The recent EU regulation on Markets in Crypto Assets Regulation (MiCA), represents a significant progress in establishing a multi-jurisdiction framework for crypto-assets that will enable the greater participation of consumers in the digital assets industry. One type of token recognized by MiCA is the asset-referenced token, where the value-bearing asset and the provenance metadata supporting the token's claim are located external to the token. We discuss a number of design considerations for the on-chain and off-chain metadata for MiCA's asset-referenced tokens, with the goal of evolving towards a framework where technical standards can be developed for the assets metadata and related smart contracts technology. The EU Data Spaces provides an interesting data management paradigm that could be used for the decentralized registries infrastructure needed to manage the provenance metadata for various assets.

As a significant form of soil degradation, soil salinization substantially impacts agricultural production and the ecological environment. Remote sensing technology allows for efficient and real-time monitoring and assessment of large-scale soil salinization. With the rapid development of remote sensing technology and the increase in satellite platforms, image acquisition has become more convenient. The significant improvement in satellites’ spatial and temporal resolution has enabled large-scale, high-precision, and continuous dynamic monitoring of soil salinization. In recent years, the introduction and promotion of precision agriculture have significantly advanced research on soil salinization information acquisition and monitoring by combining remote sensing technology with mathematical models and machine learning methods. This paper conducts a systematic literature review of the current progress in remote sensing monitoring of soil salinization. It provides a detailed review of the following aspects: (1) The development status of digital mapping of soil salinization domestically and internationally. (2) The research methods and case studies on soil salinization classification and spatial distribution mapping based on machine learning, focusing on the impact of environmental covariate selection methods in different regions on modeling accuracy and summarizing the advantages and disadvantages of various methods. (3) A systematic review of soil salinization mapping models and environmental covariates based on machine learning. Finally, this paper addresses the current research status and shortcomings, proposing prospects and directions for soil salinization monitoring and digital mapping to provide more specific guidance and recommendations for agricultural planning and development research in China.

Controlling process conditions and cell culture media components is essential for maintaining consistent glycosylation. Here, we evaluated the glycan distribution of CHO-K1 clones producing adalimumab, a biosimilar version of the anti-TNF antibody Humira. In an effort to modulate the glycan profile, the cell culture medium was supplemented with manganese, galactose, copper, or melezitose. Both manganese and galactose increased galactosylation, and the effects were synergistic. Notably, the levels of Man5 were higher than in Humira, even when galactosylation was similar. Copper addition (1.5 mM) increased Man5 levels but reduced G0F, while 25 mM melezitose slightly decreased G0F and Man5. qPCR analysis revealed few differences in glycosylation enzyme concentrations between higher and lower productivity clones, or when either 50 µM manganese or 25 mM melezitose was added. We modeled the glycosylation pathways using a dynamic mathematical model to elucidate the mechanism by which high mannose glycans increased and to develop a more predictive approach to culture modulation. Results suggest that the concentration of activated sugar carriers (i.e., uridine diphosphate, UDP) is limiting and that increased UDP-galactose results in decreased UDP-N-acetylglucosamine, leading to limitations in complex glycan synthesis. These results suggest potential strategies for host cell engineering to obtain more targeted glycan distributions.

Host cell proteins (HCP) are process-related impurities that can co-purify with therapeutic proteins. Some HCP impurities potentially can have an impact on patient safety (immunogenicity or toxicity), efficacy, and/or product quality. It is important to reduce the levels of HCP impurities with a well-controlled manufacturing process and to monitor levels with a suitable analytical assay. Biopharmaceutical companies are now routinely using mass spectrometry (MS) to identify HCPs which are present in process intermediates and potentially in bulk drug substances and using the data to make decisions to continuously improve their processes and mitigate the potential risk to patients. The timing for the identification varies from one company to another. Some companies perform identification of HCPs starting from the nonclinical stage of development, while others perform HCP identification at later stages or as a part of root cause analysis for identified HCP ELISA-related issues, process, and product quality or safety concerns. No matter the approach, a comprehensive risk assessment framework for identified HCPs is needed to support decision-making during development and is expected by regulators to ensure a safe and efficacious drug product. In this paper the BioPhorum Development Group HCP Workstream has brought together a team of industry experts to build upon existing risk assessment frameworks (e.g., de Zafra et al., 2015) and develop recommendations for assessment of clinical safety risks upon identification of individual HCPs, incorporating regulatory considerations and industry experience and using a real-world case study to illustrate the use of the updated frameworks.

