Miracle-dz/UniFAR-FTUs huggingface dataset:
Anchor Away – A Fast, Reliable and Reversible Technique To Inhibit Proteins in Drosophila melanogaster

Several techniques have been developed to study specific gene function in loss-of-function situations. In Drosophila melanogaster, RNAi and the generation of mutant clones are widely used. However, both techniques have the limitation that there is a significant time lag before gene function is abolished. Given the relatively rapid development of Drosophila, such perdurance is a serious impediment to study gene function. Here we describe the adaptation of the anchor-away technique for use in Drosophila. Anchor-away was originally developed in yeast to quickly and efficiently abrogate the function of nuclear proteins by sequestering - anchoring - them away in a different cellular compartment. The required components are present in the cells, and the system is triggered by the addition of rapamycin, resulting in a rapid generation of a loss-of-function situation. We provide here proof of principle for the system by producing loss-of-function situations for two nuclear proteins – Pygopus and Brinker. The system allows to study the requirement of any protein during any time window, and at the same time circumvents difficulties, such as off-target effects or variable phenotypes, which are inherent in other techniques, for example RNAi.
Assessment of a Single Intra-Articular Stifle Injection of Pure Platelet Rich Plasma on Symmetry Indices in Dogs with Unilateral or Bilateral Stifle Osteoarthritis from Long-Term Medically Managed Cranial Cruciate Ligament Disease

Purpose The use of platelet-rich plasma (PRP) to treat canine osteoarthritis has gained support within the scientific community. PRP effects on pain control for degenerative joint disease induced by naturally occurring cranial cruciate ligament instability are limited, particularly in a cohort of dogs with chronic instability and osteoarthritis (>12 months), representing a commonly encountered clinical population that often defaults to medical management. The goal of this study was to assess the effects of a single intra-articular PRP injection into an effected stifle in this cohort, to assess response to treatment, quantitative kinetic data as it relates to percent body weight for peak vertical force (PVF) and vertical impulse (VI) were collected, and symmetry indices related to PVF were determined. Methods Twelve dogs with unilateral or bilateral osteoarthritis with ruptured, non-stabilized cranial cruciate ligaments over 12 months duration were identified. Unilateral injections of 2.5 mL of a PRP preparation into the most severely affected stifle based on kinetic analysis was performed. Repeat pressure-sensitive walkway analysis was conducted monthly for 3 months. Peak vertical force (PVF) and vertical impulse (VI) were normalized to body weight and identified in all four limbs. Previously published symmetry indices regarding PVF were calculated, comparing the treated limb with the contralateral limb, ipsilateral forelimb, and contralateral forelimb. Results After treatment, hind limb symmetry index (SI) regarding PVF showed improved symmetry, suggesting more weight placement at all-time points after injection of the most affected limb (p < 0.01). Further, PVF asymmetry indices assessing contralateral fore (CFL) and hind limb (CHL) as well as ipsilateral forelimb (IFL) revealing a significant decrease from baseline for CHL at week 4 (p = 0.02), but not weeks 8 and 12. The CFL showed decreased differences in symmetry from baseline at each time point (p = 0.03). There were no statistically significant changes in PVF or VI over time in treated dogs. Conclusion A single injection of PRP improved kinetics for minimally 4 weeks with some data suggesting an effect for up to 12 weeks. Therefore, PRP might be a viable therapeutic option for instability and inflammation associated with chronic osteoarthritis due to cranial cruciate ligament disease in the non-surgical patient.
Performance, Behavior, and Welfare Status of Six Different Organically Reared Poultry Genotypes

Simple Summary In an extensive poultry production system, the choice of chicken strain becomes very important, because it is strictly linked to the use of outdoor space. In fact, many of the chicken strains selected for the high productive performance required by intensive production systems are not adapted to extensive rearing systems. Accordingly, in most European countries, the choice of poultry genotype usable in an organic system depends on weight gain. However, many other traits are important in the assessment of animal adaptability. The aim of this study was to investigate the behavior, the productive performance, and the welfare status of six different poultry genotypes when organically reared. The results showed that the genotypes with the best productive performance were not adapted to the organic system, because they were too static and exhibited the worst welfare status. On the contrary, strains with lower growth performance showed more active behaviors and the best welfare status. However, chickens with similar performances showed a different degree of adaptation to the extensive rearing system due to the intrinsic characteristics of the strain. In conclusion, use of an organic production system requires an equilibrium between performance and adaptability. Abstract In alterative rearing systems, the use of outdoor space has a crucial role. It is well known that only some commercial poultry genotypes are suitable to be reared in these systems. It is necessary to find a balance between productive performance and adaptability. The aim of this study was to evaluate the productive performance, behavior, and welfare status of six poultry genotypes reared in an organic system. One hundred males/genotype (Hubbard RedJA (A), CY5XJA87 (CY), M22XJA87 (M), Ranger Classic (R1), Ranger Gold (R2), and Rowan Ranger (R3)) were reared from 1 to 81 days of age. The number of culled birds was recorded daily, whereas live weight and feed consumption were recorded weekly. Behavior evaluation was undertaken through a computerized system one week before slaughtering; the breast yield and muscle/bone ratio of the drumstick was also evaluated in refrigerated carcasses. The results showed that A and R3 had good adaptability, showing active behaviors and satisfactory productive performance 3083.6 g and 3022.1 g, respectively. Although CY and M achieved the best productive performance, they did not appear adapted to the organic system due to a higher frequency of static behaviors (rest and roost), mortality, footpad dermatitis, breast blisters, and poor feather condition.
Effects of Dietary Fatty Acids on Gut Health and Function of Pigs Pre- and Post-Weaning.

