Miracle-dz/UniFAR-FTUs huggingface dataset:
SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs.
Tumor-Treating Fields Therapy for Pediatric Brain Tumors

Tumor-treating fields (TTFields) are alternating electric fields applied continuously to the brain by attaching two-pair arrays on the scalp. Although TTFields therapy has demonstrated efficacy against supratentorial glioblastoma (GBM) in adults, its safety and efficacy in children have not been confirmed. Despite differences in the genetic etiology of the adult and pediatric forms of GBM, both have certain clinical behaviors in common, allowing us to test TTFields therapy in pediatric GBM. Recently, several, pediatric case-series using TTFields therapy have been published, and a few, prospective, pediatric studies are ongoing. Because GBMs are extremely rare in pediatric patients, where they comprise a wide variety of genetic subtypes, these pediatric studies are feasibility studies targeting various types of malignant brain tumor. Although they are important for confirming the safety and feasibility of TTFields therapy in the pediatric population, confirming its efficacy against each type of pediatric brain tumor, including the GBM, is difficult. Our clinical research team, therefore, planned an investigator-initiated clinical trial targeting pediatric supratentorial GBMs (as in adults) with the aim of expanding regulatory approval of TTFields therapy for pediatric GBM treatment based on safety and exploratory efficacy data in combination with the accumulated evidence on adult GBMs.
Chloroplast Localized FIBRILLIN11 Is Involved in the Osmotic Stress Response during Arabidopsis Seed Germination

Simple Summary The FIBRILLIN11 (FBN11) of Arabidopsis has a lipid-binding FBN domain and a kinase domain. FBN11 is present in chloroplasts and is involved in salt and osmotic stress responses during seed germination. In mannitol, the seed germination rate of the fbn11 mutants significantly reduced compared to that of the wild type. The ABA-dependent and -independent stress response regulating genes were differentially expressed in fbn11 mutants and wild-type when grown in mannitol supplemented medium. These results suggest that chloroplast localized FBN11 is involved in mediating osmotic stress tolerance through the signaling pathway that regulates the stress response in the nucleus. Abstract Plants live in ever-changing environments, facing adverse environmental conditions including pathogen infection, herbivore attack, drought, high temperature, low temperature, nutrient deficiency, toxic metal soil contamination, high salt, and osmotic imbalance that inhibit overall plant growth and development. Plants have evolved mechanisms to cope with these stresses. In this study, we found that the FIBRILLIN11 (FBN11) gene in Arabidopsis, which has a lipid-binding FBN domain and a kinase domain, is involved in the plant’s response to abiotic stressors, including salt and osmotic stresses. FBN11 protein localizes to the chloroplast. FBN11 gene expression significantly changed when plants were exposed to the abiotic stress response mediators such as abscisic acid (ABA), sodium chloride (NaCl), and mannitol. The seed germination rates of fbn11 homozygous mutants in different concentrations of mannitol and NaCl were significantly reduced compared to wild type. ABA-dependent and -independent stress response regulatory genes were differentially expressed in the fbn11 mutant compared with wild type when grown in mannitol medium. These results suggest a clear role for chloroplast-localized FBN11 in mediating osmotic stress tolerance via the stress response regulatory signaling pathway in the nucleus.
The Occurrence of Mycobacterium avium Subspecies paratuberculosis Positive Milk Antibody ELISA Results in Dairy Cattle under Varying Time Periods after Skin Testing for Bovine Tuberculosis

