Miracle-dz/UniFAR-FTUs huggingface dataset:
Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.
Mental health problems in adolescents with delayed sleep phase: results from a large population‐based study in Norway

The aim of the current study was to compare mental health problems, resilience and family characteristics in adolescents with and without delayed sleep phase (DSP) in a population‐based sample. Data were taken from the youth@hordaland‐survey, a large population‐based study in Hordaland County in Norway conducted in 2012. In all, 9338 adolescents aged 16–19 years (53.5% girls) provided self‐reported data on a wide range of instruments assessing mental health symptoms, including depression, anxiety, obsessive–compulsive behaviours, attention deficit hyperactive disorder (ADHD) symptoms, perfectionism, resilience and sleep. Measures of socioeconomic status were also included. Three hundred and six adolescents (prevalence 3.3%) were classified as having DSP [according to the International Classification of Sleep Disorders‐2 (ICSD‐2)] criteria. Adolescents with DSP reported higher levels of depression, anxiety and ADHD symptoms. Adolescents with DSP also exhibited significantly lower levels of resilience. The Cohen's d effect sizes ranged from small [obsessive–compulsive disorder (OCD): d = 0.15] to moderate (inattention: d = 0.71). In the fully adjusted model, the significant predictors of DSP included inattention [odds ratio (OR): 2.11], lack of personal structure (OR: 2.07), low (OR: 1.85) and high (OR: 1.91) paternal education, parents not living together (OR: 1.81), hyperactivity/inattention (OR: 1.71) and poorer family economy (OR: 1.59). In conclusion, the high symptom load across a range of mental health measures suggests that a broad and thorough clinical approach is warranted when adolescents present with DSP.
Explaining Systemic Risk in Money Market Funds

For the first time, this study evaluates the contributions to systemic risk in the context of U.S. institutional prime money market funds (MMFs) from different sources using partial least squares structural equation modeling (PLS-SEM). The primary motivation behind this study is to trace systemic risk to its underlying sources and measure which types of relationships provide significant explanation using PLS-SEM. I illustrate the application of PLS-SEM and interpretation of results in a step-by-step manner to empower those new to PLS-SEM, and undertake robustness testing. Findings indicate that through crisis years, macroprudential indicators contribute to potential systemic risk more than prudential indicators. This suggests that macroprudential indicators that can be traced to individual MMFs market positions are more important in understanding systemic risk during crises, and further underlines the interconnectedness of markets. PLS-SEM can be used to test the explanatory power of new indicators as they emerge in an exploratory environment.
Dermoscopic Features of Mucinous Carcinoma of the Skin

BACKGROUND Dermoscopic features of nonpigmented skin lesions are seldom reported; dermoscopy might be useful in speculating pathologic features in the upper dermis. OBJECTIVE The objective was to identify additional dermoscopic criteria. METHODS Dermoscopy of the mucinous carcinoma of the skin occurring on the cheek of a 69-year-old man was performed. RESULTS We have shown characteristic dermoscopic features of whitish network and light-brown globules and they correspond to the pathologic findings of fibrous septum and mucinous deposition, respectively. DISCUSSION Dermoscopic examination seemed useful as an adjunct to the diagnosis of this rare nonpigmented malignant neoplasm.
Slow Post-Financial Crisis Recovery and Monetary Policy

Post-financial crisis recoveries tend to be slow and accompanied by slowdowns in total factor productivity (TFP) and permanent losses in GDP. To prevent them, how should monetary policy be conducted? We address this issue by developing a model with endogenous TFP growth in which an adverse financial shock can induce a slow recovery. In the model, a welfare-maximizing monetary policy rule features a strong response to output, and the welfare gain from output stabilization is much larger than when TFP expands exogenously. Moreover, inflation stabilization results in a sizable welfare loss, while nominal GDP stabilization works well, albeit causing high interest rate volatility. (JEL E12, E23, E32, E43, E44, E52, G01)
The effect of capitation on GPs' referral decisions.

In the Norwegian capitation trial, the payment system for general practitioners (GPs) has been changed; a practice allowance component has been replaced by a capitation component and the fee-per-item component constitutes a smaller part of a GPs practice income than previously. From the theoretical modelling of GPs' referral decisions, we predict that the replacement of the practice allowance by a capitation component will increase the rate of referrals to specialists. This hypothesis is supported by an exploratory empirical study with data from a sample of GPs participating in the experiment.
Diagnosis and complications of Cushing's disease: gender‐related differences

Cushing's disease (CD) presents a remarkable preponderance in female gender, with a female‐to‐male ratio of 3–8:1. The aim of this study was to evaluate gender‐related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease.
Hyaluronan expression in primary and secondary brain tumors.

