Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicentric Secretory Carcinoma of the Breast in a 35‐Year‐Old Woman: Mammographic Appearance and the Use of Core Biopsy in Preoperative Management

Abstract: Core biopsy of the breast has been increasingly utilized as a first‐line diagnostic approach for mammographic breast lesions, palpable breast lesions, or both. Core biopsy has been shown to be cost‐effective in sparing a significant fraction of women an open surgical procedure and, in conjunction with radiologic imaging studies, can allow for planning of definitive therapy in women with malignant lesions ( 1–4 ). We present a case of multicentric secretory carcinoma of the breast in which the diagnosis was suggested by core biopsy. This case represents the first reported instance of core biopsy in secretory carcinoma, one of the rarest types of mammary carcinoma. We describe the mammographic appearance of the lesion, the appearance of the tissue core, and the use of core biopsy in the proper preoperative management of this rare, multicentric lesion.
Mobile ECMO team for controlled donation after circulatory death

To the Editor: The scarcity of potential dead brain donors and the persistent mismatch between supply and demand of organs for transplantation has led the transplant community to reconsider donation after circulatory death (DCD) as a strategy to increase the donor pool. Controlled donation after circulatory death (cDCD) has emerged as the most feasible way to expand the number of transplantations. In Spain, cDCD accounted for 18% of the total number of deceased donors in 2016. At present, a total of 68 hospitals in Spain have cDCD programs.1 The experience accumulated in the past few years has demonstrated that normothermic regional perfusion (nRP) by extracorporeal membrane oxygenation (ECMO) may be the most effective method for preserving abdominal organs in DCD, especially in liver transplantation. Although the optimal duration of nRP is unknown, recipient’s outcome improves when nRP is used to restore blood flow before organ recovery and reverse the effect of ischemia. Also, nRP facilitates graft quality assessment prior to validation, prevents surgical injury in superrapid extractions, and reduces the duration of cold ischemia as it facilitates coordination between the extraction and the implantation team.2-4 A pitfall of this method is its complexity and the unavailability of this resource in some hospitals, especially in regional hospitals, where potential DCD donors may exist. The Virgen de las Nieves Hospital, Granada (Spain), launched a program of uncontrolled DCD and cDCD in 2010 and 2013, respectively. These programs were designed according to current Spanish legislation and all national and international recommendations. The method of organ preservation of choice for DCD of our group is nRP. The ECMO device is operated by transplant coordinators (intensive care specialist). 5 Since 2015 our group has worked as a mobile ECMO team for cDCD outside our center, and we report our experience: 5 donations in the same city (hospitals at a distance between 1 and 14 km), and 3 in others cities (Jaen at 92 km, Motril at 69 km, and Linares at 136 km). The portable equipment included cannulation material and the ECMO device. The transplant team consisted of 2 transplant coordinators (ECMO operator and organ extraction supervisor), and a team of surgeons (cannulation and organ extraction). The characteristics of donors are summarized in Table 1. cDCD donations achieved by the mobile ECMO team allowed for 2 liver transplants and 15 renal transplants (which would not have been possible otherwise, no possibility of superrapid technique), 10 corneal transplants, 3 osteotendinous and 1 vascular tissue extractions. The evolution of grafts and receptors was favorable, except for a liver graft receiver who died because of an intraoperative complication during transplantation surgery. To the best of our knowledge, no case series have been published on controlled donation after circulatory death by a mobile ECMO team for nRP. Mobile ECMO teams may enable cDCD in hospitals without these resources, thereby increasing the pool of donors and optimizing graft outcomes.
27.3 All-wireless 64-channel 0.013mm2/ch closed-loop neurostimulator with rail-to-rail DC offset removal

