Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptive immune defense prevents Bartonella persistence upon trans-placental transmission

Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae in wild-ranging rodent populations. Here we studied an experimental model of Bartonella infection in mice to assess the impact of maternal and newborn immune defense on vertical transmission and bacterial persistence in the offspring, respectively. Congenital infection was frequently observed in B cell-deficient mothers but not in immunocompetent dams, which correlated with a rapid onset of an antibacterial antibody response in infected WT animals. Intriguingly, B cell-deficient offspring with congenital infection exhibited long-term bacteremia whereas B cell-sufficient offspring cleared bacteremia within a few weeks after birth. Clearance of congenital Bartonella infection resulted in immunity against bacterial rechallenge, with the animals mounting Bartonella-neutralizing antibody responses of normal magnitude. These observations reveal a key role for humoral immune defense by the mother and offspring in preventing and eliminating vertical transmission. Moreover, congenital Bartonella infection does not induce humoral immune tolerance but results in anti-bacterial immunity, questioning the contribution of neonatal tolerance to Bartonella prevalence in wild-ranging rodents.
A comparative of the Northern Sea Route (NSR) in commercial and environmental perspective with focus on LNG shipping

3 Acknowledgment: 4 Preface: 5 List of Figures: 9 List of Tables: 10 List of Abbreviations: 11 1.Introduction 12 Background: 12 The search problem: 14 The Research focus: 14 The search questions and objectives: 15 Structure of thesis: . 16 2.Theoretical framework: 17 Arctic Climate Change: 17 Arctic Shipping Routes: 18 The Northern Sea Route and Suez canal Route: . 19 Comparative Economic Potential of Routes: 24 Comparative Environmental Potential of Routes: 26 Liquefied Natural gas (LNG): . 27 LNG value chain: 29 LNG Demand and Supply: 29 Arctic Hydrocarbon Reserves: 31 Norway: 31 Russia: 32 Shale Gas Revolution and LNG: 32
Writing A Built Environment Dissertation Practical Guidance And Examples

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Long term results of three anti-vascular endothelial growth factor agents in pachychoroid neovasculopathy

Abstract Purpose To assess morphological changes and visual results in eyes with pachychoroid neovasculopathy (PNV) that underwent different intravitreal anti-vascular endothelial growth factor (VEGF) agents. Materials and methods This is a retrospective, observational, comparative study that included 76 PNV eyes in 76 patients that were allocated to three groups according to the monotherapy injection procedure, as follows: the intravitreal bevacizumab (IVB) group, intravitreal ranibizumab (IVR) group, and intravitreal aflibercept (IVA) group. Central macular thickness (CMT), best-corrected visual acuity (BCVA), and subfoveal choroidal thickness (SFCT) were measured at baseline, after treatment 1st month, 3rd month, 6th month, and 12th month, and at the final post-treatment examination. Results Mean age of the patients was 57.31 ± 5.91 years (range: 34–67 years). The mean duration of follow-up was 31.50 ± 12.91 months (range: 13–60 months). The IVB group included 30 eyes, the IVR group included 22 eyes, and the IVA group included 24 eyes. There weren’t any significant differences in BCVA changes between the groups at any post-baseline measurement time point. Although CMT did not change significantly in the IVB group from baseline to the final follow-up visit (baseline: 376.33 ± 86.31 µm; final visit: 340.80 ± 122.70 µm) (p = 0.172), CMT did change significantly in the IVA group (baseline: 383.41 ± 131.83 µm; final visit: 297.33 ± 103.81 µm) (p = 0.029) and IVR group (baseline: 379.18 ± 97.93 µm; final visit: 335.72 ± 111.45 µm) (p = 0.041). SFCT decreased significantly in the IVR and IVA groups (p = 0.015 and p < 0.001, respectively). The mean number of injections was 12.06 ± 4.72 (range: 6–20) in the IVB group, 11.81 ± 3.31(range: 7–17) in the IVR group, and 7.16 ± 3.15 (range: 4–13) in the IVA group (p = 0.004). Conclusion All three anti-VEGFs were effective in terms of visual results in patients with PNV. Patients treated with IVA required fewer injections than those treated with IVB or IVR. Furthermore, IVR and IVA treatment significantly decreased SFCT, whereas IVB did not.
A narrative review of psychological theories of post‐traumatic stress disorder, voice hearing, and other psychotic symptoms

