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In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimers disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and controls, revealing decreased formate and fumarate concentrations in AD. Additionally, we utilised whole-genome sequencing (WGS) data obtained from a separate group of individuals with AD and controls. This information allowed us to create and investigate host-microbiome personalised whole-body metabolic models. Notably, AD individuals displayed diminished formate microbial secretion in these models. Additionally, we identified specific reactions responsible for the production of formate in the host, and interestingly, these reactions were linked to genes that have correlations with AD. This study suggests formate as a possible early AD marker and highlights genetic and microbiome contributions to its production. The reduced formate secretion and its genetic associations point to a complex connection between gut microbiota and AD. This holistic understanding might pave the way for novel diagnostic and therapeutic avenues in AD management.

Oleanolic acid (OA) is a triterpenoid that occurs naturally and may be isolated from various plants. Analogs of oleanolic acid can be produced artificially or naturally. The current treatments have limited selectivity and may also impact normal cells. OA and its derivatives provide a promising cancer treatment platform with greater selectivity and less toxic effects. As a result of their enhanced sensitivity, selectivity, and low toxicity, they are great options for focusing on particular biological pathways and reducing the growth of tumor cells. The effects of OA and derivatives of OA on various cancer types have been investigated. However, breast and hepatocellular malignancies are the most studied cancers. In breast cancer, derivatives such as saikosaponin A (SSa), saikosaponin B (SSb), and SZC014 influence key pathways such as the Janus kinase/signal transducer and activator of transcription (JAK/STAT), protein kinase-B (Akt), and nuclear factor-kappa B (NF-κB) pathways, inhibiting metastasis, angiogenesis, and cell migration, respectively. When a para-aminobenzoic acid (PABA)/nitric oxide (NO) derivative of OA is administered to HepG2 cells, the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)-mediated mitochondrial pathway causes apoptosis. Nanoformulations incorporating OA, such as OA-paclitaxel (PTX), show potential for suppressing tumor progression by inhibiting drug efflux mechanisms. Thus, exploring the interactions of OA and a few of its derivatives with various cellular pathways offers a promising approach to combating different types of cancer. This review delves into the potential of oleanolic acid and its derivatives in retarding cancer progression through their interactions with diverse cellular pathways. [ABSTRACT FROM AUTHOR]

The recent approval of lecanemab highlights that the amyloid beta (Aβ) protein is an important pathological target in Alzheimer's disease (AD) and further emphasizes the significance of neuroinflammatory pathways in regulating Aβ accumulation. Indeed, Aβ accumulation triggers microglia activation, which are key mediators in neuroinflammation. The inflammatory responses in this process can lead to neuronal damage and functional decline. Microglia secrete proinflammatory cytokines that accelerate neuronal death and release anti-inflammatory cytokines and growth factors contributing to neuronal recovery and protection. Thus, microglia play a dual role in neurodegeneration and neuroprotection, complicating their function in AD. Therefore, elucidating the complex interactions between Aβ protein, microglia, and neuroinflammation is essential for developing new strategies for treating AD. This review investigates the receptors and pathways involved in activating microglia and aims to enhance understanding of how these processes impact neuroinflammation in AD, as well as how they can be regulated. This review also analyzed studies reported in the existing literature and ongoing clinical trials. Overall, these studies will contribute to understanding the regulatory mechanisms of neuroinflammation and developing new therapies that can slow the pathological progression of AD. [ABSTRACT FROM AUTHOR]

This issue of the IDS Bulletin brings together a range of empirically grounded studies that add to - and challenge - contemporary debates on climate and environmental justice. Despite a growing focus on justice dimensions of climate and environmental change, we argue that there are still 'blind spots' in mainstream debates that warrant increased attention. In this brief introduction, we point to three in particular: first, a persistent failure to recognise diverse contexts and knowledges; second, a continuing failure to sufficiently appreciate the deep-seated contestations around climate and environmental justice; and third, the risks associated with 'recovery' and 'emergency' mindsets driving climate and environmental policy agendas. The articles in this collection illustrate and exemplify these issues in different ways and from a variety of methodological, philosophical, and interdisciplinary approaches and positionalities. We argue for a reframing of climate and environmental justice debates and suggest some key principles to make these 'hidden' aspects more visible in policy and practice. [ABSTRACT FROM AUTHOR]