Neuroblastoma, the most common solid tumor in children, includes a particularly favorable subtype known as MS neuroblastoma, which is seen in infants under 12 months with metastasis limited to the liver, skin, or bone marrow. Treatment for MS neuroblastoma involves observation or limited chemotherapy typically administered through central venous catheters (CVCs), which carry risks of bloodstream infections and other complications. We describe a female infant with MS neuroblastoma who developed MSSA bacteremia, deep vein thrombosis, and respiratory distress following chemotherapy via a PICC line, requiring its removal. A peripheral IV (PIV) was used for the second round of chemotherapy without complication, suggesting a safer alternative to central lines. Many studies support PIV-administered chemotherapy as a viable option, citing reduced infection rates, fewer complications, and lower costs. While not yet standard practice, PIV chemotherapy administration may be beneficial for patients with high CVC-related risks, warranting further research to establish its role in short-term treatment regimens.

Background: Though long-term outcomes for pediatric cancer continue to improve, survivors frequently develop treatment-related chronic health conditions. Physical activity may improve quality of life (QOL) and decrease chronic health conditions. Wearable activity trackers are a promising interactive intervention for improving physical activity. Procedure: Participants aged 7-21 years undergoing chemotherapy were invited to participate in a 6-week, single-arm trial. The study had 3 phases: blinded to the watch’s interface, unblinded to the watch’s interface, and unblinded to the watch’s interface while receiving encouraging text messages and suggestions for physical activity. Number of steps, hours of sleep, and minutes of moderate-vigorous activity were collected. Participants and their caregivers completed pre- and post-intervention PROMIS® surveys to assess fatigue, pain, and QOL. Results: Seventeen participants enrolled in the study and wore the activity trackers 84.9% of the study time. The median number of steps and daily active minutes increased from the blinded phase to the unblinded phases (3160 versus 3760, p=0.8951; 26.2 minutes versus 36.7, p=0.8065). Patient-reported fatigue and pain interference pre- and post-intervention improved (54.5 versus 50.2; 52.2 versus 46.6, respectively) and met the minimally important difference (MID). Additionally, caregivers’ perception of their child’s fatigue and life-satisfaction pre- and post-intervention improved (40.2 versus 43.9; 58.7 versus 55.1, respectively) and met the MID. Conclusion: The use of activity trackers was feasible for participants in our study. The results of this pilot study suggest wearing an activity tracker may increase physical activity for children undergoing chemotherapy and lead to improved QOL.

News communication is not only a process of information transmission, but also a means of expressing and shaping ideologies. Journalists often embed different political biases in news reports on the same event, depending on their perspectives. Therefore, detecting political bias in news has become a key tool for understanding media bias and uncovering hidden communication strategies. It helps identify politically biased news at its source, thereby reducing the media's influence on public perception. This paper proposes a tree-structured hierarchical model for detecting political bias in news, where elements such as titles, bodies, and sentences serve as nodes. A new method is introduced to extract the central sentence of the news, forming a primary-secondary relationship between sentences. Experimental results show that our model is highly effective in detecting political bias in news.

Background: Reliable biomarkers are critical for risk stratification and prognostic evaluation in kidney renal clear cell carcinoma (KIRC). Although NOTCH receptor 4 (NOTCH4) has been implicated in the prognosis of multiple cancers, its role in KIRC remains poorly understood. Aim: This study aimed to elucidate the role of NOTCH4 in KIRC through comprehensive bioinformatics analysis. Methods and Results: RNA sequencing data and clinical information for 21 tumor types, including KIRC, were retrieved from The Cancer Genome Atlas (TCGA). Pan-cancer analysis revealed elevated NOTCH4 expression in 9 malignancies, including KIRC. Paired t-tests confirmed significant NOTCH4 upregulation in KIRC tissues compared to adjacent normal tissues, and receiver operating characteristic (ROC) curve analysis demonstrated its diagnostic efficacy in distinguishing tumors from normal tissues. These findings were validated using Gene Expression Omnibus (GEO) datasets. KIRC patients from TCGA were stratified into NOTCH4 low- and high-expression groups. Baseline analysis revealed significant differences in gender, T classification, N classification, M classification, clinical stage, and histological grade between groups. Logistic regression confirmed associations between NOTCH4 expression and these clinical characteristics. Subgroup analysis revealed significantly lower NOTCH4 expression in male patients, tumors with T3–T4 classification, N1 classification, M1 classification, stage III–stage IV disease, and G3–G4 tumors. Kaplan-Meier survival analysis indicated that high NOTCH4 expression correlated with prolonged event-free survival and overall survival. Cox regression analyses identified age, M classification, and histological grade were independent prognostic factors. A prognostic nomogram integrating NOTCH4 expression and these independent prognostic factors effectively predicted overall survival. Immune infiltration analysis revealed significant correlations between NOTCH4 expression and endothelial cells, pericytes, macrophages and other immune-related populations. Conclusion: NOTCH4 serves as a promising prognostic biomarker in KIRC and a potential therapeutic target for immunotherapy via immune microenvironment modulation.

