Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative aspects of prepartum maturation: Provision of nutrients

At birth, the pattern of nutrition changes from a continuous but limited supply of nutrients from the placenta to an intermittent yet more plentiful provision of metabolic substrates via the gut. The success of this transition from parenteral to enteral nutrition depends on adequate fuel reserves, functional mechanisms for regulating nutrient utilization and production, a gastrointestinal tract competent at digestion and sufficient motor development to allow suckling. Maturational changes in key tissues (eg liver, gut) and endocrine systems (eg pancreas, adrenal) therefore occur during late gestation in preparation for the nutritional transition at birth. In many species, these maturational changes are dependent on the prepartum increase in cortisol secretion by the fetal adrenal. In fetal sheep, cortisol has been shown to stimulate hepatic glycogen deposition, induce hepatic gluconeogenic enzymes and adrenoreceptors and accelerate the structural and functional development of the gut. In fetal horses, prepartum maturation of the glucogenic and glucoregulatory capacities occurs comparatively late in gestation coincidentally with the natural rise in fetal plasma cortisol which occurs much closer to term in this than other domestic species. The relatively narrow window for glucocorticoid dependent maturation in the foal has consequences for survival both in utero in response to adverse conditions and at birth. Fetal foals are unable to produce glucose endogenously during late gestation and develop severe hypoglycaemia if delivered prematurely. Foals born with low cortisol levels therefore adapt poorly to extrauterine life while, conversely, increasing fetal glucocorticoid levels by betamethasone administration or by stress induced fetal cortisol secretion can lead to early delivery of viable foals which are normoglycaemic and able to digest enteral feeds. Increase prenatal exposure to glucocorticoid therefore appears to be as much a prerequisite for the neonatal transition from parenteral to enteral nutrition in the horse as it is in other species.
Effects of exposure to large sharks on the abundance and behavior of mobile prey fishes along a temperate coastal gradient

Top predators can exert strong influences on community structure and function, both via direct, consumptive effects, as well as through non-consumptive, fear-based effects (i.e. predation risk). However, these effects are challenging to quantify, particularly for mobile predators in marine ecosystems. To advance this field of research, here we used baited remote underwater video stations (BRUVs) to assess how the behavior of mobile fish species off Cape Cod, Massachusetts, was affected by exposure to large sharks. We categorized sites into three levels of differential shark predation exposure (white sharks, Carcharodon carcharias) and quantified the relative abundance and arrival times (elapsed time before appearing on screen) for six mobile fish prey groups to the BRUV stations. Increased large shark exposure was associated with a decrease in overall prey abundance, but the overall response was prey group-specific. Foraging of smooth dogfish, a likely important prey item for large sharks in the system, was significantly reduced in areas frequented by white sharks. Specifically, the predicted probabilities of smooth dogfish bait contacts or bite attempts occurring were reduced by factors of 5.7 and 8.4, respectively, in areas of high exposure as compared to low exposure. These modifications were underscored by a decrease in smooth dogfish abundance in areas of high exposure as well. Our results suggest that populations of large, roving sharks may induce food-related costs in prey. We discuss the implications of this work within the context of the control of risk (COR) hypothesis, for the purposes of advancing our understanding of the ecological role and effects of large sharks on coastal marine ecosystems.
Inhaled Corticosteroid Treatment in Chronic Obstructive Pulmonary Disease (COPD): Boon or Bane?

Inhaled corticosteroid (ICS)–based therapy is often used for patients with chronic obstructive pulmonary disease (COPD). However, this approach is under scrutiny because of ICS overuse in patients for whom it is not recommended and because of concerns about adverse events, particularly pneumonia, with long-term ICS use. Evidence suggests ICS may be beneficial in specific patients, namely, those with high blood eosinophil counts (eg, ≥300 cells/µL) or who are at a high risk of exacerbations. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 ABCD assessment tool, these patients belong in group D. For these patients, recommended initial treatment includes ICS in combination with long-acting β2-agonists (LABAs) when blood eosinophil counts are ≥300 cells/µL or LABA + long-acting muscarinic antagonist (LAMA) when patients are highly symptomatic, that is, with greater dyspnea and/or exercise limitation. Follow-up treatments for patients with persistent dyspnea and/or exacerbations may include LABA + ICS, LABA + LAMA, or LABA + LAMA + ICS, with use of ICS being guided by blood eosinophil counts. In this review, differences in the inflammatory mechanism underlying COPD and asthma and the role of ICS treatment in COPD are summarized. Furthermore, findings from recent clinical trials where use of ICS-based dual or triple therapy in COPD was compared with LABA + LAMA therapy and trials in which ICS withdrawal was evaluated in patients with COPD are reviewed. Finally, a step-by-step guide for ICS withdrawal in patients who are unlikely to benefit from this treatment is proposed. A video of the author discussing the overall takeaway of the review article could be downloaded from the link provided: https://www.youtube. com/watch? v=Uq7Sr5jqPDI.
Support System for Early Diagnosis of Chronic Obstructive Pulmonary Disease Based on the Service-Oriented Architecture Paradigm and Business Process Management Strategy: Development and Usability Survey Among Patients and Health Care Providers