Introduction: The synergistic combination of histone deacetylase inhibitors and platinum-based medicines represents a promising therapeutic strategy to efficacy and overcome drug resistance in cancer therapy, necessitating a comprehensive understanding on their molecular interactions and clinical potential. Areas covered: The objective of presented review is to investigate the molecular pathways of platinum medicines and HDAC inhibitors. A comprehensive literature review from 2011 to 2024 was conducted across multiple databases like MEDLINE, PubMed, Google Scholar, Science Direct, Scopus and official websites of ClinicalTrial.gov to explore publications on HDAC inhibitors, platinum drugs, and combination cancer therapies, revealing preliminary evidence of innovative treatment strategies involving HDAC inhibitors and platinum chemotherapeutics. Several new platinum (IV) complexes, with HDAC inhibitory moieties and better cytotoxicity profiles than conventional platinum drugs, are also reviewed here. Expert opinion: The above combination has great potential in cancer treatment, however managing toxicity, dosage regimens, and patient selection biomarkers are problematic. More selective HDAC inhibitors and innovative delivery techniques are potential areas for future research. An adaptation toward changing cancer therapeutic landscapes, highlights combining HDAC inhibitors with platinum-based medicines serves as a new concept for personalized medicine, however, a deeper research is still needed at this time. [ABSTRACT FROM AUTHOR]

Introduction: To further advance our understanding of Muscular Dystrophies (MDs) and Spinocerebellar Ataxias (SCAs), it is necessary to identify the biological patterns associated with disease pathology. Although progress has been made in the fields of genetics and transcriptomics, there is a need for proteomics and metabolomics studies. The present study aimed to be the first to document serum metabolic signatures of MDs (DMD, BMD, and LGMD 2A) SCAs (SCA 1-3), from a South Asian perspective. Methods: A total of 28 patients (SCA 1-10, SCA 2-2, SCA 3-2, DMD-10, BMD-2, LGMD-2) and eight controls (aged 8–65 years) were included. Metabolomic analysis was performed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS), with support from the Houston Omics Collaborative. Results and discussion: Amino acid metabolism was the primary altered super pathway in DMD followed by carbohydrate metabolism and lipid metabolism. In contrast, BMD and LGMD 2A exhibited a more prominent alteration in lipid metabolism followed by amino acid metabolism. In SCAs, primarily lipid, amino acid, peptide, nucleotide, and xenobiotics pathways are affected. Our findings offer new insights into the variance of metabolite levels in MD and SCA, with substantial implications for pathology, drug development, therapeutic targets and clinical management. Intriguingly, this study identified two novel metabolites associated with SCA. This pilot cross-sectional study warrants further research involving larger groups of participants, to validate our findings. [ABSTRACT FROM AUTHOR]

This paper offers a feminist reflection on the findings of an ongoing study of health and wellbeing associated with urban food security in Nairobi and Cape Town. It offers five pathways through which a strengthened informal sector can contribute to transforming urban food systems: identifying stronger entry points for institutionalized collaboration between local governments and community-based organizations; enhancing government capacities to collaborate with grassroots actors; the potential, and challenges, of controlled-environment agriculture; rethinking and shifting the regulatory environment surrounding the informal economy; and responding to detailed new data on the state of food security in South African informal settlements. Conducted in partnerships between the Urban Food Futures program and people who were permanently displaced during the colonial era, the study is informed by an emerging body of analysis that responds to the complex trauma of undernutrition, and approaches health as something far beyond an individual's own somatic/bodily state of being. Participation in the study enabled communities living in a near-permanent state of precarity and food insecurity, in the absence of culturally appropriate and readily-available supports to mental health, to move beyond an isolated focus on food to explore feelings of psychic safety and security, and also environmental wellbeing, including access to clean air and water, decent and affordable housing, safe and dignified work, and freedom from violence of all forms. [ABSTRACT FROM AUTHOR]

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Background: In children with type 1 diabetes (T1D), diabetic ketoacidosis (DKA) triggers a significant inflammatory response; however, the specific effector proteins and signaling pathways involved remain largely unexplored. This pediatric case–control study utilized plasma proteomics to explore protein alterations associated with severe DKA and to identify signaling pathways that associate with clinical variables. Methods: We conducted a proteome analysis of plasma samples from 17 matched pairs of pediatric patients with T1D; one cohort with severe DKA and another with insulin-controlled diabetes. Proximity extension assays were used to quantify 3072 plasma proteins. Data analysis was performed using multivariate statistics, machine learning, and bioinformatics. Results: This study identified 214 differentially expressed proteins (162 upregulated, 52 downregulated; adj P < 0.05 and a fold change > 2), reflecting cellular dysfunction and metabolic stress in severe DKA. We characterized protein expression across various organ systems and cell types, with notable alterations observed in white blood cells. Elevated inflammatory pathways suggest an enhanced inflammatory response, which may contribute to the complications of severe DKA. Additionally, upregulated pathways related to hormone signaling and nitrogen metabolism were identified, consistent with increased hormone release and associated metabolic processes, such as glycogenolysis and lipolysis. Changes in lipid and fatty acid metabolism were also observed, aligning with the lipolysis and ketosis characteristic of severe DKA. Finally, several signaling pathways were associated with clinical biochemical variables. Conclusions: Our findings highlight differentially expressed plasma proteins and enriched signaling pathways that were associated with clinical features, offering insights into the pathophysiology of severe DKA. [ABSTRACT FROM AUTHOR]

