Miracle-dz/UniFAR-FTUs huggingface dataset:
Gastrointestinal microphysiological systems

Gastrointestinal diseases are a significant health care and economic burden. Prevention and treatment of these diseases have been limited by the available human biologic models. Microphysiological systems comprise organ-specific human cultures that recapitulate many structural, biological, and functional properties of the organ in smaller scale including aspects of flow, shear stress and chemical gradients. The development of intestinal microphysiological system platforms represents a critical component in improving our understanding, prevention, and treatment of gastrointestinal diseases. This minireview discusses: shortcomings of classical cell culture models of the gastrointestinal tract; human intestinal enteroids as a new model and their advantages compared to cell lines; why intestinal microphysiological systems are needed; potential functional uses of intestinal microphysiological systems in areas of drug development and modeling acute and chronic diseases; and current challenges in the development of intestinal microphysiological systems. Impact statement The development of a gastrointestinal MPS has the potential to facilitate the understanding of GI physiology. An ultimate goal is the integration of the intestinal MPS with other organ MPS. The development and characterization of nontransformed human intestinal cultures for use in MPS have progressed significantly since the inception of the MPS program in 2012, and these cultures are a key component of advancing MPS. Continued efforts are needed to optimize MPS to comprehensively and accurately recapitulate the complexity of the intestinal epithelium within intestinal tissue. These systems will need to include peristalsis, flow, and oxygen gradients, with incorporation of vascular, immune, and nerve cells. Regional cellular organization of crypt and villus areas will also be necessary to better model complete intestinal structure.
Challenges and progress in interpretation of non-coding genetic variants associated with human disease

Genome-wide association studies have shown that the far majority of disease-associated variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes contribute to disease risk. To identify truly causal non-coding variants and their affected target genes remains challenging but is a critical step to translate the genetic associations to molecular mechanisms and ultimately clinical applications. Here we review genomic/epigenomic resources and in silico tools that can be used to identify causal non-coding variants and experimental strategies to validate their functionalities. Impact statement Most signals from genome-wide association studies (GWASs) map to the non-coding genome, and functional interpretation of these associations remained challenging. We reviewed recent progress in methodologies of studying the non-coding genome and argued that no single approach allows one to effectively identify the causal regulatory variants from GWAS results. By illustrating the advantages and limitations of each method, our review potentially provided a guideline for taking a combinatorial approach to accurately predict, prioritize, and eventually experimentally validate the causal variants.
Phasic GABAA‐mediated inhibition

γ‐Aminobutyric acid (GABA) is the main inhibitory transmitter in the central nervous system (CNS) and regulates via GABAA receptors tonic and phasic inhibition. This review focuses on the sequential steps leading to phasic inhibition, including vesicle exocytosis, dynamics of GABA transient in the synaptic cleft, binding to GABAA receptors, opening of anionic channels, and neurotransmitter clearance. For an expanded treatment of this topic see Cherubini E. in Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds), published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).
Hybrid Method Inference for the Construction of Cooperative Regulatory Network in Human

Reconstruction of large scale gene regulatory networks (GRNs in the following) is an important step for understanding the complex regulatory mechanisms within the cell. Many modeling approaches have been introduced to find the causal relationship between genes using expression data. However, they have been suffering from high dimensionality-large number of genes but a small number of samples, overfitting, heavy computation time and low interpretability. We have previously proposed an original Data Mining algorithm Licorn, that infers cooperative regulation network from expression datasets. In this work, we present an extension of Licorn to a hybrid inference method h-Licorn that uses search in both discrete and real valued spaces. Licorn's algorithm, using the discrete space to find cooperative regulation relationships fitting the target gene expression, has been shown to be powerful in identifying cooperative regulation relationships that are out of the scope of most GRN inference methods. Still, as many of related GRN inference techniques, Licorn suffers from a large number of false positives. We propose here an extension of Licorn with a numerical selection step, expressed as a linear regression problem, that effectively complements the discrete search of Licorn. We evaluate a bootstrapped version of h-Licorn on the in silico Dream5 dataset and show that h-Licorn has significantly higher performance than Licorn, and is competitive or outperforms state of the art GRN inference algorithms, especially when operating on small data sets. We also applied h-Licorn on a real dataset of human bladder cancer and show that it performs better than other methods in finding candidate regulatory interactions. In particular, solely based on gene expression data, h-Licorn is able to identify experimentally validated regulator cooperative relationships involved in cancer.
Speaking Stata: Multiple bar Charts in Table form

