Indian Ocean temperature anomalies predict long-term global dengue trends.

Despite identifying El Niño events as a factor in dengue dynamics, predicting the oscillation of global dengue epidemics remains challenging. Here, we investigate climate indicators and worldwide dengue incidence from 1990 to 2019 using climate-driven mechanistic models. We identify a distinct indicator, the Indian Ocean basin-wide (IOBW) index, as representing the regional average of sea surface temperature anomalies in the tropical Indian Ocean. IOBW is closely associated with dengue epidemics for both the Northern and Southern hemispheres. The ability of IOBW to predict dengue incidence likely arises as a result of its effect on local temperature anomalies through teleconnections. These findings indicate that the IOBW index can potentially enhance the lead time for dengue forecasts, leading to better-planned and more impactful outbreak responses.

Analysis of MRI features and associated factors of the pituitary neuroendocrine tumor streaky sign.

OBJECTIVES: Observation of pituitary neuroendocrine tumors with streaky sign on MRI, analysis of their features on imaging and further investigation of the relationship between the direction of the streak sign and the direction of optimal tumor expansion. METHODS: The MR images of 237 patients with pituitary neuroendocrine tumors were retrospectively analyzed. The streaky-like high signal with a substantial length of more than 10 mm and obvious enhancement on T1WI was defined as the streaky sign. Finally, 66 patients were included in the study, comprising 33 patients with streaky sign pituitary neuroendocrine tumors and 33 randomly selected patients with non-streaky sign pituitary neuroendocrine tumors. The general condition of these 66 patients, the imaging features of the tumor, and the measurement and analysis of the direction of the streaky sign in relation to the direction of optimal tumor extension were observed and analyzed. RESULTS: On MRI, 85 streaky signs were observed. The average deviation between the direction angle of all the streaky signs and the optimal extension direction angle of the tumor was approximately 11°. The longest streaky sign angle was positively correlated with the optimal extension angle of the tumor, with a correlation coefficient of 0.967. CONCLUSION: The presence of a streaky sign of pituitary neuroendocrine tumors may indicate a dilated sinus or a small blood vessel. Its direction is highly consistent with the optimal extension direction of the tumor, which has a certain supporting effect on the long-distance growth of the tumor.

Discovery of an immunosuppressive functional metabolite from the insect-derived endophytic Aspergillus taichungensis SMU01.

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

Satellite NO2 Retrieval Complicated by Aerosol Composition over Global Urban Agglomerations: Seasonal Variations and Long-Term Trends (2001-2018).

Tropospheric nitrogen dioxide (NO2) poses a serious threat to the environmental quality and public health. Satellite NO2 observations have been continuously used to monitor NO2 variations and improve model performances. However, the accuracy of satellite NO2 retrieval depends on the knowledge of aerosol optical properties, in particular for urban agglomerations accompanied by significant changes in aerosol characteristics. In this study, we investigate the impacts of aerosol composition on tropospheric NO2 retrieval for an 18 year global data set from Global Ozone Monitoring Experiment (GOME)-series satellite sensors. With a focus on cloud-free scenes dominated by the presence of aerosols, individual aerosol composition affects the uncertainties of tropospheric NO2 columns through impacts on the aerosol loading amount, relative vertical distribution of aerosol and NO2, aerosol absorption properties, and surface albedo determination. Among aerosol compositions, secondary inorganic aerosol mostly dominates the NO2 uncertainty by up to 43.5% in urban agglomerations, while organic aerosols contribute significantly to the NO2 uncertainty by -8.9 to 37.3% during biomass burning seasons. The possible contrary influences from different aerosol species highlight the importance and complexity of aerosol correction on tropospheric NO2 retrieval and indicate the need for a full picture of aerosol properties. This is of particular importance for interpreting seasonal variations or long-term trends of tropospheric NO2 columns as well as for mitigating ozone and fine particulate matter pollution.

Improved dual-aggregation polyp segmentation network combining a pyramid vision transformer with a fully convolutional network.

