Miracle-dz/UniFAR-FTUs huggingface dataset:
An automated laser fluorination technique for high-precision analysis of three oxygen isotopes in silicates.

RATIONALE The three oxygen isotopes in terrestrial/extraterrestrial silicates can provide geochemical and cosmochemical information about their origin and secondary processes that result from isotopic exchange. A laser fluorination technique has been widely used to extract oxygen from silicates for δ17 O and δ18 O measurements by isotope ratio mass spectrometry. Continued improvement of the techniques is still important for high-precision measurement of oxygen-isotopic ratios. METHODS We adopted an automated lasing technique to obtain reproducible fluorination of silicates using a CO2 laser-BrF5 fluorination system connected online to an isotope ratio mass spectrometer. The automated lasing technique enables us to perform high-precision analysis of the three oxygen isotopes of typical reference materials (e.g., UWG2 garnet, NBS28 quartz and San Carlos olivine) and in-house references (mid-ocean ridge basalt glass and obsidian). The technique uses a built-in application of laser control with which the laser power can be varied in a programmed manner with a defocused beam which is in a fixed position. RESULTS The oxygen isotope ratios of some international reference materials analyzed by the manual lasing technique were found to be isotopically lighter with wider variations in δ18 O values, whereas those measured by the automated lasing technique gave better reproducibility (less than 0.2‰, 2SD). The Δ17 O values, an excess of the δ17 O value relative to the fractionation line, also showed high reproducibility (±0.02‰, 2SD). CONCLUSIONS The system described herein provides high-precision δ17 O and δ18 O measurements of silicate materials. The use of the automated lasing technique followed by careful and controlled purification procedures is preferred to achieve satisfactory isotopic ratio results.
Do Obese Children Achieve Maximal Heart Rate during Treadmill Running?

Objective: Maximal heart rate (HR) is commonly defined as the highest HR obtained during a progressive exercise test to exhaustion. Maximal HR is considered one of the criteria to assess maximum exertion in exercise tests, and is broadly used when prescribing exercise intensity. The aim of the present study was to compare peak HR measurements during maximal treadmill running and active play in obese children and adolescents. Design: Comparison of peak heart rate during active play vs. maximal treadmill running in 39 (7–17 years old, 18 males) obese children and adolescents. Methods: Heart rate was recorded during intensive active play sessions, as well as during a progressive running test on a treadmill until exhaustion. HR, respiratory exchange ratio (RER), and oxygen uptake were continuously measured during the test. The criteria for having reached maximal effort was a subjective assessment by the technician that the participants had reached his or her maximal effort, and a RER above 1.00 or reporting perceived exertion (RPE) above 17 using the Borg-RPE6–20-Scale. Results: Thirty-four children had a RER ≥1.00, and 37 reported a RPE ≥ 17. Thirty-two children fulfilled both criteria. During active play, peak HR was significantly (p < 0.0001) increased (4%) (mean and 95% confidence intervals; 204 (201, 207) beats/min), compared to during maximal treadmill running (196 (194, 199) beats/min), respectively. Conclusion: The results of the present study indicate that peak heart rate measurements during progressive running to exhaustion in obese children and adolescents cannot necessarily be determined as maximal heart rate.
Suppressing Non-Specific Binding of Proteins onto Electrode Surfaces in the Development of Electrochemical Immunosensors

Electrochemical immunosensors, EIs, are systems that combine the analytical power of electrochemical techniques and the high selectivity and specificity of antibodies in a solid phase immunoassay for target analyte. In EIs, the most used transducer platforms are screen printed electrodes, SPEs. Some characteristics of EIs are their low cost, portability for point of care testing (POCT) applications, high specificity and selectivity to the target molecule, low sample and reagent consumption and easy to use. Despite all these attractive features, still exist one to cover and it is the enhancement of the sensitivity of the EIs. In this review, an approach to understand how this can be achieved is presented. First, it is necessary to comprise thoroughly all the complex phenomena that happen simultaneously in the protein-surface interface when adsorption of the protein occurs. Physicochemical properties of the protein and the surface as well as the adsorption phenomena influence the sensitivity of the EIs. From this point, some strategies to suppress non-specific binding, NSB, of proteins onto electrode surfaces in order to improve the sensitivity of EIs are mentioned.
Efficacy and tolerability of EH301 for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled human pilot study

