Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Sensory Loss and Falls Among Middle-Aged and Older Chinese Population: Cross-Sectional and Longitudinal Analyses

Introduction: Previous studies have suggested that sensory loss is linked to falls. However, most of these studies were cross-sectional designed, focused on single sensory loss, and were conducted in developed countries with mixed results. The current study aims to investigate the longitudinal relationship between hearing loss (HL), vision loss (VL) and dual sensory loss (DSL) with falls among middle-aged and older Chinese population over 7 years. Methods: The data was obtained from the China Health and Retirement Longitudinal Survey (CHARLS). In total, 7,623 Chinese older adults aged over 45 were included at baseline 2011 in this study. Self-reported falls and HL/VL/DSL were accepted. Other confounding variables included age, sex, BMI, educational level, marital status, various physical disorders and lifestyles. The impact of baseline sensory status on baseline prevalence of falls and incident falls over 7 years were assessed using logistic regression analyses. A logistic mixed model was used to assess the association between time-varying sensory loss with incident falls over 7 years after adjusted with multi-confounding factors. Results: Single and dual sensory loss groups had significantly higher prevalence of falls compared to no sensory loss (NSL) group (DSL: 22.4%, HL: 17.4%, VL: 15.7%, NSL: 12.3%). Baseline HL (OR: 1.503, 95% CI: 1.240–1.820), VL (OR: 1.330, 95% CI: 1.075–1.646) and DSL (OR: 2.061, 95% CI: 1.768–2.404) were significantly associated with prevalence of falls. For longitudinal observation over 7 years, baseline HL/DSL and persistence of all types of sensory loss were associated with incidence of falls. Time-varying HL (OR: 1.203, 95% CI: 1.070–1.354) and DSL (OR: 1.479, 95% CI: 1.343–1.629) were associated with incident falls after adjusted with multi-confounders, while VL was not. Conclusion: HL and DSL are significantly associated with both onset and increased incidence of falls over 7 year's observation in middle-aged and elderly Chinese population. Persistence or amelioration of sensory loss status could exert divergent influences on incidence of falls, which should be considered in the development of falls-prevention public health policies for aging population.
Tau Knockout and α-Synuclein A53T Synergy Modulated Parvalbumin-Positive Neurons Degeneration Staging in Substantia Nigra Pars Reticulata of Parkinson’s Disease-Liked Model

The loss of parvalbumin-positive (PV+) neurons in the substantia nigra pars reticulata (SNR) was observed in patients with end-stage Parkinson’s disease (PD) and our previously constructed old-aged Pitx3-A53Tα-Syn × Tau–/– triple transgenic mice model of PD. The aim of this study was to examine the progress of PV+ neurons loss. We demonstrated that, as compared with non-transgenic (nTg) mice, the accumulation of α-synuclein in the SNR of aged Pitx3-A53Tα-Syn × Tau–/– mice was increased obviously, which was accompanied by the considerable degeneration of PV+ neurons and the massive generation of apoptotic NeuN+TUNEL+ co-staining neurons. Interestingly, PV was not costained with TUNEL, a marker of apoptosis. PV+ neurons in the SNR may undergo a transitional stage from decreased expression of PV to increased expression of NeuN and then to TUNEL expression. In addition, the degeneration of PV+ neurons and the expression of NeuN were rarely observed in the SNR of nTg and the other triple transgenic mice. Hence, we propose that Tau knockout and α-syn A53T synergy modulate PV+ neurons degeneration staging in the SNR of aged PD-liked mice model, and NeuN may be suited for an indicator that suggests degeneration of SNR PV+ neurons. However, the molecular mechanism needs to be further investigated.
Application of Evans Index in Normal Pressure Hydrocephalus Patients: A Mini Review

With an ever-growing aging population, the prevalence of normal pressure hydrocephalus (NPH) is increasing. Clinical symptoms of NPH include cognitive impairment, gait disturbance, and urinary incontinence. Surgery can improve symptoms, which leads to the disease's alternative name: treatable dementia. The Evans index (EI), defined as the ratio of the maximal width of the frontal horns to the maximum inner skull diameter, is the most commonly used index to indirectly assess the condition of the ventricles in NPH patients. EI measurement is simple, fast, and does not require any special software; in clinical practice, an EI >0.3 is the criterion for ventricular enlargement. However, EI's measurement methods, threshold setting, correlation with ventricle volume, and even its clinical value has been questioned. Based on the EI, the z-EI and anteroposterior diameter of the lateral ventricle index were derived and are discussed in this review.
Prognostic Significance and Gene Co-Expression Network of PLAU and PLAUR in Gliomas

