Miracle-dz/UniFAR-FTUs huggingface dataset:
Update on new trends and progress of natural active ingredients in the intervention of Alzheimer's disease, based on understanding of traditional Chinese and Western relevant theories: A review

Alzheimer's disease (AD) is one of the major neurological disorders causing death in the elderly worldwide. As a neurodegenerative disease that is difficult to prevent and cure, the pathogenesis of AD is complex and there is no effective cure. A variety of natural products derived from plants have been reported to have promising anti‐AD activities, including flavonoids, terpenes, phenolic acids and alkaloids, which can effectively relieve the symptoms of AD in a variety of ways. This paper mainly reviews the pharmacological activity and mechanisms of natural products against AD. Although the clinical efficacy of these plants still needs to be determined by further high‐quality studies, it may also provide a basis for future researchers to study anti‐AD in depth.
Identification of Histone Lysine Acetoacetylation as a Dynamic Post‐Translational Modification Regulated by HBO1

Ketone bodies have long been known as a group of lipid‐derived alternative energy sources during glucose shortages. Nevertheless, the molecular mechanisms underlying their non‐metabolic functions remain largely elusive. This study identified acetoacetate as the precursor for lysine acetoacetylation (Kacac), a previously uncharacterized and evolutionarily conserved histone post‐translational modification. This protein modification is comprehensively validated using chemical and biochemical approaches, including HPLC co‐elution and MS/MS analysis using synthetic peptides, Western blot, and isotopic labeling. Histone Kacac can be dynamically regulated by acetoacetate concentration, possibly via acetoacetyl‐CoA. Biochemical studies show that HBO1, traditionally known as an acetyltransferase, can also serve as an acetoacetyltransferase. In addition, 33 Kacac sites are identified on mammalian histones, depicting the landscape of histone Kacac marks across species and organs. In summary, this study thus discovers a physiologically relevant and enzymatically regulated histone mark that sheds light on the non‐metabolic functions of ketone bodies.
Branched-chain actin dynamics polarizes vesicle trajectories and partitions apicobasal epithelial membrane domains

In prevailing epithelial polarity models, membrane- and junction-based polarity cues such as the partitioning-defective PARs specify the positions of apicobasal membrane domains. Recent findings indicate, however, that intracellular vesicular trafficking can determine the position of the apical domain, upstream of membrane-based polarity cues. These findings raise the question of how vesicular trafficking becomes polarized independent of apicobasal target membrane domains. Here, we show that the apical directionality of vesicle trajectories depends on actin dynamics during de novo polarized membrane biogenesis in the C. elegans intestine. We find that actin, powered by branched-chain actin modulators, determines the polarized distribution of apical membrane components, PARs, and itself. Using photomodulation, we demonstrate that F-actin travels through the cytoplasm and along the cortex toward the future apical domain. Our findings support an alternative polarity model where actin-directed trafficking asymmetrically inserts the nascent apical domain into the growing epithelial membrane to partition apicobasal membrane domains.
Creating building-level, three-dimensional digital models of historic urban neighborhoods from Sanborn Fire Insurance maps using machine learning

Sanborn Fire Insurance maps contain a wealth of building-level information about U.S. cities dating back to the late 19th century. They are a valuable resource for studying changes in urban environments, such as the legacy of urban highway construction and urban renewal in the 20th century. However, it is a challenge to automatically extract the building-level information effectively and efficiently from Sanborn maps because of the large number of map entities and the lack of appropriate computational methods to detect these entities. This paper contributes to a scalable workflow that utilizes machine learning to identify building footprints and associated properties on Sanborn maps. This information can be effectively applied to create 3D visualization of historic urban neighborhoods and inform urban changes. We demonstrate our methods using Sanborn maps for two neighborhoods in Columbus, Ohio, USA that were bisected by highway construction in the 1960s. Quantitative and visual analysis of the results suggest high accuracy of the extracted building-level information, with an F-1 score of 0.9 for building footprints and construction materials, and over 0.7 for building utilizations and numbers of stories. We also illustrate how to visualize pre-highway neighborhoods.
Statistical Characterization and Geological Correlation of Wells Using Automatic Learning Gaussian Mixture Models

