Miracle-dz/UniFAR-FTUs huggingface dataset:
Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice

Ischemic stroke is a complex and devastating event characterized by cell death resulting from a transient or permanent arterial occlusion. Astrocytic connexin43 (Cx43) gap junction (GJ) proteins have been reported to impact neuronal survival in ischemic conditions. Consequently, Cx43 could be a potential target for therapeutic approaches to stroke. We examined the effect of danegaptide (ZP1609), an antiarrhythmic dipeptide that specifically enhances GJ conductance, in two different rodent stroke models. In this study, danegaptide increased astrocytic Cx43 coupling with no significant effects on Cx43 hemichannel activity, in vitro. Using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) the presence of danegaptide within brain tissue sections were detected one hour after reperfusion indicating successful transport of the dipeptide across the blood brain barrier. Furthermore, administration of danegaptide in a novel mouse brain ischemia/reperfusion model showed significant decrease in infarct volume. Taken together, this study provides evidence for the therapeutic potential of danegaptide in ischemia/reperfusion stroke.
Chronic wasting disease (CWD) prion strains evolve via adaptive diversification of conformers in hosts expressing prion protein polymorphisms

Chronic wasting disease (CWD) is caused by an unknown spectrum of prions and has become enzootic in populations of cervid species that express cellular prion protein (PrPC) molecules varying in amino acid composition. These PrPC polymorphisms can affect prion transmission, disease progression, neuropathology, and emergence of new prion strains, but the mechanistic steps in prion evolution are not understood. Here, using conformation-dependent immunoassay, conformation stability assay, and protein-misfolding cyclic amplification, we monitored the conformational and phenotypic characteristics of CWD prions passaged through deer and transgenic mice expressing different cervid PrPC polymorphisms. We observed that transmission through hosts with distinct PrPC sequences diversifies the PrPCWD conformations and causes a shift toward oligomers with defined structural organization, replication rate, and host range. When passaged in host environments that restrict prion replication, distinct co-existing PrPCWD conformers underwent competitive selection, stabilizing a new prion strain. Nonadaptive conformers exhibited unstable replication and accumulated only to low levels. These results suggest a continuously evolving diversity of CWD conformers and imply a critical interplay between CWD prion plasticity and PrPC polymorphisms during prion strain evolution.
Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes

Retinal development is under the coordinated control of overlapping networks of signaling pathways and transcription factors. The paper was conceived as a review of the data and ideas that have been formed to date on homeobox genes mutations that lead to the disruption of eye organogenesis and result in inherited eye/retinal diseases. Many of these diseases are part of the same clinical spectrum and have high genetic heterogeneity with already identified associated genes. We summarize the known key regulators of eye development, with a focus on the homeobox genes associated with monogenic eye diseases showing retinal manifestations. Recent advances in the field of genetics and high-throughput next-generation sequencing technologies, including single-cell transcriptome analysis have allowed for deepening of knowledge of the genetic basis of inherited retinal diseases (IRDs), as well as improve their diagnostics. We highlight some promising avenues of research involving molecular-genetic and cell-technology approaches that can be effective for IRDs therapy. The most promising neuroprotective strategies are aimed at mobilizing the endogenous cellular reserve of the retina.
The Characteristics of Patients Frequently Tested and Repeatedly Infected with Neisseria gonorrhoeae

We assessed whether patients repeatedly infected with Neisseria gonorrhoeae (NG) were different compared to patients repeatedly tested negative, to obtain insight into the characteristics of patients frequently tested and infected with NG. All patients tested for NG (n = 16,662) between January 2011 and July 2018 were included. Multivariable logistic regression analyses were performed for the outcomes “repeat NG infections” and “once NG positive and not retested” versus patients “repeatedly tested NG negative”. Of the individuals tested for NG, 0.2% (40/16,662) had repeat (≥2) NG infections, and accounted for 23% of all diagnosed NG infections. STI clinic patients, men (mostly men who have sex with men (MSM)), patients aged ≥25 years, and patients co-infected with HIV or Chlamydia trachomatis (CT) more often had repeat NG infections. The number of patients not retested after their initial NG diagnosis was 29.9% (92/308). Men (mostly MSM), HIV positive patients, and patients notified for sexually transmitted infections (STIs) were more often NG positive and not retested. Concluding, only 40 patients tested for NG accounted for one in four diagnosed NG infections. However, re-infections are likely to be missed among MSM and HIV positive patients, as they were mainly not retested after NG infection. It remains important to test and re-test for NG, especially in MSM, in order to halt transmission.
Effect of sternal electrode gap and belt rotation on the robustness of pulmonary electrical impedance tomography parameters