Habitat loss and fragmentation are two of the biggest threats facing wildlife today. Understanding the role of wildlife pathways in connecting resource areas is key for maintaining landscape connectivity, reducing the impacts of habitat loss and helping address human-wildlife conflict. In this study, we used sign surveys and camera trapping to understand the fine scale movement of elephants moving between a protected area and agricultural zone in the Masai Mara, Kenya. We used generalised linear models to determine factors driving high frequency of pathway use by elephants. Our results showed strong seasonal trends in pathway use, with peaks coinciding with the dry season. However, no correlations between rainfall and pathway use were found. Temporal patterns of pathway use indicate that elephants use risk avoidance strategies by moving between the two areas at times of low human disturbance. Spatial analysis revealed that the most frequently used pathways were closer to farms, saltlicks and forest and those that had a higher percentage of forest cover. Our models also showed a positive relationship between pathway use and the number of elephant crop raiding incidents, highlighting that pathways can play a role in human-elephant conflict. As habitat loss continues, pathways may become more important for linking resources. However, they are also likely to facilitate movement into farmland. The results from this study provide an opportunity for planned management activities to ensure connectivity and to mitigated conflict. [ABSTRACT FROM AUTHOR]

The domestication and breeding of wheat genotypes through the years has led to the loss in their genetic variation, making them more prone to different abiotic stresses. Boron (B) toxicity is one of the stresses decreasing the wheat cultivars' yield in arid and semi-arid regions around the world. Wild wheat progenitors, such as Triticum urartu Thumanian ex Gandilyan, possess a broader gene pool that harbors several genes conferring tolerance to various biotic and abiotic stresses. Unfortunately, T. urartu is not well-explored at the molecular level for its tolerance towards B toxicity in soil. In this study, for the first time, we compared the transcriptomic changes in the leaves of a high B-tolerant T. urartu genotype, PI662222, grown in highly toxic B (10 mM B in the form of boric acid) with the ones grown in the control (3.1 μM B) treatment in hydroponic conditions. The obtained results suggest that several mechanisms are involved in regulating the response of the studied T. urartu genotype toward B toxicity. All the growth parameters of T. urartu genotype, including root–shoot length, root fresh weight, and root–shoot dry weight, were less affected by high boron (10 mM) as compared to the boron-tolerant bread wheat cultivar. With a significant differential expression of 654 genes, 441 and 213 genes of T. urartu genotype were down- and upregulated, respectively, in the PI662222 leaves in high B in comparison to the control treatment. While key upregulated genes included those encoding RNA polymerase beta subunit (chloroplast), ATP synthase subunit gamma, chloroplastic, 60S ribosomal protein, and RNA-binding protein 12-like, the main downregulated genes included those encoding photosystem II protein D, ribulose bisphosphate carboxylase small subunit, and peroxidase 2-like. Interestingly, both Gene Ontology enrichment and KEGG pathways emphasized the possible involvement of the genes related to the photosynthetic process and apparatus in the high B tolerance of the T. urartu genotype. The further functional characterization of the identified potential T. urartu genes will facilitate their utilization in crop improvement programs for B toxicity stress. [ABSTRACT FROM AUTHOR]

In this work, combined efforts by Greek and Turkish scientists produced an updated validated NIS inventory of the Aegean ecoregion, covering 120 years of records up to August 2024. Of the 342 NIS currently present in the Aegean Sea, the majority (281 species) have invaded the South Aegean, followed by the North Aegean (128 species out of 206 NIS). A total of 73 species were added to the list, while 56 were removed. Overall, unaided spread of Lessepsian immigrants from the Levantine Sea and shipping are equally responsible for NIS reported at the regional level. An increase in publications addressing NIS matches the upward trend of NIS since the mid-1990s, which continues to the present day. While unaided introductions of Lessepsian species and/or direct introductions via the Suez Canal peaked in the South Aegean during 2000–2005, they peaked in 2012–2017 in the North Aegean—a decade later. The opposite pattern was observed in ship-transferred NIS. The spatial distribution of introduction hotspots largely reflects the following phenomena/processes: unaided introduction is witnessed initially in the southeastern Aegean Sea; monitoring efforts are concentrated in vulnerable and at-risk areas; and research efforts relate to the spatial allocation of institutions and marine experts working on marine NIS along the Aegean coasts. [ABSTRACT FROM AUTHOR]

