Miracle-dz/UniFAR-FTUs huggingface dataset:
Polycyclic Aromatic Hydrocarbons Have Adverse Effects on Benthic Communities in the Baltic Sea: Implications for Environmental Status Assessment

Changes in benthic macrofaunal communities are indicative of environmental stressors, including eutrophication and hypoxia. However, some species are sensitive not only to hypoxia but also to various environmental contaminants. We tested which of the environmental predictors (sediment organic carbon, sediment concentrations of metals and polyaromatic hydrocarbons [PAHs], bottom water oxygen, salinity, temperature, and surface chlorophyll-a concentration) that best explained the following response variables: (1) macrofauna community composition, (2) abundance of a benthic sentinel species, the amphipod Monoporeia affinis; and (3) the Benthic Quality Index (BQI). All data originated from 29 reference monitoring stations in the Baltic Sea and the statistical tests included both uni- and multivariate analyses. The community composition and BQI were best explained by the same combination of salinity, depth, temperature and PAH concentrations. The abundance of M. affinis, which is sensitive to hypoxia and chemical exposure, was best explained by PAHs as a single predictor. Our findings suggest that benthic communities in the Baltic Sea are influenced by anthropogenic contaminants, which should be taken into account when benthos is used for eutrophication status assessment.
A Highly Sensitive and Specific Probe-Based Real-Time PCR for the Detection of Avibacterium paragallinarum in Clinical Samples From Poultry

Avibacterium paragallinarum (historically called Hemophilus paragallinarum) causes infectious coryza (IC), which is an acute respiratory disease of chickens. Recently, outbreaks of IC have been reported in Pennsylvania (PA) in broilers, layer pullets, and laying hens, causing significant respiratory disease and production losses. A tentative diagnosis of IC can be made based on history, clinical signs, and characteristic gross lesions. However, isolation and identification of the organism are required for a definitive diagnosis. Major challenges with the bacteriological diagnosis of A. paragallinarum include that the organism is difficult to isolate, slow-growing, and can only be successfully isolated during the acute stage of infection and secondary bacterial infections are also common. As there were very limited whole genomes of A. paragallinarum in the public databases, we carried out whole-genome sequencing (WGS) of PA isolates and based on the WGS data analysis; we designed a novel probe-based PCR assay targeting a highly conserved sequence in the recN, the DNA repair protein gene of A. paragallinarum. The assay includes an internal control, with a limit of detection (LOD) of 3.93 genomic copies. The PCR efficiency ranged between 90 and 97%, and diagnostic sensitivity of 98.5% compared with conventional gel-based PCR. The test was highly specific, and no cross-reactivity was observed with other species of Avibacterium and a range of other common poultry respiratory viral and bacterial pathogens. Real-time PCR testing on 419 clinical samples from suspected flocks yielded 94 positives and 365 negatives in agreement with diagnostic bacterial culture-based detection. We also compared the recN PCR assay with a previous HPG-2 based real-time PCR assay which showed a PCR efficiency of 79%.
Microneme Proteins 1 and 4 From Toxoplasma gondii Induce IL-10 Production by Macrophages Through TLR4 Endocytosis

The protozoan parasite Toxoplasma gondii modulates host cell responses to favor its success in the early stage of infections by secreting proteins from its apical organelles. Some of these proteins, including microneme proteins (MICs) 1 and 4, trigger pro-inflammatory host cell responses. The lectins MIC1 and MIC4 interact with N-linked glycans on TLR2 and TLR4, activating NF-κB and producing IL-12, TNF-α, and IL-6. Interestingly, MIC1 and MIC4 also trigger secretion of the anti-inflammatory cytokine IL-10 through mechanisms as yet unknown. Herein, we show that the ability of these MICs to induce macrophages to produce IL-10 depends on TLR4 internalization from the cell surface. Macrophages subjected to blockade of endocytosis by Dynasore continued to release TNF-α, but failed to produce IL-10, in response to MIC1 or MIC4 exposure. Similarly, IL-10 was not produced by Dynasore-conditioned T. gondii-infected macrophages. Furthermore, MIC1- or MIC4-stimulated macrophages gained transient tolerance to LPS. We report a previously undiscovered mechanism by which well-defined T. gondii components inhibit a host inflammatory response.
Predictive Factors for Live Birth in Fresh In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment in Poor Ovarian Reserve Patients Classified by the POSEIDON Criteria