BACKGROUND Collectively, primary and secondary brain tumors represent a major public health challenge. Glioblastoma (GBM) is the most common primary brain tumor in adults and is associated with a dismal 5-year survival of only 10%. Breast cancer causes secondary tumors; it occurs in 200,000 patients yearly and 30% of these individuals develop brain metastases which also lead to a very poor prognosis. GBM and primary breast tumors are known to express hyaluronan (HA) which may serve as a therapeutic target. METHODS For the present study we had two aims: (I) to identify suitable preclinical models for HA in GBM by examining HA expression in human GBM cell lines implanted orthotopically in mice; and (II) to determine whether breast cancer brain metastases in human patients express HA similar to the primary tumor. Forty human surgical samples of primary breast tumors and breast cancer brain metastases were processed and stained for HA. Athymic nu/nu mice were orthotopically implanted with one of 15 GBM lines and after tumors were established, quantitative immunohistochemistry determined whether. RESULTS HA was expressed. All GBM cell lines and patient-derived orthotopic tumors did express HA, with 3 primary human lines expressing the highest staining intensity, above that of normal brain. All 40 human primary breast tumors and brain metastases examined also contained HA, though staining intensity was highly variable. CONCLUSIONS Our data support the use of specific patient-derived GBM cell lines in nu/nu mice for preclinical studies on HA-targeting therapies. Additionally, our research provides a basis for the assessment of HA expression and HA-targeting therapeutic agents for the treatment of breast cancer brain metastases.
Detection of Escherichia coli in sewage and sludge by polymerase chain reaction

A method in which the polymerase chain reaction (PCR) was used was developed to amplify either a uidA gene fragment or a 16S rRNA gene fragment from Escherichia coli in sewage and sludge. Because of interference caused by humic acidlike substances, crude DNA extracts were purified with a Sephadex G-200 spun column before the PCR was begun. A Southern analysis in which a nonradioactive chemiluminescent method was used was performed to confirm the presence of PCR products. The sensitivity of detection for PCR products when the chemiluminescent method was used was determined to be 30 ag of E. coli genomic DNA template. In seeded sludge, the PCR amplified the target DNA from 80 E. coli cells per g of sludge and 50 Shigella dysenteriae cells per g of sludge. Because only 0.05 aliquot of a sludge extract was used for the PCR, we deduced that the PCR detected target DNA equivalent to the DNA of 2.5 to 4 cells in the extract. The PCR amplified the uidA fragment from diluted sewage influents and effluents containing E. coli cells. Therefore, the PCR performed with a chemiluminescent gene probe can be used to detect the presence of potentially pathogenic microorganisms in sewage and sludge. This technique can be expanded to permit direct detection of pathogenic microorganisms in water samples, thus leading to enhanced public health protection.
The impact of biologic response modifiers on hepatitis B virus infection

Introduction: The biologic response modifiers are a diverse group of medications that have emerged over the last decade. They target pro-inflammatory cytokines or cell surface molecules that drive illnesses such as rheumatoid arthritis. Despite the greater control afforded they have also ushered in a new spectrum of side effects. As the same immunologic machinery that helps control infections such as HBV contributes to the pathogenesis of rheumatologic diseases, persistence or reactivation of the virus remains an evolving concern. Areas covered: A systemic literature review was performed using the PubMed and Medline databases (1996 to January 2010) searching for the index term ‘Hepatitis B’ combined with the terms ‘tumor necrosis factor’, ‘B cell’, ‘rituximab’, ‘IL-1’, ‘anakinra’, ‘IL-6’, ‘tocilizumab’, ‘CTLA-4’, and ‘abatacept’. All relevant articles in English were reviewed and secondary references of interest were also retrieved. This paper addresses the role of the various cytokines and cluster of differentiation molecules in controlling HBVinfection and the currently known effect that the biologic response modifiers have on viral control by the host immune response. Expert opinion: The risk of HBV reactivation is greatest in HBsAg positive patients. These patients should start antiviral therapy one week before receiving a biologic response modifier. The risk of HBV reactivation in HBsAg negative patients appears very low but when HBsAb titers are low use of rituximab or TNF-α antagonists may increase the risk of reactivation.
The Impact of Corporate Fraud on Director‐Interlocked Firms: Evidence from Bank Loans

