Development and validation of a scoring system to predict the mortality of hospitalized patients with SARS-CoV-2 Omicron: a nationwide, multicentre study.

BACKGROUND: The Omicron variant broke out in China at the end of 2022, causing a considerable number of severe cases and even deaths. The study aimed to identify risk factors for death in patients hospitalized with SARS-CoV-2 Omicron infection and to establish a scoring system for predicting mortality. METHODS: 1817 patients were enrolled at eight hospitals in China from December 2022 to May 2023, including 815 patients in the training group and 1002 patients in the validation group. Forty-six clinical and laboratory features were screened using LASSO regression and multivariable logistic regression. RESULTS: In the training set, 730 patients were discharged and 85 patients died. In the validation set, 918 patients were discharged and 84 patients died. LASSO regression identified age, levels of interleukin (IL) -6, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and D-dimer; neutrophil count, neutrophil-to-lymphocyte ratio (NLR) as associated with mortality. Multivariable logistic regression analysis showed that older age, IL-6, BUN, LDH and D-dimer were significant independent risk factors. Based on these variables, a scoring system was developed with a sensitivity of 83.6% and a specificity of 83.5% in the training group, and a sensitivity of 79.8% and a sensitivity of 83.0% in the validation group. CONCLUSIONS: A scoring system based on age, IL-6, BUN, LDH and D-dime can help clinicians identify patients with poor prognosis early.

The Utility of Real-Time PCR, Metagenomic Next-Generation Sequencing, and Culture in Bronchoalveolar Lavage Fluid for Diagnosis of Pulmonary Aspergillosis.

Timely detection of Aspergillus infection is crucial given the high mortality rate of pulmonary aspergillosis (PA). Here, the diagnostic performances for PA of mycological culture, Aspergillus real-time PCR, and metagenomic next-generation sequencing (mNGS) assay from bronchoalveolar lavage fluid, were evaluated. In total, 139 patients with suspected fungal pneumonia were enrolled between December 2021 and July 2023, collecting 139 bronchoalveolar lavage fluid samples for real-time PCR and culture, with 87 undergoing mNGS assay. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with 95% CIs of these assays for PA were as follows: 35.3% (14.2%-61.7%), 100.0% (94.0%-100.0%), 100.0% (54.1%-100.0%), 84.5% (79.3%-88.6%), and 0.676 (0.560-0.779), respectively, for culture; 82.4% (56.6%-96.2%), 98.3% (91.1%-100.0%), 93.3% (66.4%-99.0%), 95.2% (87.6%-98.2%), and 0.903 (0.815-0.959), respectively, for same diagnostic performance of real-time PCR and mNGS; and 94.1% (71.3%-99.9%), 96.7% (88.5%-99.6%), 88.9% (67.1%-96.9%), 98.3% (89.6%-99.7%), and 0.954 (0.880-0.989), respectively, for real-time PCR combining mNGS; real-time PCR, mNGS, and their combination significantly improved in area under the curve values over culture (P < 0.001), but real-time PCR testing and mNGS had no significant difference with each other and their combination. Overall, the performance of culture was limited by low sensitivity; both real-time PCR and mNGS assays as single diagnostic tests are promising compared with culture and combined tests.

Mesoporous Vinylene-Linked Covalent Organic Frameworks with Heteroatom-Tuned Crystallinity and Photocatalytic Behaviors.

Owing to its prominent π-delocalization and stability, vinylene linkage holds great merits in the construction of covalent organic frameworks (COFs) with promising semiconducting properties. However, carbon-carbon double bond formation reaction always exhibits relatively low reversibility, unfavorable for the formation of high crystalline frameworks through self-error correction and assembling processes. In this work, we report a heteroatom-tuned strategy to build up a series of two-dimensional (2D) vinylene-linked COFs by Knoevenagel condensation of an electron-deficient methylthiazolyl-based monomer with different triformyl substituted (hetero-)aromatic derivatives. The resulting COFs show high-quality periodic mesoporous structures with high surface areas. Embedding heteroatoms into the backbones enables significantly improving their crystallinity, and finely tailoring their semiconducting structures. Upon visible light stimulation, one of the as-prepared COFs with donor-π-acceptor structure could deliver a nearly seven-fold increase in the catalytic activity of hydrogen generation as compared with the other two. Meanwhile, in combination with high crystallinity and the matched conduction band energy level, such kind of COFs can be able to selectively generate singlet oxygen and superoxide radicals in a high ratio of up to 30:1, allowing for catalyzing aerobic thioanisole oxidation in distinctly tunable activities through the substituent electronic effect of the substrates.

