Miracle-dz/UniFAR-FTUs huggingface dataset:
Validity of Three-Dimensional Tortuous Pore Structure and Fouling of Hemoconcentration Capillary Membrane Using the Tortuous Pore Diffusion Model and Scanning Probe Microscopy

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, which does not allow excessive protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, bovine blood was perfused inside the lumens of these membranes. Pure water permeability before and after bovine blood perfusion was measured using dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, many pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference, despite protein fouling on the pore inlets (membrane surface). In addition, low values of albumin sieving coefficient are attributable to protein fouling that occurs on the membrane surface. Therefore, it is essential to design the membrane structure that provides the appropriate control of fouling. The characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.
An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation

The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.
Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases

We evaluated the potential of nine vitamin B3 scaffold-based derivatives as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors, as a starting point for the development of novel drugs for treating disorders with cholinergic neurotransmission-linked pathology. As the results indicate, all compounds reversibly inhibited both enzymes in the micromolar range pointing to the preference of AChE over BChE for binding the tested derivatives. Molecular docking studies revealed the importance of interactions with AChE active site residues Tyr337 and Tyr124, which dictated most of the observed differences. The most potent inhibitor of both enzymes with Ki of 4 μM for AChE and 8 μM for BChE was the nicotinamide derivative 1-(4′-phenylphenacyl)-3-carbamoylpyridinium bromide. Such a result places it within the range of several currently studied novel cholinesterase inhibitors. Cytotoxicity profiling did not classify this compound as highly toxic, but the induced effects on cells should not be neglected in any future detailed studies and when considering this scaffold for drug development.
Metal-Free Multi-Heteroatom-Doped Carbon Bifunctional Electrocatalysts Derived from a Covalent Triazine Polymer.

The construction of multi-heteroatom-doped metal-free carbon with a reversibly oxygen-involving electrocatalytic performance is highly desirable for rechargeable metal-air batteries. However, the conventional approach for doping heteroatoms into the carbon matrix remains a huge challenge owing to multistep postdoping procedures. Here, a self-templated carbonization strategy to prepare a nitrogen, phosphorus, and fluorine tri-doped carbon nanosphere (NPF-CNS) is developed, during which a heteroatom-enriched covalent triazine polymer serves as a "self-doping" precursor with C, N, P, and F elements simultaneously, avoiding the tedious and inefficient postdoping procedures. Introducing F enhances the electronic structure and surface wettability of the as-obtained catalyst, beneficial to improve the electrocatalytic performance. The optimized NPF-CNS catalyst exhibits a superb electrocatalytic oxygen reduction reaction (ORR) activity, long-term durability in pH-universal conditions as well as outstanding oxygen evolution reaction (OER) performance in an alkaline electrolyte. These superior ORR/OER bifunctional electrocatalytic activities are attributed to the predesigned heteroatom catalytic active sites and high specific surface areas of NPF-CNS. As a demonstration, a zinc-air battery using the NPF-CNS cathode displays a high peak power density of 144 mW cm-2 and great stability during 385 discharging/charging cycles, surpassing that of the commercial Pt/C catalyst.
Toward Practice-Based Continuing Education Protocols: Using Testing to Help Physicians Update Their Knowledge.

INTRODUCTION Using assessment to facilitate learning is a well-established priority in education but has been associated with variable effectiveness for continuing professional development. What factors modulate the impact of testing in practitioners are unclear. We aimed to improve capacity to support maintenance of competence by exploring variables that influence the value of web-based pretesting. METHODS Family physicians belonging to a practice-based learning program studied two educational modules independently or in small groups. Before learning sessions they completed a needs assessment and were assigned to either sit a pretest intervention or read a relevant review article. After the learning session, they completed an outcome test, indicated plans to change practice, and subsequently documented changes made. RESULTS One hundred twelve physicians completed the study, 92 in small groups. The average lag between tests was 6.3 weeks. Relative to those given a review article, physicians given a pretest intervention: (1) reported spending less time completing the assigned task (16.7 versus 25.7 minutes); (2) performed better on outcome test questions that were repeated from the pretest (65.9% versus 58.7%); and (3) when the learning module was completed independently, reported making a greater proportion of practice changes to which they committed (80.0% versus 45.0%). Knowledge gain was unrelated to physicians' stated needs. DISCUSSION Low-stakes formative quizzes, delivered with feedback, can influence the amount of material practicing physicians remember from an educational intervention independent of perceptions regarding the need to engage in continuing professional development on the particular topic.
The Role of Endocrine Stress Systems and Sex Hormones in the Enhancing Effects of Stress on Mental Rotation Capabilities