Background Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with a high global prevalence. The main scientific societies dedicated to the management of this disease have published clinical practice guidelines for quality practice. However, at present, there are important weaknesses in COPD diagnosis criteria that often lead to underdiagnosis or misdiagnosis. Objective We sought to develop a new support system for COPD diagnosis. The system was designed to overcome the weaknesses detected in current guidelines with the goals of enabling early diagnosis, and improving the diagnostic accuracy and quality of care provided. Methods We first analyzed the main clinical guidelines for COPD to detect weaknesses that exist in the current diagnostic process, and then proposed a redesign based on a business process management (BPM) strategy for its optimization. The BPM system acts as a backbone throughout the process of COPD diagnosis in this proposed approach. The newly developed support system was integrated into a health information system for validation of its use in a hospital environment. The system was qualitatively evaluated by experts (n=12) and patients (n=36). Results Among the 12 experts, 10 (83%) positively evaluated our system with respect to increasing the speed for making the diagnosis, helping in interpreting results, and encouraging opportunistic diagnosis. With an overall rating of 4.29 on a 5-point scale, 27/36 (75%) of patients considered that the system was very useful in providing a warning about possible cases of COPD. The overall assessment of the system was 4.53 on a 5-point Likert scale with agreement to extend its use to all primary care centers. Conclusions The proposed system provides a functional method to overcome the weaknesses detected in the current diagnostic process for COPD, which can help foster early diagnosis, while improving the diagnostic accuracy and quality of care provided.
Could vascular endothelial growth factor inhibitors induce hidradenitis suppurativa? Report of three patients with renal cancer treated with sunitinib

Dear Editor, Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disease that primarily affects hair follicles. Up to date, its pathogenesis remains unclear. Drug-induced cases of HS have been described with some treatments such as rituximab, lithium, and vemurafenib. Skin adverse events are common with sunitinib use; however, to the best of our knowledge, no HS cases associated with sunitinib have been communicated in scientific literature. Herein, we report three cases of HS induced or flare-up by sunitinib. Patient 1: A 43-year-old female presented with a 6-month history of recurrent nodular lesions and reinflammation of previous fistula on her left axillae (Figure 1A). Two years before she had started sunitinib treatment because of a renal cancer pT3bN1M0. She was receiving an intermittent dosing, consisting of 4 weeks treatment followed by 2 weeks rest. The lesions spread during the administration of sunitinib and gradually improved after the completion of each cycle. Previously, she had been diagnosed with HS at 14 years old, but her HS was in remission without treatment for 16 years. So, she was diagnosed with HS Hurley II and she started treatment with oral doxycycline 100 mg achieving complete disease control after 8 weeks. Patient 2: A 58-year-old male presented with a 1-month history of a painful left inguinal abscess (Figure 1B). He had no previous history of HS. Two months before, he had started sunitinib therapy for a renal cancer pT2aN0M1. He was diagnosed with HS Hurley I and he started treatment with acitretin 20 mg daily. After 16 weeks, the lesion remained active and surgical excision was needed. Up to date, the patient continues sunitinib treatment, and HS is currently under control.
Reproduction affects immune defenses in the guinea pig even under ad libitum food

Reproduction is one of the costliest processes in the life of an animal. Life history theory assumes that when resources are limiting allocation to reproduction will reduce allocation to other essential processes thereby inducing costs of reproduction. The immune system is vital for survival. If reproduction reduces investment in immune function, this could increase the risk of disease, morbidity and mortality. We here test in the guinea pig, if even under ad libitum food conditions, pregnancy and lactation reduce the activity of the adaptive and innate immune system compared to the reaction of non-reproducing animals. In response to a challenge with keyhole limpet haemocyanin the antibody-mediated adaptive immunity during (pregnancy and) lactation was reduced. Pregnant and lactating females showed higher levels of bacterial killing activity, an integrated measure of innate immunity, than non-reproducing females. However, two major effectors of the innate immunity, the natural antibody and the complement of pregnant and lactating females showed lower levels than in non-reproducing females. Pregnant and lactating females did not differ significantly in the expressed levels of innate immunity. Our results indicate that changes in the immune response during reproduction are physiological adjustments to predictable allocation problems, because they happen even under ad libitum food availability.
Growth Performance, Nutrient Digestibility, Blood Profiles, Excreta Microbial Counts, Meat Quality and Organ Weight on Broilers Fed with De-Oiled Lecithin Emulsifier