Simple Summary Milk from dairy cows is screened for antibodies to the bacterium causing Johne’s disease, which causes diarrhoea. The bacterium causing bovine tuberculosis has similarities in its structure with the bacterium causing Johne’s disease. Bovine tuberculosis is diagnosed by injecting avian and bovine tuberculin in the skin of the neck and comparing the reactions three days later. Potentially, tuberculosis testing may interfere with Johne’s disease testing. This study aimed to clarify the relationship between the time interval between tuberculosis and Johne’s disease testing and the number of Johne’s disease-positive cows. Data were collected from 51 herds, totalling 46,738 cow observations. Analysis showed that Johne’s disease testing in each 14 day interval increased the probability of detecting Johne’s disease-positive cows compared to Johne’s disease testing over 85 days after tuberculosis testing. The probability was 2.5-fold higher in the first 14 day interval after tuberculosis testing, increasing each two-week period to 4.0-fold higher at 57–70 days before dropping again. A previous history of tuberculosis within the herd increased the probability by 1.2 fold. This was less important compared to the timing of Johne’s disease testing after tuberculosis testing. Abstract Enzyme-linked immunosorbent assays (ELISA) are used to screen cows for Mycobacterium avium subspecies paratuberculosis (MAP) infections, informing Johne’s disease (JD) management practices in dairy herds. The causative agent of bovine tuberculosis (bTB), Mycobacterium bovis, and MAP share multiple antigens. Moreover, Mycobacterium avium subspecies avium is used in the single intradermal cervical comparative tests (SICCT) that are routinely used in early detection of cows infected with bTB. Although these are different types of immune responses, potentially the SICCT may interfere with the levels of MAP antibodies. This study aimed to clarify the relationship between the SICCT-MAP milk ELISA testing interval and apparent prevalence of JD risk statuses. Data from 51 herds were used, totalling 46,738 cow observations. The Poisson models showed that MAP milk ELISA testing at 14 day intervals post-SICCT statistically significantly increased the odds of detecting JD-positive cows compared to JD testing 85+ days post-SICCT. The odds ratio (OR) started at 2.5 in the first 14 day interval post-SICCT, increasing each two-week period to an OR of 4.0 at 57–70 days, to subsequently drop. Additionally, a herd history of bTB increased the odds of detecting JD-positive cows (OR = 1.2); this was relatively limited compared to the magnitude of the post-SICCT effect.
Pan and Core Genome Analysis of 183 Mycobacterium tuberculosis Strains Revealed a High Inter-Species Diversity among the Human Adapted Strains

Tuberculosis (TB) is an airborne communicable disease with high morbidity and mortality rates, especially in developing countries. The causal agents of TB belong to the complex Mycobacterium tuberculosis (MTBc), which is composed of different human and animal TB associated species. Some animal associated species have zoonotic potential and add to the burden of TB management. The BCG (“Bacillus Calmette-Guérin”) vaccine is widely used for the prevention against TB, but its use is limited in immunocompromised patients and animals due to the adverse effects and disseminated life-threatening complications. In this study, we aimed to carry out a comparative genome analysis between the human adapted species including BCG vaccine strains to identify and pinpoint the conserved genes related to the virulence across all the species, which could add a new value for vaccine development. For this purpose, the sequences of 183 Mycobacterium tuberculosis (MTB) strains were retrieved from the freely available WGS dataset at NCBI. The species included: 168 sensu stricto MTB species with other human MTB complex associated strains: M. tuberculosis var. africanum (3), M. tuberculosis var. bovis (2 draft genomes) and 10 BCG species, which enabled the analysis of core genome which contains the conserved genes and some virulence factor determinants. Further, a phylogenetic tree was constructed including the genomes of human (183); animals MTB adapted strains (6) and the environmental Mycobacterium strain “M. canettii”. Our results showed that the core genome consists of 1166 conserved genes among these species, which represents a small portion of the pangenome (7036 genes). The remaining genes in the pangenome (5870) are accessory genes, adding a high inter-species diversity. Further, the core genome includes several virulence-associated genes and this could explain the rare infectiousness potential of some attenuated vaccine strains in some patients. This study reveals that low number of conserved genes in human adapted MTBc species and high inter-species diversity of the pan-genome could be considered for vaccine candidate development.
Evolution of Small Strain Soil Stiffness during Freeze-Thaw Cycle: Transition from Capillarity to Cementation Examined Using Magnetic and Piezo Crystal Sensors

