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Simple Summary: This review paper deals with incidentally found focal liver lesions (IFLLs) in otherwise healthy subjects, which is a frequent occurrence in daily practice. The clinical presentation and the imaging aspects play an important role in deciding whether and what further evaluation is required. In low-risk patients (i.e., those without a history of malignant or chronic liver disease or related symptoms, younger than 40 years old), more than 95% of IFLLs are benign. Shear Wave liver Elastography of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on a B-mode ultrasound of a benign lesion, no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. An incidental focal liver lesion (IFLL) is defined as a hepatic lesion identified in a patient imaged for an unrelated reason. They are frequently encountered in daily practice, sometimes leading to unnecessary, invasive and potentially harmful follow-up investigations. The clinical presentation and the imaging aspects play an important role in deciding if, and what further evaluation, is needed. In low-risk patients (i.e., without a history of malignant or chronic liver disease or related symptoms), especially in those younger than 40 years old, more than 95% of IFLLs are likely benign. Shear Wave liver Elastography (SWE) of the surrounding liver parenchyma should be considered to exclude liver cirrhosis and for further risk stratification. If an IFLL in a low-risk patient has a typical appearance on B-mode ultrasound of a benign lesion (e.g., simple cyst, calcification, focal fatty change, typical hemangioma), no further imaging is needed. Contrast-Enhanced Ultrasound (CEUS) should be considered as the first-line contrast imaging modality to differentiate benign from malignant IFLLs, since it has a similar accuracy to contrast-enhanced (CE)-MRI. On CEUS, hypoenhancement of a lesion in the late vascular phase is characteristic for malignancy. CE-CT should be avoided for characterizing probable benign FLL and reserved for staging once a lesion is proven malignant. In high-risk patients (i.e., with chronic liver disease or an oncological history), each IFLL should initially be considered as potentially malignant, and every effort should be made to confirm or exclude malignancy. US-guided biopsy should be considered in those with unresectable malignant lesions, particularly if the diagnosis remains unclear, or when a specific tissue diagnosis is needed. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic brought into prominence several emergent medical and surgical entities, but, also, it served as trigger and contributor for numerous apparently unrelated ailments such as arterial and venous thromboembolic complications. Additional risk factors for these thrombotic traits may be concurrent (known or unknown) malignancies, including at hepatic level. Among these, cholangiocarcinoma (CCA), a rare cancer of intra- and extra-hepatic biliary ducts, represents a very aggressive condition that typically associates local and distant advanced stages on first presentation requiring a prompt diagnosis and a stratified management. This neoplasia has been reported to present a large spectrum of paraneoplastic syndromes in terms of dermatologic, renal, systemic, neurologic, endocrine, and cardiovascular settings, that, overall, are exceptional in their epidemiologic impact when compared to other cancers. Our aim was to introduce a most unusual case of CCA-associated distant thrombosis in a male adult who initially was considered to experience COVID-19-related thrombotic features while having a history of obesity and bariatric surgery. This is a hybrid type of paper: this clinical vignette is accompanied by two distinct sample-focused analyses as a basis for discussion; they each had different methods depending on their current level of statistical evidence. We only included English-published articles in PubMed, as follows: Firstly, we conducted a search of reports similar to the present case, regarding distant vein thrombosis in CCA, from inception until the present time. We performed a literature search using the keywords "cholangiocarcinoma", "thrombosis", and "Trousseau's syndrome" and identified 20 cases across 19 original papers; hence, the current level of evidence remains very low Secondly, we searched for the highest level of statistical evidence concerning the diagnosis of venous thrombosis/thromboembolism in patients who underwent COVID-19 infection (key search terms were "COVID-19", alternatively, "coronavirus", and "SARS-CoV-2", and "thrombosis", alternatively, "thromboembolism") and included the most recent systematic reviews and meta-analyses that were published in 2024 (from 1 January 2024 until 8 July 2024). After excluding data on vaccination against coronavirus or long COVID-19 syndrome, we identified six such articles. To conclude, we presented a probably unique case of malignancy with an initial manifestation consisting of recurrent superficial vein thrombosis under anticoagulation therapy, with no gastrointestinal manifestations, in a patient with a notable history for multiple episodes of SARS-CoV-2 infection and a prior endocrine (gastric) surgery. To our knowledge, this is the first identification of a CCA under these specific circumstances. [ABSTRACT FROM AUTHOR]

The prevalence of nonalcoholic fatty liver disease (NAFLD) is likely to be approaching 38% of the world's population. It is predicted to become worse and is the main cause of morbidity and mortality due to hepatic pathologies. It is particularly worrying that NAFLD is increasingly diagnosed in children and is closely related, among other conditions, to insulin resistance and metabolic syndrome. Against this background is the concern that the awareness of patients with NAFLD is low; in one study, almost 96% of adult patients with NAFLD in the USA were not aware of their disease. Thus, studies on the therapeutic tools used to treat NAFLD are extremely important. One promising treatment is a well-formulated ketogenic diet (KD). The aim of this paper is to present a review of the available publications and the current state of knowledge of the effect of the KD on NAFLD. This paper includes characteristics of the key factors (from the point of view of NAFLD regression), on which ketogenic diet exerts its effects, i.e., reduction in insulin resistance and body weight, elimination of fructose and monosaccharides, limitation of the total carbohydrate intake, anti-inflammatory ketosis state, or modulation of gut microbiome and metabolome. In the context of the evidence for the effectiveness of the KD in the regression of NAFLD, this paper also suggests the important role of taking responsibility for one's own health through increasing self-monitoring and self-education. [ABSTRACT FROM AUTHOR]

Hibernation serves as an energy-conserving strategy that enables animals to withstand harsh environments by reducing their metabolic rate significantly. However, the mechanisms underlying energy adaptation in hibernating ectotherms, such as Pelodiscus sinensis , remain contentious. This paper first reports the decrease in lipid levels and the expression of metabolism-related genes in P. sinensis during hibernation. The results of physiological and biochemical analysis showed that adipocyte cell size was reduced and liver lipid droplet (LD) contents were decreased during hibernation in P. sinensis . Concurrently, serum levels of triglycerides (TGs), total cholesterol (TC), non-esterified fatty acids (NEFAs), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were diminished (n = 8, p < 0.01), while an increase in serum glucose (Glu) (n = 8, p < 0.01) was noted among hibernating P. sinensis . These observations suggest a shift in energy metabolism during hibernation. To gain insights into the molecular mechanisms, we performed integrated transcriptomic and lipidomic analyses of adipose tissue and livers from summer-active versus overwintering P. sinensis , which revealed downregulation of free fatty acids (FFAs), triglycerides (TGs), diglycerides (DGs), and ceramides (Cers) during hibernation. The results of GSEA analysis showed that metabolic pathways associated with lipid metabolism, including glycerolipid metabolism and regulation of lipolysis in adipocytes, were suppressed significantly. Notably, acute cold exposure induced significant downregulation of genes related to lipolysis such as PNPLA2 , ABHD5 , LPL , CPT1A , and PPARα . The results indicate that lipolysis is suppressed during hibernation in P. sinensis . Collectively, these findings deepen our understanding of survival mechanisms and elucidate the unique energy adaptation strategies employed by hibernating ectotherms. Future research should explore the implications of these findings for the conservation of ectotherms and the applications for artificially inducing hibernation.

