pinecone/core-2020-05-10-deduplication huggingface dataset:
Interferon alfa for chronic hepatitis B infection: Increased efficacy of prolonged treatment

Interferon alfa (IFN-a) is the primary treatment for\ud
chronic hepatitis B. The standard duration of IFN-a therapy\ud
is considered 16 weeks; however, the optimal treatment\ud
length is still poorly defined. We evaluated the efficacy and\ud
acceptability of prolonged IFN-a treatment in patients with\ud
chronic hepatitis B. To investigate whether treatment prolongation\ud
could enhance the rate of hepatitis B e antigen\ud
(HBeAg) seroconversion, we conducted a prospective, controlled,\ud
multicenter trial in which all patients were treated\ud
with a standard regimen of 10 million units IFN-a 3 times\ud
per week over 16 weeks. Patients who were still HBeAgpositive\ud
after 16 weeks of therapy were randomized to\ud
prolongation of the identical regimen up to 32 weeks\ud
(prolonged therapy) or discontinuation of treatment (standard\ud
therapy). Among the 162 patients who entered the\ud
study, 27 (17%) were HBeAg-negative after the first 16\ud
weeks of treatment, and 118 were randomized to standard\ud
or prolonged therapy. After randomization, a response\ud
(HBeAg seroconversion and sustained hepatitis B virus\ud
[HBV]-DNA negativity) was observed in 7 of the 57 (12%)\ud
patients assigned to standard therapy versus 17 of the 61\ud
(28%) patients assigned to prolonged therapy (P 5 .04). A\ud
low level of viral replication after 16 weeks of treatment, as\ud
indicated by serum HBV-DNA values under 10 pg/mL, was\ud
found to be the only independent predictor of response\ud
(52% vs. 0%; P F .001) during prolonged therapy. The\ud
prolonged IFN-a schedule was well tolerated in the large\ud
majority of patients. In chronic hepatitis B, prolongation of\ud
IFN-a therapy up to 32 weeks is superior to a standard\ud
course of 16 weeks. Those patients who exhibit a low level\ud
of viral replication at the end of the standard regimen\ud
benefit most from prolonged treatment
Retreatment of chronic hepatitis B e antigen-positive patients with recombinant interferon alfa-2a

Fifty-seven patients with chronic hepatitis B, hepatitis B virus (HBV) e antigen (HBeAg) and HBV DNA positivity, and aminotransferase elevation despite a previous course of any type of adequate interferon alfa (IFN-α) therapy were included in a multicenter prospective randomized controlled trial. The objective of the study was to compare a second course of IFN-α therapy (9 million units [MU] of IFN-α-2a, Roferon-A, thrice weekly for 6 months) versus no therapy in terms of loss of HBV DNA and HBeAg. At the end of the study, a sustained clearance of HBV DNA and HBeAg was observed in 9 of the 27 (33.3%) patients who had received retreatment with IFN-α compared with 3/30 (10%) patients who spontaneously cleared these markers in the untreated control group (χ2 = 4.66, P = .031; odds ratio: 4.5, 95%; confidence interval: 1.1-18.9). None of the responders lost HBsAg. Patients retreated with IFN-α were more likely to have biochemical remission in association with HBV clearance (5/27, 18.5%) compared with untreated patients (1/30, 3.3%; Fisher's exact test P = .09). Histological improvement in the liver necroinflammatory activity was observed among sustained responders to IFN-α retreatment, consisting of regression of the portal and periportal inflammation and of the piecemeal necrosis; there was no change in the degree of liver fibrosis. Side effects were similar to those previously reported during IFN-α treatment; these were mild and reversible on IFN-α discontinuation. None of the baseline features were associated with response by Cox's regression analysis. In summary, viremic patients with chronic HBeAg-positive hepatitis may experience disease remission following retreatment with IFN-α. Thus, retreatment with IFN-α may be considered a therapeutic option
Hepatic retransplantation in cholestatic liver disease: Impact of the interval to retransplantation on survival and resource utilization