NK Cell Mitochondrial Membrane Potential-Associated Model Predicts Outcomes in Critically Ill Patients with COVID-19.

Purpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19. Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients. Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p<0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94. Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.

AutoDock and molecular dynamics-based therapeutic potential prediction of flavonoids for primary Sjögren's syndrome.

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that leads to reduced saliva production, primarily affecting women due to estrogen deficiency. The estrogen receptor α (ERα) plays a crucial role in mediating the expression of the aquaporin 5 (AQP5) gene through the estrogen response element-dependent signaling pathway, making ERα a key drug target for pSS. Several flavonoids have been reported to have the potential to treat pSS. This study aimed to screen and compare flavonoids binding to ERα using AutoDock, providing a basis for treating pSS with flavonoids. The estrogenic potential of six representative flavonoids was examined in this study. Molecular docking revealed that the binding energy of all six flavonoids to ERα was less than -5.6 kcal/mol. Apigenin, naringenin, and daidzein were the top three flavonoids with even lower binding energies of -7.8, -8.09, and -8.59 kcal/mol, respectively. Similar to the positive control estradiol, apigenin, naringenin, and daidzein showed hydrogen bond interactions with GLU353, GLY521, and HIS524 at the active site. The results of luciferase reporter assays demonstrated that apigenin, naringenin, and daidzein significantly enhanced the transcription of estrogen receptor element (ERE) in the PGL3/AQP5 promoter. Furthermore, molecular dynamics simulations using GROMACS for a time scale of 100 ns revealed relatively stable binding of apigenin-ERα, naringenin-ERα, and daidzein-ERα. Mechanistically, homology modeling indicated that GLU353, GLY521, and HIS524 were the key residues of ERα exerting an estrogenic effect. The therapeutic effect of apigenin on dry mouth in pSS models was further validated. In conclusion, these results indicate the estrogenic and pSS therapeutic potential of apigenin, naringenin, and daidzein.

Disease types and pathogenic mechanisms induced by PM2.5 in five human systems: An analysis using omics and human disease databases.

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

Pyridazine-Promoted Construction of Vinylene-Linked Covalent Organic Frameworks with Exceptional Capability of Stepwise Water Harvesting.

In this study, we successfully developed two novel vinylene-linked covalent organic frameworks (COFs) using 2-connected 3,6-dimethylpyridazine through Knoevenagel condensation. These COFs featured finely tailored micro-/nano-scale pore sizes, high surface areas and stable non-polar vinylene linkages. Finely resolved powder X-ray diffraction patterns demonstrated highly crystalline structures with a hexagonal lattice in the AA layer stacking. The resulting one-dimensional channels possess strong hydrogen-bond accepting sites arising from the decorated cis-azo/azine units with two pairs of fully exposed lone pair electrons, endowing the as-prepared COFs with exceptional water absorption properties. The g-DZPH-COF exhibited successive steep water uptake steps starting from low relative pressures (P/PSTA=0.1), with the remarkable water uptake capacity of 0.26 g/g at P/PSTA=0.2 (25 °C), which is the optimal value recorded among the reported COFs. Dynamic vapour sorption measurements revealed the fast kinetics of these COFs, even in the cluster formation process. Water uptake and release cycling tests demonstrated their outstanding hydrolytic stability, durability, and adsorption-desorption retention ability.

Reactive oxygen species regulation by NCF1 governs ferroptosis susceptibility of Kupffer cells to MASH.