The URTeC Technical Program Committee accepted this presentation on the basis of information contained in an abstract submitt ed by the author(s). The contents of this paper have not been reviewed by URTeC and URTeC does not warrant the accuracy, reliabili ty, or timeliness of any information herein. All information is the responsibility of, and, is subject to corrections by the author(s). Any person or entity that relies on any information obtained from this paper does so at their own risk. The information herein does not necessarily reflect any position of URTeC. Any reproduction, distribution, or storage of any part of this paper without the written consent of URTeC is prohibited.
Off-the-shelf CAR–engineered natural killer cells targeting FLT3 enhance killing of acute myeloid leukemia

Key Points • Off-the-shelf FLT3 CAR_sIL-15 NK cells secrete IL-15, preferentially lyse human FLT3+ AML, and activate T cells. • FLT3 CAR_sIL-15 NK cells expressing soluble IL-15 prolong survival of FLT3+ AML–bearing mice without toxicity to normal hematopoiesis.
Resonant magnetic perturbations of edge-plasmas in toroidal confinement devices

Controlling the boundary layer in fusion-grade, high-performance, plasma discharges is essential for the successful development of toroidal magnetic confinement power generating systems. A promising approach for controlling the boundary plasma is based on the use of small, externally applied, edge resonant magnetic perturbation (RMP) fields (δb⊥ext≈10−4→10−3 T ? >). A long-term focus area in tokamak fusion research has been to find methods, involving the use of non-axisymmetric magnetic perturbations to reduce the intense particle and heat fluxes to the wall. Experimental RMP research has progressed from the early pioneering work on tokamaks with material limiters in the 1970s, to present day research in separatrix-limited tokamaks operated in high-confinement mode, which is primarily aimed at the mitigation of the intermittent fluxes due edge localized modes (ELMs). At the same time, theoretical research has evolved from analytical models to numerical simulations, including the full 3D complexities of the problem. Following the first demonstration of ELM suppression in the DIII-D tokamak during 2003, there has been a rapid worldwide growth in theoretical, numerical and experimental edge RMP research resulting in the addition of ELM control coils to the ITER baseline design (Loarte et al 2014 Nucl. Fusion 54 033007). This review provides an overview of edge RMP research including a summary of the early theoretical and numerical background along with recent experimental results on improved particle and energy confinement in tokamaks triggered by edge RMP fields. The topics covered make up the basic elements needed for developing a better understanding of 3D magnetic perturbation physics, which is required in order to utilize the full potential of edge RMP fields in fusion relevant high performance, H-mode, plasmas.
Pupil Size Encodes Uncertainty during Exploration

Abstract Exploration is an important part of decision making and is crucial to maximizing long-term rewards. Past work has shown that people use different forms of uncertainty to guide exploration. In this study, we investigate the role of the pupil-linked arousal system in uncertainty-guided exploration. We measured participants' (n = 48) pupil dilation while they performed a two-armed bandit task. Consistent with previous work, we found that people adopted a hybrid of directed, random, and undirected exploration, which are sensitive to relative uncertainty, total uncertainty, and value difference between options, respectively. We also found a positive correlation between pupil size and total uncertainty. Furthermore, augmenting the choice model with subject-specific total uncertainty estimates decoded from the pupil size improved predictions of held-out choices, suggesting that people used the uncertainty estimate encoded in pupil size to decide which option to explore. Together, the data shed light on the computations underlying uncertainty-driven exploration. Under the assumption that pupil size reflects locus coeruleus-norepinephrine neuromodulatory activity, these results also extend the theory of the locus coeruleus-norepinephrine function in exploration, highlighting its selective role in driving uncertainty-guided random exploration.
Perceptions of Autonomous Shuttles for Adults With Spinal Cord Injuries