The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into “expected” or “unexpected” groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age (OR 0.901; 95% CI 0.887~0.916; P < 0.001), body mass index (OR 0.963; 95% CI 0.951~0.982; P < 0.001), antral follicle counting (OR 1.049; 95% CI 1.009~1.042; P < 0.001) and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply (OR 0.7; 95% CI 0.7~0.8; P < 0.001). The inflection point of BMI was 23.4 kg/m2, and BMI had a negative correlation with live birth (OR 0.963; 95% CI 0.951~0.982; P < 0.001). The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.
Genome-Wide Association Studies Reveal All-Stage Rust Resistance Loci in Elite Durum Wheat Genotypes

Leaf rust, caused by Puccinia triticina (Pt), stripe rust caused by Puccinia striiformis f. sp. tritici (Pst), and stem rust caused by Puccinia graminis f. sp. tritici (Pgt) are major diseases to wheat production globally. Host resistance is the most suitable approach to manage these fungal pathogens. We investigated the phenotypic and genotypic structure of resistance to leaf rust, stem rust, and stripe rust pathogen races at the seedling stage in a collection of advanced durum wheat breeding lines and cultivars adapted to Upper Mid-West region of the United States. Phenotypic evaluation showed that the majority of the durum wheat genotypes were susceptible to Pt isolates adapted to durum wheat, whereas all the genotypes were resistant to common wheat type-Pt isolate. The majority of genotypes were resistant to stripe rust and stem rust pathogen races. The durum panel genotyped using Illumina iSelect 90 K wheat SNP assay was used for genome-wide association mapping (GWAS). The GWAS revealed 64 marker-trait associations (MTAs) representing six leaf rust resistance loci located on chromosome arms 2AS, 2AL, 5BS, 6AL, and 6BL. Two of these loci were identified at the positions of Lr52 and Lr64 genes, whereas the remaining loci are most likely novel. A total of 46 MTAs corresponding to four loci located on chromosome arms 1BS, 5BL, and 7BL were associated with stripe rust response. None of these loci correspond to designated stripe rust resistance genes. For stem rust, a total of 260 MTAs, representing 22 loci were identified on chromosome arms 1BL, 2BL, 3AL, 3BL, 4AL, 5AL, 5BL, 6AS, 6AL, 6BL, and 7BL. Four of these loci were located at the positions of known genes/alleles (Sr7b, Sr8155B1, Sr13a, and Sr13b). The discovery of known and novel rust resistance genes and their linked SNPs will help diversify rust resistance in durum wheat.
Influence of False Self-Presentation on Mental Health and Deleting Behavior on Instagram: The Mediating Role of Perceived Popularity

The present study explored motivations (need for approval, impression management) for lying self-presentation on Instagram as well as the mental and behavioral outcomes (depression, perceived popularity, deleting behavior on Instagram) of this presentation. We also examined the differential mediational roles of perceived popularity in accounting for the association between lying self-presentation and depression. Our results showed that individuals with a strong need for approval reported higher levels of lying self-presentation. The results also revealed that lying self-presentation positively influenced depression, perceived popularity and deleting behaviors. Furthermore, we found that even if lying self-presentation increased depression, perceived popularity served as a psychological buffer against depression.
ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis

Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.
Potential Mechanism Prediction of Herbal Medicine for Pulmonary Fibrosis Associated with SARS-CoV-2 Infection Based on Network Analysis and Molecular Docking

Background: Coronavirus Disease 2019 (COVID-19) is still a relevant global problem. Although some patients have recovered from COVID-19, the sequalae to the SARS-CoV-2 infection may include pulmonary fibrosis, which may contribute to considerable economic burden and health-care challenges. Convalescent Chinese Prescription (CCP) has been widely used during the COVID-19 recovery period for patients who were at high risk of pulmonary fibrosis and is recommended by the Diagnosis and Treatment Protocol for COVID-19 (Trial Version sixth, seventh). However, its underlying mechanism is still unclear. Methods: In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of CCP, data mining of the disease targets, protein-protein interaction (PPI) network construction, and analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of CCP for pulmonary fibrosis associated with SARS-CoV-2 infection. Results: The active compound of CCP and the candidate targets, including pulmonary fibrosis targets, were obtained through database mining. The Drug-Disease network was constructed. Sixty-five key targets were identified by topological analysis. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the VEGF, Toll-like 4 receptor, MAPK signaling pathway, and TGF-β1 signaling pathways may be involved in pulmonary fibrosis. In the molecular docking analyses, VEGF, TNF-α, IL-6, MMP9 exhibited good binding activity. Findings from our study indicated that CCP could inhibit the expression of VEGF, TNF-α, IL-6, MMP9, TGF-β1 via the VEGF, Toll-like 4 receptor, MAPK, and TGF-β1 signaling pathways. Conclusion: Potential mechanisms involved in CCP treatment for COVID-19 pulmonary fibrosis associated with SARS-CoV-2 infection involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of CCP.
Two Acinetobacter baumannii Isolates Obtained From a Fatal Necrotizing Fasciitis Infection Display Distinct Genomic and Phenotypic Characteristics in Comparison to Type Strains

