Serum autotaxin is a prognostic indicator of liver-related events in patients with non-alcoholic fatty liver disease.

BACKGROUND: Circulating autotaxin (ATX) levels have been reported to correlate with liver inflammation activity and liver fibrosis severity in patients with non-alcoholic fatty liver disease (NAFLD). The objective of this study is to investigate whether serum ATX could predict liver-related events (LRE) in NAFLD patients. METHODS: This retrospective investigation includes 309 biopsy-proven NAFLD patients registered at Shinshu University Hospital. All patients are followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, hepatic encephalopathy, ascites, and esophagogastric varices, is investigated in relation to ATX levels at the time of liver biopsy. RESULTS: During the median follow-up period of 7.0 years, LRE are observed in 20 patients (6.5%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE are 0.81 and 1.227 mg/l, respectively. Multivariate Cox proportional hazards models for LRE determine ATX and advanced fibrosis as independently associated factors. Furthermore, in a competing risk analysis that considered non-liver-related death as a competing event, ATX (HR 2.29, 95% CI 1.22-4.30, p = 0.010) is identified as an independent factor associated with LRE, along with advanced fibrosis (HR 8.01, 95% CI 2.10-30.60, p = 0.002). The predictive utility of ATX for LRE is validated in an independent cohort. CONCLUSIONS: Serum ATX may serve as a predictive marker for LRE in patients with NAFLD.

In non-alcoholic fatty liver disease (NAFLD), fat accumulates and can cause damage within the liver. The disease is becoming increasingly common worldwide. It is therefore important to identify individuals with NAFLD who are at higher risk of developing severe liver complications. In this study, we found that NAFLD patients with elevated levels of a substance called autotaxin (ATX) in their blood were more prone to liver-related issues. Thus, it is crucial for doctors to give special attention to NAFLD patients exhibiting high ATX levels. Through close ATX monitoring and appropriate treatment, doctors can potentially enhance their health outcomes and prevent the onset of more severe liver complications.

Autotaxin is a potential predictive marker for the development of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.

A Diagnostic Impact of Serum Autotaxin Levels in Patients with Bone Marrow Fibrosis.

BACKGROUND: Bone marrow (BM) fibrosis is a condition characterized by deposition of reticulin and collagen fibers in BM. It may confer a poor prognosis in some of hematological malignancies. However, the relationship between fibrosis and the disease pathology is not fully understood and no biomarkers for BM fibrosis are available in clinical practice. Autotaxin (ATX) is a secreted enzyme that is associated with various pathophysiological responses, including fibrosis. We conducted a pilot study to investigate the serum ATX levels in various hematological disorders in patients with or without BM fibrosis. PATIENTS AND METHODS: The serum levels of ATX in a total of 198 patients with hematological disorders and 160 healthy subjects were analyzed. Because of sexual difference in ATX level, the ATX ratio-determined by dividing the ATX level by the mean value of ATX of control subjects of the same sex-was calculated for further comparative analysis. A trephine biopsy samples from 53 patients were also evaluated to determine the Reticulin Fibrosis Index and Collagen Fibrosis Index of each sample. RESULTS: In comparison to the control group, the ATX ratio was significantly higher in patients, especially those with malignant lymphoma. The ATX ratio in lymphoma patients with BM fibrosis was significantly higher than that in patients without BM fibrosis. The Collagen Fibrosis Index showed statistically significant negative correlation with the ATX ratio. CONCLUSION: Our results suggest that the ATX ratio may be a candidate diagnostic biomarker for BM fibrosis in selected patients, including those with malignant lymphoma.

Utility of serum autotaxin levels for predicting post hepatectomy liver failure in hepatocellular carcinoma.

