Miracle-dz/UniFAR-FTUs huggingface dataset:
Activating the attachment system modulates neural responses to threat in refugees with PTSD

Abstract Social attachment systems are disrupted for refugees through trauma and forced displacement. This study tested how the attachment system mitigates neural responses to threat in refugees with posttraumatic stress disorder (PTSD). Refugees with PTSD (N = 28) and refugee trauma-exposed controls (N = 22) viewed threat-related stimuli primed by attachment cues during a functional magnetic resonance imaging scan. Group differences and the moderating effects of avoidant or anxious attachment style and grief related to separation from family on brain activity and connectivity patterns were examined. Separation grief was associated with increased amygdala but decreased ventromedial prefrontal cortical (VMPFC) activity to the attachment prime and decreased VMPFC and hippocampal activity to attachment primed threat in the PTSD (vs trauma-exposed control) group. Avoidant attachment style was connected with increased dorsal frontoparietal attention regional activity to attachment prime cues in the PTSD group. Anxious attachment style was associated with reduced left amygdala connectivity with left medial prefrontal regions to attachment primed threat in the PTSD group. Separation grief appears to reduce attachment buffering of threat reactivity in refugees with PTSD, while avoidant and anxious attachment style modulated attentional and prefrontal regulatory mechanisms in PTSD, respectively. Considering social attachments in refugees could be important to post-trauma recovery, based within changes in key emotion regulation brain systems.
Medical Care in the Digital Era

Electronic health records (EHRs), virtual office visits, and health-related apps are priming the path toward a future vision of medical care in the digital age. That future includes streamlining patient-provider interactions, making good use of the wealth of collected data, and ultimately improving all levels of care from prevention to diagnosis, treatment, and outcomes.
Aprepitant: an antiemetic drug, contributes to the prevention of acute lung injury with its anti-inflammatory and antioxidant properties.

OBJECTIVES We investigated, the effects of aprepitant (APRE) on the lung tissues of rats with an experimental polymicrobial sepsis model (CLP: cecal ligation and puncture) biochemically, molecularly and histopathologically. METHODS A total of 40 rats were divided into 5 groups with 8 animals in each group. Group 1 (SHAM), control group; Group 2 (CLP), cecal ligation and puncture; Group 3 (CLP + APRE10), rats were administered CLP + 10 mg/kg aprepitant; Group 4 (CLP + APRE20), rats were administered CLP + 20 mg/kg aprepitant; and Group 5 (CLP + APRE40), rats were administered CLP + 40 mg/kg aprepitant. A polymicrobial sepsis model was induced with CLP. After 16 h, lung tissues were taken for examination. Tumour necrosis factor α (TNF-α) and nuclear factor-kappa b (NFK-b) messenger ribonucleic acid (mRNA) expressions were analysed by real-time PCR (RT-PCR), biochemically antioxidant parameters such as superoxide dismutase (SOD) and glutathione (GSH) and oxidant parameters such as malondialdehyde (MDA) and lung damage histopathologically. KEY FINDINGS AND CONCLUSIONS The GSH level and SOD activity increased while the MDA level and the expressions of TNF-α and NFK-b were reduced in the groups treated with APRE, especially in the CLP + APRE40 group. The histopathology results supported the molecular and biochemical results.
Studying Müllerian duct anomalies – from cataloguing phenotypes to discovering causation

ABSTRACT Müllerian duct anomalies (MDAs) are developmental disorders of the Müllerian duct, the embryonic anlage of most of the female reproductive tract. The prevalence of MDAs is 6.7% in the general female population and 16.7% in women who exhibit recurrent miscarriages. Individuals affected by these anomalies suffer from high rates of infertility, first-trimester pregnancy losses, premature labour, placental retention, foetal growth retardation and foetal malpresentations. The aetiology of MDAs is complex and heterogeneous, displaying a range of clinical pictures that generally lack a direct genotype-phenotype correlation. De novo and familial cases sharing the same genomic lesions have been reported. The familial cases follow an autosomal-dominant inheritance, with reduced penetrance and variable expressivity. Furthermore, few genetic factors and molecular pathways underpinning Müllerian development and dysregulations causing MDAs have been identified. The current knowledge in this field predominantly derives from loss-of-function experiments in mouse and chicken models, as well as from human genetic association studies using traditional approaches, such as microarrays and Sanger sequencing, limiting the discovery of causal factors to few genetic entities from the coding genome. In this Review, we summarise the current state of the field, discuss limitations in the number of studies and patient samples that have stalled progress, and review how the development of new technologies provides a unique opportunity to overcome these limitations. Furthermore, we discuss how these new technologies can improve functional validation of potential causative alterations in MDAs.
Preferential Selection and Contribution of Non-Structural Protein 1 (NS1) to the Efficient Transmission of Panzootic Avian Influenza H5N8 Virus Clades 2.3.4.4A and B in Chickens and Ducks

