearable devices. All these data combined form ‘big data’ that can be utilized to optimize treatments for each unique patient (‘precision medicine’). To achieve this precision medicine, it is necessary that hospitals, academia and industry work together to bridge the ‘valley of death’ of translational medicine. However, hospitals and academia often have problems with sharing their data, even though the patient is actually the owner of his/her own health data, and the sharing of data is associated with increased citation rate. Academic hospitals usually invest a lot of time in setting up clinical trials and collecting data, and want to be the first ones to publish papers on this data. The idea that society benefits the most if the patient’s data are shared as soon as possible so that other researchers can work with it, has not taken root yet. There are some publicly available datasets, but these are usually only shared after studies are finished and/or publications have been written based on the data, which means a severe delay of months or even years before others can use the data for analysis. One solution is to incentivize the hospitals to share their data with (other) academic institutes and the industry. Here we discuss several aspects of data sharing in the medical domain: publisher requirements, data ownership, support for data sharing, data sharing initiatives and how the use of federated data might be a solution. We also discuss some potential future developments around data sharing.

As a precious natural resource, forests are being destroyed. In previous studies, there is a lack of interactive assessment of its distribution that comprehensively considers multiple external disturbances. This paper takes the Barcelona Metropolitan Region as an example. Based on remote sensing, it analyzes the development process of the forest from 2006 to 2018 through multiple landscape indicators, and OLS models were established to analyze variables that have direct and indirect effects on forest distribution. In addition, the ecological structure of the forest was analyzed based on NDVI. It was found that the forest area is the largest but has been decreasing, becoming more complex in distribution structure. Much of the forest was converted to agricultural land and grassland. The green quality of forests was increasing, and the broad-leaved forest, the second largest area, contributes the most. NDVI is the most important positively correlated variable, and daytime surface temperature is an important inverse factor related to NDVI. In addition, NDBI is also a negative condition that inhibits forest development. In conclusion: The BMR forest area is decreasing and becoming more fragmented. NDVI and daytime LST are the two most significant factors. Climate warming may lead to worse forest development.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.

There are many uncertainties and risks in residential electricity consumption during the economic development. Knowledge of the relationship between residential electricity consumption and its key determinant—income—are important to the sustainable development of electric power industry. Using panel data from 30 provinces for the 1995-2012 period, this study investigates how residential electricity consumption changes as incomes increase in China. Previous studies typically used linear or quadratic double-logarithmic models imposing ex ante restrictions on the indistinct relationship between residential electricity consumption and income. Contrary to those models, we employed a reduced piecewise linear model that is self-adaptive and highly flexible and circumvents the problem of “prior restrictions.” Robust tests of different segment specifications and regression methods are performed to ensure the conservatism of the research. The results provide strong evidence that the income elasticity was approximately one, and it remained stable throughout the estimation period. The income threshold at which residential electricity consumption automatically remains stable or slows has not been reached. To ensure the sustainable development of the electric power industry, introducing higher energy efficiency standards for electrical appliances and improving income levels are vital. And government should emphasize electricity conservation in industrial sector rather than in residential sector.

Laser-targeted weeding methods further enhance the sustainable development of green agriculture, with one key technology being the improvement of weed localization accuracy. Here, we propose an improved YOLOv8 instance segmentation based on bidirectional feature fusion and deformable convolution (BFFDC-YOLOv8-seg) to address the challenges of insufficient weed localization accuracy in complex environments with resource-limited laser weeding devices. Initially, by training on extensive datasets of plant images, the most appropriate model scale and training weights are determined, facilitating the development of a lightweight network. Subsequently, the introduction of the Bidirectional Feature Pyramid Network (BiFPN) during feature fusion effectively prevents the omission of weeds. Lastly, the use of Dynamic Snake Convolution (DSConv) to replace some convolutional kernels enhances flexibility, benefiting the segmentation of weeds with elongated stems and irregular edges. Experimental results indicate that the BFFDC-YOLOv8-seg model achieves a 4.9% increase in precision, an 8.1% increase in recall rate, and a 2.8% increase in mAP50 value to 98.8% on a vegetable weed dataset compared to the original model. It also shows improved mAP50 over other typical segmentation models such as Mask R-CNN, YOLOv5-seg, and YOLOv7-seg by 10.8%, 13.4%, and 1.8%, respectively. Furthermore, the model achieves a detection speed of 24.8 FPS on the Jetson Orin nano standalone device, with a model size of 6.8MB that balances between size and accuracy. The model meets the requirements for real-time precise weed segmentation, suitable for complex vegetable field environments and resource-limited laser weeding devices.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Selecting road networks in cartographic generalization has consistently posed formidable challenges, driving research towards the application of intelligent models. Despite previous efforts, the accuracy and connectivity preservation in these studies, particularly when dealing with road types of similar sample sizes, still warrant improvement. To address these shortcomings, we introduce a Heterogeneous Graph Attention Network (HAN) for road selection, where feature masking method is initially utilized to assess the significance of road features. Concentrating on the most relevant features, two meta-paths are introduced within the HAN framework: one for aggregating features of the same road type within the first-order neighborhood, emphasizing local connectivity, and another extending this aggregation to the second-order neighborhood, capturing a broader spatial context. For a comprehensive evaluation, we introduce a set of metrics considering both quantitative and qualitative aspects of the road network. Compared to traditional neural networks, our HAN model demonstrates superior accuracy and F1-score, particularly for road types with comparable samples. Additionally, it enhances the overall connectivity of the selected network. In summary, our HAN-based method provides an advanced solution for road network selection, surpassing previous approaches in terms of accuracy and connectivity preservation.

Brazil has ideal conditions for the large-scale use of cabotage cargo transportation: a vast coastline with almost 7,400 km, approximately 70% of the population resident in a coastal range of up to 200 km from the coast and a strong concentration of activities economic along the coast. However, there is an absolute domain of road modal for the transportation of goods, and cabotage is underused. The purpose of the study was to raise the main barriers that negatively impact the performance of Brazilian cabotage. To this end, it was used to bibliographic and documentary research, based on studies already published in journals, doctoral theses, master's dissertations, congress annals, technical reports and research on government-related government agencies sites, navigation companies and entities related to cabotage. The main barriers that contribute to the low use of cabotage in Brazil were identified and analyzed, as well as possible alternatives of solution for sustainable development of this mode of transport. Such a study will certainly serve as subsidies for the definition of public policies aimed at better use of Brazilian cabotage, as well as to encourage navigation companies to invest more in the transport of goods by cabotage, in order to contribute to the reduction of trucks on highways Brazilian and for environmental preservation.

It is important to consider both requirements and limitations for the generation and sharing of genomic data. For example, human genomic sequence data should typically not be deposited publicly without the appropriate "explicit consent" to do so. This includes genetic identifying data that may exist within raw reads for bulk RNA Sequencing (RNA-Seq) data and genomic data from cell lines that are available to purchase. At the same time, data sharing is important for re-analysis and reproducibility/replication in the scientific community. A review of known rules and guidelines for genomic data sharing is provided. This includes specific rules for NIH-funded data for controlled access deposit of HeLa cell line data, including bulk RNA-Seq data. The ability to create “partial” Gene Expression Omnibus (GEO) public deposits with only processed data is described, with search criteria that can identify many “partial” GEO deposits for a variety of data types where reads were not made public for patient privacy concerns. However, it is the opinion of the author that this should be considered a short-term solution, and additional considerations and action should be carried out for genomic data generated in future experiments. Information about how to learn more about what is known for consent for cell line samples is also briefly provided, along with search results for genomic data from widely available cell lines that is deposited in controlled access databases. Finally, it should be made clear that this article presents some amount of opinion. Additionally, open feedback for this preprint is encouraged to further enhance knowledge and communication.

“De-[Constructing] Growth” is offered as a deeper and more useful conceptualization that avoids the negative connotations of, and resistance to, “degrowth” by decoupling profit from unsustainable consumption, production, and inequality.

