Miracle-dz/UniFAR-FTUs huggingface dataset:
Advantages of everolimus therapeutic drug monitoring in oncology when drug–drug interaction is suspected: A case report

Introduction Drug interactions involving everolimus are fairly well known because of its common use, primarily as an immunosuppressant. Several recommendations regarding therapeutic drug monitoring are also available for the use of everolimus-based immunosuppression regimens. However, everolimus use in oncology differs substantially, particularly because of the high doses involved. Therapeutic drug monitoring, although sometimes necessary, is not recommended as a routine in oncology. Thus, it was deemed inapplicable due to the lack of clear recommendations. Case report Here, we present a case where a patient was prescribed everolimus for renal cell carcinoma. The patient benefitted from a pharmaceutical consultation prior to treatment initiation, and a drug interaction with verapamil was suspected. Management and outcome: Therapeutic drug monitoring of everolimus was proposed. Based on the everolimus values reported in the literature, trough plasma concentration in the patient was greatly increased. The patient was then diagnosed with grade 4 oral mucositis, thereby requiring temporary suspension of everolimus treatment. Management of adverse effects was performed through multiple medicated mouthwashes. Discussion Therapeutic drug monitoring for everolimus is important for potential drug interactions or the occurrence of severe adverse events. In such cases, dose adjustments should be managed according to everolimus plasma concentrations. Clear oncological recommendations regarding plasma everolimus thresholds are required for a successful follow-up of the patient’s condition and to ensure adequate response to treatment.
Equid Assessment, Research and Scoping (EARS): The Development and Implementation of a New Equid Welfare Assessment and Monitoring Tool

Simple Summary Animal welfare is a global concern which receives close public scrutiny. Numerous non-profit and non-governmental organisations exist to address problems relating to poor animal welfare, but there are multiple challenges surrounding how animal welfare is measured and recorded. We focus on the specific challenges around assessing equid welfare worldwide, and identify how stakeholders in this field of work are often unable to collaborate or pool resources due to differences in the welfare assessment tools they use. There is a need for a single welfare assessment tool which can be used across multiple contexts, yet which can yield comparable datasets to coordinate the approach to, and understanding of, global equid welfare. In response, we developed the Equid Assessment, Research and Scoping (EARS) tool which builds upon previously validated techniques, but extends them in a new framework which is applicable to multiple contexts. We have developed nine protocols, based upon 19 welfare indicators, and we describe the process of development here. We present the results from field-trialling three of the most frequently used protocols during the course of our work, assessing equids globally in farms and working environments, and equids on sanctuaries and properties in the UK and Europe. We found that the tool offered an easy and relatively quick way of collecting welfare data across multiple contexts, and propose that if developed further, it could be adopted by other organisations working to assess, understand and improve equid welfare worldwide. Abstract The assessment of animal welfare poses numerous challenges, yet an emerging approach is the consolidation of existing knowledge into new frameworks which can offer standardised approaches to welfare assessment across a variety of contexts. Multiple tools exist for measuring the welfare of equids, but such tools have typically been developed for specific contexts. There is no ‘one size fits all’ which means that resulting datasets are generally non-comparable, creating a barrier to knowledge-sharing and collaboration between the many organisations working to improve equid welfare around the globe. To address this, we developed the Equid Assessment, Research and Scoping (EARS) tool, which incorporates pre-existing validated welfare assessment methods alongside new welfare indicators to deliver a larger and more comprehensive series of welfare indicators than currently exists, creating a single resource that can be used to assess equid welfare in any context. We field-trialled three welfare assessment protocols within the EARS tool, and applied these to welfare assessment of equids in a variety of contexts across nineteen countries. The EARS tool proved a useful, versatile and rapid method for collecting welfare assessment data and we collected 7464 welfare assessments in a period of fifteen months. We evaluate the EARS tool and provide ideas for future development.
Is carrot consumption associated with a decreased risk of lung cancer? A meta-analysis of observational studies.

Findings of epidemiological studies regarding the association between carrot consumption and lung cancer risk remain inconsistent. The present study aimed to summarise the current epidemiological evidence concerning carrot intake and lung cancer risk with a meta-analysis. We conducted a meta-analysis of case–control and prospective cohort studies, and searched PubMed and Embase databases from their inception to April 2018 without restriction by language. We also reviewed reference lists from included articles. Prospective cohort or case–control studies reporting OR or relative risk with the corresponding 95 % CI of the risk lung cancer for the highest compared with the lowest category of carrot intake. A total of eighteen eligible studies (seventeen case–control studies and one prospective cohort study) were included, involving 202 969 individuals and 5517 patients with lung cancer. The pooledOR of eighteen studies for lung cancer was 0·58 (95%CI 0·45, 0·74) by comparing the highest category with the lowest category of carrot consumption. Based on subgroup analyses for the types of lung cancer, we pooled that squamous cell carcinoma (OR 0·52, 95 % CI 0·19, 1·45), small-cell carcinoma (OR 0·43, 95 % CI 0·12, 1·59), adenocarcinoma (OR 0·34, 95 % CI 0·15, 0·79), large-cell carcinoma (OR 0·40, 95 % CI 0·10, 1·57), squamous and small-cell carcinoma (OR 0·85, 95 % CI 0·45, 1·62), adenocarcinoma and large-cell carcinoma (OR 0·20, 95 % CI 0·02, 1·70) and mixed types (OR 0·61, 95 % CI 0·46, 0·81). Exclusion of any single study did not materially alter the pooled OR. Integrated epidemiological evidence from observational studies supported the hypothesis that carrot consumption may decrease the risk of lung cancer, especially for adenocarcinoma.
Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge

Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.
Molecular Mechanism of Viscosity Sensitivity in BODIPY Rotors and Application to Motion-Based Fluorescent Sensors.

Viscosity in the intracellular microenvironment shows a significant difference in various organelles and is closely related to cellular processes. Such microviscosity in live cells is often mapped and quantified with fluorescent molecular rotors. To enable the rational design of viscosity-sensitive molecular rotors, it is critical to understand their working mechanisms. Herein, we systematically synthesized and investigated two sets of BODIPY-based molecular rotors to study the relationship between intramolecular motions and viscosity sensitivity. Through experimental and computational studies, two conformations (i.e., the planar and butterfly conformations) are found to commonly exist in BODIPY rotors. We demonstrate that the transformation energy barrier from the planar conformation to the butterfly conformation is strongly affected by the molecular structures of BODIPY rotors, and plays a critical role in viscosity sensitivity. These findings enable rational structure modifications of BODIPY molecular rotors for highly effective protein detection and recognition.
Valproate risk form—Surveying 215 clinicians involving 4775 encounters

Annual completion of a Valproate Risk Acknowledgement Form (RAF) is mandated in the United Kingdom due to neurodevelopmental risks of in utero valproate exposure. The number of women of childbearing potential taking valproate, the uptake of the RAF within this population and their clinical outcomes is not known or monitored. This study surveyed responses of clinicians administering the RAF to women of childbearing potential taking valproate medications.
Detection of Early Signs of Diabetic Retinopathy Based on Textural and Morphological Information in Fundus Images

Estimated blind people in the world will exceed 40 million by 2025. To develop novel algorithms based on fundus image descriptors that allow the automatic classification of retinal tissue into healthy and pathological in early stages is necessary. In this paper, we focus on one of the most common pathologies in the current society: diabetic retinopathy. The proposed method avoids the necessity of lesion segmentation or candidate map generation before the classification stage. Local binary patterns and granulometric profiles are locally computed to extract texture and morphological information from retinal images. Different combinations of this information feed classification algorithms to optimally discriminate bright and dark lesions from healthy tissues. Through several experiments, the ability of the proposed system to identify diabetic retinopathy signs is validated using different public databases with a large degree of variability and without image exclusion.
Elongation of the Aorta after Thoracic Endovascular Aortic Repair: A longitudinal study

Aortic morphology is associated with age, with the diameter being larger in older people. Thoracic endovascular aortic repair (TEVAR) is a treatment for aortic diseases, such as aortic dissection. When evaluating patients, aortic elongation could interfere with the classification of TEVAR complications. The longitudinal change in aortic length has not been studied in detail. In patients receiving thoracic endovascular aortic repair between 2007 and 2013, we determined the aortic length between the sinotubular junction, left common carotid artery, subclavian artery, and celiac artery on their first five annual follow-up computed tomography (CT) exams. Using the immediate post-TEVAR follow-up CT as the comparison reference and a lengthening of the aortic segment by 10 mm or more as the definition of elongation, 16 of 41 (39%) showed elongation between the innominate artery and celiac artery. When compared with the immediate follow-up CT, a higher proportion of patients showed elongation at the fifth year’s follow-up CT than the first year’s follow-up CT (p < 0.01), and the average lengthening per year was 1.7 mm. There was progressive lengthening of the aorta after TEVAR.
Delivery of pDNA to lung epithelial cells using PLGA nanoparticles formulated with a cell-penetrating peptide: understanding the intracellular fate