Fatty acids (FA) play a major role in relation to mucosal immune responses, epithelial barrier functions, oxidative stress and inflammatory reactions. The dietary FA composition and the molecular structures (chain length and number of double bonds) influence digestion, absorption and metabolism, and the bioactivity of the FA. Piglets post-weaning having an immature intestine and not fully formed immune functions are very vulnerable to invading microorganisms. Manipulation of the milk FA composition via sow nutrition, or inclusion of dietary fat sources in the feed for newly weaned pigs, may be used as a strategic tool to enhance pig performance and their gut health and function pre- and post-weaning. Medium-chain fatty acids (MCFA) are absorbed directly into the portal blood and may contribute with immediate energy for the enterocytes. In addition, the MCFA, similarly to the short-chain fatty acids (SCFA), possess antibacterial effects and may thereby prevent overgrowth of pathogenic bacteria in the gastrointestinal tract. The essential fatty acids, linoleic (LA) and linolenic (ALA) fatty acids, form the building blocks for the long-chain polyunsaturated n-3 and n-6 FA. The conversion of ALA and LA into n-3 and n-6 eicosanoids, respectively, influences the molecular structures of metabolites and inflammatory reactions and other immune responses upon bacterial challenges. Dietary manipulation of the lactating sow influences the transfer of the n-3 and n-6 polyunsaturated fatty acids (PUFA) from the sow milk to the piglet and the incorporation of the fatty acids into piglet enteric tissues and cell membranes, which exerts bioactivity of importance for immune responses and the epithelial barrier function. Especially the n-3 PUFA present in fish oil seem to influence the gut health and function of pigs, and this is of importance during the transition periods such as post-weaning in which piglets are prone to inflammation. The proportion of unsaturated fatty acids in the cell membranes influences the susceptibility to oxidative stress. Oxidative stress accompanies infectious diseases, and the development of lipid peroxides and other reactive oxygen products may be harmful to the epithelial barrier function. Fatty acid peroxides from the feed may also be absorbed with other lipid-solubles and thereby harm the intestinal function. Hence, antioxidative protection is important for the enteric cells. In conclusion, manipulation of the dietary FA composition can influence the gut health and function in pigs and may support a normal immune system and modulate resistance to infectious diseases during especially stressful phases of a pig's life such as post-weaning.
European Guideline on Achalasia – UEG and ESNM recommendations

Introduction Achalasia is a primary motor disorder of the oesophagus characterised by absence of peristalsis and insufficient lower oesophageal sphincter relaxation. With new advances and developments in achalasia management, there is an increasing demand for comprehensive evidence-based guidelines to assist clinicians in achalasia patient care. Methods Guidelines were established by a working group of representatives from United European Gastroenterology, European Society of Neurogastroenterology and Motility, European Society of Gastrointestinal and Abdominal Radiology, and the European Association of Endoscopic Surgery in accordance with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. A systematic review of the literature was performed and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Recommendations were voted upon using a nominal group technique. Results These guidelines focus on the definition of achalasia, treatment aims, diagnostic tests, medical, endoscopic and surgical therapy, management of treatment failure, follow-up and oesophageal cancer risk. Conclusion These multidisciplinary guidelines provide a comprehensive evidence-based framework with recommendations on the diagnosis, treatment and follow-up of adult achalasia patients.
Practice advisory: Thymectomy for myasthenia gravis (practice parameter update)

