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1.
J Psychiatr Res ; 177: 66-74, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38981410

RESUMEN

It is widely accepted that loneliness is associated with health problems, but less is known about the predictors of loneliness. In this study, we constructed a model to predict individual risk of loneliness during adulthood. Data were from the prospective population-based FinHealth cohort study with 3444 participants (mean age 55.5 years, 53.4% women) who responded to a 81-item self-administered questionnaire and reported not to be lonely at baseline in 2017. The outcome was self-reported loneliness at follow-up in 2020. Predictive models were constructed using bootstrap enhanced LASSO regression (bolasso). The C-index from the final model including 11 predictors from the best bolasso -models varied between 0.65 (95% CI 0.61 to 0.70) and 0.71 (95% CI 0.67 to 0.75) the pooled C -index being 0.68 (95% CI 0.61 to 0.75). Although survey-based individualised prediction models for loneliness achieved a reasonable C-index, their predictive value was limited. High detection rates were associated with high false positive rates, while lower false positive rates were associated with low detection rates. These findings suggest that incident loneliness during adulthood. may be difficult to predict with standard survey data.

2.
Sci Total Environ ; : 174993, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39047818

RESUMEN

This study introduces a novel concept of 'Adaptively Stacked' Species Distribution Models (AS-SDMs) to predict blue carbon habitat distribution, abundance, carbon stocks, and carbon sequestration potential in Orkney. AS-SDMs are built from Weighted Boosted Regression Trees (WBRTs) that adaptively stack blue carbon sediment thickness, sediment carbon content, and sequestration potential to predicted abundance. A novel method to describe substrate types by relative inputs of mud, sand, and gravel is detailed that better characterises the determining factors of seagrass, maerl, and horse mussel abundance. This study also introduces a novel use of indexes to mitigate double counting issues of mixed species distribution models. Seagrass, maerl, horse mussel, and mixed seagrass and maerl habitats (SGM) are estimated to cover a maximum area of 657 km2 in Orkney, have a total sediment carbon stock of 16 Mt. C, and sequester 6000 t C yr-1. Applying a conservative threshold of 50 % abundance to habitat predictions, six key potential areas of blue carbon offset projects are identified. These areas cover just over 9 km2, have a total carbon stock of 330,000 t C, and sequester 330 t C yr-1. When applied to UK carbon credit value, assuming integration with regulated markets and compliance with accreditation criteria, the habitats in these areas have a potential value of £24.5 million. If applied as annualised values, these areas have carbon stocks with a potential value of £0.93 million yr-1 and a carbon sequestration potential value of £24,000 yr-1.

3.
Ecol Evol ; 14(7): e11714, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39005886

RESUMEN

Climate change is leading to advanced snowmelt date in alpine regions. Consequently, alpine plant species and ecosystems experience substantial changes due to prolonged phenological seasons, while the responses, mechanisms and implications remain widely unclear. In this 3-year study, we investigated the effects of advancing snowmelt on the phenology of alpine snowbed species. We related microclimatic drivers to species and ecosystem phenology using in situ monitoring and phenocams. We further used predictive modelling to determine whether early snowmelt sites could be used as sentinels for future conditions. Temperature during the snow-free period primarily influenced flowering phenology, followed by snowmelt timing. Salix herbacea and Gnaphalium supinum showed the most opportunistic phenology, while annual Euphrasia minima struggled to complete its phenology in short growing seasons. Phenological responses varied more between years than sites, indicating potential local long-term adaptations and suggesting these species' potential to track future earlier melting dates. Phenocams captured ecosystem-level phenology (start, peak and end of phenological season) but failed to explain species-level variance. Our findings highlight species-specific responses to advancing snowmelt, with snowbed species responding highly opportunistically to changes in snowmelt timings while following species-specific developmental programs. While species from surrounding grasslands may benefit from extended growing seasons, snowbed species may become outcompeted due to internal-clock-driven, non-opportunistic senescence, despite displaying a high level of phenological plasticity.

