Miracle-dz/UniFAR-FTUs huggingface dataset:
Measuring the Network Vulnerability Based on Markov Criticality

Vulnerability assessment—a critical issue for networks—attempts to foresee unexpected destructive events or hostile attacks in the whole system. In this article, we consider a new Markov global connectivity metric—Kemeny constant, and take its derivative called Markov criticality to identify critical links. Markov criticality allows us to find links that are most influential on the derivative of Kemeny constant. Thus, we can utilize it to identity a critical link (i, j) from node i to node j, such that removing it leads to a minimization of networks’ global connectivity, i.e., the Kemeny constant. Furthermore, we also define a novel vulnerability index to measure the average speed by which we can disconnect a specified ratio of links with network decomposition. Our method is of high efficiency, which can be easily employed to calculate the Markov criticality in real-life networks. Comprehensive experiments on several synthetic and real-life networks have demonstrated our method’s better performance by comparing it with state-of-the-art baseline approaches.
PAEP and cilia gene splicing changes in endometrial glands during the implantation window in women with recurrent pregnancy loss

Endometrial glands are essential for fertility, consisting of ciliated and secretory cells that facilitate a suitable uterine environment for embryo implantation. This study sought to determine whether an endometrial gland specific transcriptome and splicing profile are altered in women with recurrent pregnancy loss. Our data provide a comprehensive catalogue of cilia and PAEP gene isoforms and relative exon usage in endometrial glands. We report a previously unannotated endometrial gland cilia transcript GALNT11 and its susceptibility to exon skipping. Key endometrial receptivity gene transcripts are also reported to change in endometrial glands of women with recurrent pregnancy loss. The endometrial gland cilia and PAEP targets identified in this study could be used to identify a perturbed endometrium, isolate causes of recurrent pregnancy loss and develop targeted therapies in personalised medicine.
Implications of taxonomic and numerical resolution on DNA metabarcoding-based inference of benthic macroinvertebrate responses to river restoration

Exploring and clearly defining the level of taxonomic identification and quantification approaches for diversity and biomonitoring studies are essential, given its potential influence on the assessment and interpretation of ecological outcomes. In this study, we evaluated the response of benthic macroinvertebrate communities to the restoration or construction of gravel bars conducted in the dam-impacted Trinity River, with the non-dam influenced tributaries serving as the reference sites. We aim to evaluate the performance of different taxonomic and numerical (i.e., abundance vs. presence/absence data) resolutions of DNA metabarcoding with consequent comparison to morphology-based identification and how it affects assessment outcomes. DNA metabarcoding detected 93% of the morphologically identified individuals and provided finer taxonomic resolution. We also detected significant correlations between morphological sample abundance, biomass, and DNA metabarcoding read abundance. We observed a relatively high and significant congruence in macroinvertebrate community structure and composition between different taxonomic and numerical resolutions of both methods, indicating a satisfactory surrogacy between the two approaches and their varying identification levels and data transformation. Additionally, the community-environmental association were significant for all datasets but showed varying significant associations against the physicochemical parameters. Furthermore, both methods identified Simulium spp. as significant indicators of the dam-impacted gravel bars. Still, only DNA metabarcoding showed significant false discovery rate proving the method’s robustness compared to morphology-based identification. Our observations imply that coarser taxonomic resolution could be highly advantageous to DNA metabarcoding-based applications in situations where the lack of taxonomic information, e.g., poor reference database, might severely affect the quality of biological assessments.
A model-guided pipeline for drug cardiotoxicity screening with human stem-cell derived cardiomyocytes

New therapeutic compounds go through a preclinical drug cardiotoxicity screening process that is overly conservative and provides limited mechanistic insight, leading to the misclassification of potentially beneficial drugs as proarrhythmic. There is a need to develop a screening paradigm that maintains this high sensitivity, while ensuring non-cardiotoxic compounds pass this phase of the drug approval process. In this study, we develop an in vitro-in silico pipeline using human induced stem-cell derived cardiomyocytes (iPSC-CMs) to address this problem. The pipeline includes a model-guided optimization that produces a voltage-clamp (VC) protocol to determine drug block of seven cardiac ion channels. Such VC data, along with action potential (AP) recordings, were acquired from iPSC-CMs before and after treatment with a control solution or a low-, intermediate-, or high-risk drug. We identified significant AP prolongation (a proarrhythmia indicator) in two high-risk drugs and, from the VC data, determined strong ion channel blocks that led to the AP changes. The VC data also uncovered an undocumented funny current (If) block by quinine, which we confirmed with experiments using a HEK-293 expression line. We present a new approach to cardiotoxicity screening that simultaneously evaluates proarrhythmia risk (e.g. AP prolongation) and mechanism (e.g. channel block) from iPSC-CMs.
A detailed one-dimensional model to predict the unsteady behavior of turbocharger turbines for internal combustion engine applications