Background: Atopic Dermatitis (AD) is a chronic condition characterised by recurrent skin lesions and itch, significantly impacting patients’ quality of life. AD is most common during childhood, with global prevalence ranging between 10% and 20%. Objective: Identifying protein biomarkers underlying AD in children, to better understand the pathogenesis. Methods: Cross-sectional study using untargeted tandem mass spectrometry to analyse skin tape protein extracts from 71 10-year-old Singaporean children. Subjects were stratified into three groups, no history of AD (NoAD=29), history of AD but no symptoms at time of sample collection (PastAD=22) and present AD (PresentAD=20). Significant proteins were shortlisted and functional analyses were performed. Results: 397 differentially expressed proteins were identified (p-value<0.05) with 18 proteins shared with a validation cohort. Ingenuity pathway analysis shows that ‘PastAD vs PresentAD’ share common pathways with ‘NoAD vs PresentAD’. The top pathways obtained are related to inflammatory responses, such as neutrophil degranulation, JAK-STAT signalling and interleukin-1 family signalling. Conclusions: Multiple protein biomarkers and pathways, including keratinization, inflammatory responses and oxidative stress response, are involved in the onset and persistence of AD. Despite resolution of disease manifestations in PastAD subjects, functional analyses show that some pathways and biomarkers indicative of AD persist.

Objective: Comorbidity between Emotionally Unstable Personality Disorder (EUPD) and Eating Disorders (ED) is high. Literature demonstrates worse outcomes for traditional evidence-based treatments, when EUPD and an ED is comorbid. This service improvement project aimed to generate recommendations for improving care for individuals with comorbid EUPD and ED, by: (1) understanding current service-user experiences of receiving and accessing care for their difficulties; and, (2) producing recommendations for the local region to improve care. Method: The project comprised semi-structured interviews with nine service-users. Thematic Analysis [(Braun & Clarke, 2021)](#ref-0003) was used to generate themes, create recommendations to improve care for this population, and a stepped model of psychological care provision for Oxford Health NHS Foundation Trust. Results: Six themes were derived from patient interviews: (1) Navigating diagnosis: the quest for understanding and effective support; (2) “It’s either the EUPD or the ED”: experiences of disconnect and misplaced focus; (3) Crisis as a catalyst for support: “You have to be bad enough to get care”; (4) Lost in the system: waiting times and professional uncertainty; (5) What makes care meaningful; and finally, (6) “It all exists within me”: a call for integrated care. Conclusions: The project produced a set of recommendations, aimed at improving care for individuals with EUPD and EDs. These included a thorough assessment of comorbidity and consideration of patient choice, alongside differing levels of psychological intervention to be considered according to presenting needs. Highlights Most service-users experienced longer waiting times to access care, and felt care was often disjointed. Many voiced feeling compelled to pick one area of difficulty over another to work on, which often conflicted with their own goals and needs. A delayed identification of difficulties was prevalent within the sample, with ‘crisis point’ often depicted as the catalyst for support. Service-users highlighted the possible disparity between clinician knowledge and personal goals and needs. Psychoeducation regarding the interplay and aetiology between EUPD and ED was viewed as helpful. Care could be improved for service-users with EUPD and ED, to introduce a more consistent provision of support tailored to individualised needs and goals.