BACKGROUND/PURPOSE: This study aimed to evaluate the usefulness of serum autotaxin, a novel liver fibrosis marker, for predicting post hepatectomy liver failure (PHLF) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). METHODS: Autotaxin was measured in sera from 269 patients undergoing hepatectomy for HCC. Correlations between autotaxin level, liver fibrosis stage (METAVIR F0-F4), and PHLF, as assessed by the International Study Group of Liver Surgery criteria, were analyzed. RESULTS: Median autotaxin concentrations correlated significantly with fibrosis stage (F0, 0.93; F1, 0.96; F2, 1.18; F3, 1.40; and F4, 1.47 mg/l; P < .0001). Autotaxin levels were significantly higher in female patients and hepatitis C virus antibody-positive patients compared with male or antibody-negative patients (P < .0001). PHLF grade ≥ B occurred in 25 patients (9.3%). A PHLF prediction model was constructed from four variables (autotaxin, resection rate, sex, and hepatitis C virus antibody positivity) and gave an area under the receiver operating characteristic curve of 0.8 (95% confidence interval [CI]: 0.69-0.87), which was superior to models based on ALPlat and resection rate (0.75, 95% CI: 0.64-0.83) or indocyanine green retention test and resection rate (0.72, 95% CI: 0.61-0.81). CONCLUSION: Serum autotaxin has utility for predicting liver fibrosis and PHLF in patients with HCC.

Decrease in serum levels of autotaxin in COVID-19 patients.

INTRODUCTION: In order to identify therapeutic targets in Coronavirus disease 2019 (COVID-19), it is important to identify molecules involved in the biological responses that are modulated in COVID-19. Lysophosphatidic acids (LPAs) are involved in the pulmonary inflammation and fibrosis are one of the candidate molecules. The aim of this study was to evaluate the association between the serum levels of autotaxin (ATX), which are enzymes involved in the synthesis of lysophosphatidic acids. MATERIAL AND METHODS: We enrolled 134 subjects with COVID-19 and 58 normal healthy subjects for the study. We measured serum ATX levels longitudinally in COVID-19 patients and investigated the time course and the association with severity and clinical parameters. RESULTS: The serum ATX levels were reduced in all patients with COVID-19, irrespective of the disease severity, and were negatively associated with the serum CRP, D-dimer, and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels. DISCUSSION: Considering the biological properties of LPAs in the pulmonary inflammation and fibrosis, modulation of ATX might be compensatory biological responses to suppress immunological overreaction especially in the lung, which is an important underlying mechanism for the mortality of the disease. CONCLUSIONS: COVID-19 patients showed a decrease in the serum levels of ATX, irrespective of the disease severity. Key MessagesAutotaxin (ATX) is an enzyme involved in the synthesis of lysophosphatidic acid (LPA), which has been reported to be involved in pulmonary inflammation and fibrosis. Patients with COVID-19 show decrease in the serum levels of ATX. Modulation of ATX might be compensatory biological responses to suppress immunological overreaction.

Fibrotic Response of Human Trabecular Meshwork Cells to Transforming Growth Factor-Beta 3 and Autotaxin in Aqueous Humor.

This study examines the potential role of transforming growth factor-beta 3 (TGF-ß3) on the fibrotic response of cultured human trabecular meshwork (HTM) cells. The relationships and trans-signaling interactions between TGF-ß3 and autotaxin (ATX) in HTM cells were also examined. The levels of TGF-ß and ATX in the aqueous humor (AH) of patients were measured by an immunoenzymetric assay. The TGF-ß3-induced expression of the fibrogenic markers, fibronectin, collagen type I alpha 1 chain, and alpha-smooth muscle actin, and ATX were examined by quantitative real-time PCR, Western blotting, and immunocytochemistry, and the trans-signaling regulatory effect of TGF-ß3 on ATX expression was also evaluated. In HTM cells, the significant upregulation of ATX was induced by TGF-ß3 at a concentration of 0.1 ng/mL, corresponding to the physiological concentration in the AH of patients with exfoliative glaucoma (XFG). However, higher concentrations of TGF-ß3 significantly suppressed ATX expression. TGF-ß3 regulated ATX transcription and signaling in HTM cells, inducing the upregulation of fibrogenic proteins in a dose-dependent manner. Trans-signaling of TGF-ß3 regulated ATX transcription, protein expression, and signaling, and was thereby suggested to induce fibrosis of the trabecular meshwork. Modulation of trans-signaling between TGF-ß3 and ATX may be key to elucidate the pathology of XFG, and for the development of novel treatment modalities.