Automatic and precise polyp segmentation in colonoscopy images is highly valuable for diagnosis at an early stage and surgery of colorectal cancer. Nevertheless, it still posed a major challenge due to variations in the size and intricate morphological characteristics of polyps coupled with the indistinct demarcation between polyps and mucosas. To alleviate these challenges, we proposed an improved dual-aggregation polyp segmentation network, dubbed Dua-PSNet, for automatic and accurate full-size polyp prediction by combining both the transformer branch and a fully convolutional network (FCN) branch in a parallel style. Concretely, in the transformer branch, we adopted the B3 variant of pyramid vision transformer v2 (PVTv2-B3) as an image encoder for capturing multi-scale global features and modeling long-distant interdependencies between them whilst designing an innovative multi-stage feature aggregation decoder (MFAD) to highlight critical local feature details and effectively integrate them into global features. In the decoder, the adaptive feature aggregation (AFA) block was constructed for fusing high-level feature representations of different scales generated by the PVTv2-B3 encoder in a stepwise adaptive manner for refining global semantic information, while the ResidualBlock module was devised to mine detailed boundary cues disguised in low-level features. With the assistance of the selective global-to-local fusion head (SGLFH) module, the resulting boundary details were aggregated selectively with these global semantic features, strengthening these hierarchical features to cope with scale variations of polyps. The FCN branch embedded in the designed ResidualBlock module was used to encourage extraction of highly merged fine features to match the outputs of the Transformer branch into full-size segmentation maps. In this way, both branches were reciprocally influenced and complemented to enhance the discrimination capability of polyp features and enable a more accurate prediction of a full-size segmentation map. Extensive experiments on five challenging polyp segmentation benchmarks demonstrated that the proposed Dua-PSNet owned powerful learning and generalization ability and advanced the state-of-the-art segmentation performance among existing cutting-edge methods. These excellent results showed our Dua-PSNet had great potential to be a promising solution for practical polyp segmentation tasks in which wide variations of data typically occurred.

De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with NDD. The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). We estimate that variants in this region explain 0.41% of individuals with NDD. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to its contiguous counterpart RNU4-1 and other U4 homologs, supporting RNU4-2's role as the primary U4 transcript in the brain. Overall, this work underscores the importance of non-coding genes in rare disorders. It will provide a diagnosis to thousands of individuals with NDD worldwide and pave the way for the development of effective treatments for these individuals.

Molecularly-regulating oxygen-containing functional groups of ramie activated carbon for high-performance supercapacitors.

Effectively managing oxygen-containing functional groups (OCFGs) within activated carbon and methodically elucidating their intricate types and proportions are essential for considerably improving the electrochemical performance of carbon-based supercapacitors. Herein, we designed a ZnCl2-based molecular regulation strategy to introduce OCFGs into ramie-activated carbon (RAC), managing different OCFGs and revealing their structure-activity relationship with electrochemical performance. Thus, this regulated RAC, with a 3.5-fold enhancement in advantageous OCFGs (a-OCFGs: CO and COO), exhibits a supreme specific capacitance of 286.4F g-1 at 1 A/g and an excellent capacitance retention rate of 89.7 % at 20 A/g in an aqueous electrolyte, considerably surpassing that of nonregulated RAC (212.0F g-1 and 81.9 %). This confirms that a-OCFGs provide ample ion-storage accommodation and suppress solvent electronic oxidation, thereby enhancing electrochemical performance. Furthermore, its electrochemical performance is competitive with that of the commercial YP-50F (129.2F g-1 at 1 A/g). Therefore, this work not only highlights the contributions of specific OCFGs to high electrochemical performance but also designs a promising commercial electrode material to meet the demands of OCFGs-adequate carbon-based energy storage devices.

Association between ambient air pollutants and short-term mortality risks during 2015-2019 in Guangzhou, China.

