Spatially Resolved Defect Characterization and Fidelity Assessment for Complex and Arbitrary Irregular 3D Printing Based on 3D P-OCT and GCode.

To address the challenges associated with achieving high-fidelity printing of complex 3D bionic models, this paper proposes a method for spatially resolved defect characterization and fidelity assessment. This approach is based on 3D printer-associated optical coherence tomography (3D P-OCT) and GCode information. This method generates a defect characterization map by comparing and analyzing the target model map from GCode information and the reconstructed model map from 3D P-OCT. The defect characterization map enables the detection of defects such as material accumulation, filament breakage and under-extrusion within the print path, as well as stringing outside the print path. The defect characterization map is also used for defect visualization, fidelity assessment and filament breakage repair during secondary printing. Finally, the proposed method is validated on different bionic models, printing paths and materials. The fidelity of the multilayer HAP scaffold with gradient spacing increased from 0.8398 to 0.9048 after the repair of filament breakage defects. At the same time, the over-extrusion defects on the nostril and along the high-curvature contours of the nose model were effectively detected. In addition, the finite element analysis results verified that the 60-degree filling model is superior to the 90-degree filling model in terms of mechanical strength, which is consistent with the defect detection results. The results confirm that the proposed method based on 3D P-OCT and GCode can achieve spatially resolved defect characterization and fidelity assessment in situ, facilitating defect visualization and filament breakage repair. Ultimately, this enables high-fidelity printing, encompassing both shape and function.

miR-21-Mediated Endothelial Senescence and Dysfunction Are Involved in Cigarette Smoke-Induced Pulmonary Hypertension through Activation of PI3K/AKT/mTOR Signaling.

Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the lung tissue of smoking-induced PH patients, the levels of miR-21 and aging markers (p21 and p16) were upregulated, and the function of pulmonary vascular endothelial cells was also impaired. Exposure of mice to cigarette smoke (CS) for four months caused similar changes in lung tissues and increased pulmonary arterial pressure, which were attenuated by knockout of miR-21. Further, human umbilical vein endothelial cells (HUVECs) exposed to cigarette smoke extract (CSE) revealed upregulation of miR-21 levels, depression of PTEN, activation of PI3K/AKT/mTOR signaling, an increase in senescence indexes, and enhanced dysfunction. Inhibiting miR-21 overexpression reversed the PTEN-mTOR signaling pathway and prevented senescence and dysfunction of HUVECs. In sum, our data indicate that miR-21-mediated endothelial senescence and dysfunction are involved in CS-induced PH through the activation of PI3K/AKT/mTOR signaling, which suggests that selective miR-21 inhibition offers the potential to attenuate PH.

An empirical study on KDIGO-defined acute kidney injury prediction in the intensive care unit.

MOTIVATION: Acute kidney injury (AKI) is a syndrome that affects a large fraction of all critically ill patients, and early diagnosis to receive adequate treatment is as imperative as it is challenging to make early. Consequently, machine learning approaches have been developed to predict AKI ahead of time. However, the prevalence of AKI is often underestimated in state-of-the-art approaches, as they rely on an AKI event annotation solely based on creatinine, ignoring urine output.We construct and evaluate early warning systems for AKI in a multi-disciplinary ICU setting, using the complete KDIGO definition of AKI. We propose several variants of gradient-boosted decision tree (GBDT)-based models, including a novel time-stacking based approach. A state-of-the-art LSTM-based model previously proposed for AKI prediction is used as a comparison, which was not specifically evaluated in ICU settings yet. RESULTS: We find that optimal performance is achieved by using GBDT with the time-based stacking technique (AUPRC = 65.7%, compared with the LSTM-based model's AUPRC = 62.6%), which is motivated by the high relevance of time since ICU admission for this task. Both models show mildly reduced performance in the limited training data setting, perform fairly across different subcohorts, and exhibit no issues in gender transfer.Following the official KDIGO definition substantially increases the number of annotated AKI events. In our study GBDTs outperform LSTM models for AKI prediction. Generally, we find that both model types are robust in a variety of challenging settings arising for ICU data. AVAILABILITY AND IMPLEMENTATION: The code to reproduce the findings of our manuscript can be found at: https://github.com/ratschlab/AKI-EWS.

Design and synthesis of matrine derivatives for anti myocardial ischemia-reperfusion injury by promoting angiogenesis.

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.

Dynamic characterization of water hammer in gangue fly ash slurry pipelines during valve closure.