Abstract Background Most voice hearers report childhood trauma. Many voice hearers report comorbid post‐traumatic stress symptoms and that the content of their voices (auditory verbal hallucinations) is directly (voices repeat phrases spoken by perpetrators) or indirectly (voice content and trauma is thematically similar) related to their trauma. The factors that maintain trauma‐related voices are unknown, and there is limited research in this area. This study aimed to identify potential maintaining factors of trauma‐related voices by reviewing models of post‐traumatic stress disorder (PTSD) and positive symptoms of psychosis. Method Models of PTSD and positive symptoms were reviewed to identify potential factors that are unique and common to both sets of symptoms. Results We reviewed 10 models of PTSD, 4 models of positive symptoms, and 2 trauma‐informed models of voice hearing. One model provided a theoretical explanation of different types of trauma‐related voices. Twenty‐one factors were extracted from 16 theoretical models. No existing model incorporated all these factors. Discussion Existing PTSD and positive symptom models present a range of common and unique factors. There may be value in extending existing integrative models to include a broader range of potential factors that could explain different pathways to, and expressions of, trauma‐related voices. A future research agenda is presented to investigate how such an extension could lead to more complete individualized case formulations and targeted treatments.
Topical delivery of pluronic F127/TPGS mixed micelles-based hydrogel loaded with glycyrrhizic acid for atopic dermatitis treatment

Abstract Objective The purpose of this study was to develop pluronic F127/d-a-tocopheryl polyethylene glycol 1000 succinate mixed micelles-based hydrogel (MMs-gel) for topical delivery of glycyrrhizic acid (GL) to improve its skin permeability and atopic dermatitis (AD) treatment. Significance GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD. Methods GL-MMs were prepared by thin film hydration method and then loaded into carbopol gel. The formulation of GL-MMs-gel was optimized by full factorial design and systematically characterized for drug content, pH, spreadability, in vitro drug release and percutaneous permeation, etc. The therapeutic effect of GL-MMs-gel was also investigated in AD-like skin lesion model in BALB/c mice and compared with GL solution-based gel (GL-sol–gel). Results Spherical GL-MMs with particle size of ∼30 nm were successfully incorporated into carbopol gel to form GL-MMs-gel with drug content of (98.80 ± 1.30) %, pH of 6.0 ± 0.08, and spreadability of (7.1 ± 0.2) cm. In vitro drug release profile of GL-MMs-gel exhibited a sustained-release behavior. The permeation flux for GL-MMs-gel (5.15 ± 0.33 µg/cm2/h) was significantly higher than that of GL-sol–gel (3.08 ± 0.34 µg/cm2/h) and GL-MMs-gel increased the accumulative amounts of GL in rats’ skin 8.41 times than GL-sol–gel. The GL-MMs-gel was more effective than GL-sol–gel in suppressions of various AD symptoms including skin lesions, edema, high IgE levels, epidermal hyperplasia, and mast cell infiltration. Conclusion All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.
Estimation of the basic reproduction number of Alpha and Delta variants of COVID-19 pandemic in Iran

