Thermal hydrolysis alleviates polyethylene microplastic-induced stress in anaerobic digestion of waste activated sludge.

Microplastics are known to negatively affect anaerobic digestion (AD) of waste activated sludge. However, whether thermal hydrolysis (TH) pretreatment alters the impact of microplastics on sludge AD remains unknown. Herein, the effect of TH on the impact of polyethylene (PE) microplastics in sludge AD was investigated. The results showed that the inhibition of methane production by PE at 100 particles/g total solids (TS) was reduced by 31.4% from 12.1% to 8.3% after TH at 170 °C for 30 min. Mechanism analysis indicated TH reduced the potential for reactive oxygen species production induced by PE, resulting in a 29.1 ± 5.5% reduction in cell viability loss. In addition, additive leaching increased as a result of rapid aging of PE microplastics by TH. Acetyl tri-n-butyl citrate (ATBC) release from PE with 10 and 100 particles/g TS increased 11.5-fold and 8.6-fold after TH to 68.2 ± 5.5 µg/L and 124.0 ± 5.1 µg/L, respectively. ATBC at 124.0 µg/L increased methane production by 21.4%. The released ATBC enriched SBR1031 and Euryarchaeota, which facilitate the degradation of proteins and promote methane production. This study reveals the overestimated impact of PE microplastics in sludge AD and provides new insights into the PE microplastics-induced impact in practical sludge treatment and anaerobic biological processes.

TRAF6 enhances PD-L1 expression through YAP1-TFCP2 signaling in melanoma.

Immunotherapy represented by programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies has led tumor treatment into a new era. However, the low overall response rate and high incidence of drug resistance largely damage the clinical benefits of existing immune checkpoint therapies. Recent studies correlate the response to PD-1/PD-L1 blockade with PD-L1 expression levels in tumor cells. Hence, identifying molecular targets and pathways controlling PD-L1 protein expression and stability in tumor cells is a major priority. In this study, we performed a Stress and Proteostasis CRISPR interference screening to identify PD-L1 positive modulators. Here, we identified TRAF6 as a critical regulator of PD-L1 in melanoma cells. As a non-conventional E3 ubiquitin ligase, TRAF6 is inclined to catalyze the synthesis and linkage of lysine-63 (K63) ubiquitin which is related to the stabilization of substrate proteins. Our results showed that suppression of TRAF6 expression down-regulates PD-L1 expression on the membrane surface of melanoma cells. We then used in vitro and in vivo assays to investigate the biological function and mechanism of TRAF6 and its downstream YAP1/TFCP2 signaling in melanoma. TRAF6 stabilizes YAP1 by K63 poly-ubiquitination modification, subsequently promoting the formation of YAP1/TFCP2 transcriptional complex and PD-L1 transcription. Inhibition of TRAF6 by Bortezomib enhanced cytolytic activity of CD8+ T cells by reduction of endogenous PD-L1. Notably, Bortezomib enhances anti-tumor immunity to an extent comparable to anti-PD-1 therapies with no obvious toxicity. Our findings reveal the potential of inhibiting TRAF6 to stimulate internal anti-tumor immunological effect for TRAF6-PD-L1 overexpressing cancers.

Epidemiology of acute hepatitis C and hepatitis C virus-related cirrhosis in reproductive-age women, 1990-2019: An analysis of the Global Burden of Disease study.

Background: The current study uniquely focuses on the global incidence and temporal trends of acute hepatitis C (AHC) and hepatitis C virus (HCV)-related cirrhosis among women of reproductive age (15-49 years) from 1990-2019. The risk of vertical transmission and adverse perinatal outcomes associated with HCV infection underscores the importance of prioritising these women in HCV prevention efforts. Methods: Leveraging the Global Burden of Disease 2019 data, we calculated age-standardised incidence rates (ASIR) and assessed temporal trends via the average annual percent change from joinpoint regression. The age-period-cohort model was employed to understand further the effects of age, period, and birth cohort. Results: Over the 30 years, global incidences of AHC and HCV-related cirrhosis in reproductive-age women increased by 46.45 and 72.74%, respectively. The ASIR of AHC was highest in low sociodemographic index regions but showed a declining trend. Conversely, the ASIR of HCV-related cirrhosis displayed unfavourable trends in low, low-middle, and high sociodemographic index regions. Special attention is necessary for sub-Saharan Africa, high-income North America, Eastern Europe, and Central Asia due to their high incidence rates or increasing trends of AHC and HCV-related cirrhosis. Notably, the age-period-cohort model suggests a recent resurgence in AHC and HCV-related cirrhosis risk. Conclusions: The current study is the first to thoroughly evaluate the trends of AHC and HCV-related cirrhosis among reproductive-age women, shedding light on previously unexplored aspects of HCV epidemiology. Our findings identify critical areas where health care systems must adapt to the changing dynamics of HCV infection. The detailed stratification by region and nation further enables the development of localised prevention and treatment strategies.