Simple Summary Commercial broilers have a short production cycle and a high requirement for energy, so the need to add lipids to the diet of broilers is inevitable. Adding an exogenous emulsifier to diets can enhance the digestion and absorption of lipids in broiler chickens. The effect of de-oiled lecithin as emulsifier on performance, lipid blood profiles, nutrient digestibility, organ weight, meat quality, and excreta microbial counts in broilers were evaluated in the present study. It was determined that the de-oiled lecithin supplemented diets improved the digestion and absorption of lipids through its emulsification, thus promoting better growth performance and health conditions of broilers. The results of this research provide a theoretical basis and a new insight for the applications of lecithin as a feed additive in the poultry feed industry. Abstract This research evaluated the effects of de-oiled lecithin (DOL) as an exogenous emulsifier in broilers. Totally, 480 male broilers (1-d-old, Ross308) were raised for a 35-day feeding experiment. Broilers were randomly divided into three dietary groups including the addition of 0, 61.80%de-oiled lecithin (DOL-60), 97.16%de-oiled lecithin (DOL-97) into the basal diet. Broiler chickens fed with DOL-60 and DOL-97diets had greater body weight gain (BWG) during 1–7 days, 8–21 days, and the overall experimental period (p< 0.05),greater(p < 0.05) breast muscle percentages, and lower (p < 0.05) low-density lipoprotein cholesterol (LDL/C) concentrations. Furthermore, broiler chickens fed with DOL-97 diet showed the highest (p< 0.05)BWG during 22–35 days and feed intake during 8–21 days, lowest (p< 0.05) feed conversion ratio during 22–35 days and overall period, highest (p< 0.05) concentration of serum high-density lipoprotein-cholesterol (HDL/C), lowest (p < 0.05) concentration of serum low-density lipoprotein-cholesterol (LDL/C),excreta population of Escherichia coli (E. coli), and highest(p < 0.05) value of breast muscle redness. In summary, broiler diets inclusion of DOL-97 decreased the excreta E. coli counts, improved the growth performance, increased breast muscle percentage and redness, and enhanced concentrations of serum HDL/C and LDL/C.
Illuminating Macrophage Contributions to Host-Pathogen Interactions In Vivo: the Power of Zebrafish

Macrophages are a key cell type in innate immunity. Years of in vitro cell culture studies have unraveled myriad macrophage pathways that combat pathogens and demonstrated how pathogen effectors subvert these mechanisms. However, in vitro cell culture studies may not accurately reflect how macrophages fit into the context of an innate immune response in whole animals with multiple cell types and tissues. Larval zebrafish have emerged as an intermediate model of innate immunity and host-pathogen interactions to bridge the gap between cell culture studies and mammalian models. ABSTRACT Macrophages are a key cell type in innate immunity. Years of in vitro cell culture studies have unraveled myriad macrophage pathways that combat pathogens and demonstrated how pathogen effectors subvert these mechanisms. However, in vitro cell culture studies may not accurately reflect how macrophages fit into the context of an innate immune response in whole animals with multiple cell types and tissues. Larval zebrafish have emerged as an intermediate model of innate immunity and host-pathogen interactions to bridge the gap between cell culture studies and mammalian models. These organisms possess an innate immune system largely conserved with that of humans and allow state-of-the-art genetic and imaging techniques, all in the context of an intact organism. Using larval zebrafish, researchers are elucidating the function of macrophages in response to many different infections, including both bacterial and fungal pathogens. The goal of this review is to highlight studies in zebrafish that utilized live-imaging techniques to analyze macrophage activities in response to pathogens. Recent studies have explored the roles of specific pathways and mechanisms in macrophage killing ability, explored how pathogens subvert these responses, identified subsets of macrophages with differential microbicidal activities, and implicated macrophages as an intracellular niche for pathogen survival and trafficking. Research using this model continues to advance our understanding of how macrophages, and specific pathways inside these cells, fit into complex multicellular innate immune responses in vivo, providing important information on how pathogens evade these pathways and how we can exploit them for development of treatments against microbial infections.
Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation

Tremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell output blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the activity of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.
Using ESTIMATE algorithm to establish an 8-mRNA signature prognosis prediction system and identify immunocyte infiltration-related genes in Pancreatic adenocarcinoma