Estimating the basic reproduction number of a pandemic and the changes that appear on this value over time provide a good understanding of the contagious nature of the virus and efficiency of the controlling strategies. In this paper, we focus on studying the basic reproduction number (R0) for two important variants of COVID-19 pandemic in Iran: Alpha and Delta variants. We use four different methods, three statistical models and one mathematical model, to compute R0: Exponential Growth Rate (EGR), Maximum Likelihood (ML), Sequential Bayesian (SB), and time-dependent SIR model. Alpha variant of COVID-19 was active in Iran from March 10, 2021 until June 10, 2021. Our computations indicate that total R0 of this variant according to EGR, ML, SB, and SIR model is respectively 0.9999 (95% CI: 0.9994-1), 1.046 (95% CI: 1.044-1.049), 1.06 (95% CI: 1.03-1.08), and 2.79 (95% CI: 2.77-2.81) in the whole active time interval. Moreover, during the time interval from April 3, 2021 to April 9, 2021 in which this variant was in its exponential growth in Iran, R0 of Alpha variant in Iran according to SB, EGR, ML, and SIR model is respectively 2.26 (95% CI: 2.04-2.49), 2.64 (95% CI: 2.58-2.7), 11.38 (95% CI: 11.28-11.48), and 12.13 (95% CI: 12.12-12.14). Delta variant was active in Iran during the time interval from June 22, 2021 until September 22, 2021. Our computations show that during the time interval from July 3, 2021 to July 8, 2021 in which this variant was in its exponential growth in Iran, R0 of Delta variant in Iran according to SB, EGR, ML, and SIR model is respectively 3 (95% CI: 2.34-3.66), 3.1 (95% CI: 3.02-3.17), 12 (95% CI: 11.89-12.12), and 23.3 (95% CI: 23.19-23.41). Further, total R0 of Delta variant in Iran in the whole active time interval according to EGR, ML, SB, and SIR model is respectively 1.042 (95% CI: 1.04-1.043), 1.053 (95% CI: 1.051-1.055), 0.79 (95% CI: 0.63-0.95), and 5.65 (95% CI: 5.6-5.7). As the results show Delta variant was more severe than Alpha variant in Iran. Chasing the changes in R0 during each variant shows that the controlling strategies applied were effective in controlling the virus spread.
Incremental Value of Noncontrast Chest Computed Tomography-derived Parameters in Predicting Subclinical Carotid Atherosclerosis

Purpose: To investigate the incremental value of noncontrast chest computed tomography (CT)-derived parameters, such as coronary artery calcium score (CACS) and epicardial adipose tissue volume (EATv), in predicting subclinical carotid atherosclerosis above traditional risk factors in community-based asymptomatic populations of northern China. Materials and Methods: A total of 2195 community-based asymptomatic individuals were enrolled from Jidong Oilfield in accordance with the PERSUADE study. CACS and EATv were measured on noncontrast chest CT. Demographics and ideal cardiovascular health score (ICHS) were collected through questionnaires. We recalculated the ideal cardiovascular health risk score (ICHRS) (ICHRS=14−ICHS) and standardized the parameters as log-CACS and body mass index adjusted EATv (i-EATv). Subclinical carotid atherosclerosis was assessed by Doppler sonography and defined as any prevalence of average carotid intima-media thickness ≥1.00 mm, appearance of carotid plaque, and carotid arterial stenosis in the areas of extracranial carotid arteries on both sides. Results: A total of 451 (20.55%) individuals presented subclinical carotid atherosclerosis. CACS and EATv were significantly greater in the subclinical group, while ICHS was lower. In multivariate logistic regression, ICHRS (odds ratio [OR]=1.143, 95% confidence interval [CI]: 1.080-1.210, P<0.001), log-CACS (OR=1.701, 95% CI: 1.480-1.955, P<0.001), and i-EATv (OR=1.254, 95% CI: 1.173-1.341, P<0.001) were found to be independent risk predictors for subclinical carotid atherosclerosis. In receiver-operating characteristic curve analysis, when combined with male sex and age level, the area under the curve of the ICHRS basic model increased from 0.627 (95% CI: 0.599-0.654) to 0.757 (95% CI: 0.732-0.781) (P<0.0001). Further adding log-CACS and i-EATv, the area under the curve demonstrated a statistically significant improvement (0.788 [95% CI: 0.765-0.812] vs. 0.757 [95% CI: 0.732-0.781], P<0.0001). Conclusion: Noncontrast chest CT-derived parameters, including CACS and EATv, could provide significant incremental improvement for predicting subclinical carotid atherosclerosis beyond the conventional risk assessment model based on ICHRS.
Bioengineered miR-34a modulates mitochondrial inner membrane protein 17 like 2 (MPV17L2) expression toward the control of cancer cell mitochondrial functions

