Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing tissue engineered models of oral mucosa and oral cancer to study novel therapeutic and diagnostic techniques.

In the UK in 2008 over 1,800 people died from oral cancer. Despite advances in surgery and therapy the survival rates for those diagnosed with oral cancer have not significantly improved over the past 20 years. There is a need for both better detection and treatment. Early detection could reduce these mortality rates but unfortunately diagnosing oral cancer, which is often symptomless, in the early stages of the disease is incredibly challenging. More targeted treatments for oral cancer are also needed which can be administered to the site of disease with higher efficiency and accuracy to reduce side effects and allow higher concentrations of therapeutic agents to be delivered to tumour cells. This project used a tissue engineered oral mucosa model to develop models of oral cancer progression. These oral cancer models incorporated many pathological features of oral cancer progression including features seen in dysplastic epithelia, carcinoma in situ and early invasive squamous cell carcinomas. Multi-cellular tumour spheroids were created from an oral cancer cell line to model solid expanding tumour masses. The tissue engineered models of oral mucosa and the multi-cellular tumour spheroids were used to test the behaviour of polymersomes, a novel drug delivery system, in three dimensional tissues. Polymersome distribution and penetration in the tissue engineered models was examined over time, to investigate the potential of polymersomes to deliver therapeutic agents into and/or across the oral mucosa and into solid expanding tumours. Drug delivery agents that are able to reach the central hypoxic region of solid expanding tumours are particularly important as these cells are often resistant to both radio- and chemotherapy and correlate with poor patient prognosis. In addition, we explored the potential of polymersomes to cross the oral epithelial permeability barrier and act as delivery vehicles for topical delivery of therapies for oral mucosal diseases and as an alternative to parenteral administration for the systemic delivery of drugs. Results showed good penetration of polymersomes into the oral mucosa and the multi-cellular tumour spheroids demonstrating the potential to develop these drug delivery vehicles to deliver anti-cancer drugs and other therapeutic agents in the future. The tissue engineered models of cancer were next utilised to test four non-invasive diagnostic technologies. These included a cell metabolism marker, impedance spectroscopy, Fourier transform infra-red and optical coherence tomography. The results obtained from these different techniques showed varying degrees of promise with the images from OCT demonstrating that this technology has real diagnostic potential. The 3D models proved useful test-beds for some but not all of these diagnostic imaging techniques. They provide convenient models to tackle some of the key issues in the preclinical development of novel diagnostic technologies for oral cancer and oral dysplastic lesions.
Updated modelling of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus (iVDPV) excreters

Abstract Conditions and evidence continue to evolve related to the prediction of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus (iVDPV) excreters, which affect assumptions related to forecasting risks and evaluating potential risk management options. Multiple recent reviews provided information about individual iVDPV excreters, but inconsistencies among the reviews raise some challenges. This analysis revisits the available evidence related to iVDPV excreters and provides updated model estimates that can support future risk management decisions. The results suggest that the prevalence of iVDPV excreters remains highly uncertain and variable, but generally confirms the importance of managing the risks associated with iVDPV excreters throughout the polio endgame in the context of successful cessation of all oral poliovirus vaccine use.
Bridging the gap between visual temporary memory and working memory: The role of stimuli distinctiveness.

Visual working memory (VWM) is traditionally assumed to be immune to proactive interference (PI). However, in a recent study (Endress & Potter, 2014), performance in a visual memory task was superior when all items were unique and hence interference from previous trials was impossible, compared to a standard condition in which a limited set of repeating items was used and stimuli from previous trials could interfere with the current trial. Furthermore, when all the items were unique, the estimated memory capacity far exceeded typical capacity estimates. Consequently, the researchers suggested the existence of a separate memory buffer, the "temporary memory," which has an unbounded capacity for meaningful items. However, before accepting this conclusion, methodological differences between the repeated-unique procedure and typical estimates of VWM should be considered. Here, we tested the extent to which the exceptional set of heterogeneous, complex, meaningful real-world objects contributed to the large PI in the repeated-unique procedure. Thus, the same paradigm was employed with a set of real-world objects and with homogenous sets (e.g., houses, faces) in which the items were meaningful, yet less visually distinct, and participants had to rely on subtle visual details to perform the task. The results revealed a large PI effect for real-world heterogeneous objects, but substantially smaller effects for the homogenous sets. These findings suggest that there is no need to postulate a new memory buffer. Instead, we suggest that VWM capacity and vulnerability to PI are highly influenced by task characteristics, and specifically, by the stimuli distinctiveness. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Manipulation of β‐carotene levels in tomato fruits results in increased ABA content and extended shelf life