Freeze-thaw cycles caused by seasonal temperature fluctuations significantly affect the geotechnical engineering properties. This study investigated the crucial role of water distribution patterns in the characterization of elastic wave properties for the fine F-110 sand during a freeze-thaw cycle. Sand specimens with four different water distribution patterns were prepared, namely homogeneously-mixed, evaporation-driven, vertically-, and horizontally-layered specimens. The P- and S-wave signatures of the specimens were monitored using piezo crystal sensors. Results indicated the criticality of water distribution patterns in the determination of small-strain soil properties even though the specimens had identical global water saturation. The nuclear magnetic resonance-based water volume depth profiles indicated that the evaporation-driven specimens had more heterogeneous pore-invasive ice-bonding layers at a high water saturation region; by contrast, the drying process facilitated uniform meniscuses around the particle contacts near the air percolation threshold. Elastic wave measurements for laboratory-prepared specimens might over/underestimate the small-strain soil stiffness of sediments in nature, wherein the drying processes prevailed to control the water saturation. This study highlighted a clear transition from capillary-controlled to cementation-controlled elastic wave properties during temperature oscillations.
Did you know? Using entropy and fractal geometry to quantify fluctuations in physiological outputs

Physiological outputs are characterised by constant fluctuations, even under resting conditions.1 Quantifying this variability represents an important methodological challenge. Variability in physiological outputs has traditionally been quantified according to its magnitude, using measures such as the standard deviation (SD). 2 Such magnitude-based measures have provided substantial insight into the analysis of physiological outputs, with changes in the magnitude of variability associated with adverse events in a number of systems.2 However, physiological outputs are characterised by irregular self-similar fluctuations ("complexity") over multiple orders of temporal magnitude (i.e. seconds, minutes, hours), a property magnitude-based measures cannot quantify.1 Complexity measures derive from non-linear dynamics, and include metrics related to information theory (e.g. entropy statistics), which measure the apparent regularity or randomness of an output, and metrics drawn from fractal geometry, which identify long-range correlations present in an output.3 It has been suggested that neither magnitude- nor complexity-based metrics should be used as the sole indicator of system characteristics; rather, they should be used in conjunction, in order to provide a more complete understanding of variability.2,4.
Effect of Neighborhood and Individual-Level Socioeconomic Factors on Colorectal Cancer Screening Adherence

Despite the effectiveness of screenings in reducing colorectal cancer (CRC) mortality, ~25% of US adults do not adhere to screening guidelines. Prior studies associate socioeconomic status (SES) with low screening adherence and suggest that neighborhood deprivation can influence CRC outcomes. We comprehensively investigated the effect of neighborhood SES circumstances (nSES), individual SES, and race/ethnicity on adherence to CRC screening in a multiethnic cross-sectional study. Participant surveys assessing 32 individual-level socioeconomic and healthcare access measures were administered from 2017 to 2018. Participant data were joined with nine nSES measures from the US Census at the census tract level. Univariate, LASSO, and multivariable mixed-effect logistic regression models were used for variable reduction and evaluation of associations. The total study population included 526 participants aged 50–85; 29% of participants were non-adherent. In the final multivariable model, age (p = 0.02) and Non-Hispanic Black race (p = 0.02) were associated with higher odds of adherence. Factors associated with lower adherence were home rental (vs. ownership) (p = 0.003), perception of low healthcare quality (p = 0.006), no routine checkup within two years (p = 0.002), perceived discrimination (p = 0.02), and nSES deprivation (p = 0.02). After comprehensive variable methods were applied, socioeconomic indicators at the neighborhood and individual level were found to contribute to low CRC screening adherence.
On the Solubility and Stability of Polyvinylidene Fluoride