Alzheimer’s disease (AD), a prevalent neurodegenerative disorder, is marked by the progressive decline in memory and cognitive function. Despite significant research efforts in the field of AD, effective therapeutic drugs for its prevention and treatment remain elusive. Consequently, a more comprehensive understanding of the molecular mechanisms underlying the pathological processes of AD is crucial for the development of novel therapeutic strategies. Mitophagy, the selective degradation of mitochondria through autophagy, is an essential mechanism for maintaining mitochondrial homeostasis in terms of both quantity and quality. It plays a pivotal role in various cellular processes, including differentiation, inflammation, and apoptosis. Recent studies have increasingly demonstrated that mitophagy is extensively characterized in AD and may represent a novel therapeutic strategy for its treatment. The distinctive properties of natural plant products (NPPs) confer significant research potential and developmental value, making them a vital resource for novel drug discovery. This study investigates the mechanistic hypothesis concerning the relationship between mitophagy and AD pathology. Furthermore, this review provides a comprehensive analysis of the application of PNPs in the prevention and treatment of AD through the regulation of mitophagy, thereby presenting novel perspectives for the exploration of AD prophylaxis and treatment.

Objective : This study aimed to identify adverse drug event (ADE) signals associated with ambrisentan, a pulmonary arterial hypertension (PAH) treatment, and guide its safe clinical use. Methods: ADE reports from the FDA Adverse Event Reporting System (FAERS) database (Q1 2007–Q2 2024) were analyzed using the Reporting Odds Ratio (ROR) method. Data were standardized using MedDRA version 26.0. Results: Among 45,007 ADE reports, 74.26% involved females aged 18–65, with 85.75% from the U.S. Common outcomes included hospitalization (46.19%). A total of 267 positive ADE signals were detected, including hematotoxicity (e.g., decreased serum iron) and nervous system-related events (e.g., exertional dizziness), not listed in the drug insert. Time-to-onset analysis showed most ADEs occurred within 0–30 days (9.05%) or after 360 days (10.01%) of treatment. Conclusion: This study confirmed known ambrisentan ADEs (e.g., peripheral edema, headache) and identified new signals (e.g., atrial flutter, syncope, jaw pain). Comprehensive monitoring is essential to ensure patient safety and optimize treatment outcomes.

Abstract To facilitate Safe-and-Sustainable-by-Design (SSbD), the HARMLESS project developed a SSbD approach and Decision Support System (DSS) for advanced materials. The SSbD approach and DSS are in alignment with the EU recommended SSbD framework, tools and methods, including New Approach Methodologies (NAMs), and tailored to the innovation stage of the material under development. The SSbD approach follows a flexible stage-gate model with three innovation stages: 1) Ideation & Business Case Phase, 2) Lab Phase, and 3) Pilot Phase. The SSbD-DSS guides designers through a workflow starting with the Advanced Material Earliest Assessment (AMEA) tool. AMEA contains three questions enabling categorization and subsequently advice on design principles. A second tool, named Warning flags, design Advice, Screening Priorities (WASP) consists of twelve questions to identify early warning flags and provide design and assessment advice. A third tool, named Alternative SSbD Design Inspector (ASDI) provides guidance on descriptors to measure in the Lab Phase for informed decision making on the most optimal SSbD version. By adapting the data and resource requirements to each innovation stage, the SSbD-DSS facilitates practical implementation of SSbD, supporting the user to find a transparent balance between safety, sustainability and performance.

Arthritis, a chronic inflammatory condition, significantly impacts the quality of life by causing pain, swelling, and joint degeneration. Conventional therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs), often present severe side effects, necessitating alternative approaches. This review explores the therapeutic potential of traditionally used anti-arthritic plants and their bioactive phytochemical constituents. Several medicinal plants, such as Ocimum sanctum (Tulsi), Cissus quadrangularis (Devil’s Backbone), Zingiber officinale (Ginger), and Withania somnifera (Ashwagandha), have demonstrated promising anti-inflammatory and immunomodulatory effects. The primary active constituents include quercetin, kaempferol, luteolin, gallic acid, β-sitosterol, and caffeic acid, which exhibit potent antioxidant and anti-inflammatory properties by targeting key inflammatory pathways, such as NF-κB, COX-2, and cytokines like TNF-α and IL-1β. This study provides an extensive compilation of anti-arthritic plants, categorizing them by botanical names, families, parts used, and major phytochemicals. Plants such as Merremia tridentata, Justicia gendarussa, and Salacia reticulata are also highlighted for their traditional usage and emerging scientific validation in arthritis management. Furthermore, the mechanisms of action of key phytochemicals, such as their role in reducing oxidative stress, modulating immune responses, and preventing cartilage degradation, are discussed. By synthesizing traditional knowledge with scientific evidence, this review emphasizes the potential of these medicinal plants as safer, cost-effective, and sustainable alternatives or complementary therapies for arthritis. Future research directions include clinical trials, standardization of plant extracts, and the development of novel formulations to enhance bioavailability and therapeutic efficacy.