Summary Tomato fruit ripening is controlled by the hormone ethylene and by a group of transcription factors, acting upstream of ethylene. During ripening, the linear carotene lycopene accumulates at the expense of cyclic carotenoids. Fruit‐specific overexpression of LYCOPENE β‐CYCLASE (LCYb) resulted in increased β‐carotene (provitamin A) content. Unexpectedly, LCYb‐overexpressing fruits also exhibited a diverse array of ripening phenotypes, including delayed softening and extended shelf life. These phenotypes were accompanied, at the biochemical level, by an increase in abscisic acid (ABA) content, decreased ethylene production, increased density of cell wall material containing linear pectins with a low degree of methylation, and a thicker cuticle with a higher content of cutin monomers and triterpenoids. The levels of several primary metabolites and phenylpropanoid compounds were also altered in the transgenic fruits, which could be attributed to delayed fruit ripening and/or to ABA. Network correlation analysis and pharmacological experiments with the ABA biosynthesis inhibitor, abamine, indicated that altered ABA levels were a direct effect of the increased β‐carotene content and were in turn responsible for the extended shelf life phenotype. Thus, manipulation of β‐carotene levels results in an improvement not only of the nutritional value of tomato fruits, but also of their shelf life.
The use of diagnoses in mental health service eligibility and exclusion criteria

Abstract Background Diagnoses are controversial but ubiquitous in mental health; however, whether they are essential features of service entry has not been analysed. Aim To investigate the use of diagnosis in the service entry criteria of UK NHS adult mental health services. Methods Freedom of Information requests were made to 17 NHS adult mental health Trusts; responses were analysed thematically. Results Four service types were identified: broadly diagnostic, problem-specific, supporting specific life circumstances and needs-led. Diagnoses were used frequently but not universally. Non-diagnostic factors were central to service entry criteria. Conclusions Diagnoses were neither necessary nor sufficient in-service entry criteria. Broad clusters of difficulties were used rather than specific diagnoses. Extensive exceptions revealed diagnoses as inefficient proxies for risk, severity and need. Differences across criteria appeared largely driven by professional competencies. Implications for innovative care pathways include preventative services and working with psychosocial factors.
Nursing protocol in vascular trauma prevention: peripheral catheterization bundle in urgency.

OBJECTIVE to create, apply and analyze in clinical practice the effectiveness of a bundle to prevent peripheral vascular trauma to approach the peripheral venous puncture process. METHOD action research with 435 adult participants in an emergency service from 2011 to 2013. Creation of the bundle for prevention of vascular trauma based on scientific evidence, ease of operation, observation and measurement with implantation through an educational intervention of the team of nursing. Effectiveness analyzed by descriptive and inferential statistics using chi-square. Consecutive sample with 95% confidence interval. RESULTS Five stages of the bundle were related to the catheter fixation, permanence and removal process. The incidence of vascular traumas due to vein punctures reduced by 46.41% after implantation of the bundle to prevent vascular trauma associated with emergency peripheral catheterization. CONCLUSION The bundle in clinical practice reduced vascular traumas by venipuncture.
Treatment results of CHOP-21, CHOEP-21, MACOP-B and PMitCEBO with and without rituximab in young good-prognosis patients with aggressive lymphomas: Rituximab as an “equalizer” in the MInT (MABTHERA International Trial Group) study