Abstract Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by progressive loss of spinal and cortical motor neurons, leading to muscular atrophy, respiratory failure, and ultimately death. There is no known cure, and the clinical benefit of the two drugs approved to treat ALS remains unclear. Novel disease-modifying therapeutics that are able to modulate the disease course are desperately needed. Our objective was to evaluate the efficacy and tolerability of Elysium Health’s candidate drug EH301 in people with ALS (PALS). Methods: This was a single-center, prospective, double-blind, randomized, placebo-controlled pilot study. Thirty-two PALS were recruited thanks to the collaboration of the Spanish Foundation for ALS Research (FUNDELA). Study participants were randomized to receive either EH301 or placebo and underwent evaluation for 4 months. Differences between EH301 and placebo-treated participants were evaluated based on standard clinical endpoints, including the revised ALS functional rating scale (ALSFRS-R), forced vital capacity (FVC), and the Medical Research Council (MRC) grading scale. Results: Compared to placebo, participants treated with EH301 demonstrated significant improvements in the ALSFRS-R score, pulmonary function, muscular strength, and in skeletal muscle/fat weight ratio. EH301 was shown to significantly slow the progression of ALS relative to placebo, and even showed improvements in several key outcome measures compared with baseline. Conclusions: This study provides evidence in support of the disease-modifying effects of EH301 for the treatment of ALS. Trial registration: ClinicalTrials.gov identifier: NCT03489200.
Enhanced intestinal absorption of asenapine maleate by fabricating solid lipid nanoparticles using TPGS: elucidation of transport mechanism, permeability across Caco-2 cell line and in vivo pharmacokinetic studies

Abstract The aim of the present investigation was to fabricate and evaluate solid lipid nanoparticles (SLNs) of asenapine maleate (AM) to improve its oral bioavailability (BA). AM-SLNs were prepared by high speed homogenization followed by ultrasonication technique. The resultant SLNs exhibited particle size, zeta potential and entrapment efficiency of 114.3 ± 3.5 nm, −12.9 ± 3.8 mV, and 84.10% ± 2.90% respectively. In vitro release study of AM-SLNs showed 9.23% ± 2.72% and 92.09% ± 3.40% release of AM in pH 1.2 medium and phosphate buffer pH 6.8, respectively, indicating higher potential of lymphatic uptake. Cell viability study using Caco-2 cell line indicated non-toxicity of the carriers and drug. The uptake of AM-SLNs across Caco-2 cell line was time and energy dependent exhibiting clathrin-claveole mediated endocytosis transport. Cellular uptake of Coumarin loaded SLNs was effectively increased as compared to the dye solution. The pharmacokinetic results in rats showed 50.19-fold improvement in BA of AM after fabrication of SLNs. Collectively, all these findings demonstrated effectiveness of SLNs to improve therapeutic efficacy of AM in the treatment of schizophrenia.
New pieces to the lanthanide puzzle

Recently, rare‐earth elements lanthanides (Ln3+) have emerged as enzyme cofactors of methanol dehydrogenases of the XoxF type. It is now understood that XoxF enzymes can functionally replace the alternative, calcium‐dependent, MxaFI‐type methanol dehydrogenases, when Ln3+ are available. These rare‐earth metals are not only essential for XoxF activity, but they also regulate gene expression, in a reverse fashion, activating the expression of XoxF and repressing the expression of MxaFI. This type of regulation has created multiple conundrums, including the details of the solubility, transport, sensing and selection mechanisms for Ln3+ by the bacterial cells, as well as the questions relevant to the evolution of the alternative enzymes and their potentially different redox properties. Overall, the newly discovered biological activity of Ln3+ presents a big puzzle. Ochsner et al. add several pieces to this puzzle, utilizing a model phyllosphere colonizer Methylobacterium extorquens PA1. They determine that Ln3+ sensing by this organism can take place via both XoxF‐dependent and XoxF‐independent mechanisms. They also identify genes for a TonB‐dependent transporter and an ABC‐type transporter and demonstrate that both are essential for Ln3+‐dependent methanol metabolism. The puzzle still requires multiple additional pieces for completion, but great strides have been made toward the goal of solving it.
Effects of Socioeconomic Status on Physical and Psychological Health: Lifestyle as a Mediator

Health is correlated to people’s socioeconomic status (SES) and lifestyle. This study examined the impact of SES on respondents’ physical and psychological health. Moreover, we explored the potential mediating effect of lifestyle on the relationship between SES and health. The participants were 986 respondents from the 2015 Chinese General Social Survey (CGSS). Structural equation modeling (SEM) was used to test the hypothesized relationship between the variables. The results indicated that SES had a significant impact on people’s physical health, but the impact of SES on psychological health was not significant. Lifestyle had significant positive effects on both physical and psychological health. In addition, lifestyle mediated the relationship between SES and health. This research is helpful in gaining a better understanding of the relationship and mediating mechanism between SES, lifestyle, and health. It is recommended that research with longitudinal design and comprehensive indicators be undertaken in the future.
The Incorporation of Host Proteins into the External HIV-1 Envelope