The urokinase-type plasminogen activator(PLAU) and its receptor PLAUR participate in a series of cell physiological activities on the extracellular surface. Abnormal expression of PLAU and PLAUR is associated with tumorigenesis. This study aims to evaluate the prognostic value of PLAU/PLAUR transcription expression in glioma and to explore how they affect the generation and progression of glioma. In this study, online databases are applied, such as Oncomine, GEPIA, CGGA, cBioPortal, and LinkedOmics. Overexpression of PLAU/PLAUR was found to be significantly associated with clinical variables including age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. PLAU and PLAUR had a high correlation in transcriptional expression levels. High expression of PLAU and PLAUR predicted a poor prognosis in primary glioma and recurrent glioma patients, especially in lower grade gliomas. Cox regression analysis indicated that high expression of PLAU and PLAUR were independent prognostic factors for shorter overall survival in glioma patients. In gene co-expression network analysis PLAU and PLAUR and their co-expression genes were found to be involved in inflammatory activities and tumor-related signaling pathways. In conclusion, PLAU and PLAUR could be promising prognostic biomarkers and potential therapeutic targets of glioma patients.
Human Brain Organoids as an In Vitro Model System of Viral Infectious Diseases

Brain organoids, or brainoids, have shown great promise in the study of central nervous system (CNS) infection. Modeling Zika virus (ZIKV) infection in brain organoids may help elucidate the relationship between ZIKV infection and microcephaly. Brain organoids have been used to study the pathogenesis of SARS-CoV-2, human immunodeficiency virus (HIV), HSV-1, and other viral infections of the CNS. In this review, we summarize the advances in the development of viral infection models in brain organoids and their potential application for exploring mechanisms of viral infections of the CNS and in new drug development. The existing limitations are further discussed and the prospects for the development and application of brain organs are prospected.
Network Structure and Community Evolution Online: Behavioral and Emotional Changes in Response to COVID-19

Background: The measurement and identification of changes in the social structure in response to an exceptional event like COVID-19 can facilitate a more informed public response to the pandemic and provide fundamental insights on how collective social processes respond to extreme events. Objective: In this study, we built a generalized framework for applying social media data to understand public behavioral and emotional changes in response to COVID-19. Methods: Utilizing a complete dataset of Sina Weibo posts published by users in Wuhan from December 2019 to March 2020, we constructed a time-varying social network of 3.5 million users. In combination with community detection, text analysis, and sentiment analysis, we comprehensively analyzed the evolution of the social network structure, as well as the behavioral and emotional changes across four main stages of Wuhan's experience with the epidemic. Results: The empirical results indicate that almost all network indicators related to the network's size and the frequency of social interactions increased during the outbreak. The number of unique recipients, average degree, and transitivity increased by 24, 23, and 19% during the severe stage than before the outbreak, respectively. Additionally, the similarity of topics discussed on Weibo increased during the local peak of the epidemic. Most people began discussing the epidemic instead of the more varied cultural topics that dominated early conversations. The number of communities focused on COVID-19 increased by nearly 40 percent of the total number of communities. Finally, we find a statistically significant “rebound effect” by exploring the emotional content of the users' posts through paired sample t-test (P = 0.003). Conclusions: Following the evolution of the network and community structure can explain how collective social processes changed during the pandemic. These results can provide data-driven insights into the development of public attention during extreme events.
Habitat Adaptation Drives Speciation of a Streptomyces Species with Distinct Habitats and Disparate Geographic Origins

Both isolation by distance and isolation by environment occur in bacteria, and different diversification patterns may apply to different species. Streptomyces species, typified by producing useful natural products, are widespread in nature and possess high genetic diversity. However, the ecological processes and evolutionary mechanisms that shape their distribution are not well understood. ABSTRACT Microbial diversification is driven by geographic and ecological factors, but how the relative importance of these factors varies among species, geographic scales, and habitats remains unclear. Streptomyces, a genus of antibiotic-producing, spore-forming, and widespread bacteria, offers a robust model for identifying the processes underlying population differentiation. We examined the population structure of 37 Streptomyces olivaceus strains isolated from various sources, showing that they diverged into two habitat-associated (free-living and insect-associated) and geographically disparate lineages. More frequent gene flow within than between the lineages confirmed genetic isolation in S. olivaceus. Geographic isolation could not explain the genetic isolation; instead, habitat type was a strong predictor of genetic distance when controlling for geographic distance. The identification of habitat-specific genetic variations, including genes involved in regulation, resource use, and secondary metabolism, suggested a significant role of habitat adaptation in the diversification process. Physiological assays revealed fitness trade-offs under different environmental conditions in the two lineages. Notably, insect-associated isolates could outcompete free-living isolates in a free-iron-deficient environment. Furthermore, substrate (e.g., sialic acid and glycogen) utilization but not thermal traits differentiated the two lineages. Overall, our results argue that adaptive processes drove ecological divergence among closely related streptomycetes, eventually leading to dispersal limitation and gene flow barriers between the lineages. S. olivaceus may best be considered a species complex consisting of two cryptic species. IMPORTANCE Both isolation by distance and isolation by environment occur in bacteria, and different diversification patterns may apply to different species. Streptomyces species, typified by producing useful natural products, are widespread in nature and possess high genetic diversity. However, the ecological processes and evolutionary mechanisms that shape their distribution are not well understood. Here, we show that the population structure of a ubiquitous Streptomyces species complex matches its habitat distribution and can be defined by gene flow discontinuities. Using comparative genomics and physiological assays, we reveal that gains and losses of specific genomic traits play a significant role in the transition between free-living and host-associated lifestyles, driving speciation of the species. These results provide new insights into the evolutionary trajectory of Streptomyces and the notion of species.
The Role of Fatty Acid Metabolism in Drug Tolerance of Mycobacterium tuberculosis

