bluuebunny/crossref_metadata_2025_split huggingface dataset:
A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions
Authors: Cusi Kenneth 
Published: February 2020

AbstractThere is a close link between steatohepatitis (NASH) and Type 2 diabetes (T2DM). Recently, the American Diabetes Association (ADA) recommended screening for NASH and advanced fibrosis in patients with diabetes and hepatic steatosis or elevated plasma alanine aminotransferase (ALT). This is because as many as ~30% to 40% may have NASH and ~10% to 15% advanced fibrosis. The role of hyperglycemia and the natural history of NASH in diabetes remain poorly understood, as well as which diagnostic algorithm or interventions are most cost‐effective. There is significant clinical inertia and most patients today are still not receiving adequate lifestyle intervention or pharmacological treatment with diabetes agents known to be effective against NASH. Lifestyle intervention improves steatohepatitis in proportion to the magnitude of weight loss, but this trend is not as consistent for regression of fibrosis. This limited success supports the need for concomitant pharmacological therapy. Pioglitazone has been shown to consistently induce resolution of NASH in both patients with or without diabetes in a total of 498 participants in five randomized controlled trials (RCTs), but with modest effects on liver fibrosis. Proof‐of‐concept studies suggest a potential role for GLP‐1RAs and SGLT2 inhibitors. Combination therapy is on the horizon. Treating diabetes and NASH with a combination of pioglitazone, GLP‐1RAs or SGLT2i, could be a cost‐effective strategy to treat both diseases while reducing their high cardiovascular risk. Future combination therapies will likely combine existing diabetes agents with novel NASH‐spechfic drugs under development. This review highlights current knowledge gaps and proposes future directions for the treatment of NASH in diabetes.
Hepatitis C elimination – Macro‐elimination
Authors: Kåberg Martin , Weiland Ola 
Published: February 2020

AbstractIn 2016 the WHO set a goal to obtain an 80% reduction in new chronic HCV cases, requiring a level of diagnosis of 90%, treatment coverage of 80% and resulting in a 65% reduction in HCV‐related deaths by 2030. This goal is easier to reach in specific populations such as people who inject drugs (PWID), men who have sex with men (MSM) or blood‐transfusion recipients before screening for HCV became mandatory and in high‐income regions. It is much more difficult to achieve macro‐elimination throughout the population especially in low‐income areas with underdeveloped infrastructures, a high prevalence of HCV and limited economic resources. To achieve the WHO goals by 2030, awareness of HCV must increase and the cascade of care must be improved and implemented. Diagnostic procedures and treatment should be affordable and universally available. At the end of 2017 fewer than 15 countries were on track to reach these goals by 2030.
Future treatments for hepatitis delta virus infection
Authors: Asselah Tarik , Loureiro Dimitri , Tout Issam , Castelnau Corinne , Boyer Nathalie , Marcellin Patrick , Mansouri Abdellah 
Published: February 2020

AbstractAround 15‐20 million people develop chronic hepatitis delta virus worldwide. Hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the hepatitis B virus surface antigen (HBsAg) to complete its life cycle. HDV infects hepatocytes using the hepatitis B virus (HBV) receptor, the sodium taurocholate cotransporting polypeptide (NTCP). The HDV genome is a circular single‐stranded RNA which encodes for a single hepatitis delta antigen (HDAg) that exists in two forms (S‐HDAg and L‐HDAg), and its replication is mediated by the host RNA polymerases. The HBsAg‐coated HDV virions contain a ribonucleoprotein (RNP) formed by the RNA genome packaged with small and large HDAg. Farnesylation of the L‐HDAg is the limiting step for anchoring this RNP to HBsAg, and thus for assembling, secreting and propagating virion particles. There is an important risk of morbidity and mortality caused by end‐stage liver disease and hepatocellular carcinoma with HDV and current treatment is pegylated‐interferon (PEG‐IFN) for 48 weeks with no other options in patients who fail treatment. The ideal goal for HDV treatment is the clearance of HBsAg, but a reasonably achievable goal is a sustained HDV virological response (negative HDV RNA 6 months after stopping treatment). New drug development must take into account the interaction of HBV and HDV. In this review, we will present the new insights in the HDV life cycle that have led to the development of novel classes of drugs and discuss antiviral approaches in phase II and III of development: bulevirtide (entry inhibitor), lonafarnib, (prenylation inhibitor) and REP 2139 (HBsAg release inhibitor).
New epidemiology of hepatitis delta
Authors: Vlachogiannakos Jiannis , Papatheodoridis George V. 
Published: February 2020