Ambient fine particulate matter is associated with daily outpatient visits for ankylosing spondylitis: A time-series analysis in Beijing, China.

Exposure to ambient fine particulate matter (PM2.5) has a great impact on human body's immune system, but the correlation between PM2.5 and ankylosing spondylitis has not yet been clarified. We extracted 58,600 outpatient visits for ankylosing spondylitis from the Beijing Medical Claim Data for Employees database from 2010 to 2017. The percentage of outpatient visits following PM2.5 concentrations was estimated using generalized additive models with Poisson connections. Increase by 10 µ g/m3, PM2.5 is associated with daily outpatient visits for ankylosing spondylitis. In this test, the average concentration of PM2.5 was 86.8 ± 74.3 µ g/m3. For every 10 µg/m3 increase in PM2.5 concentration, there was a 0.34% (95% CI, 0.26-0.42%) increase in the risk of patients who visited the doctor on the same day. Females and younger patients were most susceptible to the impact of PM2.5 exposure (P＜0.05). This study revealed the relationship between exposure to PM2.5 and ankylosing spondylitis, and future research can further confirm this finding and explore the potential mechanisms.

Concurrent brain structural and functional alterations in the thalamus of adult survivors of childhood brain tumors: a multimodal MRI study.

Adult survivors of childhood brain tumors often present with cognitive deficits that affect their quality of life. Studying brain structure and function in brain tumor survivors can help understand the underlying mechanisms of their cognitive deficits to improve long-term prognosis of these patients. This study analyzed voxel-based morphometry (VBM) derived from T1-weighted MRI and the amplitude of low-frequency fluctuation (ALFF) from resting-state functional magnetic resonance imaging (rs-fMRI) to examine the structural and functional alterations in 35 brain tumor survivors using 35 matching healthy individuals as controls. Compared with healthy controls, brain tumor survivors had decreased gray matter volumes (GMV) in the thalamus and increased GMV in the superior frontal gyrus. Functionally, brain tumor survivors had lower ALFF values in the inferior temporal gyrus and medial prefrontal area and higher ALFF values in the thalamus. Importantly, we found concurrent but negatively correlated structural and functional alterations in the thalamus based on observed significant differences in GMV and ALFF values. These findings on concurrent brain structural and functional alterations provide new insights towards a better understanding of the cognitive deficits in brain tumor survivors.

Dynamic Molecular Interphases Regulated by Trace Dual Electrolyte Additives for Ultralong-Lifespan and Dendrite-Free Zinc Metal Anode.

Metallic zinc is a promising anode material for rechargeable aqueous multivalent metal-ion batteries due to its high capacity and low cost. However, the practical use is always beset by severe dendrite growth and parasitic side reactions occurring at anode/electrolyte interface. Here we demonstrate dynamic molecular interphases caused by trace dual electrolyte additives of D-mannose and sodium lignosulfonate for ultralong-lifespan and dendrite-free zinc anode. Triggered by plating and stripping electric fields, the D-mannose and lignosulfonate species are alternately and reversibly (de-)adsorbed on Zn metal, respectively, to accelerate Zn2+ transportation for uniform Zn nucleation and deposition and inhibit side reactions for high Coulombic efficiency. As a result, Zn anode in such dual-additive electrolyte exhibits highly reversible and dendrite-free Zn stripping/plating behaviors for >6400 hours at 1 mA cm-2, which enables long-term cycling stability of Zn||ZnxMnO2 full cell for more than 2000 cycles.