Tables that are one way, two way, or three way in structure may often be helpfully represented as multiple bar charts. The one, two, or three variables that define the structure of the table thus determine rows, columns, and panels in which bars are arranged. The merits of this design include easy focus on individual values or groups of values; leaving space for numeric information to be shown as in a table; and convenient axis or panel labeling through text rather than through a key or legend. A Stata command for these purposes, tabplot, is discussed systematically.
New recommendations for the treatment of tuberculosis

Purpose of review The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis and to review newer recommendations and common problems encountered in the treatment of patients with tuberculosis. Recent findings Recently published literature documents the increased incidence of multidrug resistant strains of Mycobacterium tuberculosis, the importance of antituberculosis drug toxicities and drug–drug interactions, persistent problems in the correct interpretation of the tuberculin skin test and ongoing problems with treatment compliance and treatment completion. Summary This article provides a practical approach to the interpretation of the tuberculin skin test, the proper approach to the treatment of latent tuberculosis infection, and a structured approach to the treatment of presumed or documented active tuberculosis infection. Questions about tuberculosis that are often asked of infectious disease and pulmonary specialists are addressed in a very practical manner.
Endovascular Treatment of a “Fishy” Ulcer Caused by a Traumatic Arteriovenous Fistula

Arteriovenous fistula secondary to trauma is an uncommon cause of leg ulcers. In this article, an unusual case of a nonhealing leg ulcer caused by a stingray is described. This case highlights the difficulty in diagnosing and treating nonhealing ulcers secondary to arteriovenous fistula.
Identification of a Family of Effectors Secreted by the Type III Secretion System That Are Conserved in Pathogenic Chlamydiae

ABSTRACT Chlamydiae are Gram-negative, obligate intracellular pathogens that replicate within a membrane-bounded compartment termed an inclusion. Throughout their development, they actively modify the eukaryotic environment. The type III secretion (TTS) system is the main process by which the bacteria translocate effector proteins into the inclusion membrane and the host cell cytoplasm. Here we describe a family of type III secreted effectors that are present in all pathogenic chlamydiae and absent in the environment-related species. It is defined by a common domain of unknown function, DUF582, that is present in four or five proteins in each Chlamydiaceae species. We show that the amino-terminal extremity of DUF582 proteins functions as a TTS signal. DUF582 proteins from C. trachomatis CT620, CT621, and CT711 are expressed at the middle and late phases of the infectious cycle. Immunolocalization further revealed that CT620 and CT621 are secreted into the host cell cytoplasm, as well as within the lumen of the inclusion, where they do not associate with bacterial markers. Finally, we show that DUF582 proteins are present in nuclei of infected cells, suggesting that members of the DUF582 family of effector proteins may target nuclear cell functions. The expansion of this family of proteins in pathogenic chlamydiae and their conservation among the different species suggest that they play important roles in the infectious cycle.
Entry of Porphyromonas gingivalis Outer Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment

ABSTRACT Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including proteases termed gingipains (Arg-gingipain [Rgp] and Lys-gingipain [Kgp]). We recently showed that P. gingivalis MVs swiftly enter host epithelial cells via an endocytosis pathway and are finally sorted to lytic compartments. However, it remains unknown whether MV entry impairs cellular function. Herein, we analyzed cellular functional impairment following entry of P. gingivalis into epithelial cells, including HeLa and immortalized human gingival epithelial (IHGE) cells. After being taken up by endocytic vacuoles, MVs degraded the cellular transferrin receptor (TfR) and integrin-related signaling molecules, such as paxillin and focal adhesion kinase (FAK), which resulted in depletion of intracellular transferrin and inhibition of cellular migration. Few Rgp-null MVs entered the cells, and these negligibly degraded TfR, whereas paxillin and FAK degradation was significant. In contrast, Kgp-null MVs clearly entered the cells and degraded TfR, while they scarcely degraded paxillin and FAK. In addition, both wild-type and Kgp-null MVs significantly impaired cellular migration, whereas the effect of Rgp-null MVs was limited. Our findings suggest that, following entry of P. gingivalis MVs into host cells, MV-associated gingipains degrade cellular functional molecules such as TfR and paxillin/FAK, resulting in cellular impairment, indicating that P. gingivalis MVs are potent vehicles for transmission of virulence factors into host cells and are involved in the etiology of periodontitis.
Macrophage Polarization Alters Postphagocytosis Survivability of the Commensal Streptococcus gordonii