The key links of face recognition are digital image preprocessing, facial feature extraction and pattern recognition, this article aimed at the current problem of slow speed and low recognition accuracy of face recognition , from the above three key links, on the basic of analyzing the therories of Fractional Differential Masks Operator (FDMO), Principal Component Analysis (PCA) and Support Vector Machine (SVM), design a kind of FDMO+PVA+SVM coupling algorithm that applies to face recognition to improve the speed and accuracy of it. To realize FDMO+PCA+SVM coupling algorithm, first, we should apply FDMO to face image processing binary marginalization, the purpose is getting face contour; Then, we apply PCA to get the feature of face image which is disposed by binary marainalization. At last, we can apply One-Against All of the SVM classifier and LibSVM software package to realize face recognition. Beside, the article with nine different coupling algorithm design four groups of experimental reaults on the ORL face database verified by comparative analysic FDMO+PCA+SVM coupling algorithm in the superiority of face recognition accuracy and speed.

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases occupy a decisive proportion in determining the composition and diversity of terpenoids; though their regulatory effects have been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we unveil linalool as the predominant volatile compound in Freesia hybrida flowers, demonstrating a gradual release pattern during flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on digital expression profile correlation analysis and homologous gene comparison. FhMYB108 is capable of regulating the expression of terpene synthase FhTPS1, and both their expression levels exhibit a gradual increase concomitant with flower opening. Moreover, transcriptional regulation and transient expression assays revealed that FhMYB108 exerts a stimulatory effect on the transcription of A. thaliana AtTPS14, while no significant increase in AtTPS14 expression was observed upon stabilization of FhMYB108 in Arabidopsis. Investigate its reason, the highly expressed AtMYC2 in A. thaliana can interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidated the regulatory mechanism underlying linalool synthesis, but also discovered the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

The scientific community has long benefited from the opportunities provided by data reuse. Recognizing the need to identify the challenges and bottlenecks to reuse in the agricultural research community and propose solutions for them, the data reuse working group was started within the AgBioData consortium (https://www.agbiodata.org/) framework. Here, we identify the limitations of data standards, metadata deficiencies, data interoperability, data ownership, data availability, user skill level, resource availability, and equity issues, with a specific focus on agricultural genomics research. We propose possible solutions stakeholders could implement to mitigate and overcome these challenges and provide an optimistic perspective on the future of genomics and transcriptomics data reuse.

Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.

Phosphite (Phi) has gained attention in agriculture due to its biostimulant effect on crops. This molecule has been found to benefit plant performance by providing protection against pathogens, improving yield and fruit quality, and improving nutrient and water use efficiency. It is still unclear how Phi enhances plant growth and protects against multiple stresses. It has been hypothesized that Phi acts by directly affecting the pathogens and interacting with the plant cellular components and molecular machinery to elicit defense responses. This study delves into elucidating the mechanisms underlying Phi’s beneficial effects on plants, revealing a complex interplay with fundamental signaling pathways. A RNA-seq study of Arabidopsis seedlings under optimal and limiting phosphate conditions helped us unveil Phi’s role in promoting plant growth by activating the expression of genes involved in the biosynthesis and signaling pathways associated with abscisic acid (ABA), salicylic acid (SA), and jasmonic acid (JA). Expression of ABA-related genes, known for their involvement in stress response and development regulation, is triggered by Phi treatment, contributing to enhanced resilience and growth. Simultaneously, the activation of the SA pathway, associated with defense responses, suggests Phi’s potential in bolstering plant immunity. Moreover, Phi influences JA biosynthesis and signaling, which are crucial for defense against herbivores and pathogens, thereby strengthening plants’ defenses. Our findings reveal a multifaceted mechanism through which Phi benefits Arabidopsis development. Understanding its intricate interplay with key signaling pathways opens avenues for leveraging Phi as a strategic tool to enhance plant resilience, immunity, and growth in agricultural and ecological contexts.

Users with Autism Spectrum Disorder may find human-computer interaction (HCI) challenging due to a number of symptoms experienced, one of which is difficulty coping with change. Through capturing, comparing and statistically analysing the reactions of autistic and neurotypical users to seven individual design changes, it has been possible to identify the changes that cause significant difficulty in autistic users. These difficulty points were then used to form heuristics that can followed by HCI practitioners in the industry to reduce the negative impact of software interface design change on autistic users, hence making software updates more accessible.

Private Set Intersection (PSI) is a cryptographic method in secure multi-party computation that allows entities to identify common elements in their datasets without revealing their private data. Traditional approaches assume similar-sized datasets and equal computational power, overlooking practical imbalances. In real-world applications, dataset sizes and computational capacities often vary, particularly in the Internet of Things and mobile scenarios where device limitations restrict computational types. Traditional PSI protocols are inefficient here, as computational and communication complexities correlate with the size of larger datasets. Thus, adapting PSI protocols to these imbalances is crucial. This paper explores unbalanced PSI scenarios where one party (the receiver) has a relatively small dataset and limited computational power, while the other party (the sender) has a large amount of data and strong computational capabilities. It introduces three innovative solutions for unbalanced PSI: unbalanced PSI protocol based on Cuckoo filters, unbalanced PSI protocol based on single cloud assistance, and unbalanced PSI protocol based on dual cloud assistance, each addressing the shortcomings of the previous solution. These protocols primarily optimize database computational load, storage capacity, protocol execution time, and security. Depending on performance and security needs, different protocols can be employed for applications such as private contact discovery.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate falls/fractures risk compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious falls risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016-2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated time to first injurious fall within 3 months post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age≥65=84.6%, female=58.1%, White=82.7%; having injurious falls=0.45%), we identified 13 distinct OPI-BZD trajectories: Group(A):Very-low OPI-only (early discontinuation)(44.9% of the cohort); (B):Low OPI-only (rapid decline)(15.1%); (C):Very-low OPI-only (late discontinuation)(7.7%); (D):Low OPI-only (gradual decline)(4.0%); (E):Moderate OPI-only (rapid decline)(2.3%); (F):Very-low BZD-only (late discontinuation)(11.5%); (G):Low BZD-only (rapid decline)(4.5%); (H):Low BZD-only (stable) (3.1%); (I):Moderate BZD-only (gradual decline)(2.1%); (J):Very-low OPI (rapid decline)/Very-low BZD (late discontinuation)(2.9%); (K):Very-low OPI (rapid decline)/Very-low BZD (increasing)(0.9%); (L):Very-low OPI (stable)/Low BZD (stable)(0.6%); and (M):Low OPI (gradual decline)/Low BZD (gradual decline)(0.6%). Compared with Group(A), 6 trajectories had increased 3-month injurious fall risks: (C): HR, 95%CI=1.78, 1.58-2.01; (D): 2.24, 1.93-2.59; (E): 2.60, 2.18-3.09; (H): 2.02, 1.70-2.40; (L): 2.73, 1.98-3.76; and (M): 1.96, 1.32-2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing fall risks of OPI-BZD use among older adults.

Europium is one of the most reactive lanthanides and humans use it in many different applica-tions, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) were obtained and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothi-oneins and/or displace essential cations of these proteins during their homeostasis function. Both lipid metabolism (lipid droplets that fuse with europium-containing vacuoles) and au-tophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Despite the high quality of soybean protein, raw soybeans and soybean meal cannot be directly included into animal feed mixtures due to the presence of Kunitz (KTi) and Bowman Birk protease inhibitors (BBi) which reduces animal performance. Heat treatment can substantially inactivate trypsin and chymotrypsin inhibitors (BBi) but such treatment is energy intensive, adds expense, and negatively impact the quality of seed proteins. As an alternative approach we have employed CRISPR/Cas9 gene editing to create mutations in BBi genes to drastically lower the protease inhibitor content in soybean seed. Agrobacterium-mediated transformation was used to generate several stable transgenic soybean events. These independent CRISPR/Cas9 events were examined in comparison to wild type plants using Sanger sequencing, proteomic analysis, trypsin/chymotrypsin inhibitor activity assays and q15RT-PCR. Collectively, our results demonstrate the creation of an allelic series of loss of function mutations affecting the major BBi gene in soybean. Mutations in two of the highly expressed seed specific BBi genes lead to substantial reductions in both trypsin and chymotrypsin inhibitor activities.

