Enhanced rare earth element recovery with cross-linked glutaraldehyde-lanthanide binding peptides in foam-based separations.

HYPOTHESIS: Lanthanide Binding Tag (LBT) peptides that coordinate selectively with lanthanide ions can be used to replace the energy intensive processes used for the separation of rare earth elements (REEs). These surface-active biomolecules, once selectively complexed with the trivalent REE cations, can adsorb to air/aqueous interfaces of bubbles for foam-based REEs recovery. Glutaraldehyde, an organic compound that is a homobifunctional crosslinker for proteins and peptides, can be used to enhance the adsorption and interfacial stabilization of lanthanide-bound peptides films. EXPERIMENTS: The stability of the interfacial cross-linked films was tested by measuring their dilational and shear surface rheological properties. Surface activity of the adsorbed species was analyzed using pendant drop tensiometry, while surface density and molecular arrangement were determined using x-ray reflectivity and x-ray fluorescence near total reflection. FINDINGS: Glutaraldehyde cross-linked REE-peptide complexes enhance the adsorption of lanthanides to air-water interfaces, resulting in thicker interfacial structures. Subsequently, these thicker layers enhance the dilational and shear interfacial rheological properties. The interfacial film stabilization and REEs extraction promoted by the cross-linker presented in this work provides an approach to integrate glutaraldehyde as a substitute of common foam stabilizers such as polymers, surfactants, and particles to optimize the recovery of REEs when using biomolecules as extractants.

Phosphorus vacancies regulation and heterogeneous interfacial engineering of coral-like ZnO/FeCoPv@N-doped carbon hierarchical microspheres to boost overall water splitting.

Vacancy engineering and heterostructure construction are regarded as potent approaches for synergistically boosting hydrogen production in renewable energy conversion. Herein, a selective phosphorization strategy was implemented to fabricate coral-like ZnO/FeCoP@N-doped carbon hierarchical microspheres (ZnO/FeCoP@NCHMS) via only controllably phosphorizing the Co and Fe atoms in a precursor, which was formed by generating ZnCoFe LDH on the surface of a zinc cobalt coordination polymer microsphere. Then, by adopting a reduction treatment for ZnO/FeCoP@NCHMS, the innovative ZnO/FeCoPv@NCHMS with abundant phosphorus vacancies (Pv) was realized. The introduction of phosphorus vacancy could optimize the electronic structures of metal phosphides and accelerate the reconstruction of active species, thus speeding up the reaction kinetic. Likewise, the plentiful heterointerfaces greatly expedite the transfer of electrons and protons, exposing ultra-high active sites. By virtue of these fascinating characters and the unique coral-like hierarchical architecture, the as-prepared ZnO/FeCoPv@NCHMS reveal preeminent electrocatalytic activities, and the overpotentials for the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) are as low as 177 and 173 mV at 10 mA cm-2 in alkaline medium, respectively. Impressively, the water electrolysis device assembled by ZnO/FeCoPv@NCHMS requires a mere cell voltage of 1.508 V to attain a current density of 10 mA cm-2. Furthermore, the ZnO/FeCoPv@NCHMS also demonstrate extraordinary durability, sustaining operation for at least 28 h (at 100 mA cm-2) during the water splitting process. This study provides novel insights into defect regulation and heterointerface construction for overall water splitting.

Flavor characterization of pork cuts in Chalu black pigs using multi-omics analysis.

The study investigated the flavor variations in four different fresh pork cuts (longissimus thoracis, LT; trapezius muscle, TM; hamstring muscle, HM; Pork Belly, PB) from Chalu black pigs (ten castrated boars) using multi-omics techniques. The research also explored the influence of muscle fiber type on the flavor profiles of these cuts. Results from quantitative real-time PCR (qRT-PCR) indicated significant differences in muscle fiber type across the four pork cuts in various anatomical locations. Each cut exhibited distinctive volatile organic compounds (VOCs) profiles, with HM displaying a sweet and fruity green flavor, LT showcasing a fatty and nutty taste, PB presenting a fresh, citrusy, and green flavor, and TM offering a floral and bitter note. Variations in fatty acid carbon number and saturation were observed among the cuts, with HM, LT, and PB being rich in fatty acids with C16-18, C19-21, and 3 double bonds, respectively. The metabolites specific to each cut were found to play key roles in different metabolic pathways, such as protein-related pathways for HM, arginine biosynthesis for LT, lysine biosynthesis for PB, and D-arginine and D-ornithine metabolism for TM. Differentially expressed genes (DEGs) were associated with amino acid metabolism for HM, glycolysis/gluconeogenesis for LT, and cellular aromatic compound organization for PB. Notably, HM and PB displayed unique flavor characteristics, while TM exhibited relatively neutral features. The study also identified correlations among VOCs, muscle fiber type, lipids, metabolites, and gene patterns specific to each cut, highlighting the complex interplay of factors influencing pork flavor.

