Miracle-dz/UniFAR-FTUs huggingface dataset:
Similar overall survival with reduced vs. standard dose bevacizumab monotherapy in progressive glioblastoma

Bevacizumab has demonstrated activity in glioblastoma (GBM), but the true benefits and optimal dose‐schedule are debated. A lower dose‐schedule than standard‐dose bevacizumab (10 mg/kg 2‐weekly) might offer similar benefits with lower costs. At our Institution, patients are randomly assigned at time of primary diagnosis to Neuro‐Oncologists, who have varying practices in terms of bevacizumab dose‐schedule upon progression.
A large real‐world cohort study examining the effects of long‐term entecavir on hepatocellular carcinoma and HBsAg seroclearance

Real‐world studies examining reduction in risk of hepatocellular carcinoma (HCC) in patients receiving antivirals are limited by the small size of the studies, or by data insufficiency and heterogeneity with short follow‐up duration. We aimed to examine the real‐world long‐term outcome of patients receiving entecavir treatment on HCC incidence and HBsAg seroclearance. The incidence of HCC in 1225 entecavir‐treated patients between 2002 and 2015 was compared with the HCC incidence estimated using the REACH‐B, GAG‐HCC and CU‐HCC scores. Standardized incidence ratios (SIR) were calculated. The impact of entecavir treatment on HBsAg seroclearance was also explored. The median follow‐up of the cohort was 6.6 years, with 66 cases of HCC development. Using the REACH‐B model, the reduction of HCC risk was significant from year 6 onwards with SIR of 0.68 (95% CI 0.535‐0.866) at year 10. In subgroup patients without cirrhosis, consistent risk reduction was observed from the fifth year and the SIR reached 0.51 (95% CI 0.271‐0.704) by year 10. Benefit in cirrhotic patients was demonstrated when using the GAG‐HCC and CU‐HCC score, with the SIR at year 10 being 0.38 (95% CI 0.259‐0.544) and 0.46 (95% CI 0.314‐0.659), respectively. The cumulative rate of HBsAg seroclearance was 5.2%. HBsAg level at third year of treatment and baseline‐to‐3‐year percentage reduction was predictive of subsequent HBsAg seroclearance. In conclusion, long‐term entecavir therapy was associated with significant reduction in the risk of HCC in the real world. However, HBsAg seroclearance rate remained low. Additional therapy may be considered in patients with adverse predictive factors for subsequent HBsAg seroclearance.
Telemedicine for Diabetic Retinopathy Screening in an Urban, Insured Population Using Fundus Cameras in a Primary Care Office Setting.

BACKGROUND AND OBJECTIVE This study examines the rate of adherence to recommended ophthalmology follow-up after primary care-based telemedicine diabetic retinopathy (DR) screening. PATIENTS AND METHODS Retrospective observational study of 5,764 insured diabetic patients undergoing telemedicine DR screening between May 2015 and April 2017 in an urban primary care setting. Patients underwent non-mydriatic fundus photography for telemedicine DR screening. The main outcome measure was the "capture rate. " RESULTS Of the patients studied, 31.7% were found to have any retinal pathology, and 20% were found to have DR. In the 11.8% percent of patients with sight-threatening retinopathy who were recommended to have a retinal examination, the capture rate was 81.9%. CONCLUSION The authors' study demonstrated higher capture rate than has been previously reported, indicating that telemedicine DR screening in an urban, insured population may be a useful method for triaging high-risk patients without losing patients to follow-up. [Ophthalmic Surg Lasers Imaging Retina. 2019;50: e274-e277. ].
Bilateral Drug-Induced Uveitis and Epiretinal Membrane during the Treatment of a Metastatic Cutaneous Melanoma

