Miracle-dz/UniFAR-FTUs huggingface dataset:
Open Agile text mining for bioinformatics: the PubAnnotation ecosystem

Abstract Motivation Most currently available text mining tools share two characteristics that make them less than optimal for use by biomedical researchers: they require extensive specialist skills in natural language processing and they were built on the assumption that they should optimize global performance metrics on representative datasets. This is a problem because most end-users are not natural language processing specialists and because biomedical researchers often care less about global metrics like F-measure or representative datasets than they do about more granular metrics such as precision and recall on their own specialized datasets. Thus, there are fundamental mismatches between the assumptions of much text mining work and the preferences of potential end-users. Results This article introduces the concept of Agile text mining, and presents the PubAnnotation ecosystem as an example implementation. The system approaches the problems from two perspectives: it allows the reformulation of text mining by biomedical researchers from the task of assembling a complete system to the task of retrieving warehoused annotations, and it makes it possible to do very targeted customization of the pre-existing system to address specific end-user requirements. Two use cases are presented: assisted curation of the GlycoEpitope database, and assessing coverage in the literature of pre-eclampsia-associated genes. Availability and implementation The three tools that make up the ecosystem, PubAnnotation, PubDictionaries and TextAE are publicly available as web services, and also as open source projects. The dictionaries and the annotation datasets associated with the use cases are all publicly available through PubDictionaries and PubAnnotation, respectively.
Predicting disease‐associated genes: Computational methods, databases, and evaluations

Complex diseases are associated with a set of genes (called disease genes), the identification of which can help scientists uncover the mechanisms of diseases and develop new drugs and treatment strategies. Due to the huge cost and time of experimental identification techniques, many computational algorithms have been proposed to predict disease genes. Although several review publications in recent years have discussed many computational methods, some of them focus on cancer driver genes while others focus on biomolecular networks, which only cover a specific aspect of existing methods. In this review, we summarize existing methods and classify them into three categories based on their rationales. Then, the algorithms, biological data, and evaluation methods used in the computational prediction are discussed. Finally, we highlight the limitations of existing methods and point out some future directions for improving these algorithms. This review could help investigators understand the principles of existing methods, and thus develop new methods to advance the computational prediction of disease genes.
Brucella Periplasmic Protein EipB Is a Molecular Determinant of Cell Envelope Integrity and Virulence

Brucella species cause brucellosis, a global zoonosis. A gene encoding a conserved DUF1849-family protein, which we have named EipB, is present in all sequenced Brucella and several other genera in the class Alphaproteobacteria. The manuscript provides the first functional and structural characterization of a DUF1849 protein. We show that EipB is secreted to the periplasm where it forms a spiral-shaped antiparallel β protein that is a determinant of cell envelope integrity in vitro and virulence in an animal model of disease. eipB genetically interacts with ttpA, which also encodes a periplasmic protein. We propose that EipB and TtpA function as part of a system required for cell envelope homeostasis in select Alphaproteobacteria. ABSTRACT The Gram-negative cell envelope is a remarkable structure with core components that include an inner membrane, an outer membrane, and a peptidoglycan layer in the periplasmic space between. Multiple molecular systems function to maintain integrity of this essential barrier between the interior of the cell and its surrounding environment. We show that a conserved DUF1849 family protein, EipB, is secreted to the periplasmic space of Brucella species, a monophyletic group of intracellular pathogens. In the periplasm, EipB folds into an unusual 14-stranded β-spiral structure that resembles the LolA and LolB lipoprotein delivery system, though the overall fold of EipB is distinct from LolA/LolB. Deletion of eipB results in defects in Brucella cell envelope integrity in vitro and in maintenance of spleen colonization in a mouse model of Brucella abortus infection. Transposon disruption of ttpA, which encodes a periplasmic protein containing tetratricopeptide repeats, is synthetically lethal with eipB deletion. ttpA is a reported virulence determinant in Brucella, and our studies of ttpA deletion and overexpression strains provide evidence that this gene also contributes to cell envelope function. We conclude that eipB and ttpA function in the Brucella periplasmic space to maintain cell envelope integrity, which facilitates survival in a mammalian host. IMPORTANCE Brucella species cause brucellosis, a global zoonosis. A gene encoding a conserved DUF1849-family protein, which we have named EipB, is present in all sequenced Brucella and several other genera in the class Alphaproteobacteria. The manuscript provides the first functional and structural characterization of a DUF1849 protein. We show that EipB is secreted to the periplasm where it forms a spiral-shaped antiparallel β protein that is a determinant of cell envelope integrity in vitro and virulence in an animal model of disease. eipB genetically interacts with ttpA, which also encodes a periplasmic protein. We propose that EipB and TtpA function as part of a system required for cell envelope homeostasis in select Alphaproteobacteria.
Bioprospection of anti‐inflammatory phytochemicals suggests rutaecarpine and quinine as promising 15‐lipoxygenase inhibitors

