Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

Pyopneumothorax with bronchopleural fistula due to pulmonary infection caused by Porphyromonas gingivalis in a patient with periodontitis.

Pyopneumothorax with bronchopleural fistula is a rare complication of lung infection. We herein report a case of pyopneumothorax with bronchopleural fistula caused by Porphyromonas gingivalis infection, a common pathogenic pathogen of periodontitis, in a 49-year-old man with periodontitis. The patient was admitted with respiratory failure. Pleural puncture yielded a lot of gas continually and foul-smelling light brown pus, which was found to be caused due to infection with P. gingivalis by the metagenomic next generation sequencing (mNGS) and anaerobic culture.

Hepatocytic ballooning in non-alcoholic steatohepatitis: Dilemmas and future directions.

Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in 'real life' situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.

Novel urinary protein panels for the non-invasive diagnosis of non-alcoholic fatty liver disease and fibrosis stages.

BACKGROUND & AIMS: There is an unmet clinical need for non-invasive tests to diagnose non-alcoholic fatty liver disease (NAFLD) and individual fibrosis stages. We aimed to test whether urine protein panels could be used to identify NAFLD, NAFLD with fibrosis (stage F ≥ 1) and NAFLD with significant fibrosis (stage F ≥ 2). METHODS: We collected urine samples from 100 patients with biopsy-confirmed NAFLD and 40 healthy volunteers, and proteomics and bioinformatics analyses were performed in this derivation cohort. Diagnostic models were developed for detecting NAFLD (UPNAFLD model), NAFLD with fibrosis (UPfibrosis model), or NAFLD with significant fibrosis (UPsignificant fibrosis model). Subsequently, the derivation cohort was divided into training and testing sets to evaluate the efficacy of these diagnostic models. Finally, in a separate independent validation cohort of 100 patients with biopsy-confirmed NAFLD and 45 healthy controls, urinary enzyme-linked immunosorbent assay analyses were undertaken to validate the accuracy of these new diagnostic models. RESULTS: The UPfibrosis model and the UPsignificant fibrosis model showed an AUROC of .863 (95% CI: .725-1.000) and 0.858 (95% CI: .712-1.000) in the training set; and .837 (95% CI: .711-.963) and .916 (95% CI: .825-1.000) in the testing set respectively. The UPNAFLD model showed an excellent diagnostic performance and the area under the receiver operator characteristic curve (AUROC) exceeded .90 in the derivation cohort. In the independent validation cohort, the AUROC for all three of the above diagnostic models exceeded .80. CONCLUSIONS: Our newly developed models constructed from urine protein biomarkers have good accuracy for non-invasively diagnosing liver fibrosis in NAFLD.

Nonmonotonic effect of CuO nanoparticles on medium-chain carboxylates production from waste activated sludge.

The growing applications of CuO nanoparticles (NPs) in industrial and agriculture has increased their concentrations in wastewater and subsequently accumulated in waste activated sludge (WAS), raising concerns about their impact on reutilization of WAS, especially on the medium-chain carboxylates (MCCs) production from anaerobic fermentation of WAS. Here we showed that CuO NPs at 10-50 mg/g-TS can significantly inhibit MCCs production, and reactive oxygen species generation was revealed to be the key factor linked to the phenomena. At lower CuO NPs concentrations (0.5-2.5 mg/g-TS), however, MCCs production was enhanced, with a maximum level of 37% compared to the control. The combination of molecular approaches and metaproteomic analysis revealed that although low dosage CuO NPs (2.5 mg/g-TS) weakly inhibited chain elongation process, they displayed contributive characteristics both in WAS solubilization and transport/metabolism of carbohydrate. These results demonstrated that the complex microbial processes for MCCs production in the anaerobic fermentation of WAS can be affected by CuO NPs in a dosage-dependent manner via regulating microbial protein expression level. Our findings can provide new insights into the influence of CuO NPs on anaerobic fermentation process and shed light on the treatment option for the resource utilization of CuO NPs polluted WAS.

Response mechanisms of anaerobic fermentative sludge to zinc oxide nanoparticles during medium-chain carboxylates production from waste activated sludge.