In the process of coal-filling mining, the gangue fly-ash slurry (GFS) needs to be transported over a long distance to reach the gobs. The abrupt closure of the valve during the transportation of GFS can result in a water hammer that significantly endangers the stability and safety of the pipeline transport system. To study the fluctuations in pressure induced by abrupt closure of the valve, experiments on the rheological parameters of gangue-coal ash slurry were conducted. Transient numerical simulations were carried out using the computational fluid dynamics method for various valve closing times. The results indicate that, with the increase of slurry concentration, the yield stress of the slurry significantly increases. When the concentration exceeds 76%, the increase in yield stress reaches 38.4% and 35.1%, respectively. Upon valve closure, the internal pressure of the slurry in the pipeline exhibits periodic dynamic oscillations. As the duration of valve closure increases, the frequency of periodic water hammer events decreases. The maximum water hammer pressure caused by valve closure decreases with the increasing distance between the valve and the closure point. At the same time, the intensity of maximum water hammer pressure fluctuations increases with the increase in slurry concentration and flow velocity in the pipeline. The results can provide references for water hammer protection and pipeline selection during the transportation of backfill slurry in mining.

Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

In Situ Fenestration and Carotid-Subclavian Bypass for Left Subclavian Artery Revascularization During Thoracic Endovascular Aortic Repair.

PURPOSE: To evaluate the safety and feasibility of left subclavian artery (LSA) revascularization techniques during thoracic endovascular aortic repair (TEVAR)-the in situ needle fenestration (ISNF) technique and the carotid-subclavian bypass (CS-Bp)-for complicated aortic pathologies. METHODS: A retrospective single-center observational study was conducted to identify all patients with thoracic aortic pathologies who underwent TEVAR with LSA revascularization using either CS-Bp or ISNFs from January 2014 to December 2020. RESULTS: One hundred and twelve consecutive patients who received TEVAR with LSA revascularization were included. Among them, 69 received CS-Bp and 43 received ISNF (29 using the Futhrough adjustable puncture needles, 14 using the binding stent-graft puncture systems). Technical success, defined as achieving aortic arch pathology exclusion and LSA preservation, was attained in 99.1% patients. Early mortality was 0.9%. Major adverse events within 30 days, including one cerebral hemorrhage, one cervical incision hemorrhage, one stroke and two paraplegia, were exclusively observed in the CS-Bp group. Immediate type I, II and III endoleaks occurred in 0%, 4.7% and 2.3% in the ISNF group, respectively, compared to 0%, 2.9% and 0% in the CS-Bp group.One hundred and eight (97.2%) patients were available for follow-up at a median 50 (maiximum of 103) months, revealing a LSA patency rates of 99.1%. Six patients died during follow-ups-five in the CS-Bp group and one in the ISNF group. Cause of death include one aortic-related stent-graft infection, three non-related and two with unknow causes. The survival exhibited no significantly different between the ISNF (97.7%) and CS-Bp (89.9%) groups (p = 0.22). CONCLUSIONS: Both CS-Bp and ISNF are feasible techniques for LSA reconstruction in TEVAR. ISNF, whether using Futhrough or BPS, seems to be competitive with CS-Bp.

Glucose-Driven Droplet Formation in Complexes of a Supramolecular Peptide and Therapeutic Protein.

Biology achieves remarkable function through processes arising from spontaneous or transient liquid-liquid phase separation (LLPS) of proteins and other biomolecules. While polymeric systems can achieve similar phenomena through simple or complex coacervation, LLPS with supramolecular materials has been less commonly shown. Functional applications for synthetic LLPS systems are an expanding area of emphasis, with particular focus on capturing the transient and dynamic state of these structures for use in biomedicine. Here, a net-cationic supramolecular peptide amphiphile building block with a glucose-binding motif is shown that forms LLPS structures when combined with a net-negatively charged therapeutic protein, dasiglucagon, in the presence of glucose. The droplets that arise are dynamic and coalesce quickly. However, the interface can be stabilized by addition of a 4-arm star PEG. When the stabilized droplets formed in glucose are transferred to a bulk phase containing different glucose concentrations, their stability and lifetime decrease according to bulk glucose concentration. This glucose-dependent formation translates into an accelerated release of dasiglucagon in the absence of glucose; this hormone analogue itself functions therapeutically to correct low blood glucose (hypoglycemia). These droplets also offer function in mitigating the most severe effects of hypoglycemia arising from an insulin overdose through delivery of dasiglucagon in a mouse model of hypoglycemic rescue. Accordingly, this approach to use complexation between a supramolecular peptide amphiphile and a therapeutic protein in the presence of glucose leads to droplets with functional potential to dissipate for the release of the therapeutic material in low blood glucose environments.