The aim of our study was to quantitatively assess the impact of hepatic retransplantation on patient and graft survival and resource utilization. We studied patients undergoing hepatic retransplantation among 447 transplant recipients with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) at 3 transplantation centers. Cox proportional hazards regression analysis was used for survival analysis. Measures of resource utilization included the duration of hospitalization, length of stay in the intensive care unit, and the duration of transplantation surgery. Forty-six (10.3%) patients received 2 or more grafts during the follow-up period (median, 2.8 years). Patients who underwent retransplantation had a 3.8-fold increase in the risk of death compared with those without retransplantation (P < .01). Retransplantation after an interval of greater than 30 days from the primary graft was associated with a 6.7-fold increase in the risk of death (P < .01). The survival following retransplantations performed 30 days or earlier was similar to primary transplantations. Resource utilization was higher in patients who underwent multiple consecutive transplantations, even after adjustment for the number of grafts during the hospitalization. Among cholestatic liver disease patients, poor survival following hepatic retransplantation is attributed to late retransplantations, namely those performed more than 30 days after the initial transplantation. While efforts must be made to improve the outcome following retransplantation, a more critical evaluation may be warranted for late retransplantation candidates
LncRNA AK054921 and AK128652 are potential serum biomarkers and predictors of patient survival with alcoholic cirrhosis

Background:

Alcoholic liver disease (ALD) is one of the leading causes of chronic liver disease. Recent studies have demonstrated the roles of long noncoding RNAs (lncRNAs) in the pathogenesis of several disease processes. However, the roles of lncRNAs in patients with ALD remain unexplored.
Methods:

Global profiling for human lncRNAs from peripheral blood RNA was performed in a well characterized cohort of healthy controls (HC, n=4), excessive drinkers without liver diseases (ED, n=4), and those with alcoholic cirrhosis with different severities (AC, n=12). The expression of unique lncRNA signatures were validated in a separate cohort of HC (n=17), ED (n=19), AC (n=48), and human liver tissues with ALD (n=19).
Results:

Detailed analysis of plasma lncRNAs in AC subjects with different severities compared to HC identified 244 commonly up-regulated lncRNAs and 181 commonly down-regulated lncRNAs. We further validated top 20 most differentially up- and down-regulated lncRNAs in ED and AC as compared to HC and also determined the expression of selected lncRNAs in human liver tissues with or without AC. Among those lncRNAs, AK128652 and AK054921 were two of the most abundantly expressed lncRNAs in normal human plasma and liver, and their levels were significantly elevated in AC. The prognostic significance of AK128652 and AK054921 was determined in 48 subjects with AC; who were prospectively followed for 520 days. The expression of AK128652 and AK054921 was inversely associated with survival in patients with AC.
Conclusions:

LncRNAs AK054921 and AK128652 are potential biomarkers to predict the progression to ALD in those with excessive alcohol consumption and are predictors of survival with patients with alcoholic cirrhosis
Drug-induced cholestasis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesCholestatic drug-induced liver injury (DILI) can be a diagnostic challenge due to a large differential diagnosis, variability in clinical presentation, and lack of serologic biomarkers associated with this condition. The clinical presentation of drug-induced cholestasis includes bland cholestasis, cholestatic hepatitis, secondary sclerosing cholangitis, and vanishing bile duct syndrome. The associate mortality of cholestatic DILI can be as high as 10%, and thus prompt recognition and removal of the offending agent is of critical importance. Several risk factors have been identified for drug-induced cholestasis, including older age, genetic determinants, and properties of certain medications. Antibiotics, particularly amoxicillin/clavulanate, remain the predominant cause of cholestatic DILI, although a variety of other medications associated with this condition have been identified. In this review, we summarize the presentation, clinical approach, risk factors, implicated medications, and management of drug-induced cholestatic liver injury. (Hepatology Communications2017;1:726-735)
Segregated hepatocyte proliferation and metabolic states within the regenerating mouse liver.