Tropical cyclones (TCs) trigger vigorous upper ocean mixing, pumping surface warm water into the ocean subsurface. TC-induced ocean subsurface warming (OSWTC) may be transported meridionally and influence ocean heat distribution, particularly in the Northwestern Pacific where TCs are most active. Based on ocean reanalysis products, a Lagrangian Particle Tracking analysis is conducted by releasing virtual particles representing OSWTC in the Northwestern Pacific to investigate the major pathways of OSWTC in the ocean. It is found that more than 50% of total particles are primarily moved westward and then join the Kuroshio Current, flowing northeastward towards the Kuroshio Extension after one year of release. Meanwhile, other particles moved eastward along the Subtropical Countercurrent (~ 4%), westward across the Luzon Strait into the South China Sea (~ 8%), and southward along Mindanao Current (~ 4%). In addition, about a quarter of the OSWTC particles remain locally beneath the mixed layer after one year of release. These results indicate that the majority of OSWTC can contribute to the meridional heat transport in the Northwestern Pacific. Both background currents and westward propagation constrained by differential rotation (Beta effect) contribute to the movements. We also find that the meridional movements of OSWTC are sensitive to the formation latitudes. A more northward formation location of OSWTC corresponds to a more northward heat transport. Since the TC tracks move poleward with global warming, our results imply more northward TC-induced ocean heat transport in the future. [ABSTRACT FROM AUTHOR]

Objectives: To examine (1) how visual green space quantity and quality affect depression among older adults; (2) whether and how the links may be mediated by perceived stress, physical activity, neighbourhood social cohesion, and air pollution (PM2.5); and (3) whether there are differences in the mediation across visual green space quantity and quality. Method: We used older adults samples (aged over 65) from the WHO Study on Global Ageing and Adult Health in Shanghai, China. Depression was quantified by two self-reported questions related to the diagnosis of depression and medications or other treatments for depression. Visual green space quantity and quality were calculated using street view images and machine learning methods (street view green space = SVG). Mediators included perceived stress, social cohesion, physical activity, and PM2.5. Multilevel logistic and linear regression models were applied to understand the mediating roles of the above mediators in the link between visual green space quantity and quality and depression in older adults. Results: SVG quantity and quality were negatively related to depression. Significant partial mediators for SVG quality were social cohesion and perceived stress. For SVG quantity, there was no evidence that any of the above mediators mediated the association. Conclusion: Our results indicated that visual green space quantity and quality may be related to depression in older adults through different mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Against a backdrop of an increasingly younger terrorist cohort within His Majesty's Prison and Probation Service, this study aims to explore the relationship between age and various Extremism Risk Guidance 22+ (ERG22+) assessment outcomes. Design/methodology/approach: A database of 490 individuals was developed by coding content of ERG22+ reports from 2010 to 2021, equating to nearly all cases in England and Wales across this time period. Socio-demographic information, offending histories, online activities and risk factors were coded for all individuals. This study focuses on 465 individuals convicted of terrorist/terrorist-related offending, with statistical analyses used to compare three age groups: "20 and under" (61 cases), 21–25 (133 cases) and "26 and over" (271 cases). Findings: Significant associations were found between presence of certain behaviours/characteristics and age groups. For those aged 20 and under, a heightened propensity for excitement, comradeship and adventure, along with greater susceptibility to influence and need for status were generally key to offending pathways, with a diminished likelihood of a prior criminal history. Of the three ERG22+ dimensions, findings indicate a weak but significant negative correlation between age and engagement levels. Practical implications: Recommendations include ensuring extremism risk assessments reflect age-specific behaviours and tendencies, that interventions are tailored to address common age-related vulnerabilities, and the need for age-specific policies to support and manage children and young adults within the counter-terrorism space. Originality/value: These novel findings point towards notable developmental milestones in adolescence, affecting behavioural tendencies and risk. This underscores the importance of age as a determinant when interpreting extremism risk assessments. [ABSTRACT FROM AUTHOR]

Rationale: Although many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient nonimaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort. Objectives: Our goals were to identify emphysema-associated biological pathways through transcriptomic analysis of bulk lung tissue, to determine the lung cell types in which these emphysema-associated pathways are altered, and to detect unique and overlapping transcriptomic signatures in blood and lung samples. Methods: Using RNA-sequencing data from 446 samples in the Lung Tissue Research Consortium and 3,606 blood samples from the COPDGene study, we examined the transcriptomic features of chest computed tomography–quantified emphysema. We also leveraged publicly available lung single-cell RNA-sequencing data to identify cell types showing chronic obstructive pulmonary disease–associated differential expression of the emphysema pathways found in the bulk analyses. Measurements and Main Results: In the bulk lung RNA-sequencing analysis, 1,087 differentially expressed genes and 34 dysregulated pathways were significantly associated with emphysema. We observed alternative splicing of several genes and increased activity in pluripotency and cell barrier function pathways. Lung tissue and blood samples shared differentially expressed genes and biological pathways. Multiple lung cell types displayed dysregulation of epithelial barrier function pathways, and distinct pathway activities were observed among various macrophage subpopulations. Conclusions: This study identified emphysema-related changes in gene expression and alternative splicing, cell type–specific dysregulated pathways, and instances of shared pathway dysregulation between blood and lung. [ABSTRACT FROM AUTHOR]