15‐Lipoxygenase (15‐LOX) belongs to the family of nonheme iron containing enzymes that catalyzes the peroxidation of polyunsaturated fatty acids (PUFAs) to generate eicosanoids that play an important role in signaling pathways. The role of 15‐LOX has been demonstrated in atherosclerosis as well as other inflammatory diseases. In the present study, drug‐like compounds were first screened from a set of anti‐inflammatory phytochemicals based on Lipinski's rule of five (ROF) and in silico toxicity filters. Two lead compounds‐quinine (QUIN) and rutaecarpine (RUT) were shortlisted by analyzing molecular interactions and binding energies of the filtered compounds with the target using molecular docking. Molecular dynamics simulation studies indicate stable trajectories of apo_15‐LOX and docked complexes (15‐LOX_QUIN and 15‐LOX_RUT). In vitro 15‐LOX inhibition studies shows that both QUIN and RUT have lower inhibitory concentration (IC50) value than the control (quercetin). Both QUIN and RUT exhibit moderate antioxidant activities. The cell viability study of these compounds suggests no significant toxicity in HEK‐293 cell lines. Further, QUIN and RUT both did not show any inhibition against selected Gram‐positive and Gram‐negative bacterial species. Thus, based on our present findings, rutaecarpine and quinine may be suggested as promising 15‐LOX inhibitor for the prevention of the atherosclerosis development.
A rapid high-performance liquid chromatography separation of a new anthocyanin from Nitraria tangutorum

Abstract In this work, a rapid high-performance liquid chromatography method was developed to efficiently purify anthocyanin from Nitraria tangutorum based on reversed-phase column. A new anthocyanin was purified from N. tangutorum and elucidated on the basis of extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance, as well as high-resolution mass spectrometry (HR-MS) data. The new anthocyanin was elucidated as cyanidin 3-[2″-(6‴-coumaroyl)-glucosyl]-glucoside. Graphical Abstract
The unique photosynthetic apparatus of Pinaceae: analysis of photosynthetic complexes in Picea abies

Abstract Pinaceae are the predominant photosynthetic species in boreal forests, but so far no detailed description of the protein components of the photosynthetic apparatus of these gymnosperms has been available. In this study we report a detailed characterization of the thylakoid photosynthetic machinery of Norway spruce (Picea abies (L.) Karst). We first customized a spruce thylakoid protein database from translated transcript sequences combined with existing protein sequences derived from gene models, which enabled reliable tandem mass spectrometry identification of P. abies thylakoid proteins from two-dimensional large pore blue-native/SDS-PAGE. This allowed a direct comparison of the two-dimensional protein map of thylakoid protein complexes from P. abies with the model angiosperm Arabidopsis thaliana. Although the subunit composition of P. abies core PSI and PSII complexes is largely similar to that of Arabidopsis, there was a high abundance of a smaller PSI subcomplex, closely resembling the assembly intermediate PSI* complex. In addition, the evolutionary distribution of light-harvesting complex (LHC) family members of Pinaceae was compared in silico with other land plants, revealing that P. abies and other Pinaceae (also Gnetaceae and Welwitschiaceae) have lost LHCB4, but retained LHCB8 (formerly called LHCB4.3). The findings reported here show the composition of the photosynthetic apparatus of P. abies and other Pinaceae members to be unique among land plants.
Pharmacomicrobiomics: The Holy Grail to Variability in Drug Response?

