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Purpose R2* (1/T2*) and single echo R2 (1/T2) have been calibrated to liver iron concentration (LIC) in patients with thalassemia and transfusion-dependent sickle cell disease at 1.5T. The R2*-LIC relationship is linear, whereas that of R2 is curvilinear. However, the increasing popularity of high-field scanners requires generalizing these relationships to higher field strengths. In this study, we tested the hypothesis that numerical simulation can accurately determine the field dependence of iron-mediated transverse relaxation rates. Methods We previously replicated the calibration curves between R2 and R2* and iron at 1.5T using Monte Carlo models incorporating realistic liver structure, iron deposit susceptibility, and proton mobility. In this paper, we extend our model to predict relaxivity-iron calibrations at higher field strengths. Predictions were validated by measuring R2 and R2* at 1.5T and 3T in six β-thalassemia major patients. Results Predicted R2* increased twofold at 3T from 1.5T, whereas R2 increased by a factor of 1.47. Patient data exhibited a coefficient of variation of 3.6% and 7.2%, respectively, to the best-fit simulated data. Simulations over the range 0.25T-7T showed R2* increasing linearly with field strength, whereas R2 exhibited a concave-downward relationship. Conclusion A model-based approach predicts alterations in relaxivity-iron calibrations with field strength without repeating imaging studies. The model may generalize to alternative pulse sequences and tissue iron distribution. Magn Reson Med 74:879-883, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: Four-dimensional magnetic resonance imaging (4DMRI) is an emerging technique in radiotherapy treatment planning for organ motion quantification. In this paper, the authors present a novel 4DMRI retrospective image-based sorting method, providing reduced motion artifacts than using a standard monodimensional external respiratory surrogate. Methods: Serial interleaved 2D multislice MRI data were acquired from 24 liver cases (6 volunteers + 18 patients) to test the proposed 4DMRI sorting. Image similarity based on mutual information was applied to automatically identify a stable reference phase and sort the image sequence retrospectively, without the use of additional image or surrogate data to describe breathing motion. Results: The image-based 4DMRI provided a smoother liver profile than that obtained from standard resorting based on an external surrogate. Reduced motion artifacts were observed in image-based 4DMRI datasets with a fitting error of the liver profile measuring 1.2±0.9 mm (median ± interquartile range) vs 2.1±1.7 mm of the standard method. Conclusions: The authors present a novel methodology to derive a patient-specific 4DMRI model to describe organ motion due to breathing, with improved image quality in 4D reconstruction. [ABSTRACT FROM AUTHOR]

Purpose: Apparent diffusion coefficient (ADC), derived from diffusion-weighted magnetic resonance images (DW-MRI), measures the motion of water molecules in vivo and can be used to quantify tumor response to therapy. The accurate measurement of ADC can be adversely affected by organ motion and imaging artifacts. In this paper, the authors' goal was to develop an automated method for reducing artifacts and thereby improve the accuracy of ADC measurements in moving organs such as liver. Methods: The authors developed a novel method of computing ADC with fewer artifacts, through simultaneous image segmentation and iterative registration (SSIR) of multiple b-value DW-MRI. The authors' approach reduces artifacts by automatically finding the best possible alignment between the individual b-value images and a reference DW image using a sequence of transformations. It selects such a sequence by an iterative choice of b-value DW images based on the accuracy of their alignment with the reference DW image. The authors' approach quantifies the accuracy of alignment between a pair of images using modified Hausdroff distance computed between the structures of interest. The structures of interest are identified by a user through strokes drawn in one or more slices in the reference DW image, which are then volumetrically segmented using GrowCut. The same structures are segmented in the remaining b-value images by transforming the user-drawn strokes through registration. The ADC values are computed from all the aligned b-value images. The images are aligned by using affine registration followed by deformable B-spline registration with cubic B-spline resampling. Results: The authors compared the results of ADC computed using their approach with ADC computed (a) without registration and (b) with basic affine registration of all b-value images to a chosen reference. The authors' approach was the most effective in reducing artifacts compared to the other two methods. It resulted in a mean artifact ratio (fraction of voxels in a structure with negative ADC over total number of voxels in the structure) of 2.7% versus 5.4% for affine registration and 32% for no registration for >200 tumors. The authors' approach also resulted in the lowest median standard deviation in the computed mean ADC for all tumors [0.05,0.09,0.07,0.58] compared to those from affine image registration [0.02, 0.14, 0.58, 0.79] and no image registration [0.64, 0.83, 0.83, 1.09] on tests where random displacement [8,10,12,16] pixels were introduced in multiple trials in the b-value images. Conclusions: The authors developed a novel approach for reducing artifacts in ADC maps through simultaneous registration and segmentation of multiple b-value DW images. The authors' method explicitly employs a registration quality metric to align images. When compared to basic affine and no image registrations, the authors' approach produces registrations of greater accuracy with lowest artifact ratio and median standard deviation of the computed mean ADC values for a wide range of displacements. [ABSTRACT FROM AUTHOR]

Withdrawal: Benhong Zhou, Liver impairment associated with disease progression in COVID‐19 patients, Accepted Articles, (https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.14481). The above article, published online on 15 April 2020 in Wiley Online Library (wileyonlinelibrary.com) as an Accepted Article, has been withdrawn by agreement between the authors, the journal Editor in Chief, and John Wiley & Sons Ltd. The article has been withdrawn at the authors' request because, on reflection, the authors decided that the opinions expressed in the paper were incomplete and not ready for publication. [ABSTRACT FROM AUTHOR]

A 46-year-old gentleman presented to the emergency department with a 3-day history of severe abdominal pain, progressive abdominal distention, vomiting, and fever. After adequate resuscitation, abdominal erect x-ray identified pneumoperitoneum and abdominal supine x-ray identified air (pneumo) tracking along the Arantius ligament (ligamentum venosum) (Fig. Endoscopic and clinical features of gastric ulcers in Japanese patients with or without Helicobacter pylori infection who were using NSAIDs or low-dose aspirin. [Extracted from the article]

Summary: Background: Epidemiological data suggest that coffee has a dose‐dependent protective effect on liver‐related mortality. Aim: To estimate the potential impact of increased per capita coffee consumption on global liver‐related mortality. Methods: Using the Global Burden of Disease 2016 dataset (adults > 15 years), we modelled the impact of increased per capita coffee consumption on liver‐related mortality in 2016 for 194 countries using published risk ratios for >2 cups coffee/ day (RR 0.54, 95% CI 0.42‐0.69) and ≥4 cups/ day (RR 0.29, 95% CI 0.17‐0.50), adjusted for confounders and tested model assumptions using sensitivity analyses. Results: Worldwide, there were an estimated 1,240,201 (95% CI 118 4300‐1 354 410) adult liver‐related deaths in 2016. Median global liver mortality rate in 2016 was 15 deaths/ 100 000 population/ year (all ages, both genders; IQR 11‐21 deaths per 100 000). If all countries with per capita coffee intake ≤2 cups/ day increased to >2 cups/ day, the predicted total number of liver‐related deaths would have been 630 947 in 2016 (95% CI 629 693‐631 861) with 452 861 (95% CI 451 948‐454 116) deaths averted (PPR 7.8 liver‐related deaths/ 100 000/ year). If per capita consumption was ≥ 4 cups/ day, the predicted number of liver‐related deaths in 2016 would have been 360 523 (95% CI 359 825‐361 992) with 723 287 (95% CI 721 817‐723 984) deaths averted (PPR 12.1 liver‐related deaths/100 000/year). Conclusion: Increasing per capita coffee consumption to > 2 cups per day on a population level has the potential to avert hundreds of thousands of liver‐related deaths annually if the impact of coffee on liver‐related mortality is confirmed in clinical trials. [ABSTRACT FROM AUTHOR]