The incorporation of biologically active host proteins into HIV-1 is a well-established phenomenon, particularly due to the budding mechanism of viral egress in which viruses acquire their external lipid membrane directly from the host cell. While this mechanism might seemingly imply that host protein incorporation is a passive uptake of all cellular antigens associated with the plasma membrane at the site of budding, this is not the case. Herein, we review the evidence indicating that host protein incorporation can be a selective and conserved process. We discuss how HIV-1 virions displaying host proteins on their surface can exhibit a myriad of altered phenotypes, with notable impacts on infectivity, homing, neutralization, and pathogenesis. This review describes the canonical and emerging methods to detect host protein incorporation, highlights the well-established host proteins that have been identified on HIV-1 virions, and reflects on the role of these incorporated proteins in viral pathogenesis and therapeutic targeting. Despite many advances in HIV treatment and prevention, there remains a global effort to develop increasingly effective anti-HIV therapies. Given the broad range of biologically active host proteins acquired on the surface of HIV-1, additional studies on the mechanisms and impacts of these incorporated host proteins may inform the development of novel treatments and vaccine designs.
Tyrosine kinase c-Abl couples RNA polymerase II transcription to DNA double-strand breaks

Abstract DNA is constantly exposed to endogenous and exogenous damage. Various types of DNA repair counteract highly toxic DNA double-strand breaks (DSBs) to maintain genome stability. Recent findings suggest that the human DNA damage response (DDR) utilizes small RNA species, which are produced as long non-coding (nc)RNA precursors and promote recognition of DSBs. However, regulatory principles that control production of such transcripts remain largely elusive. Here we show that the Abelson tyrosine kinase c-Abl/ABL1 causes formation of RNA polymerase II (RNAPII) foci, predominantly phosphorylated at carboxy-terminal domain (CTD) residue Tyr1, at DSBs. CTD Tyr1-phosphorylated RNAPII (CTD Y1P) synthetizes strand-specific, damage-responsive transcripts (DARTs), which trigger formation of double-stranded (ds)RNA intermediates via DNA–RNA hybrid intermediates to promote recruitment of p53-binding protein 1 (53BP1) and Mediator of DNA damage checkpoint 1 (MDC1) to endogenous DSBs. Interference with transcription, c-Abl activity, DNA–RNA hybrid formation or dsRNA processing impairs CTD Y1P foci formation, attenuates DART synthesis and delays recruitment of DDR factors and DSB signalling. Collectively, our data provide novel insight in RNA-dependent DDR by coupling DSB-induced c-Abl activity on RNAPII to generate DARTs for consequent DSB recognition.
Laser-based Techniques for Microcirculatory Assessment in Orthopedics and Trauma Surgery: Past, Present, and Future.

MINI: Overview of laser-based techniques for the noninvasive cutaneous microcirculatory perfusion assessment, their technological aspects, comparative advantages, current, and future applications in the field of orthopedic and trauma surgery.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 : Microcirculatory integrity and proper function are the cornerstones to tissue nourishment and viability. In the clinical environment extended immobility, injuries, and inflammatory reactions demand local microcirculatory adaption to provide adequate supply. Assessment of endothelial adjustment capability and microcirculatory perfusion status, as direct or surrogate markers of disease, are therefore of uttermost interest to the treating physician. Given the simple, noninvasive, nonradiating nature of laser-based techniques for bedside or intraoperative microcirculatory perfusion assessment, this article's objective is to present a comprehensive overview of available techniques, their technological aspects, and current application. Advantages of individual methods are pointed out and compared with each other. The areas of medical utilization relevant to orthopedics and trauma surgery are exemplified and their available evidence elaborated. A particular focus is put on laser speckle contrast imaging, with its current and future influence on medical practice.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
The Timing and Direction of Introgression Under the Multispecies Network Coalescent

Introgression is a pervasive biological process, and many statistical methods have been developed to infer its presence from genomic data. However, many of the consequences and genomic signatures of introgression remain unexplored from a methodological standpoint. Here, we develop a model for the timing and direction of introgression based on the multispecies network coalescent, and from it suggest new approaches for testing introgression hypotheses. We suggest two new statistics, D1 and D2, which can be used in conjunction with other information to test hypotheses relating to the timing and direction of introgression, respectively. D1 may find use in evaluating cases of homoploid hybrid speciation (HHS), while D2 provides a four-taxon test for polarizing introgression. Although analytical expectations for our statistics require a number of assumptions to be met, we show how simulations can be used to test hypotheses about introgression when these assumptions are violated. We apply the D1 statistic to genomic data from the wild yeast Saccharomyces paradoxus—a proposed example of HHS—demonstrating its use as a test of this model. These methods provide new and powerful ways to address questions relating to the timing and direction of introgression.
Trauma rehabilitation in a teaching hospital in Antananarivo, Madagascar: current provision and patients’ perspectives