Abstract The combination of nanoparticles (NPs) and cell-penetrating peptide (CPP) represents a new opportunity to develop plasmid DNA (pDNA) delivery systems with desirable properties for lung delivery. In this study, poly(lactide-co-glycolide) (PLGA) NPs containing pDNA were formulated with and without CPP using a double-emulsion technique. NPs were characterized in regards of size, surface charge, release profile, pDNA encapsulation efficiency and pDNA integrity. Cellular uptake, intracellular trafficking, uptake mechanism and pDNA expression were assessed in both A549 and Beas-2B cells. Manufactured PLGA-NPs efficiently encapsulated pDNA with approximately 50% released in the first 24 h of incubation. Addition of CPP was essential to promote NP internalization in both cell lines, with 83.85 ± 1.2% and 96.76 ± 1.7% of Beas-2B and A549 cells, respectively, with internalized NP–DNA–CPP after 3 h of incubation. Internalization appears to occur mainly via clathrin-mediated endocytosis, with other pathways also being used by the different cell lines. An endosomal-escape mechanism seems to happen in both cell lines, and eGFP expression was observed in Beas-2B after 96 h of incubation. In summary, the NP–DNA–CPP delivery system efficiently encapsulated and protected pDNA structure and is being investigated as a promising tool for gene delivery to the lungs.
Making heads or tails – the emergence of capicua (CIC) as an important multifunctional tumour suppressor

Capicua, encoded by the gene CIC, is an evolutionarily conserved high‐mobility group‐box transcription factor downstream of the receptor tyrosine kinase and mitogen‐activated protein kinase pathways. It was initially discovered and studied in Drosophila. Recurrent mutations in CIC were first identified in oligodendroglioma, a subtype of low‐grade glioma. Subsequent studies have identified CIC aberrations in multiple types of cancer and have established CIC as a potent tumour suppressor involved in regulating pathways related to cell growth and proliferation, invasion and treatment resistance. The most well‐known and studied targets of mammalian CIC are the oncogenic E‐Twenty Six transcription factors ETV1/4/5, which have been found to be elevated in cancers with CIC aberrations. Here, we review the role of CIC in normal mammalian development, oncogenesis and tumour progression, and the functional interactors that mediate them. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Sevoflurane inhibited inflammatory response induced by TNF-α in human trophoblastic cells through p38MAPK signaling pathway

Abstract Purpose: Excessive inflammatory response is one of the possible pathogenic mechanisms of preeclampsia (PE). It remains unclear whether sevoflurane has an anti-inflammatory effect in human trophoblastic cells, which are corresponding to the dysfunction of placentas in PE. This study probed into the regulatory function of sevoflurane toward HTR8/SVneo cells so as to find PE pathology and PE treatment. Materials and methods: HTR8/SVneo cells were treated with sevoflurane, TNF-α with different concentrations, sevoflurane plus 10 ng/mL TNF-α and SB203580 plus 10 ng/mL TNF-α. Cell counting kit-8 (CCK-8) assays were performed to detect cell viability, while enzyme linked immunoSorbent assay (ELISA) was used to measure IL-6, IL-8, GM-CSF and MCP-1 levels in HTR8/SVneo cells. Besides, relative mRNA expression levels of IL-6 and IL-8 were tested via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and p38 phosphorylation-related protein expressions were assessed through western blot. Results: Cell viability remained stable when HTR8/SVneo cells were treated with or without sevoflurane and SB203580 in inflammatory microenvironment created by TNF-α. MCP-1 and GM-CSF levels, as well as gene expressions of IL-6 and IL-8 in HTR8/SVneo cells were greatly increased by TNF-α (5, 10 and 20 ng/mL), but reversed by sevoflurane and SB203580. Simultaneously, TNF-α-induced phosphorylation of p38MAPK signaling pathway was inhibited by sevoflurane and SB203580. Conclusions: Sevoflurane inhibited inflammatory response induced by TNF-α in human trophoblastic cells HTR8/SVneo through suppressing the phosphorylation of p38MAPK signaling pathway.
Comparative study on archaeal diversity in the sediments of two urban landscape water bodies

Urban lake sediment plays a very important role in waterbody ecosystems. It is the basis of nutrient cycling and material exchange between microorganisms and lake ecosystems. In this study, Illumina high-throughput sequencing technology was employed to detect the structure and species richness of Archaea in anoxic sediments of urban waterbodies (Aohai Lake and Kunming Lake) in Beijing, and the environmental factors (pH level, organic matter, available nitrogen and total nitrogen) affecting the structure and succession of archaeal communities were also investigated. The results showed that there were 13 classified archaeal phyla, and the most frequent archaeal species in the lakes were Bathyarchaeota (MCG), Euryarchaeota, Thaumarchaeota, Aenigmarchaeota, Hadesarchaea, Lokiarchaeota, and Parvarchaeota. The top ten most abundant genera in the two lakes were significantly associated with at least one environmental factor. The results of this study enrich the understanding of microbial diversity in urban eutrophic lake sediments in northern China.
Neonatal Mortality and Temperature in Two Northern Swedish Rural Parishes, 1860–1899—The Significance of Ethnicity and Gender