The panzootic H5N8 highly pathogenic avian influenza viruses of clade 2.3. 4.4A and 2.3. 4.4B devastated the poultry industry globally. Clade 2.3. 4.4A was predominant in 2014/2015 while clade 2.3. 4.4B was widely spread in 2016/2017. ABSTRACT Highly pathogenic avian influenza virus H5N8 clade 2.3. 4.4 caused outbreaks in poultry at an unprecedented global scale. The virus was spread by wild birds in Asia in two waves: clade 2.3. 4.4A in 2014/2015 and clade 2.3. 4.4B from 2016 up to today. Both clades were highly virulent in chickens, but only clade B viruses exhibited high virulence in ducks. Viral factors which contribute to virulence and transmission of these panzootic H5N8 2.3. 4.4 viruses are largely unknown. The NS1 protein, typically composed of 230 amino acids (aa), is a multifunctional protein which is also a pathogenicity factor. Here, we studied the evolutionary trajectory of H5N8 NS1 proteins from 2013 to 2019 and their role in the fitness of H5N8 viruses in chickens and ducks. Sequence analysis and in vitro experiments indicated that clade 2.3. 4.4A and clade 2.3. 4.4B viruses have a preference for NS1 of 237 aa and 217 aa, respectively, over NS1 of 230 aa. NS217 was exclusively seen in domestic and wild birds in Europe. The extension of the NS1 C terminus (CTE) of clade B virus reduced virus transmission and replication in chickens and ducks and partially impaired the systemic tropism to the endothelium in ducks. Conversely, lower impact on fitness of clade A virus was observed. Remarkably, the NS1 of clade A and clade B, regardless of length, was efficient in blocking interferon (IFN) induction in infected chickens, and changes in the NS1 C terminus reduced the efficiency for interferon antagonism. Together, the NS1 C terminus contributes to the efficient transmission and high fitness of H5N8 viruses in chickens and ducks. IMPORTANCE The panzootic H5N8 highly pathogenic avian influenza viruses of clade 2.3. 4.4A and 2.3. 4.4B devastated the poultry industry globally. Clade 2.3. 4.4A was predominant in 2014/2015 while clade 2.3. 4.4B was widely spread in 2016/2017. The two clades exhibited different pathotypes in ducks. Virus factors contributing to virulence and transmission are largely unknown. The NS1 protein is typically composed of 230 amino acids (aa) and is an essential interferon (IFN) antagonist. Here, we found that the NS1 protein of clade 2.3. 4.4A preferentially evolved toward long NS1 with 237 aa, while clade 2.3. 4.4B evolved toward shorter NS1 with 217 aa (exclusively found in Europe) due to stop codons in the C terminus (CTE). We showed that the NS1 CTE of H5N8 is required for efficient virus replication, transmission, and endotheliotropism in ducks. In chickens, H5N8 NS1 evolved toward higher efficiency to block IFN response. These findings may explain the preferential pattern for short NS1 and high fitness of the panzootic H5N8 in birds.
Development and Comparison of Machine Learning Algorithms to Determine Visual Field Progression

