Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the LDBio Aspergillus ICT lateral flow assay for serodiagnosis of allergic bronchopulmonary aspergillosis

Background Early recognition and diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is critical to improve patient symptoms, and antifungal therapy may prevent or delay progression of bronchiectasis and development of chronic pulmonary aspergillosis. Objective A recently commercialized lateral flow assay (Aspergillus ICT) (LDBio Diagnostics, Lyons, France) detects Aspergillus-specific antibodies in <30 minutes, requiring minimal laboratory equipment. We evaluated this assay for diagnosis of ABPA compared to diseased (asthma and/or bronchiectasis) controls. Methods ABPA and control sera collected at the National Aspergillosis Centre (Manchester, UK) and/or from the Manchester Allergy, Respiratory and Thoracic Surgery research biobank were evaluated using the Aspergillus ICT assay. Results were read both visually and digitally (using a lateral flow reader). Serological Aspergillus-specific IgG and IgE, and total IgE titres were measured by ImmunoCAP. Results For 106 cases of ABPA versus all diseased controls, sensitivity and specificity for the Aspergillus ICT were 90.6% and 87.2%, respectively. Sensitivity for ‘proven’ ABPA alone (n = 96) was 89.8%, and 94.4% for ‘presumed’ ABPA (n = 18). ‘Asthma only’ controls (no bronchiectasis) and ‘bronchiectasis controls’ exhibited 91.4% and 81.7% specificity, respectively. Comparison of Aspergillus ICT result with Aspergillus-specific IgG and IgE titres showed no evident immunoglobulin isotype bias. Digital measurements displayed no correlation between ImmunoCAP Aspergillus-specific IgE level and ICT test line intensity. Conclusions The Aspergillus ICT assay exhibits good sensitivity for ABPA serological screening. It is easy to perform and interpret, using minimal equipment and resources; and provides a valuable simple screening resource to rapidly distinguish more serious respiratory conditions from Aspergillus sensitization alone.
Standardization of Prothrombin Time/International Normalized Ratio (PT/INR)

The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instrument used. The INR is created using two major PT ‘correction factors’, namely the mean normal PT (MNPT) and the international sensitivity index (ISI). Manufacturers of reagents and coagulometers have made some efforts to harmonizing INRs, for example, by tailoring reagents to specific coagulometers and provide associated ISI values. Thus, two types of ISIs may be generated, with one being a ‘general’ or ‘generic’ ISI and others being reagent/coagulometer‐specific ISI values. Although these play a crucial role in improving INR results between laboratories, these laboratories reported INR values are known to still differ, even when laboratories use the same thromboplastin reagent and coagulometer. Moreover, ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification. All these factors can be sources of error for INR reporting, which in turn can significantly affect patient management. In this narrative review, we provide some guidance to appropriate ISI verification/validation, which may help decrease the variability in cross laboratory reporting of INRs.
Impact of a Sleep Enhancement Protocol on Nighttime Room Entries in an Inpatient Rehabilitation Facility

Abstract Purpose This study examined whether a sleep enhancement protocol (SEP) could reduce nighttime room entries (NREs) for patients with orthopedic injury (OI) or acquired brain injury (ABI) in an inpatient rehabilitation facility. Design A two-wave prospective study assessing standard of care (SOC) versus SEP. Methods Sixty-five participants completed baseline and follow-up questionnaires and wore an actigraph for approximately 7 days. In the SEP, nighttime care was “bundled. ” Findings In SOC, NREs were associated with less efficient sleep and greater daytime fatigue. Nighttime room entries were approximately 50% lower in the SEP than SOC. Participants in the OI SOC had more room entries than any other group. There were no significant changes in room entries in the ABI SEP group. Conclusions There was a relationship between NREs and sleep. The SEP was effective at reducing NREs for patients with OI, but not ABI. Clinical Relevance Sleep enhancement protocols in inpatient rehabilitation facilities may be effective at improving sleep. Future research may focus on developing individualized protocols to improve sleep across patients with a variety of presenting diagnoses.
Length of hospital stay after cesarean section in Denmark from 2004 to 2016: A national register‐based study

Length of hospital stay after birth has decreased during the last decades, but nationwide data on length of hospital stay after cesarean section are lacking. Elements of Enhanced Recovery Programs were reported to reduce the length of hospital stay. The aim of this nationwide study was to describe the length of hospital stay after cesarean section in Denmark from 2004 to 2016 taking into account birth‐ and health‐related factors as well as demographic changes and, further, to assess potential differences between the five Danish regions.
Innate immunity during SARS‐CoV‐2: evasion strategies and activation trigger hypoxia and vascular damage