The conversion of waste activated sludge (WAS) into medium chain carboxylates (MCCs) has attracted much attention, while investigations of the impacts of ZnO nanoparticles (NPs) on this process are sparse. The present study showed that 8 mg/g-TSS of ZnO NPs have little effects on all key steps and the activity of anaerobes, and finally leading to unchanged MCCs production. Although 30 mg/g-TSS of ZnO NPs weakly inhibited the hydrolysis, acidogenesis, and chain elongation process, WAS solubilization was enhanced, thus, the improvement was enough to offset inhibition, also resulting in an insignificant impact on overall MCCs production. However, the improvement with ZnO NPs dosages above 100 mg/g-TSS was not sufficient to offset the biological inhibition, thus inducing negative impact on overall MCCs production. The decline of EPS induced by Zn2+ and generation of excessive reactive oxygen species (ROS) were the main factors responsible for the inhibitory effects of ZnO NPs on lower activity of anaerobes. For chain elongation process, the discriminative Clostridium IV (as MCCs-forming bacteria) with a strong adaptation to ZnO NPs (300 mg/g-TSS) was observed. The present study provided a deep understanding related to the effects of ZnO NPs on the production of MCCs production from WAS and identified a zinc resistance anaerobe, which would be significant for the evaluation of influence and alleviation of inhibition induced by ZnO NPs on the carbon cycle of organic wastes.

Fully connected neural network-based serum surface-enhanced Raman spectroscopy accurately identifies non-alcoholic steatohepatitis.

BACKGROUND/PURPOSE OF THE STUDY: There is a need to find a standardized and low-risk diagnostic tool that can non-invasively detect non-alcoholic steatohepatitis (NASH). Surface enhanced Raman spectroscopy (SERS), which is a technique combining Raman spectroscopy (RS) with nanotechnology, has recently received considerable attention due to its potential for improving medical diagnostics. We aimed to investigate combining SERS and neural network approaches, using a liver biopsy dataset to develop and validate a new diagnostic model for non-invasively identifying NASH. METHODS: Silver nanoparticles as the SERS-active nanostructures were mixed with blood serum to enhance the Raman scattering signals. The spectral data set was used to train the NASH classification model by a neural network primarily consisting of a fully connected residual module. RESULTS: Data on 261 Chinese individuals with biopsy-proven NAFLD were included and a prediction model for NASH was built based on SERS spectra and neural network approaches. The model yielded an AUROC of 0.83 (95% confidence interval [CI] 0.70-0.92) in the validation set, which was better than AUROCs of both serum CK-18-M30 levels (AUROC 0.63, 95% CI 0.48-0.76, p = 0.044) and the HAIR score (AUROC 0.65, 95% CI 0.51-0.77, p = 0.040). Subgroup analyses showed that the model performed well in different patient subgroups. CONCLUSIONS: Fully connected neural network-based serum SERS analysis is a rapid and practical tool for the non-invasive identification of NASH. The online calculator website for the estimated risk of NASH is freely available to healthcare providers and researchers ( http://www.pan-chess.cn/calculator/RAMAN_score ).

A triple-source CT system for micro-scale investigation of geological materials: A simulation study.

A triple-source CT system is proposed for micro-scale testing of geological materials. This study aims at reducing the projection acquisition time by two-thirds compared to a conventional single-source CT system. The proposed system with different positioning errors in the source-to-object distance (SOD) was simulated and tested using the Shepp-Logan phantom model, as well as slices of sand, glass beads, and concrete samples. Furthermore, the imaging quality of a single-source and the triple-source CT system with different dead detector pixels was compared. The results showed that within the maximum allowable positioning error, the pixel differences between the simulated and the original images are close to zero, and the structural similarities are greater than 0.96. In the presence of dead detector pixels, the quality of the simulated images in the triple-source CT system is superior to that of a single-source CT system. The presented triple-source CT system performs well in high-quality image reconstruction.

Arsenic bioaccumulation and biotransformation in aquatic organisms.

Arsenic exists universally in freshwater and marine environments, threatening the survival of aquatic organisms and human health. To elucidate arsenic bioaccumulation and biotransformation processes in aquatic organisms, this review evaluates the dissolved uptake, dietary assimilation, biotransformation, and elimination of arsenic in aquatic organisms and discusses the major factors influencing these processes. Environmental factors such as phosphorus concentration, pH, salinity, and dissolved organic matter influence arsenic absorption from aquatic systems, whereas ingestion rate, gut passage time, and gut environment affect the assimilation of arsenic from foodstuffs. Arsenic bioaccumulation and biotransformation mechanisms differ depending on specific arsenic species and the involved aquatic organism. Although some enzymes engaged in arsenic biotransformation are known, deciphering the complicated synthesis and degradation pathway of arsenobetaine remains a challenge. The elimination of arsenic involves many processes, such as fecal excretion, renal elimination, molting, and reproductive processes. This review facilitates our understanding of the environmental behavior and biological fate of arsenic and contributes to regulation of the environmental risk posed by arsenic pollution.

