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Abstract The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Background: Excitotoxicity is a process in which NADPH oxidase‐2 (NOX‐2) plays a pivotal role in the generation of reactive oxygen species (ROS). Oxidative stress influences the expression of Aquaporin 4 (AQP4), a water channel implicated in blood–brain barrier (BBB) permeability and edema formation. The endocannabinoid system is widely distributed in the brain, particularly through the cannabinoid receptor type 1 (CB1) and type 2 (CB2), which have been shown to have a neuroprotective function in brain injury. Given the significant involvement of NOX‐2 in ROS production during excitotoxicity, our research aims to assess the participation of NOX‐2 in the neuroprotective effect of the cannabinoid receptor agonist WIN55,212‐2 against glutamate‐induced excitotoxicity damage in the striatum using in vivo model. Methods: Wild‐type mice (C57BL/6) and NOX‐2 KO (gp91Cybbtm1Din/J) were stereotactically injected in the striatum with monosodium glutamate or vehicle. Subsequently, a group of mice was administered an intraperitoneal dose of WIN55,212‐2, AM251, or AM251/WIN55,212‐2 following the intracerebral injection. Motor activity was assessed, and the lesion was examined through histological sections stained with cresyl violet. Additionally, brain water content and Evans blue assay were conducted. The activity of NOX was quantified, and the protein expression of CB1, gp91phox, AQP4, Iba‐1, TNF‐α, and NF‐κB was analyzed using Western blot. Furthermore, ROS formation was measured through the DHE assay. Results: The activation of the endocannabinoid receptors demonstrated a neuroprotective response during excitotoxicity, meditated by NOX‐2. The reduction in ROS production led to a decrease in neuroinflammation, and AQP4 expression, resulting in reduced edema formation, and BBB permeability. Conclusions: During excitotoxic damage, WIN55,212‐2 inhibits NOX‐2‐induced ROS production, reducing brain injury. [ABSTRACT FROM AUTHOR]

Split-gate embedded Flash memory technology has been around for decades and has become the standard application for a wide range of devices such as microcontrollers and smart cards. Among them, due to a number of advantages, SuperFlash (SF) produced by Silicon Storage Technology is the most widely used nonvolatile memory technology. In this paper, the results of a study of the structure of memory cells (MCs) are presented and the principle of their operation, as well as the main technological stages of the production process of forming transistor structures, is discussed. [ABSTRACT FROM AUTHOR]

The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients. [ABSTRACT FROM AUTHOR]

Cattle and the draught force provided by its skeletal muscle have been integral to agro‐ecosystems of agricultural civilization for millennia. However, relatively little is known about the cattle muscle functional genomics (including protein coding genes, non‐coding RNA, etc.). Circular RNAs (circRNAs), as a new class of non‐coding RNAs, can be effectively translated into detectable peptides, which enlightened us on the importance of circRNAs in cattle muscle physiology function. Here, RNA‐seq, Ribosome profiling (Ribo‐seq), and peptidome data are integrated from cattle skeletal muscle, and detected five encoded peptides from circRNAs. It is further identified and functionally characterize a 907‐amino acids muscle‐specific peptide that is named circNEB‐peptide because derived by the splicing of Nebulin (NEB) gene. This peptide localizes to the nucleus and cytoplasm and directly interacts with SKP1 and TPM1, key factors regulating physiological activities of myoblasts, via ubiquitination and myoblast fusion, respectively. The circNEB‐peptide is found to promote myoblasts proliferation and differentiation in vitro, and induce muscle regeneration in vivo. These findings suggest circNEB‐peptide is an important regulator of skeletal muscle regeneration and underscore the possibility that more encoding polypeptides derived by RNAs currently annotated as non‐coding exist. [ABSTRACT FROM AUTHOR]

We study the wisdom of the crowd in three sequential decision-making tasks: the Balloon Analogue Risk Task (BART), optimal stopping problems, and bandit problems. We consider a behavior-based approach, using majority decisions to determine crowd behavior and show that this approach performs poorly in the BART and bandit tasks. The key problem is that the crowd becomes progressively more extreme as the decision sequence progresses, because the diversity of opinion that underlies the wisdom of the crowd is lost. We also consider model-based approaches to each task. This involves inferring cognitive models for each individual based on their observed behavior, and using these models to predict what each individual would do in any possible task situation. We show that this approach performs robustly well for all three tasks and has the additional advantage of being able to generalize to new problems for which there are no behavioral data. We discuss potential applications of the model-based approach to real-world sequential decision problems and discuss how our approach contributes to the understanding of collective intelligence., (© 2021 Cognitive Science Society LLC.)

Background and aims: Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). Methods: Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB). Results: Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age—46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27–40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age—44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24–40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00–28.00] vs. 17.00 [15.00–21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03–9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2–2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1–2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort. Conclusion: Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF. [ABSTRACT FROM AUTHOR]

This report describes a case of positive identification of the abuser's fingers appearing in a child sexual abuse video. A specific single frame, with the optimal conditions for fingerprint comparison, was selected from the video. The image was processed to optimize the friction skin detail. A simple scaling procedure was carried out to compensate for the lack of a forensic measurement scale on the image. Then, the image was compared to the fingerprints of the individual under investigation. The comparison revealed that fingers appearing in the video matched to the thumb and index finger from the left hand of the suspect's tenprint. Because high-quality videos are becoming increasingly available on-line, reliable extraction and processing of video frames may well be an effective method for the fingerprint identification of perpetrators of criminal acts, including child sexual abuse criminals. [ABSTRACT FROM AUTHOR]

Background and aims: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. Methods: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. Results: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36–0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43–0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. Conclusions: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002. [ABSTRACT FROM AUTHOR]