Impaired self-renewal of Kupffer cells (KCs) leads to inflammation in metabolic dysfunction-associated steatohepatitis (MASH). Here, we identify neutrophil cytosolic factor 1 (NCF1) as a critical regulator of iron homeostasis in KCs. NCF1 is upregulated in liver macrophages and dendritic cells in humans with metabolic dysfunction-associated steatotic liver disease and in MASH mice. Macrophage NCF1, but not dendritic cell NCF1, triggers KC iron overload, ferroptosis, and monocyte-derived macrophage infiltration, thus aggravating MASH progression. Mechanistically, elevated oxidized phospholipids induced by macrophage NCF1 promote Toll-like receptor (TLR4)-dependent hepatocyte hepcidin production, leading to increased KC iron deposition and subsequent KC ferroptosis. Importantly, the human low-functional polymorphic variant NCF190H alleviates KC ferroptosis and MASH in mice. In conclusion, macrophage NCF1 impairs iron homeostasis in KCs by oxidizing phospholipids, triggering hepatocyte hepcidin release and KC ferroptosis in MASH, highlighting NCF1 as a therapeutic target for improving KC fate and limiting MASH progression.

Advancements in ovarian cancer immunodiagnostics and therapeutics via phage display technology.

Ovarian cancer, ranking as the seventh most prevalent malignancy among women globally, faces significant challenges in diagnosis and therapeutic intervention. The difficulties in early detection are amplified by the limitations and inefficacies inherent in current screening methodologies, highlighting a pressing need for more efficacious diagnostic and treatment strategies. Phage display technology emerges as a pivotal innovation in this context, utilizing extensive phage-peptide libraries to identify ligands with specificity for cancer cell markers, thus enabling precision-targeted therapeutic strategies. This technology promises a paradigm shift in ovarian cancer management, concentrating on targeted drug delivery systems to improve treatment accuracy and efficacy while minimizing adverse effects. Through a meticulous review, this paper evaluates the revolutionary potential of phage display in enhancing ovarian cancer therapy, representing a significant advancement in combating this challenging disease. Phage display technology is heralded as an essential instrument for developing effective immunodiagnostic and therapeutic approaches in ovarian cancer, facilitating early detection, precision-targeted medication, and the implementation of customized treatment plans.

Semi-invasive wearable clinic: Solution-processed smart microneedle electronics for next-generation integrated diagnosis and treatment.

The integrated smart electronics for real-time monitoring and personalized therapy of disease-related analytes have been gradually gaining tremendous attention. However, human tissue barriers, including the skin barrier and brain-blood barrier, pose significant challenges for effective biomarker detection and drug delivery. Microneedle (MN) electronics present a promising solution to overcome these tissue barriers due to their semi-invasive structures, enabling effective drug delivery and target-analyte detection without compromising the tissue configuration. Furthermore, MNs can be fabricated through solution processing, facilitating large-scale manufacturing. This review provides a comprehensive summary of the recent three-year advancements in smart MNs development, categorized as follows. First, the solution-processed technology for MNs is introduced, with a focus on various printing technologies. Subsequently, smart MNs designed for sensing, drug delivery, and integrated systems combining diagnosis and treatment are separately summarized. Finally, the prospective and promising applications of next-generation MNs within mediated diagnosis and treatment systems are discussed.

[Toxicity of bisphenol S on human normal ovarian epithelial cells mediated by ERß-MAPK signaling pathway].