4.
Int J Pharm ; : 124466, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39009288

RESUMEN

Biopharmaceuticals are labile biomolecules that must be safeguarded to ensure the safety, quality, and efficacy of the product. Batch freeze-drying is an established means of manufacturing solid biopharmaceuticals but alternative technologies such as spray-drying may be more suitable for continuous manufacturing of inhalable biopharmaceuticals. Here we assessed the feasibility of spray-drying Olipudase alfa, a novel parenteral therapeutic enzyme, by evaluating some of its critical quality attributes (CQAs) in a range of excipients, namely, trehalose, arginine (Arg), and arginine hydrochloride (Arg-HCl) in the sucrose/methionine base formulation. The Arg-HCl excipient produced the best gain in CQAs of spray-dried Olipudase with a 63% reduction in reconstitution time and 83% reduction in the optical density of the solution. Molecular dynamics simulations revealed the atomic-scale mechanism of the protein-excipient interactions, substantiating the experimental results. The Arg-HCl effect was explained by the calculated thermal stability and structural order of the protein wherein Arg-HCl acted as a crowding agent to suppress protein aggregation and promote stabilization of Olipudase post-spray-drying. Therefore, by rational selection of appropriate excipients, our experimental and modelling dataset confirms spray-drying is a promising technology for the manufacture of Olipudase and demonstrates the potential to accelerate development of continuous manufacturing of parenteral biopharmaceuticals.

6.
Biol Psychiatry ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39069164

RESUMEN

BACKGROUND: Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODS: We acquired diffusion-weighted MRI to map structural connectivity between each pair of 319 parcellated brain regions in 61 antipsychotic-naive individuals with First Episode Psychosis (FEP; 15-25 years, 46% female) and a demographically matched sample of 27 control participants, along with clinical follow-up data in patients three months and 12 months after the scan. We used connectome-wide analyses to map disruptions of inter-regional pairwise connectivity and connectome-based predictive modelling to predict longitudinal change in symptoms and functioning. RESULTS: Individuals with FEP showed disrupted connectivity in a brain-wide network linking all brain regions when compared with controls (pFWE=.03). Baseline structural connectivity significantly predicted change in functioning over 12 months (r=.44;pFWE=.041), such that lower connectivity within fronto-striato-thalamic systems predicted worse functional outcomes. CONCLUSIONS: Brain-wide reductions of structural connectivity exist during the early stages of psychotic illness and cannot be attributed to antipsychotic medication. Moreover, baseline measures of structural connectivity can predict change in patient functional outcomes up to one year after engagement with treatment services.

7.
J Oral Rehabil ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38840513

RESUMEN

BACKGROUND: A quantitative approach to predict expected muscle activity and mandibular movement from non-invasive hard tissue assessments remains unexplored. OBJECTIVES: This study investigated the predictive potential of normalised muscle activity during various jaw movements combined with temporomandibular joint (TMJ) vibration analyses to predict expected maximum lateral deviation during mouth opening. METHOD: Sixty-six participants underwent electrognathography (EGN), surface electromyography (EMG) and joint vibration analyses (JVA). They performed maximum mouth opening, lateral excursion and anterior protrusion as jaw movement activities in a single session. Multiple predictive models were trained from synthetic observations generated from the 66 human observations. Muscle function intensity and activity duration were normalised and a decision support system with branching logic was developed to predict lateral deviation. Performance of the models in predicting temporalis, masseter and digastric muscle activity from hard tissue data was evaluated through root mean squared error (RMSE) and mean absolute error. RESULTS: Temporalis muscle intensity ranged from 0.135 ± 0.056, masseter from 0.111 ± 0.053 and digastric from 0.120 ± 0.051. Muscle activity duration varied with temporalis at 112.23 ± 126.81 ms, masseter at 101.02 ± 121.34 ms and digastric at 168.13 ± 222.82 ms. XGBoost predicted muscle intensity and activity duration and scored an RMSE of 0.03-0.05. Jaw deviations were successfully predicted with a MAE of 0.9 mm. CONCLUSION: Applying deep learning to EGN, EMG and JVA data can establish a quantifiable relationship between muscles and hard tissue movement within the TMJ complex and can predict jaw deviations.