6529 Background: The addition of rituximab (R) to 6 cycles of CHOP-like regimens in the MInT trial significantly improved overall results and set a new standard in young good-prognosis patients with DLBCL (Blood 2004,104:48a). As CHOEP-21 had been shown to be superior to CHOP-21 without R (NHL-B1 trial; Blood 2004, 104:626), we investigated whether these differences could be confirmed in the MInT trial where participating countries selected 1 of 4 CHOP-like regimens. Methods: Intent-to-treat-analysis of the primary endpoint time-to-treatment-failure (TTF) and the secondary endpoints complete remission (CR) rate and overall survival (OS) of different regimens with or without rituximab. Results: Of 823 evaluable patients, 48% (197/199) were randomized to CHOP-21±R, 44% (180/181) to CHOEP±R, 4% (17/17) to MACOP-B±R and 4% to (16/16) PMitCEBO. All regimens were well balanced for prognostic factors, except for MACOP-B±R with more favorable patients. Numbers for MACOP-B and PMitCEBO are too small for meaningful.
Genome‐wide screening and cohorts validation identifying novel lncRNAs as prognostic biomarkers for clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the main subtype of renal cell carcinoma with varied prognosis. We aimed to identify and assess the possible prognostic long noncoding RNA (lncRNA) biomarkers. LncRNAs expression data and corresponding clinical information of 619 ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Differentially expressed genes analysis, univariate Cox regression, the least absolute shrinkage and selection operator Cox regression model were utilized to identify hub lncRNAs. Multivariate Cox regression was used to establish the risk model. Statistical analysis was performed using R 3.5. 3. The expression value of five lncRNAs and the risk‐score levels were significantly associated with a survival prognosis of ccRCC patients (all P < .001). In the TCGA validation cohort, the area under the curve (AUC) for the integrated nomogram was 0.905 and 0.91 for 3‐, 5‐year prediction separately. The AUC reached up to 0.757 in an independent ICGC cohort. Besides, the calibration plots also illustrated well curve‐fitting between observation values and predictive values. Weighted gene co‐expression network analysis and subsequent pathway analysis revealed that the PI3K‐Akt‐mTOR and hypoxia‐inducible factor signaling crosstalk might function as the most essential mechanisms related to the five‐lncRNAs signature. Our study suggested that lncRNA AC009654.1, AC092490.2, LINC00524, LINC01234, and LINC01885 were significantly associated with ccRCC prognosis. The prognostic model based on this five lncRNA may predict the overall survival of ccRCC.
Assessing direct and indirect effects of pediatric influenza vaccination in Germany by individual-based simulations

ABSTRACT Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997–2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017–2036). Pediatric vaccination coverage of 10-60% annually prevented 218–1,732 (6.3–50.5%) infections in children, 204–1,961 (2.9–28.2%) in young adults and 95–868 (3.1–28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4–4.6 vaccinations were needed to prevent one infection among children; 1.7–1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.
Mining Twitter to Inform the Design of Online Interventions for Hispanic Alzheimer’s Disease and Related Dementias Caregivers

Background/Objective: Hispanics are about 1.5 times as likely as non-Hispanic Whites to experience Alzheimer’s disease and related dementias (AD/ADRD). Eight percent of AD/ADRD caregivers are Hispanics. The purpose of this article is to provide a methodological case study of using data mining methods and the Twitter platform to inform online self-management and social support intervention design and evaluation for Hispanic AD/ADRD caregivers. It will enable other researchers to replicate the methods for their phenomena of interest. Method: We extracted an analytic corpus of 317,658 English and Spanish tweets, applied content mining (topic models) and network structure analysis (macro-, meso-, and micro-levels) methods, and created visualizations of results. Results: The topic models showed differences in content between English and Spanish tweet corpora and between years analyzed. Our methods detected significant structural changes between years including increases in network size and subgroups, decrease in proportion of isolates, and increase in proportion of triads of the balanced communication type. Discussion/Conclusion: Each analysis revealed key lessons that informed the design and/or evaluation of online self-management and social support interventions for Hispanic AD/ADRD caregivers. These lessons are relevant to others wishing to use Twitter to characterize a particular phenomenon or as an intervention platform.
Exploring the photo-toxicity of hypoxic active iridium(III)-based sensitizers in 3D tumor spheroids.

Among all molecules developed for anticancer therapies, photodynamic therapeutic agents have a unique profile. Their maximal activity is specifically triggered in tumors by light and toxicity of even systemically delivered drug is prevented in non-illuminated parts of the body. Photosensitizers exert their therapeutic effect by producing reactive oxygen species via a light-activated reaction with molecular oxygen. Consequently, the lowering of pO2 deep in solid tumors limits their treatment and makes essential the design of oxygen-independent sensitizers. In this perspective, we have recently developed Ir(III)-based molecules able to oxidize biomolecules by type I processes under free-oxygen conditions. We examine here their photo-toxicity in relevant biological models. We show that drugs, which are mitochondria-accumulated, induce upon light irradiation a dramatic decrease of the cell viability, even under low oxygen conditions. Finally, assays on 3D tumor spheroids highlight the importance of the light-activation step and the oxygen consumption rate on the drug activity.
A guide to assessing endoplasmic reticulum homeostasis and stress in mammalian systems