This paper reports the results of a mercury (Hg) and selenium (Se) metallomic study in the liver tissues of Psectrogaster amazonica and Raphiodon vulpinus from the Brazilian Amazon. Two-dimensional electrophoresis, graphite furnace atomic absorption spectrometry, and liquid chromatography-tandem mass spectrometry were performed. Hg and Se determinations allowed the calculation of Hg:Se and Se:Hg molar ratio and Se values for health benefits (Se HBVs). The Se:Hg values were >1 for both fish species, whereas the Se HBVs were >5 for P. amazonica and >10 for R. vulpinus , indicating that both possess Se reserves to control Hg toxicity. The metallomic data allowed the identification of 11 Hg/Se-associated protein spots in the two fish species, with concentrations in the range of 9.70 ± 0.14 and 28.44 ± 0.31 mg kg -1 of Hg and 16.15 ± 0.21 and 43.12 ± 0.51 mg kg -1 of Se. Five metal binding proteins ( MBP ) in the Hg/Se-associated protein spots in the liver proteome of P. amazonica and eight in R. vulpinus were identified, indicating the possible formation of Hg/Se complexes on the MBP structures. The activities analysis of catalase, superoxide dismutase, GPx enzymes, and lipoperoxide concentrations demonstrated that Hg-induced oxidative stress did not occur, possibly because both fish species possess Se reserves necessary to inhibit the Hg's deleterious effects.

Simple Summary: This manuscript systematically reviewed the literature on the use of vascular shunts during advanced pancreatic surgery, analyzing intraoperative and postoperative outcomes, and enlightening excellent long-term patency, negligible additional operative time, and acceptable postoperative morbidity. The importance of the study was to underline feasibility of this technical artifice, which may help expert surgeons to achieve clear margins in borderline or locally advanced PDAC. Background: The rising diffusion of vascular resections during complex pancreatectomy for malignancy, for both oncological and technical matters, brought with it the use of vascular shunts, either temporary or definitive, to prevent bowel congestion and liver ischemia. This study aimed to systematically review the literature on the technical feasibility of vascular shunts during advanced pancreatic surgery, analyzing intraoperative and postoperative outcomes. Methods: A systematic literature search was performed on PubMed, Scopus, Web of Science, and the Cochrane Library Central, according to PRISMA guidelines. Studies published before 2006 were excluded, considering the lack of a standardized definition of locally advanced pancreatic cancer. The main outcomes evaluated were the overall complication rate and shunt patency. Results: Among 789 papers retrieved from the database search, only five fulfilled the inclusion criteria and were included in the review, amounting to a total of 145 patients undergoing a shunt creation at the time of pancreatectomy. Pancreatic adenocarcinoma (PDAC) was found to be the most common diagnosis and pancreaticoduodenectomy was the main surgical procedure, accounting for 88% and 83% of the overall cohort, respectively. The distal splenorenal shunt was the most performed. Overall, 44 out of 145 patients (30%) experienced postoperative complications; the long-term patency of definitive shunts was 83% (110 out of 120 patients). Conclusions: An increasing number of patients with borderline resectable or locally advanced PDAC are becoming amenable to resection and shunt creation may facilitate vascular resection with clear margins, becoming a valid tool of modern pancreatic surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation therapy is becoming increasingly important in the treatment of liver and pancreatic tumors, particularly in situations where high doses of radiation can be delivered safely. However, there are several challenges to treating tumors in the abdomen, including poor visibility of the tumor and movements due to breathing and digestion. The typical imaging available at the time of treatment makes it difficult to see both the tumor and nearby portions of the digestive tract, which is particularly sensitive to radiation damage. This paper describes the workflow involved when using high-quality computed tomography imaging at the time of treatment, to ensure that the tumor is accurately targeted and normal tissues are avoided. This study shows that by using these images and the planned dose distribution, the dose to normal structures can be maintained below specified targets. With this technology and workflow, more patients can benefit from high-dose radiation treatment to the liver and pancreas. Background/Objectives: Stereotactic body radiation therapy (SBRT) for abdominal targets faces a variety of challenges, including motion caused by the respiration and digestion and a relatively poor level of contrast between the tumor and the surrounding tissues. Breath-hold treatments with computed tomography-on-rails (CTOR) image guidance is one way of addressing these challenges, allowing for both the tumor and normal tissues to be well-visualized. Using isodose lines (IDLs) from CT simulations as a guide, the anatomical information can be used to shift the alignment or trigger a replan, such that normal tissues receive acceptable doses of radiation. Methods: This study aims to describe the workflow involved when using CTOR for pancreas and liver SBRT and demonstrates its effectiveness through several case studies. Results: In these case studies, using the anatomical information gained through diagnostic-quality CT guidance to make slight adjustments to the alignment, resulted in reductions in the maximum dose to the stomach. Conclusions: High-quality imaging, such as CTOR, and the use of IDLs to estimate the doses to OARs, enable the safe delivery of SBRT, without the added complexity and resource commitment required by daily online adaptive planning. [ABSTRACT FROM AUTHOR]

Simple Summary: In liver surgery, the complex and individualized nature of liver vascular anatomy makes planning and execution challenging. Traditional 2D intraoperative ultrasonography (IOUS) often suffers from interpretability issues due to noise and artifacts. This paper introduces an AI-based model, the "2D-weighted U-Net model," designed to enhance real-time IOUS navigation by accurately segmenting key blood vessels, including the inferior vena cava, hepatic veins, portal vein, and its major branches. Our deep learning model demonstrated high performance, with Dice scores ranging from 0.84 to 0.96 across different vessels. This advancement promises improved precision in liver resection procedures and sets the stage for future development of real-time multi-label segmentation for broader liver vasculature. Background/Objectives: In the field of surgical medicine, the planning and execution of liver resection procedures present formidable challenges, primarily attributable to the intricate and highly individualized nature of liver vascular anatomy. In the current surgical milieu, intraoperative ultrasonography (IOUS) has become indispensable; however, traditional 2D ultrasound imaging's interpretability is hindered by noise and speckle artifacts. Accurate identification of critical structures for preservation during hepatectomy requires advanced surgical skills. Methods: An AI-based model that can help detect and recognize vessels including the inferior vena cava (IVC); the right (RHV), middle (MHV), and left (LVH) hepatic veins; the portal vein (PV) and its major first and second order branches the left portal vein (LPV), right portal vein (RPV), and right anterior (RAPV) and posterior (RPPV) portal veins, for real-time IOUS navigation can be of immense value in liver surgery. This research aims to advance the capabilities of IOUS-guided interventions by applying an innovative AI-based approach named the "2D-weigthed U-Net model" for the segmentation of multiple blood vessels in real-time IOUS video frames. Results: Our proposed deep learning (DL) model achieved a mean Dice score of 0.92 for IVC, 0.90 for RHV, 0.89 for MHV, 0.86 for LHV, 0.95 for PV, 0.93 for LPV, 0.84 for RPV, 0.85 for RAPV, and 0.96 for RPPV. Conclusion: In the future, this research will be extended for real-time multi-label segmentation of extended vasculature in the liver, followed by the translation of our model into the surgical suite. [ABSTRACT FROM AUTHOR]

The modeling of fibrotic effects on fluid flow and metabolism in the liver can be computationally challenging. This paper combines innovative concepts based on fundamental physics to address such issues at the level of the liver functional unit, the lobule, and upscales and extends this to a multi-lobule tissue scale analysis. Fibrosis effects on fluid flow and metabolism are introduced using percolation theory and its consequences are explored for single lobule and multi-lobule patterns, without and with distortion. [ABSTRACT FROM AUTHOR]

Background: A few months after the COVID-19 pandemic onset, knowledge of SARS-CoV-2 infection and outcomes and treatments blew up. This paper aimed to evaluate the features of a Tuscany COVID-19 hospitalized cohort and to identify risk factors for COVID-19 severity. Methods: This retrospective observational COVID-19 cohort study (1 March 2020–1 March 2021) was conducted on patients ≥ 18 years old, admitted to Tuscany Hospital, and subjected to follow-up within 12 months after discharge. Patients were enrolled at Pisana, Senese and Careggi University Hospitals, and South East, North West, and Center Local Hospitals. Results: 2888 patients (M = 58.5%, mean age = 66.2 years) were enrolled, of whom 14.3% (N = 413) were admitted to an intensive care unit. Smokers were 25%, and overweight and obese 65%. The most used drugs were corticosteroids, antacids, antibiotics, and antithrombotics, all antiviral drugs, with slight differences between 2020 and 2021. A strong association was found between outcomes of evolution towards critical COVID-19 (non-invasive mechanical ventilation (NIV) and/or admission to intensive care) and smoking (RR = 4.91), ex-smoking (RR = 3.48), overweight (RR = 1.30), obese subjects (RR = 1.62), comorbidities (aRR = 1.38). The alteration of liver enzymes (aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyl transpeptidase) was associated with NIV (aOR = 2.28). Conclusions: Our cohort, characterized by patients with a mean age of 66.2 years, showed 65% of patients were overweight and obese. Smoking/ex-smoking, overweight/obesity, and other comorbidities were associated with COVID-19 adverse outcomes. The findings also demonstrated that alterations in liver enzymes were associated with worse outcomes. [ABSTRACT FROM AUTHOR]