8.
Heliyon ; 10(11): e30960, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38832258

RESUMEN

Distance education supports lifelong learning and empowers individuals in rapidly changing societal conditions, yet it encounters high dropout rates due to a range of individual and societal obstacles. This study addresses the challenge of creating a practical prediction model by analyzing extensive real-world time-point data from a well-established online university in Seoul. Covering 144,540 instances from 2018 to 2022, the study integrates diverse datasets to compare the accuracy of models based on longitudinal, semester-wise, and gender-specific datasets. The demographic, academic, and online metrics identified significant dropout indicators, including age (particularly when binned), residential area, specific occupations, GPA, and LMS log metrics, using a stepwise backward elimination process. The study revealed that, despite societal changes, recent data from the last four semesters can be effectively used for stable prediction training. Gender-based analysis showed different factors influencing dropout risk for males and females. The Light Gradient Boosting Machine (LGBM) algorithm excelled in prediction accuracy, with the ROC-AUC metric affirming its superiority. However, logistic regression also showed its competitive performance and offered in-depth interpretation. In South Korea's distinct educational setting, merging advanced algorithms like LGBM with the interpretive strength of logistic regression is key for effective student support strategies.

9.
Int J Integr Care ; 24(2): 23, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855028

RESUMEN

Introduction: Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This article analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020-2023). Description: The implementation research approach involved a twelve-month pre-implementation period to assess feasibility and define the local action plans, followed by a sixteen-month implementation phase. During the two periods, a well-defined combination of experience-based co-design and quality improvement methodologies were applied. Discussion: The evolution of the Catalan HRA strategy (2010-2023) illustrates its potential for health systems transformation, as well as its transferability. The main barriers and facilitators for HRA adoption were identified. The report proposes a set of key steps to facilitate site customized deployment of HRA contributing to define a roadmap to foster large-scale adoption across Europe. Conclusions: Successful adoption of the AMG algorithm was achieved in the two sites confirming transferability. Marche identified the key requirements for a population-based HRA strategy, whereas Viljandi Hospital proved its potential for clinical use paving the way toward value-based healthcare strategies.

10.
Sci Rep ; 14(1): 14409, 2024 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909127

RESUMEN

Type II diabetes mellitus (T2DM) is a rising global health burden due to its rapidly increasing prevalence worldwide, and can result in serious complications. Therefore, it is of utmost importance to identify individuals at risk as early as possible to avoid long-term T2DM complications. In this study, we developed an interpretable machine learning model leveraging baseline levels of biomarkers of oxidative stress (OS), inflammation, and mitochondrial dysfunction (MD) for identifying individuals at risk of developing T2DM. In particular, Isolation Forest (iForest) was applied as an anomaly detection algorithm to address class imbalance. iForest was trained on the control group data to detect cases of high risk for T2DM development as outliers. Two iForest models were trained and evaluated through ten-fold cross-validation, the first on traditional biomarkers (BMI, blood glucose levels (BGL) and triglycerides) alone and the second including the additional aforementioned biomarkers. The second model outperformed the first across all evaluation metrics, particularly for F1 score and recall, which were increased from 0.61 ± 0.05 to 0.81 ± 0.05 and 0.57 ± 0.06 to 0.81 ± 0.08, respectively. The feature importance scores identified a novel combination of biomarkers, including interleukin-10 (IL-10), 8-isoprostane, humanin (HN), and oxidized glutathione (GSSG), which were revealed to be more influential than the traditional biomarkers in the outcome prediction. These results reveal a promising method for simultaneously predicting and understanding the risk of T2DM development and suggest possible pharmacological intervention to address inflammation and OS early in disease progression.