Acinetobacter baumannii has been recognized as a critical pathogen that causes severe infections worldwide not only because of the emergence of extensively drug-resistant (XDR) derivatives, but also because of its ability to persist in medical environments and colonize compromised patients. While there are numerous reports describing the mechanisms by which this pathogen acquires resistance genes, little is known regarding A. baumannii’s virulence functions associated with rare manifestations of infection such as necrotizing fasciitis, making the determination and implementation of alternative therapeutic targets problematic. To address this knowledge gap, this report describes the analysis of the NFAb-1 and NFAb-2 XDR isolates, which were obtained at two time points during a fatal case of necrotizing fasciitis, at the genomic and functional levels. The comparative genomic analysis of these isolates with the ATCC 19606T and ATCC 17978 strains showed that the NFAb-1 and NFAb-2 isolates are genetically different from each other as well as different from the ATCC 19606T and ATCC 17978 clinical isolates. These genomic differences could be reflected in phenotypic differences observed in these NFAb isolates. Biofilm, cell viability and flow cytometry assays indicate that all tested strains caused significant decreases in A549 human alveolar epithelial cell viability with ATCC 17978, NFAb-1 and NFAb-2 producing significantly less biofilm and significantly more hemolysis and capacity for intracellular invasion than ATCC 19606T. NFAb-1 and NFAb-2 also demonstrated negligible surface motility but significant twitching motility compared to ATCC 19606T and ATCC 17978, likely due to the presence of pili exceeding 2 µm in length, which are significantly longer and different from those previously described in the ATCC 19606T and ATCC 17978 strains. Interestingly, infection with cells of the NFAb-1 isolate, which were obtained from a premortem blood sample, lead to significantly higher mortality rates than NFAb-2 bacteria, which were obtained from postmortem tissue samples, when tested using the Galleria mellonella in vivo infection model. These observations suggest potential changes in the virulence phenotype of the A. baumannii necrotizing fasciitis isolates over the course of infection by mechanisms and cell processes that remain to be identified.
Removal of Electrocardiogram Artifacts From Local Field Potentials Recorded by Sensing-Enabled Neurostimulator

Sensing-enabled neurostimulators are an advanced technology for chronic observation of brain activities, and show great potential for closed-loop neuromodulation and as implantable brain-computer interfaces. However, local field potentials (LFPs) recorded by sensing-enabled neurostimulators can be contaminated by electrocardiogram (ECG) signals due to complex recording conditions and limited common-mode-rejection-ratio (CMRR). In this study, we propose a solution for removing such ECG artifacts from local field potentials (LFPs) recorded by a sensing-enabled neurostimulator. A synchronized monopolar channel was added as an ECG reference, and two pre-existing methods, i.e., template subtraction and adaptive filtering, were then applied. ECG artifacts were successfully removed and the performance of the method was insensitive to residual stimulation artifacts. This approach to removal of ECG artifacts broadens the range of applications of sensing-enabled neurostimulators.
Heart Rate Changes Before, During, and After Treadmill Walking Exercise in Normal Dogs