This literature review covers the solubility and processability of fluoropolymer polyvinylidine fluoride (PVDF). Fluoropolymers consist of a carbon backbone chain with multiple connected C–F bonds; they are typically nonreactive and nontoxic and have good thermal stability. Their processing, recycling and reuse are rapidly becoming more important to the circular economy as fluoropolymers find widespread application in diverse sectors including construction, automotive engineering and electronics. The partially fluorinated polymer PVDF is in strong demand in all of these areas; in addition to its desirable inertness, which is typical of most fluoropolymers, it also has a high dielectric constant and can be ferroelectric in some of its crystal phases. However, processing and reusing PVDF is a challenging task, and this is partly due to its limited solubility. This review begins with a discussion on the useful properties and applications of PVDF, followed by a discussion on the known solvents and diluents of PVDF and how it can be formed into membranes. Finally, we explore the limitations of PVDF’s chemical and thermal stability, with a discussion on conditions under which it can degrade. Our aim is to provide a condensed overview that will be of use to both chemists and engineers who need to work with PVDF.
Restoration of gallery forest patches improves recruitment of motacú palms (Attalea princeps) while diversifying and increasing wildlife populations

Globally, forest-savanna mosaic landscapes are of significant conservation importance but have been widely impacted by human land-use. We studied how restoration, through cessation of long-term cattle grazing impacts (i) forest regeneration; (ii) forest understory structure and composition; and (iii) populations and diversity of large mammals and nocturnal birds, within naturally patchy gallery forests in the Beni Savannas of Bolivia. Comparing grazed and restored sites, we assessed the abundance and composition of tree functional types at different life stages (seedlings, saplings and adults), with focus on the region’s key palm species Attalea princeps (motacú). Additionally, we surveyed habitat structure and composition in the shrub and ground-layer, and monitored occurrence and encounter rates of large mammals and nocturnal birds along dusk and evening transects. We found evidence of lower recruitment of motacú palms on the grazed site and lower potential for natural motacú regeneration. Principal Components Analysis revealed forests on grazed sites had simpler, more open shrub-layers and altered ground-layer structure and composition including increased bare ground. Mammal species richness was greater on the restored site, and there were more declining, globally threatened and site-unique species. Species richness was similar for nocturnal birds within forests on both the grazed and restored site, but nearly all species tended to be encountered more frequently on the restored site. Our results suggest cattle negatively impact forest regeneration and alter the structure and composition of the shrub and ground layer with potential consequences for the diversity and abundance of wildlife. Our study represents one of only a handful completed in the Beni region of Bolivia to date. The Beni is currently under pressure from widespread, largely unregulated cattle ranching. Our results thus provide vital evidence to support development of restoration and conservation policy, and its integration with rangeland management in this threatened and critically understudied region.
Dampened Muscle mTORC1 Response Following Ingestion of High-Quality Plant-Based Protein and Insect Protein Compared to Whey

Increased amino acid availability acutely stimulates protein synthesis partially via activation of mechanistic target of rapamycin complex 1 (mTORC1). Plant-and insect-based protein sources matched for total protein and/or leucine to animal proteins induce a lower postprandial rise in amino acids, but their effects on mTOR activation in muscle are unknown. C57BL/6J mice were gavaged with different protein solutions: whey, a pea–rice protein mix matched for total protein or leucine content to whey, worm protein matched for total protein, or saline. Blood was drawn 30, 60, 105 and 150 min after gavage and muscle samples were harvested 60 min and 150 min after gavage to measure key components of the mTORC1 pathway. Ingestion of plant-based proteins induced a lower rise in blood leucine compared to whey, which coincided with a dampened mTORC1 activation, both acutely and 150 min after administration. Matching total leucine content to whey did not rescue the reduced rise in plasma amino acids, nor the lower increase in mTORC1 compared to whey. Insect protein elicits a similar activation of downstream mTORC1 kinases as plant-based proteins, despite lower postprandial aminoacidemia. The mTORC1 response following ingestion of high-quality plant-based and insect proteins is dampened compared to whey in mouse skeletal muscle.
Magnesium for Pain Treatment in 2021? State of the Art

