Miracle-dz/UniFAR-FTUs huggingface dataset:
CX3CR1–fractalkine axis drives kinetic changes of monocytes in fibrotic interstitial lung diseases

Circulating immune cell populations have been shown to contribute to interstitial lung disease (ILD). In this study, we analysed circulating and lung resident monocyte populations, and assessed their phenotype and recruitment from the blood to the lung in ILD. Flow cytometry analysis of blood samples for quantifying circulating monocytes was performed in 105 subjects: 83 with ILD (n=36, n=28 and n=19 for nonspecific interstitial pneumonia, hypersensitivity pneumonitis and connective-tissue disease-associated ILD, respectively), as well as 22 controls. Monocyte localisation and abundance were assessed using immunofluorescence and flow cytometry of lung tissue. Monocyte populations were cultured either alone or with endothelial cells to assess fractalkine-dependent transmigration pattern. We show that circulating classical monocytes (CM) were increased in ILD compared with controls, while nonclassical monocytes (NCM) were decreased. CM abundance correlated inversely with lung function, while NCM abundance correlated positively. Both CCL2 and CX3CL1 concentrations were increased in plasma and lungs of ILD patients. Fractalkine co-localised with ciliated bronchial epithelial cells, thereby creating a chemoattractant gradient towards the lung. Fractalkine enhanced endothelial transmigration of NCM in ILD samples only. Immunofluorescence, as well as flow cytometry, showed an increased presence of NCM in fibrotic niches in ILD lungs. Moreover, NCM in the ILD lungs expressed increased CX3CR1, M2-like and phagocytic markers. Taken together, our data support that in ILD, fractalkine drives the migration of CX3CR1+ NCM to the lungs, thereby perpetuating the local fibrotic process. The compartmental imbalance of fractalkine mediates the migration of nonclassical monocytes into fibrotic lung tissues. Furthermore, nonclassical monocyte-derived cells show a M2-like and phagocytic phenotype in ILD lungs. http://bit.ly/2CMFWex
Patients with pacemakers or defibrillators do not need to worry about e-Cars: An observational study.

BACKGROUND Electric cars are increasingly used for public and private transportation and represent possible sources of electromagnetic interference (EMI). Potential implications for patients with cardiac implantable electronic devices (CIED) range from unnecessary driving restrictions to life-threatening device malfunction. This prospective, cross-sectional study was designed to assess the EMI risk of electric cars on CIED function. METHODS One hundred and eight consecutive patients with CIED presenting for routine follow-up between May 2014 and January 2015 were enrolled in the study. The participants were exposed to electromagnetic fields generated by the four most common electric cars (Nissan Leaf, Tesla Model S, BMW i3, VW eUp) while roller-bench test-driving at Institute of Automotive Technology, Department of Mechanical Engineering, Technical University, Munich. The primary endpoint was any abnormalities in CIED function (e.g. oversensing with pacing-inhibition, inappropriate therapy or mode-switching) while driving or charging electric cars as assessed by electrocardiographic recordings and device interrogation. RESULTS No change in device function or programming was seen in this cohort which is representative of contemporary CIED devices. The largest electromagnetic field detected was along the charging cable during high current charging (116.5 μT). The field strength in the cabin was lower (2.1-3.6 μT). CONCLUSIONS Electric cars produce electromagnetic fields; however, they did not affect CIED function or programming in our cohort. Driving and charging of electric cars is likely safe for patients with CIEDs.
Legal, Economic and Cultural Aspects of File Sharing

This contribution seeks to identify the short and long-term economic and cultural effects of file sharing on music, films and games, while taking into account the legal context and policy developments. The short-term implications examined concern direct costs and benefits to society, whereas the long-term impact concerns changes in the industry's business models as well as in cultural diversity and the accessibility of content. It observes that the proliferation of digital distribution networks combined with the availability of digital technology among consumers has broken the entertainment industries' control over the access to their products. Only part of the decline in music sales can be attributed to file sharing. Despite the losses for the music industry, the increased accessibillity of culture renders the overall welfare effects of file sharing robustly positive. As a consequence the entertainment industries, particularly the music industry, have to explore new models to sustain their business.
Development and validation of LC-MS/MS method for imatinib and norimatinib monitoring by finger-prick DBS in gastrointestinal stromal tumor patients