Role of Autotaxin in High Glucose-Induced Human ARPE-19 Cells.

Autotaxin (ATX) is an enzymatic with lysophospholipase D (lysoPLD) activity. We investigated the role of ATX in high glucose (HG)-induced human retinal pigment epithelial (ARPE-19) cells to explore the pathogenesis of diabetic retinopathy (DR). We performed a quantitative real-time polymerase chain reaction, Western blotting, immunocytochemistry, enzyme-linked immunosorbent assay, cell permeability assay, and transepithelial electrical resistance measurement in HG-induced ARPE-19 cells and compared their results with those of normal glucose and osmotic pressure controls. ATX expression and its lysoPLD activity, barrier function, and expression of vascular endothelial growth factor receptors VEGFR-1 and VEGFR-2 were downregulated, while fibrotic responses, cytoskeletal reorganization, and transforming growth factor-ß expression were upregulated, in the HG group. Our results suggest that HG induces intracellular ATX downregulation, barrier dysfunction, and fibrosis, which are involved in early DR and can be targeted for DR treatment.

Long-term prediction of hepatocellular carcinoma using serum autotaxin levels after antiviral therapy for hepatitis C.

INTRODUCTION AND OBJECTIVES: Continuous monitoring for hepatocellular carcinoma is necessary following treatment with direct-acting antivirals in patients with hepatitis C virus infection. We investigated whether the long-term follow-up of serum autotaxin levels could predict the development of hepatocellular carcinoma. PATIENTS AND METHODS: This prospective observational study enrolled adult patients with chronic hepatitis C virus infection who presented to the study center from January 2016 to March 2021. Among the patients who achieved a sustained viral response, the relationship between the development of hepatocellular carcinoma and serum autotaxin levels was assessed before treatment with direct-acting antivirals; at the end of therapy; at 12 and 24 weeks; and at 12, 24, 36, and 48 months after treatment. RESULTS: Data were analyzed for 139 patients. Thirteen patients developed hepatocellular carcinoma 48 months after treatment. The cut-off serum autotaxin values that predicted hepatocellular carcinoma after 24 weeks were 1.22 (men) and 1.92 (women) mg/L. The area under the curve for serum autotaxin was 0.83 (95% confidence interval [CI]:0.71-0.95) in men and 0.90 (95% CI: 0.82-0.99) in women. The positive predictive value of serum autotaxin was 0.208 (95% CI: 0.139-0.248), and the negative predictive value was 0.971 (95% CI: 0.939-0.990). The cumulative incidence of hepatocellular carcinoma was significantly higher when serum autotaxin levels were above the cut-off value after 24 weeks (p < 0.0001). CONCLUSIONS: Serum autotaxin is a candidate biomarker for predicting hepatocellular carcinoma during the long-term follow-up of patients with a sustained viral response following treatment with direct-acting antivirals.

Development of plasma ghrelin level as a novel marker for gastric mucosal atrophy after Helicobacter pylori eradication.

BACKGROUND AND AIM: The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. METHODS: Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). RESULTS: Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. CONCLUSION: Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication.KEY MESSAGESGhrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication.Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication.Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

Crosstalk between transforming growth factor ß-2 and Autotaxin in trabecular meshwork and different subtypes of glaucoma.