ABSTRACT Genome-derived microRNAs (miRNAs or miRs) control post-transcriptional gene expression critical for various cellular processes. Recently, we have invented a novel platform technology to achieve high-yield production of fully humanized, bioengineered miRNA agents (hBERAs) for research and development. This study is aimed to produce and utilize a new biologic miR-34a-5p (or miR-34a) molecule, namely, hBERA/miR-34a, to delineate the role of miR-34a-5p in the regulation of mitochondrial functions in human carcinoma cells. Bioengineered hBERA/miR-34a was produced through in vivo fermentation production and purified by anion exchange fast protein liquid chromatography. hEBRA/miR-34a was processed to target miR-34a-5p in human osteosarcoma and lung cancer cells, as determined by selective stem-loop reverse transcription quantitative polymerase chain reaction analysis. The mitochondrial inner membrane protein MPV17 like 2 (MPV17L2) was validated as a direct target for miR-34a-5p by dual luciferase reporter assay. Western blot analysis revealed that bioengineered miR-34a-5p effectively reduced MPV17L2 protein outcomes, leading to much lower levels of respiratory chain Complex I activities and intracellular ATP that were determined with specific assay kits. Moreover, Seahorse Mito Stress Test assay was conducted, and the results showed that biologic miR-34a-5p sharply reduced cancer cell mitochondrial respiration capacity, accompanied by a remarkable increase of oxidative stress and elevated apoptotic cell death, which are manifested by greater levels of reactive oxygen species and selective apoptosis biomarkers, respectively. These results demonstrate the presence and involvement of the miR-34a-5p-MPV17L2 pathway in the control of mitochondrial functions in human carcinoma cells and support the utility of novel bioengineered miRNA molecules for functional studies. GRAPHICAL ABSTRACT
SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples

Abstract SynergyFinder (https://synergyfinder.fimm.fi) is a free web-application for interactive analysis and visualization of multi-drug combination response data. Since its first release in 2017, SynergyFinder has become a popular tool for multi-dose combination data analytics, partly because the development of its functionality and graphical interface has been driven by a diverse user community, including both chemical biologists and computational scientists. Here, we describe the latest upgrade of this community-effort, SynergyFinder release 3.0, introducing a number of novel features that support interactive multi-sample analysis of combination synergy, a novel consensus synergy score that combines multiple synergy scoring models, and an improved outlier detection functionality that eliminates false positive results, along with many other post-analysis options such as weighting of synergy by drug concentrations and distinguishing between different modes of synergy (potency and efficacy). Based on user requests, several additional improvements were also implemented, including new data visualizations and export options for multi-drug combinations. With these improvements, SynergyFinder 3.0 supports robust identification of consistent combinatorial synergies for multi-drug combinatorial discovery and clinical translation.
A novel eudesmol derivative from the leaf essential oil of Guatteria friesiana (Annonaceae) and evaluation of the antinociceptive activity

Abstract In the present study, it was evaluated the chemical composition and the antinociceptive activity of the essential oil obtained from the leaves of Guatteria friesiana. Seven compounds corresponding to 96.2% of the crude essential oil were identified. The main components identified were the mixture of β-eudesmol and α-eudesmol (58.1%), and γ-eudesmol (16.8%). A new α-eudesmol derivative, named 5-hydroxy-α-eudesmol, was isolated together with the known compounds β-eudesmol and a mixture of α-eudesmol, β-eudesmol and γ-eudesmol of the essential oil. The chemical structures were determined by 1D and 2D NMR, and MS experiments. Essential oil has significant antinociceptive properties, which are related probably with the involvement of the opioid receptors and K+-ATP channels.
Association between nontraditional lipid profiles and the severity of obstructive sleep apnea: A retrospective study

Due to the significant role of dyslipidemia, cardiovascular diseases (CVDs) are very common in obstructive sleep apnea (OSA). Nontraditional lipid indices are considered to be a better predictive index for cardiovascular risk. Nevertheless, the association between nontraditional lipid profiles and the severity of OSA is not clear.
SWORD2: hierarchical analysis of protein 3D structures