The possible effects of stress and neurobiological stress mechanisms on visuospatial abilities remain largely unknown. In the current study, we examined the combined effect of sex hormones and both the hypothalamic–pituitary–adrenal axis (HPA-A) and the sympathetic nervous system (SNS) on stress-induced changes in visuospatial performance. A total of 107 participants completed a mental rotation task and were subsequently exposed to either to the Trier social stress test (TSST) or to a control condition before completing the mental rotation task again. HPA-A and SNS reactivity of the participants were evaluated by measuring salivary alpha amylase (sAA; an SNS activation marker) and cortisol in four saliva samples. Pre-stress levels of sex hormones (progesterone, estradiol, and testosterone) were also measured. The TSST enhanced mental rotation performance, and this enhancement was negatively correlated with baseline estradiol levels and positively correlated with the level of cortisol reactivity among men. In addition, controlling for baseline levels of testosterone, estradiol, and progesterone diminished this effect of stress. These results imply that the stress-induced facilitation of mental rotation performance is modulated by baseline sex hormones and provide preliminary support to the notion that a complex interaction between sex hormones and neuroendocrine stress mechanisms mediates the influence of stress on visuospatial performance.
The Self-Care of Heart Failure Index version 7.2: Further psychometric testing.

Clinicians and researchers need valid and reliable instruments to evaluate heart failure (HF) self-care. The Self-Care of Heart Failure Index (SCHFI) is a theoretically driven instrument developed for this purpose. The SCHFI measures self-care with three scales: self-care maintenance, measuring behaviors to maintain HF stability; symptom perception, measuring monitoring behaviors; and self-care management, assessing the response to symptoms. After the theory underpinning the SCHFI was updated, the instrument was updated to version 7.2 but it was only tested in the United States. In this study we tested the psychometric characteristics (structural and construct validity, internal consistency, and test-retest reliability) of the SCHFI v.7.2 in an Italian population of HF patients. We used a cross-sectional design to study 280 HF patients with additional data collected after 2 weeks for test-retest reliability. Adults with HF (mean age 75.6 (±10.8); 70.8% in New York Heart Association [NYHA] classes II and III) were enrolled from six centers across Italy. Confirmatory factor analysis showed supportive structural validity in the three SCHFI v.7.2 scales (CFI from 0.94 to 0.95; RMSEA from 0.05 to 0.07). Internal consistency reliability estimated with Cronbach's α and composite reliability ranged between . 73 and . 88; test-retest reliability ranged between 0.73 and 0.92. Construct validity was supported with significant correlations between the SCHFI v.7.2 scale scores and quality of life, brain natriuretic peptide levels and NYHA class. This study further supports the psychometric characteristics of the SCHFI v.7.2, illustrating that it can be used in clinical practice and research also in an Italian population.
Impact of Switching from Intermittently Scanned to Real-Time Continuous Glucose Monitoring Systems in a Type 1 Diabetes Patient French Cohort: An Observational Study of Clinical Practices

Aim: Assess the impact of switching from intermittently scanned (FreeStyle Libre [FSL]) to real-time (Dexcom G4 platinum [DG4]) continuous glucose monitoring systems on glycemia control in type 1 diabetes (T1D) patients with high risk of hypoglycemia and/or elevated glycated hemoglobin (HbA1c). Methods: We conducted an observational study in 18 T1D adults with poor glycemic control on FSL. Ambulatory glucose profile data were collected during the last 3 months of FSL use before inclusion (M0 period), during the first 3 months (M3 period) and the last 3 months (M6 period) of DG4 use. Data were then expressed as 24-h averages. Biological HbA1c was measured for all three periods. Patients were their own-controls and statistics were performed using paired t-test or Wilcoxon for matched-pairs. Results: The switch to DG4 at M3 resulted in a higher time-in-range (TIR) 70–180 mg/dL (median [Q1;Q3], 53.1 [44.5;67.3] vs. 41.5 [28.5;62.0], P = 0.0008), and a lower time-below-range <70 mg/dL (TBR mean ± standard deviation (SD), 5.4 ± 3.7 vs. 10.9 ± 7.1, P = 0.0009) and in the glucose % coefficient of variation (%CV mean ± SD, 40.1 vs. 46.9, P = 0.0001). Mean (SD) changes were +10.3 (8.0) percentage points for TIR, −5.5 (5.8) percentage points for TBR, and −6.8 (5.8) percentage points for %CV. These results were confirmed at the M6 period. Conclusions: Switching from FSL to DG4 appears to provide a beneficial therapeutic option without changing insulin delivery systems, regardless of the origin of the patient's initial glycemic issue.
TREE1-EIN3–mediated transcriptional repression inhibits shoot growth in response to ethylene