Glycogen shortage during fasting coincides with dramatic changes in hepatic adenine nucleotide levels. The aim of this work was to study the relevance of liver glycogen in the regulation of the hepatic energy state during food deprivation. To this end, we examined the response of mice with sustained increased liver glycogen content to prolonged fasting. In order to increase hepatic glycogen content, we generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTGOE mice). Control and PTGOE mice were fed ad libitum or fasted for 36 h. Upon fasting, PTGOE mice retained significant hepatic glycogen stores and maintained hepatic energy status. Furthermore, we show that liver glycogen controls insulin sensitivity, gluconeogenesis, lipid metabolism, and ketogenesis upon nutrient deprivation. [ABSTRACT FROM AUTHOR]

Deregulation of microRNAs expression is symptomatic of cancer disease and occurs before the awareness of cancer signs. Early detection of cancer disease can improve or drop the disease entirely. DNA computing is an emerging field of detecting microRNAs based on toehold‐mediated strand displacement reactions, which is a more efficient method than the commonly used method like real‐time PCR. Accuracy and cost of diagnostic applications are essential criteria that are achieved by using the DNA logic gates based on the DNA computing method. In this study, the authors proposed the multi‐input liver cancer biosensor with the RNA secondary structure motifs as the computational module and two approaches are suggested. [ABSTRACT FROM AUTHOR]

Although epidural analgesia is routinely used in many institutions for patients undergoing hepatic resection, there are unresolved issues regarding its safety and efficacy in this setting. We performed a review of papers published in the area of anaesthesia and analgesia for liver resection surgery and selected four areas of current controversy for the focus of this review: the safety of epidural catheters with respect to postoperative coagulopathy, a common feature of this type of surgery; analgesic efficacy; associated peri-operative fluid administration; and the role of epidural analgesia in enhanced recovery protocols. In all four areas, issues are raised that question whether epidural anaesthesia is always the best choice for these patients. Unfortunately, the evidence available is insufficient to provide definitive answers, and it is clear that there are a number of areas of controversy that would benefit from high-quality clinical trials., (Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.)

Liver viability using normothermic regional perfusion in uncontrolled donation after circulatory death deserves a multi-parametric assessment In this regard, the 20-min no-touch period enforced in Italy has spurred national transplant centers to implement NRP followed by ex-situ perfusion of DCD liver grafts. On a different note, AST and ALT have failed to predict clinical outcome in LT as previously described in ex-situ MP trials,6,7 since their levels may be influenced by donor age, liver steatosis, and ischemia time among others. [Extracted from the article]

Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for experimental induction of hepatic fibrosis. Thus, the objective of the present study was to elucidate the possible protective effects of lactéol® forte (LF) and quercetin dihydrate (QD) against TAA‐induced hepatic damage in male albino rats. Induction of hepatotoxicity was performed by TAA injection (200 mg/kg I/P, twice/ week) in rats. LF (1 × 109 CFU/rat 5 times/week) and QD (50 mg/kg 5 times/week) treated groups were administered concurrently with TAA injection (200 mg/kg I/P, twice/ week). The experimental treatments were conducted for 12 weeks. Hepatotoxicity was evaluated biochemically by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma‐glutamyl transferase (GGT) in the serum and histopathologically with the scoring of histopathological changes besides histochemical assessment of collagen by Masson's trichrome and immunohistochemical analysis for α‐smooth muscle actin (α‐SMA), Ki67 and caspase‐3 expression in liver sections. Our results indicated that LF and QD attenuated some biochemical changes and histochemical markers in TAA‐mediated hepatotoxicity in rats by amelioration of biochemical markers and collagen, α‐SMA, Ki67 and caspase3 Immunoexpression. Additionally, LF and QD supplementation downregulated the proliferative, necrotic, fibroblastic changes, eosinophilic intranuclear inclusions, hyaline globules and Mallory‐like bodies that were detected histopathologically in the TAA group. In conclusion, LF showed better hepatic protection than QD against TAA‐induced hepatotoxicity in rats by inhibiting inflammatory reactions with the improvement of some serum hepatic transaminases, histopathological picture and immunohistochemical markers. [ABSTRACT FROM AUTHOR]

Introduction. To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods. Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results. After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion. Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: This study identifies key characteristics to help build a physical liver computed tomography (CT) phantom for radiomics harmonization; particularly, the higher‐order texture metrics. Materials and methods: CT scans of a radiomics phantom comprising of 18 novel 3D printed inserts with varying size, shape, and material combinations were acquired on a 64‐slice CT scanner (Brilliance 64, Philips Healthcare). The images were acquired at 120 kV, 250 mAs, CTDIvol of 16.36 mGy, 2 mm slice thickness, and iterative noise‐reduction reconstruction (iDose, Philips Healthcare, Andover, MA). Radiomics analysis was performed using the Cancer Imaging Phenomics Toolkit (CaPTk), following automated segmentation of 3D regions of interest (ROI) of the 18 inserts. The findings were compared to three additional ROI obtained of an anthropomorphic liver phantom, a patient liver CT scan, and a water phantom, at comparable imaging settings. Percentage difference in radiomic metrics values between phantom and tissue was used to assess the biological equivalency and <10% was used to claim equivalent. Results: The HU for all 18 ROI from the phantom ranged from −30 to 120 which is within clinically observed HU range of the liver, showing that our phantom material (T3‐6B) is representative of biological CT tissue densities (liver) with >50% radiomic features having <10% difference from liver tissue. Based on the assessment of the Neighborhood Gray Tone Difference Matrix (NGTDM) metrics it is evident that the water phantom ROI show extreme values compared to the ROIs from the phantom. This result may further reinforce the difference between a structureless quantity such as water HU values and tissue HU values found in liver. Conclusion: The 3‐D printed patterns of the constructed radiomics phantom cover a wide span of liver tissue textures seen in CT images. Using our results, texture metrics can be selectively harmonized to establish clinically relevant and reliable radiomics panels. [ABSTRACT FROM AUTHOR]