ABSTRACT Purpose: To report the case of a drug-induced uveitis during the treatment of a metastatic cutaneous melanoma. Case report: A 75-year-old female treated with Dabrafenib and Trametinib due to a cutaneous melanoma stage IV presented with blurriness in both eyes. The examination revealed bilateral intraocular signs of inflammation, and fundoscopy showed bilateral changes at the posterior pole, such as chorioretinal folds and Neurosensory Retinal Detachment (NRD). Due to a worsening of Visual Acuity (VA) and persistence of intraocular inflammation in spite of topical prednisolone acetate treatment, the therapy with Dabrafenib + Trametinib was interrupted, after having been administered for 4 months, and replaced by Nivolumab. Fundus abnormalities and intraocular inflammation improved, but VA remained low due to the presence of an epiretinal membrane in the right eye. Then, a decreasing course of prednisolone eye drops was introduced for one more month and finally interrupted without the cessation of Nivolumab. Conclusion: Drug-induced uveitis has been increasing in the last few years due to the development of new biological agents for treatment of different types of tumours. The management of these adverse events should be handled in collaboration with oncologists and ophthalmologists and must be individualised and based on the risk-benefit balance. A case report of an uveitis and subsequent development of an epiretinal membrane during the treatment with Dabrafenib, Trametinib and subsequent Nivolumab for a metastatic cutaneous melanoma is reported here, in order to note the importance of an adequate follow-up of patients treated with these drugs.
A super enhancer controls expression and chromatin architecture within the MHC class II locus

A super enhancer termed DR/DQ-SE within the MHC-II locus was examined by CRISPR mutagenesis. DR/DQ-SE was found to regulate HLA-DRB1, -DQA1, and -DQB1 gene expression by controlling chromatin interactions/looping between MHC-II gene promoters and CTCF binding elements.
An easy method for the clear detection of beige fat UCP1 by Western blotting

ABSTRACT Beige adipocytes, which consume energy mainly in an uncoupling protein 1 (UCP1)-dependent manner, are risen in white adipose tissue (WAT) depots. Since beige adipocyte development is gaining attention as a potential strategy for conquering obesity, worldwide researchers are making efforts to study its biological aspects. However, assessing UCP1 protein levels in beige adipocytes is challenging because of the high level of lipid contaminants in WAT. This study showed that an acetone precipitation method had advantages over conventional methods for eliminating lipid contaminants, achieving clear Western blot bands for WAT proteins, especially UCP1. Our results suggest that the acetone precipitation cleaning method could be useful for the clear analysis and precise evaluation of WAT proteins.
A longitudinal assessment of occupational stress in Emergency Department Nursing Staff.

AIMS To examine perceptions of occupational stress in Emergency Department (ED) nurses and measure the impact of interventions to address them. BACKGROUND Cross-sectional studies internationally have established that Emergency Department (ED) nursing staff experience high levels of occupational stress. Few however have examined changes in perceptions of stress over time or the impact of interventions to address them. Evaluation A structured questionnaire completed by volunteer nursing staff in one United Kingdom ED assessing perceptions of occupational stress and job satisfaction. Questionnaire rounds were administered in 2014 (T1), 2015 (T2) and 2017 (T3) at 18-month intervals. Statistical analyses were conducted using multivariate regression, t-tests and Mann Whitney U-Tests. Key Issue Statistically significant improvements in effort-reward balance, relational justice and job satisfaction were seen between T2 and T3 for nurses completing questionnaires at all three timepoints, but not for other stressors. CONCLUSION This study suggests that organisational interventions, supported by robust research data and consistent departmental leadership can positively influence perceptions of organisational stress in ED nurses. Our approach is generic, internationally applicable and can be adopted in all EDs. Implications for Nursing Management These occupational stressors are common to all EDs. Nurse managers should know their distribution amongst their staff. Such data can inform interventions to achieve maximal benefits for staff wellbeing and may be of value when targeting resources in times of financial pressure.
DNA loop extrusion by human cohesin