This study analyzes 4,095 proactive safety inspection records obtained from a large dispatching centre by utilising the HFACS framework. These proactive safety inspection records offer comprehensive documentation of incidents, capturing major accidents and numerous minor discrepancies and lapses that often go unnoticed in accident reports. The analysis revealed that most incidents were attributed to unsafe actions, primarily skill-based errors and poor decision-making. Additionally, contributing factors such as adverse mental states, personal readiness, and crew resource management were found to play a significant role as preconditions for unsafe acts. Path analyses further established a significant correlation between factors such as unsafe supervision, preconditions for unsafe acts, and the occurrence of unsafe acts. In our discussion, we critically evaluate the strengths and limitations of proactive safety inspection records in safety research. Moreover, we emphasise these findings' potential to enhance safety within the railway industry. PRACTITIONER SUMMARY: Based on a substantial dataset comprising proactive safety inspection records of railway dispatchers rather than the incident reports utilised in prior studies, this paper presents a causal model of human error among railway dispatchers in combination with HFACS and critically evaluates the strengths and limitations of active safety inspection records. [ABSTRACT FROM AUTHOR]

Tea production and quality are largely determined by the many genetic and biochemical characteristics that occur in tea plant cultivars. Worldwide, tea is consumed for its pleasing and refreshing effects due to its caffeine content. The present study performed transcriptomics analyses of two tea species (Camellia sinensis var. Shuchazao (SCZ) and Camellia ptilophylla (CAF)) and identified diversity in the gene expression levels and major regulatory transcription factors (TFs) for the characterization of purine alkaloids and phenylpropanoid biosynthesis pathways. The RNA-seq analysis of two species (SCZ and CAF) revealed the differences in caffeine and catechins synthesis. In the purine alkaloid biosynthesis pathway, the S-adenosyl methionine (SAM) and adenosine monophosphate (AMP) pathway genes were significantly related to xanthosine synthesis in contrasting purine alkaloids among (Camellia sinensis var. Shuchazao (SCZ) and Camellia ptilophylla (CAF)). The significant expression of SAMS-5, PPAT-2, IMPDH-2, TCS-2, TCS-3, XMT-1, XMT-13, and XDH-4 in the xanthosine degradation pathway in CAF is attributed to higher theobromine content as compared to SCZ. Moreover, the transcription factors (TFs) AP2/ERF (20%), WRKY (12%), NAC (11%), and MYB (8%) were significantly correlated. The upregulated expression of caffeine synthesis genes in SCZ was correlated with MYB and AP2/ERF transcription factors. This study provides the basis for differences in the genetic mechanism in purine alkaloids, phenylpropanoid, and flavonoid biosynthesis pathways, which would be helpful in the development and selection of tea plant species with high or low caffeine concentrations. This study also provides a road map for future genetic improvement in tea species and cultivars. [ABSTRACT FROM AUTHOR]

Context: Agroforestry plays a crucial role in increasing tree-based food production for healthy and sustainable food systems. However, the potential of farm trees to contribute to farmers' dietary diversity along multiple paths remains under-researched. Objectives: This study aimed to fill existing knowledge gaps by investigating the role of native trees (toddy palm, jujube, and thanakha) in increasing dietary diversity within dryland agroforestry systems. Methods: We conducted face-to-face qualitative interviews with 47 farmers from the Central Dry Zone of Myanmar (i) to appraise the multiple roles of native tree species in agroforestry landscapes, (ii) to unravel their contributions to four dietary diversity paths, and (iii) to elucidate factors driving the stability of or changes in these pathways. Results: We found that native trees provide food directly and through interaction with crop production and livestock farming, leading to dietary diversification. Agroforestry byproducts are used as fuel and manure, and income from trading agroforestry products provides access to additional food sources. Farmers emphasized the ease of tree management and the roles they play in providing passive income and enhancing resilience to climate stressors as stabilizing factors. However, social-cultural changes, lack of extension services, the unsustainable use of tree products, and market instability were identified as destabilizing factors. Conclusions: This study advances knowledge about the holistic contribution of agroforestry landscapes to dietary diversity by presenting evidence from dryland agroforestry systems in Myanmar. Our findings suggest a need for enhanced understanding of social and ecological changes and cultural factors in agroforestry landscapes to maintain the role of native trees in strengthening dietary diversity. [ABSTRACT FROM AUTHOR]