Abstract Purpose: This study aims to describe the current provision of trauma rehabilitation in Antananarivo, Madagascar and explore the experiences and perspectives of users of this service in order to inform future research and service development. Material and methods: A qualitative study supplemented by a descriptive service review were applied in the central government hospital in Antananarivo. Registers in the rehabilitation department were analyzed for a 3 month period. Semi-structured interviews were conducted with a convenience sample of users of the rehabilitation service and were subject to thematic analysis. Results: One in six patients treated in the rehabilitation department has survived a traumatic injury, with limb injuries comprising the majority. Analysis of interviews with 10 adult patients, following traumatic injuries to the lower limbs (6), upper limbs (3) or polytrauma (1) generated seven broad themes: health seeking behavior, organization of services, clinical management, costs and financial impact, effect on function and role, psychological impact and societal attitudes. Conclusions: Financial constraints and impact on personal finances pervade the overall picture. The perspectives and experiences elucidated will inform future research into the development of context-specific models of care for people with trauma-related disabilities in Madagascar. Implications for rehabilitation Potentially treatable traumatic injury can have a profound effect on function and societal participation in Madagascar. Interventions to increase access to timely acute trauma care and rehabilitation are needed, and may include different models of financing and innovations to reduce materials costs and length of stay. A structured rehabilitation pathway must be integrated to the earliest stages of trauma care, including scrutinizing the use of prolonged immobilization. Consideration should be given to models of care which are financially and geographically accessible to the population.
Growing pigs developed different types of diabetes induced by streptozotocin depending on their transcription factor 7-like 2 gene polymorphisms

The different polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene promote variances in diabetes susceptibility in humans. We investigated whether these genotypes also promote differences in diabetic susceptibility in commercial pigs. Growing pigs (Landrace, both sex, 50–60 kg) with the C/C (n=4) and T/T (n=5) TCF7L2 genotypes were identified and intravenously injected with streptozotocin (STZ, 40 mg/kg) twice in weekly intervals, then a high-energy diet was offered. Oral glucose tolerance tests, blood analyses and the homeostasis model assessment-insulin resistance (HOMA-IR) index calculations were performed. The animals were sacrificed at the end of 12 weeks of treatment to reveal the pancreas histomorphometry. The results showed that all of the treated pigs grew normally despite exhibiting hyperglycemia at two weeks after the induction. The glycemic level of the fasting or postprandial pigs gradually returned to normal. The fasting insulin concentration was significantly decreased for the T/T carriers but not for the C/C carriers, and the resulting HOMA-IR index was significantly increased for the C/C genotype, indicating that the models of insulin dependence and resistance were respectively developed by T/T and C/C carriers. The histopathological results illustrated a significant reduction in the pancreas mass and insulin active sites, which suggested increased damage. The results obtained here could not be compared with previous studies because the TCF7L2 background has not been reported. Growing pigs may be an excellent model for diabetic in children if the animals are genetically pre-selected.
Importance of Mean Platelet Volume in Predicting Cardiac Mechanics Parameters and Carotid‐Intima Media Thickness in Children With End‐Stage Renal Disease and Comparison With Healthy Children

Cardiovascular disease (CVD) is the major cause of death in children with ESRD. Echocardiography and Doppler ultrasound are useful devices for diagnosing cardiovascular abnormalities in such patients. However, they are expensive, difficult to perform as a routine, and not available in many centers. Therefore, finding a more accessible and inexpensive method for CVD evaluation biomarkers is needed. The aim of this study was to evaluate the relationship between mean platelet volume (MPV) as a routine hematological parameter with cardiac mechanics characteristics in children with ESRD. Forty‐two children under dialysis and 60 age‐ and sex‐matched healthy subjects as control group were enrolled in the study. Carotid‐intima media thickness (CIMT) and echocardiographic parameters were measured in both groups. In addition, hematological and biochemical variables were evaluated in blood samples of participants. MPV was significantly higher in patients than in controls. CIMT, left ventricular mass index (LVMI), end diastolic diameter, strain rate, and global longitudinal strain were significantly different between the two groups. MPV was positively correlated with LVMI and inversely with ejection fraction. In receiver operating characteristic (ROC) curve analysis, the area under the ROC curve (AUC) values for MPV in predicting left ventricular hypertrophy (LVH) and abnormal CIMT were 0.65 (P = 0.07) and 0.53 (P = 0.74), respectively. MPV was correlated with some cardiac abnormalities in children with ESRD. However, it could not show appropriate predictive values in diagnosing LVH and subclinical atherosclerosis. Further studies with prospective design could shed more light in this topic.