Transcriptome Analysis of miRNA and mRNA in Porcine Skeletal Muscle following Glaesserella parasuis Challenge.

Glaesserella parasuis (G. parasuis) causes systemic infection in pigs, but its effects on skeletal muscle and underlying mechanisms are poorly understood. We investigated G. parasuis infection in colostrum-deprived piglets, observing decreased daily weight gain and upregulation of inflammatory factors in skeletal muscle. Muscle fiber area and diameter were significantly reduced in the treated group (n = 3) compared to the control group (n = 3), accompanied by increased expression of FOXO1, FBXO32, TRIM63, CTSL, and BNIP3. Based on mRNA and microRNA (miRNA) sequencing, we identified 1642 differentially expressed (DE) mRNAs and 19 known DE miRNAs in skeletal muscle tissues between the two groups. We predicted target genes with opposite expression patterns to the 19 miRNAs and found significant enrichment and activation of the FoxO signaling pathway. We found that the upregulated core effectors FOXO1 and FOXO4 were targeted by downregulated ssc-miR-486, ssc-miR-370, ssc-miR-615, and ssc-miR-224. Further investigation showed that their downstream upregulated genes involved in protein degradation were also targeted by the downregulated ssc-miR-370, ssc-miR-615, ssc-miR-194a-5p, and ssc-miR-194b-5p. These findings suggest that G. parasuis infection causes skeletal muscle atrophy in piglets through accelerated protein degradation mediated by the "miRNAs-FOXO1/4" axis, while further research is necessary to validate the regulatory relationships. Our results provide new insights into the understanding of systemic inflammation growth mechanisms caused by G. parasuis and the role of miRNAs in bacterial infection pathogenesis.

Pregnancy-Specific Beta-1-Glycoprotein 1 Increases HTR-8/SVneo Cell Migration through the Orai1/Akt Signaling Pathway.

The impaired invasion ability of trophoblast cells is related to the occurrence of preeclampsia (PE). We previously found that pregnancy-specific beta-1-glycoprotein 1 (PSG1) levels were decreased in the serum of individuals with early-onset preeclampsia (EOPE). This study investigated the effect of PSG1 on Orai1-mediated store-operated calcium entry (SOCE) and the Akt signaling pathway in human trophoblast cell migration. An enzyme-linked immunosorbent assay (ELISA) was used to determine the level of PSG1 in the serum of pregnant women with EOPE. The effects of PSG1 on trophoblast proliferation and migration were examined using cell counting kit-8 (CCK8) and wound healing experiments, respectively. The expression levels of Orai1, Akt, and phosphorylated Akt (p-Akt) were determined through Western blotting. The results confirmed that the serum PSG1 levels were lower in EOPE women than in healthy pregnant women. The PSG1 treatment upregulated the protein expression of Orai1 and p-Akt. The selective inhibitor of Orai1 (MRS1845) weakened the migration-promoting effect mediated by PSG1 via suppressing the Akt signaling pathway. Our findings revealed one of the mechanisms possibly involved in EOPE pathophysiology, which was that downregulated PSG1 may reduce the Orai1/Akt signaling pathway, thereby inhibiting trophoblast migration. PSG1 may serve as a potential target for the treatment and diagnosis of EOPE.

A Prediction Model of Preeclampsia in Hyperglycemia Pregnancy.

Purpose: To investigate the risk factors associated with preeclampsia in hyperglycemic pregnancies and develop a predictive model based on routine pregnancy care. Patients and Methods: The retrospective collection of clinical data was performed on 951 pregnant women with hyperglycemia, including those diagnosed with diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM), who delivered after 34 weeks of gestation at the Maternal and Child Health Hospital Affiliated to Anhui Medical University between January 2017 and December 2019. Observation indicators included liver and kidney function factors testing at 24-29+6 weeks gestation, maternal age, and basal blood pressure. The indicators were screened univariately, and the "rms" package in R language was applied to explore the factors associated with PE in HIP pregnancy by stepwise regression. Multivariable logistic regression analysis was used to develop the prediction model. Based on the above results, a nomogram was constructed to predict the risk of PE occurrence in pregnant women with HIP. Then, the model was evaluated from three aspects: discrimination, calibration, and clinical utility. The internal validation was performed using the bootstrap procedure. Results: Multivariate logistic regression analysis showed that cystatin C, uric acid, glutamyl aminotransferase, blood urea nitrogen, and basal systolic blood pressure as predictors of PE in pregnancy with HIP. The predictive model yielded an area under curve (AUC) value of 0.8031 (95% CI: 0.7383-0.8679), with an optimal threshold of 0.0805, at which point the sensitivity was 0.8307 and specificity of 0.6604. Hosmer-Lemeshow test values were P = 0.3736, Brier score value was 0.0461. After 1000 Bootstrap re-samplings for internal validation, the AUC was 0.7886, the Brier score was 0.0478 and the predicted probability of the calibration curve was similar to the actual probability. A nomogram was constructed based on the above to visualize the model. Conclusion: This study developed a model for predicting PE in pregnant women with HIP, achieving high predictive performance of PE risk through the information of routine pregnancy care.