Accurate capture and efficient control of neurological disorders such as epileptic seizures that often originate in multiple regions of the brain, requires neural interface microsystems with an ever-increasing need for higher channel counts. Addressing this demand within the limited energy and area of brain-implantable medical devices necessitates a search for new circuit architectures. In the conventional designs [1–5], the channel area is dominated by the bulky coupling capacitors and/or capacitor banks of the in-channel ADC, both unavoidable due to the channel architecture, and unscalable with CMOS technology. Additionally, channel power consumption, typically dominated by the LNA, cannot be reduced lower than a certain limit without sacrificing gain and/or noise performance. In this paper, we present a 64-channel wireless closed-loop neurostimulator with a compact and energy-efficient channel architecture that performs both amplification and digitization in a single ΔΣ-based neural ADC, while removing rail-to-rail input DC offset using a digital feedback loop. The channel area and power consumption depend only on the active components and switching frequency, respectively, making the design both technology- and frequency-scalable.
Th17 polarization of memory Th cells in early arthritis: the vasoactive intestinal peptide effect

Several studies in humans indicate the implication of Th17 cells in RA. Therapies targeting their pathogenicity, as well as their plasticity to the Th17/1 phenotype, could ameliorate the progression of the pathology. The neuroendocrine environment has a major impact on the differentiation of lymphoid cells. VIP is present in the microenvironment of the joint, and its known therapeutic effects are supported by several studies on RA. We examine the ability of VIP to modulate the differentiation of Th17 cells. Peripheral blood CD4+CD45RO+ T cells from HD and eRA patients were expanded under Th17‐polarizing conditions in the presence of TGF‐β. After 7 days, the higher IL‐17A, IL‐21, and IL‐9 levels and lower IL‐22 levels indicate the nonpathogenic profile for Th17 cells in HD. In contrast, Th17 cells from eRA patients produced significantly more IL‐22 and IFN‐γ, and these cells show a more Th17/1 profile, indicating a pathogenic phenotype. Interestingly, when VIP was present in the Th17 conditioned medium, increased levels of IL‐10 and IL‐9 were detected in HD and eRA patients. VIP also reduced the levels of IL‐22 in eRA patients. These data suggest that VIP reduces the pathogenic profile of the Th17‐polarized cells. This effect was accompanied by an increased in the Treg/Th17 profile, as shown by the increase levels of Foxp3. In conclusion, this report addresses a novel and interesting question on the effect of VIP on human Th17 cells and adds clinical relevance by analyzing, in parallel, HD and eRA patients.
Interleukin (IL)‐31 activates signal transducer and activator of transcription (STAT)‐1, STAT‐5 and extracellular signal‐regulated kinase 1/2 and down‐regulates IL‐12p40 production in activated human macrophages

Interleukin‐31 is a cytokine expressed by activated T cells. A major function of IL‐31 in atopic dermatitis (AD) is the induction of pruritus in the skin. We recently showed that IL‐31 induces pro‐inflammatory cytokines following staphylococcal exotoxins’ stimulation in human macrophages. However, signalling pathways of IL‐31 in activated human macrophages still remain unclear. The aim of the study was to investigate the signalling pathways of IL‐31 receptor as well as functional effects of IL‐31 in activated macrophages.
Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations

Background Leber congenital amaurosis (LCA) is the earliest and most severe inherited retinal degeneration. Isolated forms of LCA frequently result from mutation of the CEP290 gene which is expressed in various ciliated tissues. Methods Seven LCA patients with CEP290 mutations were investigated to study otorhinolaryngologic phenotype and respiratory cilia. Nasal biopsies and brushing were performed to study cilia ultrastructure using transmission electron microscopy and ciliary beating using high-speed videomicroscopy, respectively. CEP290 expression in normal nasal epithelium was studied using real-time RT-PCR. Results When electron microscopy was feasible (5/7), high levels of respiratory cilia defects were detected. The main defects concerned dynein arms, central complex and/or peripheral microtubules. All patients had a rarefaction of ciliated cells and a variable proportion of short cilia. Frequent but moderate and heterogeneous clinical and ciliary beating abnormalities were found. CEP290 was highly expressed in the neural retina and nasal epithelial cells compared with other tissues. Discussion These data provide the first clear demonstration of respiratory cilia ultrastructural defects in LCA patients with CEP290 mutations. The frequency of these findings in LCA patients along with the high expression of CEP290 in nasal epithelium suggest that CEP290 has an important role in the proper development of both the respiratory ciliary structures and the connecting cilia of photoreceptors. The presence of respiratory symptoms in patients could represent additional clinical criteria to direct CEP290 genotyping of patients affected with the genetically heterogeneous cone-rod dystrophy subtype of LCA.
Serum allergen‐specific IgA is not associated with natural or induced tolerance to egg in children