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long‐term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B‐Se) and urine selenium (U‐Se) levels were detected in these areas, measuring 416.977 μg/L and 352.690 μg/L and 104.527 μg/L and 51.820 μg/L, respectively. Additionally, the median blood Cd (B‐Cd) and urine Cd (U‐Cd) levels were markedly elevated at 4.821 μg/L and 3.848 μg/L and at 7.750 μg/L and 7.050 μg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 μmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 μmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent. Plain Language Summary: Se is an essential trace element for humans. However, excessive intake of Se can harm humans. Cd is a carcinogen and a chronic potent nephrotoxin that mostly accumulates in the human liver and kidneys. Animal experiments suggest that Se may alleviate Cd toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale exposure have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. Our results suggested that the exposed black shale areas are simultaneously enriched with Se and Cd. However, residents in these areas were exposed to excessive Se and Cd long‐term without significant damage to liver and kidney functions. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. The risk assessment of heavy metals in high‐Se geological background areas cannot be separated from human health surveys. Our study provides evidence for the antagonistic effects of Se and Cd on the human body. Key Points: Residents in exposed black shale areas consume excessive Se and Cd through local riceHuman liver and kidney functions are not significantly damaged in exposed black shale areasThe USEPA method may not accurately assess Cd risk in exposed black shale areas [ABSTRACT FROM AUTHOR]

Cancer cachexia is a complex, multifaceted condition that negatively impacts the health, treatment efficacy, and economic status of cancer patients. The management of cancer cachexia is an essential clinical need. Cancer cachexia is currently defined mainly according to the severity of weight loss and sarcopenia (i.e., macrosymptoms). However, such macrosymptoms may be insufficient to give clinicians clues on how to manage this condition as these symptoms appear at the late stage of cancer. We need to understand earlier events during the progression of cancer cachexia so as not to miss a clinical opportunity to control this complex syndrome. Recent research indicates that cancer‐induced changes in the host are much wider than previously recognized, including disruption of liver function and the immune system. Furthermore, such changes are observed before the occurrence of visible distant metastases (i.e., in early, localized cancers). In light of these findings, we propose to expand the definition of cancer cachexia to include all cancer‐induced changes to host physiology, including changes caused by early, localized cancers. This new definition of cancer cachexia can provide a new perspective on this topic, which can stimulate the research and development of novel cancer cachexia therapies. [ABSTRACT FROM AUTHOR]

The dietary protein levels and source of starch are factors in the economical production of feeds, which may change the physical quality of extruded pellets and the growth performance of fish. Eight feeds contained two protein levels and four levels of wheat flour substitutions by corn, as a 2 × 4 factorial experimental design, were produced by a twin‐screw extruder machine and fed to 800 rainbow trout. The results showed corn grain reduced expansion ratio, water stability at 120 and 260 min, starch gelatinization (SG), and apparent degradability, while bulk density (BD) and oil leakage of feed pellets increased. The high protein diets displayed the most BD, lower oil leakage, SG, and elastic modulus. The high protein feeds improved the final body weight, weight gain, specific growth rate, and feed conversion ratio (FCR) of fish. The corn grain reduced the FCR and promoted the trout's protein efficiency ratio. Lipid proportions of fish livers corresponded to hepatosomatic index and serum concentrations of aspartate aminotransferase and alanine aminotransferase. In general, corn, as the starch source in the high and low‐protein extruded feeds, can be replaced at levels of 33%–66% of wheat flour without adverse effects on the physical characteristics of feed pellets and the growth performance of rainbow trout. [ABSTRACT FROM AUTHOR]

Primary liver cancer is the sixth most common cancer and the third leading cause of cancer‐related death worldwide. The role of the 'Other' subfamily of HECT E3 ligases (E3s) in hepatocellular carcinoma (HCC) remains unknown. The expression of the 'Other' HECT E3s was performed using The Cancer Genome Atlas (TCGA) data, and the authors found that the 'Other' HECT E3s were differentially expressed in HCC. Prognostic values were assessed using the Kaplan–Meier method and indicated that the high expressions of HECTD2, HECTD3, and HACE1 were associated with a worse clinical prognosis of HCC patients. The expression of HECTD2 was significantly correlated with the infiltration of CD4+T cells and neutrophils. The levels of HECTD3 and HACE1 were notably related to the dendritic cells and memory B cells infiltrated in HCC. In addition, the three previously mentioned genes have shown to be associated with immune checkpoint genes, such as FOXP3, CCR8, STAT5B, TGFB1 and TIM‐3. Moreover, HECTD2 could promote the proliferative activity, cell migration and invasive ability of HCC cells. Collectively, the authors' study demonstrated that HECTD2 was a novel immune‐related prognostic biomarker for HCC, providing new insight into the treatment and prognosis of HCC. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have been involved in metabolic syndrome, although their specific role in the development of the pathology is still unknown. To further study the role of EVs, we have analysed by Raman tweezers microspectroscopy and mass spectrometry‐based lipidomics the small EVs population secreted by fatty (ZF) and lean (ZL) hepatocytes obtained from Zucker rats. We have also explored in vivo and ex vivo biodistribution of these EVs through fluorine‐18‐radiolabelling using a positron emission tomography imaging. Based on the proportion of proteins to lipids and the types of lipids, our results indicate that within the range of small EVs, primary hepatocytes secrete different subpopulations of particles. These differences were observed in the enrichment of triglyceride species in EVs secreted by ZF hepatocytes. Biodistribution experiments showed accumulation in the brain, heart, lungs, kidney and specially in bladder after intravenous administration. In summary, we show that EVs released by a fatty hepatocytes carry a different lipid signature compared to their lean counterpart. Biodistribution experiment has shown no difference in the distribution of EVs secreted by ZF and ZL hepatocytes but has given us a first view of possible target organs for these particles. Our results might open a door to both pathology studies and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: To assess the feasibility of using the diaphragm as a surrogate for liver targets during MDTT. Methods: Diaphragm as surrogate for markers: a dome‐shaped phantom with implanted markers was fabricated and underwent dual‐orthogonal fluoroscopy sequences on the Vero4DRT linac. Ten patients participated in an IRB‐approved, feasibility study to assess the MDTT workflow. All images were analyzed using an in‐house program to back‐project the diaphragm/markers position to the isocenter plane. ExacTrac imager log files were analyzed. Diaphragm as tracking structure for MDTT: The phantom "diaphragm" was contoured as a markerless tracking structure (MTS) and exported to Vero4DRT/ExacTrac. A single field plan was delivered to the phantom film plane under static and MDTT conditions. In the patient study, the diaphragm tracking structure was contoured on CT breath‐hold‐exhale datasets. The MDTT workflow was applied until just prior to MV beam‐on. Results: Diaphragm as surrogate for markers: phantom data confirmed the in‐house 3D back‐projection program was functioning as intended. In patients, the diaphragm/marker relative positions had a mean ± RMS difference of 0.70 ± 0.89, 1.08 ± 1.26, and 0.96 ± 1.06 mm in ML, SI, and AP directions. Diaphragm as tracking structure for MDTT: Building a respiratory‐correlation model using the diaphragm as surrogate for the implanted markers was successful in phantom/patients. During the tracking verification imaging step, the phantom mean ± SD difference between the image‐detected and predicted "diaphragm" position was 0.52 ± 0.18 mm. The 2D film gamma (2%/2 mm) comparison (static to MDTT deliveries) was 98.2%. In patients, the mean difference between the image‐detected and predicted diaphragm position was 2.02 ± 0.92 mm. The planning target margin contribution from MDTT diaphragm tracking is 2.2, 5.0, and 4.7 mm in the ML, SI, and AP directions. Conclusion: In phantom/patients, the diaphragm motion correlated well with markers' motion and could be used as a surrogate. MDTT workflows using the diaphragm as the MTS is feasible using the Vero4DRT linac and could replace the need for implanted markers for liver radiotherapy. [ABSTRACT FROM AUTHOR]