The introduction of imatinib, an oral tyrosine kinase inhibitor, as first-line standard therapy in patients with unresectable, metastatic, or recurrent gastro-intestinal stromal tumor (GIST), strongly improved their treatment outcomes. However, therapeutic drug monitoring (TDM) is recommended for this drug due to the large inter-individual variability in plasma concentration when standard dose is administered. A Cmin higher than 760 ng/mL was associated with a longer progression free survival. Thus, a LC-MS/MS method has been developed and fully validated to quantify imatinib and its active metabolite, norimatinib, in finger-prick dried blood spot (DBS). The influence of hematocrit, sample homogeneity, and spot size and the correlation between finger-prick and venous DBS measurements were also assessed. The method showed a good linearity (R2 > 0,996) between 50–7500 ng/mL for imatinib and 10–1500 ng/mL for norimatinib. Analytes were extracted from DBS samples by simply adding to 3 mm-discs 150 μL of acidified methanol containing IMA-D8. The collected extract was then injected on a LC Nexera system in-house configured for the on-line cleanup, coupled with an API-4000 QT. The chromatographic separation was conducted on a Synergi Fusion-RP column (4 μm, 2x50 mm) while the trapping column was a POROS R1/20 (20 μm, 2x30 mm). The total run time was 8.5 min. DBSs stored at room temperature in plastic envelopes containing a silica-gel drying bag were stable up to 16 months. The proposed method was applied to 67 clinical samples, showing a good correlation between patients’ finger-prick DBS and plasma concentrations, measured by the reference LC-MS/MS method, internally validated. Imatinib and norimatinib concentrations found in finger-prick DBS were adjusted by hematocrit or by an experimental correction factor to estimate the corresponding plasma measurements. At the best of our knowledge, the proposed LC-MS/MS method is the first analytical assay to measure imatinib and norimatinib in DBS samples.
Relationship between macro-ergonomics and occupational stress in casting industry

Introduction: Macro-ergonomics is an important factor that affects behavior, favorable performance and personnel’s efficiency that can cause conformity of employees by increasing labor and efficiency and in result decreasing employees’ stress amount. The aim of the present study was to investigate relationship between Macro-ergonomics and occupational stress in employees working in one casting industry in Isfahan. Materials and methods: This study was analytical-descriptive and of the type sectional that was conducted on 100 employees. To determine Macro-ergonomics status score, the Macro-ergonomics status evaluation questionnaire and the standard questionnaire of occupational stress (HSE) was used. Data were analyzed using SPSS software, version 20 and using Pearson correlation tests and regression analysis and couple-t. Results: Pearson correlation test showed that there was negative relation between Macro-ergonomics score and occupational stress (r= -0.62, P<0.05). Also results showed that there was adverse relation between occupational stress with all of Macro-ergonomics areas (r= -0.598, P<0.05). Conclusion: According to the results, Ergonomic factors have important role in occupational stress among employees. The more effect on decrease of occupational stress was observed when using suitable strategies and correction of this aspect of the organization.
Regulation and Effects of FGF23 in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a global health epidemic that accelerates cardiovascular disease, increases risk of infection, and causes anemia and bone disease, among other complications that collectively increase risk of premature death. Alterations in calcium and phosphate homeostasis have long been considered nontraditional risk factors for many of the most morbid outcomes of CKD. The discovery of fibroblast growth factor 23 (FGF23), which revolutionized the diagnosis and treatment of rare hereditary disorders of FGF23 excess that cause hypophosphatemic rickets, has also driven major paradigm shifts in our understanding of the pathophysiology and downstream end-organ complications of disordered mineral metabolism in CKD. As research of FGF23 in CKD has rapidly advanced, major new questions about its regulation and effects continuously emerge. These are promoting exciting innovations in laboratory, patient-oriented, and epidemiological research and stimulating clinical trials of new therapies and repurposing of existing ones to target FGF23. Expected final online publication date for the Annual Review of Physiology, Volume 82 is February 10, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Interleukin-37 is increased in peripheral blood mononuclear cells of coronary heart disease patients and inhibits the inflammatory reaction