High potential in synergizing the reduction of dissolved organic carbon concentration and carbon dioxide emissions for submerged-vegetation-covered river networks.

Various technologies and projects have been explored and developed for the synergetic control of environmental pollution and carbon emissions in aquatic ecosystems. Planting submerged vegetation in shallow waters was also expected to achieve this purpose. However, the magnitude and mechanism of carbon dioxide (CO2) emission affected by submerged vegetation is not clear enough in complex aquatic ecosystems. This study investigated the influences of submerged plants on CO2 emission, ecosystem metabolism features, and microbial community traits based on observations in river networks on the Changjiang River Delta. The results showed that CO2 emission from planted waters accounted for 73% of unplanted waters. Meanwhile, planted waters had higher dissolved organic carbon removal capacity in overlying water and higher potential of carbon sequestration in sediment at the same time. These distinctions between the two habitats were attributed to (1) improved CO2 and bicarbonate consumption in water columns via enhancing photosynthesis and (2) inhibited CO2 production by reconstructing the benthic microbial community. Additional eco-advantages were found in planted sediments, such as a high potential of methane oxidation and xenobiotics biodegradation and a low risk of becoming black and odorous. In brief, submerged vegetation is beneficial in promoting pollution removal and carbon retention synchronously. This study advances our understanding of the feedback between aquatic metabolism and CO2 emission.

Highly ordered aggregation of soy protein isolate particles for enhanced gel-related properties through konjac glucomannan addition.

This study assessed the effect of konjac glucomannan (KGM) on the aggregation of soy protein isolate (SPI) and its gel-related structure and properties. Raman results showed that KGM promoted the rearrangement of SPI to form more ß-sheets, contributing to the formation of an ordered structure. Atomic force microscopy, confocal laser scanning microscopy, and small-angle X-ray scattering results indicated that KGM reduced the size of SPI particles, narrowed their size distribution, and loosened the large aggregates formed by the stacking of SPI particles, improving the uniformity of gel system. As the hydrogen bonding between the KGM and SPI molecules enhanced, a well-developed network structure was obtained, further reducing the immobilized water's content (T22) and increasing the water-holding capacity (WHC) of SPI gel. Furthermore, this gel structure showed improved gel hardness and resistance to both small and large deformations. These findings facilitate the design and production of SPI-based gels with desired performance.

Effects of degree of milling on bran layer structure, physicochemical properties and cooking quality of brown rice.

Effects of varying degree of milling (DOM) (0-22%) on the bran layer structure, physicochemical properties, and cooking quality of brown rice were explored. As the DOM increased, bran degree, protein, lipid, dietary fiber, amylose, mineral elements, and color parameters (a* and b* values) of milled rice decreased while starch and L* value increased. Microscopic fluorescence images showed that the pericarp, combined seed coat-nucellus layer, and aleurone layer were removed in rice processed at DOM of 6.6%, 9.2%, and 15.4%, respectively. The pasting properties, thermal properties, and palatability of rice increased as the DOM increased. Principal component and correlation analysis indicated that excessive milling lead to a decline in nutritional value of rice with limited impact on enhancing palatability. Notably, when parts of aleurone cell wall were retained, rice samples exhibited high cooking and sensory properties. It serves as a potential guide to the production of moderately milled rice.

A novel fluorescent probe with high sensitivity and selectivity for "On-Off-On" sensors for Cu2+ cations and CN- anions.

A novel fluorescent probe NIPF was synthesized by the Suzuki reaction to recognize Cu2+ and CN-. With the addition of Cu2+, NIPF exhibited strong fluorescence quenching (90 % for NIPF) with a Ksv value of 3.4 × 106 M-1 and a detection limit of 9.04 × 10-10 M. Subsequently, CN- was added to the NIPF-Cu2+ solution, and [Cu(CN)x]n- was formed due to the strong interaction between Cu2+ and CN- leading to fluorescence recovery (89 % for NIPF-Cu2+). In addition, a detection limit of 3.6 × 10-8 M was obtained by fluorescence titration. Meanwhile, it was demonstrated that the sensor achieved 93 %-105 % recovery of Cu2+ in the tested environmental samples, and the practicability of Cu2+ and CN- detection were verified using hydrogels test, with significant color changes observed under 365 nm light. Accordingly, the fluorescent probe NIPF was used to recognize Cu2+ and CN- by the "on-off-on" sensors.

Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY: To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin. RESULTS: The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone. CONCLUSIONS: Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.

Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress-induced anxiety-like behavior.

JOURNAL/nrgr/04.03/01300535-202506000-00024/figure1/v/2024-08-05T133530Z/r/image-tiff The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions. Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress-induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2 agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice. After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.

The possible inhibition mechanism of low salt dry-curing on volatile flavor deterioration in refrigerated grass carp (Ctenopharyngodon idella) blocks: Metabolomics and microorganisms.

Complex microbial communities have an important impact on the flavor of low salt dry-curing (LSD)-pretreated grass carp blocks. Here, the flavors, metabolites, and bacterial diversity of LSD-pretreated fish during cold storage were analyzed using flavor analysis, metabolomics, and high-throughput sequencing to investigate their correlations in detail. LSD promoted the volatile flavor deterioration of grass carp blocks under 6 days of refrigeration but inhibited it under 15 days of refrigeration. Furthermore, 924 metabolites were identified in the refrigerated grass carp blocks, and LSD inhibited the growth of Psychrophilic dominant spoilage microorganisms (Proteobacteria) and promoted microbial abundance (Actinobacteriota, Firmicutes, Bacteroidota, and Cyanobacteria). Correlation analysis revealed that the degradation of phosphatidylcholine connected with the monomonas genus in LSD-pretreated fish blocks played a vital role in inhibiting the key volatile flavor (esters, aldehydes, and alcohols) deterioration. This information is useful for elucidating the inhibition mechanism of LSD on flavor deterioration in refrigerated fish blocks.

Generation of advanced glycation end products from glycated protein or fructose/glyoxal-protein adducts under in vitro simulated gastrointestinal digestion.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds formed both endogenously and exogenously through reactions between reducing sugars and amino acids within the proteins. The digestive tract may also serve as a site for endogenous AGEs generation. This study examined whether additional AGEs are formed during the digestion of glycated protein diets and meal-resembling systems (dietary proteins with fructose or glyoxal). The digestion of glycated protein showed that free AGEs were gradually released, but no additional AGEs were generated. In contrast, co-digestion of dietary proteins with fructose or glyoxal resulted in the formation of additional AGEs, and the reaction substrates (fructose or glyoxal) were depleted during digestion. Additionally, the lysine released from proteins decreased, leading to a loss of nutritional value of the food during co-digestion. The formation of AGEs and the depletion of essential amino acids in the gut may have significant implications for human health.

A novel micro-aqueous cold extraction of salmon head oil to reduce lipid oxidation and fishy odor: Comparison with common methods.

Traditional heat extraction (HE) has a low efficiency (75.2 wt%) and induces lipid oxidation of PUFAs. The novel micro-aqueous cold (<25 °C) extraction (MAE) was applied to extract salmon head oil. The recovery rate was 93.4 wt% at oil volume fraction Φ = 74 %. The extraction mechanism was agitation-induced droplet coalescence at an unstable and close-packing state (Φ = 74 %), increasing the portions of the large-sized droplets (>50 µm) from 2.8 vol% to 91.7 vol%. The MAE reduced the oil oxidation level and odor intensity compared to HE, although the lipid profile differed slightly. The HE head oil had more key fishy odor compounds, including hexanal (0.98 mg/kg), 3-methyl-butanal (0.25 mg/kg), 1-penten-3-ol (0.49 mg/kg), and 2-ethylfuran (0.19 mg/kg). The MAE oil had only 2-methyl-butanal (0.10 mg/kg) and 1-penten-3-ol (0.47 mg/kg). Overall, micro-aqueous extraction has great potential to replace industrial heat extraction with a better product quality.

Electrophilic aromatic substitution of electron-rich arenes with N-fluorobenzenesulfonimide (NFSI) as an electrophile.

An efficient amidation of electron-rich arenes using NFSI as a nitrogen source has been successfully disclosed. This amidation process can be easily conducted at elevated temperatures, without the need for catalysts or additives. A wide range of arenes substituted with hydroxy, alkoxy, or carbonyl groups were found to be compatible, yielding the desired amination products. Computational study shows that the amidation proceeds via an electrophilic aromatic substitution pathway, comprising a three-step process that includes substitution, addition, and elimination, which differs slightly from the classical mechanism.

Assessing contrast-induced nephropathy risk in older adults undergoing coronary angiography and intervention: The CV/GFR ratio versus Mehran score.