BACKGROUND: Elevated transforming growth factor (TGF)-ß2 in aqueous humor (AH) has been suggested to contribute to trabecular meshwork (TM) fibrosis and intraocular pressure (IOP) regulation in primary open-angle glaucoma (POAG), but TGF-ß2 is downregulated in secondary open-angle glaucoma (SOAG). Because autotaxin (ATX) is upregulated in SOAG, we investigated the relationships and trans-signaling interactions of these mediators. METHODS: The level of ATX in AH was determined using a two-site immunoenzymetric assay, and TGF-ß levels were measured using the Bio-Plex Pro TGF-ß Assay. RNA scope was used to assess the expression of ATX and TGF-ß2 in human's eye specimen. And in vitro studies were performed using hTM cells to explore if trans-signaling of TGF-ß2 regulates ATX expressions. RESULTS: TGF-ß2/ATX ratio was significantly high in AH of control or POAG compared with SOAG, and negatively correlated with IOP. RNA scope revelated positive expressions of both TGF-ß2 and ATX in ciliary body (CB) and TM in control, but ATX expressions was significantly enhanced in SOAG. In hTM cells, ATX expressions were regulated by TGF-ß2 with concentration-dependent manner. In counter, ATX also induced TGF-ß1, TGF-ß2 and TGFBI upregulations and activation of the Smad-sensitive promoter, as well as upregulation of fibrotic markers, and these upregulation was significantly suppressed by both TGF-ß and ATX inhibition. CONCLUSIONS: Trans-signaling of TGF-ß2 regulates ATX expressions and thereby induced upregulations of TGF-ßs or fibrosis of hTM. TGF-ß2 trans-signaling potently regulate ATX transcription and signaling in hTM cells, which may reflect different profile of these mediators in glaucoma subtypes. Trial Registration This prospective observational study was approved by the Institutional Review Board of the University of Tokyo and was registered with the University Hospital Medical Information Network Clinical Trials Registry of Japan (ID: UMIN000027137). All study procedures conformed to the Declaration of Helsinki. Written informed consent was obtained from each patient.

The usefulness of plasma levels of mature and total adrenomedullin as biomarkers indicating the magnitude of surgical stress responses: A single-center, prospective, observational study.

BACKGROUND AND AIM: Adrenomedullin (AM), a vasodilatory peptide, is known for its pleiotropic actions. AM levels are increased under inflammatory conditions such as sepsis and can be useful as a prognostic biomarker. However, there are only a few reports on the physiological actions of AM in the perioperative period. The aim of this single-center, prospective, and observational study was to investigate the changes in the plasma levels of mature AM (mAM) and total AM (tAM) observed during the perioperative period. In addition, we aimed to determine the association between each AM level and immune-inflammatory parameters to explore the usefulness of AM as a biomarker of the magnitude of surgical stress responses. METHODS: The levels of both mAM and tAM, in addition to the levels of presepsin, interleukin-6, procalcitonin, white blood cell, and C-reactive protein, were measured in blood samples obtained during the perioperative period. Other laboratory data, including sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) II scores, were obtained from individual clinical records. Correlations between each AM and clinical parameters were determined using Spearman's rank correlation. P<0.05 were considered statistically significant. RESULTS: One hundred and twenty-three perioperative patients scheduled for three types of surgical procedures, including cardiopulmonary bypass surgery, abdominal surgery, and cervical laminoplasty, were included in this study. There was a moderate to strong correlation between each AM and immune-inflammatory parameters, SOFA score, and APACHE II score, as related to surgical trauma. Specifically, the strongest correlation was observed between each AM and SOFA score. CONCLUSIONS: These findings suggest that plasma AM levels may represent the most important inflammatory mediators that are evident in surgical stress responses. RELEVANCE FOR PATIENTS: Since the levels of both tAM and mAM show the same trend, mAM and tAM may be equally used as biomarkers for the evaluation of the physiological status of surgical patients. TRIAL REGISTRATION: This observational study was retrospectively registered with Japanese Clinical Trial Registry "UMIN-CTR" on March 19, 2018, and was given a trial ID number UMIN000031792.

Plasma adrenomedullin level and year-by-year variability of body mass index in the general population.

Plasma levels of the hypotensive peptides of adrenomedullin and atrial and B-type natriuretic peptides (AM, ANP, BNP) are possible biomarkers for cardiovascular diseases. Increased variability of body mass index (BMI) over a certain period of time has been reported to be associated with cardiovascular morbidity or mortality. The aim of this study is to examine clinical significance of those hypotensive peptides as biomarkers by analyzing the relationship between plasma levels of the peptides and year-by-year variability of BMI in the general population without overt cardiovascular diseases. The subjects were 427 local residents (141 males and 286 females) attending their annual health check-up, who had been examined at least 5 times over the preceding period of 10 years. They were divided into two groups of low or high variability by the median of coefficient of variation (CV) of BMI values for each gender. Plasma AM levels of those with high year-by-year variability of BMI were significantly increased, as compared to the group with low variability, in both genders; meanwhile, such a difference was not noted in plasma levels of the natriuretic peptides. No significant differences were found in the basal parameters, which could affect plasma AM level, such as age, BMI, blood pressure or serum creatinine, between two groups. In conclusion, increase in plasma AM was associated with high year-by-year variability of BMI in the general population without overt heart disease. This relationship between the two suggests that increased plasma AM level is a cardiovascular risk marker.