The aim of the study was to analyse papers describing the use of Electrochemotherapy (ECT) in local treatment of primary and secondary liver tumours located at different sites and with different histologies. Other Local Ablative Therapies (LAT) are also discussed. Analyses of these papers demonstrate that ECT use is safe and effective in lesions of large size, independently of the histology of the treated lesions. ECT performed better than other thermal ablation techniques in lesions > 6 cm in size and can be safely used to treat lesions distant, close, or adjacent to vital structures. ECT spares vessel and bile ducts, is repeatable, and can be performed between chemotherapeutic cycles. ECT can fill the gap in local ablative therapies due to being lesions too large or localized in highly challenging anatomical sites. [ABSTRACT FROM AUTHOR]

Transplantation is currently the only effective treatment for patients with end-stage liver failure. In recent years, many advanced studies have been conducted to improve the efficiency of organ preservation techniques. Modifying the composition of the preservation fluids currently used may improve graft function and increase the likelihood of transplantation success. The modified fluid is expected to extend the period of safe liver storage in the peri-transplantation period and to increase the pool of organs for transplantation with livers from marginal donors. This paper provides a literature review of the effects of antioxidants on the efficacy of liver preservation fluids. Medline (PubMed), Scopus, and Cochrane Library databases were searched using a combination of MeSH terms: "liver preservation", "transplantation", "preservation solution", "antioxidant", "cold storage", "mechanical perfusion", "oxidative stress", "ischemia-reperfusion injury". Studies published up to December 2023 were included in the analysis, with a focus on publications from the last 30 years. A total of 45 studies met the inclusion criteria. The chemical compounds analyzed showed mostly bioprotective effects on hepatocytes, including but not limited to multifactorial antioxidant and free radical protective effects. It should be noted that most of the information cited is from reports of studies conducted in animal models, most of them in rodents.

Drug-induced liver injury (DILI) is a common clinical pharmacogenic disease. In the United States and Europe, DILI is the most common cause of acute liver failure. Drugs can cause hepatic damage either directly through inherent hepatotoxic properties or indirectly by inducing oxidative stress, immune responses, and inflammatory processes. These pathways can culminate in hepatocyte necrosis. The role of the gut microecology in human health and diseases is well recognized. Recent studies have revealed that the imbalance in the gut microecology is closely related to the occurrence and development of DILI. The gut microecology plays an important role in liver injury caused by different drugs. Recent research has revealed significant changes in the composition, relative abundance, and distribution of gut microbiota in both patients and animal models with DILI. Imbalance in the gut microecology causes intestinal barrier destruction and microorganism translocation; the alteration in microbial metabolites may initiate or aggravate DILI, and regulation and control of intestinal microbiota can effectively mitigate drug-induced liver injury. In this paper, we provide an overview on the present knowledge of the mechanisms by which DILI occurs, the common drugs that cause DILI, the gut microbiota and gut barrier composition, and the effects of the gut microbiota and gut barrier on DILI, emphasizing the contribution of the gut microecology to DILI. [ABSTRACT FROM AUTHOR]

Currently, staging the degree of liver fibrosis predominantly relies on liver biopsy, a method fraught with potential risks, such as bleeding and infection. With the rapid development of medical imaging devices, quantification of liver fibrosis through image processing technology has become feasible. Stacking technology is one of the effective ensemble techniques for potential usage, but precise tuning to find the optimal configuration manually is challenging. Therefore, this paper proposes a novel EVO-MS model—a multiple stacking ensemble learning model optimized by the energy valley optimization (EVO) algorithm to select most informatic features for fibrosis quantification. Liver contours are profiled from 415 biopsied proven CT cases, from which 10 shape features are calculated and inputted into a Support Vector Machine (SVM) classifier to generate the accurate predictions, then the EVO algorithm is applied to find the optimal parameter combination to fuse six base models: K-Nearest Neighbors (KNNs), Decision Tree (DT), Naive Bayes (NB), Extreme Gradient Boosting (XGB), Gradient Boosting Decision Tree (GBDT), and Random Forest (RF), to create a well-performing ensemble model. Experimental results indicate that selecting 3–5 feature parameters yields satisfactory results in classification, with features such as the contour roundness non-uniformity (Rmax), maximum peak height of contour (Rp), and maximum valley depth of contour (Rm) significantly influencing classification accuracy. The improved EVO algorithm, combined with a multiple stacking model, achieves an accuracy of 0.864, a precision of 0.813, a sensitivity of 0.912, a specificity of 0.824, and an F1-score of 0.860, which demonstrates the effectiveness of our EVO-MS model in staging the degree of liver fibrosis. [ABSTRACT FROM AUTHOR]

This technical paper introduces a novel organ preservation system based on isochoric (constant volume) supercooling. The system is designed to enhance the stability of the metastable supercooling state, offering potential long-term preservation of large biological organs at subfreezing temperatures without the need for cryoprotectant additives. Detailed technical designs and usage protocols are provided for researchers interested in exploring this field. The paper also presents a control system based on the thermodynamics of isochoric freezing, utilizing pressure monitoring for process control. Sham experiments were performed using whole pig liver sourced from a local food supplier to evaluate the system's ability to sustain supercooling without ice nucleation for extended periods. The results demonstrated sustained supercooling without ice nucleation in pig liver tissue for 24 and 48 h. These findings suggest the potential of this technology for large-volume, cryoprotectant-free organ preservation with real-time control over the preservation process. The simplicity of the isochoric supercooling device and the design details provided in the paper are expected to serve as encouragement for other researchers in the field to pursue further research on isochoric supercooling. However, final evidence that these preserved organs can be successfully transplanted is still lacking. [ABSTRACT FROM AUTHOR]

Simple Summary: Most of the existing data on the resection of liver metastases with inferior vena cava infiltration come from case reports or small case series. This systematic review on the subject found postoperative morbidity and mortality rates and overall survival to be acceptable, offering a surgical alternative to these patients previously considered unresectable. Combined hepatic and inferior vena cava (IVC) resection is the only potentially curative treatment for patients with colorectal liver metastases (CRLM) involving the IVC. Most of the existing data come from case reports or small case series. In this paper, a systematic review based on the PICO strategy was performed in accordance with the PRISMA statement. Papers from January 1980 to December 2022 were searched in Embase, PubMed, and the Cochrane Library databases. Articles considered for inclusion had to present data on simultaneous liver and IVC resection for CRLM and report surgical and/or oncological outcomes. From a total of 1175 articles retrieved, 29, including a total of 188 patients, met the inclusion criteria. The mean age was 58.3 ± 10.8 years. The most frequent techniques used were right hepatectomy ± caudate lobe for hepatic resections (37.8%), lateral clamping (44.8%) for vascular control, and primary closure (56.8%) for IVC repair. The thirty-day mortality reached 4.6%. Tumour relapse was reported in 65.8% of the cases. The median overall survival (OS) was 34 months (with a confidence interval of 30–40 months), and the 1-year, 3-year, and 5-year OS were 71.4%, 19.8%, and 7.1%, respectively. In the absence of prospective randomized studies, which are difficult to perform, IVC resection seems to be safe and feasible. [ABSTRACT FROM AUTHOR]