NSUN2 promotes lung adenocarcinoma progression through stabilizing PIK3R2 mRNA in an m5C-dependent manner.

It is well known that 5-methylcytosine (m5C) is involved in variety of crucial biological processes in cancers. However, its biological roles in lung adenocarcinoma (LAUD) remain to be determined. The LUAD samples were used to assess the clinical value of NOP2/Sun RNA Methyltransferase 2 (NSUN2). Dot blot was used to determine global m5C levels. ChIP and dual-luciferase assays were performed to investigate the MYC-associated zinc finger protein (MAZ)-binding sites in NSUN2 promoter. RNA-seq was used to explore the downstream molecular mechanisms of NSUN2. Dual luciferase reporter assay, m5C-RIP-qPCR, and mRNA stability assay were conducted to explore the effect of NSUN2-depletion on target genes. Cell viability, transwell, and xenograft mouse model were designed to demonstrate the characteristic of NSUN2 in promoting LUAD progression. The m5C methyltransferase NSUN2 was highly expressed and caused elevated m5C methylation in LUAD samples. Mechanistically, MAZ positively regulated the transcription of NSUN2 and was related to poor survival of LUAD patients. Silencing NSUN2 decreased the global m5C levels, suppressed proliferation, migration and invasion, and inhibited activation of PI3K-AKT signaling in A549 and SPAC-1 cells. Phosphoinositide-3-Kinase Regulatory Subunit 2 (PIK3R2) was upregulated by NSUN2-mediated m5C methylation by enhancing its mRNA stabilization and activated the phosphorylation of the PI3K-AKT signaling. The present study explored the underlying mechanism and biological function of NSUN2-meditated m5C RNA methylation in LUAD. NSUN2 was discovered to facilitate the malignancy progression of LUAD through regulating m5C modifications to stabilize PIK3R2 activating the PI3K-AKT signaling, suggesting that NSUN2 could be a novel biomarker and promising therapeutic target for LUAD patients.

Biochar application can enhance phosphorus solubilization by strengthening redox properties of humic reducing microorganisms during composting.

Phosphorus (P) in nature mostly exists in an insoluble state, and humic reducing microorganisms (HRMs) can dissolve insoluble substances through redox properties. This study aimed to investigate the correlations between insoluble P and dominant HRMs amenable to individual culture during biochar composting. These analyses revealed that, in comparison to the control, biochar addition increased the relative abundance of dominant HRMs by 20.3% and decreased redox potential (Eh) levels by 15.4% hence, enhancing the moderately-labile-P and non-labile-P dissolution. The pathways underlying the observed effects were additionally assessed through structural equation modeling, revealing that biochar addition promoted insoluble P dissolution through both the direct effects of bacterial community structure as well as the direct effects of HRMs community structure and indirect effects based on Eh of HRMs community structure. This research offers a better understanding of the effect of HRMs on insoluble P during the composting process.

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Therapy in Mice and Swine.

The management of diabetes in a manner offering autonomous insulin therapy responsive to glucose-directed need, and moreover with a dosing schedule amenable to facile administration, remains an ongoing goal to improve the standard of care. While basal insulins with reduced dosing frequency, even once-weekly administration, are on the horizon, there is still no approved therapy that offers glucose-responsive insulin function. Herein, a nanoscale complex combining both electrostatic- and dynamic-covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high-affinity glucose-binding motif yields an injectable insulin depot affording both glucose-directed and long-lasting insulin availability. Following a single injection, it is even possible to control blood glucose for at least one week in diabetic swine subjected to daily oral glucose challenges. Measurements of serum insulin concentration in response to challenge show increases in insulin corresponding to elevated blood glucose levels, an uncommon finding even in preclinical work on glucose-responsive insulin. Accordingly, the subcutaneous nanocomplex that results from combining electrostatic- and dynamic-covalent interactions between a modified insulin and a synthetic dendrimer carrier affords a glucose-responsive insulin depot for week-long control following a single routine injection.

Construction of an adverse outcome pathway framework based on integrated data to evaluate arsenic-induced non-alcoholic fatty liver disease.