The role of specific IgA (sIgA) in oral immunotherapy (OIT) and natural tolerance to foods is poorly understood. We aimed to study serum sIgA in induced and natural tolerance to egg. Children aged 5–16 years diagnosed with IgE‐mediated egg allergy were recruited. After egg challenge, patients were classified as transient (TEA) or persistent (PEA) egg‐allergic. PEA children were further divided into oral immunotherapy (PEA‐OIT) or egg avoidance (PEA‐EA). Allergy/tolerance was reassessed 9–12 months later (T1) in PEA‐EA. Serum sIgA to ovalbumin and ovomucoid were determined at inclusion in all patients and repeated in PEA at T1. 21 TEA and 52 PEA children were recruited (28 PEA‐OIT, 24 PEA‐EA). Serum sIgA remained unchanged after OIT. TEA and PEA had similar serum sIgA. No specific trend on serum sIgA was observed in five PEA‐EA who developed natural tolerance over follow‐up. Thus, serum sIgA seems not to be associated with induced or natural egg tolerance.
Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies

Diets high in n‐3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE‐mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n‐3 LCPUFA supplementation of pregnant women reduces IgE‐mediated allergic disease in their children.
Improving allergy management in the primary care network – a holistic approach

The incidence, prevalence and costs of allergy have increased substantially in recent decades in many parts of Europe. The dominant model of allergy care within Europe is at the moment specialist‐based. This model will become unsustainable and undeliverable with increasing disease prevalence. One solution to increase provision of allergy services is to diversify the providers. A new model for the provision of allergy care in the community with the general practitioner at the forefront is proposed. Pre‐ and postgraduate allergy education and training, implementation of pathways of care, allergy specialization and political will to generate resources and support are essential to achieve this new model. In parallel the holistic view of allergic diseases should be maintained, including assessment of severity and risk, psychological factors and health‐care related costs in the context of the patient‐centered decision making process.
A Fatality Involving 5-Methoxy-N, N-Diisopropyltryptamine (“Foxy”) and Cocaine

ABSTRACT A 29-year-old male was found dead in his apartment with no visible injuries and after autopsy, no known cause of death could be determined. Suspicious circumstances including blood stains on the walls led the police to believe that foul play may have occurred. Toxicology results revealed high concentrations of 5-methoxy-N, N-diisopropyltryptamine in the blood, urine, arid vitreous humour, as well as cocaine and significant concentrations of cocaine metabolites.
Connecting the molecular scale to the continuum scale for diffusion processes in smectite-rich porous media.

In this paper, we address the manner in which the continuum-scale diffusive properties of smectite-rich porous media arise from their molecular- and pore-scale features. Our starting point is a successful model of the continuum-scale apparent diffusion coefficient for water tracers and cations, which decomposes it as a sum of pore-scale terms describing diffusion in macropore and interlayer "compartments. " We then apply molecular dynamics (MD) simulations to determine molecular-scale diffusion coefficients D(interlayer) of water tracers and representative cations (Na(+), Cs(+), Sr(2+)) in Na-smectite interlayers. We find that a remarkably simple expression relates D(interlayer) to the pore-scale parameter δ(nanopore) ≤ 1, a constrictivity factor that accounts for the lower mobility in interlayers as compared to macropores: δ(nanopore) = D(interlayer)/D(0), where D(0) is the diffusion coefficient in bulk liquid water. Using this scaling expression, we can accurately predict the apparent diffusion coefficients of tracers H(2)0, Na(+), Sr(2+), and Cs(+) in compacted Na-smectite-rich materials.
EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence‐based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review.
CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154