Abstract Understanding the functions and origins of proteins requires splitting these macromolecules into fragments that could be independent in terms of folding, activity, or evolution. For that purpose, structural domains are the typical level of analysis, but shorter segments, such as subdomains and supersecondary structures, are insightful as well. Here, we propose SWORD2, a web server for exploring how an input protein structure may be decomposed into ‘Protein Units’ that can be hierarchically assembled to delimit structural domains. For each partitioning solution, the relevance of the identified substructures is estimated through different measures. This multilevel analysis is achieved by integrating our previous work on domain delineation, ‘protein peeling’ and model quality assessment. We hope that SWORD2 will be useful to biologists searching for key regions in their proteins of interest and to bioinformaticians building datasets of protein structures. The web server is freely available online: https://www.dsimb. inserm.fr/SWORD2.
Analysis and interpretation of interdependencies between economic activities and freight transportation for selected European countries

The thesis contributes to the discussion about the coupling or decoupling of transport and economy. For this purpose, a methodology developed by Stephan Muller, Jens Klauenberg, and Axel Wolfermann from the Institute of Transport Research at the German Aerospace Center (DLR) (51, 52) is taken up, developed, and applied in a broader European context. The methodology contributes to freight generation modelling as first step of the 4-step modelling approach, which comprises furthermore freight distribution, choice of mode, and assignment. In short, the methodology provides a way to build an economic indicator, which when used alongside the freight variable – transported tonnes or ton kilometres – allows for correlation analysis to be devised, through which relationships are established. The indicator, as well as the freight volume or transport performance, are considered on the level of commodities and are classified according to NST/R. This disaggregated approach is an important advance compared to aggregated models, wherein, for example, the gross domestic product alone is used to derive freight data as input for transport models. Consequently, the findings of this thesis serve as input data for freight generation models as well as a comparison for models that have their own freight generation modules. Furthermore, it represents quantitative evidences to the coupling/decoupling discussion and enables the projection of future transport volumes.
Transcytosis of IgA Attenuates Salmonella Invasion in Human Enteroids and Intestinal Organoids

Secretory IgA (SIgA) is the most abundant antibody type in intestinal secretions where it contributes to safeguarding the epithelium from invasive pathogens like the Gram-negative bacterium, Salmonella enterica serovar Typhimurium (STm). For example, we recently reported that passive oral administration of the recombinant monoclonal SIgA antibody, Sal4, to mice promotes STm agglutination in the intestinal lumen and restricts bacterial invasion of Peyer’s patch tissues. ABSTRACT Secretory IgA (SIgA) is the most abundant antibody type in intestinal secretions where it contributes to safeguarding the epithelium from invasive pathogens like the Gram-negative bacterium, Salmonella enterica serovar Typhimurium (STm). For example, we recently reported that passive oral administration of the recombinant monoclonal SIgA antibody, Sal4, to mice promotes STm agglutination in the intestinal lumen and restricts bacterial invasion of Peyer’s patch tissues. In this report, we sought to recapitulate Sal4-mediated protection against STm in human Enteroids and human intestinal organoids (HIOs) as models to decipher the molecular mechanisms by which antibodies function in mucosal immunity in the human gastrointestinal tract. We confirm that Enteroids and HIO-derived monolayers are permissive to STm infection, dependent on HilD, the master transcriptional regulator of the SPI-I type three secretion system (T3SS). Stimulation of M-like cells in both Enteroids and HIOs by the addition of RANKL further enhanced STm invasion. The apical addition of Sal4 mouse IgA, as well as recombinant human Sal4 dimeric IgA (dIgA) and SIgA resulted a dose-dependent reduction in bacterial invasion. Moreover, basolateral application of Sal4 dIgA to Enteroid and HIO monolayers gave rise to SIgA in the apical compartment via a pathway dependent on expression of the polymeric immunoglobulin receptor (pIgR). The resulting Sal4 SIgA was sufficient to reduce STm invasion of Enteroid and HIO epithelial cell monolayers by ~20-fold. Recombinant Sal4 IgG was also transported in the Enteroid and HIOs, but to a lesser degree and via a pathway dependent on the neonatal Fc receptor (FCGRT). The models described lay the foundation for future studies into detailed mechanisms of IgA and IgG protection against STm and other pathogens.