AbstractHepatitis D virus (HDV) is a defective pathogen that needs hepatitis B virus (HBV) for infection. Co‐infection of HBsAg‐positive individuals with HDV is commonly associated with a more rapid progression to cirrhosis, a higher incidence of hepatocellular carcinoma (HCC) and increased mortality. Initial studies have shown that about 5% of chronic HBV carriers worldwide (15‐20 millions) were also infected with HDV. However, recent studies suggest that the prevalence of HDV is at least two‐ to three‐fold higher than previous estimations. Improved diagnostic techniques have shown that HDV infection remains endemic in certain areas of the world. Injection drug users, individuals with high‐risk sexual behaviour and patients co‐infected with human immunodeficiency virus (HIV) represent the major reservoir of the disease in the Western world. Although the burden of HDV infection significantly decreased in Europe in the nineties, there has been no further decrease in the last decade, probably because of migration from HDV endemic countries. Until new and more effective therapies are available, public health measures should be reinforced by increasing prophylactic HBV vaccination programs, preventing transmission of the virus among parenteral drug users and implementing universal HDV screening of all HBV‐infected individuals.
Approach to the patient with chronic hepatitis B and decompensated cirrhosis
Authors: Shiffman Mitchell L. 
Published: February 2020

AbstractPatients with chronic hepatitis B virus (HBV) can develop progressive fibrosis, cirrhosis and hepatocellular carcinoma. Patients with chronic HBV and cirrhosis are at risk of developing hepatic decompensation and have high mortality without antiviral therapy and/or liver transplantation. Treatment of chronic HBV with antiviral therapy is indicated in all patients with cirrhosis whatever the HBe‐antigen status and serum alanine aminotransferase (ALT), so that hepatic decompensation can be prevented. Initiating antiviral therapy in patients with decompensated cirrhosis can improve liver function, Child‐Turcotte‐Pugh (CTP) and model for end‐stage liver disease (MELD) scores, as well as the need for liver transplantation and mortality. Patients with chronic HBV and cirrhosis who do not respond to antiviral therapy with normalization of ALT may have a co‐existent liver disorder. One of the most common co‐existent liver disorders present in patients with chronic HBV is non‐alcoholic fatty liver disease (NAFLD). Patients with chronic HBV, NAFLD and cirrhosis may be at risk of developing decompensated cirrhosis and require a liver transplant. If patients with chronic HBV require liver transplantation, infection of the liver graft with HBV can be prevented with antiviral therapy.
Micro‐elimination of hepatitis C virus
Authors: Hollande Clémence , Parlati Lucia , Pol Stanislas 
Published: February 2020

AbstractBackground & AimsHCV affects about 71 million people worldwide with 1.75 million new infections a year, mainly associated with healthcare, blood transfusion before screening of donors and drug use. Hepatitis C is a systemic disease with hepatic and extrahepatic manifestations resulting in increased morbidity and mortality in HCV‐infected patients compared to cured or uninfected individuals.ResultsThe goal of eliminating hepatitis C by 2030 is based on the following three main actions: strengthening and increasing outreach screening; increasing access to treatment; and improving prevention. Although the tools and the targets of HCV elimination have now been well established, micro‐elimination, a cure in high‐risk populations, is possible, but has not been achieved. These populations are mainly migrants, prisoners, drug users, HIV co‐infected patients and psychiatric patients. New tools must be developed to achieve micro‐elimination, in particular, rapid diagnostic orientation tests for better screening, delocalization of healthcare services to improve access to care, and training physicians to raise awareness of the disease, increase understanding of its pathogenesis and provide information on the availability of safe and effective treatment to cure chronic infection and reverse hepatic and extrahepatic manifestations.ConclusionThus, while the goal of complete elimination of hepatitis C virus was feasible in Western countries, it was more difficult in high‐prevalence countries where improvement in the detection of chronic infection (with rapid serological and virological diagnostic tests), outsourcing of diagnostic and therapeutic care and access to direct oral antivirals are urgently needed.
What's new in portal hypertension?
Authors: Mauro Ezequiel , Gadano Adrián 
Published: February 2020