With the development of technology and industry, the problem of global air pollution has become difficult to ignore. We investigated the association between air pollutant concentrations and daily all-cause mortality and stratified the analysis by sex, age, and season. Data for six air pollutants [fine particulate matter (PM2.5), inhalable particles (PM10), nitric dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO)] and daily mortality rates were collected from 2015 to 2019 in Guangzhou, China. A time-series study using a quasi-Poisson generalized additive model was used to examine the relationships between environmental pollutant concentrations and mortality. Mortality data for 296,939 individuals were included in the analysis. The results showed that an increase of 10 µg/m3 in the concentrations of PM2.5, PM10, SO2, O3, NO2, and CO corresponded to 0.84% [95% confidence interval (CI): 0.47, 1.21%], 0.70% (0.44, 0.96%), 3.59% (1.77, 5.43%), 0.21% (0.05, 0.36%), 1.06% (0.70, 1.41%), and 0.05% (0.02, 0.09%), respectively. The effects of the six air pollutants were more significant for male individuals than female individuals, the cool season than the warm season, and people 75 years or older than those younger than 75 years. PM2.5, PM10, SO2, and NO2 were all associated with neoplasms and circulatory and respiratory diseases. The two-pollutant models found that PM2.5, PM10, and NO2 may independently affect the risk of mortality. The results showed that exposure to PM2.5, PM10 and NO2 may increase the risk of daily all-cause excessive mortality in Guangzhou.

MRI 3D SPACE T2WI for Pituitary Adenoma Cavernous Sinus Invasion Diagnosis.

OBJECTIVE: This study aims to assess the utility of magnetic resonance imaging (MRI) 3D SPACE T2-weighted imaging (T2WI) sequences in evaluating cavernous sinus invasion by pituitary adenomas. METHODS: Data were collected from patients who underwent continuous pituitary MRIexaminations at the Medical Imaging Center of our hospital from October 2019 to February 2021. Eligible cases were evaluated for sagittal and axial T1WI sequences, coronal 3D SPACE T2WI sequences, and sagittal and coronal enhanced T1-weighted imaging (T1WI) sequences using the INFINITT PACS workstation. The Wilcoxon signed-rank test for paired samples and the Mann-Whitney U test for 2 independent samples were used to statistically analyze differences in image quality scores among various groups. In addition, the sensitivity, specificity, positive predictive value, and negative predictive value of each observation index were compared with intraoperative results. RESULTS: 3D SPACE T2WI showed superior cavernous sinus imaging quality compared with contrast enhanced T1WI and T2WI plain scans (P < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 90.0%, 55.60%, and 100.0%, respectively. The accuracy for pituitary adenoma invasiveness diagnosis based on cavernous sinus medial wall integrity was 94.40%. CONCLUSIONS: The imaging quality of the medial wall of the cavernous sinus on the 3D SPACE T2WI plain scan sequence surpassed that of contrast enhanced T1WI TSE-enhanced scans and T2WI TSE plain scans. The continuous observation of the medial wall of the cavernous sinus using this sequence holds great diagnostic value for assessing cavernous sinus invasion by pituitary adenomas. This strategy is more reliable than traditional MRI observation indicators.

Dynamic Transition between Monomer and Excimer Phosphorescence in Organic Near-Infrared Phosphorescent Crystals.

Achieving efficient near-infrared room-temperature phosphorescence of purely organic phosphors remains scarce and challenging due to strong nonradiative decay. Additionally, the investigation of triplet excimer phosphorescence is rarely reported, despite the fact that excimer, a special emitter commonly formed in crystals with strong π-π interactions, can efficiently change the fluorescent properties of compounds. Herein, a series of dithienopyrrole derivatives with low triplet energy levels and stable triplet states, exhibiting persistent near-infrared room-temperature phosphorescence, is developed. Via the modification of halogen atoms, the crystals display tunable emissions of monomers from 645 to 702 nm, with a maximum lifetime of 3.68 ms under ambient conditions. Notably, excimer phosphorescence can be switched on at low temperatures, enabled by noncovalent interactions rigidifying the matrix and stabilizing triplet excimer. Unprecedentedly, the dynamic transition process is captured between the monomer and excimer phosphorescence with temperature variations, revealing that the unstable triplet excimers in crystals with a tendency to dissociate can result in the effective quench of room-temperature phosphorescence. Excited state transitions across varying environments are elucidated, interpreting the structural dynamics of the triplet excimer and demonstrating strategies for devising novel near-infrared phosphors.