Understanding the consumer-citizen gap in Chinese public attitudes toward farm animal welfare.

Individuals of the general public can perform both consumer and citizen roles in farm animal welfare, and attitudes toward farm animal welfare may differ between these roles. However, scant research is available regarding this distinction, especially in developing countries such as China. The present study aimed to explore consumer-citizen gaps in Chinese public attitudes toward farm animal welfare across three dimensions and across demographic characteristics. A 36-item scale was designed, and completed by 5284 Chinese participants in a large-scale cross-sectional survey. Consumer-citizen gaps in attitudes toward farm animal welfare across three dimensions and demographic characteristics were analyzed using the Wilcoxon signed-rank test, and effects of demographic characteristics on attitudes were further explored by linear regression analysis. A significant consumer-citizen gap was found in overall attitudes, although the consumer role was only slightly more positive than the citizen role. The consumer-citizen gap is driven by differences in both cognitive attitudes and behavioral attitudes. The gap is most pronounced in cognitive attitudes, where the consumer role is significantly more positive, and smaller in behavioral attitudes, where the citizen role is significantly more positive. The consumer-citizen gap varies significantly among different demographic groups, including gender, age, education, monthly household income, area of residence, and occupation. Additionally, education, monthly household income, and area of residence have significant effects on attitudes in the dual role, whereas gender only affect consumer-role attitudes significantly. The findings provide evidence that consumer-citizen gaps in Chinese public attitudes toward farm animal welfare exist, and this distinction is mainly determined by demographic characteristics.

Efficacy observation, complications and nursing of enteral nutrition suspension in patients with acute ischemic stroke.

OBJECTIVE: This study focuses on exploring the efficacy observation, complications and nursing aspects of using enteral nutrition suspension in patients with acute ischemic stroke. METHODS: This study retrospectively analyzed clinical data from 188 patients with acute ischemic stroke treated in the Neurology Department of our hospital from October 2022 to September 2023. Patients who received intermittent enteral nutrition and nursing interventions were included in the control group (n=96), while patients who received continuous enteral nutrition and nursing interventions were included in the treatment group (n=92). Relevant indicators data changes before and after treatment were recorded for each patient, along with the occurrence of complications in both groups, and statistical analysis was conducted. RESULTS: The treatment group had fewer days in the ICU and total hospitalization days compared to the control group, with p < .05. Patients in the treatment group had higher levels of serum albumin and serum prealbumin than those in the control group, with p < .05. The occurrence of abdominal pain, diarrhea, constipation, bloating and acid reflux in the treatment group was lower than in the control group, with p < .05. There was no significant difference in the occurrence of adverse outcomes at discharge, death at discharge, cerebral hemorrhage, lung infection and gastrointestinal bleeding between the two groups (p > .05). CONCLUSION: The application of enteral nutrition suspension in patients with acute ischemic stroke effectively provides the necessary nutrients, maintains nutritional balance, promotes tissue repair and recovery and reduces the length of hospital stay.

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

LD-UNet: A long-distance perceptual model for segmentation of blurred boundaries in medical images.