AbstractPortal hypertension is defined as increased pressure in the portal venous system. The most common cause of portal hypertension is cirrhosis. In this setting, there is an increase in intrahepatic resistance leading to an increase in portal pressure. By increasing portal blood flow, splanchnic vasodilation further aggravates portal hypertension. New pathogenic pathways are being established which might result in new therapeutic strategies. The presence of varices at endoscopy and/or other abdominal portosystemic collaterals confirms the diagnosis of portal hypertension. The role of non‐invasive and imaging tests in the diagnosis and prognosis of portal hypertension has been clarified. Non‐selective beta‐blockers decrease both the risk of variceal haemorrhage and hepatic decompensation. Terlipressin, somatostatin or octreotide, in combination with early endoscopic therapy, are recommended for the treatment of acute variceal haemorrhage. Early Transjugular intrahepatic portosystemic shunt (TIPS) is effective as salvage therapy in acute variceal bleeding in selected patients and prevents rebleeding more effectively than endoscopic and medical therapy resulting in an increased survival.
Optimization of hepatitis C virus screening strategies by birth cohort in Italy
Authors: Kondili Loreta A. , Gamkrelidze Ivane , Blach Sarah , Marcellusi Andrea , Galli Massimo , Petta Salvatore , Puoti Massimo , Vella Stefano , Razavi Homie , Craxi Antonio , Mennini Francesco S. ,   PITER collaborating group
Published: February 2020

AbstractBackground and AimsCost‐effective screening strategies are needed to make hepatitis C virus (HCV) elimination a reality. We determined if birth cohort screening is cost‐effective in Italy.MethodsA model was developed to quantify screening and healthcare costs associated with HCV. The model‐estimated prevalence of undiagnosed HCV was used to calculate the antibody screens needed annually, with a €25 000 cost‐effectiveness threshold. Outcomes were assessed under the status quo and a scenario that met the World Health Organization's targets for elimination of HCV. The elimination scenario was assessed under five screening strategies.ResultsA graduated birth cohort screening strategy (graduated screening 1: 1968‐1987 birth cohorts, then expanding to 1948‐1967 cohorts) was the least costly. This strategy would gain approximately 144 000 quality‐adjusted life years (QALYs) by 2031 and result in an 89.3% reduction in HCV cases, compared to an 89.6%, 89.0%, 89.7% and 88.7% reduction for inversed graduated screening, 1948‐77 birth cohort, 1958‐77 birth cohort and universal screening, respectively. Graduated screening 1 yielded the lowest incremental cost‐effectiveness ratio (ICER) of €3552 per QALY gained.ConclusionsIn Italy, a graduated screening scenario is the most cost‐effective strategy. Other countries could consider a similar birth cohort approach when developing HCV screening strategies.
Time spent in distinct life history stages has sex‐specific effects on reproductive fitness in wild Atlantic salmon
Authors: Mobley Kenyon B. , Granroth‐Wilding Hanna , Ellmén Mikko , Orell Panu , Erkinaro Jaakko , Primmer Craig R. 
Published: February 2020