This paper, the second in the series, will build on the first and explore the importance of liver and pancreatic manifestations of cystic fibrosis ( CF) and the effect on morbidity and mortality of this multifaceted genetic condition. It will also further develop the critical role of the gastroenterologist as part of the multidisciplinary group of clinicians and allied health staff in the effective management of patients with CF. [ABSTRACT FROM AUTHOR]

Enzyme kinetics studies reported in the literature showed that human liver Cathepsin L is active only at lysosomal acidic pH values, while biochemical studies in living cells showed that the enzyme works even at neutral pH values (in a condition compatible with the extracellular compartment). Such an apparent ambiguity highlighted the need of analysing in depth the kinetics of ~29-kDa Cathepsin L, which is the form commonly used in experiments. The stability and catalytic activity of this enzyme were investigated at different pH values, reducing and non-reducing environments, presence of copper, iron and zinc ions, and presence of the natural modulator/inhibitor cystatin B. Our experiments showed that ~29-kDa human liver Cathepsin L is stable and catalytically functional even at neutral pH values and under non-reducing conditions, which simulate the extracellular compartment. Under these conditions, Cathepsin L was also proved to interact with cystatin B, being also modulated by physiological concentrations of Cu++, Fe++ and Zn++. This paper suppose an advance in the comprehension of the catalytic properties of human liver Cathepsin L, its implications in different physiological processes and its potential use within a drug screening programme in which agents acting extracellularly are being considered. [ABSTRACT FROM AUTHOR]

Introduction Liver transplant candidates are vulnerable to develop depression. This paper aims to ascertain the prevalence of depression in liver transplant candidates and its psychosocial factors in a systematic review. Methods An extensive review via electronic databases (PubMed, EMBASE, CINAHL) and hand search were carried out to retrieve published articles up to December 15, 2013, using (Incidence OR Prevalence) AND Depress* AND liver transplant as the keywords. Information on the study design, patient characteristics, prevalence of depression, and its associated risk factors were extracted from included studies. Results There were 22 studies included in this review with a total of 3055 patients. The prevalence of depression in the liver transplant candidates ranges between 2% and 80%. Studies that used diagnostic tools found a narrower range of prevalence (4.5-43%) as compared to the self-administered questionnaires (2-80%). Studies that used Beck Depression Inventory reported a higher prevalence than those studies which used Hospital Anxiety and Depression Scale (median = 28%, range = 2-80% versus median 17%, range 6.1-25.8%). A number of socio-demographic factors, illness-related and psychosocial factors were found to be associated with depression. Conclusion Prevalence of depression in liver transplant candidates is high, and early detection will improve survival and quality of life. [ABSTRACT FROM AUTHOR]

Objective Previous Australian studies have suggested poorer survival of patients with colorectal cancer in remote areas. To date no studies have assessed the geographic disparity in patients with metastatic disease. This retrospective cohort study looks at geographic differences in the surgical care and survival of patients with metastatic colorectal disease. The paper utilises data from the South Australian Clinical Registry for Metastatic Colorectal Cancer ( SACRMCC). Design, participants, interventions and main outcome measures Data on patients' socio-economic status, primary and metastatic tumour characteristics, treatment and survival was extracted from the SACRMCC database. A binomial model analysis was used to identify geographical differences in the surgical treatment of patients and a Cox proportional hazards model was used to identify any geographic differences in survival. Results The findings showed no differences in the diagnosis of liver metastases or provision of liver surgery between geographic areas, however there was a reduced likelihood of liver surgery with increasing age. The median overall survival rate, from the date of diagnosis of metastatic disease, was 20.0 months and the distribution by geographic remoteness was 19.1 months, 20.2 months, 22.0 months and 20.4 months in Major Cities, Inner Regional, Outer Regional and Remote areas respectively. This was not statistically significant. Conclusion Overall, there was no evidence of a geographical disparity in the diagnosis, surgical treatment or survival in metastatic colorectal cancer. This may be due to the shift toward centralising surgical care in South Australia. Nevertheless, there remains a need to improve the uptake of surgical care in the growing elderly population. [ABSTRACT FROM AUTHOR]

Purpose: The level-set method is known to require long computation time for 3D image segmentation, which limits its usage in clinical workflow. The goal of this study was to develop a fast level-set algorithm based on the coherent propagation method and explore its character using clinical datasets. Methods: The coherent propagation algorithm allows level set functions to converge faster by forcing the contour to move monotonically according to a predicted developing trend. Repeated temporary backwards propagation, caused by noise or numerical errors, is then avoided. It also makes it possible to detect local convergence, so that the parts of the boundary that have reached their final position can be excluded in subsequent iterations, thus reducing computation time. To compensate for the overshoot error, forward and backward coherent propagation is repeated periodically. This can result in fluctuations of great magnitude in parts of the contour. In this paper, a new gradual convergence scheme using a damping factor is proposed to address this problem. The new algorithm is also generalized to non-narrow band cases. Finally, the coherent propagation approach is combined with a new distance-regularized level set, which eliminates the needs of reinitialization of the distance. Results: Compared with the sparse field method implemented in the widely available ITKSnap software, the proposed algorithm is about 10 times faster when used for brain segmentation and about 100 times faster for aorta segmentation. Using a multiresolution approach, the new method achieved 50 times speed-up in liver segmentation. The Dice coefficient between the proposed method and the sparse field method is above 99% in most cases. Conclusions: A generalized coherent propagation algorithm for level set evolution yielded substantial improvement in processing time with both synthetic datasets and medical images. [ABSTRACT FROM AUTHOR]