Arsenic is a recognized environmental pollutant naturally occurring in aquifers through geological processes. Toxicological studies have revealed that liver is the main target organ harmed by arsenic exposure. However, systematic studies of non-alcoholic fatty liver disease (NAFLD) are not comprehensive, and information regarding threats and risk assessment remains insufficient. This research aimed to examine the association between arsenic exposure and NAFLD and uncover the role of molecular initiating events and key events in disease development using the Adverse Outcome Pathway (AOP). Data from 8,104 adults in the National Health and Nutrition Examination Survey were used to explore the relationship between urinary arsenic and NAFLD. In a logistic regression model, urinary inorganic arsenic levels positively correlated with NAFLD (odds ratio = 1.12, 95 % confidence interval = 1.07-1.16). Subsequently, to gain a deeper understanding of arsenic-induced NAFLD, an AOP framework was constructed, revealing that arsenic exposure led to elevate levels of TNF-α, which regulated the NF-κB pathway and led to hepatic lipid deposition, causing NAFLD. This AOP was assessed as "high" according to the Organization for Economic Co-operation and Development users' handbook, and in vitro and in vivo models validated the AOP framework. In summary, this study highlights the potential mechanisms of arsenic-induced NAFLD. We combined the AOP with classical toxicological approaches with a view of establishing, rapidly and accurately, the lowest level at which environmental arsenic exposure can have adverse effects on the body, thereby contributing to risk assessment strategies for arsenic exposure through iterative and animal modeling at the population level.

A novel method for the measurement of superconducting transmission lines at terahertz frequencies.

Characterizing the properties (e.g., effective dielectric constant εeff, attenuation constant α, and characteristic impedance Z0) of terahertz (THz) superconducting transmission lines is of particular interest in designing on-chip integrated THz bandpass filters, which are a critical component for THz astronomical instruments, such as multi-color camera and broadband imaging spectrometers. Here, we propose a novel method for the characterization of three parameters (εeff, α, and Z0) of THz superconducting transmission lines. This method measures the ratio of the THz signal powers through two different-length branches of the superconducting transmission line to be measured. In addition, only one measurement is required for an all-in-one device chip, including an antenna, a half-power divider, the superconducting transmission line to be measured, and two detectors. The key point is that the superconducting transmission line to be measured is impedance-mismatched with the two integrated detectors. The method is validated through simulation and measurement for superconducting coplanar waveguide transmission lines around 400 GHz.

CUL4B functions as a tumor suppressor in KRAS-driven lung tumors by inhibiting the recruitment of myeloid-derived suppressor cells.

Lung cancer is the leading cause of cancer-related death worldwide. KRAS mutations are the most common oncogenic alterations found in lung cancer. Unfortunately, treating KRAS-mutant lung adenocarcinoma (ADC) remains a major oncotherapeutic challenge. Here, we used both autochthonous and transplantable KRAS-mutant tumor models to investigate the role of tumor-derived CUL4B in KRAS-driven lung cancers. We showed that knockout or knockdown of CUL4B promotes lung ADC growth and progression in both models. Mechanistically, CUL4B directly binds to the promoter of Cxcl2 and epigenetically represses its transcription. CUL4B deletion increases the expression of CXCL2, which binds to CXCR2 on myeloid-derived suppressor cells (MDSCs) and promotes their migration to the tumor microenvironment. Targeting of MDSCs significantly delayed the growth of CUL4B knockdown KRAS-mutant tumors. Collectively, our study provides mechanistic insights into the novel tumor suppressor-like functions of CUL4B in regulating KRAS-driven lung tumor development.

Automatically Identifying Sickness Behavior in Grazing Lambs with an Acceleration Sensor.

Acute disease of grazing animals can lead to alterations in behavioral patterns. Relatively recent advances in accelerometer technology have resulted in commercial products, which can be used to remotely detect changes in animals' behavior, the pattern and extent of which may provide an indicator of disease challenge and animal health status. The objective of this study was to determine if changes in behavior during use of a lipopolysaccharide (LPS) challenge model can be detected using ear-mounted accelerometers in grazing lambs. LPS infusion elevated rectal temperatures from 39.31 °C to 39.95 °C, indicating successful establishment of an acute fever response for comparison with groups (p < 0.001). For each of the five recorded behaviors, time spent eating, ruminating, not active, active, and highly active, the accelerometers were able to detect an effect of LPS challenge. Compared with the control, there were significant effects of LPS infusion by hour interaction on durations of eating (-6.71 min/h, p < 0.001), inactive behavior (+16.00 min/h, p < 0.001), active behavior (-8.39 min/h, p < 0.001), and highly active behavior (-2.90 min/h, p < 0.001) with a trend for rumination time (-1.41 min/h, p = 0.075) in lambs after a single LPS infusion. Results suggest that current sensors have the capability to correctly identify behaviors of grazing lambs, raising the possibility of detecting changes in animals' health status.