Understanding the mechanisms underlying M. tuberculosis adaptive strategies to achieve drug tolerance is crucial for the identification of new targets and the development of new drugs. Here, we show that acetate medium triggers a drug-tolerant state in M. tuberculosis when challenged with antituberculosis (anti-TB) drugs. ABSTRACT Mycobacterium tuberculosis can cocatabolize a range of carbon sources. Fatty acids are among the carbons available inside the host’s macrophages. Here, we investigated the metabolic changes of the fatty acid-induced dormancy-like state of M. tuberculosis and its involvement in the acquisition of drug tolerance. We conducted metabolomics profiling using a phosphoenolpyruvate carboxykinase (PEPCK)-deficient M. tuberculosis strain in an acetate-induced dormancy-like state, highlighting an overaccumulation of methylcitrate cycle (MCC) intermediates that correlates with enhanced drug tolerance against isoniazid and bedaquiline. Further metabolomics analyses of two M. tuberculosis mutants, an ICL knockdown (KD) strain and PrpD knockout (KO) strain, each lacking an MCC enzyme—isocitrate lyase (ICL) and 2-methylcitrate dehydratase (PrpD), respectively—were conducted after treatment with antibiotics. The ICL KD strain, which lacks the last enzyme of the MCC, showed an overaccumulation of MCC intermediates and a high level of drug tolerance. The PrpD KO strain, however, failed to accumulate MCC intermediates as it lacks the second step of the MCC and showed only a minor level of drug tolerance compared to the ICL KD mutant and its parental strain (CDC1551). Notably, addition of authentic 2-methylisocitrate, an MCC intermediate, improved the M. tuberculosis drug tolerance against antibiotics even in glycerol medium. Furthermore, wild-type M. tuberculosis displayed levels of drug tolerance when cultured in acetate medium significantly greater than those in glycerol medium. Taken together, the fatty acid-induced dormancy-like state remodels the central carbon metabolism of M. tuberculosis that is functionally relevant to acquisition of M. tuberculosis drug tolerance. IMPORTANCE Understanding the mechanisms underlying M. tuberculosis adaptive strategies to achieve drug tolerance is crucial for the identification of new targets and the development of new drugs. Here, we show that acetate medium triggers a drug-tolerant state in M. tuberculosis when challenged with antituberculosis (anti-TB) drugs. This carbon-induced drug-tolerant state is linked to an accumulation of the methylcitrate cycle (MCC) intermediates, whose role was previously known as a detox pathway for propionate metabolism. Three mutant strains with mutations in gluconeogenesis and MCC were used to investigate the correlation between drug tolerance and the accumulation of MCC metabolites. We herein report a new role of the MCC used to provide a survival advantage to M. tuberculosis as a species against both anti-TB drugs upon specific carbon sources.
Disentangling the Evolutionary History of Feo, the Major Ferrous Iron Transport System in Bacteria