Background: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. Methods: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. Results: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I–II in 981 (74.6%) and grades III–IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III–IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients. Conclusions: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Plasma‐exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients. Methods: Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE. Results: ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS‐matched cohort (n = 208, [ALS‐119; PE‐94, FPSA‐25)], SMT‐89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42‐24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5‐11.1), and lower liver‐failure‐related deaths as compared to FPSA and SMT (P <.05). PE cleared inflammatory cytokines, damage‐associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti‐inflammatory cytokine interleukin‐1 receptor antagonist (IL‐1RA) compared to non‐responders. PE was associated with lesser adverse effects as compared to FPSA. Conclusions: PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma‐exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients. [ABSTRACT FROM AUTHOR]

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here. Article Highlights: Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectively ACLF is distinct form Acute Decompensation of cirrhosis Newer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLF Reversibility of Chronic Liver Disease in ACLF Portal and systemic hemodynamics and their relevance in ACLF Acute Portal Hypertension and Variceal progression in ACLF AARC score as a guide for treatment strategies in ACLF ACLF in Children-first consensus on pediatric ACLF [ABSTRACT FROM AUTHOR]

Aim: We compared the vaccine effectiveness of monovalent and combination hepatitis B vaccine regimens in infants born to chronic hepatitis B carrier mothers.Methods: An observational cohort of neonates was recruited over 78 months from two public hospital maternity units in Singapore. We enrolled term infants, born to chronic hepatitis B surface antigen-positive mothers regardless of their hepatitis Be antigen status, who completed the hepatitis B virus (HBV) vaccination programme in Singapore. Infants born to mothers on antiviral therapy, or with concurrent hepatitis C or human immunodeficiency virus infection were excluded. All infants received hepatitis B immunoglobulin at birth. One group received three doses of monovalent hepatitis B vaccine (0, 1, 6 months) (regimen A). The other group received two doses of monovalent vaccine, followed by one dose combination vaccine DTaP-IPV-Hib-HBV (0, 1, 6 months) (regimen B). Vaccine effectiveness was determined by immunoprophylaxis failure leading to HBV vertical transmission. Immunogenicity was assessed by hepatitis B surface antibody (anti-HBs) levels at 9 months of age.Results: Total of 177 term neonates received regimen A and 115 received regimen B. Immunoprophylaxis failure rate was low, 2.3 and 2.6% (P = 1.00) in regimen A and B, respectively. Mean anti-HBs titres were similar at 643 ± 374 and 561 ± 396 IU/L (P = 0.08) for regimen A and B, respectively.Conclusion: Hepatitis B vaccine regimens using monovalent or combination vaccine for the third dose showed similarly high vaccine effectiveness and low immunoprophylaxis failure rate in term infants born to chronic hepatitis B carrier mothers. [ABSTRACT FROM AUTHOR]

Background and Aim Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis. Methods Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death. Results Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%, P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively ( P < 0.001). Conclusion Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF. [ABSTRACT FROM AUTHOR]

The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 06, 2019 without open access. [ABSTRACT FROM AUTHOR]

A systematic methodology is presented to scale split-gate (SG) flash memory cells in the sub-90 nm regime within the presently known scaling constraints of flash memory. The numerical device simulation results show that the high performance sub-90 nm NOR-type SG cells can be achieved by a suitable channel and source–drain engineering. An asymmetric channel doping profile along with ultra-shallow source–drain junctions was used to achieve the target drain programming voltage (Vsp) for an efficient cell programming while keeping the cell breakdown voltage, BV>Vsp, with tolerable leakage currents. The study shows that with properly optimised technology parameters, 65 nm SG-NOR flash memory can be achieved with an adequate cell read current, a tolerable programmed cell leakage current at the read condition and efficient write and erase times. [ABSTRACT FROM AUTHOR]

An analytical model for evaluating the bias-dependent and dynamic drain coupling ratio of the drain-coupling source-side injection split gate flash is developed with comparisons of classical extraction methods. A new method to measure the technology-dependent select gate coupling ratio is also presented. Starting with the quasi-two-dimensional analyses on separate channel regions, the channel potential distributions are utilised to derive the analytical expressions of the drain coupling ratio as functions of the applied bias and storage charge. In good agreement with the experimental programming transient, full dynamics of the analytical drain coupling ratio not only explain the discrepant experimental results from classical extraction methods but also provide a solid base on designing split gate devices. Additionally, the characteristic lengths and saturation voltages of high field regions are extracted by the substrate current and the programming transient. A mean free path of about 92 Å and a impact ionisation field of 1.74 MV/cm are also verified from the source-side injection device. [ABSTRACT FROM AUTHOR]

We describe the performance of graphene oxide (GO) membranes stabilized by crosslinkers and supported on polyethersulfone films in the dehydration of ethanol in a continuous cross-flow pervaporation set-up. We used two crosslinker species with branched structures (humic acid-like substances derived from urban waste and a synthetic hyperbranched polyol). The supported crosslinked GO films were prepared by rod coating on a polyethersulfone ultrafiltration membrane. Pervaporation experiments were carried out at temperatures of 40, 50, 60 and 70 °C. When the feed comprised pure water and ethanol, a much higher flux of water than ethanol was observed at all temperatures through GO films stabilized by the two crosslinkers (humic acid, GO-HAL, and the synthetic hyperbranched polyol, GO-HBPO), indicating the separation ability of these crosslinked membranes. For feed mixtures of water and ethanol, the GO-HAL and GO-HBPO membranes showed good separation performances by producing permeates with a significantly higher water content than the feed at all temperatures. [ABSTRACT FROM AUTHOR]