The blurriness of boundaries in medical image target regions hinders further improvement in automatic segmentation accuracy and is a challenging problem. To address this issue, we propose a model called long-distance perceptual UNet (LD-UNet), which has a powerful long-|distance perception ability and can effectively perceive the semantic context of an entire image. Specifically, LD-UNet utilizes global and local long-distance induction modules, which endow the model with contextual semantic induction capabilities for long-distance feature dependencies. The modules perform long-distance semantic perception at the high and low stages of LD-UNet, respectively, effectively improving the accuracy of local blurred information assessment. We also propose a top-down deep supervision method to enhance the ability of the model to fit data. Then, extensive experiments on four types of tumor data with blurred boundaries are conducted. The dataset includes nasopharyngeal carcinoma, esophageal carcinoma, pancreatic carcinoma, and colorectal carcinoma. The dice similarity coefficient scores obtained by LD-UNet on the four datasets are 73.35%, 85.93%, 70.04%, and 82.71%. Experimental results demonstrate that LD-UNet is more effective in improving the segmentation accuracy of blurred boundary regions than other methods with long-distance perception, such as transformers. Among all models, LD-UNet achieves the best performance. By visualizing the feature dependency field of the models, we further explore the advantages of LD-UNet in segmenting blurred boundaries.

Aminoguanidine alleviates gout in goslings experimentally infected with goose astrovirus-2 by reducing kidney lesions.

Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no commercial veterinary products are available to prevent and treat the disease. Our previous studies showed that nitric oxide (NO) and inducible NO synthase (iNOS) were markedly higher in the kidney and spleen of goslings infected with GAstV-2, but their effects during GAstV-2 infection remain unclear. In the present study, goslings were intraperitoneally injected with aminoguanidine (AG)-an iNOS inhibitor-to examine the role of NO during GAstV-2 infection. AG significantly decreased the serum NO concentration and iNOS mRNA expression in the kidney. Moreover, AG reduced the mortality, serum uric acid and creatinine content, and urate deposition in visceral organs and joints. Histopathological analysis demonstrated that AG reduced renal tubular cell necrosis, inflammatory cell infiltration, glycogen deposition in glomerular mesangium, and interstitial fibrosis, suggesting alleviation of kidney lesions. Furthermore, AG decreased the expression of renal injury markers such as KIM-1 and desmin; inflammatory cytokine-related genes such as IL-1ß, IL-8, and MMP-9; and autophagy-related genes and proteins such as LC3II, ATG5, and Beclin1. However, quantitative real-time PCR and immunohistochemistry showed that treatment with AG did not affect the kidney and liver viral load. These findings suggest that AG decreases the mortality rate and kidney lesions in goslings infected with GAstV-2 through mechanisms associated with autophagy and inhibition of inflammatory cytokine production in the kidney but not with GAstV-2 replication.

Transcriptomic analysis of bovine endometrial epithelial cells in response to interferon tau and hormone stimulation.

The embryonic loss during early stage of gestation is one of the major causes of infertility for domestic ruminants, causing huge economic losses to pasture. Maternal recognition of pregnancy and implantation are the crucial process for determining the successful establishment and development of pregnancy in cattle. The research on molecular mechanisms of pregnancy recognition will facilitate illustrating the complex process of pregnancy establishment and help to improve pregnancy outcomes. In this study, we performed transcriptomic analysis of primary bovine endometrial epithelial cells (BEND) with or without IFNT and hormones intervention through RNA sequencing. We eventually identified 608 differentially expressed genes (DEGs) including 409 up-regulated genes and 199 down-regulated genes in IFNT and hormones-treated group compared with control group. Gene Ontology (GO) enrichment analysis demonstrated that the majority of DEGs were implicated in immune system process, response to external stimulus, response to cytokine, regulation of response to stress. Results from KEGG analysis showed a significant enrichment of NOD-like receptor signaling pathway, antigen processing and presentation, necroptosis, oxidative phosphorylation, RIG-I-like receptor signaling pathway. Additionally, a set of promising candidate genes, including (USP18, STAT1, PSMB8, IFIH1, MX2, IFI44, DHX58, CASP8, DRAM1, CXCR4), were characterized by constructing an integrated interaction network. Specifically, the mRNA expression of HOXA11, PTGS1 and PTGS2 were remarkably suppressed by silencing DRAM1 under IFNT and hormone administration, thus speculating that DRAM1 might play a crucial role in early pregnancy by regulating endometrial function. The results of this study depicted a relatively comprehensive transcriptional profiles of BEND in response to IFNT and hormones, which contributes to a better understanding of gene interaction network and underlying regulatory mechanisms in endometrium of ruminants during early pregnancy.