A sensitive lateral flow immunoassay relying on time-resolved fluorescent microspheres immune probe for determination of ceftiofur and its metabolite.

Ceftiofur (CEF) is an antimicrobial agent with high efficiency and low toxicity, desfuroylceftiofur is its main metabolite, but they are also have potential harm to human health. In this study, ceftiofur was combined with carrier proteins to get artificial antigens. A specific antibody (pAb) against CEF and desfuroylceftiofur was prepared. A sensitive and rapid paper-based sensor relying on time-resolved fluorescent microspheres (TRFMs) immune probes was developed, which were time-resolved fluorescent immunochromatographic strips (TRFMs-LFIA). The concentrations of T line and C line, activated pH, antibody volume and probe volume were optimized. Quantitative limits of detection (qLODs) of TRFMs-LFIA for CEF and desfuroylceftiofur were 0.97 ng/mL and 0.41 ng/mL, respectively. And 50 % inhibiting concentrations (IC50) were 12.92 ng/mL and 12.58 ng/mL, respectively. Pretreatment procedures of real samples were simple and rapid. Detection time of TRFMs-LFIA strip was 15 min. Qualitative analysis of CEF and desfuroylceftiofur was achieved under a UV light, quantitative analysis was implemented with a fluorescent immunoassay analyzer. The average recovery rates ranged from 91.4 % to 107.7 % and corresponding coefficients of variation (CV) was 1.5%-9.7 %. Concentration levels of artificially-spiked samples were measured by TRFMs-LFIA and compared with detection results of High performance liquid chromatography (HPLC), which showed a good accordance. These results indicated that the proposed assay can provide an effective strategy for on-site detection of CEF and desfuroylceftiofur simultaneously.

Camera calibration using the dual double-contact property of circles.

To mitigate the influence of the relative positional relationship between circles on camera calibration, this study explores the double contact of dual circles with dual circular points. We demonstrate that one of the generalized eigenvectors of two dual circles corresponds to the line passing through their respective centers. Moreover, we establish a methodology to identify this line from the three generalized eigenvectors and show that, regardless of the positional arrangement of the three co-planar circles, the image of the circular points can be constructed by calculating the image of this line. Consequently, the applicability of circles as calibration templates is expanded, enabling the development of a novel optimization technique for fitting circular images with enhanced calibration precision.

Self-Charging, Breathable, and Antibacterial Poly(lactic acid) Nanofibrous Air Filters by Surface Engineering of Ultrasmall Electroactive Nanohybrids.

Despite the great promise in the development of biodegradable and ecofriendly air filters by electrospinning of poly(lactic acid) (PLA) nanofibrous membranes (NFMs), the as-electrospun PLA nanofibers are generally characterized by poor electroactivity and smooth surface, challenging the exploitation of electrostatic adsorption and physical interception that are in need for efficient removal of pathogens and particulate matters (PMs). Herein, a combined "electrospinning-electrospray" strategy was disclosed to functionalize the PLA nanofibers by direct anchoring of highly dielectric BaTiO3@ZIF-8 nanohybrids (BTO@ZIF-8), conferring simultaneous promotion of surface roughness, electret properties (surface potential as high as 7.5 kV), and self-charging capability (∼190% increase in tribo-output voltage compared to that of pure PLA). Benefiting from the well-tailored morphology and increased electroactivity, the electrospun-electrosprayed PLA/BTO@ZIF-8 exhibited excellent PM-capturing performance (up to 96.54% for PM0.3 and 99.49% for PM2.5) while providing desirable air resistance (only 87 Pa at 32 L/min) due primarily to the slip flow of air molecules over the nanohybrid protrusions. This was accompanied by excellent antibacterial properties (99.9% inhibition against both Staphylococcus aureus and Escherichia coli), arising presumably from the synergistic effects of enhanced reactive oxygen species (ROS) generation, plentiful ion release, and surface charges. Our proposed strategy opens up pathways to afford exceptional combination of high-efficiency and low-resistance filtration, excellent antibacterial performance, and mechanical robustness without sacrificing the biodegradation profiles of PLA NFMs, holding potential implications for efficient and long-term healthcare.