Asunto(s)
Biomarcadores , Diabetes Mellitus Tipo 2 , Aprendizaje Automático , Estrés Oxidativo , Humanos , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores de Riesgo , Glucemia/análisis , Glucemia/metabolismo , Inflamación , Algoritmos
11.
Br J Anaesth ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38902116

RESUMEN

The increased availability of large clinical datasets together with increasingly sophisticated computing power has facilitated development of numerous risk prediction models for various adverse perioperative outcomes, including acute kidney injury (AKI). The rationale for developing such models is straightforward. However, despite numerous purported benefits, the uptake of preoperative prediction models into clinical practice has been limited. Barriers to implementation of predictive models, including limitations in their discrimination and accuracy, as well as their ability to meaningfully impact clinical practice and patient outcomes, are increasingly recognised. Some of the purported benefits of predictive modelling, particularly when applied to postoperative AKI, might not fare well under detailed scrutiny. Future research should address existing limitations and seek to demonstrate both benefit to patients and value to healthcare systems from implementation of these models in clinical practice.

12.
medRxiv ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38854022

RESUMEN

Importance: Despite the availability of disease-modifying therapies, scalable strategies for heart failure (HF) risk stratification remain elusive. Portable devices capable of recording single-lead electrocardiograms (ECGs) can enable large-scale community-based risk assessment. Objective: To evaluate an artificial intelligence (AI) algorithm to predict HF risk from noisy single-lead ECGs. Design: Multicohort study. Setting: Retrospective cohort of individuals with outpatient ECGs in the integrated Yale New Haven Health System (YNHHS) and prospective population-based cohorts of UK Biobank (UKB) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants: Individuals without HF at baseline. Exposures: AI-ECG-defined risk of left ventricular systolic dysfunction (LVSD). Main Outcomes and Measures: Among individuals with ECGs, we isolated lead I ECGs and deployed a noise-adapted AI-ECG model trained to identify LVSD. We evaluated the association of the model probability with new-onset HF, defined as the first HF hospitalization. We compared the discrimination of AI-ECG against the pooled cohort equations to prevent HF (PCP-HF) score for new-onset HF using Harrel's C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Results: There were 194,340 YNHHS patients (age 56 years [IQR, 41-69], 112,082 women [58%]), 42,741 UKB participants (65 years [59-71], 21,795 women [52%]), and 13,454 ELSA-Brasil participants (56 years [41-69], 7,348 women [55%]) with baseline ECGs. A total of 3,929 developed HF in YNHHS over 4.5 years (2.6-6.6), 46 in UKB over 3.1 years (2.1-4.5), and 31 in ELSA-Brasil over 4.2 years (3.7-4.5). A positive AI-ECG screen was associated with a 3- to 7-fold higher risk for HF, and each 0.1 increment in the model probability portended a 27-65% higher hazard across cohorts, independent of age, sex, comorbidities, and competing risk of death. AI-ECG's discrimination for new-onset HF was 0.725 in YNHHS, 0.792 in UKB, and 0.833 in ELSA-Brasil. Across cohorts, incorporating AI-ECG predictions in addition to PCP-HF resulted in improved Harrel's C-statistic (Δ=0.112-0.114), with an IDI of 0.078-0.238 and an NRI of 20.1%-48.8% for AI-ECG vs. PCP-HF. Conclusions and Relevance: Across multinational cohorts, a noise-adapted AI model with lead I ECGs as the sole input defined HF risk, representing a scalable portable and wearable device-based HF risk-stratification strategy.

