Statistical and Biological Evaluation of Different Gene Set Analysis Methods

AbstractGene-set analysis (GSA) methods have been widely used in microarray data analysis. Owing to the unusual characteristics of microarray data, such as multi-dimension, small sample size and complicated relationship between genes, no generally accepted methods have been used to detect differentially expressed gene sets (DEGs) up to now. Our group assessed the statistical performance of some commonly used methods through Monte Carlo simulation combined with the analysis of real-world microarray data sets. Not only did we discover a few novel features of GSA methods during experiences, but also we find that some GSA methods are effective only if genes were assumed to be independent. And we also detected that model-based methods (GlobalTest and PCOT2) performed well when analyzing our simulated data sets in which the inter-gene correlation structure was incorporated into each gene set separately for more reasonable. Through analysis of real-world microarray data, we found GlobalTest is more effective. Then we concluded that GlobalTest is a more effective gene set analysis method, and recommended using it with microarray data analysis

Tunable Band Structure Effects on Ballistic Transport in Graphene Nanoribbons

Graphene nanoribbons (GNR) in mutually perpendicular electric and magnetic fields are shown to exhibit dramatic changes in their band structure and electron transport properties. A strong electric field across the ribbon induces multiple chiral Dirac points, closing the semiconducting gap in armchair GNR's. A perpendicular magnetic field induces partially formed Landau levels as well as dispersive surface-bound states. Each of the applied fields on its own preserves the even symmetry $E_{k} = E_{-k}$ of the subband dispersion. When applied together, they reverse the dispersion parity to be odd and gives $E_{e,k} = -E_{h,-k}$ and mix the electron and hole subbands within the energy range corresponding to the change in potential across the ribbon. This leads to oscillations of the ballistic conductance within this energy range

Distinct patterns of temporal and directional connectivity among intrinsic networks in the human brain

To determine the spatiotemporal relationships among intrinsic networks of the human brain, we recruited seven neurosurgical patients (four males and three females) who were implanted with intracranial depth electrodes. We first identified canonical resting-state networks at the individual subject level using an iterative matching procedure on each subject's resting-state fMRI data. We then introduced single electrical pulses to fMRI pre-identified nodes of the default network (DN), frontoparietal network (FPN), and salience network (SN) while recording evoked responses in other recording sites within the same networks. We found bidirectional signal flow across the three networks, albeit with distinct patterns of evoked responses within different time windows. We used a data-driven clustering approach to show that stimulation of the FPN and SN evoked a rapid (&lt;70 ms) response that was predominantly higher within the SN sites, whereas stimulation of the DN led to sustained responses in later time windows (85–200 ms). Stimulations in the medial temporal lobe components of the DN evoked relatively late effects (&gt;130 ms) in other nodes of the DN, as well as FPN and SN. Our results provide temporal information about the patterns of signal flow between intrinsic networks that provide insights into the spatiotemporal dynamics that are likely to constrain the architecture of the brain networks supporting human cognition and behavior.SIGNIFICANCE STATEMENTDespite great progress in the functional neuroimaging of the human brain, we still do not know the precise set of rules that define the patterns of temporal organization between large-scale networks of the brain. In this study, we stimulated and then recorded electrical evoked potentials within and between three large-scale networks of the brain, the default network (DN), frontoparietal network (FPN), and salience network (SN), in seven subjects undergoing invasive neurosurgery. Using a data-driven clustering approach, we observed distinct temporal and directional patterns between the three networks, with FPN and SN activity predominant in early windows and DN stimulation affecting the network in later windows. These results provide important temporal information about the interactions between brain networks supporting human cognition and behavior.</jats:p

Performing group-level functional image analyses based on homologous functional regions mapped in individuals