Individuals with a spinal cord injury (SCI) have challenges using transportation. Autonomous shuttles (ASs), if accessible, may support their transportation needs. This study quantified the perceptions of AS for adults with and without SCI, before and after riding in the AS. We hypothesized that the perceptions of AS for individuals with SCI would improve, by the greatest magnitude, after riding in the AS. This mixed-method quasi-experimental design included 16 adults with SCI and 16 age-matched controls. While there were no differences between the groups, both groups reported having fewer perceived barriers to using AS after riding in the AS (p = .025). After riding in the AS, both groups stated that the AS must be available, accessible, and affordable if they are to use AS. In conclusion, adults with SCI should experience AS if they are to accept and adopt this mode of transportation.
The Tolerance of Gut Commensal Faecalibacterium to Oxidative Stress Is Strain Dependent and Relies on Detoxifying Enzymes

Commensal bacteria in the genus Faecalibacterium have been proposed for use as next-generation probiotics, but efforts to cultivate and exploit the potential of these strains have been limited by their sensitivity to O2. More broadly, little is known about how commensal and health-associated bacterial species in the human microbiome respond to the oxidative stress that occurs as a result of inflammation in the colon. ABSTRACT Obligate anaerobic bacteria in genus Faecalibacterium are among the most dominant taxa in the colon of healthy individuals and contribute to intestinal homeostasis. A decline in the abundance of this genus is associated with the occurrence of various gastrointestinal disorders, including inflammatory bowel diseases. In the colon, these diseases are accompanied by an imbalance between the generation and elimination of reactive oxygen species (ROS), and oxidative stress is closely linked to disruptions in anaerobiosis. In this work, we explored the impact of oxidative stress on several strains of faecalibacteria. An in silico analysis of complete genomes of faecalibacteria revealed the presence of genes encoding O2- and/or ROS-detoxifying enzymes, including flavodiiron proteins, rubrerythrins, reverse rubrerythrins, superoxide reductases, and alkyl peroxidase. However, the presence and the number of these detoxification systems varied greatly among faecalibacteria. These results were confirmed by O2 stress survival tests, in which we found that strains differed widely in their sensitivity. We showed the protective role of cysteine, which limited the production of extracellular O2•− and improved the survival of Faecalibacterium longum L2-6 under high O2 tension. In the strain F. longum L2-6, we observed that the expression of genes encoding detoxifying enzymes was upregulated in the response to O2 or H2O2 stress but with different patterns of regulation. Based on these results, we propose a first model of the gene regulatory network involved in the response to oxidative stress in F. longum L2-6. IMPORTANCE Commensal bacteria in the genus Faecalibacterium have been proposed for use as next-generation probiotics, but efforts to cultivate and exploit the potential of these strains have been limited by their sensitivity to O2. More broadly, little is known about how commensal and health-associated bacterial species in the human microbiome respond to the oxidative stress that occurs as a result of inflammation in the colon. In this work, we provide insights regarding the genes that encode potential mechanisms of protection against O2 or ROS stress in faecalibacteria, which may facilitate future advances in work with these important bacteria.
Association between Risk of Malnutrition Defined by the Nutritional Risk Screening 2002 and Postoperative Complications and Overall Survival in Patients with Cancer: A Meta-Analysis

Abstract The Nutritional Risk Screening 2002 (NRS 2002) has been applied as a nutritional screening tool in oncology patients. This meta-analysis aimed to assess the association between the risk of malnutrition defined by the NRS 2002 and adverse outcomes in patients with cancer. We comprehensively searched PubMed, Embase, and Web of Science until May 7, 2023. Studies investigating the association between the risk of malnutrition defined by the NRS 2002 and overall survival or postoperative complications in adult patients with cancer were included. Patients were grouped as being at risk of malnutrition (NRS2002 ≥ 3) and not at risk (NRS 2002 < 3). Twenty-two studies involving 9,332 patients were identified. The reported prevalence of the risk of malnutrition ranged from 12.8% to 80.8%. Meta-analysis indicated that cancer patients with a risk of malnutrition had a poor overall survival (hazard ratio 1.66; 95% confidence intervals [CI] 1.40–1.97). Furthermore, the pooled adjusted odds ratio of postoperative complications was 2.27 (95% CI 1.81–2.84) for the risk of malnutrition. The risk of malnutrition defined by the NRS 2002 is independently associated with an increased risk of postoperative complications and worse overall survival in patients with cancer. NRS 2002 can serve as a promising risk stratification tool in cancer patients.
Machine learning in predicting outcomes for stroke patients following rehabilitation treatment: A systematic review