Feo, a ferrous iron transport system composed of three proteins (FeoA, -B, and -C), is the most prevalent bacterial iron transporter. It plays an important role in iron acquisition in low-oxygen environments and some host-pathogen interactions. ABSTRACT Iron acquisition is essential for almost all living organisms. In certain environments, ferrous iron is the most prevalent form of this element. Feo is the most widespread system for ferrous iron uptake in bacteria and is critical for virulence in some species. The canonical architecture of Feo consists of a large transmembrane nucleoside triphosphatase (NTPase) protein, FeoB, and two accessory cytoplasmic proteins, FeoA and FeoC. The role of the latter components and the mechanism by which Feo orchestrates iron transport are unclear. In this study, we conducted a comparative analysis of Feo protein sequences to gain insight into the evolutionary history of this transporter. We identified instances of how horizontal gene transfer contributed to the evolution of Feo. Also, we found that FeoC, while absent in most lineages, is largely present in the Gammaproteobacteria group, although its sequence is poorly conserved. We propose that FeoC, which may couple FeoB NTPase activity with pore opening, was an ancestral element that has been dispensed with through mutations in FeoA and FeoB in some lineages. We provide experimental evidence supporting this hypothesis by isolating and characterizing FeoC-independent mutants of the Vibrio cholerae Feo system. Also, we confirmed that the closely related species Shewanella oneidensis does not require FeoC; thus, Vibrio FeoC sequences may resemble transitional forms on an evolutionary pathway toward FeoC-independent transporters. Finally, by combining data from our bioinformatic analyses with this experimental evidence, we propose an evolutionary model for the Feo system in bacteria. IMPORTANCE Feo, a ferrous iron transport system composed of three proteins (FeoA, -B, and -C), is the most prevalent bacterial iron transporter. It plays an important role in iron acquisition in low-oxygen environments and some host-pathogen interactions. The large transmembrane protein FeoB provides the channel for the transport of iron into the bacterial cell, but the functions of the two small, required accessory proteins FeoA and FeoC are not well understood. Analysis of the evolution of this transporter shows that FeoC is poorly conserved and has been lost from many bacterial lineages. Experimental evidence indicates that FeoC may have different functions in different species that retain this protein, and the loss of FeoC is promoted by mutations in FeoA or by the fusion of FeoA and FeoB.
Experimental validation of inviscid linear stability theory applied to an axisymmetric jet

Abstract We study the development of perturbations in a submerged air jet with a round cross-section and a long laminar region (five jet diameters) at a Reynolds number of 5400 by both inviscid linear stability theory and experiments. The theoretical analysis shows that there are two modes of growing axisymmetric perturbations, which are generated by three generalized inflection points of the jet's velocity profile. To validate the results of linear stability theory, we conduct experiments with controlled axisymmetric perturbations to the jet. The characteristics of growing waves are obtained by visualization, thermoanemometer measurements and correlation analysis. Experimentally measured wavelengths, growth rates and spatial distributions of velocity fluctuations for both growing modes are in good agreement with theoretical calculations. Therefore, it is demonstrated that small perturbations to the laminar jet closely follow the predictions of inviscid linear stability theory.
Performance-based reliability analysis and code calibration for RC column subject to vehicle collision

Performance-Based Reliability Analysis and Code Calibration for RC Column Subject to Vehicle Collision. (May 2012) Hrishikesh Sharma, B.E. , Visvesvaraya National Institute of Technology, Nagpur, India; M.S., Texas A&M University Chair of Advisory Committee: Dr. Stefan Hurlebaus Infrastructure and transportation facilities have increased rapidly over the years. The progress has been accompanied by an increasing number of vehicle collisions with structures. This type of collision might lead to the damage, and often, collapse of the structure. In reinforced concrete (RC) structures, columns are usually the most vulnerable members exposed to collisions. However, the existing design guidelines and provisions for protection of these members against collision of vehicles are not adequate. In particular, the desired behavior and the associated performance levels of a structure during a vehicle collision are not defined. Therefore, there is need to assess the vulnerability of structures against such collisions. This research aims to develop a framework for the performance-based analysis and design of RC columns subject to vehicle impact. It helps mitigate maximum damage and achieve an economical design. The current research takes into account performance-based analysis and design as opposed to only collapse prevention design. The performance level is tied to the impact levels to estimate the reliability of the RC
Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives

Astrocytes play key roles in the regulation of brain energy metabolism, which has a major impact on brain functions, including memory, neuroprotection, resistance to oxidative stress and homeostatic tone. Energy demands of the brain are very large, as they continuously account for 20–25% of the whole body’s energy consumption. Energy supply of the brain is tightly linked to neuronal activity, providing the origin of the signals detected by the widely used functional brain imaging techniques such as functional magnetic resonance imaging and positron emission tomography. In particular, neuroenergetic coupling is regulated by astrocytes through glutamate uptake that triggers astrocytic aerobic glycolysis and leads to glucose uptake and lactate release, a mechanism known as the Astrocyte Neuron Lactate Shuttle. Other neurotransmitters such as noradrenaline and Vasoactive Intestinal Peptide mobilize glycogen, the reserve for glucose exclusively localized in astrocytes, also resulting in lactate release. Lactate is then transferred to neurons where it is used, after conversion to pyruvate, as a rapid energy substrate, and also as a signal that modulates neuronal excitability, homeostasis, and the expression of survival and plasticity genes. Importantly, glycolysis in astrocytes and more generally cerebral glucose metabolism progressively deteriorate in aging and age-associated neurodegenerative diseases such as Alzheimer’s disease. This decreased glycolysis actually represents a common feature of several neurological pathologies. Here, we review the critical role of astrocytes in the regulation of brain energy metabolism, and how dysregulation of astrocyte-mediated metabolic pathways is involved in brain hypometabolism. Further, we summarize recent efforts at preclinical and clinical stages to target brain hypometabolism for the development of new therapeutic interventions in age-related neurodegenerative diseases.