ABSTRACT Oral streptococci are generally considered commensal organisms; however, they are becoming recognized as important associate pathogens during the development of periodontal disease as well as being associated with several systemic diseases, including as a causative agent of infective endocarditis. An important virulence determinant of these bacteria is an ability to evade destruction by phagocytic cells, yet how this subversion occurs is mostly unknown. Using Streptococcus gordonii as a model commensal oral streptococcus that is also associated with disease, we find that resistance to reactive oxygen species (ROS) with an active ability to damage phagosomes allows the bacterium to avoid destruction within macrophages. This ability to survive relies not only on the ROS resistance capabilities of the bacterium but also on ROS production by macrophages, with both being required for maximal survival of internalized bacteria. Importantly, we also show that this dependence on ROS production by macrophages for resistance has functional significance: S. gordonii intracellular survival increases when macrophages are polarized toward an activated (M1) profile, which is known to result in prolonged phagosomal ROS production compared to that of alternatively (M2) polarized macrophages. We additionally find evidence of the bacterium being capable of both delaying the maturation of and damaging phagosomes. Taken together, these results provide essential insights regarding the mechanisms through which normally commensal oral bacteria can contribute to both local and systemic inflammatory disease.
Vigilant Keratinocytes Trigger Pathogen-Associated Molecular Pattern Signaling in Response to Streptococcal M1 Protein

ABSTRACT The human skin exerts many functions in order to maintain its barrier integrity and protect the host from invading microorganisms. One such pathogen is Streptococcus pyogenes, which can cause a variety of superficial skin wounds that may eventually progress into invasive deep soft tissue infections. Here we show that keratinocytes recognize soluble M1 protein, a streptococcal virulence factor, as a pathogen-associated molecular pattern to release alarming inflammatory responses. We found that this interaction initiates an inflammatory intracellular signaling cascade involving the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), p38, and Jun N-terminal protein kinase and the subsequent induction and mobilization of the transcription factors NF-κB and AP-1. We also determined the imprint of the inflammatory mediators released, such as interleukin-8 (IL-8), growth-related oncogene alpha, migration inhibitory factor, extracellular matrix metalloproteinase inducer, IL-1α, IL-1 receptor a, and ST2, in response to streptococcal M1 protein. The expression of IL-8 is dependent on Toll-like receptor 2 activity and subsequent activation of the mitogen-activated protein kinases ERK and p38. Notably, this signaling seems to be distinct for IL-8 release, and it is not shared with the other inflammatory mediators. We conclude that keratinocytes participate in a proinflammatory manner in streptococcal pattern recognition and that expression of the chemoattractant IL-8 by keratinocytes constitutes an important protective mechanism against streptococcal M1 protein.
Roadside units deployment for content downloading in vehicular networks

The Vehicular Ad hoc Networks (VANETs) have been recently introduced to provide high-speed Internet access to vehicles by deploying 802.11 enhanced Roadside Units (RSUs) along roads. However, few content downloading oriented RSU deployment strategies have been proposed. In this paper, we propose a new RSU deployment strategy for content downloading in VANETs. The encounters between vehicles and RSUs are modeled as a time continuous homogeneous Markov chain. The optimal inter-meeting time between vehicles and RSUs is analyzed based on the encounter model. Then, the road network is modeled as a weighted undirected graph, and a RSU deployment algorithm is designed based on the depth-first traversal algorithm for edges of a graph. Simulation results show that the proposed RSU deployment algorithm can satisfy the file downloading service requirements with the lowest RSU deployment cost.
Information-centric collaborative data collection for mobile devices in wireless sensor networks

The advancement of smart phones enables mobile users to collect data from their surrounding sensors using short-range wireless communication. However, the limited contact time and the wireless capacity constrain the amount of data to be collected by the mobile users. It is crucial for mobile users to collect sensing data that can maximize their data utility. In this paper, we propose a distributed algorithm to provide information-centric ubiquitous data collection for multiple mobile users. The mobile users construct data collection trees adaptively according to their dynamic moving speeds. They prioritize data collection according to the information value carried by the sensing data. The distributed algorithm can support smooth data collection and coordination among multiple mobile users. We evaluate the data utility, energy efficiency and scalability of our solution with extensive simulations. The results showed that our distributed algorithm can improve information value up to 50% and reduce energy consumption to half compared with the existing approach.
The Transcriptional Regulator CpsY Is Important for Innate Immune Evasion in Streptococcus pyogenes