Leveraging baseline transcriptional features and information from single-cell data to power the prediction of influenza vaccine response.

Introduction: Vaccination is still the primary means for preventing influenza virus infection, but the protective effects vary greatly among individuals. Identifying individuals at risk of low response to influenza vaccination is important. This study aimed to explore improved strategies for constructing predictive models of influenza vaccine response using gene expression data. Methods: We first used gene expression and immune response data from the Immune Signatures Data Resource (IS2) to define influenza vaccine response-related transcriptional expression and alteration features at different time points across vaccination via differential expression analysis. Then, we mapped these features to single-cell resolution using additional published single-cell data to investigate the possible mechanism. Finally, we explored the potential of these identified transcriptional features in predicting influenza vaccine response. We used several modeling strategies and also attempted to leverage the information from single-cell RNA sequencing (scRNA-seq) data to optimize the predictive models. Results: The results showed that models based on genes showing differential expression (DEGs) or fold change (DFGs) at day 7 post-vaccination performed the best in internal validation, while models based on DFGs had a better performance in external validation than those based on DEGs. In addition, incorporating baseline predictors could improve the performance of models based on days 1-3, while the model based on the expression profile of plasma cells deconvoluted from the model that used DEGs at day 7 as predictors showed an improved performance in external validation. Conclusion: Our study emphasizes the value of using combination modeling strategy and leveraging information from single-cell levels in constructing influenza vaccine response predictive models.

TdDS-UNet: top-down deeply supervised U-Net for the delineation of 3D colorectal cancer.

Automatically delineating colorectal cancers with fuzzy boundaries from 3D images is a challenging task, but the problem of fuzzy boundary delineation in existing deep learning-based methods have not been investigated in depth. Here, an encoder-decoder-based U-shaped network (U-Net) based on top-down deep supervision (TdDS) was designed to accurately and automatically delineate the fuzzy boundaries of colorectal cancer. TdDS refines the semantic targets of the upper and lower stages by mapping ground truths that are more consistent with the stage properties than upsampling deep supervision. This stage-specific approach can guide the model to learn a coarse-to-fine delineation process and improve the delineation accuracy of fuzzy boundaries by gradually shrinking the boundaries. Experimental results showed that TdDS is more customizable and plays a role similar to the attentional mechanism, and it can further improve the capability of the model to delineate colorectal cancer contours. A total of 103, 12, and 29 3D pelvic magnetic resonance imaging volumes were used for training, validation, and testing, respectively. The comparative results indicate that the proposed method exhibits the best comprehensive performance, with a dice similarity coefficient (DSC) of 0.805 ± 0.053 and a hausdorff distance (HD) of 9.28 ± 5.14 voxels. In the delineation performance analysis section also showed that 44.49% of the delineation results are satisfactory and do not require revisions. This study can provide new technical support for the delineation of 3D colorectal cancer. Our method is open source, and the code is available athttps://github.com/odindis/TdDS/tree/main.

Clinical prediction models for knee pain in patients with knee osteoarthritis: a systematic review.

OBJECTIVE: To identify and describe existing models for predicting knee pain in patients with knee osteoarthritis. METHODS: The electronic databases PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library were searched from their inception to May 2023 for any studies to develop and validate a prediction model for predicting knee pain in patients with knee osteoarthritis. Two reviewers independently screened titles, abstracts, and full-text qualifications, and extracted data. Risk of bias was assessed using the PROBAST. Data extraction of eligible articles was extracted by a data extraction form based on CHARMS. The quality of evidence was graded according to GRADE. The results were summarized with descriptive statistics. RESULTS: The search identified 2693 records. Sixteen articles reporting on 26 prediction models were included targeting occurrence (n = 9), others (n = 7), progression (n = 5), persistent (n = 2), incident (n = 1), frequent (n = 1), and flares (n = 1) of knee pain. Most of the studies (94%) were at high risk of bias. Model discrimination was assessed by the AUROC ranging from 0.62 to 0.81. The most common predictors were age, BMI, gender, baseline pain, and joint space width. Only frequent knee pain had a moderate quality of evidence; all other types of knee pain had a low quality of evidence. CONCLUSION: There are many prediction models for knee pain in patients with knee osteoarthritis that do show promise. However, the clinical extensibility, applicability, and interpretability of predictive tools should be considered during model development.