Delay-Dependent Stability Analysis of Load Frequency Control Systems With Electric Vehicles.

This article investigates the problem of delay-dependent stability for the one-area load frequency control (LFC) system with electric vehicles (EVs). Two closed-loop models of the LFC system with EVs are proposed, including the model based on the model reconstructed technique and the model with uncertain parameters that considers state of charge. By employing the Lyapunov-Krasovskii functional method, two delay-dependent stability criteria are presented for the systems under study such that a more accurate admissible delay upper bound (ADUB) can be obtained. Case studies are finally carried out to disclose the interrelationship between the ADUB, PI controller gains, and other parameters of the EVs.

Harmful algal blooms and their eco-environmental indication.

Harmful algal blooms (HABs) in freshwater lakes and oceans date back to as early as the 19th century, which can cause the death of aquatic and terrestrial organisms. However, it was not until the end of the 20th century that researchers had started to pay attention to the hazards and causes of HABs. In this study, we analyzed 5720 published literatures on HABs studies in the past 30 years. Our review presents the emerging trends in the past 30 years on HABs studies, the environmental and human health risks, prevention and control strategies and future developments. Therefore, this review provides a global perspective of HABs and calls for immediate responses.

Bioremediation of oily sludge by solid complex bacterial agent with a combined two-step process.

In the present research, a bioremediation process was developed using solid complex bacterial agents (SCBA) through a combined two-step biodegradation process. Four isolated strains showed high efficiency for the degradation of total petroleum hydrocarbons (TPH) and the reduction of COD of the oily sludge, at 96.6% and 92.6%, respectively. The mixed strains together with bran prepared in form of SCBA exhibited improved performance compared to individual strains, all of which had an optimal temperature of around 35 °C. The use of SCBA provided advantages over commonly used liquid media for storage and transportation. The two-step process, consisting of firstly biosurfactant-assisted oil recovery and secondly biodegradation of the remaining TPH with SCBA, demonstrated the capability for treating oily sludge with high TPH content (>10 wt%) and short process period (60 days). The large-scale (5 tons oily sludge) field test, achieving a TPH removal efficiency of 93.8% and COD reduction of 91.5%, respectively, confirmed the feasibility and superiority of the technology for industrial applications.

Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin.

INTRODUCTION: Mannose, a major monosaccharide component of N-glycans, involves in the glycometabolism of human body. Recently, mannose has been shown to suppress tumor growth through enhancing chemosensitivity and reducing the activity of mannose phosphate isomerase (MPI). However, it is largely unknown whether mannose exerts effects on non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: First, a mannose IC50 assay was conducted to find a suitable concentration of mannose for cell experiments. Then, vitro studies including CCK-8 assay, scratch wound healing assay, and TUNEL assay were performed to evaluate the effects of mannose on A549 cells, and an animal model was established to evaluate the antitumoural effect of mannose on NSCLC in vivo. Finally, immunohistochemistry was done to detect the expression of MPI by Rabbit Anti-MPI. RESULTS: In this study, a concentration of mannose, 15mM, was used to explore the suppressive effect of mannose on A549 cells. CCK-8 assay demonstrated that mannose significantly inhibited the proliferation of A549 cells and enhanced the anti-tumor efficacy of carboplatin. Wound healing assay showed that mannose inhibits the migration of A549 cells, and mannose-induced migration inhibition was more efficient in A549 cells treated with carboplatin. TUNEL assay demonstrated that mannose significantly enhanced the efficacy of carboplatin to promote apoptosis treated by mannose (15mM) or carboplatin. The results of animal experiments revealed that the size and weight of tumors derived from A549 cells treated with mannose were smaller than those derived from control cells, and co-treatment with mannose and carboplatin had most efficient inhibition on tumor growth. MPI expression detection showed that the expression level of MPI in the stage Tis (tumor in situ) was the highest, while the stage IV has the lowest. DISCUSSION: Collectively, our findings suggest that mannose inhibited cell proliferation and migration, promoted cell apoptosis and enhanced the efficacy of carboplatin in lung adenocarcinoma. Preliminary results showed that mannose had less side effect on health. In the future, mannose may be a potential candidate drug for adjuvant therapy of lung adenocarcinoma.