Objective: The tumour microenvironment is one of the significant factors driving the carcinogenesis of Pancreatic adenocarcinoma (PAAD). However, the underlying mechanism of how the tumour microenvironment impacts the prognosis of PAAD is not completely clear. Results: The transcriptome and clinical data of 182 PAAD program cases were downloaded from the TCGA database. Three hundred thirty-three differentially expressed genes (DEGs) between high and low stromal groups and 314 DEGs between high and low immune score groups were identified using ESTIMATE score. Based on the 203 genes differentially expressed simultaneously in two score-related comparisons, we established an 8-mRNA signature to evaluate the prognosis of PAAD patients. Kaplan-Meier curves showed significantly worse survival for patients with high-risk scores in both the training and validation groups. The risk score was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. By searching the TCGA database, we showed that CA9, CXCL9, and GIMAP7 from the 8-mRNA signature were associated with the infiltration levels of immunocytes by regulating FOXO1 expression in PAAD. Conclusions: Unlike traditional methods of screening for differential genes in cancer and healthy tissues, we constructed a novel 8-mRNA signature to predict the prognosis of PAAD patients by applying ESTIMATE scoring to RNA-seq-based transcriptome data. Most importantly, we identified CA9, CXCL9, and GIMAP7 from the above eight genes as regulators of immunocyte infiltration by adjusting the expression of FOXO1 in PAAD. Thus, CA9, CXCL9, and GIMAP7 might be the ideal targets of immune therapy of PAAD. Methods: ESTIMATE scoring was used to determine the stromal and immune scores of transcriptome datasets downloaded from the TCGA database. An mRNA-based prognostic signature was built for the training cohort via the LASSO Cox regression model. The signature was verified using a validation cohort. Kaplan-Meier curves and log-rank analysis were used to identify survival differences. Western blot analysis and RT-qPCR analysis were carried out to analyze the expression of specific proteins and mRNAs. IHC was performed to assess the protein levels of Forkhead box-O 1 (FOXO1), Carbonic anhydrase 9 (CA9), C-X-C motif chemokine ligand 9 (CXCL9), and GTPase, IMAP family member 7 (GIMAP7) in the tissue microarray of PAAD.
Evaluating the outcomes of a concept-based curriculum in an associate degree nursing program

A complete overhaul of nursing education has been commanded due to concerns regarding the proficiency of novice nurses and the clinical care they provide in today’s increasingly complex health care environment. Novice nurses are struggling to utilize effective critical thinking skills in order to practice at minimal competency levels. Delivering nursing education using a concept-based curriculum may provide the opportunity to prepare novice nurses to practice in a twenty-first century health care environment. However, limited literature exists examining the outcomes of a conceptbased curriculum. The purpose of this study was to evaluate critical thinking scores, National Council Licensure Examination for Registered Nurses (NCLEX-RN) pass rate prediction scores, and NCLEX-RN pass rates in associate degree nursing (ADN) students completing a concept-based curriculum. The theoretical framework for this study was founded on the experiential learning theory, which postulates students learn through experience, reflection, and by actively participating in the learning process. A retrospective, descriptive, correlational design was utilized to evaluate secondary data from a convenience sample of ADN students (N = 258) from one college of nursing, located in a Midwestern state. Data analysis revealed critical thinking program exit score was significantly higher than critical thinking program entry score (p <0.001).
Functional imaging in congenital heart disease with 3D cine phase contrast MRI

Volumetric, time-resolved, phase contrast Magnetic Resonance Imaging (MRI) with three-directional velocity encoding (4D PC MRI) can provide both anatomical and hemodynamic information with high spatial resolution in clinically feasible scan times. This work focuses on the application of 4D PC MRI to congenital heart disease (CHD). Major and minor CHD defects occur in approximately nine defects per 1000 live births, of which about a quarter would be expected to require invasive treatment or result in death within the first year of life. Imaging modalities such as Doppler Ultrasound and CT have been used extensively in CHD patients. Despite several appealing properties, MRI use has
Theoretical explanation The Intel Optimization Reference Manual says the following regarding

Posted by Jann Horn, Project Zero We have discovered that CPU data cache timing can be abused to efficiently leak information out of misspeculated execution, leading to (at worst) arbitrary virtual memory read vulnerabilities across local security boundaries in various contexts. Variants of this issue are known to affect many modern processors, including certain processors by Intel, AMD and ARM. For a few Intel and AMD CPU models, we have exploits that work against real software. We reported this issue to Intel, AMD and ARM on 2017-06-01 [1]. So far, there are three known variants of the issue: Variant 1: bounds check bypass (CVE-2017-5753) Variant 2: branch target injection (CVE-2017-5715) Variant 3: rogue data cache load (CVE-2017-5754)