The Chikungunya virus (CHIKV) poses a significant global public health concern, especially in Africa. Since its first isolation in Tanzania in 1953, CHIKV has caused recurrent outbreaks, challenging healthcare systems in low-resource settings. Recent outbreaks in Africa highlight the dynamic nature of CHIKV transmission and the challenges of underreporting and underdiagnosis. Here, we review literature and analyze publicly available cases, outbreaks, and genomic data providing insights into the epidemiology, genetic diversity, and transmission dynamics of CHIKV in Africa. Our analyses reveal the circulation of geographically distinct CHIKV genotypes, with certain regions experiencing a disproportionate burden of disease. Phylogenetic analysis of sporadic outbreaks in West Africa suggests repeated emergence of the virus through enzootic spillover, which is markedly different from inferred transmission dynamics in East Africa, where the virus is often introduced from Asian outbreaks, including the recent reintroduction of the Indian Ocean lineage from the Indian subcontinent to east Africa. Furthermore, there is limited evidence of viral movement between these two regions. Understanding the history and transmission dynamics of outbreaks is crucial for public health planning. Despite advances in surveillance and research, diagnostic and surveillance challenges persist. This review and secondary analysis highlight the importance of ongoing surveillance, research, and collaboration to mitigate the burden of CHIKV in Africa and improve public health outcomes.

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

Over the past decade and a half, dynamic functional imaging has revolutionized the neuroimaging field. Since 2009, it has revealed low dimensional brain connectivity measures, has identified potential common human spatial connectivity states, has tracked the transition patterns of these states, and has demonstrated meaningful alterations in these transition and spatial patterns in neurological disorders, psychiatric disorders, and over the course of development. Recently, researchers have begun to analyze this data from the perspective of dynamic system and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Consciousness, in particular, appears to be strongly linked to entropy production in the brain. Little attention has been paid to the effects of psychiatric disease on entropy production in the human brain, however. Even disorders characterized by substantial changes in conscious experience have not been widely analyzed from this perspective. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls, and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

One of today’s most critical challenges is ensuring a sufficient food production and supply for the ever-expanding global population. Recently, many countries around the world, particularly those in Africa, grapple with severe hunger and food insecurity, frequently exacerbated by escalating global prices, persistent insecurity, and the repercussion of the COVID-19 pandemic. However, this study undertook an extensive review of the prevalence and severity of hunger and food insecurity across diverse countries and regions. The review utilised several metrics, including Global Hunger Index (GHI) scores, Global Food Security index (GFSI) scores, 2023 data (related to two Sustainable Development Goal 2 (SDG2) target) from the Food and Agriculture Organization (FAO), and other pertinent sources to assess the current status of the countries included in this study. The 20 countries with 2023 GHI scores below 5 were collectively ranked from 1 to 20, signifying low hunger levels. However, Central African Republic (CAR) received the lowest ranking at 125 out of 125, with a score of 42.3, indicating an alarming level of hunger. Finland achieved the highest GFSI score of 83.7, with Oman showing the most notable GFSI improvement at +13.8, while Syria experienced a significant decline in GFSI score by -10.5. Over time, many countries, particularly the developed ones, witnessed significant improvement in their GHI and GFSI scores. Meanwhile, most countries in sub-Saharan Africa experienced the most deterioration in their GFSI scores and notable increases in their GHI scores. The review documented the significant progress made by countries and regions in reducing levels of hunger and food insecurity, while highlighting the substantial burden borne by sub-Saharan Africa (SSA) in combating global hunger and food insecurity.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

This research introduces a hybrid feature extraction approach that combines Linear Discriminant Analysis (LDA) and Multilayer Perceptron (MLP) methods to address the challenges of reducing feature vector dimensionality and accurately classifying smartphone-based human activities. Moreover, to refine activity classification accuracy, Support Vector Machine (SVM) optimization with Stochastic Gradient Descent (SGD) is employed. LDA, a statistical tool, is leveraged to derive a new feature space for data projection, enhancing class separation and test feature label prediction. The proposed approach, named LMSS, was evaluated using the UCI-HAR dataset and compared with state-of-the-art models. The results demonstrate that the proposed approach outperformed the best-performing method over this dataset. It achieved an accuracy rate of 99.52%, precision of 99.55%, recall of 99.53%, and an F1-score of 99.54%, highlighting the effectiveness of the proposed method in accurately classifying the data.

In this paper, we first discuss the research status and application progress of the finite element method and the smoothed particle method. By analyzing the advantages of the smoothed particle method and the finite element method, a new coupling algorithm, namely FEM-SPH algorithm, is proposed. By the method of comparison, it shows that finite element method and SPH method in the simulation of large deformation problems each have advantages and disadvantages, the finite element method smoothed particle coupling algorithm is effective to achieve the performance of high computational efficiency and can naturally simulate large deformation problems across. In the process of calculation, the large deformation unit can be freely into an algorithm to facilitate the calculation accuracy and efficiency of three methods of numerical simulation. Through the study found, FEM-SPH algorithm not only overcome the defect of smooth particle tensile instability, but also overcomes the problem of low efficiency of finite element computation. To further test the FEM-SPH algorithm has advantages in the practical engineering, we have carried out the actual test to the example of the super high speed collision, concluded that, since the target of most of the computational domain is always finite element, smoothed particle focused only in contact with the projectile and target of local area, particle number is not much, the whole calculation process just ten minutes, computational efficiency has been greatly improved, at the same time in the simulation of large deformation, the advantage is very obvious .This provides a criterion for the actual project, depending on the specific material deformation mode and choose a more appropriate conversion algorithm.

Salinity stress emerges as an important menace to global food security, particularly affecting susceptible crops such as common bean plants (Phaseolus vulgaris L.). The disruption of ion balances caused by salt stress withing plants cells reduces water and nutrient absorption, and hampers growth and productivity. Sacchorhiza polyschides, a brown macroalga rich in essential elements, and macrominerals, has drawn attention as a natural biostimulant, being a potential remedy to bolster crop resilience against salt stress. This study delves into the effect of water extracts of Sacchorhiza polyschides (SPE) across varying concentrations (1%, 2%, and 5%) in common bean plants under salt stress (68.4 mM NaCl) conditions. Two different methods of application were used: by spraying the aerial part of the plant or by irrigation together with the watering solution. The effects of both systems of application were studied on the aerial parts of the plants. SPE exhibited significant enhancements in morphological parameters, chlorophyll content, carbon-nitrogen activities, and antioxidant enzymatic system activities, alongside increasing osmolyte accumulation, compared to salt-stressed plants without biostimulation. Moreover, SPE reduced reactive oxygen species (ROS) levels caused by salt stress, mitigating lipid peroxidation. The concentrations of 2% and 5% SPE applied by spraying showed the most significant results in most of the parameters analyzed. By shedding light on the underlying science behind this biostimulant effect, this research underscores the potential of SPE to enhance crop resilience and augment food production in salt-challenged environments.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

In order to meet the needs of an increasingly complex research landscape, researchers engage in “collaborative prosumption” through open data sharing and reuse. Although significant gains have been achieved in this regards because of growing requirements from funding agencies, governments and journals, the question of how reuse of openly available data for new research contribute to sustainability is yet to be appropriately addressed in the literature. Therefore, relying on a three stage stratified clustered random sampling of the Journal of Applied Econometrics data archive (JAEDA), the present research provides a case study of the value of research data recycling for sustainable research and economic development. More specifically our analysis show that reformatting from wide to long format, openly shared equity price index data on eleven European countries’ extracted from JAEDA, and augmented with country level geospatial Meta data, provides a new basis for interesting descriptive analytics and spatio-temporal econometric modeling and inference. Given the ever-increasing volume of openly available research data, our study provides a first-hand insight on open data reuse, which should benefit all stakeholders in the research community, as they seek sustainable solutions for scientific productivity and progress.