Non-adhesive textile electrode belts offer several advantages over adhesive electrodes and are increasingly used in neonatal patients during continuous electrical impedance tomography (EIT) lung monitoring. However, non-adhesive belts may rotate in unsedated patients and discrepancies between chest circumference and belt sizes may result in a gap between electrodes near the sternum. This project aimed to determine the effects of belt rotation and sternal electrode gap on commonly used lung EIT parameters. We developed a simulation framework based on a 3D finite-element model and introduced lung regions with little or no ventilation that could be changed according to a decremental positive end-expiratory pressure (PEEP) trial. Four degrees of sternal gap and belt rotation were simulated and their effect on the EIT parameters silent spaces, centre of ventilation, global inhomogeneity index and overdistension/collapsed lung (OD/CL) analysed. Additionally, seven premature infants were examined to assess the influence of leftward and rightward belt rotations in a clinical setting. Small violations of the electrode equidistance criterion and rotations of the belts less than one electrode space exert only minor effects on the EIT parameters and do not impede the interpretation. Rotations of two and three electrode spaces induce non-negligible effects that might lead to flawed interpretations. The ‘best PEEP’ determined with the OD/CL approach was robust and identifiable with all studied sternal gaps and belt rotations. We revealed an important challenge for neonatal EIT applications related to a wide electrode gap at the sternum and belt rotation, which should be avoided in clinical application.
Nutritional Quality of Fast Food Kids Meals and Their Contribution to the Diets of School-Aged Children

International data indicate that children and adolescents obtain around one third of their daily food intake from products consumed outside their home. Food products from restaurants are usually higher in calories and lower in nutritional value than those prepared home. We evaluated the nutritional quality in kids’ meals from three fast food chains and two movie theaters and compared them with nutritional recommendations for Mexican school-age population. Results showed that the menu options marketed for school-age children have higher caloric contributions than those recommended, in addition to a deficient nutritional quality. The contribution of caloric and of almost all macronutrients for all mealtimes is not only high but even above 100% or 200% of the mean recommended daily intake (reaching to more than 400% of the recommendations of carbohydrates and lipids of preschool age group). In particular, the snack main dish (popcorn), provides over 100% of the mean energy intake recommendations for the three school age groups and for preschool age group, this contribution could reach to 270%. Therefore, regulations regarding nutritional recommendations should exist for these types of commercialized food products for school-age children, along with mandatory and clear labeling that allows consumers to be able to make better choices for their kids.
Determinants of Resistance to Checkpoint Inhibitors

The development of immune checkpoint inhibitors (ICIs) has drastically altered the landscape of cancer treatment. Since approval of the first ICI for the treatment of advanced melanoma in 2011, several therapeutic agents have been Food and Drug Administration (FDA)-approved for multiple cancers, and hundreds of clinical trials are currently ongoing. These antibodies disrupt T-cell inhibitory pathways established by tumor cells and thus re-activate the host’s antitumor immune response. While successful in many cancers, several types remain relatively refractory to treatment or patients develop early recurrence. Hence, there is a great need to further elucidate mechanisms of resistant disease and determine novel, effective, and tolerable combination therapies to enhance efficacy of ICIs.
Translational Regulations in Response to Endoplasmic Reticulum Stress in Cancers

During carcinogenesis, almost all the biological processes are modified in one way or another. Among these biological processes affected, anomalies in protein synthesis are common in cancers. Indeed, cancer cells are subjected to a wide range of stresses, which include physical injuries, hypoxia, nutrient starvation, as well as mitotic, oxidative or genotoxic stresses. All of these stresses will cause the accumulation of unfolded proteins in the Endoplasmic Reticulum (ER), which is a major organelle that is involved in protein synthesis, preservation of cellular homeostasis, and adaptation to unfavourable environment. The accumulation of unfolded proteins in the endoplasmic reticulum causes stress triggering an unfolded protein response in order to promote cell survival or to induce apoptosis in case of chronic stress. Transcription and also translational reprogramming are tightly controlled during the unfolded protein response to ensure selective gene expression. The majority of stresses, including ER stress, induce firstly a decrease in global protein synthesis accompanied by the induction of alternative mechanisms for initiating the translation of mRNA, later followed by a translational recovery. After a presentation of ER stress and the UPR response, we will briefly present the different modes of translation initiation, then address the specific translational regulatory mechanisms acting during reticulum stress in cancers and highlight the importance of translational control by ER stress in tumours.
Effect of Volume on Eccentric Overload-Induced Postactivation Potentiation of Jumps.