13.
Sci Rep ; 14(1): 14903, 2024 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-38942825

RESUMEN

Remote sensing has been increasingly used in precision agriculture. Buoyed by the developments in the miniaturization of sensors and platforms, contemporary remote sensing offers data at resolutions finer enough to respond to within-farm variations. LiDAR point cloud, offers features amenable to modelling structural parameters of crops. Early prediction of crop growth parameters helps farmers and other stakeholders dynamically manage farming activities. The objective of this work is the development and application of a deep learning framework to predict plant-level crop height and crown area at different growth stages for vegetable crops. LiDAR point clouds were acquired using a terrestrial laser scanner on five dates during the growth cycles of tomato, eggplant and cabbage on the experimental research farms of the University of Agricultural Sciences, Bengaluru, India. We implemented a hybrid deep learning framework combining distinct features of long-term short memory (LSTM) and Gated Recurrent Unit (GRU) for the predictions of plant height and crown area. The predictions are validated with reference ground truth measurements. These predictions were validated against ground truth measurements. The findings demonstrate that plant-level structural parameters can be predicted well ahead of crop growth stages with around 80% accuracy. Notably, the LSTM and the GRU models exhibited limitations in capturing variations in structural parameters. Conversely, the hybrid model offered significantly improved predictions, particularly for crown area, with error rates for height prediction ranging from 5 to 12%, with deviations exhibiting a more balanced distribution between overestimation and underestimation This approach effectively captured the inherent temporal growth pattern of the crops, highlighting the potential of deep learning for precision agriculture applications. However, the prediction quality is relatively low at the advanced growth stage, closer to the harvest. In contrast, the prediction quality is stable across the three different crops. The results indicate the presence of a robust relationship between the features of the LiDAR point cloud and the auto-feature map of the deep learning methods adapted for plant-level crop structural characterization. This approach effectively captured the inherent temporal growth pattern of the crops, highlighting the potential of deep learning for precision agriculture applications.


Asunto(s)
Productos Agrícolas , Aprendizaje Profundo , Productos Agrícolas/crecimiento & desarrollo , Tecnología de Sensores Remotos/métodos , Verduras/crecimiento & desarrollo , India , Agricultura/métodos , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/anatomía & histología , Solanum melongena/crecimiento & desarrollo , Solanum melongena/anatomía & histología
14.
Res Social Adm Pharm ; 20(8): 796-803, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38772838

RESUMEN

BACKGROUND: Medication harm affects between 5 and 15% of hospitalised patients, with approximately half of the harm events considered preventable through timely intervention. The Adverse Inpatient Medication Event (AIME) risk prediction model was previously developed to guide a systematic approach to patient prioritisation for targeted clinician review, but frailty was not tested as a candidate predictor variable. AIM: To evaluate the predictive performance of an updated AIME model, incorporating a measure of frailty, when applied to a new multisite cohort of hospitalised adult inpatients. METHODS: A retrospective cohort study was conducted at two tertiary Australian hospitals on patients discharged between 1st January and April 31, 2020. Data were extracted from electronic medical records (EMRs) and clinical coding databases. Medication harm was identified using ICD-10 Y-codes and confirmed by senior pharmacist review of medical records. The Hospital Frailty Risk Score (HFRS) was calculated for each patient. Logistic regression analysis was used to construct a modified AIME model. Candidate variables of the original AIME model, together with new variables including HFRS were tested. Performance of the final model was reported using area under the curve (AUC) and decision curve analysis (DCA). RESULTS: A total of 4089 patient admissions were included, with a mean age ± standard deviation (SD) of 64 years (±19 years), 2050 patients (50%) were males, and mean HFRS was 6.2 (±5.9). 184 patients (4.5%) experienced one or more medication harm events during hospitalisation. The new AIME-Frail risk model incorporated 5 of the original variables: length of stay (LOS), anti-psychotics, antiarrhythmics, immunosuppressants, and INR greater than 3, as well as 5 new variables: HFRS, anticoagulants, antibiotics, insulin, and opioid use. The AUC was 0.79 (95% CI: 0.76-0.83) which was superior to the original model (AUC = 0.70, 95% CI: 0.65-0.74) with a sensitivity of 69%, specificity of 81%, positive predictive value of 0.14 (95% CI: 0.10-0.17) and negative predictive value of 0.98 (95% CI: 0.97-0.99). The DCA identified the model as having potential clinical utility between the probability thresholds of 0.05-0.4. CONCLUSION: The inclusion of a frailty measure improved the predictive performance of the AIME model. Screening inpatients using the AIME-Frail tool could identify more patients at high-risk of medication harm who warrant timely clinician review.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fragilidad , Pacientes Internos , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Australia , Hospitalización/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Adulto , Registros Electrónicos de Salud , Estudios de Cohortes
15.
Artículo en Inglés | MEDLINE | ID: mdl-38733108