OBJECTIVE: To investigate the effects of long-term(7 days and 14 days) bisphenol S(BPS) exposure on the ERß-MAPK signaling pathway, hormone secretion phenotype and cell cycle in human normal ovarian epithelial cells IOSE 80 at actual human exposure level. METHODS: Physiologically based pharmacokinetic model combined with BPS levels in the serum of women along the Yangtze River in China was used to determine the dosing concentrations of BPS, and vehicle control and 17 ß-estradiol(E_2) control were used. Complete medium with corresponding concentrations(0, 6.79×10~(-6), 6.79×10~(-4), 6.79×10~(-2), 6.79 µmol/L BPS and 10 nmol/L E_2) was replaced every 2 days. mRNA expressions of estrogen receptor(ERß and GPR30), key genes in MAPK signaling pathway(P38/JNK/ERK signaling pathway) and gonadotropin-releasing hormone-related genes(GnRH-I, GnRH-II and GnRH-R) were measured by qPCR. The ERß-MAPK signaling pathway inhibitors were employed to detect the effect of long-term exposure to BPS on the cell cycle by flow cytometry. Dose-response relationship analysis was performed to calculate the benchmark does lower confidence limits. RESULTS: Compared to the vehicle control, after 7 days exposure to BPS, the ratio of G_2/M phase was significantly increased(P<0.05), and the mRNA expressions of GnRH-I, GnRH-II and GnRH-R were significantly decreased(P<0.05); after 14 days exposure to BPS, the mRNA expressions of ESR2, MAPK3, and MAPK9 were significantly increased(P<0.05), and the mRNA expressions of GnRH-II and GnRH-R were significantly decreased(P<0.05). The GnRH-II mRNA expression level of BPS treatment for 7 days; the G_0/G_1 phase ratio, MAPK3 and MAPK8 mRNA expression level of BPS exposure for 14 days; and the GnRH-I mRNA expression level after BPS treatment for 7 days and 14 days showed a good dose-response relationship but with poor fit. CONCLUSION: Long-term low-dose exposure to BPS may cause cell cycle arrest by activating the ERß-MAPK signaling pathway, and may lead to changes in the hormone secretion of IOSE 80 cells.

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease.

In the advancement of Inflammatory Bowel Disease (IBD) treatment, existing therapeutic methods exhibit limitations; they do not offer a complete cure for IBD and can trigger adverse side effects. Consequently, the exploration of novel therapies and multifaceted treatment strategies provides patients with a broader range of options. Within the framework of IBD, gut microbiota plays a pivotal role in disease onset through diverse mechanisms. Bacteriophages, as natural microbial regulators, demonstrate remarkable specificity by accurately identifying and eliminating specific pathogens, thus holding therapeutic promise. Although clinical trials have affirmed the safety of phage therapy, its efficacy is prone to external influences during storage and transport, which may affect its infectivity and regulatory roles within the microbiota. Improving the stability and precise dosage control of bacteriophages-ensuring robustness in storage and transport, consistent dosing, and targeted delivery to infection sites-is crucial. This review thoroughly explores the latest developments in IBD treatment and its inherent challenges, focusing on the interaction between the microbiota and bacteriophages. It highlights bacteriophages' potential as microbiome modulators in IBD treatment, offering detailed insights into research on bacteriophage encapsulation and targeted delivery mechanisms. Particular attention is paid to the functionality of various carrier systems, especially regarding their protective properties and ability for colon-specific delivery. This review aims to provide a theoretical foundation for using bacteriophages as microbiome modulators in IBD treatment, paving the way for enhanced regulation of the intestinal microbiota.

MACSPI enables tissue-selective proteomic and interactomic analyses in multicellular organisms.

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells. We applied MACSPI in Caenorhabditis elegans, a model multicellular organism, to selectively label, capture, and profile the proteomes of the body wall muscle and the nervous system, which led to the identification of tissue-specific proteins. Using the photo-cross-linker, we successfully profiled HSP90 interactors in muscles and neurons and identified tissue-specific interactors and stress-related interactors. Our study demonstrates that MACSPI can be used to profile tissue-specific proteomes and interactomes in intact multicellular organisms.

In Vivo Corneal Biomechanical Response to Three Different Laser Corneal Refractive Surgeries.