The endoplasmic reticulum (ER) is a multifunctional organelle that constitutes the entry into the secretory pathway. The ER contributes to the maintenance of cellular calcium homeostasis, lipid synthesis and productive secretory, and transmembrane protein folding. Physiological, chemical, and pathological factors that compromise ER homeostasis lead to endoplasmic reticulum stress (ER stress). To cope with this situation, cells activate an adaptive signaling pathway termed the unfolded protein response (UPR) that aims at restoring ER homeostasis. The UPR is transduced through post‐translational, translational, post‐transcriptional, and transcriptional mechanisms initiated by three ER‐resident sensors, inositol‐requiring protein 1α, activating transcription factor 6α, and PRKR‐like endoplasmic reticulum kinase. Determining the in and out of ER homeostasis control and UPR activation still represents a challenge for the community. Hence, standardized criteria and methodologies need to be proposed for monitoring ER homeostasis and ER stress in different model systems. Here, we summarize the pathways that are activated during ER stress and provide approaches aimed at assess ER homeostasis and stress in vitro and in vivo mammalian systems that can be used by researchers to plan and interpret experiments. We recommend the use of multiple assays to verify ER stress because no individual assay is guaranteed to be the most appropriate one.
Deep Unbiased Embedding Transfer for Zero-Shot Learning

Zero-shot learning aims to recognize objects which do not appear in the training dataset. Previous prevalent mapping-based zero-shot learning methods suffer from the projection domain shift problem due to the lack of image classes in the training stage. In order to alleviate the projection domain shift problem, a deep unbiased embedding transfer (DUET) model is proposed in this paper. The DUET model is composed of a deep embedding transfer (DET) module and an unseen visual feature generation (UVG) module. In the DET module, a novel combined embedding transfer net which integrates the complementary merits of the linear and nonlinear embedding mapping functions is proposed to connect the visual space and semantic space. What’s more, the end-to-end joint training process is implemented to train the visual feature extractor and the combined embedding transfer net simultaneously. In the UVG module, a visual feature generator trained with a conditional generative adversarial framework is used to synthesize the visual features of the unseen classes to ease the disturbance of the projection domain shift problem. Furthermore, a quantitative index, namely the score of resistance on domain shift (ScoreRDS), is proposed to evaluate different models regarding their resistance capability on the projection domain shift problem. The experiments on five zero-shot learning benchmarks verify the effectiveness of the proposed DUET model. As demonstrated by the qualitative and quantitative analysis, the unseen class visual feature generation, the combined embedding transfer net and the end-to-end joint training process all contribute to alleviating projection domain shift in zero-shot learning.
Rhabdo-immunodeficiency virus, a murine model of acute HIV-1 infection

Numerous challenges have impeded HIV-1 vaccine development. Among these is the lack of a convenient small animal model in which to study antibody elicitation and efficacy. We describe a chimeric Rhabdo-Immunodeficiency virus (RhIV) murine model that recapitulates key features of HIV-1 entry, tropism and antibody sensitivity. RhIVs are based on vesicular stomatitis viruses (VSV), but viral entry is mediated by HIV-1 Env proteins from diverse HIV-1 strains. RhIV infection of transgenic mice expressing human CD4 and CCR5, exclusively on mouse CD4+ cells, at levels mimicking those on human CD4+ T-cells, resulted in acute, resolving viremia and CD4+ T-cell depletion. RhIV infection elicited protective immunity, and antibodies to HIV-1 Env that were primarily non-neutralizing and had modest protective efficacy following passive transfer. The RhIV model enables the convenient in vivo study of HIV-1 Env-receptor interactions, antiviral activity of antibodies and humoral responses against HIV-1 Env, in a genetically manipulatable host.
Global Exponential Stability and Synchronization for Novel Complex-Valued Neural Networks With Proportional Delays and Inhibitory Factors

In this article, complex-valued neural networks (CVNNs) with proportional delays and inhibitory factors are proposed. First, the global exponential stability of the model addressed is investigated by employing the Halanay inequality technique and the matrix measure method. Some criteria are derived to guarantee the global exponential stability of CVNNs with proportional delays and inhibitory factors. The obtained criteria are applicable not only to systems with proportional delays but also to systems with arbitrary delays. Here, the Lyapunov functions are not constructed. Compared with the Lyapunov method, the matrix measure method makes the obtained criteria more concise, and the Halanay inequality makes the analytical procedure more compact. Furthermore, the global exponential synchronization of two neural-network models with proportional delays and inhibitory factors is also studied. By designing a feedback controller and giving some limitation conditions, the drive system and the response system realize global exponential synchronization. Finally, numerical simulation examples are provided to validate the effectiveness of the theoretical results obtained.