Background: Contrast-induced nephropathy is a prevalent cause of hospital-acquired renal insufficiency and increases adverse events in older patients undergoing angiography and percutaneous coronary intervention. The Mehran risk score has been widely used in Vietnam to assess contrast-induced nephropathy risk in patients before coronary angiography and percutaneous coronary intervention. Recently, there has been a shift toward the adoption of simpler risk prediction models, such as the contrast volume-to-glomerular filtration rate ratio. This study aimed to (1) determine the incidence of contrast-induced nephropathy in older patients undergoing coronary angiography and/or percutaneous coronary intervention, and (2) compare the validity of the contrast volume-to-glomerular filtration rate ratio and the Mehran score in predicting contrast-induced nephropathy. Method: This is a prospective cohort study conducted at a hospital in Vietnam from September 2019 to May 2020. Consecutive patients aged ⩾60 years who underwent coronary angiography and/or percutaneous coronary intervention were recruited. The contrast volume-to-glomerular filtration rate ratio and the Mehran score were evaluated for their predictive utility regarding contrast-induced nephropathy risk. The receiver operator characteristic was employed to calculate the area under the curve for both the contrast volume-to-glomerular filtration rate ratio and the Mehran score in predicting contrast-induced nephropathy. Results: The study included 170 participants with a mean age of 70 years and 33.1% were female. Contrast-induced nephropathy was diagnosed in 9.4% of the participants. Participants with contrast-induced nephropathy exhibited a higher prevalence of chronic kidney disease, anemia, and heart failure. There was no significant difference between the area under the curves of the contrast volume-to-glomerular filtration rate ratio (0.79, 95% CI: 0.65-0.92), and the Mehran score (0.65, 95% CI: 0.51-0.82) in predicting contrast-induced nephropathy. Conclusion: Our findings indicate that contrast-induced nephropathy was prevalent among older patients following percutaneous coronary intervention. The contrast volume-to-glomerular filtration rate ratio demonstrated a good prognostic value for predicting contrast-induced nephropathy comparable to that of the Mehran score. Further research is needed to identify optimal cutoff values for the contrast volume-to-glomerular filtration rate ratio in older patients.

Improving Soil Quality and Crop Yields Using Enhancing Sustainable Rice Straw Management Through Microbial Enzyme Treatments.

This study develops a model to raise public awareness about the consequences of burning rice straw after harvest, including environmental pollution, soil degradation, and increased CO2 emissions that contribute to the greenhouse effect. The distinctive feature of the research is the introduction of a post-harvest rice straw treatment process using microbial products capable of secreting cellulase enzymes, which can break down the cellulose in the straw. This process shortens the decomposition time and produces natural organic fertilizer, thus reducing cultivation costs by 60% and increasing crop yields by 20%. The experimental model was carried out in Cam My district, Dong Nai province, Vietnam, including 4 models: no microbial products; using Bio Decomposer; using NTT-01; and using NTT-02. Each experimental field had an area of 650 m². The results showed a significant reduction in straw decomposition time after 14 days of use of the products, with a decomposition rate of up to 80%, nearly twice as fast as without the products. This helps save time, produce natural organic fertilizers, reduce care costs, and increase rice yields, resulting in more income for local residents. These findings demonstrate the effectiveness of microbial treatments in sustainable agriculture and their potential for a broader application in the management of agricultural waste.

Diagnostic Value of Magnetocardiography to Detect Abnormal Myocardial Perfusion: A Pilot Study.

Background: Magnetocardiography (MCG) is a novel non-invasive technique that detects subtle magnetic fields generated by cardiomyocyte electrical activity, offering sensitive detection of myocardial ischemia. This study aimed to assess the ability of MCG to predict impaired myocardial perfusion using single-photon emission computed tomography (SPECT). Methods: A total of 112 patients with chest pain underwent SPECT and MCG scans, from which 65 MCG output parameters were analyzed. Using least absolute shrinkage and selection operator (LASSO) regression to screen for significant MCG variables, three machine learning models were established to detect impaired myocardial perfusion: random forest (RF), decision tree (DT), and support vector machine (SVM). The diagnostic performance was evaluated based on the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: Five variables, the ratio of magnetic field amplitude at R-peak and positive T-peak (RoART+), R and T-peak magnetic field angle (RTA), maximum magnetic field angle (MAmax), maximum change in current angle (CCAmax), and change positive pole point area between the T-wave beginning and peak (CPPPATbp), were selected from 65 automatic output parameters. RTA emerged as the most critical variable in the RF, DT, and SVM models. All three models exhibited excellent diagnostic performance, with AUCs of 0.796, 0.780, and 0.804, respectively. While all models showed high sensitivity (RF = 0.870, DT = 0.826, SVM = 0.913), their specificity was comparatively lower (RF = 0.500, DT = 0.300, SVM = 0.100). Conclusions: Machine learning models utilizing five key MCG variables successfully predicted impaired myocardial perfusion, as confirmed by SPECT. These findings underscore the potential of MCG as a promising future screening tool for detecting impaired myocardial perfusion. Clinical Trial Registration: ChiCTR2200066942, https://www.chictr.org.cn/showproj.html?proj=187904.