Abstract: Introduction: Variations in pneumatization patterns and frontal sinus ostium morphology complicate surgical navigation and management of frontal sinus pathology. This study aimed to evaluate the morphological characteristics of the frontal sinus in a South Asian population using computed tomography (CT) imaging, focusing on pneumatization patterns, frontal ostium diameter, and frontal ostium grading. Methods A retrospective review of 106 patients (212 frontal sinuses) who underwent CT scans of the paranasal sinuses at Aga Khan University Hospital, Karachi, Pakistan, was conducted. Data on frontal sinus pneumatization, frontal ostium diameter, and frontal ostium grading were analyzed. The study population had a mean age of 40.4 ± 14.4 years, with a male-to-female ratio of 2:1. Results: Our study revealed that the majority of patients (95.5%) exhibited medium pneumatization (Type 2), while aplasia/hypoplasia (Type 1) and hyperplasia (Type 3) were rare (2% and 3%, respectively). The mean frontal ostium diameter was 7.8 ± 2.0 mm on the left and 7.4 ± 2.1 mm on the right, with minimal gender-based differences. Frontal ostium grading showed that 81.1% of left-sided and 67.9% of right-sided ostia were classified as FOG-positive, indicating easier surgical access. Conclusion Our findings highlight that the population exhibited medium pneumatization (Type 2) of the frontal sinuses. The mean diameter of the frontal sinus ostia showed slight variations between genders and between the right and left sides, with overall averages of 7.8 mm on the left and 7.4 mm on the right.

Antihistamines are commonly used to treat allergic diseases in children, such as rhinitis, asthma, and urticaria. They are classified into first and second-generation. First-generation antihistamines can cross the blood-brain barrier, causing significant sedation and other side effects, including new-onset seizures, poor academic performance, and paradoxical agitation. Recent studies show an increased risk of seizures, particularly in children aged 6 to 24 months. Although effective, first-generation antihistamines pose serious risks like sedation, cognitive impairment, and increased seizure risk. It is recommended to use newer, nonsedating antihistamines, which have fewer side effects. Children under six years old, especially those under two, should not be given first-generation antihistamines, particularly during flu season.

OBJECTIVE: To investigate the prevalence and clinical correlates of serum C1q and anti-C1q antibody titres in black South Africans with systemic lupus erythematosus (SLE). METHODS: Cross-sectional study of 96 black South African SLE patients, 49 with lupus nephritis (LN). Anti-C1q antibodies were tested using an enzyme linked immunoassay. Serum C1q was measured as a percentage of normal by immunoelectrophoresis, using an in-house rabbit-anti-C1q antiserum. Disease activity was assessed using SELENA-SLE disease activity index. RESULTS: Most patients were female (90.7%), mean (SD) age and follow-up period diagnosis of 38.1(13.0) and 4.2 (4.4) years, respectively. Low serum C1q and positive anti-C1q antibody test were detected in 17 (17.7%) and 12 (12.5%) patients, respectively, overall. There was inverse correlation between serum C1q and anti-C1q antibodies titres (r=-0.22, p=0.03) and a direct correlation of anti-C1q antibodies titres with SELENA-SLEDAI scores (r=0.27, p=0.008). Patients with an active urine sediment (n=21) had higher anti-C1q antibodies titres (p=0.007) and low serum C1q (OR=4.51, p=0.01), compared to the remainder of patients. Anti-C1q antibody titres were higher in patients with C3/C4 hypocomplementaemia (n=14) than those with normal C3/C4 (p=0.02). A positive Coombs test (without evidence of red cell haemolysis) (n=17) was associated with a positive anti-C1q antibody test (OR=4.29, p=0.02), low serum C1q (OR=3.37, p=0.04), and C3/C4 hypocomplementaemia (OR=4.84, p=0.02). CONCLUSION: Our findings broadly confirm the clinical utility of anti-C1q antibody test in SLE, particularly as a biomarker of active LN, as evidenced by an active urine sediment. The association and clinical relevance of a Direct Coombs test with elevated anti-C1q antibodies and low C1q merits further study and confirmation.