As previous study in many countries shown that stroke patient onsets are not distributed randomly, but associate with meteorological factors. However, the relationship between stroke occurence and meteorological factors remain unknown in mountain area in Guizhou China. This paper firstly introduces multi-source fusion data which is integrated by the mountain meteorological factor, geographic mapping elevation information data and stroke population monitoring of Guizhou province. Mainly elaborates from a few aspects, which concludes data collection, data sorting, data extraction, data cleaning and data production in detail. A completed and detailed meteorological stroke data set was successfully established and multi-source data fusion was realized by the use of Gbase and unified data service interface of Guizhou meteorological big data cloud platform. And we report the impact of meteorological variables in Guizhou mountain area climate on stroke. In this study, we performed a statistical fusion data between January 2017 and December 2020 about stroke incidence rate and meteorological factors respectively, for instance, concerning the mean (Mean), maximum (Max), minimum (Min), median (Median), standard deviation (Std) . We calculated stroke rates (date stroke occurence)/(year stroke occurence) and we investigated the distribution of days included in the label. Results: the distribution of the incidence rate basically conforms to the normal distribution with the label Max 0.007399, label Min 0.000204, label Mean 0.002738, label Median 0.002643, label Std 0.00076. We observed a positive significant correlation of stroke incidence rate directly proportional to the daily temperature difference (between 0 and 20 degrees Celsius), as the value of this factor exhibits variation larger, the incidence rate is gradually increasing. And we investigated from the Pearson correlation coefficients that stroke incidence increasing when meteorological factors at low humidity (less than 40% (RH 80%), temperature higher than 31℃); the 24-hour daily temperature difference varies between 6 and 10℃ (6

Network effects, economies of scale, and lock-in-effects increasingly lead to a concentration of digital resources and capabilities, hindering the free and equitable development of digital entrepreneurship (SDG9), new skills, and jobs (SDG8), especially in small communities (SDG11) and their small and medium-sized enterprises (“SMEs”). To ensure the affordability and accessibility of technologies, promote digital entrepreneurship and community well-being (SDG3), and protect digital rights, we propose data cooperatives [1,2] as a vehicle for secure, trusted, and sovereign data exchange [3,4]. In post-pandemic times, community/SME-led cooperatives can play a vital role by ensuring that supply chains to support digital commons are uninterrupted, resilient, and decentralized [5]. Digital commons and data sovereignty provide communities with affordable and easy access to information and the ability to collectively negotiate data-related decisions. Moreover, cooperative commons (a) provide access to the infrastructure that underpins the modern economy, (b) preserve property rights, and (c) ensure that privatization and monopolization do not further erode self-determination, especially in a world increasingly mediated by AI. Thus, governance plays a significant role in accelerating communities’/SMEs’ digital transformation and addressing their challenges. Cooperatives thrive on digital governance and standards such as open trusted Application Programming Interfaces (APIs) that increase the efficiency, technological capabilities, and capacities of participants and, most importantly, integrate, enable, and accelerate the digital transformation of SMEs in the overall process. This policy paper presents and discusses several transformative use cases for cooperative data governance. The use cases demonstrate how platform/data-cooperatives, and their novel value creation can be leveraged to take digital commons and value chains to a new level of collaboration while addressing the most pressing community issues. The proposed framework for a digital federated and sovereign reference architecture will create a blueprint for sustainable development both in the Global South and North.

External motivational stimuli have been shown to improve athletic performance. However, the neurophysiological mechanisms underlying this improvement remain poorly understood. This randomized crossover study investigated the effects of music and verbal encouragement on measures of muscle excitation and myoelectric manifestations of fatigue in the biceps brachii (BB) and brachioradialis (BR) muscles during an endurance task. Fifteen untrained (mean age 29.57 ± 2.77 years) and 13 trained individuals (mean age 32.92 ± 2.90 years) were included. The endurance task, performed to exhaustion, consisted of keeping the dominant arm flexed to 90 degrees while holding a dumbbell loaded to 80% of 1RM with a supine grip in three randomized conditions: standard, with self-selected music, and with verbal encouragement. The untrained subjects showed an increase in task duration of 15.26% (p < 0.003) with music and 15.85% (p < 0.002) with verbal encouragement compared to the condition without external stimuli. There were no significant differences in the myoelectric manifestations of fatigue between the dif-ferent conditions. Regarding the muscle excitation metrics, although the mean amplitude, peak value and area under the curve remained unchanged across conditions, a significant reduction in the trend coefficient, indicating motor unit recruitment over time, was observed with both music (BB: -10.39%, p < 0.001; BR: -9.40%, p < 0.001) and verbal encouragement (BB: -7.61%, p < 0.001; BR: -6.51%, p < 0.001) compared to the standard condition. For the trained participants, no significant differences were observed between conditions in terms of task duration and outcome measures related to muscle excitation and myoelectric manifestations of fatigue, suggesting the possible presence of a ceiling effect on motivation. These results highlight the significant role of external motivational stimuli, such as music and verbal encouragement, in improving task performance in untrained subjects, probably through more ef-fective and efficient recruitment of motor units.

Lyme disease is a highly prevalent tick-borne infection caused by Borrelia burgdorferi spirochetes in North America and Eurasia. Diagnosis of the early disease remains difficult with the currently approved serological tests in the absence of noticeable tick bite or erythema migrans due to presentation of non-specific symptoms and the absence of antibodies early in infection. Furthermore, it is difficult to distinguish persistence of disease and reinfection in the endemic regions. If not treated early, infection spreads throughout the body and affects most organs with disease manifestations including arthritis, musculoskeletal pain, neuroborreliosis and acrodermatitis chronicum atrophicans. Although most patients recover after antibiotic treatment, ~10-12% of show recurrence of symptoms known as post-treatment Lyme disease syndrome (PTLDS). Various causes of PTLDS are not well-defined; however, the spirochete persisters, antigenic debris, dysregulation of immunological response in individuals or a combination of these factors are proposed to result in continuation of Lyme disease manifestations. Based on these considerations, this review highlights currently employed treatment approaches with antimicrobials and vaccines being tried for prevention of B. burgdorferi infection. We also summarize combinatorial approaches that could be employed to alleviate symptoms to improve the quality of life of the individuals suffering from long Lyme disease.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

Timely and accurate information on tree species is crucial for the sustainable management of natural resources, forest inventory, biodiversity detection, and carbon stock calculation. The advancement of remote sensing technology and artificial intelligence has facilitated the acquisition and analysis of remote sensing data, resulting in more precise and effective classification of tree species. Multimodal remote sensing data and deep learning seem to be the current tree species classification research mainstream, whether or not. The current review on the remote sensing data and deep learning tree species classification methods perspectives to analyze the unimodal and multimodal remote sensing data and classification methods in this realm is missing. To bridge the gap, we search for major trends in the remote sensing data and tree species classification methods, provide a detailed overview of classic deep learning-based methods for tree species classification, and discuss the limitations.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Free Floating Car Sharing (FFCS) services are a flexible alternative to car ownership. These transportation services show highly dynamic usage both over different hours of the day, and across different city areas. In this work, we study the problem of predicting FFCS demand patterns -- a problem of great importance to an adequate provisioning of the service. We tackle both the prediction of the demand i) over time and ii) over space. We rely on months of real FFCS rides in Vancouver, which constitute our ground truth. We enrich this data with detailed socio-demographic information obtained from large open-data repositories to predict usage patterns. Our aim is to offer a thorough comparison of several machine learning algorithms in terms of accuracy and easiness of training, and to assess the effectiveness of current state-of-art approaches to address the prediction problem. Our results show that it is possible to predict the future usage with relative errors down to 10%, and the spatial prediction can be estimated with relative errors of about 40%. Our study also uncovered the socio-demographic features that most strongly correlate with FFCS usage, providing interesting insights for providers opening service in new regions.

Understanding morphological and genetic diversity of forest trees is essential to facilitate their conservation, sustainable management and genetic improvement for addressing the economic and environmental demands and challenges. We have examined variation in morphometric seed and pod traits and seed germination of multipurpose and widely distributed forest tree Albizia lebbek (Indian siris) from 12 provenances covering the species’ range in northern India and its relationships with bioclimatic factors. Highly significant inter-provenance variation was observed in seed size (seed length (SL), seed width (SW), SW/SL, SL×SW), seed mass (1000 seed weight), pod size (pod length (PL), pod width (PW), PW/PL), seed germination, number of seeds per pod, and insect infected seeds (IIS). The provenance effect contributed a major portion to the total phenotypic variance. Morphometric variation in all traits except for IIS was not clinal related to longitude, latitude, altitude or rainfall. There was an indication of the presence of ecotypic variation. IIS showed clinal variation with significant negative correlation with latitude. Most seed size and pod size traits showed positive correlations with several temperature bioclimatic factors and negative correlations with several precipitation bioclimatic factors. Our results have significance for genetic improvement, population genetics and genomics studies and conservation and sustainable management of A. lebbek genetic resources.