Aqueous autotaxin and TGF-ßs are promising diagnostic biomarkers for distinguishing open-angle glaucoma subtypes.

The purpose of this study is to examine if aqueous autotaxin (ATX) and TGF-ß levels could be used for differentiating glaucoma subtypes. This prospective observational study was performed using aqueous humor samples obtained from 281 consecutive patients. Open angle glaucoma patients were classified into three groups: primary open-angle glaucoma (POAG), secondary open-angle glaucoma (SOAG), and exfoliation glaucoma (XFG). Aqueous levels of ATX and TGF-ßs were quantified. The AUC as well as sensitivity and specificity for the classification into normal and glaucoma subtypes using four indicators-ATX, TGF-ß1, TGF-ß2, and TGF-ß3, upon the application of three machine learning methods. ATX, TGF-ß1, and TGF-ß3 were positively correlated with IOP, and ATX was significantly and negatively correlated with the mean deviation. From least absolute shrinkage and selection operator regression analysis, the AUC values to distinguish each subgroup [normal, POAG, SOAG, and XFG] ranged between 0.675 (POAG vs. normal) and 0.966 (XFG vs. normal), when four variables were used. High AUC values were obtained with ATX for discriminating XFG from normal eyes and with TGF-ß3 for discriminating XFG from normal eyes, POAG, or SOAG. Aqueous TGF-ß and ATX exhibited high diagnostic performance in detecting glaucoma subtypes, and could be promising biomarkers for glaucoma.

Effect of postoperative corticosteroids on surgical outcome and aqueous autotaxin following combined cataract and microhook ab interno trabeculotomy.

To evaluate the effect of postoperative corticosteroids on surgical outcome and autotaxin (ATX) levels after microhook ab interno trabeculotomy combined with cataract surgery (µLOT-CS), prospective, consecutive non-randomized case series comparing outcomes of 30 eyes with primary open angle glaucoma was performed. The aqueous ATX, intraocular pressure (IOP) and glaucoma medications were monitored for 3 months postoperatively. An in-vivo mouse µLOT model was generated. In vitro, ATX and fibrotic changes induced by dexamethasone (Dex) treatment following scratch (S) in cultured human trabecular meshwork (hTM) cells were assessed by immunofluorescence, immunoenzymatic assay, and RT-qPCR. Postoperative ATX at 1 week and the number of antiglaucoma medications at 3 months were significantly lower in non-steroid group, and steroid use was the only variable significantly associated with postoperative medications at 3 months in multiregression analyses. In vitro, ATX activity was significantly upregulated in the Dex + S group, and αSMA was significantly upregulated in the Dex and Dex + S groups. Fibronectin and COL1A1 were significantly upregulated in the S group. µLOT-CS decreased IOP and medications in the overall cohort, and non-use of postoperative steroids resulted in a smaller number of postoperative medications. Limiting postoperative steroids in µLOT may minimize IOP elevation and postoperative fibrosis.

The diagnostic and prognostic value of mature and total adrenomedullin for sepsis: a prospective observational study.

