Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug Eluting Stent Implantation for High Risk Patients and Novel Technologies in Percutaneous Coronary Intervention

textabstractPercutaneous coronary intervention is a major treatment strategy for patients with coronary artery disease, and currently coronary stents are widely used in the world.1 Although stent implantation itself has shown to reduce restenosis by preventing both early elastic recoil and late vascular remodeling compared to balloon angioplasty, in-stent restenosis (ISR) still occurs in 10-40% of patients and has been the ‘Achilles’ heel’ of coronary interventions, frequently resulting in repeated revascularization.2,3 Restenosis after coronary stenting occurs secondary to the accumulation of smooth muscle cells and extracellular matrix proteoglycans.4 Despite the sophistication of the new techniques and enormous advance in devices, ISR requiring repeat procedure has been considered as a main limitation of coronary stenting. The advent of drug eluting stents (DES), which consist of a drug (immunosuppressive or antiproliferative drug), a polymer and a metallic platform, has revolutionized the practice of interventional cardiology by significantly reducing the rates of restenosis and repeat revascularization as compared to bare metal stents.5 After the first approval of DES, a large number of patients with coronary artery disease have undergone percutaneous revascularization with DES. However, many trials conducted in the ‘real world’ showed that the problem of restenosis was not completely resolved and still persists. Effect of DES for patients at high risk for ISR, such as acute myocardial infarction, small coronary vessels, aorto-ostial lesions, or lesions of chronic total occlusion (Part 1 of this thesis), have not been fully investigated. In addition, certain potential safety concerns regarding the widespread use of DES have arisen. The most notable drawback of DES is that they could increase the risk of thrombotic complication, especially late stent thrombosis6, although its incidence is low.7 The increased risk of thrombosis with DES utilization may be associated with altered endothelial function8 and/or delayed vascular healing9 induced by cytotoxic and cytostatic drug use. Localized hypersensitivity reactions to the polymer coating of DES and drug itself may also contribute to stent thrombosis.10 To retain the positive clinical aspects of DES and overcome their drawbacks, new concept stents have been developed (Part 2 of this thesis).
Social inequalities in health: duration of unemployment unevenly effects on the health of men and women.

BACKGROUND Employment status is an important determinant of health inequalities. The aim of this article is to analyze the association between duration of unemployment and the presence of cardiovascular risk factors, self-perception of health and presence of depression and anxiety, assessing differences in the effects of unemployment by sex and age. METHODS The sample was composed of 12 123 people (52.4% men), 18 to 74 years old (mean age= 43.5 years, SD = 10.4). Logistic regression analyses were used to study the influence of duration of unemployment on health ('0 days', '≤11 months' and '≥12 months'). Sex, age, level of education, employment status and time spent unemployed, as well as tobacco and alcohol use and physical activity, were considered. Morbidity variables were hypertension, hypercholesterolemia, diabetes, obesity, depression and anxiety, and a subjective health assessment. RESULTS The results showed both unemployed men and women had worse outcome in health compared with their active counterparts. The risk of hypertension was presented in long-term unemployed men, which had 1.3 times more likely to suffer from hypertension. The risk of obesity was presented only in unemployed women, which had 1.5 times more risk of obesity, doubling the risk (OR= 2.2) among women under age 40. The unemployment had a protective effect against anxiety among younger women (OR = 0.53). CONCLUSION It has been observed a different influence of unemployment time on men and women's health. The employment status should be considered in public health policy agendas with the purpose of reducing inequalities in health.
Human umbilical-cord mesenchymal stem cells inhibit bacterial growth and alleviate antibiotic resistance in neonatal imipenem-resistant Pseudomonas aeruginosa infection

Human umbilical-cord mesenchymal stem cells (hUCMSCs) are a safe and convenient source of MSCs and have shown beneficial effects in neonatal infection and sepsis animal models. However, the factors leading to improved outcomes are still unclear. The aim of this study was to investigate the antibacterial effect and regulation of antimicrobial resistance of hUCMSCs. We separated imipenem-resistant Pseudomonas aeruginosa (PA) from neonates and incubated it with hUCMSCs as well as their culture medium. Assessment of direct inhibition of bacterial growth was done by counting CFUs. The concentration of antibacterial peptides in the culture medium of hUCMSCs was measured. Standard PA was inoculated with a sub-inhibitory concentration of imipenem with and without hUCMSC conditioned medium and antimicrobial peptides. The sensitivity to imipenem was detected until PA showed resistance to imipenem. Outer membrane protein (OprD2) mRNA expression in PA before and after the induction of imipenem resistance was analysed. We found that HUCMSCs possessed direct antimicrobial properties against bacteria and could alleviate antibiotic resistance via reserving OprD2 expression in PA.
The fibro‐adipose structure of the female breast: A dissection study