PURPOSE: To compare the effects of three common refractive surgeries on corneal biomechanics. METHODS: Two hundred seven patients who had refractive surgery were included in this study, of whom 65 received transepithelial photorefractive keratectomy (tPRK), 73 received femtosecond laser-assisted laser in situ keratomileusis (FSLASIK), and 69 received small incision lenticule extraction (SMILE). Each patient had biomechanical measurements using the Corvis ST (Oculus Optikgeräte GmbH) preoperatively and at 3 and 6 months postoperatively. The measurements included five parameters expected to be associated with corneal biomechanics: deformation amplitude ratio at 2 mm (DAR2), integrated inverse radius (IIR), stiffness parameter at first applanation (SP-A1), highest concavity time (HCT), and the updated stress-strain index (SSIv2). The variations in these parameters postoperatively among the three surgeries, and their relationship with corneal thickness (CCT) and intraocular pressure measured by the Dynamic Contour Tonometer (DCT-IOP) were analyzed. RESULTS: SP-A1 decreased significantly from preoperatively to 3 months postoperatively in all three groups, whereas DAR2 and IIR increased significantly, all indicating stiffness losses. Between 3 and 6 months postoperatively, the results were inconsistent, with DAR2 decreasing (indicating stiffness increases) and IIR increasing (denoting stiffness decreases) in the FS-LASIK and SMILE groups. The decrease in SSIv2 (the only measure of corneal material stiffness) postoperatively was comparatively less pronounced at both 3 and 6 months postoperatively. On the other hand, HCT remained generally stable after all three surgeries. Unlike DAR2, IIR, and SP-A1, the changes postoperatively in stiffness parameters HCT and SSIv2 were independent of the corresponding changes in both DCT-IOP and CCT. CONCLUSIONS: Among the stiffness parameters considered, SSIv2 was not correlated with CCT or DCT-IOP, and holds promise for representing the corneal material stiffness and how it remains largely unaffected by refractive surgeries. Overall, FS-LASIK had the most significant impact on corneal stiffness, followed by SMILE, and finally tPRK. [J Refract Surg. 2024;40(5):e344-e352.].

Intelligent Fusion of Multi-Source Senses Information for Identifying the Nature of Five Flavors in Chinese Medicine: A Comprehensive Study of Five Classifications.

Objective: To develop a classification model for the five flavors of Chinese medicine using advanced multi-source intelligent sensory information fusion technology. The primary aim is to investigate the feasibility of applying this model to classify and identify the flavors of various Chinese medicines effectively. Methods: We selected 122 representative Chinese medicines, each exhibiting a single distinct flavor (sour, pungent, salty, sweet, bitter), along with 14 common foods. Utilizing the nature and flavors of these decoction pieces specified in Chinese Pharmacopeia (ChP)2020 and the inherent attributes of food components, we obtained valuable data from various sensors, including the PEN3 electronic nose, ASTREE electronic tongue, and SA402B electronic tongue. We then collected single-source data matrices from these sample sensors and a multi-source data matrix that combined the data from all sensors. Using discriminant analysis (DA), principal component analysis-discriminant analysis (PCA-DA), and K-nearest neighbor algorithm (KNN) three kinds of chemometric methods were used to establish five flavors and five-category discrimination models. The results were comprehensively evaluated with the highest correct rate of the model of leave-one-out cross-validation as the index. Results: Upon leave-one-out cross-validation, the correct judgment rate of the five flavors, five-category two-source fusion DA discrimination model (83.8%; ASTREE + SA402B) was significantly higher than the correct judgment rate of the single-source optimal DA and KNN model (73.5%; ASTREE). Following full-sample modeling, the correct judgment rate of the five flavors, five-category three-source fusion DA discrimination model (94.9%; PEN3+ASTREE+SA402B) rose substantially. This was higher than the correct judgment rate of the single-source optimal DA model (77.9%; ASTREE) and slightly higher than the two-source optimal correct judgment rate (89.7%; PEN3 + ASTREE). Conclusions: Compared to single-source identification, multi-source intelligent senses information fusion (MISIF) significantly improved accuracy, providing a new outlook for identifying flavor in Chinese medicine.

Construction of a physiologically based pharmacokinetic model of paclobutrazol and exposure estimation in the human body.