Purpose To develop and test machine learning classifiers (MLCs) for determining visual field progression. Methods In total, 90,713 visual fields from 13,156 eyes were included. Six different progression algorithms (linear regression of mean deviation, linear regression of the visual field index, Advanced Glaucoma Intervention Study algorithm, Collaborative Initial Glaucoma Treatment Study algorithm, pointwise linear regression [PLR], and permutation of PLR) were applied to classify each eye as progressing or stable. Six MLCs were applied (logistic regression, random forest, extreme gradient boosting, support vector classifier, convolutional neural network, fully connected neural network) using a training and testing set. For MLC input, visual fields for a given eye were divided into the first and second half and each location averaged over time within each half. Each algorithm was tested for accuracy, sensitivity, positive predictive value, and class bias with a subset of visual fields labeled by a panel of three experts from 161 eyes. Results MLCs had similar performance metrics as some of the conventional algorithms and ranged from 87% to 91% accurate with sensitivity ranging from 0.83 to 0.88 and specificity from 0.92 to 0.96. All conventional algorithms showed significant class bias, meaning each individual algorithm was more likely to grade uncertain cases as either progressing or stable (P ≤ 0.01). Conversely, all MLCs were balanced, meaning they were equally likely to grade uncertain cases as either progressing or stable (P ≥ 0.08). Conclusions MLCs showed a moderate to high level of accuracy, sensitivity, and specificity and were more balanced than conventional algorithms. Translational Relevance MLCs may help to determine visual field progression.
Curcumin plays a protective role against septic acute kidney injury by regulating the TLR9 signaling pathway

Background This study aims to evaluate the inhibitory effect of curcumin (Cur) on the progression of septic acute kidney injury (SAKI), in order to improve the survival rate in this patient population. Methods Acute kidney injury (AKI) was induced by cecal ligation perforation (CLP) in Sprague-Dawley (SD) rats. Using this AKI animal model, the survival rate of the rats was evaluated at different time points after Cur treatment to explore whether Cur can improve survival in an animal model of AKI. The expression levels of inflammatory factors (NF-κB, TNF-α, and IL-10), organ injury markers [urea nitrogen (UN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, creatine kinase (CK), and lactate dehydrogenase (LDH)], and disease progression markers [neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C (CysC)] were determined using an enzyme-linked immunosorbent assay (ELISA). Results The serum levels of UN, Cr, NF-κB, ALT, AST, amylase, CK, LDH, inflammatory factors TNF-α and IL-10, and markers of early diagnosis of SAKI (NGAL, CysC, KIM-1) were significantly lower in the curcumin group than those in the placebo group (P<0.05). In addition, serum levels of TLR9 and its downstream molecules MyD88, IRF5, and IRF7 in the curcumin group were significantly lower than those in the placebo group (P<0.05). The application of TLR9-specific inhibitors to experimental rats led to similar results as those obtained in the curcumin group, whose detection indexes were significantly lower than those in the placebo treatment group (P<0.05). Conclusions Given the excellent performance of Cur in anti-tumor, anti-oxidation, anti-inflammatory, and other clinical trials, it is very likely to be further developed as a potential drug for the clinical treatment of AKI.
Quantitative Microbial Risk Assessment for Contaminated Private Wells in the Fractured Dolomite Aquifer of Kewaunee County, Wisconsin

Background: Private wells are an important source of drinking water in Kewaunee County, Wisconsin. Due to the region’s fractured dolomite aquifer, these wells are vulnerable to contamination by human and zoonotic gastrointestinal pathogens originating from land-applied cattle manure and private septic systems. Objective: We determined the magnitude of the health burden associated with contamination of private wells in Kewaunee County by feces-borne gastrointestinal pathogens. Methods: This study used data from a year-long countywide pathogen occurrence study as inputs into a quantitative microbial risk assessment (QMRA) to predict the total cases of acute gastrointestinal illness (AGI) caused by private well contamination in the county. Microbial source tracking was used to associate predicted cases of illness with bovine, human, or unknown fecal sources. Results: Results suggest that private well contamination could be responsible for as many as 301 AGI cases per year in Kewaunee County, and that 230 and 12 cases per year were associated with a bovine and human fecal source, respectively. Furthermore, Cryptosporidium parvum was predicted to cause 190 cases per year, the most out of all 8 pathogens included in the QMRA. Discussion: This study has important implications for land use and water resource management in Kewaunee County and informs the public health impacts of consuming drinking water produced in other similarly vulnerable hydrogeological settings. https://doi.org/10.1289/EHP7815
The Soluble (Pro)Renin Receptor in Health and Diseases: Foe or Friend?