We examine the impact of corporate fraud committed by one firm (the “fraudulent firm”) on other firms with interlocking directors (the “interlocked firms”), focusing on the debtholder side. We argue that the revelation of a fraudulent firm's fraud can damage the reputation of the interlocked firms because corporate governance can propagate via director interlocks. Empirically, we find that the interlocked firms' cost of debt is higher and the loan covenants become stricter after the fraud cases of the fraudulent firms are revealed. Consistent with the corporate governance propagation explanation, our results are weaker (stronger) for interlocked firms that have better (worse) pre‐event corporate governance standards. Our findings suggest that corporate fraud of fraudulent firms can affect other firms through director‐interlocks beyond shareholder value.
Comparison of nuclear ribosomal RNA genes among Solanum species and other Solanaceae.

The organization of the nuclear-encoded 18S, 5.8S, and 25S ribosomal RNA genes (ribosomal DNA; rDNA) of 21 New World species from different sections of the genus Solanum, of two Old World Solanum species, and of representatives of other Solanaceae (Nicotiana, Atropa, Datura, Physalis, and Capsicum) was analyzed by restriction enzyme mapping using different rDNA specific hybridization probes. All Solanum species investigated exhibited rDNA repeats between 8.7 and 9.3 kb in length; the only exception was S. neorossii with a repeat length of 10.3 kb. Sequence heterogeneity was observed mostly in the intergenic spacer (IGS) region. Restriction sites for EcoRI and DraI in the spacer sequences were found to be characteristic for the New World species of the genus Solanum and for Lycopersicon esculentum. An additional XbaI site was detected in the spacer region of two nontuber-bearing species, S. brevidens and S. etuberosum (subsection Estolonifera Hawkes; series Etuberosa), as well as in the primitive tuber-bearing species of the series Pinnatisecta and Polyadenia (subsection Potatoe G. Don), thus demonstrating that these Mexican species are separated from the other tuber-bearing species but are closely linked to the nontuber-bearing Estolonifera group. Two EcoRI sites mapped at the 3' end of the 25S rRNA coding region seem to be characteristic for members of the Solanaceae; the first EcoRI site is apparently methylated in approximately 50% of the rDNA repeats. Southern hybridization with an IGS fragment of Solanum tuberosum as hybridization probe and nucleotide sequence analysis of the phylogenetically informative 3' end of the 25S rDNA support the assumption that the New World species of the genus Solanum are closely related to Lycopersicon (tomato) in contrast with other Solanaceae investigated, Nicotiana, Atropa, Datura, Physalis, and Capsicum. (ABSTRACT TRUNCATED AT 250 WORDS)
The Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Ertugliflozin in Subjects With Type 2 Diabetes Mellitus

Ertugliflozin is a highly selective and potent inhibitor of the sodium‐glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The glycemic efficacy of sodium‐glucose cotransporter 2 inhibitors such as ertugliflozin depends on glucose filtration through the kidney. This phase 1, open‐label study evaluated the effect of renal impairment on the pharmacokinetics, pharmacodynamics, and tolerability of ertugliflozin (15 mg) in type 2 diabetes mellitus and healthy subjects with normal renal function (estimated glomerular filtration rate not normalized for body surface area ≥90 mL/min) and type 2 diabetes mellitus subjects with mild (60‐89 mL/min), moderate (30‐59 mL/min), or severe (<30 mL/min) renal impairment (n = 36). Blood and urine samples were collected predose and over 96 hours postdose for pharmacokinetic evaluation and measurement of urinary glucose excretion over 24 hours. Log‐linear regression analyses indicated predicted mean area under the concentration‐time curve values for mild, moderate, and severe renal function groups that were ≤70% higher relative to subjects with normal renal function. Generally consistent results were obtained with categorical analysis based on analysis of variance. The increase in ertugliflozin exposure in subjects with renal impairment is not expected to be clinically meaningful. Regression analysis of change from baseline in urinary glucose excretion over 24 hours vs estimated glomerular filtration rate showed a decrease in urinary glucose excretion with declining renal function. A single 15‐mg dose of ertugliflozin was well tolerated in all groups.
Immunoglobulin G and complement immunoreactivity in the cerebral cortex of patients with Rasmussen’s encephalitis