Mammalian partial hepatectomy (PH) induces an orchestrated compensatory hyperplasia, or regeneration, in remaining tissue to restore liver mass; during this process, liver functions are maintained. We probed this process in mice with feeding- and light/dark-entrained animals subjected to sham or PH surgery. Early on (i.e., 10 hours), irrespective of sham or PH surgery, hepatocytes equidistant from the portal and central veins (i.e., midlobular) accumulated the G1-phase cell-division-cycle marker cyclin D1. By 24 hours, however, cyclin D1 disappeared absent PH but was reinforced in midlobular hepatocytes after PH. At 48 hours after PH and 2 hours fasting, synchronously mitotic hepatocytes possessed less glycogen than surrounding nonproliferating hepatocytes. The differential glycogen content generated a conspicuous entangled pattern of proliferating midlobular and nonproliferating periportal and pericentral hepatocytes. The nonproliferating hepatocytes maintained aspects of normal liver properties. Conclusion: In the post-PH regenerating mouse liver, a binary switch segregates midlobular cells to proliferate side-by-side with nonproliferating periportal and pericentral cells, which maintain metabolic functions. Our results also indicate that mechanisms of liver regeneration display evolutionary flexibility. (Hepatology Communications 2017;1:871-885)
Interaction between the patatin-like phospholipase domain-containing protein 3 genotype and coffee drinking and the risk for acute alcoholic hepatitis

Only a subset of subjects with excessive alcohol consumption develops alcoholic liver disease (ALD). One of the major risk factors for ALD is the genetic variant of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene. Coffee is one of the most commonly consumed beverages, and coffee consumption has been associated with lower levels of serum alanine aminotransferase. The aim of this study was to investigate the role of coffee drinking and PNPLA3 rs738409 and their association with alcoholic hepatitis (AH) in a well-characterized cohort of subjects from the Translational Research and Evolving Alcoholic Hepatitis Treatment consortium. AH subjects and heavy drinking controls without a history of liver disease who were enrolled between May 2013 and May 2016 were included (n = 339), and the details of alcohol and coffee consumption were assessed. The PNPLA3 variant was determined among participants of European ancestry (n = 183). Relationships between baseline data and AH status were determined, and multivariable logistic regression modeling was performed. During the study period, 189 cases with AH and 150 heavy drinking controls were prospectively enrolled. The prevalence of regular coffee consumption was significantly lower in patients with AH compared to controls (20% versus 43%; P < 0.0001). The overall minor allele frequency of the PNPLA3 variant was higher in AH cases. Multivariable logistic regression revealed that coffee consumption and PNPLA3 were significantly associated with AH status at baseline after adjusting for relevant patient characteristics. Conclusion: We found a higher prevalence of AH among heavy drinkers with PNPLA3 G/G and G/C genotypes regardless of coffee consumption status and a higher prevalence of AH among heavy drinkers who were not regular coffee drinkers. These findings remained after considering relevant baseline patient characteristics. Further studies are needed to confirm our observation
Age-dependent glycosylation of the sodium taurocholate cotransporter polypeptide: From fetal to adult human livers