Functional MRI (fMRI) studies have traditionally relied on intersubject normalization based on global brain morphology, which cannot establish proper functional correspondence between subjects due to substantial intersubject variability in functional organization. Here, we reliably identified a set of discrete, homologous functional regions in individuals to improve intersubject alignment of fMRI data. These functional regions demonstrated marked intersubject variability in size, position, and connectivity. We found that previously reported intersubject variability in functional connectivity maps could be partially explained by variability in size and position of the functional regions. Importantly, individual differences in network topography are associated with individual differences in task-evoked activations, suggesting that these individually specified regions may serve as the localizer to improve the alignment of task-fMRI data. We demonstrated that aligning task-fMRI data using the regions derived from resting state fMRI may lead to increased statistical power of task-fMRI analyses. In addition, resting state functional connectivity among these homologous regions is able to capture the idiosyncrasies of subjects and better predict fluid intelligence (gF) than connectivity measures derived from group-level brain atlases. Critically, we showed that not only the connectivity but also the size and position of functional regions are related to human behavior. Collectively, these findings suggest that identifying homologous functional regions across individuals can benefit a wide range of studies in the investigation of connectivity, task activation, and brain-behavior associations. Author summary No two individuals are alike. The size, shape, position, and connectivity patterns of brain functional regions can vary drastically between individuals. While interindividual differences in functional organization are well recognized, to date, standard procedures for functional neuroimaging research still rely on aligning different subjects' data to a nominal average brain based on global brain morphology. We developed an approach to reliably identify homologous functional regions in each individual and demonstrated that aligning data based on these homologous functional regions can significantly improve the study of resting state functional connectivity, task-fMRI activations, and brain-behavior associations. Moreover, we showed that individual differences in size, position, and connectivity of brain functional regions are dissociable, and each can provide nonredundant information in explaining human behavior

The oral microbiome of patients with ischemic stroke predicts their severity and prognosis

Background and objectivesStroke is a common group of cerebrovascular diseases that can lead to brain damage or death. Several studies have shown a close link between oral health and stroke. However, the oral microbiome profiling of ischemic stroke (IS) and its potential clinical implication are unclear. This study aimed to describe the oral microbiota composition of IS, the high risk of IS, and healthy individuals and to profile the relationship between microbiota and IS prognosis.MethodsThis observational study recruited three groups: IS, high-risk IS (HRIS), and healthy control (HC) individuals. Clinical data and saliva were collected from participants. The modified Rankin scale score after 90 days was used to assess the prognosis of stroke. Extracted DNA from saliva and performed 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing. Sequence data were analyzed using QIIME2 and R packages to evaluate the association between the oral microbiome and stroke.ResultsA total of 146 subjects were enrolled in this study according to the inclusion criteria. Compared with HC, HRIS and IS demonstrated a progressive increase trend in Chao1, observed species richness, and Shannon and Simpson diversity index. On the basis of permutational multivariate analysis of variance, the data indicate a great variation in the saliva microbiota composition between HC and HRIS (F = 2.40, P &lt; 0.001), HC and IS (F = 5.07, P &lt; 0.001), and HRIS and IS (F = 2.79, P &lt; 0.001). The relative abundance of g_Streptococcus, g_Prevotella, g_Veillonella, g_Fusobacterium, and g_Treponema was higher in HRIS and IS compared with that in HC. Furthermore, we constructed the predictive model by differential genera to effectively distinguish patients with IS with poor 90-day prognoses from those with good (area under the curve = 79.7%; 95% CI, 64.41%–94.97%; p &lt; 0.01).DiscussionIn summary, the oral salivary microbiome of HRIS and IS subjects have a higher diversity, and the differential bacteria have some predictive value for the severity and prognosis of IS. Oral microbiota may be used as potential biomarkers in patients with IS

Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential

Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca2+ overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS

S1 is associated with chronic low back pain: a functional and structural MRI study

A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients

Soil diazotrophic abundance, diversity, and community assembly mechanisms significantly differ between glacier riparian wetlands and their adjacent alpine meadows

Global warming can trigger dramatic glacier area shrinkage and change the flux of glacial runoff, leading to the expansion and subsequent retreat of riparian wetlands. This elicits the interconversion of riparian wetlands and their adjacent ecosystems (e.g., alpine meadows), probably significantly impacting ecosystem nitrogen input by changing soil diazotrophic communities. However, the soil diazotrophic community differences between glacial riparian wetlands and their adjacent ecosystems remain largely unexplored. Here, soils were collected from riparian wetlands and their adjacent alpine meadows at six locations from glacier foreland to lake mouth along a typical Tibetan glacial river in the Namtso watershed. The abundance and diversity of soil diazotrophs were determined by real-time PCR and amplicon sequencing based on nifH gene. The soil diazotrophic community assembly mechanisms were analyzed via iCAMP, a recently developed null model-based method. The results showed that compared with the riparian wetlands, the abundance and diversity of the diazotrophs in the alpine meadow soils significantly decreased. The soil diazotrophic community profiles also significantly differed between the riparian wetlands and alpine meadows. For example, compared with the alpine meadows, the relative abundance of chemoheterotrophic and sulfate-respiration diazotrophs was significantly higher in the riparian wetland soils. In contrast, the diazotrophs related to ureolysis, photoautotrophy, and denitrification were significantly enriched in the alpine meadow soils. The iCAMP analysis showed that the assembly of soil diazotrophic community was mainly controlled by drift and dispersal limitation. Compared with the riparian wetlands, the assembly of the alpine meadow soil diazotrophic community was more affected by dispersal limitation and homogeneous selection. These findings suggest that the conversion of riparian wetlands and alpine meadows can significantly alter soil diazotrophic community and probably the ecosystem nitrogen input mechanisms, highlighting the enormous effects of climate change on alpine ecosystems