It has been universally acknowledged that interleukin-37 (IL-37) has an immunosuppressive effect on various inflammatory disorders. However, whether IL-37 participates in the acute inflammation associated with coronary heart disease (CHD) has not yet been clarified. In the present study, the association between the serum levels of IL-37 and the clinical indexes of CHD were analysed. In addition, the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) were studied in CHD patients. PBMCs from 46 healthy controls (HCs) and 92 CHD patients were cultured in vitro and stimulated using the recombinant IL-37 protein. The protein levels, as well as the mRNA expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17) were analysed by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR). Spearman's correlation test was performed to examine the association between the serum level of IL-37 and the levels of pro-inflammatory cytokines, certain clinical indexes, and disease activity during CHD. Compared to the HCs, the CHD patients, especially those with acute myocardial infarction, exhibited higher levels of IL-37 in their PBMCs and sera. Serum levels of IL-37 were associated with the levels of IL-17, IL-6, and TNF-α, and clinical indexes such as the left ventricular ejection fraction (LVEF), amino-N-terminal pro-plasma brain natriuretic peptide (NT-proBNP) levels, and cardiac troponin T (cTnT) levels in CHD patients. Compared to the HC group, the production of inflammatory cytokines such as IL-17, IL-6, TNF-α, and IL-1β increased in the PBMCs of CHD patients and significantly decreased after the stimulation of the cells with recombinant IL-37. The IL-37 levels in CHD patients were high, and were correlated with the levels of CHD-related pro-inflammatory cytokines and disease activity. Notably, the expression of CHD-related pro-inflammatory cytokines in the PBMCs of CHD patients decreased following the stimulation of the cells with recombinant IL-37, indicating that IL-37 exerts anti-inflammatory effects during CHD.
Free-Living Sleep, Food Intake, and Physical Activity in Night and Morning Shift Workers

Abstract Objective: Shift work is associated with risk for adverse health outcomes including cardiovascular disease, type 2 diabetes, cancer, and obesity. Short sleep duration combined with disruptions to the circadian system may alter factors involved with the behavioral regulation of energy intake and expenditure. We aimed to determine how shift work affects sleep, food intake, and physical activity. Methods: This was a field-based observational study using objective assessments of sleep and physical activity and a 24-hour dietary recall in shift workers. Day (n = 12) and night (n = 12) hospital shift workers (nurses and technicians) who were women had their free-living sleep and physical activity tracked via accelerometry, and completed a computer-assisted 24-hour food recall, during a series of work shifts. Results: Compared to day workers, night workers had significantly shorter sleep duration and reported more premature awakenings and feeling less refreshed upon awakening. Daily self-reported energy and macronutrient intakes were not different between groups, although the night shift workers reported a significantly longer total daily eating duration window than day workers. Objectively recorded physical activity levels were not different between groups. Conclusions: The present findings confirm that sleep is disturbed in women night workers, while there are relatively less effects on objectively recorded physical activity and self-reported food intake. We also observed a prolonged daily eating duration in night vs. day workers. These observations can help inform the design of novel behavioral interventions, including, potentially, time restricted feeding approaches (e.g., by limiting daily eating episodes to within a 10–12 h window), to optimize weight management in shift workers.
Dietary Approaches to the Prevention of Vitamin A Deficiency: Indian Experience with Red Palm Oil as a Source of Vitamin A

In an effort to continue to reduce vitamin A deficiency in India, studies have been conducted using red palm oil. The bioavailability of β-carotene in red palm oil is higher that than of green and yellow vegetables, with an absorption rate of nearly 90%. Studies have shown that red palm oil is safe and acceptable. Refined red palm oil (Carotino) can be mixed with other refined edible oils without affecting their taste. It does add a yellow color, for which consumer education is needed. Because of stability problems, the final product selected for feeding would need to contain 7% to 10% of the Carotino, depending on the form used. Further studies are being planned to evaluate the effect of Carotino-containing supplements on growth and vitamin A status of children. A major limitation to producing supplementary foods containing red palm oil is the small amount of red palm oil produced in India at this time; most of it has to be imported from Malaysia.
ASD symptoms in toddlers and preschoolers: An examination of sex differences