Single cell multi-omics of fibrotic kidney reveal epigenetic regulation of antioxidation and apoptosis within proximal tubule.

BACKGROUND: Until now, there has been no particularly effective treatment for chronic kidney disease (CKD). Fibrosis is a common pathological change that exist in CKD. METHODS: To better understand the transcriptional dynamics in fibrotic kidney, we make use of single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-cell RNA sequencing (scRNA-seq) from GEO datasets and perform scRNA-seq of human biopsy to seek possible transcription factors (TFs) regulating target genes in the progress of kidney fibrosis across mouse and human kidneys. RESULTS: Our analysis has displayed chromatin accessibility, gene expression pattern and cell-cell communications at single-cell level in kidneys suffering from unilateral ureteral obstruction (UUO) or chronic interstitial nephritis (CIN). Using multimodal data, there exists epigenetic regulation producing less Sod1 and Sod2 mRNA within the proximal tubule which is hard to withstand oxidative stress during fibrosis. Meanwhile, a transcription factor Nfix promoting the apoptosis-related gene Ifi27 expression found by multimodal data was validated by an in vitro study. And the gene Ifi27 upregulated by in situ AAV injection within the kidney cortex aggravates kidney fibrosis. CONCLUSIONS: In conclusion, as we know oxidation and apoptosis are traumatic factors during fibrosis, thus enhancing antioxidation and inhibiting the Nfix-Ifi27 pathway to inhibit apoptosis could be a potential treatment for kidney fibrosis.

A Machine Learning Approach with Human-AI Collaboration for Automated Classification of Patient Safety Event Reports: Algorithm Development and Validation Study.

BACKGROUND: Adverse events refer to incidents with potential or actual harm to patients in hospitals. These events are typically documented through patient safety event (PSE) reports, which consist of detailed narratives providing contextual information on the occurrences. Accurate classification of PSE reports is crucial for patient safety monitoring. However, this process faces challenges due to inconsistencies in classifications and the sheer volume of reports. Recent advancements in text representation, particularly contextual text representation derived from transformer-based language models, offer a promising solution for more precise PSE report classification. Integrating the machine learning (ML) classifier necessitates a balance between human expertise and artificial intelligence (AI). Central to this integration is the concept of explainability, which is crucial for building trust and ensuring effective human-AI collaboration. OBJECTIVE: This study aims to investigate the efficacy of ML classifiers trained using contextual text representation in automatically classifying PSE reports. Furthermore, the study presents an interface that integrates the ML classifier with the explainability technique to facilitate human-AI collaboration for PSE report classification. METHODS: This study used a data set of 861 PSE reports from a large academic hospital's maternity units in the Southeastern United States. Various ML classifiers were trained with both static and contextual text representations of PSE reports. The trained ML classifiers were evaluated with multiclass classification metrics and the confusion matrix. The local interpretable model-agnostic explanations (LIME) technique was used to provide the rationale for the ML classifier's predictions. An interface that integrates the ML classifier with the LIME technique was designed for incident reporting systems. RESULTS: The top-performing classifier using contextual representation was able to obtain an accuracy of 75.4% (95/126) compared to an accuracy of 66.7% (84/126) by the top-performing classifier trained using static text representation. A PSE reporting interface has been designed to facilitate human-AI collaboration in PSE report classification. In this design, the ML classifier recommends the top 2 most probable event types, along with the explanations for the prediction, enabling PSE reporters and patient safety analysts to choose the most suitable one. The LIME technique showed that the classifier occasionally relies on arbitrary words for classification, emphasizing the necessity of human oversight. CONCLUSIONS: This study demonstrates that training ML classifiers with contextual text representations can significantly enhance the accuracy of PSE report classification. The interface designed in this study lays the foundation for human-AI collaboration in the classification of PSE reports. The insights gained from this research enhance the decision-making process in PSE report classification, enabling hospitals to more efficiently identify potential risks and hazards and enabling patient safety analysts to take timely actions to prevent patient harm.