The aim of this study was to analyze the association between season of birth and daily temperature for neonatal mortality in two Swedish rural parishes between 1860 and 1899. Further, we aimed to study whether the association varied according to ethnicity (indigenous Sami reindeer herders and non-Sami settlers) and gender. The source material for this study comprised digitized parish records from the Demographic Data Base, Umeå University, combined with local weather data provided by the Swedish Meteorological and Hydrological Institute. Using a time event-history approach, we investigated the association between daily temperature (at birth and up to 28 days after birth) and the risk of neonatal death during the coldest months (November through March). The results showed that Sami neonatal mortality was highest during winter and that the Sami neonatal mortality risk decreased with higher temperatures on the day of birth. Male neonatal risk decreased with higher temperatures during the days following birth, while no effect of temperature was observed among female neonates. We conclude that weather vulnerability differed between genders and between the indigenous and non-indigenous populations.
Physically-inspired Deep Light Estimation from a Homogeneous-Material Object for Mixed Reality Lighting

In mixed reality (MR), augmenting virtual objects consistently with real-world illumination is one of the key factors that provide a realistic and immersive user experience. For this purpose, we propose a novel deep learning-based method to estimate high dynamic range (HDR) illumination from a single RGB image of a reference object. To obtain illumination of a current scene, previous approaches inserted a special camera in that scene, which may interfere with user's immersion, or they analyzed reflected radiances from a passive light probe with a specific type of materials or a known shape. The proposed method does not require any additional gadgets or strong prior cues, and aims to predict illumination from a single image of an observed object with a wide range of homogeneous materials and shapes. To effectively solve this ill-posed inverse rendering problem, three sequential deep neural networks are employed based on a physically-inspired design. These networks perform end-to-end regression to gradually decrease dependency on the material and shape. To cover various conditions, the proposed networks are trained on a large synthetic dataset generated by physically-based rendering. Finally, the reconstructed HDR illumination enables realistic image-based lighting of virtual objects in MR. Experimental results demonstrate the effectiveness of this approach compared against state-of-the-art methods. The paper also suggests some interesting MR applications in indoor and outdoor scenes.
FUNMarker: Fusion Network-Based Method to Identify Prognostic and Heterogeneous Breast Cancer Biomarkers

Breast cancer is a heterogeneous disease with many clinically distinguishable molecular subtypes each corresponding to a cluster of patients. Identification of prognostic and heterogeneous biomarkers for breast cancer is to detect cluster-specific gene biomarkers which can be used for accurate survival prediction of breast cancer outcomes. In this study, we proposed a FUsion Network-based method (FUNMarker) to identify prognostic and heterogeneous breast cancer biomarkers by considering the heterogeneity of patient samples and biological information from multiple sources. To reduce the affect of heterogeneity of patients, samples were first clustered using the K-means algorithm based on the principal components of gene expression. For each cluster, to comprehensively evaluate the influence of genes on breast cancer, genes were weighted from three aspects: biological function, prognostic ability and correlation with known disease genes. Then they were ranked via a label propagation model on a fusion network that combined physical protein interactions from seven types of networks and thus could reduce the impact of incompleteness of interactome. We compared FUNMarker with three state-of-the-art methods and the results showed that biomarkers identified by FUNMarker were biological interpretable and had stronger discriminative power than the existing methods in differentiating patients with different prognostic outcomes.
Structural basis for stabilization of human telomeric G-quadruplex [d-(TTAGGGT)]4 by anticancer drug adriamycin

Abstract Besides inhibiting DNA duplication, DNA dependent RNA synthesis and topoisomerase-II enzyme action, anticancer drug adriamycin is found to cause telomere dysfunction and shows multiple strategies of action on gene functioning. We present evidence of binding of adriamycin to parallel stranded intermolecular [d-(TTAGGGT)]4 G-quadruplex DNA comprising human telomeric DNA by proton and phosphorus-31 nuclear magnetic resonance spectroscopy. Diffusion ordered spectroscopy shows formation of complex between the two molecules. Changes in chemical shift and line broadening of DNA and adriamycin protons suggest participation of specific chemical groups/moieties in interaction. Presence of sequential nuclear Overhauser enhancements at all base quartet steps and absence of large downfield shifts in 31P resonances give clear proof of absence of intercalation of adriamycin chromophore between base quartets. Restrained molecular dynamics simulations using observed 15 short intermolecular inter proton distance contacts depict stacking of ring D of adriamycin with terminal G6 quartet by displacing T7 base and external groove binding close to T1–T2–A3 bases. The disappearance of imino protons monitored as a function of temperature and differential scanning calorimetry experiments yield thermal stabilization of 24 °C, which is likely to come in the way of telomerase association with telomeres. The findings pave the way for design of alternate anthracycline based drugs with specific modifications at ring D to enhance induced thermal stabilization and use alternate mechanism of binding to G-quadruplex DNA for interference in functional pathway of telomere maintenance by telomerase enzyme besides their well known action on duplex DNA. Communicated by Ramaswamy H. Sarma