Background: Magnesium (Mg) is commonly used in clinical practice for acute and chronic pain and has been reported to reduce pain intensity and analgesics consumption in a number of studies. Results are, however, contested. Objectives: This review aims to investigate randomised clinical trials (RCTs) on the effectiveness of Mg treatment on pain and analgesics consumption in situations including post-operative pain, migraine, renal pain, chronic pain, neuropathic pain and fibromyalgia. Results: The literature search identified 81 RCTs (n = 5447 patients) on Mg treatment in pain (50 RCTs in post-operative pain, 18 RCTs in migraine, 5 RCTs in renal pain, 6 RCTs in chronic/neuropathic pain, 2 RCTs in fibromyalgia). Conclusion: The level of evidence for the efficacy of Mg in reducing pain and analgesics consumption is globally modest and studies are not very numerous in chronic pain. A number of gaps have been identified in the literature that need to be addressed especially in methodology, rheumatic disease, and cancer. Additional clinical trials are needed to achieve a sufficient level of evidence and to better optimize the use of Mg for pain and pain comorbidities in order to improve the quality of life of patients who are in pain.
Short-Term Effects of Particulate Matter and Its Constituents on Emergency Room Visits for Chronic Obstructive Pulmonary Disease: A Time-Stratified Case-Crossover Study in an Urban Area

Background: PM2.5 exposure is associated with pulmonary and airway inflammation, and the health impact might vary by PM2.5 constitutes. This study evaluated the effects of increased short-term exposure to PM2.5 constituents on chronic obstructive pulmonary disease (COPD)-related emergency department (ED) visits and determined the susceptible groups. Methods: This retrospective observational study performed in a medical center from 2007 to 2010, and enrolled non-trauma patients aged >20 years who visited the emergency department (ED) and were diagnosed as COPD. Concentrations of PM2.5, PM10, and the four PM2.5 components, including organic carbon (OC), elemental carbon (EC), nitrate (NO3−), and sulfate (SO42−), were collected by three PM supersites in Kaohsiung City. We used an alternative design of the Poisson time series regression models called a time-stratified and case-crossover design to analyze the data. Results: Per interquartile range (IQR) increment in PM2.5 level on lag 2 were associated with increments of 6.6% (95% confidence interval (CI), 0.5–13.0%) in risk of COPD exacerbation. An IQR increase in elemental carbon (EC) was significantly associated with an increment of 3.0% (95% CI, 0.1–5.9%) in risk of COPD exacerbation on lag 0. Meanwhile, an IQR increase in sulfate, nitrate, and OC levels was not significantly associated with COPD. Patients were more sensitive to the harmful effects of EC on COPD during the warm season (interaction p = 0.019). The risk of COPD exacerbation after exposure to PM2.5 was higher in individuals who are currently smoking, with malignancy, or during cold season, but the differences did not achieve statistical significance. Conclusion: PM2.5 and EC may play an important role in COPD events in Kaohsiung, Taiwan. Patients were more susceptible to the adverse effects of EC on COPD on warm days.
Studying Collaboration Dynamics in Physical Learning Spaces: Considering the Temporal Perspective through Epistemic Network Analysis

The role of the learning space is especially relevant in the application of active pedagogies, for example those involving collaborative activities. However, there is limited evidence informing learning design on the potential effects of collaborative learning spaces. In particular, there is a lack of studies generating evidence derived from temporal analyses of the influence of learning spaces on the collaborative learning process. The temporal analysis perspective has been shown to be essential in the analysis of collaboration processes, as it reveals the relationships between students’ actions. The aim of this study is to explore the potential of a temporal perspective to broaden understanding of the effects of table shape on collaboration when different group sizes and genders are considered. On-task actions such as explanation, discussion, non-verbal interaction, and interaction with physical artefacts were observed while students were engaged in engineering design tasks. Results suggest that table shape influences student behaviour when taking into account different group sizes and different genders.