Although considerable work has documented higher prevalence rates of autism spectrum disorder (ASD) in boys, fewer studies have focused on sex differences within samples of young children at‐risk for ASD. This study examined sex differences in ASD symptom domains and ASD screening outcomes among toddlers (18–35 months) and preschoolers (36–72 months) with ASD‐related concerns. Participants included 480 children between 18 and 72 months evaluated by university‐based ASD specialty clinics. Results revealed significant sex differences in severity of social communication (SC) deficits across age groups. Within the toddler group, girls diagnosed with ASD displayed greater SC deficits according to standardized observation and clinician severity ratings. Within the preschool group, girls diagnosed with ASD were rated by parents as having more severe SC deficits, but these differences were not corroborated by standardized observations or clinician ratings. No sex differences emerged for severity of restricted repetitive behaviors (RRBs) for either age group. Across the entire referred sample, boys and girls did not differ in terms of scores on commonly used screening instruments. Importantly, results suggest that two of the most commonly used ASD screeners (i.e., Modified‐Checklist for Autism in Toddlers‐Revised with Follow‐up and Social Communication Questionnaire ) may underidentify RRBs in toddler and preschool‐aged girls as screening scores were only influenced by severity of SC deficits. Greater SC deficits in young girls with ASD along with its impact on screening status suggests greater attention be placed on the under‐identification of ASD in girls as well as current screening measures' ability to tap into the topography of ASD symptoms across genders. Autism Res 2020, 13: 157–166. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Genetic toxicity assessment using liver cell models: past, present, and future

ABSTRACT Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.
In vivo epigenetic CRISPR screen identifies Asf1a as an immunotherapeutic target in Kras-mutant lung adenocarcinoma.

Despite substantial progress in lung cancer immunotherapy, the overall response rate in KRAS-mutant lung adenocarcinoma (ADC) patients remains low. Combining standard immunotherapy with adjuvant approaches that enhance adaptive immune responses-such as epigenetic modulation of anti-tumor immunity-is therefore an attractive strategy. To identify epigenetic regulators of tumor immunity, we constructed an epigenetic-focused sgRNA library, and performed an in vivo CRISPR screen in a KrasG12D/P53-/- (KP) lung ADC model. Our data showed that loss of the histone chaperone Asf1a in tumor cells sensitizes tumors to anti-PD-1 treatment. Mechanistic studies revealed that tumor cell-intrinsic Asf1a deficiency induced immunogenic macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression and potentiated T cell activation in combination with anti-PD-1. Our results provide rationale for a novel combination therapy consisting of ASF1A inhibition and anti-PD-1 immunotherapy.
Development of MyTeen Text Messaging Program to Support Parents of Adolescents: Qualitative Study

Background Parents play an important role in the lives of adolescents, and supporting and addressing the needs of families continue to be the focus of many researchers and policy makers. Mobile health interventions have great potential for supporting parents at a population level because of their broad reach and convenience. However, limited evidence exists for such interventions for parents of adolescents. This study reports on the formative work conducted with parents and/or primary caregivers to identify their needs and preferences for the development of MyTeen—an SMS text messaging program on promoting parental competence and mental health literacy for parents of adolescents (aged 10-15 years). Objective The aim of this qualitative study was to explore parents and/or primary caregivers’ perspectives around youth well-being, parenting, and parenting support and their input on the development of MyTeen SMS text messaging parenting intervention. Methods A total of 5 focus groups (n=45) were conducted with parents or primary caregivers of adolescents aged 10 to 15 years between October and December 2017 in New Zealand. A semistructured interview guideline and prompts were used. Data were audiotaped, transcribed, and analyzed using inductive thematic analysis. Results Participants were concerned about youth mental health (ie, stigma and increasing demand on adolescents), and a number of parenting challenges (ie, social expectations, time, impact of technology, changes in family communication pattern, and recognizing and talking about mental health issues) were noted. Importantly, participants reported the lack of services and support available for families, and many were not aware of services for parents themselves. A number of recommendations were given on the style, content, and frequency of developing the text messaging program. Conclusions Findings from this qualitative work informed the development of MyTeen, an SMS text messaging program designed to increase parental competence and improve mental health literacy for parents of adolescents.
Preliminary study on the influence of collaboration on the success and efficiency of postgraduate students

Postgraduate research calls for a novel contribution to the existing literature, which should be made independently by the researcher. In many institutions, the traditional approach does not encourage or promote collaboration with others as it is thought that a student of higher education should be able to function independently. This paper argues that postgraduate students could be more successful through increased collaboration with both other PhD students and their supervisor. This proposition is supported by a survey, which shows that students are highly in favour of increasing the extent of their collaboration with others. It is envisaged that collaboration should take place from the early stages of a PhD in the form of mentoring and working closely with a supervisor to the later stages, where experience enables guidance of others to more efficient methods and analysis techniques. Increased collaboration can also provide sidebenefits such as better communication and leadership skills.