Cohesin extrudes DNA loops DNA is folded into loops in eukaryotic cells by a process that depends on a ring-shaped adenosine triphosphatase complex called cohesin. Davidson et al. and Kim et al. now show that in the presence of the NIPBLMAU2 protein complex, the human cohesin complex can function as a molecular motor that extrudes DNA loops with high speed in vitro. In contrast to how it mediates sister chromatid cohesion, cohesin does not appear to entrap DNA topologically during loop extrusion. The results provide direct evidence for the loop extrusion model of chromatin organization and suggest that genome architecture is highly dynamic. Science, this issue p. 1338, p. 1345 A cohesin-NIPBL-MAU2 complex acts as a DNA loop–extruding holoenzyme. Eukaryotic genomes are folded into loops and topologically associating domains, which contribute to chromatin structure, gene regulation, and gene recombination. These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion. Such an activity has been observed for condensin, which forms loops in mitosis, but not for cohesin. Using biochemical reconstitution, we found that single human cohesin complexes form DNA loops symmetrically at rates up to 2.1 kilo–base pairs per second. Loop formation and maintenance depend on cohesin’s ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin. During loop formation, cohesin and NIPBL-MAU2 reside at the base of loops, which indicates that they generate loops by extrusion. Our results show that cohesin and NIPBL-MAU2 form an active holoenzyme that interacts with DNA either pseudo-topologically or non-topologically to extrude genomic interphase DNA into loops.
Clinical course and need for hospital admission after lithium discontinuation in patients with bipolar disorder type I or II: mirror-image study based on the LiSIE retrospective cohort

Background Currently, the evidence for lithium as a maintenance treatment for bipolar disorder type II (BD-II) remains limited. Guidelines commonly extrapolate recommendations for BD-II from available evidence for bipolar disorder type I (BD-I). Comparing the impact of lithium discontinuation is one way of assessing effectiveness in both groups. Aims To compare the impact of lithium discontinuation on hospital admissions and self-harm in patients with BD-I or schizoaffective disorder (SZD) and patients with BD-II or other bipolar disorder. Method Mirror-image study, examining hospital admissions within 2 years before and after lithium discontinuation in both patient groups. This study was part of a retrospective cohort study (LiSIE) into effects and side-effects of lithium for maintenance treatment of bipolar disorder as compared with other mood stabilisers. Results For the whole sample, the mean number of admissions/patient/review period doubled from 0.44 to 0.95 (P<0.001) after lithium discontinuation. The mean number of bed days/patient/review period doubled from 11 to 22 (P = 0.025). This increase in admissions and bed days was exclusively attributable to patients with BD-I/SZD. Not having consulted with a doctor prior to lithium discontinuation or no treatment with an alternative mood stabiliser at the time of lithium discontinuation led to more admissions. Conclusions The higher relapse risk in patients with BD-I/SZD suggests a higher threshold for discontinuing lithium than for patients with BD-II/other bipolar disorder. In patients with BD-II/other bipolar disorder, however, judged on the impact of discontinuation alone, lithium did not appear to prevent more severe depressive episodes requiring hospital admission.
A Role for COX20 in Tolerance to Oxidative Stress and Programmed Cell Death in Saccharomyces cerevisiae

Industrial production of bioethanol from lignocellulosic materials (LCM′s) is reliant on a microorganism being tolerant to the stresses inherent to fermentation. Previous work has highlighted the importance of a cytochrome oxidase chaperone gene (COX20) in improving yeast tolerance to acetic acid, a common inhibitory compound produced during pre-treatment of LCM’s. The presence of acetic acid has been shown to induce oxidative stress and programmed cell death, so the role of COX20 in oxidative stress was determined. Analysis using flow cytometry revealed that COX20 expression was associated with reduced levels of reactive oxygen species (ROS) in hydrogen peroxide and metal-induced stress, and there was a reduction in apoptotic and necrotic cells when compared with a strain without COX20. Results on the functionality of COX20 have revealed that overexpression of COX20 induced respiratory growth in Δimp1 and Δcox18, two genes whose presence is essential for yeast respiratory growth. COX20 also has a role in protecting the yeast cell against programmed cell death.
The Non-Canonical Aspects of MicroRNAs: Many Roads to Gene Regulation