Purpose: Pulsed RF (PRF) is a nonablative technique for treating neuropathic pain. Bipolar PRF application is currently aimed at creating a "strip lesion" to connect the electrode tips; however, the electrical and thermal performance during bipolar PRF is currently unknown. The objective of this paper was to study the temperature and electric field distributions during bipolar PRF. Methods: The authors developed computer models to study temperature and electric field distributions during bipolar PRF and to assess the possible ablative thermal effect caused by the accumulated temperature spikes, along with any possible electroporation effects caused by the electrical field. The authors also modeled the bipolar ablative mode, known as bipolar Continuous Radiofrequency (CRF), in order to compare both techniques. Results: There were important differences between CRF and PRF in terms of electrical and thermal performance. In bipolar CRF: (1) the initial temperature of the tissue impacts on temperature progress and hence on the thermal lesion dimension; and (2) at 37℃, 6-min of bipolar CRF creates a strip thermal lesion between the electrodes when these are separated by a distance of up to 20 mm. In bipolar PRF: (1) an interelectrode distance shorter than 5 mm produces thermal damage (i.e., ablative effect) in the intervening tissue after 6 min of bipolar RF; and (2) the possible electroporation effect (electric fields higher than 150 kV m-1) would be exclusively circumscribed to a very small zone of tissue around the electrode tip. Conclusions: The results suggest that (1) the clinical parameters considered to be suitable for bipolar CRF should not necessarily be considered valid for bipolar PRF, and vice versa; and (2) the ablative effect of the CRF mode is mainly due to its much greater level of delivered energy than is the case in PRF, and therefore at same applied energy levels, CRF, and PRF are expected to result in same outcomes in terms of thermal damage zone dimension. [ABSTRACT FROM AUTHOR]

In recent years, there has been an active movement to ensure the greater safety of actual surgeries, by simulating it preoperatively with the use of three‐dimensional image visualization technologies. Along with this movement, the Ministry of Health, Labour and Welfare has named “Image‐supported navigation in hepatectomy” as part of advanced medical techniques. This method aims to improve the safety during a surgery by calculating the volume of the liver dominated by each blood vessel or simulating, prior to surgery, the volume of resection zone or the remaining liver volume. These calculations and simulations are carried out using the three‐dimensional images produced by extractions of the liver, vascular and tumor regions from the computed tomography images, which were collected using the tomography apparatus prior to hepatectomy. In order to facilitate the achievement of such preoperative simulations, the volume analyzer SYNAPSE VINCENT (VINCENT, hereafter) by Fujifilm, in its Liver Analysis Application, comes equipped with unique features. This paper will introduce the technologies behind those unique features and provide a direction for future research and developments. [ABSTRACT FROM AUTHOR]

Purpose: In multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), liver segmentation is an important preprocessing step for the computer-aided evaluation of liver disease. However, because of the liver's irregular shape, proximity to surrounding organs, and large intensity variation, and peripheral contrast enhancement in the kidney, liver segmentation has been very challenging. This paper presents a novel hybrid active contour model and overall procedures that are specific to liver segmentation. Methods: The authors introduced an edge-function-scaled (weighted) region-based active contour model (ESRAC) and utilization of registered, multiphase sequences to address leakage-to-kidney and oversegmentation problems. The model incorporated weighted regional information with a compactly supported edge map, computed from a combination of images obtained during arterial and delayed phases, and it was coupled with a geodesic edge term. To cope with signal-inhomogeneity on MRI, all of the axial slices were partitioned into eight sectors with an angular span of 45°, centered on the inferior vena cava, each in the superior and inferior regions and the regional information regarding ESRAC was computed for each partition, henceforth the so-called partitioned ESRAC (p-ESRAC). Initialization of the active contour was performed by thresholding with a range of [200, +8) and simple morphological operation during the delayed phase. At the end, to fill the holes in the segmented images caused by high gradients around the vasculature, noise, or outstanding texture features, iterative morphological operations were performed until convergence. The authors compared the segmentation accuracy of p-ESRAC to that with geodesic active contour, region-based active contour, geodesic active region, and localized region-based active contour using quantitative and visual assessments. Results: In three-dimensional experimental studies conducted on 30 subjects (14 normal or benign cases and 16 malignant cases), compared with other active contours, p-ESRAC achieved the highest dice similarity coefficients of 93.9 ± 1.6% (normal) and 91.6 ± 2.2% (malignant), respectively. In addition, p-ESRAC resulted in the lowest false positive rates of 4.5 ± 3.2% (normal) and 7.9 ± 3.0% (malignant), demonstrating it to be the most effective in reducing oversegmentation. The partition scheme improved segmentation accuracy by 5.4 ± 9.2% (normal) and 22.2 ± 27.6% (malignant) of the true segmentation that was missed by ESRAC. Visual assessment confirmed that p-ESRAC prevented leakage of the segmentation results of the liver into the kidney. Conclusions: A novel active-contour model was developed, allowing for accurate liver segmentation on multiphase CE-MRI, with conditions that include signal inhomogeneity and weak boundary conditions. Such a technique could be useful for applications that involve computeraided diagnosis of liver disease. [ABSTRACT FROM AUTHOR]

We have been interested in the metabolic effects of ingested fuels, both in normal subjects and in people with type 2 diabetes. Recently, we have become interested in the regulation of glucose production and the regulation of gluconeogenesis in particular. We are not aware of a recent comprehensive review of these topics. Therefore, we have reviewed the currently available literature. The pertinent papers obtained from a Medline search of the words gluconeogenesis, glycogenolysis, hepatic glucose output, as well as papers from our personal files, form the basis of this review. In order to analyse the data, it also was necessary to review the relevant methodology used in determining gluconeogenesis. Pathway diagrams have been included with this review in order to illustrate and highlight key aspects of the methodologies. Current data support the hypothesis that the rate of glucose appearance changes but the rate of gluconeogenesis remains remarkably stable in widely varying metabolic conditions in people without diabetes. In people with diabetes, whether gluconeogenesis remains unchanged is at present uncertain. Available data are very limited. The mechanism by which gluconeogenesis remains relatively constant, even in the setting of excess substrates, is not known. One interesting speculation is that gluconeogenic substrates substitute for each other depending on availability. Thus, the overall rate is either unaffected or only modestly changed. This requires further confirmation.

1. Hepatic resection with concomitant periods of ischaemia and reperfusion (I/R) is required to perform reduced-size liver (RSL) transplantation procedures, such as living donor or split liver transplantation. Although a great deal of progress has been made using these types of surgical procedures, a significant number of patients develop tissue injury from these procedures, ultimately resulting in graft failure. 2. Because of this, there is a real need to understand the different mechanisms responsible for the tissue injury induced by I/R of RSL transplantation (RSL + I/R), with the ultimate goal to develop new and improved therapeutic agents that may limit the tissue damage incurred during RSL transplantation. 3. The present paper reviews the recent studies that have been performed examining the role of reactive metabolites of oxygen and nitrogen in a mouse model of RSL + I/R. In addition, we present data demonstrating how the pathophysiological mechanisms identified in this model compare with those observed in a model of RSL transplantation in rats.