Objective This review aimed to summarize the use of machine learning for predicting the potential benefits of stroke rehabilitation treatments, to evaluate the risk of bias of predictive models, and to provide recommendations for future models. Materials and methods This systematic review was conducted in accordance with the PRISMA statement and the CHARMS checklist. The PubMed, Embase, Cochrane Library, Scopus, and CNKI databases were searched up to April 08, 2023. The PROBAST tool was used to assess the risk of bias of the included models. Results Ten studies within 32 models met our inclusion criteria. The optimal AUC value of the included models ranged from 0.63 to 0.91, and the optimal R2 value ranged from 0.64 to 0.91. All of the included models were rated as having a high or unclear risk of bias, and most of them were downgraded due to inappropriate data sources or analysis processes. Discussion and conclusion There remains much room for improvement in future modeling studies, such as high-quality data sources and model analysis. Reliable predictive models should be developed to improve the efficacy of rehabilitation treatment by clinicians.
Stability Indicating HPLC Method for Simultaneous Determination of Repaglinide and Metformin Hydrochloride in Pharmaceutical Dosage Form

A simple, specific and accurate stability-indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of Repaglinide and Metformin hydrochloride. An isocratic RP-HPLC was achieved on younglin HPLC system using Varian C18 (250 × 4.6 mm i.d, 5 μm particle size) column with the mobile phase containing mixture of acetonitrile: 10mM ammonium acetate(pH 3.0, adjusted with phosphoric acid) (70: 30, v/v). The flow rate was 1.0ml/min and the eluent was monitored at 230nm. The retention times of Repaglinide and Metformin hydrochloride were found to be 3.1 min and 5.58 min, respectively. Linearity was established for Repaglinide and Metformin hydrochloride in the range of 0.5–3 μg/ml and 200–1200 μg/ml, respectively. The percentage recoveries of Repaglinide and Metformin hydrochloride were found to be in the range of 99.87%±0.7 and 99.89%±0.15 respectively. Both the drugs were subjected to acid, alkali, oxidation, and dry heat degradation. The degradation studies indicated, Repaglinide and Metformin hydrochloride showed degradation in acid, alkaline, H2O2, and in dry heat condition. The degradation products of Repaglinide and Metformin hydrochloride were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of Repaglinide and Metformin hydrochloride in bulk drugs and formulations.
Vitamin E modified polyamidoamine dendrimer for piperine delivery to alleviate Aβ1–42 induced neurotoxicity in Balb/c mice model

Abstract In Alzheimer’s disease (AD), amyloid beta (Aβ1-42) aggregate formation and neurofibrillary tangles are major pathological hallmarks which are related to neurodegeneration in the brain. To alleviate Aβ1-42 fibrils toxicity vitamin E derivative tocopheryl polyethylene glycol succinate (TPGS) was conjugated with polyamidoamine (PAMAM) dendrimer through carbodiimide reaction to synthesize TPGS-PAMAM. This TPGS-PAMAM was employed to entrap neuroprotective agent piperine (PIP) through an anti-solvent technique to prepare PIP-TPGS-PAMAM. The dendrimer conjugate was prepared to reduce Aβ1-42 induced neurotoxicity and increase acetylcholine levels in AD mice models. The synthesis of dendrimer conjugate was characterized through proton nuclear magnetic resonance (NMR) and Trinitrobenzene sulphonic acid assay (TNBS). Physical characterization of dendrimers conjugates were done through various spectroscopic, thermal and microscopy based techniques. PIP-TPGS-PAMAM showed 43.25 nm particle size with PIP percentage encapsulation efficiency of 80.35%. Further Aβ1-42 fibril disaggregation effect of nanocarrier was evaluated using Thioflavin–T (ThT) assay and circular dichroism (CD). The neuroprotection studies for PIP-TPGS-PAMAM was evaluated against neurotoxicity induced using Aβ1–42 intracerebroventricular (ICV) injected in Balb/c mice. The group of mice administered with PIP-TPGS-PAMAM exhibited an increase in the proportion of random alternations in T-maze test and novel object recognition test (NORT) exhibited an increase in working memory cognitive functions. The biochemical and histopathological analysis revealed PIP-TPGS-PAMAM treated groups enhanced acetylcholine levels, reduced ROS and Aβ1-42 content significantly. Our findings imply that PIP-TPGS-PAMAM enhanced memory and reduced cognitive deficit in mice brain induced by Aβ1-42 toxicity.
Functional analysis of two SLC9A6 frameshift variants in lymphoblastoid cells from patients with Christianson syndrome