ABSTRACT As an exclusively human pathogen, Streptococcus pyogenes (the group A streptococcus [GAS]) has specifically adapted to evade host innate immunity and survive in multiple tissue niches, including blood. GAS can overcome the metabolic constraints of the blood environment and expresses various immunomodulatory factors necessary for survival and immune cell resistance. Here we present our investigation of one such factor, the predicted LysR family transcriptional regulator CpsY. The encoding gene, cpsY, was initially identified as being required for GAS survival in a transposon-site hybridization (TraSH) screen in whole human blood. CpsY is homologous with transcriptional regulators of Streptococcus mutans (MetR), Streptococcus iniae (CpsY), and Streptococcus agalactiae (MtaR) that regulate methionine transport, amino acid metabolism, resistance to neutrophil-mediated killing, and survival in vivo. Our investigation indicated that CpsY is involved in GAS resistance to innate immune cells of its human host. However, GAS CpsY does not manifest the in vitro phenotypes of its homologs in other streptococcal species. GAS CpsY appears to regulate a small set of genes that is markedly different from the regulons of its homologs. The differential expression of these genes depends on the growth medium, and CpsY modestly influences their expression. The GAS CpsY regulon includes known virulence factors (mntE, speB, spd, nga [spn], prtS [SpyCEP], and sse) and cell surface-associated factors of GAS (emm1, mur1.2, sibA [cdhA], and M5005_Spy0500). Intriguingly, the loss of CpsY in GAS does not result in virulence defects in murine models of infection, suggesting that CpsY function in immune evasion is specific to the human host.
Using dynamic pseudo-IDs to protect privacy in location-based services

Location-based services (LBSs) are attracting more and more attentions with the increasing popularity of mobile devices and online social networking. In LBSs, users can conveniently obtain their interested information by sending queries to the LBS server. However, users' queries include their identities, locations, interests, etc, which may result in the leakage of users' trajectory and other sensitive information. Although the existing obfuscation and location anonymization techniques along with a long-term pseudonym can protect users' location privacy to some extent, users' real identities and moving trajectories can still be deduced through long-term observation and side information aided inference attacks. To address these problems, we propose a dynamic pseudo-ID system, where unlinkable pseudo-IDs are used by users to completely hide their identities in the queries, in order to break the link between users' identities and their locations. Moreover, we employ certificates to ensure the verifiability and traceability of the dynamic pseudo-IDs. Security analysis and evaluation results show that the proposed scheme can enhance user' privacy and is feasible to implement into mobile devices.
Robust Network Traffic Classification

As a fundamental tool for network management and security, traffic classification has attracted increasing attention in recent years. A significant challenge to the robustness of classification performance comes from zero-day applications previously unknown in traffic classification systems. In this paper, we propose a new scheme of Robust statistical Traffic Classification (RTC) by combining supervised and unsupervised machine learning techniques to meet this challenge. The proposed RTC scheme has the capability of identifying the traffic of zero-day applications as well as accurately discriminating predefined application classes. In addition, we develop a new method for automating the RTC scheme parameters optimization process. The empirical study on real-world traffic data confirms the effectiveness of the proposed scheme. When zero-day applications are present, the classification performance of the new scheme is significantly better than four state-of-the-art methods: random forest, correlation-based classification, semi-supervised clustering, and one-class SVM.
The Salmonella enterica Serotype Typhi Vi Capsular Antigen Is Expressed after the Bacterium Enters the Ileal Mucosa

ABSTRACT Salmonella enterica serotype Typhi, the etiological agent of typhoid fever, produces the Vi capsular antigen, a virulence factor absent in Salmonella enterica serotype Typhimurium. Previous studies suggest that the capsule-encoding viaB locus reduces inflammatory responses in intestinal tissue; however, there are currently no data regarding the in vivo expression of this locus. Here we implemented direct and indirect methods to localize and detect Vi antigen expression within polarized intestinal epithelial cells and in the bovine ileal mucosa. We report that tviB, a gene necessary for Vi production in S. Typhi, was significantly upregulated during invasion of intestinal epithelial cells in vitro. During infection of bovine ligated loops, tviB was expressed at levels significantly higher in calf tissue than those in the inoculum. The presence of the Vi capsular antigen was detected in calf ileal tissue via fluorescence microscopy. Together, these results support the concept that expression of the Vi capsular antigen is induced when S. Typhi transits from the intestinal lumen into the ileal mucosa.
Cost-Effective Diagnostic Strategies in Patients With a High, Intermediate, or Low Clinical Probability of Pulmonary Embolism

Rapid quantitative D-dimer assays (DD), lower extremity venous duplex ultrasonography (US), and multislice computed tomographic (CT) angiography have been shown to have adequate sensitivities and specificities for diagnostic purpose. The purpose of this study was to evaluate cost-effectiveness of diagnostic strategies for pulmonary embolism (PE) in patients with a high, intermediate, or low clinical probability of PE. A formal cost-effectiveness analysis for the diagnosis of PE was performed. The main outcome measure for effectiveness was 3-month expected survival. The strategy of DD followed by CT was cost-effective and had the lowest cost per life saved for all patients suspected with PE. The conventional strategy including ventilation and perfusion lung scanning followed by pulmonary angiography (PA) or CT was not cost-effective. The leg US after CT was not also cost-effective. In clinical practice, the individual patient’s condition should be considered when choosing appropriate diagnostic tests.