This article describes an investigation of the unsteady behavior of turbocharger turbines by one-dimensional modeling and experimental analysis. A one-dimensional model has been developed to predict the performance of a vaneless radial-inflow turbine submitted to unsteady flow conditions. Different from other approaches proposed in the literature, the turbine has been simulated by separating the effects of casing and rotor on the unsteady flow and by modeling the multiple rotor entries from the volute. This is a simple and effective way to represent the turbine volute by a network of one-dimensional pipes, in order to capture the mass storage effect due to the system volume, as well as the circumferential variation of fluid dynamic conditions along the volute, responsible for variable admittance of mass into the rotor through blade passages. The method developed is described, and the accuracy of the one-dimensional model is shown by comparing predicted results with measured data, achieved on a test rig dedicated to the investigation of automotive turbochargers. The validation of the code is presented and an analysis of the flow unsteadiness, based on a variety of parameters, is proposed.
The Xer activation factor of TLCΦ expands the possibilities for Xer recombination

Many mobile elements take advantage of the highly-conserved chromosome dimer resolution system of bacteria, Xer. They participate in the transmission of antibiotic resistance and pathogenicity determinants. In particular, the toxin-linked cryptic satellite phage (TLCΦ) plays an essential role in the continuous emergence of new toxigenic clones of the Vibrio cholerae strain at the origin of the ongoing 7th cholera pandemic. The Xer machinery is composed of two chromosomally-encoded tyrosine recombinases, XerC and XerD. They resolve chromosome dimers by adding a crossover between sister copies of a specific 28 base pair site of bacterial chromosomes, dif. The activity of XerD depends on a direct contact with a cell division protein, FtsK, which spatially and temporally constrains the process. TLCΦ encodes for a XerD-activation factor (XafT), which drives the integration of the phage into the dif site of the primary chromosome of V. cholerae independently of FtsK. However, XerD does not bind to the attachment site (attP) of TLCΦ, which raised questions on the integration process. Here, we compared the integration efficiency of thousands of synthetic mini-TLCΦ plasmids harbouring different attP sites and assessed their stability in vivo. In addition, we compared the efficiency with which XafT and the XerD activation domain of FtsK drive recombination reactions in vitro. Taken together, our results suggest that XafT promotes the formation of synaptic complexes between canonical Xer recombination sites and imperfect sites.
Comparing heritability estimators under alternative structures of linkage disequilibrium

SNP heritability of a trait is the proportion of its variance explained by the additive effects of the genome-wide single nucleotide polymorphisms (SNPs). The existing approaches to estimate SNP heritability can be broadly classified into two categories. One set of approaches model the SNP effects as fixed effects and the other treats the SNP effects as random effects. These methods make certain assumptions about the dependency among individuals (familial relationship) as well as the dependency among markers (linkage disequilibrium, LD) to provide consistent estimates of SNP heritability as the number of individuals increases. While various approaches have been proposed to account for such dependencies, it remains unclear which estimates reported in the literature are more robust against various model mis-specifications. Here we investigate the impact of different structures of LD and familial relatedness on heritability estimation. We show that the performance of different methods for heritability estimation depends heavily on the structure of the underlying pattern of LD and the degree of relatedness among sampled individuals. However, contrary to the claim in the current literature, we did not find significant differences in the performance of these fixed-SNP-effects and random-SNP-effects approaches. Moreover, we established the equivalence between the two method-of-moments estimators, one from each of these two lines of approaches.
Working memory performance is tied to stimulus complexity

Working memory is the cognitive capability to maintain and process information over short periods. Behavioral and computational studies have shown that visual information is associated with working memory performance. However, the underlying neural correlates remain unknown. To identify how visual information affects working memory performance, we conducted behavioral experiments in pigeons ( Columba livia ) and single unit recordings in the avian prefrontal analog, the nidopallium caudolaterale (NCL). Complex pictures featuring luminance, spatial and color information, were associated with higher working memory performance compared to uniform gray pictures in conjunction with distinct neural coding patterns. For complex pictures, we found a multiplexed neuronal code displaying visual and value-related features that switched to a representation of the upcoming choice during a delay period. When processing gray stimuli, NCL neurons did not multiplex and exclusively represented the choice already during stimulus presentation and throughout the delay period. The prolonged representation possibly resulted in a decay of the memory trace ultimately leading to a decrease in performance. In conclusion, we found that high stimulus complexity is associated with neuronal multiplexing of the working memory representation possibly allowing a facilitated read-out of the neural code resulting in enhancement of working memory performance. An electrophysiological study in pigeons suggests that high stimulus complexity ensues multiplexed representations enabling a delayed switch from stimulus- to choice-coding resulting in stable working memory representations and reduced trace-decay.
Functionalized Organic–Inorganic Liposome Nanocomposites for the Effective Photo-Thermal Therapy of Breast Cancer