A web-based appointment system to reduce waiting for outpatients: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Long waiting times for registration to see a doctor is problematic in China, especially in tertiary hospitals. To address this issue, a web-based appointment system was developed for the Xijing hospital. The aim of this study was to investigate the efficacy of the web-based appointment system in the registration service for outpatients.</p> <p>Methods</p> <p>Data from the web-based appointment system in Xijing hospital from January to December 2010 were collected using a stratified random sampling method, from which participants were randomly selected for a telephone interview asking for detailed information on using the system. Patients who registered through registration windows were randomly selected as a comparison group, and completed a questionnaire on-site.</p> <p>Results</p> <p>A total of 5641 patients using the online booking service were available for data analysis. Of them, 500 were randomly selected, and 369 (73.8%) completed a telephone interview. Of the 500 patients using the usual queuing method who were randomly selected for inclusion in the study, responses were obtained from 463, a response rate of 92.6%. Between the two registration methods, there were significant differences in age, degree of satisfaction, and total waiting time (<it>P </it>< 0.001). However, gender, urban residence, and valid waiting time showed no significant differences (<it>P </it>> 0.05). Being ignorant of online registration, not trusting the internet, and a lack of ability to use a computer were three main reasons given for not using the web-based appointment system. The overall proportion of non-attendance was 14.4% for those using the web-based appointment system, and the non-attendance rate was significantly different among different hospital departments, day of the week, and time of the day (<it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Compared to the usual queuing method, the web-based appointment system could significantly increase patient's satisfaction with registration and reduce total waiting time effectively. However, further improvements are needed for broad use of the system.</p

Mapping the Distribution of Water Resource Security in the Beijing-Tianjin-Hebei Region at the County Level under a Changing Context

The Beijing-Tianjin-Hebei (Jingjinji) region is the most densely populated region in China and suffers from severe water resource shortage, with considerable water-related issues emerging under a changing context such as construction of water diversion projects (WDP), regional synergistic development, and climate change. To this end, this paper develops a framework to examine the water resource security for 200 counties in the Jingjinji region under these changes. Thus, county-level water resource security is assessed in terms of the long-term annual mean and selected typical years (i.e., dry, normal, and wet years), with and without the WDP, and under the current and projected future (i.e., regional synergistic development and climate change). The outcomes of such scenarios are assessed based on two water-crowding indicators, two use-to-availability indicators, and one composite indicator. Results indicate first that the water resources are distributed unevenly, relatively more abundant in the northeastern counties and extremely limited in the other counties. The water resources are very limited at the regional level, with the water availability per capita and per unit gross domestic product (GDP) being only 279/290 m3 and 46/18 m3 in the current and projected future scenarios, respectively, even when considering the WDP. Second, the population carrying capacity is currently the dominant influence, while economic development will be the controlling factor in the future for most middle and southern counties. This suggests that significant improvement in water-saving technologies, vigorous replacement of industries from high to low water consumption, as well as water from other supplies for large-scale applications are greatly needed. Third, the research identifies those counties most at risk to water scarcity and shows that most of them can be greatly relieved after supplementation by the planned WDP. Finally, more attention should be paid to the southern counties because their water resources are not only limited but also much more sensitive and vulnerable to climate change. This work should benefit water resource management and allocation decisions in the Jingjinji region, and the proposed assessment framework can be applied to other similar problems.This study is supported by the National Key Research and Development Program of China (2016YFC0401401) and the National Natural Science Foundation of China (51609256, 51609122, 51522907, 51739011, and 51569026). Partial support is also from the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2017QNRC001