A paucity of dissection evidence and quantitative data exists to base anatomical descriptions and illustrations of the fibro‐adipose structure of the female breast. The aim of this study was to dissect and provide quantitative data of the fibro‐adipose structure of the female breast. The fibro‐adipose structure of female embalmed breasts were dissected in the coronal (n = 15) and sagittal planes (n = 3). Quantitative data of breast volume, surface area, fibro‐adipose pocket number, size and regional variation were collected. Pearson's correlations were used to investigate pocket number and size with breast volume and surface area. Regional variation in pocket number and size were compared using T tests. Throughout the dissection, photographic evidence was collected to support detailed anatomical descriptions. The mean (SD; range) number of pockets located in the superficial region of the breast was 199 ± 53 (108–306) and the mean pocket surface area was 0.88 ± 0.37 cm2 (0.31–1.97). A strong correlation was found between mean pocket number and breast surface area (r2 = 0.8064) and a very weak correlation between mean individual pocket surface area and breast surface area (r2 = −0.1427; P < 0.01). The pockets located anterior to the corpus mamma were significantly larger and less in number (P < 0.05) than those located posterior. The fibro‐adipose structure of the female breast is formed by complex scaffolding, consisting of layers of fibrous tissue pockets embedded with adipose tissue which surrounds the corpus mamma and is firmly attached to the perimeter of the breast. Detailed descriptions are supported by quantitative data and photographic evidence. Clin. Anat. 32:146–155, 2019. © 2019 Wiley Periodicals, Inc.
Emotionally expressed voices are retained in memory following a single exposure

Studies of voice recognition in biology suggest that long exposure may not satisfactorily represent the voice acquisition process. The current study proposes that humans can acquire a newly familiar voice from brief exposure to spontaneous speech, given a personally engaging context. Studies have shown that arousing and emotionally engaging experiences are more likely to be recorded and consolidated in memory. Yet it remains undemonstrated whether this advantage holds for voices. The present study examined the role of emotionally expressive context in the acquisition of voices following a single, 1-minute exposure by comparing recognition of voices experienced in engaging and neutral contexts at two retention intervals. Listeners were exposed to a series of emotionally nuanced and neutral videotaped narratives produced by performers, and tested on the recognition of excerpted voice samples, by indicating whether they had heard the voice before, immediately and after a one-week delay. Excerpts were voices from exposed videotaped narratives, but utilized verbal material taken from a second (nonexposed) narrative provided by the same performer. Overall, participants were consistently able to distinguish between voices that were exposed during the video session and voices that were not exposed. Voices experienced in emotional, engaging contexts were significantly better recognized than those in neutral ones both immediately and after a one-week delay. Our findings provide the first evidence that new voices can be acquired rapidly from one-time exposure and that nuanced context facilitates initially inducting new voices into a repertory of personally familiar voices in long-term memory. The results converge with neurological evidence to suggest that cerebral processes differ for familiar and unfamiliar voices.
An interdisciplinary approach to investigate collective cell migration in neural crest

The neural crest serves as a powerful and tractable model paradigm for understanding collective cell migration. The neural crest cell populations are well‐known for their long‐distance collective migration and contribution to diverse cell lineages during vertebrate development. If neural crest cells fail to reach a target or populate an incorrect location, then improper cell differentiation or uncontrolled cell proliferation can result. A wide range of interdisciplinary studies has been carried out to understand the response of neural crest cells to different stimuli and their ability to migrate to distant targets. In this critical commentary, we illustrate how an interdisciplinary collaboration involving experimental and mathematical modeling has led to a deeper understanding of cranial neural crest cell migration. We identify open questions and propose possible ways to start answering some of the challenges arising.
Genetics in the Honey Bee: Achievements and Prospects toward the Functional Analysis of Molecular and Neural Mechanisms Underlying Social Behaviors

The European honey bee is a model organism for studying social behaviors. Comprehensive analyses focusing on the differential expression profiles of genes between the brains of nurse bees and foragers, or in the mushroom bodies—the brain structure related to learning and memory, and multimodal sensory integration—has identified candidate genes related to honey bee behaviors. Despite accumulating knowledge on the expression profiles of genes related to honey bee behaviors, it remains unclear whether these genes actually regulate social behaviors in the honey bee, in part because of the scarcity of genetic manipulation methods available for application to the honey bee. In this review, we describe the genetic methods applied to studies of the honey bee, ranging from classical forward genetics to recently developed gene modification methods using transposon and CRISPR/Cas9. We then discuss future functional analyses using these genetic methods targeting genes identified by the preceding research. Because no particular genes or neurons unique to social insects have been found yet, further exploration of candidate genes/neurons correlated with sociality through comprehensive analyses of mushroom bodies in the aculeate species can provide intriguing targets for functional analyses, as well as insight into the molecular and neural bases underlying social behaviors.
Testing the role of ecological selection on colour pattern variation in the butterfly Parnassius clodius