Objective: To provide evidence that complement (C′)-dependent processes may be involved in Rasmussen’s encephalitis (RE). Background: RE is a rare, progressive, childhood epilepsy syndrome associated with inflammation and neuronal cell loss in a single cerebral hemisphere. Recent work suggests an autoimmune immunoglobulin (Ig) G-mediated process is important in disease pathogenesis. Methods: Brain samples from RE and complex partial epilepsy control patients were analyzed immunohistochemically. Sections were stained for IgG and the C′ factors C4, C8, and the membrane attack complex (MAC). Results: Brain samples from three of five patients with active, progressive RE but neither of two chronic RE nor five control epilepsy patients demonstrated immunoreactivity for IgG, C4, C8, and MAC on discrete patches of cerebrocortical neurons. Intensely activated glial fibrillary acid protein–positive astrocytes were found in areas overlapping these patches. Conclusion: Focally distributed IgG- and C′-positive neurons were found to colocalize with activated astrocytes, suggesting focal IgG-dependent classical C′ cascade pathway activation with attendant tissue damage in this subset of RE patients. Intraparenchymal C′ activation triggered by pathogenic antibodies may contribute to the development of focal inflammation, neuronal cell loss, and pharmacoresistant seizures in some patients with this disease. This process may be an important component in the initial, active phase of RE.
Changing facets of leadership in East Asia: globalization, innovation and performance in Japan, South Korea and China

ABSTRACT Japan, South Korea and China are the three juggernauts of the East Asian economy. In gross domestic product terms, China is the world’s second largest economy, Japan the third and South Korea the eleventh. Also, Japan and South Korea are the only two of the OECD’s prestigious Development Assistance Committee members from Asia, providing a large combined annual budget to developing countries, and the only two Asian countries of the seven-member 50–20 Club with members with a population of 50 million or more and a per capita GDP of US$20,000 or more. Many studies have offered explanations of this Asian economic and corporate success, although few have attempted to explain the leadership styles in these three countries. Globalization has also changed these economies enormously, leading to the possible convergence with universalism forces and commensurate globalization of their leadership styles. This collection, therefore, presents some of the most recent findings of leadership studies on Japan, South Korea and China in light of this.
Experience with on-line partial discharge measurement in high voltage inverter fed motors

Partial discharge (PD) testing has long been an important tool for assessing the condition of the high voltage insulation in motor and generator stator windings. In the past several years, many motors have been powered from inverters which facilitate variable speed motor operation. The most common drive used today is the voltage-source, pulse width modulation (VS-PWM) type. VS-PWM drives rated up to 13.8 kV are becoming more common in natural gas processing plants, as well as in other petrochemical facilities. Such drives generate high voltage impulses in the kV range with risetimes in the sub-microsecond range. These impulses are a form of severe electrical interference that can make the on-line detection of partial discharge (with magnitudes 1000 times smaller) difficult due to the overlapping frequency content in PD and in the impulses. Thus, PD detection on medium voltage VS-PWM systems has been a challenge in spite of the serious stator winding insulation aging that such drives may cause to these motors. This paper discusses the stator winding failure mechanisms which produce PD, including the insulation problems that VS-PWM drives can accelerate. A research project that lasted several years is reviewed. It culminated in a prototype on-line PD monitoring system suitable for motors fed by VS-PWM drives.
Intra‐arterial magnetic resonance angiography of the iliac arteries: clinical experience using two different protocols

Purpose: To assess the feasibility of intra‐arterial magnetic resonance angiography (iaMRA) with two different protocols. Material and Methods: Twenty patients were prospectively examined after digital subtraction angiography. Contrast‐enhanced iaMRA was performed using a 1.5T magnetic resonance imaging (MRI) system. Contrast agent (gadodiamide) was injected through a conventional angiography catheter placed in the abdominal aorta. The patients were randomized into two groups each comprising 10 patients. Group 1 was examined with a FLASH‐3D (fast low‐angle shot) sequence, allowing the center of the k‐space to be acquired 0.5 s after initiation of the measurement. Group 2 was examined with the identical sequence, but the center of the k‐space was acquired after 8.7 s. The increase in the intravascular signal intensity was determined and the diagnostic value of the angiograms was independently scored by 4 investigators using a 5‐point scale. Results: Nineteen of 20 MRAs were scored as diagnostic; only 1 was scored as non‐diagnostic by 2 observers. The diagnostic value of the angiograms of group 2 was judged superior to that of group 1 owing to a more homogeneous intravascular contrast distribution. Conclusion: Intra‐arterial MRA is feasible. The diagnostic value of angiograms using a flash sequence with center of the k‐space acquisition after 8.7 s ranged from good to excellent. This sequence is appropriate for iaMRA of iliac arteries to support MR guided intervention.