Corrigendum: Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review.

[This corrects the article DOI: 10.3389/fphar.2023.1156655.].

Inflammation biomarkers and neurobehavioral performance in rural adolescents.

Background: Systemic inflammation has been associated with lower neurobehavioral performance in diverse populations, yet the evidence in adolescents remains lacking. Cytokines can alter neural network activity to induce neurocognitive changes. This work seeks to investigate the association between inflammation and neurobehavior in adolescents living in a rural region of Ecuador. Methods: We examined 535 adolescents in rural communities of Ecuador (ESPINA study), 508 of which had neurobehavioral assessments (NEPSY-II) and circulating plasma levels of inflammatory markers (CRP, IL-6, TNF-⍺, sICAM-1, sVCAM-1, SAA, and sCD14). Associations between inflammatory biomarker concentrations and neurobehavioral scores were examined using adjusted bivariate semi-parametric models with generalized estimating equations. A partial least square regression approach was used to create composite variables from multiple inflammation biomarkers and model their association with cognitive outcomes. Results: Higher sCD14 and TNF-α concentrations were significantly associated with lower social perception scores, by -0.47 units (95% CI: -0.80, -0.13) and -0.42 (-0.72, -0.12) for every 50% increase in inflammatory marker concentration, respectively. Similarly, every 50% increase in the inflammation summary score was associated with a significantly lower Social Perception score by -0.11 units (-0.19, -0.03). A unit increase in inflammatory composites of seven markers were associated with lower scores in language (-0.11 units, p=0.04), visuospatial processing (-0.15, p= 0.09), and social perception (-0.22, p=0.005) domains. Conclusions: Higher levels of inflammation were associated with lower neurobehavioral performance in adolescents, especially with social perception. In addition, using a robust analytic method to examine an association between a composite inflammatory variable integrating seven markers led to additional findings, including the domains of language and visuospatial processing. A longitudinal follow-up of such investigations could unveil potential changes in inflammation-neurobehavior performance links through developmental stages and intervention opportunities.

Predicting deterioration in dengue using a low cost wearable for continuous clinical monitoring.

Close vital signs monitoring is crucial for the clinical management of patients with dengue. We investigated performance of a non-invasive wearable utilising photoplethysmography (PPG), to provide real-time risk prediction in hospitalised individuals. We performed a prospective observational clinical study in Vietnam between January 2020 and October 2022: 153 patients were included in analyses, providing 1353 h of PPG data. Using a multi-modal transformer approach, 10-min PPG waveform segments and basic clinical data (age, sex, clinical features on admission) were used as features to continuously forecast clinical state 2 h ahead. Prediction of low-risk states (17,939/80,843; 22.1%), defined by NEWS2 and mSOFA < 6, was associated with an area under the precision-recall curve of 0.67 and an area under the receiver operator curve of 0.83. Implementation of such interventions could provide cost-effective triage and clinical care in dengue, offering opportunities for safe ambulatory patient management.

Genomic and transcriptomic landscape of human gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. We comprehensively describe the genomic and transcriptomic landscape of a cohort of 117 GISTs including 31 low-risk, 18 intermediate-risk, 29 high-risk, 34 metastatic and 5 neoadjuvant GISTs from 105 patients. GISTs have notably low tumor mutation burden but widespread copy number variations. Aggressive GISTs harbor remarkably more genomic aberrations than low-/intermediate-risk GISTs. Complex genomic alterations, chromothripsis and kataegis, occur selectively in aggressive GISTs. Despite the paucity of mutations, recurrent inactivating YLPM1 mutations are identified (10.3%, 7 of 68 patients), enriched in high-risk/metastatic GIST and functional study further demonstrates YLPM1 inactivation promotes GIST proliferation, growth and oxidative phosphorylation. Spatially and temporally separated GISTs from individual patients demonstrate complex tumor heterogeneity in metastatic GISTs. Finally, four prominent subtypes are proposed with different genomic features, expression profiles, immune characteristics, clinical characteristics and subtype-specific treatment strategies. This large-scale analysis depicts the landscape and provides further insights into GIST pathogenesis and precise treatment.