Cysteine and its derivatives, including H2S, can influence bacterial virulence and sensitivity to antibiotics. In minimal sulfate media, H2S is generated under stress to prevent excess cysteine and, together with incorporation into glutathione and export into the medium, is a mechanism of cysteine homeostasis. Here, we studied the features of cysteine homeostasis in LB medium, where the main source of sulfur is cystine, whose import can create excess cysteine inside cells. We used mutants in the mechanisms of cysteine homeostasis and a set of microbiological and biochemical methods, including real-time monitoring of sulfide and oxygen, determination of cysteine and glutathione, and expression of the Fur, OxyR, and SOS regulons genes. During normal growth, the parental strain generated H2S when switching respiration to another substrate. The mutations affected the onset time, intensity and duration of H2S production, cysteine and glutathione levels, bacterial growth and respiration rates, and induction of defense systems. Exposure to chloramphenicol and high doses of ciprofloxacin increased cysteine content and GSH synthesis. A high inverse relationship between log CFU/ml and bacterial growth rate before ciprofloxacin addition was revealed. The study points to the important role of maintaining cysteine homeostasis during normal growth and antibiotic exposure in LB medium.

The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances which have investigated the contribution of cell intrinsic mechanisms as well as of the immune system to myeloid leukemogenesis in this specific subset of AML. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes for these patients

The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the most ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, South America. Due to their natural characteristics as a hermaphroditic species with high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments to reactively control invasive mollusc populations and proactively prevent their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in open water systems was performed to evaluate molluscicides and identify toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize negative impact to water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners on invasive Asian clam management.

Digital federated platforms and data cooperatives for secure, trusted and sovereign data exchange will play a central role in the construction industry of the future. With the help of platforms, cooperatives and their novel value creation, the digital transformation and the degree of organization of the construction value chain can be taken to a new level of collaboration. The goal of this research project was to develop an experimental prototype for a federated innovation data platform along with a suitable exemplary use case. The prototype is to serve the construction industry as a demonstrator for further developments and form the basis for an innovation platform. It exemplifies how an overall concept is concretely implemented along one or more use cases that address high-priority industry pain points. This concept will create a blueprint and a framework for further developments, which will then be further established in the market. The research project illuminates the perspective of various governance innovations to increase industry collaboration, productivity and capital project performance and transparency as well as the overall potential of possible platform business models. However, a comprehensive expert survey revealed that there are considerable obstacles to trust-based data exchange between the key stakeholders in the industry value network. The obstacles to cooperation are predominantly not of a technical nature, but of a competitive, predominantly trust-related nature. To overcome these obstacles and create a pre-competitive space of trust, the authors therefore propose the governance structure of a data cooperative model, which is discussed in detail in this paper.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

Pancreatic neuroendocrine neoplasms (pNENs) are rare tumors accounting for only 1-2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2 and neuroendocrine carcinoma: NEC) on the basis of Ki-67 proliferation index and mitotic count according to the 2010 WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic backround together with preclinical studies to develop new agents, including those already under investigation for SCLC, will be needed to improve the prognosis.

Science continues to become more interdisciplinary and to involve increasingly complex data sets. Many projects in the biomedical and health-related sciences follow or aim to follow the principles of FAIR data sharing, which has been demonstrated to foster collaboration, to lead to better research outcomes, and to help ensure reproducibility of results. Data generated in the course of biomedical and health research present specific challenges for FAIR sharing in the sense that they are heterogeneous and highly sensitive to context and the needs of protection and privacy. Data sharing must respect these features without impeding timely dissemination of results, so that they can contribute to time-critical advances in medical therapy and treatment. Modeling and simulation of biomedical processes have become established tools, and a global community has been developing algorithms, methodologies, and standards for applying biomedical simulation models in clinical research. However, it can be difficult for clinician scientists to follow the specific rules and recommendations for FAIR data sharing within this domain. We seek to clarify the standard workflow for sharing experimental and clinical data with the simulation modeling community. By following these recommendations, data sharing will be improved, collaborations will become more effective, and the FAIR publication and subsequent reuse of data will become possible at the level of quality necessary to support biomedical and health-related sciences.

Next-generation sequencing (NGS) has been a widely-used technology in biomedical research for understanding the role of molecular genetics of cells in health and disease. A variety of computational tools have been developed to analyse the vastly growing NGS data, which often require bioinformatics skills, tedious work and significant amount of time. To facilitate data processing steps minding the gap between biologists and bioinformaticians, we developed CSI NGS Portal, an online platform which gathers established bioinformatics pipelines to provide fully automated NGS data analysis and sharing in a user-friendly website. The portal currently provides 16 standard pipelines for analysing data from DNA, RNA, smallRNA, ChIP, RIP, 4C, SHAPE, circRNA, eCLIP, Bisulfite and scRNA sequencing, and is flexible to expand with new pipelines. The users can upload raw data in fastq format and submit jobs in a few clicks, and the results will be self-accessible via the portal to view/download/share in real-time. The output can be readily used as the final report or as input for other tools depending on the pipeline. Overall, CSI NGS Portal helps researchers rapidly analyse their NGS data and share results with colleagues without the aid of a bioinformatician. The portal is freely available at: https://csibioinfo.nus.edu.sg/csingsportal

Cybersecurity is a crucial concern for local governments, as they serve as the primary interface between public and government services, managing sensitive data and critical infrastructure. While technical safeguards are integral to cybersecurity, the role of well-structured policy is equally important, as it provides structured guidance to translate technical requirements into actionable protocols. This study reviews local governments’ cybersecurity policies to provide a comprehensive assessment of how these policies align with NIST CSF, which is a widely adopted and commonly used cybersecurity assessment framework. The review offers local governments a mirror to reflect on their cybersecurity stance, identifying potential vulnerabilities and areas needing urgent attention. The study further extends to developing a cybersecurity policy framework, which local governments can use as a strategic tool. It provides valuable information on crucial cybersecurity elements that local governments must incorporate into their policies to protect confidential data and critical infrastructure.

Spontaneous tumours in higher plants can develop depending on plant genotype without any pathogen invasion. Spontaneous tumour formation on the taproots is consistently observed in certain inbred lines of radish (Raphanus sativus var. radicula Pers.). In this work, we have sequenced the genomes of two closely related radish inbred lines that differ in their ability to spontaneously form tumours. We have identified numerous single nucleotide variants (amino acid substitutions, insertions or deletions) that are likely to be associated with the spontaneous tumour formation. Furthermore, we performed the identification of CLE and WOX genes the genomic sequences of the radish inbred lines and, as a result, identified two unique radish CLE genes which probably encode proteins with multiple CLE domains. The results obtained provide a basis for investigating the mechanisms of plant tumour formation and also for future genetic and genomic studies of radish.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

(1) Background: in the context of sustainable development goals (SDGs), this work explores the repair direction of future cultivated land protection policies based on the Smith policy implementation model from the historical evolution to ensure that the cultivated land protection policy does not deviate during the implementation process. (2) Methods: this paper uses literature research and inductive deduction methods to sort out the evolution process of Chinese cultivated land protection policy, summarize the successful experience of transferring the focus of cultivated land protection in chronological order, and conclude the repair direction of Chinese cultivated land protection. (3) Results: although the Chinese cultivated land protection policy in the historical evolution has through three significant phases, there are still certain issues in the development trend of Chinese cultivated land protection policy based on regional division of labor for grain transportation and sales. (4) Conclusion: directly utilizing feedback from farmers as stakeholders will contribute to the maturity and improvement of cultivated land protection policies in the specific implementation of cultivated land protection policies.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia by surveying rare pathogenic variants. The analysis was performed on 91 patients, the DNA samples of which were pooled and then subjected to whole exome sequencing. Among detected variants two are rare pathogenic and show significant difference in frequency between the analyzed pool and gnomAD Bulgarian control exomes. The rs373478202, G&gt;T, B9D1 variant, most likely present in heterozygous state; is causative for the autosomal recessive ciliopathy- Joubert syndrome, which involves specific CNS malformation. The rs148918985, C&gt;T, ASS1 variant leads to arginosuccinate enzyme deficiency and in compound heterozygosity with other rare pathogenic variant detected in the same gene causes the late-onset form of citrullinemia type I. This disorder causes high ammonia levels, which can lead to cerebral dysfunction. In conclusion, the detected rare pathogenic variants suggest that, in certain cases, the development of non-AD and non-FTD dementia can be mediated by structural alterations in neuronal cilia or by hyperammoniemia.