Unlabelled: The safety of paracetamol when given in the recommended dosage is well documented. However, in recent years there have been many reports of liver failure associated with repeated exposure to supratherapeutic doses of paracetamol. This paper reviews the literature on chronic supratherapeutic paracetamol exposure in children and the different dosing guidelines. Based on which, we suggest the following approach: liver injury secondary to repeated dosing of paracetamol should be considered when a child has received more than 75 mg/kg/d for at least 2 d, or if risk factors for paracetamol toxicity have been identified. Liver transaminases, coagulation factors, and paracetamol serum concentrations should be measured in these children and in symptomatic children with vomiting, right upper quadrant abdominal pain, and jaundice who have taken paracetamol. Treatment with N-acetyl cysteine should be started regardless of paracetamol concentrations if transaminases or INR are elevated., Conclusion: Liver injury secondary to repeated dosing of paracetamol is rare but may result in severe morbidity and mortality. The cumulative dose of paracetamol should not exceed 75 mg/kg/d. Children treated with higher doses for more than 2 d should be evaluated for possible liver injury and treated with N-acetyl cysteine if evidence of liver injury is found.

LINKED CONTENT This article is linked to Viuff et al paper. To view this article, visit https://doi.org/10.1111/apt.16277 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Chon et al paper. To view this article, visit https://doi.org/10.1111/apt.16267 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Ponziani et al paper. To view this article, visit https://doi.org/10.1111/apt.15996 [ABSTRACT FROM AUTHOR]

Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis in China. This paper reports the protective action of bicyclol against experimental liver injury in mice and its mechanism of action. Oral administration of bicyclol markedly reduced the elevated serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal lipids and proteins in vitro, and decreased the level of the trichloromethyl free radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver microsomes. On the other hand, bicyclol neither directly inhibited the activity of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These results suggest that bicyclol has remarkable hepatoprotective effects and its mechanism of action may be related to a decrease in free radical-induced damage to hepatocytes.

Purpose: Two-dimensional ultrasound (2D US) imaging is commonly used for diagnostic and intraoperative guidance of interventional liver procedures; however, 2D US lacks volumetric information that may benefit interventional procedures. Over the past decade, three-dimensional ultrasound (3D US) has been developed to provide the missing spatial information. 3D US image acquisition is mainly based on mechanical, electromagnetic, and freehand tracking of conventional 2D US transducers, or 2D array transducers available on high-end machines. These approaches share many problems during clinical use for interventional liver imaging due to lack of flexibility and compatibility with interventional equipment, limited field-of-view (FOV), and significant capital cost compared to the benefits they introduce. In this paper, a novel system for mechanical 3D US scanning is introduced to address these issues. Methods: The authors have developed a handheld mechanical 3D US system that incorporates mechanical translation and tilt sector sweeping of any standard 2D US transducer to acquire 3D images. Each mechanical scanning function can be operated independently or may be combined to allow for a hybrid wide FOV acquisition. The hybrid motion mode facilitates registration of other modalities (e.g., CT or MRI) to the intraoperative 3D US images by providing a larger FOV in which to acquire anatomical information. The tilting mechanism of the developed mover allows image acquisition in the intercostal rib space to avoid acoustic shadowing from bone. The geometric and volumetric scanning validity of the 3D US system was evaluated on tissue mimicking US phantoms for different modes of operation. Identical experiments were performed on a commercially available 3D US system for direct comparison. To replicate a clinical scenario, the authors evaluated their 3D US system by comparing it to CT for measurement of angle and distance between interventional needles in different configurations, similar to those used for percutaneous ablation of liver tumors. Results: The mean geometrical hybrid 3D reconstruction error measured from scanning of a known string phantom was less than 1 mm in two directions and 2.5 mm in the scanning direction, which was comparable or better than the same measurements obtained from a commercially available 3D US system. The error in volume measurements of spherical phantom models depended on depth of the object. For a 20 cm3 model at a depth of 15 cm, a standard depth for liver imaging, the mean error was 3.6% ± 4.5% comparable to the 2.3% ± 1.8% error for the 3D US commercial system. The error in 3D US measurement of the tip distance and angle between two microwave ablation antennas inserted into the phantom was 0.9 ± 0.5 mm and 1.1° ± 0.7°, respectively. Conclusions: A 3D US system with hybrid scanning motions for large field-of-view 3D abdominal imaging has been developed and validated. The superior spatial information provided by 3D US might enhance image-guidance for percutaneous interventional treatment of liver malignancies. The system has potential to be integrated with other liver procedures and has application in other abdominal organs such as kidneys, spleen, or adrenals. [ABSTRACT FROM AUTHOR]

Purpose: In image-guided surgery (IGS) intraoperative image acquisition of tissue shape, motion, and morphology is one of the main challenges. Recently, time-of-flight (ToF) cameras have emerged as a new means for fast range image acquisition that can be used for multimodal registration of the patient anatomy during surgery. The major drawbacks of ToF cameras are systematic errors in the image acquisition technique that compromise the quality of the measured range images. In this paper, we propose a calibration concept that, for the first time, accounts for all known systematic errors affecting the quality of ToF range images. Laboratory and in vitro experiments assess its performance in the context of IGS. Methods: For calibration the camera-related error sources depending on the sensor, the sensor temperature and the set integration time are corrected first, followed by the scene-specific errors, which are modeled as function of the measured distance, the amplitude and the radial distance to the principal point of the camera. Accounting for the high accuracy demands in IGS, we use a custom-made calibration device to provide reference distance data, the cameras are calibrated too. To evaluate the mitigation of the error, the remaining residual error after ToF depth calibration was compared with that arising from using the manufacturer routines for several state-of-the-art ToF cameras. The accuracy of reconstructed ToF surfaces was investigated after multimodal registration with computed tomography (CT) data of liver models by assessment of the target registration error (TRE) of markers introduced in the livers. Results: For the inspected distance range of up to 2 m, our calibration approach yielded a mean residual error to reference data ranging from 1.5 ± 4.3 mm for the best camera to 7.2 ± 11.0 mm. When compared to the data obtained from the manufacturer routines, the residual error was reduced by at least 78% from worst calibration result to most accurate manufacturer data. After registration of the CT data with the ToF data, the mean TRE ranged from 3.7 ± 2.1 mm for point-based and 5.7 ± 1.9 mm for surface-based registration for the best camera to 6.2 ± 3.4 and 11.1 ± 2.8 mm, respectively. Compared to data provided by the manufacturer, the mean TRE decreased by 8%-60% for point-based and by 18%-74% for surface-based registration. Conclusions: Using the proposed calibration approach improved the measurement accuracy of all investigated ToF cameras. Although evaluated in the context of intraoperative image acquisition, the proposed calibration procedure can easily be applied to other medical applications using ToF cameras, such as patient positioning or respiratory motion tracking in radiotherapy. [ABSTRACT FROM AUTHOR]

A quantitative trait locus ( QTL) study of the concentrations of 14 trace and macro elements (minerals) in tissues of beef cattle was conducted in New Zealand. Back-cross calves with Jersey and Limousin ancestry (202 heifers and 211 steers) were generated using first-cross sires. This paper reports on testing for effects of QTL on the concentrations of minerals in liver, kidney and muscle in cattle at slaughter, following a growth phase during which rearing and finishing stages were on pasture. Fifteen QTL were identified ( P < 0.05) on a genome-wide basis in combined-sire and within-sire analyses. In addition, the possible effect of the Limousin myostatin F94L allele was tested by fitting each calf's myostatin genotype , and 16 QTL were identified. Twelve were in common with those QTL identified previously, comprising six affecting the liver (copper and zinc, on two chromosomes each; plus iron and molybdenum), three affecting the kidney (calcium, copper and iron), and three affecting muscle (iron, strontium and zinc). [ABSTRACT FROM AUTHOR]