This paper discusses the design of an extremum seeking controller that relies on a monitoring function for a class of SISO uncertain nonlinear systems characterized by arbitrary and uncertain relative degree. Our demonstration illustrates the feasibility of achieving an arbitrarily small proximity to the desired optimal point through output feedback. The core concept involves integrating a monitoring function with a norm state observer for the unitary relative degree case and its expansion to arbitrary relative degrees by means of the employment of a time-scaling technique. Significantly, our proposed scheme attains the extremum of an unknown nonlinear mapping across the entire domain of initial conditions, ensuring global convergence and stability for the real-time optimization algorithm. Furthermore, we provide tuning rules to ensure convergence to the global maximum in the presence of local extrema. To validate the effectiveness of the proposed approach, we present a numerical example and apply it to a source-seeking problem involving a cart-track linear positioning servomechanism. Notably, the cart lacks the ability to sense its velocity or the source's position, but can detect the source of a light signal of unknown concentration field.

A document by Paolo Scanagatta. Click on the document to view its contents.

Introduction:Qat, also known as “khat”, is an evergreen plant. It grows wildly, along with being cultivated, in many countries in African horn. It is cultivated in Yemen. Nowadays due to the ongoing civil war therein, qat represents an economic backbone for Yemeni people: Many Yemenis work in qat cultivation, transportation, and marketing.Qat is habitually chewed due to the said “amphetamine-like stimulating effect”. Indeed, qat chewing is a deep-rooted habit in Yemen and many of the African horn countries. The session of qat chewing lasts several hours. Briefly, the fresh leaves and twigs of qat are chewed to form a bolus which kept on one side of the mouth, and continually chewed to release the qat extract which swallowed and/or absorbed through oral mucosa. In Yemen, qat sessions mostly take place in gatherings. It also takes place at private works, home, or even in streets.It is well-documented that qat has economic, sociocultural, and health negative implications. These implications have been critically reviewed by Al-Shubbar [1] and Alshoabi et al. [2]. In brief, qat has been reportedly to cause (or be associated with) many systemic diseases like autoimmune hepatitis [3], and mental disorders [4]; increasing diabetes parameters like HbA1c [5]; myocardial infarction [6, 7]; adverse birth outcomes [8, 9]; adverse effects on the genitourinary system like reduced semen volume [10], toxic effects on the male fertility, and sexual health [11]; and gastrointestinal disturbances [12, 13].The burden of qat chewing on oral cavity represents a hot area of debates. Al-Maweri et al. have recently reviewed this topic extensively [14]. Qat chewing is said to have detrimental effects on dental and oral tissues including association with or inducing periodontal diseases [15, 16], dental caries [17], dental discoloration and attrition [18], temporomandibular joint disorders [19-21], plasma cell stomatitis [22, 23], mucosal pigmentation [18], white (keratotic) lesions [18, 24, 25], and dry mouth/xerostomia [14, 18]. Although no sound evidence has been available yet, a possible link between qat chewing and oral cancer has been suggested [26-30].This current report presents a case of a patient who developed extensive deep oral and oropharyngeal ulcers with bone denudation secondary to chronic qat chewing.Key clinical message : qat chewing can predispose to extensive chronic deep oral ulcers that might be associated with bleeding. Dental professionals must stress on such complications while providing qat chewing quitting counseling.

Objective The study aims to evaluate psychosis-related questions to provide accurate, clear, and clinically relevant individualized information for patients and caregivers. Design This cross-sectional study uses a qualitative analysis design. The researchers specifically employed a question-answering system (GPT-4 via ChatGPT) to generate responses to common questions about psychosis. Experts in the field then evaluated these responses to assess their quality for use in a clinical setting. Primary Outcome Researchers presented ChatGPT with 20 common questions frequently asked by patients’ caregivers and relatives. Two experts in psychosis then assessed the quality of the responses using six criteria: accuracy (1-3), clarity (1-3), inclusivity (1-3), completeness (0-1), clinical utility (1-5) and an overall score (1-4). Results The evaluation yielded positive results overall. Responses were rated as accurate (M±SD= 2.89±0.22) and clear (mean score of 2.93±0.18). There was potential for improvement in terms of inclusivity (mean score of 2.30±0.41), suggesting a need to incorporate more diverse perspectives. Completeness received high ratings (mean score of 0.93±0.18), indicating responses addressed all aspects of the questions. Most importantly, the responses were deemed clinically useful (mean score of 4.35±0.52). Conclusions In summary, this study underscores the significant promise of ChatGPT as a psychoeducational tool for patients with psychosis, their relatives, and their caregivers. The experts’ findings affirm that the information delivered by ChatGPT is not only accurate and clinically relevant but also conveyed conversationally, enhancing its accessibility and usability. The initial performance of ChatGPT as a psychoeducational tool in the context of psychosis education is undeniably positive.