: A comprehensive analysis was performed, considering blockchain technology (BT) proprieties in digital health, addressing medico-legal, privacy, and regulatory considerations. Adherence to personal data protection and healthcare regulatory guidelines were analyzed and compared for GDPR (Europe), HIPAA (United States), CCPA (California), PIPEDA (Canada), Privacy Act of 1988 (Australia), APPI (Japan), and LGPD (Brazil). Issues such as Health Systems, Strengthening and aligning policy orientations and initiatives, and emphasizing the role of data analysis in shaping health policies were explored. The study addressed conflicts between the legal frameworks and blockchain, comparing and suggesting solutions like revision of laws and integration of com-pliance mechanisms. Additionally, it sought to enhance IT-health literacy by integrating healthcare and legal domains. Ongoing collaboration between legal, health, and IT experts is essential for designing systems that effectively balance privacy rights and data protection while maximizing the benefits of disruptive technologies like blockchain.

Extracellular vesicles represent a large heterogeneous class of near and long-distance intercellular communication mediators, released by both prokaryotic and eukaryotic cells. Specifically, the scientific community has shown a growing interest in exosomes, which are nano-sized vesicles with an endosomal origin. Not so long ago, the physiological goal of exosome generation was largely unknown and required more investigation; at first, it was hypothesized that exosomes are able to remove excess, rejects and unnecessary constituents from cells to preserve cellular homeostasis. However, thanks to recent studies, the central role of exosomes in regulating cellular dialogue has emerged. Exosomes act as vectors on cell-cell signaling by their cargo, proteins, lipids, and nucleic acids, and influence physiological and pathological processes. The findings on exosomes are widespread in a large spectrum of biomedical applications from diagnosis and prognosis to thera-pies. In this review, we describe exosome biogenesis and the current methods for their isolation and characterization, emphasizing the role of their cargo in female reproductive processes, from gametogenesis to implantation, and the potential involvement in human female disorders.

Frailty is a common condition in older adults that negatively impacts health and quality of life. This study evaluated a comprehensive, personalized, and coordinated intervention under the Value-Based Care approach to address frailty's multidimensional nature in older people. It em-ployed a pre-post randomized controlled design, involving frail individuals over 65 years in Valencia, Spain. Assessments were conducted at baseline, 12 months (immediately post-intervention), and 18 months. The intervention included a personalized care plan supported by technology, with monthly motivational follow-ups and plan updates by health professionals and participants. Outcomes were measured using an assessment questionnaire that included the International Consortium for Health Outcomes Measurement dataset for the older population: physical health, physical functioning, general mental health, satisfaction with social activities and relationships, ability to carry out usual social roles and activities, pain, general quality of life, loneliness, physical frailty, psychological frailty and social frailty. The study found signifi-cant improvements in physical frailty, quality of life, reduced health resource use and hospitali-zations, and lower levels of pain and depression/anxiety compared to baseline. The findings suggest further research into value-based care approaches, emphasizing the development and activation of personalized, comprehensive programs for older individuals with frailty.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Efficient gene transfer and expression tool is lacking for shrimps and shrimp cells. To solve this, this study has developed a shrimp DNA virus-mediated gene transfer and expression system, consisting of insect Sf9 cells for viral packaging, shrimp viral vector of pUC19-IHHNV-PH-GUS and baculoviral vector of Bacmid or Bacmid-VP28 encoding shrimp WSSV envelope protein VP28. The pUC19-IHHNV-PH-GUS vector was constructed by assembling the genomic DNA of shrimp infectious hypodermal and hematopoietic necrosis virus (IHHNV), which had shortened inverted terminal repeats, into pUC19 backbone, and then an expression cassette of baculoviral polyhedron (PH) promoter-driven GUS reporter gene was inserted immediately downstream of IHHNV for proof-of-concept. It was found that the viral vector of pUC19-IHHNV-PH-GUS could be successfully packaged into IHHNV-like infective virions in the Sf9 cells, and gene transfer efficiency of this system had been evaluated and verified in three systems of Sf9 cells, shrimp hemolymph cells and tissues of infected shrimps, but GUS expression could be detected only in the cases when the viral vector was co-transfected or co-infected with a baculovirus of Bacmid or Bacmid-VP28 due to the Bacmid-dependence of PH promoter. Moreover, the packaging and infection efficiencies could be significantly improved when Bacmid-VP28 was used instead of Bacmid.

Members of the genus Armillaria are widespread forest pathogens against which effective protection has not yet been developed. Due to their longevity and the creation of large-scale cloning of Armillaria individuals, the use of mycoviruses as biocontrol agents (BCAs) against these pathogens could be an effective alternative. This work describes the screening of double-stranded RNA banding patterns as a first approach for potential virus discovery and the use of stranded total RNA-seq for viral detection and characterization in Armillaria spp. collected in the Czech Republic. A total of five single-stranded RNA viruses were detected in Armillaria ostoyae and A. cepistipes, including the first virus of the family Tymoviridae found infecting a member the genus Armillaria and four viruses belonging to the recently described virus group "ambiviruses" with circular ambisense genome organization. Both hammerhead (HHRz) and hairpin (HpRz) ribozymes were detected in all the ambiviricot sequences. Armillaria viruses were compared by phylogenetic analysis and confirmed their specific host by direct RT-PCR, which showed the occurrence of interspecies transmission.

Current antibiograms cannot discern the particular effect of a specific antibiotic when the bacteria are incubated with a mixture of antibiotics. To prove that this task is achievable, Escherichia coli strains were treated with ciprofloxacin for 45 min, immobilized on a slide and stained with SYBR Gold. In susceptible strains, the nucleoid relative surface started to decrease near the MIC, being progressively condensed as dose increased. The shrinkage level correlated with the DNA fragmentation degree. Ciprofloxacin-resistant bacilli showed no change. Additionally, E. coli strains were incubated with ampicillin for 45 min and processed similarly. The ampicillin-susceptible strain revealed intercellular DNA fragments that increased with dose, unlike the resistant strain. Co-incubation with both antibiotics revealed that ampicillin did not modify the nucleoid condensation effect of ciprofloxacin, whereas the quinolone partially decreased the background of DNA fragments induced by ampicillin. Sixty clinical isolates, with different combinations of susceptibility-resistance to each antibiotic, were co-incubated with the EUCAST breakpoints of susceptibility of ciprofloxacin and ampicillin. The morphological assay correctly categorized all the strains for each antibiotic in 60 min, demonstrating the feasible independent evaluation of a mixture of quinolone and beta-lactam. The rapid phenotypic assay may shorten the incubation times and necessary microbial mass currently required for evaluation.

Beaches are among the habitats most frequented by migratory birds for breeding and/or wintering. However, threats such as human pressure and sea level rise can reduce the availability of these habitats for different species. The presence of alternative areas, such as salt pans and brackish habitats, is essential for many migratory shorebird populations. This study addresses the post-breeding dispersal of the Kentish plover (Charadrius alexandrinus) in the Iberian Peninsula by analysing C and N isotopes in feathers. The study was conducted at six locations along the Iberian coast, which were categorized in three areas: NW Atlantic coast, the Atlantic coast of Andalusia and the Mediterranean coast. Although linear mixed models did not reveal any significant effects of sex or coastal area on isotopic levels, the variability in the data suggests different habitat-use strategies in the post-reproductive period. Birds from the northwest of the Iberian Peninsula exhibit greater fidelity to a single habitat type, i.e. coastal beaches, while populations from the Mediterranean coast and the Atlantic coast of Andalusia show different individual dispersal strategies, occupying coastal habitats and freshwater wetlands. The lack of alternative habitats for the northwest Iberian population, the reduction in available habitat due to rising sea levels and human pressure together pose a serious threat to the survival of this species, already with an unfavourable conservation status.