CD4+ T cells are essential for human CMV infection control. CMV‐specific CD4+ T cells possess antiviral functions and participate in anti‐CMV humoral/cellular responses. In the elderly, CMV infection impairs immunity to other viruses and has been traditionally associated with T cell senescence; however, recent results suggest that, in younger people, CMV confers immune protection against other pathogens (heterologous immunity). To shed light on this controversy, we analyzed latent CMV infection effects on the quality of young individuals’ immune response, specifically, the presence of polyfunctional T cells through an extensive phenotypic and functional characterization of the CD4+ T cell subset. CD154 expression, degranulation (CD107a), and cytokine production (IFN‐γ, TNF‐α, and IL‐2) as well as T cell phenotype markers (CD57, CD28, and CD27) were analyzed. We demonstrate that CD4+ T cells that coexpress CD57 and CD154, which are exclusively present in CMV‐positive individuals, are the most polyfunctional CD4+ subset, whereas CD4+CD27+CD28− T cells associate with lower polyfunctionality. Conversely, the frequency of CD4+CD28+ T cells correlates with higher polyfunctionality of CD4+CD57− T cells from CMV‐seronegative individuals and CD4+CD57+CD154+ T cells from CMV‐seropositive individuals. Thus, polyfunctionality is a property of central memory CD4+ T cells in CMV‐seronegative individuals, whereas after CMV infection, polyfunctional T cells become highly differentiated, which allows efficient eradication of infections. We extend previous observations of the impact of CMV on CD8+ T cell functionality to the CD4+ T cell compartment, revealing CD57 as a polyfunctionality marker of T cells which expands after CMV infection. CD57+ T cells have been associated with inflammatory conditions, but their potential role in the response against infectious disease and vaccination should now be investigated.
Environmental health criteria 59: principles for evaluating health risks from chemicals during infancy and early childhood: the need for a special approach

SIR,-The objective of many research investigations is to assess the effect of a stimulus on some quantitative response. This often entails comparing the mean value of the response variable between groups of subjects exposed to contrasting stimuli. Thus an occupational health study might be undertaken to compare the mean pulmonary function-for example, FEV1/FVC ratio between firefighters and police officers. Comparing the crude means between two or more groups, however, may give rise to a misleading impression about the effect of stimulus (chemicals inhaled during firefighting) and the response variable (FEV1/FVC), since such a comparison is potentially biased by confounding variables such as smoking and age. Similarly, a clinical trial might be carried out to compare the mean reduction of blood pressure in hypertensive subjects given either a new or established antihypertensive drug. Again, comparing the crude mean reduction is potentially biased by differences in baseline blood pressure in the two groups. ' Analysis of covariance (ANCOVA), a statistical technique for comparing means with adjustment for confounding bias, is usually the method of choice for adjusting the crude mean values.24 It must be noted, however, that ANCOVA is a parametric statistical method based on a mathematical model. Any mathematical model which attempts to represent reality necessarily stipulates conditions about the data. Some of the conditions stipulated by the ANCOVA model are that the relation between the covariate and the response is linear and equal in each comparison group, and that the error terms in the model are independent, normally distributed, and have the same variance.2 Hence, unless the data meet all the model assumptions (to within statistical limits), the ensuing statistical results obtained by ANCOVA may be uninformative and misleading. An alternative statistical procedure to ANCOVA for the comparison of means with adjustment for confounding bias is the Z-score method.3 5 The main appeal of this essentially non-parametric method is that it stipulates only one condition about the data: the relation between the covariate and the response is the same in each comparison group-that is, there is no interaction. When the data show interaction, neither ANCOVA nor the Z-score method is applicable to analysis.3 One drawback of the Z-score method is that it accomplishes adjustment by stratification (analogous to the standardisation procedure for the comparison of rates). Consequently, the method is generally not feasible for adjustment of more than one or two confounders. In our view the Z-score method should be used when ANCOVA is clearly inappropriate for a given set of data. Correspondence We have written a computer procedure to perform the Z-score method in SAS6 for the mainframe computer as well as in dBase III* for the microcomputer. The programme listing, including a worked example, is available on request.
Placental transfer of bupivacaine, pethidine and lignocaine in the rabbit. Effect of umbilical flow rate and protein content