Colour pattern has served as an important phenotype in understanding the process of natural selection, particularly in brightly coloured and variable species like butterflies. However, different selective forces operate on aspects of colour pattern, for example by favouring warning colours in eyespots or alternatively favoring investment in thermoregulatory properties of melanin. Additionally, genetic drift influences colour phenotypes, especially in populations undergoing population size change. Here, we investigated the relative roles of genetic drift and ecological selection in generating the phenotypic diversity of the butterfly Parnassius clodius. Genome‐wide patterns of single nucleotide polymorphism data show that P. clodius forms three population clusters, which experienced a period of population expansion following the last glacial maximum and have since remained relatively stable in size. After correcting for relatedness, morphological variation is best explained by climatic predictor variables, suggesting ecological selection generates trait variability. Solar radiation and precipitation are both negatively correlated with increasing total melanin in both sexes, supporting a thermoregulatory function of melanin. Similarly, wing size traits are significantly larger in warmer habitats for both sexes, supporting a Converse Bergmann Rule pattern. Bright red coloration is negatively correlated with temperature seasonality and solar radiation in males, and weakly associated with insectivorous avian predators in univariate models, providing mixed evidence that selection is linked to warning coloration and predator avoidance. Together, these results suggest that elements of butterfly wing phenotypes respond independently to different sources of selection and that thermoregulation is an important driver of phenotypic differentiation in Parnassian butterflies.
Arginine‐enveloped virus inactivation and potential mechanisms

Arginine synergistically inactivates enveloped viruses at a pH or temperature that does little harm to proteins, making it a desired process for therapeutic protein manufacturing. However, the mechanisms and optimal conditions for inactivation are not fully understood, and therefore, arginine viral inactivation is not used industrially. Optimal solution conditions for arginine viral inactivation found in the literature are high arginine concentrations (0.7–1 M), a time of 60 min, and a synergistic factor of high temperature (≥40°C), low pH (≤pH 4), or Tris buffer (5 mM). However, at optimal conditions full inactivation does not occur over all enveloped viruses. Enveloped viruses that are resistant to arginine often have increased protein stability or membrane stabilizing matrix proteins. Since arginine can interact with both proteins and lipids, interaction with either entity may be key to understanding the inactivation mechanism. Here, we propose three hypotheses for the mechanisms of arginine induced inactivation. Hypothesis 1 describes arginine‐induced viral inactivation through inhibition of vital protein function. Hypothesis 2 describes how arginine destabilizes the viral membrane. Hypothesis 3 describes arginine forming pores in the virus membrane, accompanied by further viral damage from the synergistic factor. Once the mechanisms of arginine viral inactivation are understood, further enhancement by the addition of functional groups, charges, or additives may allow the inactivation of all enveloped viruses in mild conditions.
Processed meat intake and chronic disease morbidity and mortality: An overview of systematic reviews and meta-analyses

Despite the nutritional value of meat, a large volume of reviews and meta-analyses suggests that processed meat intake is associated with an increased risk of chronic diseases. However, assessments of the quality of these published reviews internal validity are generally lacking. We systematically reviewed and assessed the quality alongside summarizing the results of previously published systematic reviews and meta-analyses that examined the association between processed meat intake and cancers, type II diabetes (T2D), and cardiovascular diseases (CVD). Reviews and meta-analyses published until May 2018 were identified through a systematic literature search in the databases MEDLINE and EMBASE, and reference lists of included reviews. The quality of the systematic reviews and meta-analyses was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR). All eligible reviews had to comply with two quality requirements: providing sufficient information on quality assessment of the primary studies and a comprehensive search. The results were summarized for T2D, CVD, and each of the different cancer types. The certainty in the estimates of the individual outcomes was rated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. In total, 22 systematic reviews were eligible and thus included in this review. More than 100 reviews were excluded because quality assessment of the primary studies had not been performed. The AMSTAR score of the included reviews ranged from 5 to 8 indicating moderate quality. Overall, the quality assessments of primary studies of the reviews are generally lacking; the scientific quality of the systematic reviews reporting positive associations between processed meat intake and risk of various cancers, T2D and CVD is moderate, and the results from case-control studies suggest more often a positive association than the results from cohort studies. The overall certainty in the evidence was very low across all individual outcomes, due to serious risk of bias and imprecision.
Development and validation of a digital quantitative orthoptics workstation