RESUMEN

BACKGROUND: Older adults (≥65 years) account for a disproportionately high proportion of hospitalization and in-hospital mortality, some of which may be avoidable. Although machine learning (ML) models have already been built and validated for predicting hospitalization and mortality, there remains a significant need to optimize ML models further. Accurately predicting hospitalization may tremendously affect the clinical care of older adults as preventative measures can be implemented to improve clinical outcomes for the patient. METHODS: In this retrospective cohort study, a data set of 14 198 community-dwelling older adults (≥65 years) with complex care needs from the International Resident Assessment Instrument-Home Care database was used to develop and optimize 3 ML models to predict 30-day hospitalization. The models developed and optimized were Random Forest (RF), XGBoost (XGB), and Logistic Regression (LR). Variable importance plots were generated for all 3 models to identify key predictors of 30-day hospitalization. RESULTS: The area under the receiver-operating characteristics curve for the RF, XGB, and LR models were 0.97, 0.90, and 0.72, respectively. Variable importance plots identified the Drug Burden Index and alcohol consumption as important, immediately potentially modifiable variables in predicting 30-day hospitalization. CONCLUSIONS: Identifying immediately potentially modifiable risk factors such as the Drug Burden Index and alcohol consumption is of high clinical relevance. If clinicians can influence these variables, they could proactively lower the risk of 30-day hospitalization. ML holds promise to improve the clinical care of older adults. It is crucial that these models undergo extensive validation through large-scale clinical studies before being utilized in the clinical setting.


Asunto(s)
Hospitalización , Vida Independiente , Aprendizaje Automático , Humanos , Anciano , Masculino , Femenino , Hospitalización/estadística & datos numéricos , Estudios Retrospectivos , Anciano de 80 o más Años , Evaluación Geriátrica/métodos
16.
Pharm Res ; 41(5): 833-837, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38698195

RESUMEN

Currently, the lengthy time needed to bring new drugs to market or to implement postapproval changes causes multiple problems, such as delaying patients access to new lifesaving or life-enhancing medications and slowing the response to emergencies that require new treatments. However, new technologies are available that can help solve these problems. The January 2023 NIPTE pathfinding workshop on accelerating drug product development and approval included a session in which participants considered the current state of product formulation and process development, barriers to acceleration of the development timeline, and opportunities for overcoming these barriers using new technologies. The authors participated in this workshop, and in this article have shared their perspective of some of the ways forward, including advanced manufacturing techniques and adaptive development. In addition, there is a need for paradigm shifts in regulatory processes, increased pre-competitive collaboration, and a shared strategy among regulators, industry, and academia.


Asunto(s)
Aprobación de Drogas , Humanos , Desarrollo de Medicamentos/métodos , Industria Farmacéutica/métodos , Tecnología Farmacéutica/métodos , Preparaciones Farmacéuticas/química , Química Farmacéutica/métodos , Composición de Medicamentos/métodos
17.
Materials (Basel) ; 17(9)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38730877

RESUMEN

This study employs a systematic and predictive modelling approach to investigate the structure and properties of multi-component borate glasses. In particular, this work is focused on understanding the individual and interaction effects of multiple constituents on several material properties. By leveraging advanced modeling techniques, this work examines how the inclusion and variation of B2O3, CaF2, TiO2, ZnO, and Na2CO3 influence the glass network, with particular attention to modifier fractions ≥ 30 mol%. This research addresses the gap in knowledge regarding the complex behavior of borate glasses in this high modifier fraction range, known as the borate anomaly, where prediction of glass structure and properties becomes particularly challenging. The use of a design of mixtures (DoM) approach facilitated the generation of polynomial equations indicating the influence of mixture components on various responses, enabling the prediction and optimization of glass properties over broad compositional ranges despite being within the anomalous region. This methodical approach not only advances our understanding of borate glass systems but also underscores the importance of predictive modelling in the accelerated design and development of novel glass materials for diverse applications.