We present a derivation of an ab intio model potential (AIMP) based on the Van Vleck Perturbation theory. We applied the derivation to the specific case of a molecular system made of one alkali atom interacting with rare gas atoms. Our approach provides a formal background for the empirical potential often used to study this kind of molecular systems and allows us to discuss their intrinsic limitations and some possible improvements. In particular, the use of AIMP, which keeps the nodal structure of the orbitals, allows us to take into account accurately the spin-orbit relativistic correction. Its application to alkali-rare gas diatomic molecules allows us to reproduce rather well the known experimental and the best ab initio calculations at a lower computational cost.

Genome modification would be useful for developing breeding techniques for haploid Zygosaccharomyces rouxii and natural hybrid allodiploid Zygosaccharomyces sp. yeast strains used in miso and soy sauce production. In this study, genome editing using CRISPR-Cas9 was attempted in Zygosaccharomyces sp. strains. Based on techniques in Saccharomyces cerevisiae, the Cas9 gene and guide RNA (gRNA) were expressed from the same plasmid. Targeting of the ZygoLEU2 gene of haploid Z. rouxii strain DA2 led to of a single-nucleotide insertion in the ORF, resulting in termination of translation at 10 amino acids. This single-base insertion was 3-bp upstream of the protospacer-associated motif (PAM) sequence, suggesting that it occurred during the repair process following the Cas9-induced double-strand break. The transformant was auxotrophic for leucine, verifying that genome editing using CRISPR-Cas9 had occurred. Application of the CRISPR-Cas9 system to allodiploid Zygosaccharomyces sp. strains, which have T- and P-subgenomes, resulted in transformants with base insertions or deletions upstream of the PAM sequence, or insertions of different subgenome sequences. Leucine-auxotrophic transformants were obtained in which the ORF of the ZygoLEU2 gene in both subgenomes were mutated. In some genome-edited strains, a significant region of one subgenome chromosome was missing. Lastly, we applied CRISPR-Cas9 to the gene encoding Hog1, a protein kinase involved in adaptation to high-salt and high-osmolarity conditions. Mutation of the HOG1 genes of both the T- and P-subgenomes by CRISPR-Cas9 significantly reduced growth in high salt and high osmolarity conditions.

In the Prairie Pothole Region (PPR), potholes govern catchment hydrologic behavior through complex and dynamic fill-spill-connection mechanisms. This complexity—combined with predominantly ungauged catchments and limited fine-resolution pothole inventories—challenges the hydrologic models and purely data-driven deep learning approaches. To address this, we developed the δHBV-Pot model within differentiable modeling framework (δ). This physics-informed deep learning model integrates the conceptual HBV model with a probabilistic algorithm that emulates the aggregated effects of pothole fill-spill-connection processes. Applied to 98 PPR catchments, δHBV-Pot demonstrates stronger predictive accuracy and physical realism than purely data-driven Long Short-Term Memory (LSTM) model and two conceptual hydrology models. PPR-scale regional δHBV-Pot model successfully simulates the hydrologic behavior of the majority of pseudo-ungauged (or test) catchments withheld during model development, effectively regionalizing (1) high-flow magnitude and inter-annual variability, (2) intra-annual flashiness of high-flow and normal flow, and (3) inter-annual variability in pothole water storage dynamics. Moreover, the model identifies vulnerable catchments with large high-flow magnitude and variability—even where no streamflow data exist—and delineates catchments with varying temporal variability in pothole water storage without relying on detailed pothole inventories. Our analysis reveals a negative correlation between pothole storage extent and high-flow metrics, suggesting that greater pothole storage reduces both high-flow magnitude and variability. Our findings underscore the value of integrating conceptual hydrology with data-driven approaches in pothole-dominated regions. This combined strategy uncovers new patterns from big data while enabling the regionalization of high-flow and pothole storage characteristics to ungauged catchments—critical for vulnerability assessment and designing sustainable water/ecological strategies in these landscapes.