The raw material purchasing (RMP) problem is to determine the purchasing quantities of raw materials in given periods or cycles. Raw material purchasing optimization is crucial for large-scale steel plants because it is closely related to the supply of raw materials and cost savings. The raw material purchasing of large-scale steel enterprises is characterized by many varieties, large quantities, and high costs. The RMP objective is to minimize the total purchasing cost consisting of the price of raw materials, purchasing set-up costs, and inventory costs and meet product demand. We present a mixed integer linear programming (MILP) model and a column generation (CG) solution for the resulting optimization problem. The column generation algorithm is the generalization of the branch & bound algorithm with solving the linear programming (LP) relaxation of MILP using column generation (CG), and its advantage is to handle large-sized MILPs. Experimental results show the effectiveness and efficiency of the solution.

Many fundamental molecular techniques (PCR, Microarray, Southern and northern hybridization, siRNA, CRISPR/Cas9 etc.) developed so far shows errors. I wish to highlight these molecular techniques are developed on basis of Watson-Crick DNA model, ignoring the concept of parallel stranded DNA. Through this opinion article, I wish to highlight specificity and accuracy of these molecular techniques can be enhanced by considering both parallel and anti parallel hybridization of DNA. Hopefully my views will also solve issue of irreproducibility in life science research.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

The digital era offers many opportunities to the wind energy industry and research community. Digitalisation is one of the key drivers for reducing costs and risks over the whole wind energy project life cycle. One of the largest challenges in successfully implementing digitalisation is the lack of data sharing and collaboration between organisations in the sector. In order to overcome this challenge, a new collaboration method called WeDoWind was developed in recent work. The main innovation of this method is the way it creates tangible incentives to motivate and empower different types of people from all over the world to actually share data and knowledge in practice. In this present paper, the challenges related to comparing and evaluating different SCADA data based wind turbine fault detection models are investigated by carrying out a new case study, the "WinJi Gearbox Fault Detection Challenge", based on the WeDoWind Method. Six new solutions were submitted to the challenge, and a comparison and evaluation of the results show that, in general, some of the approaches (Particle Swarm Optimisation algorithm for constructing health indicators, performance monitoring using Deep Neural Networks, Combined Ward Hierarchical Clustering and Novelty Detection with Local Outlier Factor and Time-to-failure prediction using Random Forest Regression) appear to have a high potential to reach the goals of the Challenge. However, there are a number of concrete things that would have to have been done by the Challenge providers and the Challenge moderators in order to ensure success. This includes enabling access to more details of the different failure types, access to multiple data sets from more wind turbines experiencing gearbox failure, provision of a model or rule relating fault detection times or a remaining useful lifetime to the estimated costs for repairs, replacements and inspections, provision of a clear strategy for training and test periods in advance, as well as provision of a pre-defined template or requirements for the results. These learning outcomes are used directly to define a set of best practice data sharing guidelines for wind turbine fault detection model evaluation. They can be used by the sector in order to improve model evaluation and data sharing in the future.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

With increasing air and sea temperatures, the thermodynamic environments over the oceans become more favourable for the development of intense tropical cyclones (TCs) with rapid intensification (RI). In fact, the number of TCs undergoing RI is rising (Zhao, et al., 2018; Bhatia, et al., 2019; Song, et al., 2020; Hong & Wu, 2021; Liu, et al., 2022). RI over coastal sea areas before landfalling is particularly impactful and threatening to coastal lives and properties. There have been studies showing that offshore areas within 400 km of the coastline have experienced a significant increase in RI events with the count tripling from 1980 to 2020 (Li et al., 2023). The south China coastal region consists of highly densely populated cities especially the Pearl River Delta (PRD) region. Intense TCs maintaining its strength or RI of TCs close to the coastal region presents substantial forecasting challenges. This study investigates the effect of sea surface and subsurface temperature and salinity on the intensification of five TCs, namely Super Typhoons Hato in 2017 and Mangkhut in 2018, Typhoon Talim, Super Typhoon Saola and Severe Typhoon Koinu in 2023, which significantly affected the south China coastal region and triggered high TC warning signals in Hong Kong. The analysis utilized the Hong Kong Observatory (HKO) TC track and intensity data, along with the sea temperature and salinity profiles generated using the China Ocean ReAnalysis version 2 (CORA2) of the National Marine Data and Information Service (NMDIS) of China. While high sea surface temperature (SST) of 30°C or above, low surface sea surface salinity (SSS) of 34 psu or below, and strong salinity stratification of at least 0.8 psu per 100 m depth may offer useful hints for predicting RI, they are part of a broader set of contributing factors. This study represents the initial documentation of sub-surface salinity's impact on intense TCs over the South China Sea (SCS) in recent years and will encourage further research to refine forecasting RI of TCs before making landfall near PRD taking into account the effect of freshwater from the Pearl River.

Cloud computing refers to applications delivered as services over the Internet. Cloud systems employ policies that are inherently dynamic in nature and that depend on temporal conditions defined in terms of external events, such as the measurement of bandwidth, use of hosts, intrusion detection or specific time events. In this paper, we investigate an optimized resource management scheme named v-Mapper. The basic premise of v-Mapper is to exploit application-awareness concepts using software-defined networking (SDN) features. This paper makes three key contributions to the field: (1) We propose a virtual machine (VM) placement scheme that can effectively mitigate the VM placement issues for data-intensive applications; (2) We propose a validation scheme that will ensure that a service is entertained only if there are sufficient resources available for its execution and (3) We present a scheduling policy that aims to eliminate network load constraints. An evaluation was carried out with various benchmarks and demonstrated that v-Mapper shows improved performance over other state-of-the-art approaches in terms of average task completion time, service delay time and bandwidth utilization. Given the growing importance of supporting large-scale data processing and analysis in datacentres, the v-Mapper system has the potential to make a positive impact in improving datacentre performance in the future.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

This study presents a detailed assessment on the impact of the Brazilian legal framework related to the access and benefit sharing provisions of the UN Convention on Biological Diversity. The research is based on a comprehensive dataset that was systematically collected over several years, directly from the official government bodies responsible for its implementation. The aim of the study is to contribute to a fact-based discussion on the effectiveness of national ABS laws, focusing on the Brazilian legal framework, first established in the year 2000 and revised in 2015, as a case example. This study balances the costs and benefits of the Brazilian ABS system and assesses the regulatory challenges it poses to individuals, companies, and institutions that perform research, share knowledge, develop, manufacture or market products derived from Brazilian biodiversity. The study indicates that, after over 22 years of operation, the regulatory challenges are still real and relevant, and that the significant volume of data collected from users on access, prior commercialization and shipment of genetic materials abroad was never systematically assessed by the agencies in charge. Besides, it shows that the costs incurred by the government in managing the policy itself have been higher than the economic benefits it has made possible, and that the institutional mechanisms in place since 2015 have not been able to allocate the monetary benefits contributed by users to the National Benefit Sharing Fund to any projects aimed at developing sustainable uses or preserving Brazilian biodiversity.

The current green development in the context of public policy and industrial economy is difficult to fully match the new infrastructure process driven by massive data. Its connotation and exten-sion and the level of rule of law need to be deepened to ensure that data production, processing, circulation, elimination and other activities can get high-quality and sustainable development in the collaborative construction of hard facilities and soft environment in the new era. Based on the practical needs of data industry green development in key areas, we can resolve the legal risk of data industry green development from three aspects: improving the legal level of green public policy, clarifying the green legal benchmark of data industry development, and improving the green legal system of digital society. Then, it considers the design of environmental protection system based on hardware facilities and the structural and readable clean data system innova-tion of soft data industry development framework mode, so as to clarify the legalization scheme of data industry green development under the new infrastructure. Overall, achieving the green development of the data industry requires not only active attempts by China but also joint efforts by China and other countries.