Segmenting medical images is a necessary prerequisite for disease diagnosis and treatment planning. Among various medical image segmentation tasks, U-Net-based variants have been widely used in liver tumor segmentation tasks. In view of the highly variable shape and size of tumors, in order to improve the accuracy of segmentation, this paper proposes a U-Net-based hybrid variable structure—RDCTrans U-Net for liver tumor segmentation in computed tomography (CT) examinations. We design a backbone network dominated by ResNeXt50 and supplemented by dilated convolution to increase the network depth, expand the perceptual field, and improve the efficiency of feature extraction without increasing the parameters. At the same time, Transformer is introduced in down-sampling to increase the network's overall perception and global understanding of the image and to improve the accuracy of liver tumor segmentation. The method proposed in this paper tests the segmentation performance of liver tumors on the LiTS (Liver Tumor Segmentation) dataset. It obtained 89.22% mIoU and 98.91% Acc, for liver and tumor segmentation. The proposed model also achieved 93.38% Dice and 89.87% Dice, respectively. Compared with the original U-Net and the U-Net model that introduces dense connection, attention mechanism, and Transformer, respectively, the method proposed in this paper achieves SOTA (state of art) results. [ABSTRACT FROM AUTHOR]

MR is a powerful diagnostic tool in the diagnosis and management of most hepatic and pancreatic diseases. Thanks to its multiple sequences, the use of dedicated contrast media and special techniques, it allows a multiparametric approach able to provide both morphological and functional information for many pathological conditions. The knowledge of correct technique is fundamental in order to obtain a correct diagnosis. In this paper, different MR sequences will be illustrated in the evaluation of liver and pancreatic diseases, especially those sequences which provide information not otherwise obtainable with other imaging techniques. Practical MR protocols with the most common indications of MR in the study of the liver and pancreas are provided. [ABSTRACT FROM AUTHOR]

The liver is the second most common solid organ injured in blunt and penetrating abdominal trauma. Non-operative management (NOM) has become the standard of care for liver injuries in stable patients, where transarterial embolization (TAE) represents the main treatment, increasing success rates and avoiding invasive surgical procedures. In hemodynamically (HD) unstable patients, operative management (OM) is the standard of care. To date, there are no consensus guidelines about the endovascular treatment of patients with HD instability or in ones that responded to initial infusion therapy. A review of the literature was performed for published papers addressing the outcome of using TAE as the primary treatment for HD unstable/transient responder trauma liver patients with hemorrhagic vascular lesions, both as a single treatment and in combination with surgical treatment, focusing additionally on the different definitions used in the literature of unstable and transient responder patients. Our review demonstrated a good outcome in HD unstable/transient responder liver trauma patients treated with TAE but there still remains much debate about the definition of unstable and transient responder patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Yaks are a major economic source for people in the Tibetan Plateau region. Yaks are rich in nutrients, but their low fat content is not conducive to the large-scale promotion of yak meat, so the study of the mechanism of yak lipid deposition is beneficial to the marketing of yak meat. In this paper, the results of transcriptome sequencing analysis of yak liver showed that it could be determined that the expression levels of genes associated with partial lipid deposition were significantly up-regulated during yak fattening. In addition, this study found that the tenderness of yak meat improved during this process. Fattening significantly affects fat deposition in yaks, which may be realized through its effects on lipid metabolic pathways. Therefore, studying the mechanism of lipid deposition in yaks and fattening yaks will improve the quality of yak meat. Yak meat is nutritionally superior to beef cattle but has a low fat content and is slow-growing. The liver plays a crucial role in lipid metabolism, and in order to determine whether different feeding modes affect lipid metabolism in yaks and how it is regulated, we employed RNA sequencing (RNA-seq) technology to analyze the genome-wide differential gene expression in the liver of yaks maintained under different raising systems. A total of 1663 differentially expressed genes (DEGs) were identified (|log2FC| ≥ 0 and p-value ≤ 0.05), including 698 down-regulated and 965 up-regulated genes. According to gene ontology (GO) and KEGG enrichment analyses, these DEGs were significantly enriched in 13 GO terms and 26 pathways (p < 0.05). Some DEGs were enriched in fatty acid degradation, PPAR, PI3K-Akt, and ECM receptor pathways, which are associated with lipid metabolism. A total of 16 genes are well known to be related to lipid metabolism (e.g., APOA1, FABP1, EHHADH, FADS2, SLC27A5, ACADM, CPT1B, ACOX2, HMGCS2, PLIN5, ACAA1, IGF1, FGFR4, ALDH9A1, ECHS1, LAMA2). A total of 11 of the above genes were significantly enriched in the PPAR signaling pathway. The reliability of the transcriptomic data was verified using qRT-PCR. Our findings provide new insights into the mechanisms regulating yak meat quality. It shows that fattening improves the expression of genes that regulate lipid deposition in yaks and enhances meat quality. This finding will contribute to a better understanding of the various factors that determine yak meat quality and help develop strategies to improve yield and quality. [ABSTRACT FROM AUTHOR]

Background: Liver diseases are constantly increasing throughout the world and are often associated with other diseases, but above all they are caused by improper diet. Adherence to a diet with abundant vegetables has now been widely demonstrated to be important in combating this pathological condition. The aim of this study was to explore the protective role of lycopene (LYC) extracts from cooked and fresh tomato. Methods: The study cohort included 969 participants assessed in the NUTRIHEP cohort (2005–2006) and the associated follow-up (2014–2016), divided into two groups, based on liver condition: NAFLD, or AFLD and FLD. Results: The results indicated a statistical significance of LYC consumption, showing a protective role against liver disease, the best concentration being 9.50 mg/die, with an RR value of 0.59, p = 0.01, 0.39 to 0.90 at 95% C.I., and RRR = 0.40, p = 0.002, 0.22 to 0.71 at 95% C.I. Conclusions: The protective role of LYC extracts from tomato has not been amply demonstrated in humans. We conclude that this is one of the few papers in the literature to evaluate the protective effect of LYC against liver disease, as well as how this molecule could be used in future possible treatments. Utilizing lycopene as a supplement alone or in combination with other foods could be useful for developing treatments with reduced contraindications. [ABSTRACT FROM AUTHOR]

A pressing health problem, both in clinical and socio-economic terms, is the increase in the number of patients with liver damage caused by viral diseases (hepatitis), cancer, toxicological damage, or metabolic disorders. Liver function assessment is a complex task, for which various existing diagnostic methods are used. Unfortunately, they all have several limitations which frequently make prompt and accurate diagnosis impossible. The high level of disability and mortality caused by liver diseases makes the development of new liver diagnostic methods very urgent. In this paper, we describe a new joint methodology for studying liver function based on optical densitometry and dynamic light scattering. This will help to diagnose and predict the dynamics of liver function during treatment with greater efficiency, due to including in consideration the individual characteristics of the cardiovascular system and tissue metabolism. In this paper, we present a laboratory model of a combined sensor for optical densitometry and dynamic light scattering. We also developed special software for controlling the sensor and processing the recorded data. Modeling experiments and physical medical studies were carried out to adjust and calibrate the sensor and software. We also assessed the sensor resolution when registering the concentration of dye in the human body and the minimum measured flow rate. [ABSTRACT FROM AUTHOR]

Liver segmentation is a prerequisite for various hepatic interventions and is a time-consuming manual task performed by radiology experts. Recently, various computationally expensive deep learning architectures tackled this aspect without considering the resource limitations of a real-life clinical setup. In this paper, we investigated the capabilities of a lightweight model, UNeXt, in comparison with the U-Net model. Moreover, we conduct a broad analysis at the micro and macro levels of these architectures by using two training loss functions: soft dice loss and unified focal loss, and by substituting the commonly used ReLU activation function, with the novel Funnel activation function. An automatic post-processing step that increases the overall performance of the models is also proposed. Model training and evaluation were performed on a public database—LiTS. The results show that the UNeXt model (Funnel activation, soft dice loss, post-processing step) achieved a 0.9902 dice similarity coefficient on the whole CT volumes in the test set, with 15× fewer parameters in nearly 4× less inference time, compared to its counterpart, U-Net. Thus, lightweight models can become the new standard in medical segmentation, and when implemented thoroughly can alleviate the computational burden while preserving the capabilities of a parameter-heavy architecture. [ABSTRACT FROM AUTHOR]