Purpose: In yttrium-90 (90Y) microsphere brachytherapy (radioembolization) of unresectable liver cancer, posttherapy 90Y bremsstrahlung single photon emission computed tomography (SPECT) has been used to document the distribution of microspheres in the patient and to help predict potential side effects. The energy window used during projection acquisition can have a significant effect on image quality. Thus, using an optimal energy window is desirable. However, there has been great variability in the choice of energy window due to the continuous and broad energy distribution of 90Y bremsstrahlung photons. The area under the receiver operating characteristic curve (AUC) for the ideal observer (IO) is a widely used figure of merit (FOM) for optimizing the imaging system for detection tasks. The IO implicitly assumes a perfect model of the image formation process. However, for 90Y bremsstrahlung SPECT there can be substantial model-mismatch (i.e., difference between the actual image formation process and the model of it assumed in reconstruction), and the amount of the model-mismatch depends on the energy window. It is thus important to account for the degradation of the observer performance due to model-mismatch in the optimization of the energy window. The purpose of this paper is to optimize the energy window for 90Y bremsstrahlung SPECT for a detection task while taking into account the effects of the model-mismatch. Methods: An observer, termed the ideal observer with model-mismatch (IO-MM), has been proposed previously to account for the effects of the model-mismatch on IO performance. In this work, the AUC for the IO-MM was used as the FOM for the optimization. To provide a clinically realistic object model and imaging simulation, the authors used a background-known-statistically and signal-known-statistically task. The background was modeled as multiple compartments in the liver with activity parameters independently following a Gaussian distribution; the signal was modeled as a tumor with a Gaussian-distributed activity parameter located randomly with equal probability at one of three positions. The IO test statistics (i.e., likelihood ratios) were estimated using Markov-chain Monte Carlo methods. The authors realistically modeled human anatomy using a digital phantom code, and realistically simulated 90Y bremsstrahlung SPECT imaging with a clinical SPECT system and typical imaging parameters using a previously validated Monte Carlo bremsstrahlung simulation method. Model-mismatch was included by modeling image formation process in the calculation of IO test statistics using an analytic modeling method previously developed for quantitative 90Y bremsstrahlung SPECT. To demonstrate the effects of the model-mismatch on the detection task, the authors optimized the energy window both with and without model-mismatch included in the IO. Results: For all the energy windows, the AUC values for the IO-MM were smaller than that for the IO. The optimal windows for the IO-MM and the IO were 80-180 and 60-400 keV, respectively. Conclusions: The authors have demonstrated the degradation of the ideal performance due to model-mismatch and optimized the energy window for 90Y bremsstrahlung SPECT for detection tasks by accounting for the effects of the model-mismatch. The obtained optimal window was much narrower when taking into account the model-mismatch and similar to that obtained previously for estimation tasks. [ABSTRACT FROM AUTHOR]

Purpose: To improve the accuracy and the robustness of the segmentation in living donor liver transplantation (LDLT) surgery planning system, the authors present a new segmentation framework that addresses challenges induced by the complex shape variations of patients' livers with cancer. It is designed to achieve the accurate and robust segmentation of hepatic parenchyma, portal veins, hepatic veins, and tumors in the LDLT surgery planning system. Methods: The segmentation framework proposed in this paper includes two important modules: (1) The robust shape prior modeling for liver, in which the sparse shape composition (SSC) model is employed to deal with the complex variations of liver shapes and obtain patient-specific liver shape priors. (2) The integration of the liver shape prior with a minimally supervised segmentation algorithm to achieve the accurate segmentation of hepatic parenchyma, portal veins, hepatic veins, and tumors simultaneously. The authors apply this segmentation framework to our previously developed LDLT surgery planning system to enhance its accuracy and robustness when dealing with complex cases of patients with liver cancer. Results: Compared with the principal component analysis, the SSC model shows a great advantage in handling the complex variations of liver shapes. It also effectively excludes gross errors and outliers that appear in the input shape and preserves local details for specific patients. The proposed segmentation framework was evaluated on the clinical image data of liver cancer patients, and the average symmetric surface distance for hepatic parenchyma, portal veins, hepatic veins, and tumors was 1.07 ± 0.76, 1.09 ± 0.28, 0.92 ± 0.35 and 1.13 ± 0.37 mm, respectively. The Hausdorff distance for these four tissues was 7.68, 4.67, 4.09, and 5.36 mm, respectively. Conclusions: The proposed segmentation framework improves the robustness of the LDLT surgery planning system remarkably when dealing with complex clinical liver shapes. The SSC model is able to handle non-Gaussian errors and preserve local detail information of the input liver shape. As a result, the proposed framework effectively addresses the problems caused by the complex shape variations of livers with cancer. Our framework not only obtains accurate segmentation results for healthy persons and common patients, but also shows high robustness when dealing with specific patients with large variations of liver shapes in complex clinical environments. [ABSTRACT FROM AUTHOR]

Blood glucose (BG) is the primary metabolic fuel for, among others, cancer cell progression, cardiovascular disease and inflammation. Stress is an important contributor to the amount of BG produced especially by the liver. In this paper, we attempt to quantify the BG production due to chronic (in the order of weeks) high-level psychological stress in a manner that a lay person will understand. Three independent approaches were used. The first approach was based on a literature survey of stress hormone data from healthy individuals and its subsequent mathematical manipulation. The next approach was a deductive process where BG levels could be deduced from published stress data of large cardiovascular clinical trials. The third approach used empirical BG data and a BG simulation model. The three different methods produced an average BG increase of 2.2-fold above basal for high levels of stress over a period of more than a day. The standard deviation normalized to the average value was 4.5%. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Li X, Song Y, Han Y, Wang D, Zhu Y. Liver X receptor agonist alleviated high glucose-induced endothelial progenitor cell dysfunction via inhibition of reactive oxygen species and activation of AMP-activated protein kinase. Microcirculation 19: 547-553, 2012. Abstract Objective: Liver X receptors (LXRs) are key regulators of cholesterol homeostasis. Synthetic LXR agonists are anti-atherogenic and anti-inflammatory. However, the effect of LXR agonists on endothelial progenitor cell (EPC) function is largely unknown. Here, we explored the effect of the LXR agonist TO901317 (TO) on EPC biology and the underlying mechanisms. Methods: Endothelial progenitor cells were cultured in mannitol or 30 m m glucose (high glucose) for 24 hours. For TO treatments, cells were pretreated with TO (10 μ m) for 12 hours, then mannitol or high glucose was added for an additional 24 hours. EPCs function, reactive oxygen species (ROS) release, and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were analyzed. Results: TO could restore the high glucose-impaired adhesion and migration capacity of EPCs. High glucose impaired EPC-mediated angiogenesis, and TO reversed the impairment. TO also alleviated ROS release induced by high glucose. Western blot analysis revealed that high glucose downregulated the phosphorylation of AMPK and endothelial nitric oxide synthase, which could be reversed with TO treatment. Furthermore, inhibiting AMPK activation by compound C could abolish the protective effects of TO on EPCs. Conclusions: TO had a protective effect on EPCs under high glucose by inhibiting ROS release and activating AMPK. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Papic et al. (2011) Liver involvement during influenza infection: perspective on the 2009 influenza pandemic. Influenza and Other Respiratory Viruses 6(3), e2-e5. Elevation of liver transaminase levels is a frequent observation during systemic infections. The aim of our study was to investigate liver damage during pandemic 2009 influenza A/H1N1 infection in comparison with seasonal influenza. Serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase (GGT) were significantly higher in patients with pandemic influenza compared to seasonal influenza, which was strongly correlated with hypoxia. Moreover, a positive correlation between C-reactive protein and serum GGT, alkaline phosphatase, and lactate dehydrogenase was noticed. Our findings support the hypothesis that the pandemic 2009 influenza A/H1N1 is an illness with a significant immune response to infection leading to hepatocellular injury. [ABSTRACT FROM AUTHOR]