Accurate power curve modelling is essential to continuously evaluate the performance of a wind turbine (WT). In this work, we characterize the wind power curves using SCADA data acquired at a frequency of 5 minutes in a wind farm (WF) consisting of 5 WTs. Regarding the non-parametric methods, we select artificial neural networks (ANNs) to make curve estimations. Given that, we have the curves provided by the manufacturer of the WTs given by some very precisely measured pair of wind speed and power points. We can evaluate the difference between the manufacturer characterization and the ones estimated with the data provided by the SCADA system. Before the estimation, we propose a method of filtering the anomalies based on the characteristics provided by the manufacturer. We use three-quarters of the available data for curve estimation and one-quarter for the test. One WT suffered a break in the test part, so we can check how the test estimates reflect this problem in its wind-power curve compared to the estimations obtained in the WTs that worked adequately.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (version 2.0) contains increased 24,145 predicted genes from previous version (24317 genes) with a higher BUSCO value of 96.9%. 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjust genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserve their original des ignations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using newly obtained transcriptome data with the revised gene prediction model. This improved annotation of cucumber genome will provide essential and accurate resources for studies in cucumber.

Accurate forecasting of crop yields holds paramount importance in guiding decision-making processes related to breeding efforts. This study focused on the application of multi-sensor data fusion and machine learning algorithms based on unmanned aerial vehicles (UAVs) in wheat yield prediction. Five machine learning (ML) algorithms namely random forest (RF), partial least squares (PLS), ridge regression (RR), K-Nearest Neighbor (KNN) and eXtreme Gradient Boosting Decision Tree (XGboost) were utilized for multi-sensor data fusion, and three ensemble methods including the second-level ensemble methods (stacking and feature-weighted) and the third-level ensemble method (simple average) for wheat yield prediction. The 270 wheat hybrids were used as planting materials under full and limited irrigation treatments. A cost-effective multi-sensor UAV platform, equipped with red–green–blue (RGB), multispectral (MS), and thermal infrared (TIR) sensors, was utilized to gather remote sensing data. The results revealed that the XGboost algorithm exhibited outstanding performance in multi-sensor data fusion, with the RGB+MS+Texture+TIR combination demonstrating the highest fusion performance (R2=0.660, RMSE= 0.754). Compared with the single ML model, the employment of three ensemble methods significantly enhanced the prediction accuracy of wheat yield. Notably, the third-layer simple average ensemble method demonstrated superior performance (R2 = 0.733, RMSE= 0.668 t ha-1). It significantly outperformed both the second-layer ensemble methods of Stacking (R2= 0.668, RMSE= 0.673 t ha-1) and feature-weighted (R2= 0.667, RMSE= 0.674 t ha-1), thereby exhibiting superior predictive capabilities. This finding demonstrated that the third-layer ensemble method not only augments the predictive ability of the model but also fine-tuned the accuracy of wheat yield prediction through the employment of simple average ensemble learning. Consequently, it offers a novel perspective for crop yield prediction and breeding selection.

Following the adoption of the Kunming-Montreal Global Biodiversity Framework (KM-GBF), with the Convention on Biological Diversity serving as its guiding treaty, the European Union (EU) has just reached an agreement on an EU Nature Restoration Regulation. This study carries out a systematic cross-walk between the restoration regulation and the KM-GBF, focusing on their implications for forest ecosystems. This paper identifies areas of alignment, divergence, and potential gaps related to habitat restoration, species protection, climate resilience, and the sustainable use of natural resources. The methodology adopts a grounded approach, starting with the 23 targets outlined in the KM-GBF and proceeding to the 28 articles set out in the restoration regulation. The results highlight the need for better alignment between the KM-GBF, the restoration regulation, and other forest-relevant EU policy instruments. The study stresses the need for a coherent and integrated EU policy approach that can address the diverse challenges and policy objectives facing forests. It concludes that amendments to the restoration regulation have significantly diluted its potential impact, limiting the EU Members States accountability and ability to meet KM-GBF goals and targets. It further stresses the need for strategies that can reconcile divergent EU policy pathways, support forest management and restoration efforts, while aligning with global biodiversity objectives.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Prochlorococcus, a cyanobacteria genus of the smallest and most abundant oceanic phototrophs, encompasses ecotype strains adapted to high-light (HL) and low-light (LL) niches. To elucidate the adaptive evolution of this genus, we analyzed 40 Prochlorococcus marinus ORFeomes, including two cornerstone strains, MED4 and NATL1A. Employing deep learning with robust statistical methods, we detected new protein family distributions in the strains and identified key genes differentiating HL and LL strains. HL strains harbor genes (ABC-2 transporters) related to stress resistance, such as DNA repair and RNA processing, while LL strains exhibit unique chlorophyll adaptations (ion transport proteins, HEAT repeats). We report variable, depth-dependent endogenous viral elements in the 40 strains. We constructed the ORFeomes of MED4 and NATL1A covering 99 % of the annotated protein-coding sequences of the two species, totaling 3976 cloned, sequence-verified ORFs. These comparative genomics analyses, paired with MED4 and NATL1A ORFeomes, will facilitate future genotype-to-phenotype mappings and systems biology exploration of Prochlorococcus ecology.

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations, as well as research. In order to make use of pathogen genomics data, it must be interpreted using contextual data (metadata). Contextual data includes sample metadata, laboratory methods, patient demographics, clinical outcomes, and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration, and its use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating, and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool’s web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission.In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.

Clustered regularly interspaced short palindromic repeats (CRISPR) based gene-editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single guide RNA (sgRNA)-based gene-editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, instructive, and inspiring for future advances. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent beta thalassemia has renewed hope for treating other hematologic diseases, including patients with germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-based gene therapies. The purpose of this manuscript is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy; and third, the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with germline predisposition to hematologic malignancies.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

The Indonesia’s Tobacco Excise Sharing Fund (DBHCHT) policy mandates that part of the fund should be allocated for tobacco crop diversification – reducing the farmers’ reliance on tobacco industry as well as implementing Article 17 of Framework Convention on Tobacco Control (FCTC). However, very little is known on practical implication of this fund on tobacco farmers livelihood. We collected primary data from key stakeholders in four main tobacco producing municipalities. The data were analyzed using qualitative content analysis with NVivo 12. Numbers of challenges on DBHCHT utilization remained at sub-national levels. The sub-optimal use of DBHCHT could partly be explained by: (i) constantly changing central government regulation; (ii) farmers’ unawareness of DBHCHT regulation; (iii) the delay in DBHCHT allocation; and (iv) supply and demand mismatch. Although Indonesia has not been a part of the FCTC ratification, the DBHCHT mandate is in line with the FCTC article 17, i.e., promoting economically viable alternatives for tobacco farmers. This study concluded that DBHCHT utilization needs to go a long way to void this mandate given the challenges at sub-national level. Therefore, this study recommends more technical and practical regulations involving multisectoral stakeholders and the use of DBHCHT to facilitate financial needs of crop diversification.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Cybercrime Threat Intelligence (CTI) allows us to change our actions from reactive to proactive in the fight against threat actors, and to make more informed, data-driven security decisions. Thus this study proposes the practical implementation of CTI in the Arab world. This study focuses on strengthening CTI by integrating Indicators of Compromise (IoCs) and collecting realistic security alerts from honeypot systems and open source intelligence. The collected data is stored in the Malware Information Sharing Platform (MISP), an open source platform that allows users to create and share IoCs with other organizations while staying informed about new threats. It features an intuitive interface for data analysis and threat identification, facilitating sharing, storage, and correlation of IoCs. Therefore, we leveraged MISP to generate IoCs based on the collected data and analyzed the results to identify potential cyber threats. The implemented platform aims to provide organizations with actionable information to prevent, detect and respond to cybercrime. This study presents a practical approach to strengthening CTI in the Arab world and provides an opportunity to strengthen the region’s security posture.