Purpose of Review: Apraxia typically involves impairments in gesture production and tool use, affecting daily life activities. This article reviews current conceptualizations and developments in diagnostic and therapy. Recent Findings: Apraxia has been studied in various neurological conditions, particularly stroke and dementia, but recent studies show gesturing deficits in psychiatric populations as well. Promising results have emerged from integrative treatment approaches involving intensive practice of gestures or daily activities. However, several reviews have noted the only marginal progress in apraxia therapy research despite new technologies, like virtual reality and brain stimulation, offering fresh opportunities for assessment and therapy. Summary: Advances in lesion-symptom mapping and connectivity analyses led to more detailed neuroanatomical models emphasizing parallel and gradual processing. These models facilitate the understanding of underlying mechanisms of motor cognitive performance and its decline. Finally, the digital era prompts the need to study digital tool use in apraxia, with initial efforts underway. [ABSTRACT FROM AUTHOR]

Background: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes (T1D), arising from relative insulin deficiency and leading to hyperglycemia, ketonemia, and metabolic acidosis. Early detection and treatment are essential to prevent severe outcomes. This pediatric case–control study utilized plasma metabolomics to explore metabolic alterations associated with DKA and to identify predictive metabolite patterns. Methods: We examined 34 T1D participants, including 17 patients admitted with severe DKA and 17 age- and sex-matched individuals in insulin-controlled states. A total of 215 plasma metabolites were analyzed using proton nuclear magnetic resonance and direct-injection liquid chromatography/mass spectrometry. Multivariate statistical methods, machine learning techniques, and bioinformatics were employed for data analysis. Results: After adjusting for multiple comparisons, 65 metabolites were found to differ significantly between the groups (28 increased and 37 decreased). Metabolomics profiling demonstrated 100% accuracy in differentiating severe DKA from insulin-controlled states. Random forest analysis indicated that classification accuracy was primarily influenced by changes in ketone bodies, acylcarnitines, and phosphatidylcholines. Additionally, groups of metabolites (ranging in number from 8 to 18) correlated with key clinical and biochemical variables, including pH, bicarbonate, glucose, HbA1c, and Glasgow Coma Scale scores. Conclusions: These findings underscore significant metabolic disturbances in severe DKA and their associations with critical clinical indicators. Future investigations should explore if metabolic alterations in severe DKA can identify patients at increased risk of complications and/or guide future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: Responding to calls for deeper analysis of the conceptual foundations of service infusion in manufacturing, this paper examines the underlying assumptions that: (i) manufacturing firms incorporating services follow a pathway, moving from pure-product to pure-service offerings, and (ii) profits increase linearly with this process. We propose that these assumptions are inconsistent with the premises of behavioural and learning theories. Design/methodology/approach: Machine learning algorithms are applied to test whether a successive process, from a basic to a more advanced offering, creates optimal performance. The data were gathered through two surveys administered to USA manufacturing firms in 2021 and 2023. The first included a training sample comprising 225 firms, whilst the second encompassed a testing sample of 105 firms. Findings: Analysis shows that following the base-intermediate-advanced services pathway is not the best predictor of optimal performance. Developing advanced services and then later adding less complex offerings supports better performance. Practical implications: Manufacturing firms follow heterogeneous pathways in their service development journey. Non-servitised firms need to carefully consider their contextual conditions when selecting their initial service offering. Starting with a single service offering appears to be a superior strategy over providing multiple services. Originality/value: The machine learning approach is novel to the field and captures the key conditions for manufacturers to successfully servitise. Insight is derived from the adoption and implementation year datasets for 17 types of services described in previous qualitative studies. The methods proposed can be extended to assess other process-based models in related management fields (e.g., sand cone). [ABSTRACT FROM AUTHOR]

Arsenic is a common toxic heavy metal contaminant that is widely present in the ocean, and seaweeds have a strong ability to concentrate arsenic, posing a potential risk to human health. This study first analyzed the arsenic content in two different seaweeds and then used an innovative method to categorize the seaweeds into low-arsenic and high-arsenic groups based on their arsenic exposure levels. Finally, a non-targeted metabolomic analysis based on mass spectrometry was conducted on seaweed from different arsenic exposure groups. The results indicated that as the arsenic concentration increased in the seaweeds, linolenic acid, tyrosine, pheophorbide a, riboflavin, and phenylalanine were upregulated, while arachidonic acid, eicosapentaenoic acid (EPA), betaine, and oleamide were downregulated. The following four key metabolic pathways involving unsaturated fatty acids and amino acids were identified: isoquinoline alkaloid biosynthesis, tyrosine metabolism, phenylalanine metabolism, and riboflavin metabolism. The identification of biomarkers and the characterization of key metabolic pathways will aid in the selection and breeding of low-arsenic-accumulating seaweed varieties, providing insights into the metabolic and detoxification mechanisms of arsenic in seaweeds. [ABSTRACT FROM AUTHOR]