INTRODUCTION: Information about biologically active adrenomedullin (mature AM), a potential new biomarker for sepsis and septic shock, is limited. Here, we investigated the value of mature AM for diagnosis and outcome prediction in sepsis. MATERIAL AND METHODS: Patients admitted to the intensive care unit (ICU) were retrospectively cate-gorised into non-sepsis or sepsis groups, according to the Sepsis-3 definitions. Plasma levels of mature and total (the sum of the levels of intermediate and mature forms) AM were measured, and their usefulness was compared with that of other sepsis biomarkers, such as procalcitonin and presepsin. RESULTS: Of the 98 patients analysed, 42 were assigned to the non-sepsis and 56 to the sepsis group. Mature and total AM levels on admission were significantly higher in patients with than in those without sepsis. The areas under the receiver operating characteristic curves (AUCs) of mature and total AM for diagnosing sepsis were 0.85 and 0.88, whereas those of procalcitonin and presepsin were 0.83 and 0.68, respectively. AUCs of mature and total AM for predicting 28-day mortality in patients with sepsis became significant on day 3 after admission. A good correlation between the AM forms was found, indicating that changes in their plasma levels may directly reflect each other. CONCLUSIONS: Because mature and total AM levels increased significantly in patients with sepsis on admission, both forms may be used as reliable and early biomarkers for diagnosing sepsis according to the Sepsis-3 definitions. However, prediction of 28-day mortality in such patients would require several days of ICU stay.

Screening and follow-up of chronic liver diseases with understanding their etiology in clinics and hospitals.

BACKGROUND AND AIM: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. METHODS: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). RESULTS: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/µL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. CONCLUSIONS: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

Measuring complex field waveforms of quadrature amplitude modulation optical signals using a spectrally slicing-and-synthesizing coherent optical spectrum analyzer.

We propose a spectrally slicing-and-synthesizing coherent optical spectrum analyzer to measure complex field waveforms of quadrature amplitude modulation (QAM) optical signals with ultralong periods. The optical spectrum of a measured optical signal is divided into multiple narrowband spectral components, called slices. The slices are sequentially measured using low-speed coherent detection. After phase noise suppression and frequency fluctuation compensation on each slice, the measured slices are synthesized to recover the original signal spectrum. Our numerical and experimental results confirm that the proposed method can overcome the limitation of the measurement bandwidth because the signal spectrum can synthesize more than 100 slices. We experimentally demonstrate complex field measurements of 16QAM optical signals. Our method can measure high-speed optical complex field waveforms with no bandwidth limitation.

Weakly coupled 10-mode-division multiplexed transmission over 48-km few-mode fibers with real-time coherent MIMO receivers.

For weakly coupled mode-division multiplexed (MDM) transmission systems, we design and implement optical coherent receiver prototypes with real-time multiple-input multiple-output (MIMO) digital signal processing to equalize two degenerate linearly polarized modes with dual polarization. Using field programmable gate array circuits, we implement real-value 8 × 2 MIMO adaptive equalization with externally separated phase compensators based on the least mean square algorithm, which enables not only training equalization but also fast carrier-phase tracking. With the optical coherent MIMO receiver prototype, we demonstrate real-time weakly coupled 10 × MDM wavelength-division multiplexed dual-polarization quadrature phase shift keying transmission over 48-km few-mode fibers. This report shows a record number of multiplexed spatial modes, namely, 10 modes with dual polarization, in real-time MDM transmission experiments.

Urinary autotaxin concentrations are associated with kidney injury.

BACKGROUND: While basic researches have shown the involvement of the autotaxin-lysophosphatidic acid (ATX-LPA) axis in the pathogenesis of kidney diseases, no clinical studies have revealed the association between urinary ATX concentrations and kidney disease yet. We investigate the clinical characteristics in relation to the urinary ATX concentrations and the potential association between urinary ATX concentrations and various kidney diseases. METHODS: We measured the urinary ATX concentrations in residual urine samples after routine clinical testing from a total of 326 subjects with various kidney diseases and healthy subjects. We compared the urinary ATX concentrations in relation to clinical parameters and urinary biomarkers, and investigated their association with various kidney diseases. RESULTS: The urinary ATX concentrations were associated with the gender, eGFR, presence/absence of hematuria, serum ATX, urinary concentrations of total protein (TP), microalbumin, N-acetyl-ß-D-glucosaminidase (NAG), α1-microglobulin (α1-MG), and transforming growth factor-ß. Multiple regression analyses identified urinary α1-MG, age, urinary TP, NAG, and hematuria as being significantly associated with the urinary ATX concentrations. Urinary ATX concentrations were higher in subjects with membranous nephropathy and systemic lupus erythematosus than in the control subjects. CONCLUSIONS: Urinary ATX might be associated with pathological conditions of the kidney associated with kidney injury.