Objective To review updated evidence regarding the effectiveness of thymectomy for treating patients with myasthenia gravis (MG). Methods The practice advisory panel performed a systematic review and developed practice recommendations using methods developed by the American Academy of Neurology. Results One Class I study of patients younger than 65 years with nonthymomatous acetylcholine receptor antibody–positive (AChR ab+) generalized MG demonstrated better clinical outcomes in patients treated with oral prednisone and undergoing thymectomy compared with patients treated with prednisone alone, including an increased probability of attaining minimal manifestation status (no symptoms or functional limitations). Conclusion For patients with nonthymomatous AChR ab+ generalized MG, treatment with thymectomy plus prednisone is probably more effective than treatment with prednisone alone for increasing the chance of attaining minimal manifestation status (risk difference at 36 months, 20%; 95% confidence interval, 1.6%–37%; moderate confidence in the evidence). Recommendations Clinicians should discuss thymectomy treatment with patients with AChR ab+ generalized MG (Level B). Clinicians should counsel patients with AChR ab+ generalized MG considering minimally invasive thymectomy techniques that it is uncertain whether the benefit attained by extended transsternal thymectomy will also be attained by minimally invasive approaches (Level B).
Mitophagy in Cardiovascular Diseases

Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes.
Specific NDM-1 Inhibitor of Isoliquiritin Enhances the Activity of Meropenem against NDM-1-positive Enterobacteriaceae in vitro

NDM-1-positive Enterobacteriaceae have caused serious clinical infections, with high mortality rates. Carbapenem was the ultimate expectation for the treatment of such infections in clinical practice. However, since the discovery of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1), the efficient therapeutic effects of carbapenems have been increasingly restricted. Here, we identified isoliquiritin, a novel specific inhibitor of the NDM-1 enzyme that restored the activity of carbapenem against NDM-1-producing E. coli isolates and K. pneumoniae isolates without affecting the growth of bacteria. A checkerboard test, growth curve assays and time-kill assays confirmed the significant synergistic effect of isoliquiritin combined with meropenem in vitro. It is worth noting that isoliquiritin only inhibited the activity of NDM-1 and had no obvious inhibitory effect on other class B metallo-β-lactamases (VIM-1) or NDM-1 mutants (NDM-5). The FIC indices of meropenem with isoliquiritin on NDM-1-positive E. coli and K. pneumoniae were all less than 0.5. Isoliquiritin had no influences on the expression of NDM-1-positive strains at concentrations below 64 µg/mL. Collectively, our results show that isoliquiritin is a potential adjuvant therapy drug that could enhance the antibacterial effect of carbapenems, such as meropenem, on NDM-1-positive Enterobacteria and lay the foundation for subsequent clinical trials.
The effect of changing arterial blood pressure and carbon dioxide on cerebral blood flow

The short article entitled ‘Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial blood pressures’, published in 1965 in the JNNP by A Murray Harper and HI Glass,1 is among the most cited articles ever published in the journal (429 citations as of 21 January 2020). Interestingly, the same first author published the subsequent year in the JNNP another highly cited article2 on a closely related subject (372 citations as of 2020). The effect of changing arterial blood pressure and carbon dioxide on cerebral blood flow Authors : Harper AM, Glass HI Year Published : 1965 Number of times cited : 548 The Harper and Glass 1965 article was the first to assess the effects of changes in the arterial partial pressure of CO2 (PaCO2) on the cerebral circulation in conditions of normal arterial blood pressure, moderate hypotension and severe hypotension. To this end, the authors applied in anaesthetised mongrel dogs the technique that Lassen and Ingvar had just developed to measure quantitative regional blood flow of the exposed cerebral cortex using radioactive krypton injected in the internal carotid artery.3 The strong effects of changes in PaCO2 on the cerebral vasculature, first discovered in 1928 by Forbes and Wolff via direct observation of the pial arteries through a glass window in animals, …
23Na‐MRI as a Noninvasive Biomarker for Cancer Diagnosis and Prognosis

The influx of sodium (Na+) ions into a resting cell is regulated by Na+ channels and by Na+/H+ and Na+/Ca2+ exchangers, whereas Na+ ion efflux is mediated by the activity of Na+/K+‐ATPase to maintain a high transmembrane Na+ ion gradient. Dysfunction of this system leads to changes in the intracellular sodium concentration that promotes cancer metastasis by mediating invasion and migration. In addition, the accumulation of extracellular Na+ ions in cancer due to inflammation contributes to tumor immunogenicity. Thus, alterations in the Na+ ion concentration may potentially be used as a biomarker for malignant tumor diagnosis and prognosis. However, current limitations in detection technology and a complex tumor microenvironment present significant challenges for the in vivo assessment of Na+ concentration in tumor. 23Na‐magnetic resonance imaging (23Na‐MRI) offers a unique opportunity to study the effects of Na+ ion concentration changes in cancer. Although challenged by a low signal‐to‐noise ratio, the development of ultrahigh magnetic field scanners and specialized sodium acquisition sequences has significantly advanced 23Na‐MRI. 23Na‐MRI provides biochemical information that reflects cell viability, structural integrity, and energy metabolism, and has been shown to reveal rapid treatment response at the molecular level before morphological changes occur. Here we review the basis of 23Na‐MRI technology and discuss its potential as a direct noninvasive in vivo diagnostic and prognostic biomarker for cancer therapy, particularly in cancer immunotherapy. We propose that 23Na‐MRI is a promising method with a wide range of applications in the tumor immuno‐microenvironment research field and in cancer immunotherapy monitoring.
Nonalcoholic fatty liver disease, insulin resistance, and sweeteners: a literature review