Simple Summary: This article explores the molecular pathways involved in lung cancer, alongside genomic alterations and genetic syndromes associated with the disease. It also reviews testing methods and their role in advancing personalized treatment approaches, offering insights into current therapeutic strategies. This article provides a comprehensive overview of lung cancer from a genetic perspective, emphasizing the molecular pathways involved in its pathogenesis. This review presents the genetic syndromes and key genomic variations, including alterations and instabilities, contributing to tumor development and progression. Furthermore, advancements in genomic testing, such as liquid biopsy, are explored, highlighting their utility in early diagnosis, prognostic evaluation, and personalized treatment strategies. The role of biomarkers in informing therapeutic decisions and optimizing patient outcomes is also examined, offering insights into their potential to refine clinical interventions. This review aims to enrich the understanding of the genetic landscape of lung cancer, providing insights that may lead to improved diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Simple Summary: High-grade serous ovarian cancer (HGSC) has a high heterogeneity both among patients and within a single tumor. Four molecular subtypes of HGSC were previously described. These studies were based on analysis of several types of microarrays. Then, classifiers were created based on these results to determine the molecular subtype. When developing these classifiers, the application to high-throughput sequencing data, especially single-cell data, was not considered. In this paper, we created OVsignGenes, a neural network model for determining the HGSC subtype that can process bulk RNA-Seq or single-cell RNA-Seq data, including spatial transcriptomic data. Background/Objectives: High-grade serous carcinomas (HGSCs) are highly heterogeneous tumors, both among patients and within a single tumor. Differences in molecular mechanisms significantly describe this heterogeneity. Four molecular subtypes have been previously described by the Cancer Genome Atlas Consortium: differentiated, immunoreactive, mesenchymal, and proliferative. These subtypes may have varying degrees of progression, relapse-free survival, and overall survival, as well as response to therapy. The precise determination of these subtypes is certainly necessary both for diagnosis and future development of targeted therapies within personalized medicine. Methods: In this study, we analyzed gene expression data based on bulk RNA-seq, scRNA-seq, and spatial transcriptomic data from six cohorts (totaling 535 samples, including 60 single-cell samples). Differential expression analysis was performed using the edgeR package. The KEGG database and GSVA package were used for pathways enrichment analysis. As a predictive model, a deep neural network was created using the keras and tensorflow libraries. Results: We identified 357 differentially expressed genes among the four subtypes: 96 differentiated, 33 immunoreactive, 91 mesenchymal, and 137 proliferative. Based on these, we created OVsignGenes, a neural network model resistant to the effects of platform (test dataset AUC = 0.969). We then ran data from five more cohorts through our model, including scRNA-seq and spatial transcriptomics. Conclusions: Because the differentiated subtype is located at the intersection of the other three subtypes based on PCA and does not have a unique profile of differentially expressed genes or enriched pathways, it can be considered an initiating subtype of tumor that will develop into one of the three other subtypes. [ABSTRACT FROM AUTHOR]

Congenital anomalies of the kidney and urinary tract (CAKUT) and congenital heart disease (CHD) are the most common congenital defects and constitute a major cause of morbidity in children. Anomalies of both systems may be isolated or associated with congenital anomalies of other organ systems. Various reports support the co‐occurrence of CAKUT and CHD, although the prevalence can vary. Cardiovascular anomalies occur in 11.2% to 34% of patients with CAKUT, and CAKUT occur in 5.3% to 35.8% of those with CHD. The co‐occurrence of genetic factors in both CAKUT and CHD would raise common etiologies including genetics, genetic‐environmental interactions, or shared molecular mechanisms and pathways such as NODAL, NOTCH, BMP, WNT, and VEGF. Studies in animal models and humans have indicated a genetic etiology for CHD and CAKUT with hundreds of genes recognized and thousands of entries, found in a catalog of human genetic disorders. There are over 80 CAKUT genes and over 100 CHD genes available for clinical testing. For example, the HNFIB gene accounts for 5% to 31% of reported cases of CAKUT. In view of the association between CAKUT and CHD, a thorough cardiac examination should be performed in patients with CAKUT, and a similar evaluation for CAKUT in the presence of CHD. This will allow early diagnosis and therapeutic intervention to improve the long‐ term outcome of patients affected, and test for at‐risk family members. We present here evidence for an association of anomalies involving the two organ systems, and discuss possible etiologies of targeted genes, their functions, biological processes and interactions on embryogenesis. [ABSTRACT FROM AUTHOR]