PURPOSE To investigate the postactivation potentiation (PAP) effects of different eccentric overload (EOL) exercise volumes on countermovement-jump (CMJ) and standing-long-jump (LJ) performance. METHODS In total, 13 male university soccer players participated in a crossover design study following a familiarization period. Control (no PAP) CMJ and LJ performances were recorded, and 3 experimental protocols were performed in a randomized order: 1, 2, or 3 sets of 6 repetitions of flywheel EOL half-squats (inertia = 0.029 kg·m2). Performance of CMJ and LJ was measured 3 and 6 minutes after all experimental conditions. The time course and magnitude of the PAP were compared between conditions. RESULTS Meaningful positive PAP effects were reported for CMJ after 2 (Bayes factor [BF10] = 3.15, moderate) and 3 (BF10 = 3.25, moderate) sets but not after 1 set (BF10 = 2.10, anecdotal). Meaningful positive PAP effects were reported for LJ after 2 (BF10 = 3.05, moderate) and 3 (BF10 = 3.44, moderate) sets but not after 1 set (BF10 = 0.53, anecdotal). The 2- and 3-set protocols resulted in meaningful positive PAP effects on both CMJ and LJ after 6 minutes but not after 3 minutes. CONCLUSION This study reported beneficial effects of multiset EOL exercise over a single set. A minimum of 2 sets of flywheel EOL half-squats are required to induce PAP effects on CMJ and LJ performance of male university soccer players. Rest intervals of around 6 minutes (>3 min) are required to maximize the PAP effects via multiple sets of EOL exercise. However, further research is needed to clarify the optimal EOL protocol configurations for PAP response.
The Productivity and Financial Impacts of Eight Types of Environmental Enrichment for Broiler Chickens

Simple Summary Fast growing broiler birds have an elevated risk of leg health problems through inactivity. Increasing the complexity (enriching) of the rearing environment, e.g., adding straw bales into broiler houses, is suggested as a way of increasing activity levels. While a number of studies have examined the impact of enrichments on bird activity levels and health, few have examined their financial impacts. This is problematic, because enrichments which cost money to implement that do not provide an obvious financial benefit are unlikely to be adopted without regulation. This study examines the financial impacts of eight enrichments, accounting for the cost of the enrichment and changes to both bird productivity, e.g., growth rates and market prices. The study found financial benefits from only one of the enrichments (increased distance between feed and water to 3.5 m) and financial losses in most cases, due to the costs of the enrichments. The impacts of the enrichments on bird productivity are relatively minor. The study suggests that if widespread adoption of these enrichments, to obtain welfare benefits, is to be achieved, some form of market incentive will need to be provided, such as a price premium paid by consumers in return for an enhanced rearing environment. Abstract Reduced mobility in broilers can contribute to leg health problems. Environmental enrichment has been suggested as one approach to combat this through stimulating increased physical activity. Past studies have tested the effect of environmental enrichments on bird behaviour, health and welfare, but few have estimated their financial impacts. This study tested the impact of eight types of environmental enrichment on enterprise net margin, accounting for direct intervention costs plus indirect effects via changes to bird mortality, weight, feed intake, feed conversion ratio, and foot pad dermatitis. The trial used 58 pens each containing approximately 500 broilers (Ross 308) at a stocking density of 40 kg/m2. The environmental enrichments were: roughage, vertical panels, straw bales, elevated platforms (5 and 30 cm), increased distances between feed and water (7 and 3.5 m) and stocking density reduced to 34 kg/m2, plus a control group. Mortality was recorded daily and feed intake and weight weekly. Footpad dermatitis was assessed on day 35. Only one intervention improved financial performance (3.5 m between feed and water) above the control, suggesting that most environmental enrichment would have a negative financial impact due to the additional intervention costs, unless consumers were willing to pay a price premium.
Effect of Maternal Water Restriction on Sexual Behavior, Reproductive Performance, and Reproductive Hormones of Male Rat Offspring

Simple Summary Drinking water restriction that a pregnant female may encounter is one of the major stressors that could affect pregnancy outcome and understanding its effects is important in animal welfare concerns and pregnancy outcomes for women or animals. To the best of our knowledge, maternal drinking water restriction has not yet been investigated in previous studies as a potential factor affecting reproductive performance of male rat offspring over first and second generations. Therefore, we aimed to assess the consequences of maternal drinking water restriction stress on sexual behavior, reproductive performance, and reproductive hormones of male rat offspring. The 50% maternal water restriction during the second half of pregnancy reduced body weights of rat dams and offspring at birth and negatively impacted some reproductive characteristics. However, reproductive performance and hormones of males were not adversely affected. Abstract The present study aimed to investigate the effect of maternal water restriction on sexual behavior, reproductive performance, and reproductive hormones of male rat offspring. Forty pregnant female rats were divided into two equal groups: Control (C) and water-restricted (WR). Control dams had ad libitum water access throughout pregnancy, while dams in the WR group were subjected to 50% water-restriction from day 10 of pregnancy onwards. The maternal water restriction provoked a significant reduction (p < 0.05) in body weight of dams before delivery and at birth and litter body weights of offspring at birth. Maternal water restriction did not affect relative weights of reproductive and body organs of male rat offspring. All hormonal concentrations, sperm count, and vitality in male rat offspring were not significantly affected by maternal water restriction. Maternal water restriction exposure induced significant (p < 0.05) reduction in intromission latency, intromission frequency, and post-ejaculation interval in male rat offspring while a significant (p < 0.05) increase in the ejaculation latency was detected in maternal WR group. In conclusion, this study suggests that maternal water restriction had a negative impact on some reproductive characteristics but did not severely affect reproductive performance and reproductive hormones of male rat offspring.
Atypical reversed pressure-induced phase transformation in Ge nanowires