Study of Pharmacokinetics for Ivermectin B1a from Beagle Dogs.

Ivermectin has been widely used for antiparasitic drug, and has recently shown a broad-spectrum antiviral activity, including anti-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the pharmacokinetic property of ivermectin has not been fully investigated yet. During the plasma preparation, ~32-46% of ivermectin was found in the precipitation. An Liquid Chromatograph-Mass Spectrometer (LC-MS/MS) method for ivermectin in the whole blood samples from beagle dogs was developed and validated. The specificity, accuracy, precision (intra-day and inter-day), matrix effect, recovery and stability of analyte reported here are satisfied with the criteria of Food and Drug Administration (FDA)-Bioanalysis guideline. The oral administrations pharmacokinetics of ivermectin in beagle dogs under fasting and after high-fat meal were studied, and the following parameters were obtained: fasting Cmax, 104 ± 35 µg·L-1; area under the concentration-time curve (AUC0-∞), 2,555 ± 941 h·µg·L-1; and high-fat meal Cmax, 147 ± 35 µg·L-1; AUC0-∞, 4,198 ± 1,279 h·µg·L-1. When the P-gp inhibitor curcumin was also coadministrated orally, Cmax and AUC0-∞ were found to be 177 ± 57 and 4,213 ± 948 h·µg·L-1, respectively. With the comparison to fasting treatment, coadministration of P-gp inhibitor curcumin resulted in increase of the exposure of ivermectin by 1.6-fold, while the exposure after the high-fat diet versus fasting was increased approximately in 1.4-fold, indicating that alternative absorption might play an important role for increasing the exposure of ivermectin for future clinic applications.

Oxidation engineering triggered peroxidase-like activity of VOxC for detection of dopamine and glutathione.

MXenes, two-dimensional nanomaterials, are gaining traction in catalysis and biomedicine. Yet, their oxidation instability poses significant functional constraints. Gaining insight into this oxidation dynamic is pivotal for designing MXenes with tailored functionalities. Herein, we crafted VOxC nanosheets by oxidatively engineering V4C3 MXene. Interestingly, while pristine V4C3 displays pronounced antioxidant behavior, its derived VOxC showcases enhanced peroxidase-like activity, suggesting the crossover between antioxidant and pro-oxidant capability. The mixed valence states and balanced composition of V in VOxC drive the Fenton reaction through multiple pathways to continually generate hydroxyl radicals, which was proposed as the mechanism underlying the peroxidase-like activity. Furthermore, this unique activity rendered VOxC effective in dopamine and glutathione detection. These findings underscore the potential of modulating MXenes' oxidation state to elicit varied catalytic attributes, providing an avenue for the judicious design of MXenes and derivatives for bespoke applications.

Powerful Synergy of Traditional Chinese Medicine and Aggregation-Induced Emission-Active Photosensitizer in Photodynamic Therapy.