The (pro)renin receptor (PRR) is a single-transmembrane protein that regulates the local renin-angiotensin system and participates in various intracellular signaling pathways, thus exhibiting a significant physiopathologic relevance in cellular homeostasis. A soluble form of PRR (sPRR) is generated through protease-mediated cleavage of the full-length PRR and secreted into extracellular spaces. Accumulating evidence indicates pivotal biologic functions of sPRR in various physiopathological processes. sPRR may be a novel biomarker for multiple diseases. SIGNIFICANCE STATEMENT Circulating sPRR concentrations are elevated in patients and animals under various physiopathological conditions. This minireview highlights recent advances in sPRR functions in health and pathophysiological conditions. Results suggest that sPRR may be a novel biomarker for multiple diseases, but further studies are needed to determine the diagnostic value of sPRR.
Structural basis for the binding of a selective inverse agonist AF64394 with the human G-protein coupled receptor 3 (GPR3)

Abstract The orphan class A G-protein coupled receptor 3 (GPR3) is highly expressed in brain and linked with various neuronal functions, and therefore, expected to play a vital role in the progression of Alzheimer’s disease. In view of the lack of its experimental structure, we describe herein the three-dimensional structure and conformational dynamics of GPR3 complexed with the inverse agonist AF64394. The GPR3 model was predicted using the Iterative Threading ASSEmbly Refinement (I-TASSER) method. The Induced Fit Docking predicted two unique poses, Pose 1 and Pose 2, for AF64394, and then, molecular dynamics (MD) simulations followed by binding free-energy calculation revealed the Pose 1 as a very stable pose with the least fluctuation during the MD simulation while the Pose 2 underwent a significant fluctuation. The [1,2,4]triazolo[1,5-a]pyrimidine core was engaged in multiple hydrogen bonds (H-bonds), such as a water-mediated H-bond between the triazole nitrogen and T31, two direct H-bonds between the protonated triazole-ring nitrogen and V186 and T279, a direct H-bond between the secondary amine and V187. The phenyl substituent of AF64394 exhibited aromatic π-π stacking interactions with F97, F101, W43 and Y280. AF64394 showed a direct interaction with E28 and polar interactions with H96, T31 and T279. Throughout the MD simulation, the toggle switch residues, F120 and W260, remained in close contact, indicating that the GPR3 conformation represented an inactive state. The 4-(3-chloro-5-isopropoxyphenethyl) group resided near to the toggle switch residues. The insights gained here are expected to be useful in the structure-based design of new ligands targeting GPR3 modulation. Communicated by Ramaswamy H. Sarma
Utilization Impact of Cost-Sharing Elimination for Preventive Care Services: A Rapid Review

Consumer cost-sharing has been shown to diminish utilization of preventive services. Recent efforts, including provisions within the Affordable Care Act, have sought to increase use of preventive care through elimination of cost-sharing for clinically indicated services. We conducted a rapid review of the literature to determine the impact of cost-share elimination on utilization of preventive services. Searches were conducted in PubMed, Scopus, and CINAHL Complete databases as well as in grey literature. A total of 35 articles were included in qualitative synthesis and findings were summarized for three clinical service categories: cancer screenings, contraceptives, and additional services. Impacts of cost-sharing elimination varied depending on clinical service, with a majority of findings showing increases in use. Studies that included socioeconomic status reported that those who were financially vulnerable incurred substantial increases in utilization. Future investigations on additional clinical services are warranted as is research to better elucidate populations who most benefit from cost-sharing elimination.
Comparative Study of Batch and Fluidized Bed Bioreactors for Lipase-Catalyzed Ethyl Cinnamate Synthesis