Phase transformations of Ge under compression/decompression cycle at room temperature were studied in a diamond anvil cell (DAC) using in situ synchrotron x-ray diffraction, Raman spectroscopy and near infrared absorption techniques. Upon compression similar behavior is observed in nanowires and in bulk although a higher stability is observed in nanowires. The cubic-diamond phase (Ge-3C), the most energetically favorable phase, transforms into the β-tin metallic phase at high pressure and the reverse Ge-β-tin to Ge-3C transformation is generally inhibited by kinetics when pressure is released. While the transformation in Ge bulk leads mostly to Ge-ST12 phase, the loading/unloading cycle of Ge nanowires in DAC leads back to Ge-3C, exhibiting unprecedented size effects. A comprehensive characterization of the final states is described.
Human serum mast cell tryptase levels in elbow fractures or dislocations and its association with injury severity.

Mast cells contain an abundance of tryptase, and preclinical models have shown elevated serum mast cell tryptase (SMCT) in the setting of post-traumatic joint contractures. Therefore, SMCT emerged as a potential biomarker to help recognize patients with more severe injuries and a higher likelihood of developing contractures. The objective of this study is to assess SMCT levels in participants with varying severity of elbow fractures and/or dislocations. A prospective cohort including 13 participants with more severe injuries that required an operation and 28 participants with less severe injuries managed non-operatively were evaluated. A control group of 8 individuals without elbow injuries was also evaluated. The SMCT levels were measured using an ELISA kit specific for human mast cell tryptase. A one-way ANOVA and Tukey's Honest Significance Test was used to assess for statistical significance among and between the three groups. The average time from injury to collection of the blood samples was 4 ± 2 days. Highly significant differences were identified between the operative, non-operative, and control groups (p = 0.0005). In the operative group, SMCT levels were significantly higher than the non-operative group (p=0.0005) and the control group (p=0.009), suggesting a correlation between SMCT levels and injury severity. There was no statistically significant difference in SMCT levels between the non-operative and control groups. The SMCT levels were elevated in participants with acute elbow injuries requiring operative intervention, suggesting that SMCT levels were higher in injuries regarded as more severe. This article is protected by copyright. All rights reserved.
Predictors of mathematics in primary school: magnitude comparison, verbal and spatial working memory measures.

We determined the relative importance of the so-called approximate number system, symbolic number comparison and verbal and spatial short-term and working memory capacity for mathematics achievement in 1254 Grade 2, 4 and 6 children. The large sample size assured high power and low false report probability and allowed us to determine effect sizes precisely. We used reading decoding as a control outcome measure to test whether findings were specific to mathematics. Bayesian analysis allowed us to provide support for both null and alternative hypotheses. We found very weak zero-order correlations between approximate number system (ANS) measures and math achievement. These correlations were not specific to mathematics, became non-significant once intelligence was considered, and ANS measures were not selected as predictors of math by regression models. In contrast, overall symbolic number comparison accuracy and spatial working memory measures were reliable and mostly specific predictors of math achievement. Verbal short-term and working memory and symbolic number comparison reaction time were predictors of both reading and math achievement. We conclude that ANS tasks are not suitable as measures of math development in school-age populations. In contrast, all other cognitive functions we studied are promising markers of mathematics development.
Butyrate inhibits human mast cell activation via epigenetic regulation of FcεRI‐mediated signaling

Short‐chain fatty acids (SCFAs) are fermented dietary components that regulate immune responses, promote colonic health, and suppress mast cell–mediated diseases. However, the effects of SCFAs on human mast cell function, including the underlying mechanisms, remain unclear. Here, we investigated the effects of the SCFAs (acetate, propionate, and butyrate) on mast cell–mediated pathology and human mast cell activation, including the molecular mechanisms involved.