Breast cancer (BC) remains a significant global health challenge for women despite advancements in early detection and treatment. Isoliquiritigenin (ISL), a compound derived from traditional Chinese medicine, has shown potential as an anti-BC therapy, but its low bioavailability and poor water solubility restrict its effectiveness. In this study, we created theranostic nanoparticles consisting of ISL and a near-infrared (NIR) photosensitizer, TBPI, which displays aggregation-induced emission (AIE), with the goal of providing combined chemo- and photodynamic therapies (PDT) for BC. Initially, we designed an asymmetric organic molecule, TBPI, featuring a rotorlike triphenylamine as the donor and 1-methylpyridinium iodide as the acceptor, which led to the production of reactive oxygen species in mitochondria. We then combined TBPI with ISL and encapsulated them in DSPE-PEG-RGD nanoparticles to produce IT-PEG-RGD nanoparticles, which showed high affinity for BC, better intersystem crossing (ISC) efficiency, and Förster resonance energy transfer (FRET) between TBPI and ISL. In both 4T1 BC cell line and a 4T1 tumor-bearing BC mouse model, the IT-PEG-RGD nanoparticles demonstrated excellent drug delivery, synergistic antitumor effects, enhanced tumor-killing efficacy, and reduced drug dosage and side effects. Furthermore, we exploited the optical properties of TBPI with ISL to reveal the release process and distribution of nanoparticles in cells. This study provides a valuable basis for further exploration of IT-PEG-RGD nanoparticles and their anticancer mechanisms, highlighting the potential of theranostic nanoparticles in BC treatment.

Association of vaccination, international travel, public health and social measures with lineage dynamics of SARS-CoV-2.

Continually emerging SARS-CoV-2 variants of concern that can evade immune defenses are driving recurrent epidemic waves of COVID-19 globally. However, the impact of measures to contain the virus and their effect on lineage diversity dynamics are poorly understood. Here, we jointly analyzed international travel, public health and social measures (PHSM), COVID-19 vaccine rollout, SARS-CoV-2 lineage diversity, and the case growth rate (GR) from March 2020 to September 2022 across 63 countries. We showed that despite worldwide vaccine rollout, PHSM are effective in mitigating epidemic waves and lineage diversity. An increase of 10,000 monthly travelers in a single country-to-country route between endemic countries corresponds to a 5.5% (95% CI: 2.9 to 8.2%) rise in local lineage diversity. After accounting for PHSM, natural immunity from previous infections, and waning immunity, we discovered a negative association between the GR of cases and adjusted vaccine coverage (AVC). We also observed a complex relationship between lineage diversity and vaccine rollout. Specifically, we found a significant negative association between lineage diversity and AVC at both low and high levels but not significant at the medium level. Our study deepens the understanding of population immunity and lineage dynamics for future pandemic preparedness and responsiveness.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Large-Scale Cell Production Based on GMP-Grade Dissolvable Porous Microcarriers.

Researchers in the cell and gene therapy (CGT) industry have long faced a formidable challenge in the efficient and large-scale expansion of cells. To address the primary shortcomings of the two-dimensional (2D) planar culturing system, we innovatively developed an automated closed industrial scale cell production (ACISCP) platform based on a GMP-grade, dissolvable, and porous microcarrier for the 3D culture of adherent cells, including human mesenchymal stem/stromal cells (hMSCs), HEK293T cells, and Vero cells. To achieve large-scale expansion, a two-stage expansion was conducted with 5 L and 15 L stirred-tank bioreactors to yield 1.1 x 1010 hMSCs with an overall 128-fold expansion within 9 days. The cells were harvested by completely dissolving the microcarriers, concentrated, washed and formulated with a continuous-flow centrifuge-based cell processing system, and then aliquoted with a cell filling system. Compared with 2D planar culture, there are no significant differences in the quality of hMSCs harvested from 3D culture. We have also applied these dissolvable porous microcarriers to other popular cell types in the CGT sector; specifically, HEK293T cells and Vero cells have been cultivated to peak cell densities of 1.68 x 107 cells/mL and 1.08 x 107 cells/mL, respectively. This study provides a protocol for using a bioprocess engineering platform harnessing the characteristics of GMP-grade dissolvable microcarriers and advanced closed equipment to achieve the industrial-scale manufacturing of adherent cells.