Ethyl cinnamate, an ester known as flavor and fragrance compound, has been synthesized using two immobilized bioreactor systems, batch and fluidized bed bioreactors. The enzyme used for this synthesis is a commercial lipase B preparation, Novozyme 435. Initial kinetic studies were conducted in both employed bioreactor configurations, and kinetic constants were obtained. Several models were tried for fitting of experimental data, but the best fit, for both bioreactors, was obtained when the ping-pong bi-bi mechanism was used. Interestingly enough, ethanol inhibition occurred in batch bioreactor, but it did not exist in the fluidized bed bioreactor. Solid–liquid mass transfer coefficients were calculated for both bioreactors to determine whether mass transfer limitations existed in either of these systems. The calculation of Damkohler numbers and Thiele modulus confirmed that mass transfer limitations had no effect on the overall reaction in both bioreactors.
O ct 2 01 4 Average Thermal Evolution of the Universe

We sketch the average behaviour of the temperatures and densities of the main components of the ΛCDM universe after inflation. It is modelled as a perfect fluid with dark energy associated with the macroscopic effect of conformal variations of the metric. The main events of the thermal evolution are studied, such as the effect of particle annihilations and decoupling, and the transitions between the eras dominated by different entities. Estimates of the average present epoch temperature of baryonic matter and dark matter composed of neutralinos are given. We study the eventual presence of a sterile neutrino component and find that the sterile neutrino density at the epoch of primordial nucleosynthesis is in agreement with expectations when their evolution starts, at the end of inflation, in temperature equilibrium with the rest of the universe.
Development and validation of RP-HPLC method for loxapine in capsule dosage form

A reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for the determination of loxapine drug in tablet dosage form. The developed method was validated by measuring linearity, precision, limit of detection (LOD), robustness and ruggedness, drug recovery and for system suitability. Water and acetonitrile in the ratio 55:45 v/v was the mobile phase with C 18 column (250 mm x 4.5 mm x 5 µm) as a stationary phase and 265 nm was the detection wavelength. The HPLC system was operated in isocratic mode. The measured retention time of loxapine drug was 6.88 minutes and the limit of detection was 0.035 µg/ml, respectively. The linearity measured in the range 10-100 µg/ml had a correlation coefficient of 0.999. The results of the parameters precision, robustness, recovery and formulation assay indicate that the developed method is a very good tool for the analysis of loxapine drug in tablet dosage form in bulk.
Ju l 2 01 0 More on New Massive Gravity : Exact Solutions

We give a novel description of the recently proposed theory of new massive gravity (NMG) in three dimensions. We show that in terms of a Dirac type differential operator acting on the traceless Ricci tensor, the field equations of the theory reduce to the massive Klein-Gordon type equation with a curvature-squared source term and to a constraint equation. Under a certain relation between the source tensor and the traceless Ricci tensor, fulfilled for constant scalar curvature, the field equations of topologically massive gravity (TMG) can be thought of as the “square-root” of the massive Klein-Gordon type equation. Using this fact, we establish a simple framework for mapping all known algebraic types D and N solutions of TMG into NMG. We also present new exact solutions of algebraic types D and N which are only inherent in NMG.
Isolation and Purification Technology of Monomeric Alkaloids from Seeds of Sophora alopecuroides L.

After ultrafiltration and decoloration of the acidic water extract of Sophora alopecuroides L. seeds, the monomer alkaloids in it were further extracted by using different solvents and the suitable isolation conditions were searched. Chloroform with pH of 10.5 was found to be the most suitable solvent, and the chloroform extract was then loaded on a silica gel column using chloroform-methanol-ammonia water (5 : 0.4 : 0.01, V/V/V) as mobile phase with flow rate of 1 bed volume per hour. During which three peaks were obtained, compounds corresponding to peak 1 and peak 2 were crystallized and recrystallized in acetone and correspondingly crystal A (oxymatrine) and crystal B (oxysophocarpine) were gained with purities over 99%, respectively. Compounds corresponding to peak 3 were re-loaded on a silica gel column once more using acetone-methanol (10 : 1, V/V) as mobile phase with flow rate of 1 bed volume per hour, and during which another three peaks, peak 4 to peak 6, were observed. Compounds corresponding to peak 5 and peak 6 can not form crystal, and compounds corresponding to peak 4 were crystallized and recrystallized in petroleum and crystal C (sophoridine) was obtained with purity over 95.8%. The molecular structure determinations and the qualitative and quantitative analyses of the obtained monomer alkaloids were conducted by HPLC-MS, IR, melting point measurement and thin layer chromatography techniques.