Summary. The factors determining the placental transfer of drugs used in labour were studied in the rabbit placenta perfused in situ with Krebs bicarbonate buffer. During concurrent maternal intravenous infusion of bupivacaine, lignocaine, pethidine and antipyrine, drug concentrations were measured in maternal arterial plasma and placental effluent perfusate, the flow rate and protein content of which were varied. Protein binding and content were also measured. Placental clearance of antipyrine, which is unbound, was unaltered by perfusate protein content, and increased with umbilical perfusate flow up to 2 ml/min. Clearance of lignocaine and pethidine, which were 20–30% protein bound, increased to a small extent with perfusate protein, and were flow‐dependent up to the maximum perfusate flow of 4 ml/min. Clearances of bupivacaine, which was > 80% bound, increased markedly with perfusate protein but, though flow‐dependent, was one‐tenth to one‐fifth that of the other drugs. Fetal binding and glycoprotein content were less than maternal, hence the equilibrium fetal: maternal ratio is predictably lower for the highly bound bupivacaine than for lignocaine or pethidine. Measured fetal: maternal ratios of bupivacaine were, however, only one‐half to one‐third of the predicted equilibrium values, suggesting that bupivacaine does not unbind readily in a single transit through the rabbit placenta. Thus, though bupivacaine crosses the placenta more slowly than thc other drugs, the fetal dose of all these drugs will be greatest in healthy babies with good placental blood flows and high plasma proteins.
Superantigens produced by catheter‐associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia

SAgs, produced by Staphylococcus aureus, play a major role in the pathogenesis of invasive staphylococcal diseases by inducing potent activation of the immune system. However, the role of SAgs, produced by S. aureus, associated with indwelling devices or tissues, are not known. Given the prevalence of device‐associated infection with toxigenic S. aureus in clinical settings and the potency of SAgs, we hypothesized that continuous exposure to SAgs produced by catheter‐associated S. aureus could have systemic consequences. To investigate these effects, we established a murine in vivo catheter colonization model. One centimeter long intravenous catheters were colonized with a clinical S. aureus isolate producing SAgs or isogenic S. aureus strains, capable or incapable of producing SAg. Catheters were subcutaneously implanted in age‐matched HLA‐DR3, B6, and AEo mice lacking MHC class II molecules and euthanized 7 d later. There was no evidence of systemic infection. However, in HLA‐DR3 transgenic mice, which respond robustly to SSAgs, the SSAg‐producing, but not the nonproducing strains, caused a transient increase in serum cytokine levels and a protracted expansion of splenic CD4+ T cells expressing SSAg‐reactive TCR Vβ8. Lungs, livers, and kidneys from these mice showed infiltration with CD4+ and CD11b+ cells. These findings were absent in B6 and AEo mice, which are known to respond poorly to SSAgs. Overall, our novel findings suggest that systemic immune activation elicited by SAgs, produced by S. aureus colonizing foreign bodies, could have clinical consequences in humans.
Bacterial secretion systems and regulation of inflammasome activation

Innate immunity is critical for host defenses against pathogens, but many bacteria display complex ways of interacting with innate immune signaling, as they may both activate and evade certain pathways. Gram‐negative bacteria can exhibit specialized nanomachine secretion systems for delivery of effector proteins into mammalian cells. Bacterial types III, IV, and VI secretion systems (T3SS, T4SS, and T6SS) are known for their impact on caspase‐1‐activating inflammasomes, necessary for producing bioactive inflammatory cytokines IL‐1β and IL‐18, key participants of anti‐bacterial responses. Here, we discuss how these secretion systems can mediate triggering and inhibition of inflammasome signaling. We propose that a fine balance between secretion system‐mediated activation and inhibition can determine net activation of inflammasome activity and control inflammation, clearance, or spread of the infection.