Sodium taurocholate cotransporter polypeptide (NTCP), mainly expressed on the sinusoidal membrane of hepatocytes, is one of the major transporters responsible for liver bile acid (BA) re‐uptake. NTCP transports conjugated BA from the blood into hepatocytes and is crucial for correct enterohepatic circulation. Studies have shown that insufficient hepatic clearance of BA correlates with elevated serum BA in infants younger than 1 year of age. In the current study, we investigated human NTCP messenger RNA and protein expression by using reverse‐transcription quantitative polymerase chain reaction and immunoblotting in isolated and cryopreserved human hepatocytes from two different age groups, below and above 1 year of age. Here, we show that NTCP messenger RNA expression is not modulated whereas NTCP protein posttranslational glycosylation is modulated in an age‐dependent manner. These results were confirmed by quantification analysis of NTCP 55‐kDa N‐glycosylated bands, which showed significantly less total NTCP protein in donors below 1 year of age compared to donors older than 1 year. NTCP tissue localization was also analyzed by means of immunofluorescence. This revealed that NTCP cellular localization in fetal samples was mainly perinuclear, suggesting that NTCP is not glycosylated, while its postnatal localization on the plasma membrane is age dependent compared to multidrug resistant protein 2, which is apical starting in fetal life. Conclusion: After birth, the NTCP age‐dependent maturation process requires approximately 1 year to complete NTCP glycosylation in human hepatocytes. Therefore, NTCP late posttranslational glycosylation appears to be important for correct NTCP membrane localization, which might explain physiologic cholestasis in neonatal life and might play a central role for HBV infection after birth. (Hepatology Communications 2018;2:693‐702
Building Entrepreneurial Capacity in Post-Communist Poland: A Case Study

International audienceProcess of globalisation defines the new frontiers, leaving more importance to the territory. In the context of a rapidly changing international environment it is of no small importance to ask some question about the present situation in the bordering regions, their foreseeable evolution, both short- and long-term, and the economic and social consequences liable to results, considering their geographical and demographic situation, and their structures of activity. The redrawing of old national territories no longer seems to be the product of diplomacy and, in particular, wars; henceforth, it would appear to depend upon industrial economics. This is especially significant in the case of “Neisse” Euroregion located on Polish-Czech-German borders. Here are, at the present time, the chances of reviving a localized productive system that would give life to new forms of interregional co-operation. The aim of this article is to offer a reflection on the relevance of the marshallian district concept in the analysis of this interregional co-operation. The marshallian industrial district is based on the external economies of agglomerations and the economics of urbanisation, and this kind of development we can see today in Poland. The study of localized productive systems must be thorough and multidisciplinary and carried out through fieldwork. The aim is to understand how work, relationships and culture as well as material and immaterial infrastructures that give a place its original identity within the international division of labour regenerate in locally coherent forms. Regional production system grouped together on spatial level and integrated company networks at the regional level could serve to create local hubs of competition in Central and Eastern Europe
A Framework for Interactive Work Design based on Digital Work Analysis and Simulation

International audienceDue to the flexibility and adaptability of human, manual handling work is still very important in industry, especially for assembly and maintenance work. Well-designed work operation can improve work efficiency and quality; enhance safety, and lower cost. Most traditional methods for work system analysis need physical mock-up and are time consuming. Digital mockup (DMU) and digital human modeling (DHM) techniques have been developed to assist ergonomic design and evaluation for a specific worker population (e.g. 95 percentile); however, the operation adaptability and adjustability for a specific individual are not considered enough. In this study, a new framework based on motion tracking technique and digital human simulation technique is proposed for motion-time analysis of manual operations. A motion tracking system is used to track a worker's operation while he/she is conducting a manual handling work. The motion data is transferred to a simulation computer for real time digital human simulation. The data is also used for motion type recognition and analysis either online or offline for objective work efficiency evaluation and subjective work task evaluation. Methods for automatic motion recognition and analysis are presented. Constraints and limitations of the proposed method are discussed
Dancing between theory and practice: work stress intervention through the action-research

This quasi-experimental and longitudinal study assesses the effectiveness of a work stress intervention (i.e., Team Redesign) to increase job and personal resources and to consequently reduce job strain and increase employee psychosocial well-being in an enamel manufacturing company following the Resources-Experiences-Demands Model (RED Model) and within the Action-Research approach. The sample consisted of 108 employees at Time 1 and 72 employees at Time 2. Repeated-measures multivariable analysis of variance (MANOVA) showed that the Time × Intervention interaction had reliable, positive, and incremental effects on job resources (i.e., innovation climate), personal resources (i.e., professional self-efficacy and perceived competence), and motivational outcomes (i.e., work engagement, vigor, and dedication) on the intervention group (laboratory team, n = 9) when compared with the control group (n = 63 employees from different departments). Finally, we discuss the theoretical and practical implications based on the RED Model, including the feedback from Intervention (Action) to Theory (Research
Motivation requested - Work motivation and the work environment of IT consultants