Significance Ethylene is an important plant hormone that is essential for many physiological and developmental processes such as apical hook formation, shoot and root growth, root nodulation, flower senescence, abscission, and fruit ripening. Transcriptional activation in the ethylene response has been well studied. However, the transcriptional repression in the ethylene response remains unclear. Here, by combined approaches of data analysis, molecular biology, and genetics, we found that a transcriptional repressor TREE1 interacts with EIN3 to regulate transcriptional repression, leading to an inhibition of shoot growth in response to ethylene. Our work provides insight into how the transcriptional activator can be tuned to repress downstream gene expression in hormone signals. Ethylene is an important plant hormone that regulates plant growth, in which the master transcriptionactivator EIN3 (Ethylene Insensitive 3)-mediated transcriptional activation plays vital roles. However, the EIN3-mediated transcriptional repression in ethylene response is unknown. We report here that a Transcriptional Repressor of EIN3-dependent Ethylene-response 1 (TREE1) interacts with EIN3 to regulate transcriptional repression that leads to an inhibition of shoot growth in response to ethylene. Tissue-specific transcriptome analysis showed that most of the genes are down-regulated by ethylene in shoots, and a DNA binding motif was identified that is important for this transcriptional repression. TREE1 binds to the DNA motif to repress gene expression in an EIN3-dependent manner. Genetic validation demonstrated that repression of TREE1-targeted genes leads to an inhibition of shoot growth. Overall, this work establishes a mechanism by which transcriptional repressor TREE1 interacts with EIN3 to inhibit shoot growth via transcriptional repression in response to ethylene.
The evolutionary origin and domestication history of goldfish (Carassius auratus)

Significance We assembled one of the most contiguous genomes for the common goldfish and unveiled the genetic architecture of many well-known and anatomically interesting traits, owing to the sequencing of a large collection of goldfish varieties. The datasets that we have generated for candidate genes or genomic regions based on population genomics may help to elucidate the evolution of goldfish and goldfish varieties and may provide a resource for a wide range of studies with important implications for the use of goldfish as a model for vertebrate and fish genetics. Goldfish have been subjected to over 1,000 y of intensive domestication and selective breeding. In this report, we describe a high-quality goldfish genome (2n = 100), anchoring 95.75% of contigs into 50 pseudochromosomes. Comparative genomics enabled us to disentangle the two subgenomes that resulted from an ancient hybridization event. Resequencing 185 representative goldfish variants and 16 wild crucian carp revealed the origin of goldfish and identified genomic regions that have been shaped by selective sweeps linked to its domestication. Our comprehensive collection of goldfish varieties enabled us to associate genetic variations with a number of well-known anatomical features, including features that distinguish traditional goldfish clades. Additionally, we identified a tyrosine-protein kinase receptor as a candidate causal gene for the first well-known case of Mendelian inheritance in goldfish—the transparent mutant. The goldfish genome and diversity data offer unique resources to make goldfish a promising model for functional genomics, as well as domestication.
Akt3 induces oxidative stress and DNA damage by activating the NADPH oxidase via phosphorylation of p47phox

Significance Although the three Akt isoforms share mechanisms of activation and exhibit overlaps in their downstream signaling pathways, significant differences are now being uncovered. Here, we show that among Akt isoforms, Akt3 preferably phosphorylates p47phox and activates NADPH oxidase, resulting in robust induction of reactive oxygen species (ROS). Akt3-induced ROS activate the DNA damage response and upregulate p53 expression. Consequently, the proliferation rate of Akt3-expressing cells is reduced, an effect reversed by p53 loss. In cancer, Akt3 expression correlates with the abundance of p53; however, tumors can adapt to high Akt3 activity by inactivating the DNA damage response. These findings reveal differences in the regulation of ROS by Akt isoforms, which may be exploited therapeutically for Akt3-driven cancers. Akt activation up-regulates the intracellular levels of reactive oxygen species (ROS) by inhibiting ROS scavenging. Of the Akt isoforms, Akt3 has also been shown to up-regulate ROS by promoting mitochondrial biogenesis. Here, we employ a set of isogenic cell lines that express different Akt isoforms, to show that the most robust inducer of ROS is Akt3. As a result, Akt3-expressing cells activate the DNA damage response pathway, express high levels of p53 and its direct transcriptional target miR-34, and exhibit a proliferation defect, which is rescued by the antioxidant N-acetylcysteine. The importance of the DNA damage response in the inhibition of cell proliferation by Akt3 was confirmed by Akt3 overexpression in p53−/− and INK4a−/−/Arf−/− mouse embryonic fibroblasts (MEFs), which failed to inhibit cell proliferation, despite the induction of high levels of ROS. The induction of ROS by Akt3 is due to the phosphorylation of the NADPH oxidase subunit p47phox, which results in NADPH oxidase activation. Expression of Akt3 in p47phox−/− MEFs failed to induce ROS and to inhibit cell proliferation. Notably, the proliferation defect was rescued by wild-type p47phox, but not by the phosphorylation site mutant of p47phox. In agreement with these observations, Akt3 up-regulates p53 in human cancer cell lines, and the expression of Akt3 positively correlates with the levels of p53 in a variety of human tumors. More important, Akt3 alterations correlate with a higher frequency of mutation of p53, suggesting that tumor cells may adapt to high levels of Akt3, by inactivating the DNA damage response.
Smoking and Radiolucent Periapical Lesions in Root Filled Teeth: Systematic Review and Meta-Analysis