Organic–inorganic nanocomposites for photothermal therapy of cancers emerged as a promising strategy against malignant tumors. However, it is still a big challenge to develop a nanocomposite system that can maximize the synergistic photo-thermal therapy effect as well as preserve high stability for simultaneous delivery of the chemotherapeutic drugs and photo-thermal agents. Here, we have exploited an organic liposome containing inorganic core for co-loading the aggregates of bovine serum albumin (BSA), indocyanine green (ICG), and doxorubicin (DOX), abbreviated as BID-liposomal nanocomposites. The three kinds of substances were aggregated in the core of liposomal nanocomposites through hydrophobic and electrostatic interactions. In vitro characterization shows that BID-liposomal nanocomposites were spherical nanoparticles with size of 30–50 nm and good storage stability. Moreover, BID-Liposomal nanocomposites illustrate the strongest cytotoxicity among all the formulations against murine 4T1 tumor cells. In breast cancer-bearing mouse models, BID liposomes lead to significant improvements in tumor inhibition effects with no obvious toxicity. Therefore, the BID-liposomal nanoparticle is believed to be a promising strategy for chemo-photo-thermal therapy against cancers.
Vulnerable Narcissism in Social Networking Sites: The Role of Upward and Downward Social Comparisons

Social networking sites (SNSs) have provided a new platform for people to present their narcissism. The objective of the current study was to investigate the underlying mechanisms between active and passive SNS use and vulnerable narcissism among college students. In achieving this, the study based its method on the media effect and social comparative theory and recruited 529 participants to complete the Surveillance Use Scale, Iowa–Netherlands Comparison Orientation Measure, and Hypersensitivity Narcissistic Scale. The results showed that active and passive SNS use were positively related to upward and downward social comparisons. Active and passive SNS use also indirectly predicted vulnerable narcissism through the parallel mediation of upward and downward social comparisons. This study also revealed the vital role of social comparison in the association between SNS use and vulnerable narcissism.
Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.
Development of a novel system for monitoring tritium in gaseous form

Tritium real-time measurement in glovebox or workplace is important to ensure safe operation of tritium. A novel tritium monitor system including an open-walled ionization chamber, an electrometer and an IPC (Industrial Personal Computer) has been developed to measure tritium in gaseous form. Using mesh walls, instead of sealed wall, the open-walled ionization chamber has less tritium absorption and lower memory effect. In addition, tritium gas can diffuse into the chamber’s sensitive region without the assistant of sampling system and ion trap, which are installed at the front-end of commonly used flow-through ionization chambers. Background signal of this monitor system is about 3.7× 10 Bq/m, and after exposed to tritium concentration at about 10 Bq/m for 4h, background of the monitor can recover after purging it several times with dry air. It is suitable for longtime tritium measurements in both glovebox and workplace.
Construction of a 5 immune-related lncRNA-based prognostic model of NSCLC via bioinformatics

Abstract Participate in tumorigenic, oncogenic, and tumor suppressive pathways through gene expression regulation. We aimed to build an immune-related long noncoding RNA (lncRNA) prognostic model to enhance nonsmall cell lung cancer (NSCLC) prognostic prediction. The original data were collected from the cancer genome atlas database. Perl and R software were used for statistical analysis. The effects of lncRNAs expression on prognosis were analyzed by Gene Expression Profiling Interactive Analysis. Silico functional analysis were performed by DAVID Bioinformatics Resources. The median risk score as a dividing value separated patients into high- and low-risk groups. These 2 groups had different 5-year survival rates, median survival times, and immune statuses. The 5-lncRNA signature was validated as an independent prognostic factor with high accuracy (area under the receiver operating characteristic = 0.722). Silico functional analysis connected the lncRNAs with immune-related biological processes and pathways in carcinogenesis. The novel immune-related lncRNA prognostic model had significant clinical implication for enhancing lung adenocarcinoma outcome prediction and guiding the choice of treatment.
Investigation on the mechanisms of guiqi huoxue capsule for treating cervical spondylosis based on network pharmacology and molecular docking