The human body, with 3.0 × 1013 cells and more than 3.8 × 1013 microorganisms, has nearly a one‐to‐one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents, i.e., pharmacomicrobiomics, has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics, and chemotherapeutic agents to human disease and treatment outcomes. We also discuss the significance of studying diet–gene–drug interactions and further address the key challenges associated with pharmacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other ‐omics data, and provide approaches to elucidate microbiome–drug interactions to improve future translation to personalized medicine.
The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down‐regulation and mitochondrial dynamics alteration

The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin‐related protein‐1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8‐week rapid atrial pacing or 4‐week rapid atrial pacing and 4‐week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin‐II and angiotensin‐II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down‐regulating MCU and up‐regulating DNM1L/Drp1. Cell stretching reversed the angiotensin‐II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down‐regulated MCU, up‐regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin‐II‐induced cellular enlargement.
Oily wastewater treatment using membrane bioreactor

A novel implementation of a membrane bioreactor (MBR) has been studied in this paper. It is utilised as combination of rotating biological contractor (RBC) and an external membrane for oily wastewater treatment. The performance of MBR was compared with the standalone RBC. The RBC used in this investigation is the same one combined with the membrane to form the MBR. Wastewater biodegradability has been evaluated by two factors: chemical oxygen demand (COD) and total petroleum hydrocarbon (TPH). They are both compared together for different hydraulic retention times (HRTs) and petroleum pollution concentrations in RBC and MBR. The ratio of TPH to COD of molasses has been varied between 0.2 to 0.8 at two HRTs of 18 and 24 h while the temperature, pH and dissolved oxygen were kept in the range of 20–25°C, 6.5–7.5, and 2–3.5 mg/L, respectively. Optimal TPH removal efficiency (99%) observed at TPH/COD = 0.6 and HRT = 24 h in MBR. The experimental results showed that MBR had higher treatment efficiency than RBC at all ratios and HRTs.
Disposition toward privacy and information disclosure in the context of emerging health technologies

Abstract Objective We sought to present a model of privacy disposition and its development based on qualitative research on privacy considerations in the context of emerging health technologies. Materials and Methods We spoke to 108 participants across 44 interviews and 9 focus groups to understand the range of ways in which individuals value (or do not value) control over their health information. Transcripts of interviews and focus groups were systematically coded and analyzed in ATLAS.ti for privacy considerations expressed by respondents. Results Three key findings from the qualitative data suggest a model of privacy disposition. First, participants described privacy related behavior as both contextual and habitual. Second, there are motivations for and deterrents to sharing personal information that do not fit into the analytical categories of risks and benefits. Third, philosophies of privacy, often described as attitudes toward privacy, should be classified as a subtype of motivation or deterrent. Discussion This qualitative analysis suggests a simple but potentially powerful conceptual model of privacy disposition, or what makes a person more or less private. Components of privacy disposition are identifiable and measurable through self-report and therefore amenable to operationalization and further quantitative inquiry. Conclusions We propose this model as the basis for a psychometric instrument that can be used to identify types of privacy dispositions, with potential applications in research, clinical practice, system design, and policy.
Multi‐tasking as an ancient skill: When one gene does many things well

Multi‐tasking is in our DNA. Many genes perform more than one function, and the question is how well it can do them all. Pleiotropy is frequently considered to be an adaptive constraint that prevents optimal phenotypes from evolving because of antagonistic indirect selection acting on genetically correlated traits. However, as geneticists increasingly study the effects of genes under more realistic natural environments, even the most well studied genes are expressing fascinating pleiotropic effects. Pleiotropy appears to be utterly common. The genes involved in the regulation of flowering time in Arabidopsis thaliana, such as FLOWERING LOCUS C (FLC), offer case examples of such pleiotropy. Studying an ortholog of FLC in Arabis alpina, PERPETUAL FLOWERING 1 (PEP1), Hughes, Soppe and Albani (2019) present evidence that such pleiotropy in flowering‐time genes persists through taxonomic diversification, albeit the precise function of the genes has evolved in response to taxon‐specific natural selection. Their observation that trait‐specific function can evolve even in highly pleiotropic genes suggests that pleiotropy may not constrain adaptation as much as is commonly assumed.
An Unusual Presentation of Merkel Cell Carcinoma in a HIV Patient: A Case Report and Literature Review