The objective of the research is to provide the clinician with a simple system for making quantitative measurements that is comparable to the services of a skilled orthoptist. As many optometrists do not possess the necessary equipment for making such assessments, this technology would significantly enhance their referral capabilities. Reviews of the tests involved and instruments available are detailed in Chapter II and III. Chapter IV presents the various validation experiments carried out on the Tobii X120 eye tracker, concentrating on technical specifications such as, linearity range, optimum measurement distance and setup (with and without chin rest). We also investigated the effect of wearing different types of lens materials and pupil size measurements on the eye tracker system. We established the inter-examiner agreement of cover test measurements on groups of non-strabismic and strabismic subjects. This study, as detailed in Chapter V, involved collaboration with two clinical orthoptists. We found a good inter-examiner agreement for both the non-strabismic and strabismic cover tests. We further investigated the use of the eye tracker in providing more reliable findings for cover test measurements as compared to the conventional cover test (Chapter VI). Finally we extended the investigation to a number of different clinical subjects attending the Bristol Eye Hospital (Chapter VII) in order to evaluate our purpose-developed monocular calibration routine. Performing quantitative eye movement analysis will provide valuable additional information in any clinical investigation of patients with ophthalmological and/or neurological disorders, leading to greater precision in diagnosis. Traditional methods for the evaluation of oculomotor disorders rely on the diagnostic and therapeutic judgements by the examining clinicians and subjective responses from the patient. However, the use of currently available eye movement recording system will provide valuable alternatives for obtaining more objective and quantitative measurements.
Optimal Location of Wells for Storage and Recovery of Surplus Desalinated Water in Coastal Aquifers

Storage of water in aquifers using injection wells is an efficient way for utilizing excess desalinated water in arid regions. In this investigation we estimate the benefits of optimally recharging seasonal surplus desalinated water into a strategic coastal aquifer already benefitting from natural recharge of flash‐floods water by a recharge dam. Since, usually the buyers of desalinated water commit to purchase surplus desalinated water under take‐or‐pay contracts, any attempt in utilizing the paid water is beneficial. Coastal cities are observing an increased urbanization leaving limited space for aquifer recharge infrastructure. In order to determine the optimal location of wells and maximize the use of surplus desalinated water available in winter period, a decision tool combining a numerical groundwater flow simulation model (MODFLOW) with an optimization model is developed. The results of this study show that increasing the number of wells from the existing 45 wells to 173 would allow storing 31.4 million cubic meter per year of excess desalinated water into the aquifer that can be used during later during summer months. The net benefit would reach US$55 million/year while the cost of drilling the new wells is US$5.11 million.
Normal gut microbiome in NMDA receptor encephalitis

Objective To determine whether the gut microbiota shows overabundance of commensal bacteria species in patients with anti-NMDA receptor (NMDAR) encephalitis, similar to patients with MS or neuromyelitis optica where they potentially balance pro- and anti-inflammatory immune responses or participate in disease pathogenesis by molecular mimicry. Methods Intestinal microbiota was characterized in patients with NMDAR encephalitis (n = 23, mean age: 34 ± 12.7 years; 21 females) and age/sex/environment-matched healthy controls (n = 24, 40 ± 14.2 years; 22 females) using stool bacteria 16S rDNA sequencing and classification in operational taxonomic units (OTUs). Statistical analyses focused on intraindividual and interindividual bacterial diversity and identification of differentially abundant taxa. Results Patients with NMDAR encephalitis and controls had similar microbiome profiles of the gut microbiota regarding intraindividual bacterial diversity, OTU distribution, ratio between regional and local species diversity when testing all OTUs, and genera with a relative abundance greater than 0.5%. Similarly, the subgroup of NMDAR encephalitis patients with an ovarian teratoma (n = 3) showed no differences in microbiome variation compared with controls. Patients in the acute encephalitis stage (n = 8) showed significant differences in the numbers of Clostridium XVIII, Clostridium IV, Oscillibacter, Prevotella, and Blautia; however, significance was lost after correction for multiple testing. Conclusion Patients with NMDAR encephalitis and controls both had a normal gut microbiome. The lack of overabundance of certain bacterial species in patients suggests that microbiome changes are no major contributors to the pathogenesis, disease course, or prognosis in NMDAR encephalitis. Despite the small sample size and heterogeneous groups, findings indicate differences to other neuroimmunologic diseases.
Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs

Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill‐defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3‐interacting regions (LIRs) in several SNAREs that broaden the landscape of the mAtg8‐SNARE interactions. We found that Syntaxin 16 (Stx16) and its cognate SNARE partners all have LIR motifs and bind mAtg8s. Knockout of Stx16 caused defects in lysosome biogenesis, whereas a Stx16 and Stx17 double knockout completely blocked autophagic flux and decreased mitophagy, pexophagy, xenophagy, and ribophagy. Mechanistic analyses revealed that mAtg8s and Stx16 control several properties of lysosomal compartments including their function as platforms for active mTOR. These findings reveal a broad direct interaction of mAtg8s with SNAREs with impact on membrane remodeling in eukaryotic cells and expand the roles of mAtg8s to lysosome biogenesis.