Paclobutrazol (PBZ) is a plant growth regulator that can delay plant growth and improve plant resistance and yield. Although it has been widely used in the growth of medicinal plants, human beings may take it by taking traditional Chinese medicine. There are no published studies on PBZ exposure in humans or standardized limits for PBZ in medicinal plants. We measured the solubility, oil-water partition coefficient (logP), and pharmacokinetics of PBZ in rats and established a physiologically based pharmacokinetic (PBPK) model of PBZ in rats. This was followed by extrapolation to healthy Chinese adult males as a theoretical foundation for future risk assessment of PBZ. The results showed that PBZ had low solubility and high fat solubility. Pharmacokinetic experiments showed that PBZ was absorbed rapidly but eliminated slowly in rats. On this basis, the rat PBPK model was successfully constructed and extrapolated to healthy Chinese adult males to predict the plasma concentration-time curve and exposure of PBZ in humans. The construction of the PBPK model of PBZ in this study facilitates the determination of the standard formulation limits and risk assessment of PBZ residues in medicinal plants.

A Pilot, Predictive Surveillance Model in Pharmacovigilance Using Machine Learning Approaches.

INTRODUCTION: The identification of a new adverse event (AE) caused by a drug product is one of the key activities in the pharmaceutical industry to ensure the safety profile of a drug product. Machine learning (ML) has the potential to assist with signal detection and supplement traditional pharmacovigilance (PV) surveillance methods. This pilot ML modeling study was designed to detect potential safety signals for two AbbVie products and test the model's capability of detecting safety signals earlier than humans. METHODS: Drug X, a mature product with post-marketing data, and Drug Y, a recently approved drug in another therapeutic area, were selected. Gradient boosting-based ML approaches (e.g., XGBoost) were applied as the main modeling strategy. RESULTS: For Drug X, eight true signals were present in the test set. Among 12 potential new signals generated, four were true signals with a 50.0% sensitivity rate and a 33.3% positive predictive value (PPV) rate. Among the remaining eight potential new signals, one was confirmed as a signal and detected six months earlier than humans. For Drug Y, nine true signals were present in the test set. Among 13 potential new signals generated, five were true signals with a 55.6% sensitivity rate and a 38.5% PPV rate. Among the remaining eight potential new signals, none were confirmed as true signals upon human review. CONCLUSION: This model demonstrated acceptable accuracy for safety signal detection and potential for earlier detection when compared to humans. Expert judgment, flexibility, and critical thinking are essential human skills required for the final, accurate assessment of adverse event cases.

Fair evaluation of federated learning algorithms for automated breast density classification: The results of the 2022 ACR-NCI-NVIDIA federated learning challenge.

The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical Schools' Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.

Intraoperative Intraocular Lens Waste: Incidence, Cost and Reasons.

PURPOSE: To evaluate the incidence and cost of intraocular lens(IOL) waste during IOL implantation, as well as the reasons for it. METHODS: A retrospective analysis was conducted on the data of 485 patients from the IOL waste registers of a single tertiary eye hospital in China during 2016-2020. The primary outcomes were the incidence, cost, and reasons for different IOL properties. Cases were examined to ascertain IOL material, design, procedural details, and causes of waste. RESULTS: IOL waste occurred in 485 (6.62‰) of the 73,246 IOL implantations during the study period. The total cost of IOL waste was 429, 850.26 Chinese Yuan (CNY) related to waste with an average cost of 2, 442.33 CNY per procedure during the study period. Comparisons between IOL properties showed that polymethyl methacrylate (PMMA) material (39, 2.05%), three-piece design (142, 1.49%), and secondary IOL implantation (26, 2.16%) were associated with IOL wastage, and the difference was statistically significant. The causes of IOL waste were damage (107, 60.80%), patient reasons (37, 21.26%), aseptic errors (22, 12.50%), IOL quality problems (8, 4.55%), and loss (2, 1.14%). CONCLUSIONS: The incidence of IOL waste is low, but still leads to a significant cost burden due to a large number of cataract surgeries. PMMA material, three-piece design, and secondary implantation were identified as factors increasing IOL waste. Damage emerged as the primary reason for waste, largely attributed to human error. Therefore, the development of strategies to mitigate IOL waste is imperative.

Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy.

BACKGROUND: The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state. METHODS: CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023. DISCUSSION: The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases. TRIAL REGISTRATION: The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.