The emerging role of XBP1 in cancer.

X-box binding protein 1 (XBP1) is a unique basic-region leucine zipper (bZIP) transcription factor whose dynamic form is controlled by an alternative splicing response upon disturbance of homeostasis in the endoplasmic reticulum (ER) and activation of the unfolded protein response (UPR). XBP1 was first distinguished as a key regulator of major histocompatibility complex (MHC) class II gene expression in B cells. XBP1 communicates with the foremost conserved signalling component of the UPR and is essential for cell fate determination in response to ER stress (ERS). Here, we review recent advances in our understanding of this multifaceted translation component in cancer. In this review, we briefly discuss the role of XBP1 mediators in the UPR and the transcriptional function of XBP1. In addition, we describe how XBP1 operates as a key factor in tumour progression and metastasis. We mainly review XBP1's expression, function and prognostic value in research on solid tumours. Finally, we discuss multiple approaches, especially those involving XBP1, that overcome the immunosuppressive effect of the UPR in cancer that could potentially be useful as antitumour therapies.

Heat shock protein 90 relieves heat stress damage of myocardial cells by regulating Akt and PKM2 signaling in vivo.

Heat shock protein 90 (Hsp90) is associated with resisting heat­stress injury to the heart, particularly in myocardial mitochondria. However, the mechanism underlying this effect remains unclear. The present study was based on the high expression of Hsp90 during heat stress (HS) and involved inducing higher expression of Hsp90 using aspirin in mouse hearts. Higher Hsp90 levels inhibited HS­induced myocardial damage and apoptosis, and mitochondrial dysfunction, by stimulating Akt (protein kinase B) activation and PKM2 (pyruvate kinase M2) signaling, and subsequently increasing mitochondrial Bcl­2 (B­cell lymphoma 2) levels and its phosphorylation. Functional inhibition of Hsp90 using geldanamycin verified that reducing the association of Hsp90 with Akt and PKM2 caused the functional decline of phosphorylated (p)­Akt and PKM2 that initiate Bcl­2 to move into mitochondria, where it is phosphorylated. Protection by Hsp90 was weakened by blocking Akt activation using Triciribine, which could not be recovered by normal initiation of the PKM2 pathway. Furthermore, increased Hsp70 levels induced by Akt activation in myocardial cells may flow into the blood to resist heat stress. The results provided in vivo mechanistic evidence that in myocardial cells, Hsp90 resists heat stress via separate activation of the Akt­Bcl­2 and PKM2­Bcl­2 signaling pathways, which contribute toward preserving cardiac function and mitochondrial homeostasis.

LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2.

Lung adenocarcinoma (LUAD), a histological subclass of non-small-cell lung cancer, is globally the leading cause of cancer-related deaths. Long noncoding RNAs (lncRNAs) are emerging as cancer regulators. Zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is an oncogene in gastric cancer, but its functions have not been investigated in LUAD. We showed that ZFPM2-AS1 expression is high in LUAD samples based on GEPIA database (http://gepia.cancer-pku.cn/) and validated ZFPM2-AS1 upregulation in LUAD cell lines. Functionally, ZFPM2-AS1 facilitated proliferation, invasion, and epithelial-to-mesenchymal transition of LUAD cells. Thereafter, we found that ZFPM2 was negatively regulated by ZFPM2-AS1, and identified the suppressive effect of ZFPM2 regulation by ZFPM2-AS1 on LUAD progression. Mechanistically, we showed that ZFPM2-AS1 interacted with up-frameshift 1 (UPF1) to regulate mRNA decay of ZFPM2. Rescue assays in vitro and in vivo confirmed that ZFPM2-AS1 regulated LUAD progression and tumor growth through ZFPM2. Taken together, our findings demonstrate a role for the ZFPM2-AS1-UPF1-ZFPM2 axis in LUAD progression, suggesting ZFPM2-AS1 as a new potential target for LUAD treatment.

Advances In Research Of Spreading Through Air Spaces And The Effects On The Prognosis Of Lung Cancer.