MicroRNAs (miRNAs) are critical regulators of gene expression. As miRNAs are frequently deregulated in many human diseases, including cancer and immunological disorders, it is important to understand their biological functions. Typically, miRNA-encoding genes are transcribed by RNA Polymerase II and generate primary transcripts that are processed by RNase III-endonucleases DROSHA and DICER into small RNAs of approximately 21 nucleotides. All miRNAs are loaded into Argonaute proteins in the RNA-induced silencing complex (RISC) and act as post-transcriptional regulators by binding to the 3′- untranslated region (UTR) of mRNAs. This seed-dependent miRNA binding inhibits the translation and/or promotes the degradation of mRNA targets. Surprisingly, recent data presents evidence for a target-mediated decay mechanism that controls the level of specific miRNAs. In addition, several non-canonical miRNA-containing genes have been recently described and unexpected functions of miRNAs have been identified. For instance, several miRNAs are located in the nucleus, where they are involved in the transcriptional activation or silencing of target genes. These epigenetic modifiers are recruited by RISC and guided by miRNAs to specific loci in the genome. Here, we will review non-canonical aspects of miRNA biology, including novel regulators of miRNA expression and functions of miRNAs in the nucleus.
The decline in attitudes toward physician-nurse collaboration from medical school to residency

ABSTRACT While interprofessional collaboration is a critical aspect of optimal patient care, practicing physicians often have sub-optimal attitudes regarding the importance of collaboration with their nursing colleagues. The impact of clinical training on medical students’ and residents’ attitudes toward physician-nurse collaboration has not been investigated. The primary goal of our study was to examine if learners at different stages in their medical training had more or less favorable attitudes regarding interprofessional collaboration (IPC). A secondary goal was to compare residents in procedural versus non-procedural specialties to determine if attitudes toward IPC varied by specialty type. Third-year medical students and residents at a large public university completed the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration. Student (n = 129) and resident (n = 292) scores were compared using Student’s t-tests. Resident responses were further analyzed by specialty type. Students’ perceptions of the physician-nurse relationship were significantly more favorable than the views of residents, particularly in the “Authority” and “Responsibility” domains. Residents in procedural specialties had less favorable attitudes toward physician-nurse collaboration than those in non-procedural specialties. Our findings highlight the importance of developing effective interventions for improving interprofessional collaboration during medical training.
Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.
Perceived attractiveness of Czech faces across 10 cultures: Associations with sexual shape dimorphism, averageness, fluctuating asymmetry, and eye color

Research on the perception of faces typically assumes that there are some universal values of attractiveness which are shared across individuals and cultures. The perception of attractiveness may, however, vary across cultures due to local differences in both facial morphology and standards of beauty. To examine cross-cultural consensus in the ratings of attractiveness, we presented a set of 120 non-manipulated photographs of Czech faces to ten samples of raters from both European (Czech Republic, Estonia, Sweden, Romania, Turkey, Portugal) and non-European countries (Brazil, India, Cameroon, Namibia). We examined the relative contribution of three facial markers (sexual shape dimorphism, averageness, fluctuating asymmetry) to the perception of attractiveness as well as the possible influence of eye color, which is a locally specific trait. In general, we found that both male and female faces which were closer to the average and more feminine in shape were regarded as more attractive, while fluctuating asymmetry had no effect. Despite a high cross-cultural consensus on attractiveness standards, significant differences in the perception of attractiveness seem to be related to the level of socio-economic development (as measured by the Human Development Index, HDI). Attractiveness ratings by raters from low-HDI countries (India, Cameroon, Namibia) converged less with ratings from Czech Republic than ratings from high-HDI countries (European countries and Brazil). With respect to eye color, some local patterns emerged which we discuss as a consequence of negative frequency-dependent selection.
Synthesis and In Vitro Growth Inhibition of 2-Allylphenol Derivatives Against Phythopthora cinnamomi Rands