Merkel cell carcinoma (MCC) is a rare, rapidly growing, aggressive neuroendocrine skin cancer that generally arises on sun-exposed areas of body such as head, neck, upper limbs, and shoulders of people with light complexity. Typically, MCC presents as shiny, flesh-colored or bluish-red, intracutaneous nodule, possibly with ulceration or crusting. In most of the cases, there is an association with Merkel cell polyomavirus. Even though these are very aggressive tumors, early detection and treatment has always given favorable outcome. There seems to be no consensus in definite prognostic markers, and advanced stages have the worst outcome even with treatment. There has been a recent trend in using PD-I/PD-L1 target therapy rather than chemotherapy in these cancers and have shown to improve survival by many months. In this article, we report a very unusual presentation of MCC first found on left frontoparietal skull as an 8-cm diameter fixed, subcutaneous mass without any typical features of MCC and was found to have metastatic spread to lung and liver. The patient was treated with palliative radiotherapy to brain and chemotherapy with cisplatin/etoposide with addition of immunotherapy later.
Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Abstract Aims Transthyretin amyloidosis (ATTR amyloidosis) is a heterogeneous disorder with cardiac, neurologic, and mixed phenotypes. We describe the phenotypic and genotypic profiles of this disease in continental Western Europe as it appears from the Transthyretin Amyloidosis Survey (THAOS). Methods and results THAOS is an ongoing, worldwide, longitudinal, observational survey established to study differences in presentation, diagnosis, and natural history in ATTR amyloidosis subjects. At data cut-off, 1411 symptomatic subjects from nine continental Western European countries were enrolled in THAOS [1286 hereditary (ATTRm) amyloidosis; 125 wild-type ATTR (ATTRwt) amyloidosis]. Genotypes and phenotypes varied notably by country. Four mutations (Val122Ile, Leu111Met, Thr60Ala, and Ile68Leu), and ATTRwt, were associated with a mainly cardiac phenotype showing symmetric left ventricular (LV) hypertrophy, normal diastolic LV dimensions and volume, and mildly depressed LV ejection fraction (LVEF). Morphologic and functional abnormalities on echocardiogram were significantly more severe in subjects with cardiac (n‘= 210), compared with a mixed (n = 298), phenotype: higher median (Q1–Q3) interventricular septal thickness [18 (16–21) vs. 16 (13–20) mm; P = 0.0006]; and more frequent incidence of LVEF <50% (38.1 vs. 17.5%; P = 0.0008). Subjects with cardiac mutations or ATTRwt (or cardiac or mixed phenotype) had a lower survival rate than subjects in other genotype (or the neurologic phenotype) categories (P < 0.0001, for both). Conclusion ATTR amyloidosis genotypes and phenotypes are highly heterogeneous in continental Western Europe. A geographic map of the different disease profiles and awareness that a subset of subjects have a dominant cardiac phenotype, mimicking hypertrophic cardiomyopathy, at presentation can facilitate the clinical recognition of this underdiagnosed disease. Trial registration ClinicalTrials.gov: NCT00628745.
The debated toxic role of aggregated TDP-43 in amyotrophic lateral sclerosis: a resolution in sight?

Cytoplasmic aggregation of TDP-43 is a hallmark of ALS, but its role in neurodegeneration remains controversial. After close examination of the current literature, Hergesheimer et al. conclude that TDP-43 aggregation is a major factor in neuronal death in ALS, with potential therapeutic implications.
A bipartite iron-dependent transcriptional regulation of the tryptophan salvage pathway in Chlamydia trachomatis

During infection, pathogens are starved of essential nutrients such as iron and tryptophan by host immune effectors. Without conserved global stress response regulators, how the obligate intracellular bacterium Chlamydia trachomatis arrives at a physiologically similar ‘persistent’ state in response to starvation of either nutrient remains unclear. Here, we report on the iron-dependent regulation of the trpRBA tryptophan salvage pathway in C. trachomatis. Iron starvation specifically induces trpBA expression from a novel promoter element within an intergenic region flanked by trpR and trpB. YtgR, the only known iron-dependent regulator in Chlamydia, can bind to the trpRBA intergenic region upstream of the alternative trpBA promoter to repress transcription. Simultaneously, YtgR binding promotes the termination of transcripts from the primary promoter upstream of trpR. This is the first description of an iron-dependent mechanism regulating prokaryotic tryptophan biosynthesis that may indicate the existence of novel approaches to gene regulation and stress response in Chlamydia.
The relationship between working capital and profitability – evidence from listed food & beverages companies in vietnam

The study explores the relationship between working capital and profitability using data collected from the financial statements of 17 food and beverage companies listed on HOSE and HNX from 2008 to 2017. The three models used in this research are Pooled Ordinary Least Squares, Fixed Effects Model (FEM), Random Effects Model (REM). The results of the model tests show that REM is the most suitable. To enhance the reliability and efficiency of the model, we conduct robustness tests. The findings indicate the presence of heteroskedasticity in the model. Therefore, the adjusted REM with the GLS method is used to handle this issue. The results of the regression analysis reveal that when the average collection period increases, gross operating profit (GOP) decreases and return on assets (ROA) increases; the average payment period has a negative influence on ROA; cash conversion cycle has a negative influence on GOP and when the inventory period increases, ROA and GOP decrease.