Aim: This systematic review and meta-analysis aimed to investigate the association between smoking habits and the prevalence of radiolucent periapical lesions (RPLs) in root-filled teeth (RFT). Methods: The Population, Intervention, Comparison, and Outcome (PICO) question was: in adult patients who have RFT, does the absence or presence of a smoking habit affect the prevalence of RPLs associated with RFT? Systematic MEDLINE/PubMed, Wiley Online Database, Web of Science, Scopus, and PRISMA protocol were used to evaluate and present the results. Studies comparing smokers with control non-smoker subjects, including RFT, and providing data on the prevalence of RFT with RPLs, were included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for certainty in the evidence. The risk of bias was assessed according to Cochrane Collaboration common scheme for bias and ROBINS-I tool. Cumulative meta-analysis was performed with a random effects model. PROSPERO registration code: CRD42020165279. Results: Four studies reported data on inclusion criteria, representing data from 9257 root-filled teeth—4465 from non-smokers and 4792 from smoker patients. The meta-analysis provided an odds ratio indicating a significant association between smoking and higher prevalence of root filled teeth with radiolucent periapical lesions (OR = 1.16; 95% CI = 1.07–1.26; p = 0.0004). The certainty of the literature assessment was moderate per GRADE. The ROBINS-I tool classified three studies as low risk of bias, and the fourth as moderate risk of bias. Conclusions: Moderate, quality scientific evidence indicates a weak but significant relationship between smoking and the prevalence of RPLs in RFT. Smoking can be considered a negative prognostic factor for the outcome of root canal treatment. Endodontic providers should be aware of the relationship between smoking and persistent apical periodontitis, assessed as RPLs, in RFT.
Mechanical injuries of neurons induce tau mislocalization to dendritic spines and tau-dependent synaptic dysfunction

Significance Athletes and soldiers exposed to repeated traumatic brain injuries have increased risk of developing chronic traumatic encephalopathy (CTE), which is a neurodegenerative disease characterized by tangled deposits of the protein tau in the brain and loss of cognitive function. This study provides the first experimental evidence showing that mechanical stretching of neurons induces tau to be mislocalized to dendritic spines where it causes synaptic dysfunction. This cross-disciplinary study utilizes computational modeling, imaging, and electrophysiology to unravel a cellular framework for how tau phosphorylation mediates trauma-induced synaptic dysfunction, highlighting the essential role of tau in functional deficits caused by traumatic brain injury. Chronic traumatic encephalopathy (CTE) is associated with repeated traumatic brain injuries (TBI) and is characterized by cognitive decline and the presence of neurofibrillary tangles (NFTs) of the protein tau in patients’ brains. Here we provide direct evidence that cell-scale mechanical deformation can elicit tau abnormalities and synaptic deficits in neurons. Using computational modeling, we find that the early pathological loci of NFTs in CTE brains are regions of high deformation during injury. The mechanical energy associated with high-strain rate deformation alone can induce tau mislocalization to dendritic spines and synaptic deficits in cultured rat hippocampal neurons. These cellular changes are mediated by tau hyperphosphorylation and can be reversed through inhibition of GSK3β and CDK5 or genetic deletion of tau. Together, these findings identify a mechanistic pathway that directly relates mechanical deformation of neurons to tau-mediated synaptic impairments and provide a possibly exploitable therapeutic pathway to combat CTE.
Effect of Different Ethephon Concentrations on Olive Fruits Harvesting at Different Orchard Locations

An experiment was conducted to determine the optimum ethephon concentration on olive fruit harvesting at different Jordan locations. The study was carried out on Nabali olive cultivar at “Irbid and Ajlon” locations. Treatments were consisted of five ethephon concentrations, which are: 0, 1000, 2000, 3000 and 4000 ppm, each concentration was repeated 4 times. 10 days after ethephon applications, data were collected and analyzed according to the randomized completely block design. Results revealed that all of the used ethephon concentrations promote leaf drop, which remains within the acceptable ranges in both locations. Although, ethephon dosage had significant effects on harvesting productivity at 0.05 levels; best results were obtained by using 3000 ppm concentration at Irbid location, while at Ajlon; best results were observed with treating the olive fruits with 4000 ppm ethephon concentration. On the other hand, positive correlation were observed between the percent of leaf drop and the total harvested fruits