Effects of adding corn steep liquor on bacterial community composition and carbon and nitrogen transformation during spent mushroom substrate composting.

BACKGROUND: Carbon and nitrogen are essential energy and nutrient substances in the composting process. Corn steep liquor (CSL) is rich in soluble carbon and nitrogen nutrients and active substances and is widely used in the biological industry. Nonetheless, limited research has been done on the effect of CSL on composting. This work firstly reveals the effect of adding CSL to bacterial community composition and carbon and nitrogen conversion during composting. This study provides the choice of auxiliary materials for the spent mushroom substrate compost (SMS) and some novel knowledge about the effect of bacterial community on C and N cycling during composting of SMS and CSL. Two treatments were set up in the experiment: 100% spent mushroom substrate (SMS) as CK and SMS + 0.5% CSL (v/v) as CP. RESULTS: The results showed that the addition of CSL enhanced the initial carbon and nitrogen content of the compost, altered the bacterial community structure, and increased the bacterial diversity and relative abundance, which might be beneficial to the conversion and retention of carbon and nitrogen in the composting process. In this paper, network analysis was used to screen the core bacteria involved in carbon and nitrogen conversion. In the CP network, the core bacteria were divided into two categories, synthesizing and degrading bacteria, and there were more synthesizing bacteria than degrading bacteria, so the degradation and synthesis of organic matter were carried out simultaneously, while only degrading bacteria were found in the CK network. Functional prediction by Faprotax identified 53 groups of functional bacteria, among which 20 (76.68% abundance) and 14 (13.15% abundance) groups of functional bacteria were related to carbon and nitrogen conversion, respectively. Adding CSL stimulated the compensatory effect of core and functional bacteria, enhanced the carbon and nitrogen transformation ability, stimulated the activity of low-abundance bacteria, and reduced the competitive relationship between the bacterial groups. This may be why the addition of CSL accelerated the organic matter degradation and increased carbon and nitrogen preservation. CONCLUSIONS: These findings indicate that the addition of CSL promoted the cycling and preservation of carbon and nitrogen in the SMS composts, and the addition of CSL to the compost may be an effective way to dispose of agricultural waste.

Chemical signal regulated injectable coacervate hydrogels.

In the quest for stimuli-responsive materials with specific, controllable functions, coacervate hydrogels have become a promising candidate, featuring sensitive responsiveness to environmental signals enabling control over sol-gel transitions. However, conventional coacervation-based materials are regulated by relatively non-specific signals, such as temperature, pH or salt concentration, which limits their possible applications. In this work, we constructed a coacervate hydrogel with a Michael addition-based chemical reaction network (CRN) as a platform, where the state of coacervate materials can be easily tuned by specific chemical signals. We designed a pyridine-based ABA triblock copolymer, whose quaternization can be regulated by an allyl acetate electrophile and an amine nucleophile, leading to gel construction and collapse in the presence of polyanions. Our coacervate gels showed not only highly tunable stiffness and gelation times, but excellent self-healing ability and injectability with different sized needles, and accelerated degradation resulting from chemical signal-induced coacervation disruption. This work is expected to be a first step in the realization of a new class of signal-responsive injectable materials.

Dynamic Covalent Dextran Hydrogels as Injectable, Self-Adjuvating Peptide Vaccine Depots.

Dextran-based hydrogels are promising therapeutic materials for drug delivery, tissue regeneration devices, and cell therapy vectors, due to their high biocompatibility, along with their ability to protect and release active therapeutic agents. This report describes the synthesis, characterization, and application of a new dynamic covalent dextran hydrogel as an injectable depot for peptide vaccines. Dynamic covalent crosslinks based on double Michael addition of thiols to alkynones impart the dextran hydrogel with shear-thinning and self-healing capabilities, enabling hydrogel injection. These injectable, non-toxic hydrogels show adjuvant potential and have predictable sub-millimolar loading and release of the peptide antigen SIINFEKL, which after its release is able to activate T-cells, demonstrating that the hydrogels deliver peptides without modifying their immunogenicity. This work demonstrates the potential of dynamic covalent dextran hydrogels as a sustained-release material for the delivery of peptide vaccines.

Prediction of recovery from multiple organ dysfunction syndrome in pediatric sepsis patients.

MOTIVATION: Sepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking. RESULTS: This study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care. AVAILABILITY AND IMPLEMENTATION: Code available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.