Malignant focal liver lesions (FLLs) represent various kinds of epithelial and mesenchymal tumors. In pediatric patients, the understanding of pediatric liver diseases and associated imaging manifestations is essential for making accurate diagnosis and differential diagnosis. This paper will discuss the latest knowledge of the common pediatric malignant FLLs, including undifferentiated embryonal sarcoma, rhabdomyosarcoma, epithelioid hemangioendothelioma, angiosarcoma, and malignant rhabdoid tumor. Medical imaging features are not only helpful for clinical diagnosis, but can also be useful in the evaluation and follow-up of pre- and post-treatment. The future perspectives of contrast-enhanced ultrasound (CEUS) enhancement patterns of FLLs in pediatric patients are also mentioned. [ABSTRACT FROM AUTHOR]

Hepatocellular adenomas are benign endothelial tumors of the liver, mostly associated with female individual users of estrogen-containing medications. However, the precise factors underlying the selective development of hepatic adenomas in certain females remain elusive. Additionally, the conventional profile of individuals prone to hepatic adenoma is changing. Notably, male patients exhibit a higher risk of malignant progression of hepatocellular adenomas, and there are instances where hepatic adenomas have no identifiable cause. In this paper, we theorize the role of the human gastrointestinal microbiota, specifically, of bacterial species producing β-glucuronidase enzymes, in the development of hepatic adenomas through the estrogen recycling pathway. Furthermore, we aim to address some of the existing gaps in our knowledge of pathophysiological pathways which are not yet subject to research or need to be studied further. As microbial β-glucuronidases proteins recycle estrogen and facilitate the conversion of inactive estrogen into its active form, this process results in elevated levels of unbound plasmatic estrogen, leading to extended exposure to estrogen. We suggest that an imbalance in the estrobolome could contribute to sex hormone disease evolution and, consequently, to the advancement of hepatocellular adenomas, which are estrogen related. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatoblastoma is a rare childhood liver cancer with poor outcomes for high-risk patients. Better treatments and better ways of identifying patients who respond poorly to treatment are needed. This paper uses new methods for identifying chemicals or metabolites produced in the tumour. By comparing the profiles of these metabolites in tumour tissue versus normal liver tissue taken from the same patient, we demonstrated that some metabolites differ significantly in hepatoblastoma. This correlates with gene expression data, suggesting that we identified the metabolites correctly. We also stained tumour tissues for proteins (enzymes) that regulate transport of fatty acids into the mitochondria, which are the cell's powerhouses. Taken together, our results indicate that tumour cells change the energy sources they use and rewire the cellular systems accordingly. Further work is required to verify this, but these leads could improve our understanding of the disease and lead to the development of novel therapies. Hepatoblastoma (HB) is a rare childhood tumour with an evolving molecular landscape. We present the first comprehensive metabolomic analysis using untargeted and targeted liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS) of paired tumour and non-tumour surgical samples in HB patients (n = 8 pairs). This study demonstrates that the metabolomic landscape of HB is distinct from that of non-tumour (NT) liver tissue, with 35 differentially abundant metabolites mapping onto pathways such as fatty acid transport, glycolysis, the tricarboxylic acid (TCA) cycle, branched-chain amino acid degradation and glutathione synthesis. Targeted metabolomics demonstrated reduced short-chain acylcarnitines and a relative accumulation of branched-chain amino acids. Medium- and long-chain acylcarnitines in HB were similar to those in NT. The metabolomic changes reported are consistent with previously reported transcriptomic data from tumour and non-tumour samples (49 out of 54 targets) as well as metabolomic data obtained using other techniques. Gene set enrichment analysis (GSEA) from RNAseq data (n = 32 paired HB and NT samples) demonstrated a downregulation of the carnitine metabolome and immunohistochemistry showed a reduction in CPT1a (n = 15 pairs), which transports fatty acids into the mitochondria, suggesting a lack of utilisation of long-chain fatty acids in HB. Thus, our findings suggest a reduced metabolic flux in HB which is corroborated at the gene expression and protein levels. Further work could yield novel insights and new therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Developmental programming is now an area of considerable interest throughout the biomedical research community as it is now well accepted that challenges during fetal and early neonatal life program the trajectory of the development and function of multiple systems across the life span. There is now also compelling evidence that developmental programming alters the trajectory of aging, beginning early in life. The present study links mitochondrial function to molecular signaling pathways that regulate life span and to the aging process; it demonstrates the role and importance of mitochondria in the predisposition to developing a fatty liver. The overall message we wish to emphasize is that hepatic aging in offspring caused by maternal obesity in rats involves changes in the mitochondrial function pathways that result in fatty livers. These processes show sexual dimorphism as they occur in males and females at different ages. These findings throw new light on the mechanisms that underlie the well-established sexual dimorphism in aging. We hope this paper will be a stimulus to similar studies on other tissues. We investigated whether maternal obesity affects the hepatic mitochondrial electron transport chain (ETC), sirtuins, and antioxidant enzymes in young (110 postnatal days (PND)) and old (650PND) male and female offspring in a sex- and age-related manner. Female Wistar rats ate a control (C) or high-fat (MO) diet from weaning, through pregnancy and lactation. After weaning, the offspring ate the C diet and were euthanized at 110 and 650PND. The livers were collected for RNA-seq and immunohistochemistry. Male offspring livers had more differentially expressed genes (DEGs) down-regulated by both MO and natural aging than females. C-650PND vs. C-110PND and MO-110PND vs. C-110PND comparisons revealed 1477 DEGs in common for males (premature aging by MO) and 35 DEGs for females. Analysis to identify KEGG pathways enriched from genes in common showed changes in 511 and 3 KEGG pathways in the male and female livers, respectively. Mitochondrial function pathways showed ETC-related gene down-regulation. All ETC complexes, sirtuin2, sirtuin3, sod-1, and catalase, exhibited gene down-regulation and decreased protein expression at young and old ages in MO males vs. C males; meanwhile, MO females down-regulated only at 650PND. Conclusions: MO accelerates the age-associated down-regulation of ETC pathway gene expression in male offspring livers, thereby causing sex-dependent oxidative stress, premature aging, and metabolic dysfunction. [ABSTRACT FROM AUTHOR]

In recent decades, significant progress has been made in liver tissue engineering through the use of 3D bioprinting technology. This technology offers the ability to create personalized biological structures with precise geometric design capabilities. The complex and multifaceted nature of liver diseases underscores the need for advanced technologies to accurately mimic the physiological and mechanical characteristics, as well as organ-level functions, of liver tissue in vitro. Bioprinting stands out as a superior option over traditional two-dimensional cell culture models and animal models due to its stronger biomimetic advantages. Through the use of bioprinting, it is possible to create liver tissue with a level of structural and functional complexity that more closely resembles the real organ, allowing for more accurate disease modeling and drug testing. As a result, it is a promising tool for restoring and replacing damaged tissue and organs in the field of liver tissue engineering and drug research. This article aims to present a comprehensive overview of the progress made in liver tissue engineering using bioprinting technology to provide valuable insights for researchers. The paper provides a detailed account of the history of liver tissue engineering, highlights the current 3D bioprinting methods and bioinks that are widely used, and accentuates the importance of existing in vitro liver tissue models based on 3D bioprinting and their biomedical applications. Additionally, the article explores the challenges faced by 3D bioprinting and predicts future trends in the field. The progress of 3D bioprinting technology is poised to bring new approaches to printing liver tissue in vitro, while offering powerful tools for drug development, testing, liver disease modeling, transplantation, and regeneration, which hold great academic and practical significance. [ABSTRACT FROM AUTHOR]