ABSTRACT Introduction: Sweeteners are substances used to replace sugar. They can either be chemically produced (artificial sweeteners) or extracted from plants (natural sweeteners). In the last two decades, there is an increased popularity in their role as sugar substitutes in individuals to promote weight loss or maintain glycemic control. However, despite their favorable effects, there is concern regarding their side effects and especially their influence in the development of nonalcoholic fatty liver disease (NAFLD). Areas covered: A comprehensive literature search was conducted on Medline including systematic reviews, longitudinal controlled studies, and retrospective cohort studies. We present an up-to-date systematic review of the current literature regarding the safety in artificial and natural sweeteners use as a means of weight loss or diabetes control. Expert opinion: Natural sweeteners have not been associated directly with NAFLD, and on the contrary, some, such as stevia, and trehalose, may have a protective effect. Rare sugars and polyols can be used safely and have significant benefits that include anti-oxidant effect and optimal glycemic control. Artificial sweeteners, due to their effect on NAFLD development and insulin resistance, are not indicated in patients with obesity or diabetes. Further studies in human subjects are required to verify the above findings.
Theoretical Insights into the Structures and Capacitive Performances of Confined Ionic Liquids

Room-temperature ionic liquids (RTILs) together with nano-porous electrodes are the most promising materials for supercapacitors and batteries. Many theoretical works have addressed the structures and performances of RTILs inside nanopores. However, only limited attention has been given to how the dispersion forces of RTILs influence the behavior of ions inside the slit pores. Toward this aim, we investigate the effects of various dispersion forces between ions on the macroscopic structures in nanoconfinement and the capacitance performance of supercapacitors by the classical density functional theory (CDFT). The results show that the dispersion force can significantly change the mechanism of the charging process and even the shape of differential capacitance curves. In addition, the voltage-dependent structures of RTILs with appropriate dispersion force appears in a given silt pore, which leads to extremely high capacitance and enhances the energy storage density. We hope that this work could further offer guidance for the optimizing of electrolytes for electrical double layer capacitors, like tuning the dispersion force between ions by adding/removing certain chemical groups on the cations and anions of RTILs.
Verbesserte Protein- und Energiezufuhr senkt Mortalität schwer kranker Patienten

Risiken und Vorteile einer verbesserten Energieund Proteinzufuhr bei Patienten der Intensivstation werden derzeit kontrovers diskutiert. Diese prospektive multinationale Multicenterstudie untersucht in zwei unterschiedlich schwer erkrankten Patientenpopulationen den Zusammenhang von Proteinund Energiezufuhr auf das Überleben bis zur Krankenhausentlassung und die 60-Tage Mortalität.
Análisis cuantitativo de la expresión de genes de resistencia a fluconazol en cepas de Candida albicans aisladas al ingreso de adultos mayores a una unidad de cuidados intensivos de Manizales, Colombia

Resumen Introducción. Las infecciones oportunistas asociadas con Candida albicans han tenido gran repercusión en la salud pública por la mortalidad que generan en determinados grupos poblacionales. Aunque existen tratamientos farmacológicos disponibles, es evidente el aumento de la resistencia desarrollada por el agente patógeno, por lo que la determinación de los mecanismos de resistencia de las cepas presentes en las áreas hospitalarias es importante, ya que permitiría plantear mejores esquemas de tratamiento. Objetivo. Analizar la expresión de los genes ERG11, CDR1 y MDR1 en cepas de C. albicans aisladas de adultos mayores a su ingreso en la unidad de cuidados intensivos del Hospital Santa Sofía de Manizales, Colombia. Materiales y métodos. Se seleccionaron 29 muestras (21 resistentes y 8 sensibles) y se conformaron dos grupos de trabajo, uno de muestras con exposición al fluconazol y el otro sin esta. El ARN extraído se cuantificó mediante reacción en cadena de la polimerasa con transcriptasa inversa en tiempo real (RT-qPCR). Resultados. Se encontraron diferencias significativas en la expresión del gen MDR1 en el grupo de cepas de C. albicans resistentes. Dos de las cepas resistentes (104 y 62-2) expuestas al antifúngico presentaron valores muy elevados en la expresión de este gen. La expresión del ERG11 y del CDR1 no fue significativa en los grupos estudiados. Conclusión. El aumento de sobreexpresión del gen MDR1 indica que este puede ser el responsable de la resistencia; sin embargo, algunas cepas resistentes no sobreexpresaron los genes analizados, lo que indica que puede haber otros genes involucrados en la resistencia de las cepas estudiadas.