The increasing availability of high-dimensional, longitudinal measures of gene expression can facilitate understanding of biological mechanisms, as required for precision medicine. Biological knowledge suggests that it may be best to describe complex diseases at the level of underlying pathways, which may interact with one another. We propose a Bayesian approach that allows for characterizing such correlation among different pathways through dependent Gaussian processes (DGP) and mapping the observed high-dimensional gene expression trajectories into unobserved low-dimensional pathway expression trajectories via Bayesian sparse factor analysis. Our proposal is the first attempt to relax the classical assumption of independent factors for longitudinal data and has demonstrated a superior performance in recovering the shape of pathway expression trajectories, revealing the relationships between genes and pathways, and predicting gene expressions (closer point estimates and narrower predictive intervals), as demonstrated through simulations and real data analysis. To fit the model, we propose a Monte Carlo expectation maximization (MCEM) scheme that can be implemented conveniently by combining a standard Markov Chain Monte Carlo sampler and an R package GPFDA,which returns the maximum likelihood estimates of DGP hyperparameters. The modular structure of MCEM makes it generalizable to other complex models involving the DGP model component. Our R package DGP4LCF that implements the proposed approach is available on the Comprehensive R Archive Network (CRAN). [ABSTRACT FROM AUTHOR]

Exoskeletons are a defining character of all arthropods that provide physical support for their segmented bodies and appendages as well as protection from the environment and predation. This ubiquitous yet evolutionarily variable feature has been instrumental in facilitating the adoption of a variety of lifestyles and the exploitation of ecological niches across all environments. Throughout the radiation that produced the more than one million described modern species, adaptability afforded by segmentation and exoskeletons has led to a diversity that is unrivalled amongst animals. However, because of the limited extensibility of exoskeleton chitin and cuticle components, they must be periodically shed and replaced with new larger ones, notably to accommodate the growing individuals encased within. Therefore, arthropods grow discontinuously by undergoing periodic moulting events, which follow a series of steps from the preparatory pre‐moult phase to ecdysis itself and post‐moult maturation of new exoskeletons. Each event represents a particularly vulnerable period in an arthropod's life cycle, so processes must be tightly regulated and meticulously executed to ensure successful transitions for normal growth and development. Decades of research in representative arthropods provide a foundation of understanding of the mechanisms involved. Building on this, studies continue to develop and test hypotheses on the presence and function of molecular components, including neuropeptides, hormones, and receptors, as well as the so‐called early, late, and fate genes, across arthropod diversity. Here, we review the literature to develop a comprehensive overview of the status of accumulated knowledge of the genetic toolkit governing arthropod moulting. From biosynthesis and regulation of ecdysteroid and sesquiterpenoid hormones, to factors involved in hormonal stimulation responses and exoskeleton remodelling, we identify commonalities and differences, as well as highlighting major knowledge gaps, across arthropod groups. We examine the available evidence supporting current models of how components operate together to prepare for, execute, and recover from ecdysis, comparing reports from Chelicerata, Myriapoda, Crustacea, and Hexapoda. Evidence is generally highly taxonomically imbalanced, with most reports based on insect study systems. Biases are also evident in research on different moulting phases and processes, with the early triggers and late effectors generally being the least well explored. Our synthesis contrasts knowledge based on reported observations with reasonably plausible assumptions given current taxonomic sampling, and exposes weak assumptions or major gaps that need addressing. Encouragingly, advances in genomics are driving a diversification of tractable study systems by facilitating the cataloguing of putative genetic toolkits in previously under‐explored taxa. Analysis of genome and transcriptome data supported by experimental investigations have validated the presence of an "ultra‐conserved" core of arthropod genes involved in moulting processes. The molecular machinery has likely evolved with elaborations on this conserved pathway backbone, but more taxonomic exploration is needed to characterise lineage‐specific changes and novelties. Furthermore, linking these to transformative innovations in moulting processes across Arthropoda remains hampered by knowledge gaps and hypotheses based on untested assumptions. Promisingly however, emerging from the synthesis is a framework that highlights research avenues from the underlying genetics to the dynamic molecular biology through to the complex physiology of moulting. [ABSTRACT FROM AUTHOR]

In Australia, much like other colonized locations such as Canada, New Zealand, and the USA, the colonial legacies embedded within higher education institutions, including the history of exclusion and the privileging of Western epistemologies, continue to make universities challenging places for Indigenous PhD scholars. Despite this, and while the numbers of Indigenous PhD scholars remain well below population parity, they are carving a space within the academy that is shifting the academic terrain and enriching the research process. Drawing on in-depth interviews with Indigenous PhD scholars working in the field of health and a qualitative survey of doctoral Supervisors and Advisory Committee Chairs, this paper explores the doctoral experience of Indigenous scholars. What becomes apparent, through this research, is that despite ongoing experiences of racism and alienation, these scholars are finding ways to circumvent inadequate supervisory processes, systems support, and research paradigms, to carve a path that centers Indigenous ways of knowing, being, and doing. [ABSTRACT FROM AUTHOR]