Primary hepatic angiosarcoma (PHA) is a rare liver malignancy with few studies describing its radiological characteristics. This article aims to assess the imaging features of each of the multiple delayed contrast-enhanced magnetic resonance imaging (MRI) scans, in addition to the conventional MRI protocol, in a patient with PHA. Standard MRI sequences and a liver protocol were used in the examination of a 71 year-old male with pathologically proven PHA after current imaging evaluation. In addition, the patient underwent transversal and coronal MRI T1-weighted scans at 10 min, 20 min and 90 min after intravenous (IV) administration of gadobenatedimeglumine (Gd-BOPTA). The PHA revealed a variable appearance on MRI, with classic imaging being insufficient in making a reliable diagnosis. Lesions have increased vascularity, which translates into increased IV contrast uptake in the MRI arterial phase, showing progressive and globular enhancement in the portal and parenchymatous phases. On delayed scans, at 10 min after IV administration, the lesions maintained no washout, but slightly began to washout at 20 min post-contrast. However, in the hepatobiliary phase (90 min post-contrast injection), on an MRI T1-weighted sequence, PHA lesions were hypointense, suggesting the absence of hepatocytes, thus indicating high-grade malignancy. This approach proved the conclusion that in a patient with PHA, an extra MRI T1-weighted scan at 90 min post-gadobenatedimeglumine injection can provide helpful information in differential diagnosis. [ABSTRACT FROM AUTHOR]

In this paper, we designed and demonstrated a stimuli-responsive hydrogel that mimics the mass diffusion function of the liver. We have controlled the release mechanism using temperature and pH variations. Additive manufacturing technology was used to fabricate the device with nylon (PA-12), using selective laser sintering (SLS). The device has two compartment sections: the lower section handles the thermal management, and feeds temperature-regulated water into the mass transfer section of the upper compartment. The upper chamber has a two-layered serpentine concentric tube; the inner tube carries the temperature-regulated water to the hydrogel using the given pores. Here, the hydrogel is present in order to facilitate the release of the loaded methylene blue (MB) into the fluid. By adjusting the fluid's pH, flow rate, and temperature, the deswelling properties of the hydrogel were examined. The weight of the hydrogel was maximum at 10 mL/min and decreased by 25.29% to 10.12 g for the flow rate of 50 mL/min. The cumulative MB release at 30 °C increased to 47% for the lower flow rate of 10 mL/min, and the cumulative release at 40 °C climbed to 55%, which is 44.7% more than at 30 °C. The MB release rates considerably increased when the pH dropped from 12 to 8, showing that the lower pH had a major impact on the release of MB from the hydrogel. Only 19% of the MB was released at pH 12 after 50 min, and after that, the release rate remained nearly constant. At higher fluid temperatures, the hydrogels lost approximately 80% of their water in just 20 min, compared to a loss of 50% of their water at room temperature. The outcomes of this study may contribute to further developments in artificial organ design. [ABSTRACT FROM AUTHOR]

Voxel-wise quantitative assessment of typical characteristics in three-dimensional (3D) multiphase computed tomography (CT) imaging, especially arterial phase hyperenhancement (APHE) and subsequent washout (WO), is crucial for the diagnosis and therapy of hepatocellular carcinoma (HCC). However, this process is still missing in practice. Radiologists often visually estimate these features, which limit the diagnostic accuracy due to subjective interpretation and qualitative assessment. Quantitative assessment is one of the solutions to this problem. However, performing voxel-wise assessment in 3D is difficult due to the misalignments between images caused by respiratory and other physiological motions. In this paper, based on the Liver Imaging Reporting and Data System (v2018), we propose a registration-based quantitative model for the 3D voxel-wise assessment of image characteristics through multiple CT imaging phases. Specifically, we selected three phases from sequential CT imaging phases, i.e., pre-contrast phase (Pre), arterial phase (AP), delayed phase (DP), and then registered Pre and DP images to the AP image to extract and assess the major imaging characteristics. An iterative reweighted local cross-correlation was applied in the proposed registration model to construct the fidelity term for comparison of intensity features across different imaging phases, which is challenging due to their distinct intensity appearance. Experiments on clinical dataset showed that the means of dice similarity coefficient of liver were  98.6 % and  98.1 % , those of surface distance were  0.38 and  0.54 mm, and those of Hausdorff distance were  4.34 and  6.16 mm, indicating that quantitative estimation can be accomplished with high accuracy. For the classification of APHE, the result obtained by our method was consistent with those acquired by experts. For the WO, the effectiveness of the model was verified in terms of WO volume ratio. [ABSTRACT FROM AUTHOR]

Featured Application: The selected attributes and their ranking and weights can be used in decision support algorithms in computer aided diagnosis. The liver is one of the most common locations for incidental findings during abdominal CT scans. There are multiple types of disease that can arise within the liver and many of them are nodular. The ultimate goal of our research is to develop an expert knowledge-based system using fuzzy signatures, to support decisions during diagnosis of the most frequent of these nodular lesions. Since the literature contains limited information about the graphical properties of CT images that must be taken into consideration and their relationship to one another, in this paper we focused on selecting and ranking the input parameters using expert knowledge and determining their importance. Six visual attributes of lesions (size, shape, density, homogeneity contour, and other features) were selected based on textbooks of radiology and expert opinion. The importance of these attributes was ranked by radiologist experts using questionnaires and a pairwise comparison technique. The most important feature was found to be the density of the lesion on the various CT phases, and the least important was the size, the order of the other attributes was other features, contour, homogeneity, and shape, with a Kendall concordance coefficient of 0.612. Weights for the attributes, to be used in the future fuzzy signatures, were also determined. As a last step, several statistical parameter-based quantities were generated to represent the above abstract attributes and evaluated by comparing them to expert opinions. [ABSTRACT FROM AUTHOR]

Generative adversarial networks (GANs) have become increasingly powerful, generating mind-blowing photorealistic images that mimic the content of datasets they have been trained to replicate. One recurrent theme in medical imaging, is whether GANs can also be as effective at generating workable medical data, as they are for generating realistic RGB images. In this paper, we perform a multi-GAN and multi-application study, to gauge the benefits of GANs in medical imaging. We tested various GAN architectures, from basic DCGAN to more sophisticated style-based GANs, on three medical imaging modalities and organs, namely: cardiac cine-MRI, liver CT, and RGB retina images. GANs were trained on well-known and widely utilized datasets, from which their FID scores were computed, to measure the visual acuity of their generated images. We further tested their usefulness by measuring the segmentation accuracy of a U-Net trained on these generated images and the original data. The results reveal that GANs are far from being equal, as some are ill-suited for medical imaging applications, while others performed much better. The top-performing GANs are capable of generating realistic-looking medical images by FID standards, that can fool trained experts in a visual Turing test and comply to some metrics. However, segmentation results suggest that no GAN is capable of reproducing the full richness of medical datasets. [ABSTRACT FROM AUTHOR]

The automatic recognition of CT (Computed Tomography) images of liver cancer is important for the diagnosis and treatment of early liver cancer. However, there are problems such as single model structure and loss of pooling layer information when using a traditional convolutional neural network to recognize CT images of liver cancer. Therefore, this paper proposes an efficient method for liver CT image recognition based on the capsule network (CapsNet). Firstly, the liver CT images are preprocessed, and in the process of image denoising, the traditional non-local mean (NLM) denoising algorithm is optimized with a superpixel segmentation algorithm to better protect the information of image edges. After that, CapsNet was used for image recognition for liver CT images. The experimental results show that the average recognition rate of liver CT images reaches 92.9% when CapsNet is used, which is 5.3% higher than the traditional CNN model, indicating that CapsNet has better recognition accuracy for liver CT images. [ABSTRACT FROM AUTHOR]