Christianson syndrome (CS) is caused by mutations in SLC9A6 and is characterized by global developmental delay, epilepsy, hyperkinesis, ataxia, microcephaly, and behavioral disorder. However, the molecular mechanism by which these SLC9A6 mutations cause CS in humans is not entirely understood, and there is no objective method to determine the pathogenicity of single SLC9A6 variants.
Test cricketers score quickly during the ‘nervous nineties’: Evidence from a regression discontinuity design

The ‘nervous nineties’ is a well-known cricket colloquialism that implies that batting within reach of 100 runs is mentally demanding. Despite common acceptance of this phenomenon, no study has used a historical test cricket dataset to examine how batting behaviour and performance changes on approach to a century. Accordingly, we explored opensource ball-by-ball data from 712 test cricket matches played between 2004 and 2022 to model the regression discontinuity of batting performance metrics either side of 100 runs. Models were fit using multi-level regression, adjusted for the clustering of balls within players (and where possible, the clustering of matches and innings within players). The analysis revealed that runs per ball and the probability of scoring a boundary increased as batters approached 100 runs. This was followed by a decline of -0.18 runs per ball (95% CI -0.22 to -0.14) and a three-percentage point decline (95% CI 2.2 to 3.8) in the probability of a boundary once a batter reached 100. The modelling revealed no evidence of a change in the probability of a dismissal before and after 100. Our results suggest many batters cope effectively with the psychological demands of playing through the nineties, including by batting aggressively and/or opportunistically to swiftly reach the milestone.
Density functional theory and ab initio molecular dynamics reveal atomistic mechanisms for carbonate clumped isotope reordering

Carbon (13C) and oxygen (18O) isotopes in carbonates form clumped isotope species inversely correlated with temperature, providing a valuable paleothermometer for sedimentary carbonates and fossils. However, this signal resets (“reorders”) with increasing temperature after burial. Research on reordering kinetics has characterized reordering rates and hypothesized the effects of impurities and trapped water, but the atomistic mechanism remains obscure. This work studies carbonate-clumped isotope reordering in calcite via first-principles simulations. We developed an atomistic view of the isotope exchange reaction between carbonate pairs in calcite, discovering a preferred configuration and elucidating how Mg2+ substitution and Ca2+ vacancies lower the free energy of activation (ΔA‡) compared to pristine calcite. Regarding water-assisted isotopic exchange, the H+-O coordination distorts the transition state configuration and reduces ΔA‡. We proposed a water-mediated exchange mechanism showing the lowest ΔA‡ involving a reaction pathway with a hydroxylated four-coordinated carbon atom, confirming that internal water facilitates clumped isotope reordering.
Spit, Disgust, and Parasite Stress Theory: A Message Experiment

Public health interventions targeting coughing and spitting during the Tuberculosis and 1918 flu epidemics were largely successful. Specifically, public health officials’ messaging framed the behavior of spitting as repulsive and endangering to others, prompting an elicitation of disgust. Anti-spitting campaigns – messaging that focuses on the threat of spit or sputum – have long been common during pandemics and manifested once again to combat the spread of COVID-19. Yet, few scholars have theorized if and how anti-spitting campaigns function to change behavior. One possibility is parasite stress theory, which posits that human behavior is driven by a desire to avoid pathogenic threats like spit. The application of these types of disgust appeals in public health messaging remains understudied and warrants exploration. To test the applicability of the parasite stress theory, our message experiment with US adults (N = 488) examined reactions to anti-spit messages that varied in visual disgust (low and high). For more highly educated respondents, the high disgust appeal directly decreased spitting intentions, and this relationship was stronger for individuals with higher levels of pathogen and moral disgust. Given the importance of public messaging during pandemics, future research should continue to examine the efficacy and theoretical underpinnings of specific disgust appeals.