The aim of the thesis is to examine the psychosocial work environment, with a focus on the work motivation, of Information Technology (IT) consultants. The thesis is based on five empirical studies. Study I (N=167) and Study II (N=380) are cross sectional studies, and Study III (N=320) is a two-wave longitudinal study. All participants in Studies I, II and III responded to a questionnaire on background variables, job demands, job control, motivators and perceived stress. The model used in Studies I, II and III is a mediational one that proposes that the effect of job demands and job control on perceived stress is indirect rather than direct. The hypothesis of motivators as a mediator was tested using full structural equation modeling (SEM) to estimate direct, indirect and total effects. The sample in Study IV consists of 12 IT consultants who were interviewed in order to understand what motivates IT consultants in their work environment. In Study V, six team leaders at an IT consultancy firm were interviewed in order to understand how team leaders perceive and construct their subordinates’ motivation. The results from Studies I, II and III highlight the importance of the presence of high levels of motivators in reducing the perceived stress among IT consultants. High job control was significantly related to high appraisals of motivators, and motivators were negatively related to perceived stress. Additionally, the results from these three studies indicate that job demands are positively related to perceived stress. In Studies I, II and III, motivators were measured using antecedent conditions that may lead to motivation (e.g., recognition, achievement, variety and the possibility for growth). The results from Study IV confirm that variety in tasks, job autonomy, praise for a job well done, the chance to acquire new skills, and the sense of accomplishment affect IT consultants’ work motivation. One of the main results from Study V is that managers have rather vague ideas about the motivation of their subordinates. One interpretation is that managers do not think that increasing the work motivation of their subordinates is an important part of their job.
The conclusion of this thesis is that, among IT consultants, motivators and job demands are important elements in the job stress framework. Motivation is a major component that explains organizational behavior and increases commitment and performance among employees. If a healthy work environment cannot be provided at the individual level, over time, the lack of such an environment will have implications at the organizational level. IT workers, who live at the edge of constant change, such as new technologies, require a high degree of flexibility and adaptability. In its study of contemporary IT workers, this thesis may generate important lessons for managing a major sector of the workforce of tomorrow
Health care and patient safety: The failure of traditional approaches – how human factors and ergonomics can and MUST help

Hazard and harm to patients as well as inefficiencies associated with health care have been well described as worldwide problems that result in hundreds of thousands of patient deaths and billions of dollars of waste every year. The underlying causes for these problems have not been nearly so well described; more importantly, generalizable mitigation strategies have not been effectively identified or used. The current state of health care and patient safety will be discussed with particular attention to the essential role that an engineering‐based approach, which is heavily rooted in human factors and ergonomics, must play if real and sustainable progress in the safe and efficient delivery of health care is to be achieved. Specific case studies that illustrate the compelling opportunities for the application of human factors and ergonomics–related knowledge will be discussed. © 2011 Wiley Periodicals, Inc
Human factors and ergonomics in patient safety curriculum

The importance of teaching human factors and ergonomics (HFE) and patient safety is registered in two compelling facts: 1) the numbers of physicians who train in VA hospitals and 2) in the need for hospitals to function as highly reliable organizations. In the United States, more than half of the physicians‐in‐training do at least part of their medical school and residency training at veterans' health care facilities. Health care currently does not measure up to other high‐reliability organizations. By providing a HFE‐based patient safety curriculum, we hope to improve patient safety at the frontlines. We see the lasting benefit as residency programs that produce physicians who are competent, patient safety problem solvers throughout their careers who will assist health care organizations to become highly reliable. © 2011 Wiley Periodicals, Inc