A precise and accurate method for the simultaneous determination of azaperone and azaperol in meat tissues has been developed. This paper describes the first method to be so fast, simple, and useful, especially for many laboratories that do not have sophisticated equipment. This method is based on LC separation and UV-Vis detection. During the sample preparation, the meat tissue was homogenized in acetonitrile at a ratio of 1:4 (tissue weight:acetonitrile volume). The homogenate was centrifuged, the supernatant was evaporated in a lyophilizator, and then the evaporation residue was dissolved in 20 µL of ethanol. For deproteinization, 15 µL of perchloric acid was added, and the sample prepared in this way was injected into a chromatographic column and analyzed using reversed-phased HPLC. The mobile phase consisted of 0.05 mol/L phosphate buffer pH 3.00 (component A) and acetonitrile (component B). UV detection was conducted at 245 nm. The experimentally determined LOQs were 0.25 µg/kg for azaperone and 0.12 µg/kg for azaperol. For both analytes, the calibration curves showed linearity in the tested concentration range from 50 to 300 µg/kg of tissue. The accuracy of the presented method did not exceed 15%, and the recovery was in the range of 85–115%. A validated analytical procedure was implemented for the analysis of various animal tissues for their content of azaperone and azaperol. [ABSTRACT FROM AUTHOR]

Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound Pd2Spermine (Pd2Spm) has emerged as a potential alternative drug, with favorable pharmacokinetic/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to Pd2Spm, compared to cDDP, and (ii) correlate brain-liver metabolic variations. Multivariate and correlation analysis of the spectra of polar and lipophilic brain and liver extracts from an MDA-MB-231 cell-derived mouse model revealed a stronger impact of Pd2Spm on brain metabolome, compared to cDDP. This was expressed by changes in amino acids, inosine, cholate, pantothenate, fatty acids, phospholipids, among other compounds. Liver was less affected than brain, with cDDP inducing more metabolite changes. Results suggest that neither drug induces neuronal damage or inflammation, and that Pd2Spm seems to lead to enhanced brain anti-inflammatory and antioxidant mechanisms, regulation of brain bioactive metabolite pools and adaptability of cell membrane characteristics. The cDDP appears to induce higher extension of liver damage and an enhanced need for liver regeneration processes. This work demonstrates the usefulness of untargeted metabolomics in evaluating drug impact on multiple organs, while confirming Pd2Spm as a promising replacement of cDDP. [ABSTRACT FROM AUTHOR]

Finasteride (Fin) causes androgen imbalance by inhibiting the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Androgen receptors (AR) are present (e.g., in hepatocytes), which have well-developed endoplasmic reticulum (ERet). Cellular protein quality control is carried out by ERet in two paths: (i) unfolded protein response (UPR) and/or (ii) endoplasmic reticulum associated degradation (ERAD). ERet under continuous stress can generate changes in the UPR and can direct the cell on the pathway of life or death. It has been demonstrated that genes involved in ERet stress are among the genes controlled by androgens in some tissues. Oxidative stress is also one of the factors affecting the functions of ERet and androgens are one of the regulators of antioxidant enzyme activity. In this paper, we discuss/analyze a possible relationship between androgen imbalance in paternal generation with ERet stress and liver disorders in both paternal and filial generation. In our rat model, hyperglycemia and subsequent higher accumulation of hepatic glycogen were observed in all filial generation obtained from females fertilized by Fin-treated males (F1:Fin). Importantly, genes encoding enzymes involved in glucose and glycogen metabolism have been previously recognized among UPR targets. [ABSTRACT FROM AUTHOR]

The aim of the present paper is twofold. Firstly, to assess the absorbed dose in small lesions using Monte Carlo calculations in a scenario of intratumoral injection of 90Y (e.g., percutaneous ablation). Secondly, to derive a practical analytical formula for the calculation of the absorbed dose that incorporates the absorbed fractions for 90Y. The absorbed dose per unit administered activity was assessed using Monte Carlo calculations in spheres of different size (diameter 0.5–20 cm). The spheres are representative of tumor regions and are assumed to be uniformly filled with 90Y. Monte Carlo results were compared with the macrodosimetric approach used for dose calculation in liver radioembolization. The results of this analysis indicate that the use of the analytic model provides dose overestimates below 10% for lesions with diameter larger than approximately 2 cm. However, for lesions smaller than 2 cm the analytic model is likely to deviate significantly (>10%) from Monte Carlo results, providing dose overestimations larger than 50% for lesions of 0.5 cm diameter. In this paper an analytical formula derived from MC calculations that incorporates the absorbed fractions for 90Y is proposed. In a scenario of intratumoral injection of microspheres, the proposed equation can be usefully employed in the treatment planning of spherical lesions of small size (down to 0.5 cm diameter) providing dose estimates in close agreement with Monte Carlo calculations (maximum deviation below 0.5%). [ABSTRACT FROM AUTHOR]

The cause of liver damage by using black cohosh preparation has been concerned but remains unclear. After a preliminary investigation, the black cohosh medicinal materials sold in the market were adulterated with Asian cohosh (Cimicifuga) without removing the fibrous roots. The safety of Cimicifuga rhizome and fibrous roots is unknown and has not been reported. Therefore, in this paper, the rhizome and fibrous roots of Cimicifuga dahurica (Turcz.) Maxim ( C. dahurica ) were completely separated, extracted with 70% ethanol, and freeze-dried to obtain crude rhizome extract (RC) and fibrous roots extract (FRC). UHPLC-Q-TOF-MS was used to identify 39 compounds in the rhizome and fibrous roots of Cimicifuga, mainly saponins and phenolic acids. In the L-02 cytotoxicity experiment, the IC 50 of fibrous roots (1.26 mg/mL) was slightly lower than that of rhizomes (1.417 mg/mL). In the 90-day sub-chronic toxicity study, the FRC group significantly increased the level of white blood cells, ALP, ALT, AST, BILI and CHOL ( p < 0.05); large area of granular degeneration and balloon degeneration occurred in liver tissue; and the expression of p-NF-kB in the nucleus increased in a dose-dependent manner. Overall, Fibrous roots of Cimicifuga are at risk of hepatotoxicity and should be strictly controlled and removed during the processing.

This paper introduces an approach for 3D organ segmentation that generalizes in multiple ways the Chan-Vese level set method. Chan-Vese is a segmentation method that simultaneously evolves a level set while fitting locally constant intensity models for the interior and exterior regions. First, its simple length-based regularization is replaced with a learned shape model based on a Fully Convolutional Network (FCN). We show how to train the FCN and introduce data augmentation methods to avoid overfitting. Second, two 3D variants of the method are introduced, one based on a 3D U-Net that makes global shape modifications and one based on a 3D FCN that makes local refinements. These two variants are integrated in a full 3D organ segmentation approach that is capable and efficient in dealing with the large size of the 3D volumes with minimal overfitting. Experiments on liver segmentation on a standard benchmark dataset show that the method obtains 3D segmentation results competitive with the state of the art while being very fast and having a small number of trainable parameters. [ABSTRACT FROM AUTHOR]