The concept of spread through air spaces (STAS) has been described as a new form of invasion in the lung in the 2015 WHO classification of Lung Tumors, namely invasion through alveolar spaces. STAS is a prognostic factor independent of growth pattern and tumor stage, and it is also an independent risk factor for unfavorable prognosis of stage I lung adenocarcinoma (ADC) and stage I lung squamous cell carcinoma (SCC). The pathological characteristics are different between ADC and SCC. STAS is not reported as routine, so setting a unified pathological reading standard, and hunting for STAS as a regular reading process is urgently advocated. We write this review to investigate the research progress of STAS and its effects on the prognosis of lung cancer.

Prognostic role of the advanced lung cancer inflammation index in cancer patients: a meta-analysis.

BACKGROUND: Inflammation plays a critical role in the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is thought to be able to reflect systemic inflammation better than current biomarkers. However, the prognostic significance of the ALI in various types of cancer remains unclear. Our meta-analysis aimed to comprehensively investigate the relationship between the ALI and oncologic outcomes to help physicians better assess the prognosis of cancer patients. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated and pooled from the included studies. Furthermore, a sensitivity analysis was performed to evaluate the reliability of the articles. Finally, Begg's test, Egger's test, and the funnel plot were applied to assess the significance of publication bias. RESULTS: In total, 1736 patients from nine studies were included in our meta-analysis. The median cutoff value for the ALI was 23.2 (range, 15.5-37.66) in the analyzed studies. The meta-analysis showed that there was a statistically significant relationship between a low ALI and worse overall survival (OS) in various types of cancer (HR = 1.70, 95% CI = 1.41-1.99, P < 0.001). Moreover, results from subgroup meta-analysis showed that the ALI had a significant prognostic value in non-small cell lung cancer, small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma (P < 0.05 for all). CONCLUSIONS: These results showed that a low ALI was associated with poor OS in various types of cancer, and the ALI could act as an effective prognostic biomarker in cancer patients.

Clinical features of pulmonary embolism in patients with lung cancer: A meta-analysis.

BACKGROUND: Pulmonary embolism (PE) is correlated with increased mortality among patients with lung cancer (LC). The characteristics of patients with LC presenting with PE have not been fully established, and our meta-analysis aims to comprehensively investigate the clinical characteristics associated with PE in patients with LC to help physicians identify PE earlier in these patients. METHODS: Multiple databases were searched, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Wanfang. Odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were used as effect measures for dichotomous and continuous variables, respectively. Moreover, Egger's test, Begg's test and a sensitivity analysis were performed to assess the publication bias and reliability of the articles. RESULTS: In total, 16 studies were included in our meta-analysis. The results indicated that history of chronic obstructive pulmonary disease (OR = 2.59, 95% CI: 1.09, 6.15; P = 0.03), adenocarcinoma (OR = 2.28, 95% CI: 1.88, 2.77; P < 0.01), advanced tumour stage (TNM III-IV vs. I-II, OR = 2.38, 95% CI: 1.99, 2.86; P < 0.01), history of central venous catheter (OR = 1.95, 95% CI: 1.36, 2.78; P < 0.01), history of chemotherapy (OR = 2.32, 95% CI: 1.80, 2.99, P < 0.01), high levels of D-dimer (WMD = 4.31, 95% CI: 2.53, 6.10; P < 0.01) and carcinoembryonic antigen (WMD = 10.30, 95% CI: 9.95, 10.64; P < 0.01) and a low level of partial pressure of oxygen (WMD = -25.97, 95% CI: -31.31, -20.62; P < 0.01) were clinical features of LC patients with PE compared to those without PE. CONCLUSIONS: These results reveal that LC patients with PE have specific clinical features, including but not limited to several cancer- and treatment-related factors, that may help their early identification.

Circular RNAs in drug resistant tumors.

Chemotherapy is an effective method to treat patients with advanced malignant tumors. However, tumor cells can develop resistance to multiple drugs during the therapy process, leading to treatment failure. Circular RNAs (circRNAs) are a new class of regulatory RNAs that can regulate endogenous gene expression. Previous studies revealed the diagnostic and prognostic value of circRNAs in malignant cancer and other diseases, but few reports have examined their association with clinical drug resistance. In this review, we summarize the up-to-date information regarding the role of circRNAs in the resistance of tumors to chemotherapy and discuss specific regulatory mechanisms. This analysis is expected to provide direction for the prevention and management of drug resistance in tumors.