18.
EBioMedicine ; 103: 105142, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38691939

RESUMEN

BACKGROUND: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. METHODS: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. FINDINGS: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. INTERPRETATION: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. FUNDING: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).


Asunto(s)
Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Inestabilidad de Microsatélites , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Anciano , Mutación , Biomarcadores de Tumor/genética , Adulto , Perfilación de la Expresión Génica , Proteína 3 Homóloga de MutS/genética , Proteína 3 Homóloga de MutS/metabolismo , Estadificación de Neoplasias
19.
Heliyon ; 10(10): e31545, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38818211

RESUMEN

The compressibility of bank soils is a critical consideration in t riverbank protection project, construction. In the Inner Mongolia section of the Yellow River, a seasonal frozen soil region, the impact of F-T cycles on soil compressibility cannot be overlooked. This study, based on F-T cycle tests, conducted orthogonal consolidation tests on embankment sandy silt from the Inner Mongolia section of the Yellow River, considering varying initial w and ρd. It investigated the effects of different initial w, ρd, and F-T cycles on soil compressibility, ranked and assessed the significance of influencing factors, and established a predictive model for the compressibility of Inner Mongolia section Yellow River embankment sandy silt. The results show that: the embankment sandy silt is medium-high compression soil, with a between 0.1 and 0.74 MPa-1, Es between 2.65 and 18.47 MPa, and Cc between 0.04 and 0.24 MPa. The greater the ρd of soil, the smaller the initial w, the smaller the a and Cc, and the greater the Es of soil. The F-T effect affects soil compressibility, and soil a, Es and Cc are linearly related to the number of F-T cycles. The ranking of factors influencing soil compressibility is ρd > w > F-T cycles. The initial ρd and w are decisive factors affecting soil compressibility, while the impact of F-T cycles is relatively minor. Additionally, a regression predictive model based on the initial ρd and w of the soil demonstrates good performance in predicting soil compression indices. This model can be utilized for predicting the compressibility indices of embankment soil in the Inner Mongolia section of the Yellow River.

20.
Sci Rep ; 14(1): 11643, 2024 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773169

RESUMEN

Mycotoxin contamination of agricultural commodities is a global public health problem that has remained elusive to various mitigation approaches, particularly in developing countries. Climate change and its impact exacerbates South Africa's vulnerability to mycotoxin contamination, and significantly threatens its's food systems, public health, and agro-economic development. Herein we analyse sixteen years (2005/2006-2020/2021) of annual national meteorological data on South Africa which reveals both systematic and erratic variability in critical climatic factors known to influence mycotoxin contamination in crops. Within the same study period, data on fumonisin (FB) monitoring show clear climate-dependent trends. The strongest positive warming trend is observed between 2018/2019 and 2019/2020 (0.51 °C/year), and a strong positive correlation is likewise established between FB contamination and temperature (r ranging from 0.6 to 0.9). Four machine learning models, viz support vector machines, eXtreme gradient boosting, random forest, and orthogonal partial least squares, are generalized on the historical data with suitable performance (RMSE as low as 0.00). All the adopted models are able to predict future FB contamination patterns with reasonable precision (R2 ranging from 0.34 to 1.00). The most important model feature for predicting average FB contamination (YA) is the historical pattern of average FB contamination in maize within the region (ΣFBs_avg). The two most significant features in modelling maximum FB contamination (YM) are minimum temperature from the CMIP6 data (Pro_tempMIN) and observed precipitation from the CRU data (O_prep). Our study provides strong evidence of the impact of climate change on FB in South Africa and reiterates the significance of machine learning modelling in predicting mycotoxin contamination in light of changing climatic conditions, which could facilitate early warnings and the adoption of relevant mitigation measures that could help in mycotoxin risk management and control.


Asunto(s)
Cambio Climático , Fumonisinas , Zea mays , Sudáfrica , Fumonisinas/análisis , Zea mays/microbiología , Clima , Contaminación de Alimentos/análisis , Aprendizaje Automático , Productos Agrícolas
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