Supplemental Digital Content is available in the text Abstract Background: Guiqi huoxue capsule (GQHXC) is a patented Chinese medicine used for treating a liver and kidney deficiency and blood stasis syndrome due to qi deficiency. It is caused by cervical spondylosis (cervical spondylotic radiculopathy (CSR), mixed cervical spondylosis mainly composed of nerve root type). Its underlying mechanisms need, however, to be further clarified. Methods: In this study, collecting compounds, predicting therapeutic targets, constructing networks, and analyzing biological functions and pathways were based on network pharmacology analysis. In addition, molecular docking verification was engaged to assess the binding potential of selected target-compound pairs. Results: We established 5 networks: compound-putative target network of GQHXC, protein-protein interaction (PPI) network related to CSR, compound-CSR target network, potential therapeutic targets PPI network, and herb-compound-target-pathway network. Network analysis indicated that 7 targets (tumor necrosis factor [TNF], interleukin 6 [IL6], nitric oxide synthase 3 [NOS3], Interleukin-8 [CXCL8], prostaglandin-endoperoxide synthase 2 [PTGS2], vascular endothelial growth factor A [VEGFA], and AP-1 transcription factor subunit [JUN]) might be the therapeutic targets of GQHXC in CSR. Moreover, molecular docking verification showed that TNF, IL6, NOS3, CXCL8, PTGS2, VEGFA, and JUN had a good is interaction with the corresponding compounds. Furthermore, enrichment analysis indicated that GQHXC might exert a curative role in CSR by regulating some important pathways, such as TNF signaling pathway, NF–kappa B signaling pathway, AGE–RAGE signaling pathway in diabetic complications, and so on. Conclusion: Our study preliminarily explained the underlying mechanisms of GQHXC for treating CSR, and molecular docking verification was adopted as an additional verification. These findings laid a valuable foundation for experimental research and further application of GQHXC in the clinical treatment of CSR.
A protocol for systematic review and network meta-analysis

Background: Neurogenic bladder (NB), a refractory disease, is characterized by voiding dysfunction of bladder and/or urethra, and spinal cord injury (SCI) is a common cause. Chinese medicine therapies have been applied extensively in the treatment of NB, especially in China, and the results are promising but varying. Thus, the aim of this work is to assess the efficacy and safety of various Chinese medicine therapies for NB after SCI. Methods:A retrieval will be performed in 8 online databases (the Cochrane Library, Web of Science, PubMed, EMBASE Database, China Biological Medicine Database, Chinese Scientific Journals Database, Wan Fang databases, and China National Knowledge Infrastructure) from their inception throughout June 2021. Only randomized controlled trials of testing Chinese medicine therapies for NB after SCI will be enrolled. The outcome indicators measured will be overall response rate, urodynamic tests, clinical assessment, and safety assessments. The methodological quality of this Bayesian-based network meta-analysis will be conducted with the “Risk of Bias” tool. Stata14.0 and WinBUGS 1.4. 3 will be used to analyze the data. Furthermore, the assessment of heterogeneity, inconsistency, subgroup, sensitivity, and publication bias will also be taken into consideration with the help of Cochrane Collaboration’s tool. Results: The findings of this study will be submitted to a peer-reviewed journal for publication. Conclusion: This work will furnish evidence-based recommendations to figure out the optimal Chinese medicine therapy or their combinations for NB induced by SCI, and in turn contribute to further research and public health. Abbreviations: IC = intermittent catheterization, NB = neurogenic bladder, NMA = network meta-analysis, RCTs = randomized controlled trials, SCI = spinal cord injury.
Safety, Power Imbalances, Ethics and Proxy Sex: Surveying In-The-Wild Interactions Between VR Users and Bystanders

VR users and bystanders must sometimes interact, but our understanding of these interactions - their purpose, how they are accomplished, attitudes toward them, and where they break down - is limited. This current gap inhibits research into managing or supporting these interactions, and preventing unwanted or abusive activity. We present the results of the first survey (N=100) that investigates stories of actual emergent in-the-wild interactions between VR users and bystanders. Our analysis indicates VR user and bystander interactions can be categorised into one of three categories: coexisting, demoing, and interrupting. We highlight common interaction patterns and impediments encountered during these interactions. Bystanders play an important role in moderating the VR user’s experience, for example intervening to save the VR user from potential harm. However, our stories also suggest that the occlusive nature of VR introduces the potential for bystanders to exploit the vulnerable state of the VR user; and for the VR user to exploit the bystander for enhanced immersion, introducing significant ethical concerns.