Phytophthora cinnamomi is a phytopathogen that causes extensive damage in different crops, and therefore, produces important economic losses all around the world. Chemical fungicides are a key factor for the control of this disease. However, ecological and environmental considerations, as well as the appearance of strains that are resistant to commercial fungicides, have prompted the quest for new antifungal agents which are of low ecological impact. In this work, a series of new 2-allylphenol derivatives was synthesized, and their structures were confirmed by FT-IR, NMR, and MS. Some of the synthesized compounds, more specifically nitro derivatives, exhibit strong growth inhibition of P. cinnamomi with EC50 as low as 10.0 µg/mL. This level of activity is similar to that exhibited by METALAXYL MZ 58 WP, a commonly-used commercial fungicide; therefore, these compounds might be of agricultural interest due to their potential use as fungicides against P. cinnamomi. The results indicate that this activity depends on the chemical structures of the 2-allylphenol derivatives, and that it is strongly enhanced in molecules where nitro and hydroxyl groups adopt a -para configuration. These effects are discussed in terms of the electronic distribution of the aromatic ring induced by substituent groups.
Bidimensional Multiscale Fuzzy Entropy and Its Application to Pseudoxanthoma Elasticum

<italic>Objective:</italic> We propose a new bidimensional entropy measure and its multiscale form and evaluate their behavior using various synthetic and real images. The bidimensional multiscale measure finds application in helping clinicians for pseudoxanthoma elasticum (PXE) detection in dermoscopic images. <italic>Method:</italic> We developed bidimensional fuzzy entropy (<inline-formula><tex-math notation="LaTeX">$FuzEn_{2D}$</tex-math></inline-formula>) and its multiscale extension (<inline-formula><tex-math notation="LaTeX">$MSF_{2D}$</tex-math></inline-formula>) and then evaluated them on a set of synthetic images and texture datasets. Afterwards, we applied <inline-formula><tex-math notation="LaTeX">$ MSF_{2D}$</tex-math></inline-formula> to dermoscopic PXE images and compared the results to those obtained by bidimensional multiscale sample entropy (<inline-formula><tex-math notation="LaTeX">$MSE_{2D}$</tex-math></inline-formula>). <italic>Results:</italic> The results for the synthetic images illustrate that <inline-formula><tex-math notation="LaTeX">$FuzEn_{2D}$</tex-math></inline-formula> has the ability to quantify images irregularity. Moreover, <inline-formula><tex-math notation="LaTeX">$FuzEn_{2D}$</tex-math></inline-formula>, compared with bidimensional sample entropy (<inline-formula><tex-math notation="LaTeX">$SampEn_{2D}$</tex-math></inline-formula>), leads to more stable results. The tests with the multiscale version show that <inline-formula><tex-math notation="LaTeX">$ MSF_{2D}$</tex-math></inline-formula> is a proper image complexity measure. When applied to the dermoscopic PXE images, the paired <italic>t</italic>-test illustrates a significant statistical difference between <inline-formula><tex-math notation="LaTeX">$ MSF_{2D}$</tex-math></inline-formula> of neck images with papules and normal skin images at a couple of scale factors. <italic>Conclusion:</italic> The results for the synthetic data illustrate that <inline-formula><tex-math notation="LaTeX">$FuzEn_{2D}$</tex-math></inline-formula> is an image irregularity measure that overcomes <inline-formula><tex-math notation="LaTeX">$SampEn_{2D}$</tex-math></inline-formula> in terms of reliability, especially for small-sized images, and stability of results. The results for the PXE dermoscopic images demonstrate the ability of <inline-formula><tex-math notation="LaTeX">$MSF_{2D}$</tex-math></inline-formula> to recognize dermoscopic images of normal zones from PXE papules zones with a large effect size. <italic>Significance:</italic> This work introduces new image irregularity and complexity measures and shows the potential for <inline-formula><tex-math notation="LaTeX">$ MSF_{2D}$</tex-math></inline-formula> to serve as a possible tool helping medical doctors in PXE diagnosis.