AbstractIn species with complex life cycles, life history theory predicts that fitness is affected by conditions encountered in previous life history stages. Here, we use a 4‐year pedigree to investigate if time spent in two distinct life history stages has sex‐specific reproductive fitness consequences in anadromous Atlantic salmon (Salmo salar). We determined the amount of years spent in fresh water as juveniles (freshwater age, FW, measured in years), and years spent in the marine environment as adults (sea age, SW, measured in sea winters) on 264 sexually mature adults collected on a river spawning ground. We then estimated reproductive fitness as the number of offspring (reproductive success) and the number of mates (mating success) using genetic parentage analysis (>5,000 offspring). Sea age is significantly and positively correlated with reproductive and mating success of both sexes whereby older and larger individuals gained the highest reproductive fitness benefits (females: 62.2% increase in offspring/SW and 34.8% increase in mate number/SW; males: 201.9% offspring/SW and 60.3% mates/SW). Younger freshwater age was significantly related to older sea age and thus increased reproductive fitness, but only among females (females: −33.9% offspring/FW and −32.4% mates/FW). This result implies that females can obtain higher reproductive fitness by transitioning to the marine environment earlier. In contrast, male mating and reproductive success was unaffected by freshwater age and more males returned at a younger age than females despite the reproductive fitness advantage of later sea age maturation. Our results show that the timing of transitions between juvenile and adult phases has a sex‐specific consequence on female reproductive fitness, demonstrating a life history trade‐off between maturation and reproduction in wild Atlantic salmon.
Two Phytophthora parasitica cysteine protease genes, PpCys44 and PpCys45, trigger cell death in various Nicotiana spp. and act as virulence factors
Authors: Zhang Qiang , Li Weiwei , Yang Jiapeng , Xu Junjie , Meng Yuling , Shan Weixing 
Published: February 2020

AbstractProteases secreted by pathogens have been shown to be important virulence factors modifying plant immunity, and cysteine proteases have been demonstrated to participate in different pathosystems. However, the virulence functions of the cysteine proteases secreted by Phytophthora parasitica are poorly understood. Using a publicly available genome database, we identified 80 cysteine proteases in P. parasitica, 21 of which were shown to be secreted. Most of the secreted cysteine proteases are conserved among different P. parasitica strains and are induced during infection. The secreted cysteine protease proteins PpCys44/45 (proteases with identical protein sequences) and PpCys69 triggered cell death on the leaves of different Nicotiana spp. A truncated mutant of PpCys44/45 lacking a signal peptide failed to trigger cell death, suggesting that PpCys44/45 functions in the apoplastic space. Analysis of three catalytic site mutants showed that the enzyme activity of PpCys44/45 is required for its ability to trigger cell death. A virus‐induced gene silencing assay showed that PpCys44/45 does not induce cell death on NPK1 (Nicotiana Protein Kinase 1)‐silenced Nicotiana benthamiana plants, indicating that the cell death phenotype triggered by PpCys44/45 is dependent on NPK1. PpCys44‐ and PpCys45‐deficient double mutants showed decreased virulence, suggesting that PpCys44 and PpCys45 positively promote pathogen virulence during infection. PpCys44 and PpCys45 are important virulence factors of P. parasitica and trigger NPK1‐dependent cell death in various Nicotiana spp.
Towards a relational conceptualization of empathy
Authors: van Dijke Jolanda , van Nistelrooij Inge , Bos Pien , Duyndam Joachim 
Published: February 2020

AbstractEmpathy is a fundamental concept in health care and nursing. In academic literature, it has been primarily defined as a personal ability, act or experience. The relational dimensions of empathy have received far less attention. In our view, individualistic conceptualizations are restricted and do not adequately reflect the practice of empathy in daily care. We argue that a relational conceptualization of empathy contributes to a more realistic, nuanced and deeper understanding of the functions and limitations of empathy in professional care practices. In this article, we explore the relational aspects of empathy, drawing on sources that offer a relational approach, such as the field of care ethics, the phenomenology of Edith Stein and qualitative research into interpersonal and interactive empathy. We analyse the relational aspects of three prevalent components of empathy definitions: the underlying ability or act (i.e. the cognitive, affective and perception abilities that enable empathy); the resulting experience (i.e. empathic understanding and affective responsivity) and the expression of this experience (i.e. empathic expression). Ultimately, we propose four inter‐related understandings of empathy: (a) A co‐creative practice based on the abilities and activities of both the empathizer and the empathee; (b) A fundamentally other‐oriented experience; (c) A dynamic, interactive process in which empathizer and empathee influence each other's experiences; (d) A quality of relationships.
Influence of Ketorolac Supplementation on Pain Control for Knee Arthroscopy: A Meta‐Analysis of Randomized Controlled Trials
Authors: Wan Rui‐jie , Liu Shao‐fan , Kuang Zhi‐ping , Ran Qiang , Zhao Chen , Huang Wei 
Published: February 2020