Evidence for a relationship between T4 and T3 and glucose metabolism appeared over 100 years ago when the influence of thyroid hormone excess in the deterioration of glucose metabolism was first noticed. Since then, it has been known that hyperthyroidism is associated with insulin resistance. More recently, hypothyroidism has also been linked to decreased insulin sensitivity. The explanation to this apparent paradox may lie in the differential effects of thyroid hormones at the liver and peripheral tissues level. The purpose of this paper is to explore the effects of thyroid hormones in glucose metabolism and analyze the mechanisms whereby alterations of thyroid hormones lead to insulin resistance. [ABSTRACT FROM AUTHOR]

Hepatoblastoma (HB) is a rare malignant tumour of the liver and usually occurs in the first three years of life. Most of these tumours arise in the embryo; hence it seems to be unusual that hepatoblastoma occurs in adults and is an exceptional cause of primarymalignant liver tumour in adult patients. The diagnosis is often overlooked, and patientsmight be diagnosed at late stages of the disease at risk of increased mortality. In this paper we report a case of a 30-year-old man with mixed hepatoblastoma and abdominal pain, hepatomegaly and fever. The patient under went noninvasive diagnostic methods: duplex scanning, Computed Tomography (CT), and Magnetic Resonance imaging (MRI). In our experience, despite the important role of histological sample provided by biopsy in defining the diagnosis, very important was the role of MRI, more than ultrasonography and enhanced CT. The MRI detects tumor features as size, margins, and ratio with neighboring organs in order to get the best surgical approach. [ABSTRACT FROM AUTHOR]

The liver plays a central role in coordinating the body’s metabolism, including glucose homeostasis, xenobiotic metabolism and detoxification, and steroid hormone synthesis and degradation. Many of the regulatory effects in response to diet initially occur in the liver, which then modulates the activities of other organs in terms of nutrient utilization and metabolism. The health consequences of abnormal liver function are widespread, many of which are not entirely understood. Recent advances in genomic biology, nanotechnology, computer science and related fields have supplied researchers with a powerful set of tools for the laboratory and clinic. Because nutrient status has been proven to be an important factor in health and disease, the use of these tools to identify nutrient–gene interactions and their association with disease has greatly increased over the past decade. Given its great importance to intermediary metabolism, the liver has been one of the primary organs of focus in recent nutrigenomic experiments. This paper will provide a brief synopsis of the recent technological advancements that may be applied to nutrition research, common mechanisms by which nutrients and genes interact with one another, a few examples pertaining to hepatic function, and future directions in the field. [ABSTRACT FROM AUTHOR]

The purpose of the present paper was to investigate the heterogeneous nature of amyloid deposits in the liver, by immunohistochemical and immunochemical examination of liver samples from cases of immunoglobulin λ light chain amyloidosis (Aλ amyloidosis) with antibodies generated against the peptides corresponding to the three different regions of the λ light chain. Amyloid deposits in the hepatic artery tended to react better with anti-λ(118–134) than with anti-λ(159–175). Amyloid deposits in the space of Disse tended to react weakly or partially with anti-λ(118–134) but well with anti-λ(159–175). Amyloid deposits in the portal vein reacted relatively well with both antibodies. By western blotting of water-extracted amyloid in which amyloid deposits were not stained with anti-λ(118–134) immunohistochemically, the three antibodies detected 27 kDa bands consistent with the full-length Ig λ chain and some smaller bands. These findings indicate that amyloid deposits may not be homogeneous in the liver of AL amyloidosis, and that molecular heterogeneity of amyloid fibril protein or a difference in the mode of deposition results in the histopathological heterogeneity of AL amyloid deposits even within a single patient. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Huang et al and Packer and Bangash papers. To view these articles, visit https://doi.org/10.1111/apt.15962 and https://doi.org/10.1111/apt.16014 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Huang et al papers. To view these articles, visit https://doi.org/10.1111/apt.15962 and https://doi.org/10.1111/apt.16046 [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Mederacke et al and Huang and Chuang papers. To view these articles, visit https://doi.org/10.1111/apt.15722 and https://doi.org/10.1111/apt.15788. [ABSTRACT FROM AUTHOR]

Background: Steatosis occurs frequently in hepatitis C. However, the mechanisms leading to this lesion are still unknown, and the role of steatosis in the progression of the disease remains controversial. The aim of the present paper was to determine the prevalence of steatosis in hepatitis C and its association with hepatitis C virus (HCV) genotype, viral load and the presence of risk factors for steatosis, and to analyze the association between steatosis and the intensity of liver disease. Methods: Patients infected with HCV who underwent liver biopsy were included. Patients coinfected with hepatitis B virus and/or human immunodeficiency virus and those previously treated for hepatitis C were excluded. The following risk factors for steatosis were investigated: obesity (body mass index [BMI] > 25 kg/m2), diabetes mellitus, hyperlipidemia, alcoholism, and use of potential steatosis-inducing drugs. Histological analysis evaluated the presence of steatosis, the degree of periportal activity and staging. Patients with and without steatosis were compared regarding demographic, epidemiological, laboratory and histological characteristics. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. Results: Ninety patients (55 men, 35 women) with a mean age of 45 ± 13 years were included. The prevalence of steatosis was 67%. Variables that remained independently associated with steatosis were age, female gender, obesity and genotype 3. Conclusions: The prevalence of steatosis in hepatitis C was high. Risk factors usually related to steatosis such as age, female gender and obesity, as well as genotype 3, were independently associated with the presence of steatosis. Steatosis was not independently associated with the intensity of histological liver disease. [ABSTRACT FROM AUTHOR]