In dogs, changes in heart rate (HR) can reflect conditioning, fear, anticipation, and pain; however, these are not routinely assessed in veterinary rehabilitation patients. Knowing the expected HR changes during rehabilitation exercises can guide protocols and can optimize post-operative therapy. The primary objectives of the study were to assess HR in dogs undergoing treadmill exercise (TE) during the walk and to compare the three collection techniques of HR, namely, auscultation, a HR monitor (HR MONITOR), and a Holter monitor (HOLTER). We hypothesized that the HR would increase by 20% during TE, that HR taken after TE would not be the same as the HR during TE, and that all methods of measurement would have good agreement. HR was recorded in all methods simultaneously, in eight adult healthy large breed dogs during rest (REST), immediately before TE (PRE), during TE (WALK), and 15 and 60 s after TE (POST-15, POST-60). Statistical analyses included Spearman and Pearson correlations, Bland-Altman analyses, and a repeated measures ANOVA with Sidak's post-hoc test (significant at value of p < 0.05). Increased HR was reflected in TE during WALK, and elevations in HR during WALK were not reflected in POST timepoints. Auscultation was also not possible during WALK. Significant moderate-to-strong correlations existed among all monitoring options at each of the timepoints (rho range = 0.5–0.9, p < 0.05). There were no correlations between peak HR and age or weight. The main limitation of this study is that only healthy and large breed dogs were used. Both monitors captured the increase in HR during exercise and could guide TE regimens to minimize patient risk of injury and to maximize training effectiveness.
Personalised, Rational, Efficacy-Driven Cancer Drug Dosing via an Artificial Intelligence SystEm (PRECISE): A Protocol for the PRECISE CURATE.AI Pilot Clinical Trial

Introduction: Oncologists have traditionally administered the maximum tolerated doses of drugs in chemotherapy. However, these toxicity-guided doses may lead to suboptimal efficacy. CURATE.AI is an indication-agnostic, mechanism-independent and efficacy-driven personalised dosing platform that may offer a more optimal solution. While CURATE.AI has already been applied in a variety of clinical settings, there are no prior randomised controlled trials (RCTs) on CURATE.AI-guided chemotherapy dosing for solid tumours. Therefore, we aim to assess the technical and logistical feasibility of a future RCT for CURATE.AI-guided solid tumour chemotherapy dosing. We will also collect exploratory data on efficacy and toxicity, which will inform RCT power calculations. Methods and analysis: This is an open-label, single-arm, two-centre, prospective pilot clinical trial, recruiting adults with metastatic solid tumours and raised baseline tumour marker levels who are planned for palliative-intent, capecitabine-based chemotherapy. As CURATE.AI is a small data platform, it will guide drug dosing for each participant based only on their own tumour marker levels and drug doses as input data. The primary outcome is the proportion of participants in whom CURATE.AI is successfully applied to provide efficacy-driven personalised dosing, as judged based on predefined considerations. Secondary outcomes include the timeliness of dose recommendations, participant and physician adherence to CURATE.AI-recommended doses, and the proportion of clinically significant dose changes. We aim to initially enrol 10 participants from two hospitals in Singapore, perform an interim analysis, and consider either cohort expansion or an RCT. Recruitment began in August 2020. This pilot clinical trial will provide key data for a future RCT of CURATE.AI-guided personalised dosing for precision oncology. Ethics and dissemination: The National Healthcare Group (NHG) Domain Specific Review Board has granted ethical approval for this study (DSRB 2020/00334). We will distribute our findings at scientific conferences and publish them in peer-reviewed journals. Trial registration number: NCT04522284
Higher Risk for Sjögren’s Syndrome in Patients With Fibromyalgia: A Nationwide Population-Based Cohort Study

Objectives Clinically, associations have been observed between Sjögren’s syndrome and fibromyalgia. Nonetheless, population-based evidence evaluating the risk of Sjögren’s syndrome in fibromyalgia patients is lacking. The main purpose of this retrospective cohort study was to determine the association between fibromyalgia and subsequent development of Sjögren’s syndrome. Methods This retrospective cohort study extracted data from the Longitudinal Health Insurance Database (LHID) of the Taiwan National Health Insurance (NHI). During 2000-2012, patients with newly-diagnosed fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1) were defined as the exposure cohort. Age- and gender-matched individuals without fibromyalgia were used as the comparison cohort. The adjusted hazard ratios (aHR) for the occurrence of Sjögren’s syndrome in those with fibromyalgia were evaluated along with stratified analyses of different subgroups. Results Of the 149,706 subjects whose data were extracted from the LHID, 74,853 subjects had coded fibromyalgia and 74,853 control subjects were without fibromyalgia. Compared to the control group, patients with fibromyalgia had an aHR of 2.00 (95% Confidence Interval [CI], 1.52-2.61) for developing Sjögren’s syndrome. In fibromyalgia patients aged 20-49 years, the aHR for future Sjögren’s syndrome was 3.07 (95% CI, 1.92-4.89). Conclusion Patients with fibromyalgia, both males and females, have a higher risk for developing Sjögren’s syndrome than those without fibromyalgia, especially those aged 20-49 years. While managing patients, clinicians should be aware of the bidirectional association between the two diseases, which helps to understand the impact of the association on disease activity and diagnosis.