IntroductionThe efficacy of ketorolac supplementation on pain control for knee arthroscopy remains controversial. We conduct a systematic review and meta‐analysis to explore the impact of ketorolac supplementation on pain intensity after knee arthroscopy.MethodsWe search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2018 for randomized controlled trials (RCTs) assessing the effect of ketorolac supplementation vs placebo on pain management after knee arthroscopy. This meta‐analysis is performed using the random‐effect model.ResultsTen RCTs involving 402 patients are included in the meta‐analysis. Overall, compared with control group for knee arthroscopy, ketorolac supplementation is associated with notably reduced pain scores at 1 h (MD = −0.66; 95% CI = −1.12 to −0.21; P = 0.004) and 2 h (MD = −0.90; 95% CI = −1.74 to −0.07; P = 0.03), prolonged time for first analgesic requirement (MD = 1.94; 95% CI = 0.33 to 3.55; P = 0.02) and decreased number of analgesic requirement (RR = 0.41; 95% CI = 0.23 to 0.75; P = 0.003), but has no obvious impact on analgesic consumption (MD = −0.56; 95% CI = −1.14 to 0.02; P = 0.06), as well as nausea and vomiting (RR = 0.44; 95% CI = 0.12 to 0.21; P = 0.21).ConclusionsKetorolac supplementation is effective to produce pain relief for knee arthroscopy.
Combined 3D Printed Template to Guide Iliosacral Screw Insertion for Sacral Fracture and Dislocation: A Retrospective Analysis
Authors: Wu Chao , Deng Jia‐yan , Li Tao , Tan Lun , Yuan De‐chao 
Published: February 2020

ObjectiveTo evaluate the accuracy and safety of a combined 3D printed guide template (combined template) to assist iliosacral (IS) screw placement for sacral fracture and dislocation.MethodsA total of 37 patients, 24 men and 13 women, age from 22 to 68 years old, diagnosed with a sacral fracture and dislocation were involved in this study for retrospective analysis from January 2016 to February 2018. There were 19 patients in the template group (42 screws) and 18 patients in the conventional group (31 screws). In the combined template group, IS screw placement was assisted by a combined 3D printed template; in the conventional group, the IS screws were placed freehand under fluoroscopy. The accuracy of the IS screw placement was evaluated by comparing the screw angle and the location of the screw entry point between the actual and the simulated screw in the combined template group. The safety of the IS screw placement was evaluated by comparing the quality of the reduction, the grading of the screws, the operation time, and radiation exposure times between groups.ResultsA total of 73 pedicle screws were placed in 37 patients: 42 screws (30 S1, 12 S2) in the combined template group and 31 screws (23 S1, 8 S2) in the conventional group. In the conventional group, 1 patient developed symptoms of L5 nerve stimulation. In the combined template group, the average operative time of each screw was 25.01 ± 2.90 min, with average radiation exposure times of 12.05 ± 4.00. In the conventional group, the average operative time of each screw was 46.24 ± 9.59 min, with an average radiation exposure time of 56.10 ± 6.75. There were significant differences in operation and radiation exposure times between groups. The rate of screw perforation was lower in the combined template group (2 of 42 screws, 0 at grade III and 2 at grade II) than in the conventional group (5 of 38 screws, 2 at grade III and 3 at grade III). In the combined template group, the mean distance between the entry points of the actual and simulated screws was 1.4 ± 0.9 mm, with a mean angle of deviation of 2.1° ± 1.6°. All patients were followed up once every 3 months and were followed for 3 to 12 months.ConclusionUsing the combined template to assist with the insertion of IS screws delivered good accuracy, less fluoroscopy and shorter operation time, and avoided neurovascular injury as a result of screw malposition.