Ferritin, as an iron storage protein, regulates iron metabolism and delivers bioactive substances. It has been regarded as a safe, new type of natural iron supplement, with high bioavailability. In this paper, we extracted and purified ferritin from northern pike liver (NPLF). The aggregation stabilities, assemble properties, and structural changes in NPLF were investigated using electrophoresis, dynamic light scattering (DLS), circular dichroism (CD), UV–Visible absorption spectroscopy, fluorescence spectroscopy, and transmission electron microscopy (TEM) under various thermal treatments. The solubility, iron concentration, and monodispersity of NPLF all decreased as the temperature increased, and macromolecular aggregates developed. At 60 °C and 70 °C, the α-helix content of ferritin was greater. The content of α-helix were reduced to 8.10% and 1.90% at 90 °C and 100 °C, respectively, indicating the protein structure became loose and lost its self-assembly ability. Furthermore, when treated below 80 °C, NPLF maintained a complete cage-like shape, according to the microstructure. Partially unfolded structures reassembled into tiny aggregates at 80 °C. These findings suggest that mild thermal treatment (80 °C) might inhibit ferritin aggregation while leaving its self-assembly capacity unaffected. Thus, this study provides a theoretical basis for the processing and use of NPLF. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV)-induced liver disease contributes to chronic hepatitis. The immune factors identified in HCV include changes in the innate and adaptive immune system. The inflammatory mediators, known as "inflammasome", are a consequence of the metabolic products of cells and commensal or pathogenic bacteria and viruses. The only effective strategy to prevent disease progression is eradication of the viral infection. Immune cells play a pivotal role during liver inflammation, triggering fibrogenesis. The present paper discusses the potential role of markers in cell death and the inflammatory cascade leading to the severity of liver damage. We aim to present the clinical parameters and laboratory data in a cohort of 88 HCV-infected non-cirrhotic and 25 HCV cirrhotic patients, to determine the characteristic light microscopic (LM) and transmission electron microscopic (TEM) changes in their liver biopsies and to present the link between the severity of liver damage and the serum levels of cytokines and caspases. A matched HCV non-infected cohort was used for the comparison of serum inflammatory markers. We compared the inflammation in HCV individuals with a control group of 280 healthy individuals. We correlated the changes in inflammatory markers in different stages of the disease and the histology. We concluded that the serum levels of cytokine, chemokine, and cleaved caspase markers reveal the inflammatory status in HCV. Based upon the information provided by the changes in biomarkers the clinician can monitor the severity of HCV-induced liver damage. New oral well-tolerated treatment regimens for chronic hepatitis C patients can achieve cure rates of over 90%. Therefore, using the noninvasive biomarkers to monitor the evolution of the liver damage is an effective personalized medicine procedure to establish the severity of liver injury and its repair.

Background: Cardiovascular dysfunction is linked to insulin-resistant states. In this paper, we analyzed whether the severe hepatic insulin resistance of an inducible liver-specific insulin receptor knockout (iLIRKO) might generate vascular insulin resistance and dysfunction, and whether insulin receptor (IR) isoforms gene therapy might revert it., Methods: We studied in vivo insulin signaling in aorta artery and heart from iLIRKO. Vascular reactivity and the mRNA levels of genes involved in vascular dysfunction were analyzed in thoracic aorta rings by qRT-PCR. Finally, iLIRKO mice were treated with hepatic-specific gene therapy to analyze vascular dysfunction improvement., Results: Our results suggest that severe hepatic insulin resistance was expanded to cardiovascular tissues. This vascular insulin resistance observed in aorta artery from iLIRKO mice correlated with a reduction in both PI3K/AKT/eNOS and p42/44 MAPK pathways, and it might be implicated in their vascular alterations characterized by endothelial dysfunction, hypercontractility and eNOS/iNOS levels' imbalance. Finally, regarding long-term hepatic expression of IR isoforms, IRA was more efficient than IRB in the improvement of vascular dysfunction observed in iLIRKO mice., Conclusion: Severe hepatic insulin resistance is sufficient to produce cardiovascular insulin resistance and dysfunction. Long-term hepatic expression of IRA restored the vascular damage observed in iLIRKO mice.

Within the European Joint Program on Human Biomonitoring HBM4EU, human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GVGenPop) or for occupationally exposed adults (HBM-GVWorker) are derived for prioritized substances including dimethylformamide (DMF). The methodology to derive these values that was agreed upon within the HBM4EU project was applied. A large database on DMF exposure from studies conducted at workplaces provided dose–response relationships between biomarker concentrations and health effects. The hepatotoxicity of DMF has been identified as having the most sensitive effect, with increased liver enzyme concentrations serving as biomarkers of the effect. Out of the available biomarkers of DMF exposure studied in this paper, the following were selected to derive HBM-GVWorker: total N-methylformamide (tNMF) (sum of N-hydroxymethyl-N-methylformamide and NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine. The proposed HBM-GVWorker is 10 mg·L−1 or 10 mg·g−1 creatinine for both biomarkers. Due to their different half-lives, tNMF (representative of the exposure of the day) and AMCC (representative of the preceding days' exposure) are complementary for the biological monitoring of workers exposed to DMF. The levels of confidence for these HBM-GVWorker are set to "high" for tNMF and "medium-low" for AMCC. Therefore, further investigations are required for the consolidation of the health-based HBM-GV for AMCC in urine. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip (OOAC) is an emerging technology based on microfluid platforms and in vitro cell culture that has a promising future in the healthcare industry. The numerous advantages of OOAC over conventional systems make it highly popular. The chip is an innovative combination of novel technologies, including lab-on-a-chip, microfluidics, biomaterials, and tissue engineering. This paper begins by analyzing the need for the development of OOAC followed by a brief introduction to the technology. Later sections discuss and review the various types of OOACs and the fabrication materials used. The implementation of artificial intelligence in the system makes it more advanced, thereby helping to provide a more accurate diagnosis as well as convenient data management. We introduce selected OOAC projects, including applications to organ/disease modelling, pharmacology, personalized medicine, and dentistry. Finally, we point out certain challenges that need to be surmounted in order to further develop and upgrade the current systems. [ABSTRACT FROM AUTHOR]

The liver is among the most frequently targeted organs by noxious chemicals of diverse nature. Liver toxicity testing using laboratory animals not only raises serious ethical questions, but is also rather poorly predictive of human safety towards chemicals. Increasing attention is, therefore, being paid to the development of non-animal and human-based testing schemes, which rely to a great extent on in vitro methodology. The present paper proposes a rationalized tiered in vitro testing strategy to detect liver toxicity triggered by chemicals, in which the first tier is focused on assessing general cytotoxicity, while the second tier is aimed at identifying liver-specific toxicity as such. A state-of-the-art overview is provided of the most commonly used in vitro assays that can be used in both tiers. Advantages and disadvantages of each assay as well as overall practical considerations are discussed.

The hepatotoxic potential of drugs is one of the main reasons why a number of drugs never reach the market or have to be withdrawn from the market. Therefore, the evaluation of the hepatotoxic potential of drugs is an important part of the drug development process. The aim of this work was to evaluate the relative abilities of different supervised self-organizing algorithms in classifying the hepatotoxic potential of drugs. Two modifications of standard counter-propagation training algorithms were proposed to achieve good separation of clusters on the self-organizing map. A series of optimizations were performed using genetic algorithm to select models developed with counter-propagation neural networks, X-Y fused networks, and the two newly proposed algorithms. The cluster separations achieved by the different algorithms were evaluated using a simple measure presented in this paper. Both proposed algorithms showed a better formation of clusters compared to the standard counter-propagation algorithm. The X-Y fused neural network confirmed its high ability to form well-separated clusters. Nevertheless, one of the proposed algorithms came close to its clustering results, which also resulted in a similar number of selected models.

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular-pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice. In a preliminary MCLR dose-response study of 3 to 9 mg/kg doses, ≥5 mg/kg induced clinical changes, increased serum levels of ALT, AST, and GLDH, liver congestion, increased liver/body weight ratios, and reduced serum glucose and total protein. Based on the extent of these effects, the 10 congeners were administered as single 7 mg/kg oral doses and toxicity evaluated. The greatest toxicity was observed with MCLA and MCLR including a high percentage of moribundity. In addition to eliciting effects similar to those listed above for MCLR, MCLA also induced serum alterations indicative of jaundice. MCLY, and MCYR induced changes like those noted with MCLR, but to lesser extents. MCLW and MCLF exhibited some serum and morphological changes associated with hepatic toxicity, while there were few indications of toxicity after exposures to MCRR, [Asp 3 ]MCRR, [Asp 3 ,Dhb 7 ]MCRR, or MCWR. These data illustrate a wide spectrum of hepatic effects and different potencies of these MC congeners.