Innate immune sensing of viral molecular patterns is essential for development of antiviral responses. Like many viruses, SARS‐CoV‐2 has evolved strategies to circumvent innate immune detection, including low cytosine–phosphate–guanosine (CpG) levels in the genome, glycosylation to shield essential elements including the receptor‐binding domain, RNA shielding and generation of viral proteins that actively impede anti‐viral interferon responses. Together these strategies allow widespread infection and increased viral load. Despite the efforts of immune subversion, SARS‐CoV‐2 infection activates innate immune pathways inducing a robust type I/III interferon response, production of proinflammatory cytokines and recruitment of neutrophils and myeloid cells. This may induce hyperinflammation or, alternatively, effectively recruit adaptive immune responses that help clear the infection and prevent reinfection. The dysregulation of the renin–angiotensin system due to down‐regulation of angiotensin‐converting enzyme 2, the receptor for SARS‐CoV‐2, together with the activation of type I/III interferon response, and inflammasome response converge to promote free radical production and oxidative stress. This exacerbates tissue damage in the respiratory system, but also leads to widespread activation of coagulation pathways leading to thrombosis. Here, we review the current knowledge of the role of the innate immune response following SARS‐CoV‐2 infection, much of which is based on the knowledge from SARS‐CoV and other coronaviruses. Understanding how the virus subverts the initial immune response and how an aberrant innate immune response contributes to the respiratory and vascular damage in COVID‐19 may help to explain factors that contribute to the variety of clinical manifestations and outcome of SARS‐CoV‐2 infection.
Genome-wide identification and characterization of Respiratory Burst Oxidase Homolog genes in six Rosaceae species and an analysis of their effects on adventitious rooting in apple

Adventitious root formation is essential for plant propagation, development, and response to various stresses. Reactive oxygen species (ROS) are essential for adventitious root formation. However, information on Respiratory Burst Oxidase Homolog (RBOH), a key enzyme that catalyzes the production ROS, remains limited in woody plants. Here, a total of 44 RBOH genes were identified from six Rosaceae species (Malus domestica, Prunus avium, Prunus dulcis 'Texas’, Rubus occidentalis, Fragaria vesca and Rosa chinensis), including ten from M. domestica. Their phylogenetic relationships, conserved motifs and gene structures were analyzed. Exogenous treatment with the RBOH protein inhibitor diphenyleneiodonium (DPI) completely inhibited adventitious root formation, whereas exogenous H2O2 treatment enhanced adventitious root formation. In addition, we found that ROS accumulated during adventitious root primordium inducing process. The expression levels of MdRBOH-H, MdRBOH-J, MdRBOH-A, MdRBOH-E1 and MdRBOH-K increased more than two-fold at days 3 or 9 after auxin treatment. In addition, cis-acting element analysis revealed that the MdRBOH-E1 promoter contained an auxin-responsive element and the MdRBOH-K promoter contained a meristem expression element. Based on the combined results from exogenous DPI and H2O2 treatment, spatiotemporal expression profiling, and cis-element analysis, MdRBOH-E1 and MdRBOH-K appear to be candidates for the control of adventitious rooting in apple.
The axis of the receptor for advanced glycation endproducts in asthma and allergic airway disease

Asthma is a generalized term that describes a scope of distinct pathologic phenotypes of variable severity, which share a common complication of reversible airflow obstruction. Asthma is estimated to affect almost 400 million people worldwide, and nearly ten percent of asthmatics have what is considered “severe” disease. The majority of moderate to severe asthmatics present with a “type 2‐high” (T2‐hi) phenotypic signature, which pathologically is driven by the type 2 cytokines Interleukin‐(IL)‐4, IL‐5, and IL‐13. However, “type 2‐low” (T2‐lo) phenotypic signatures are often associated with more severe, steroid‐refractory neutrophilic asthma. A wide range of clinical and experimental studies have found that the receptor for advanced glycation endproducts (RAGE) plays a significant role in the pathogenesis of asthma and allergic airway disease (AAD). Current experimental data indicates that RAGE is a critical mediator of the type 2 inflammatory reactions which drive the development of T2‐hi AAD. However, clinical studies demonstrate that increased RAGE ligands and signaling strongly correlate with asthma severity, especially in severe neutrophilic asthma. This review presents an overview of the current understandings of RAGE in asthma pathogenesis, its role as a biomarker of disease, and future implications for mechanistic studies, and potential therapeutic intervention strategies.
Development of cortical auditory responses to speech in noise in unilaterally deaf adults following cochlear implantation

Background For patients with single-sided deafness (SSD), restoration of binaural function via cochlear implant (CI) has been shown to improve speech understanding in noise. The objective of this study was to investigate changes in behavioral performance and cortical auditory responses following cochlear implantation. Design Prospective longitudinal study. Setting Tertiary referral center. Methods Six adults with SSD were tested before and 12 months post-activation of the CI. Six normal hearing (NH) participants served as experimental controls. Speech understanding in noise was evaluated for various spatial conditions. Cortical auditory evoked potentials were recorded with /ba/ stimuli in quiet and in noise. Global field power and responses at Cz were analyzed. Results Speech understanding in noise significantly improved with the CI when speech was presented to the CI ear and noise to the normal ear (p<0.05), but remained poorer than that of NH controls (p<0.05). N1 peak amplitude measure in noise significantly increased after CI activation (p<0.05), but remained lower than that of NH controls (p<0.05) at 12 months. After 12 months of CI experience, cortical responses in noise became more comparable between groups. Conclusion Binaural restoration in SSD patients via cochlear implantation improved speech performance noise and cortical responses. While behavioral performance and cortical auditory responses improved, SSD-CI outcomes remained poorer than that of NH controls in most cases, suggesting only partial restoration of binaural hearing.
Promoterless, Nuclease‐Free Genome Editing Confers a Growth Advantage for Corrected Hepatocytes in Mice With Methylmalonic Acidemia

Adeno‐associated viral (AAV) gene therapy has shown great promise as an alternative treatment for metabolic disorders managed using liver transplantation, but remains limited by transgene loss and genotoxicity. Our study aims to test an AAV vector with a promoterless integrating cassette, designed to provide sustained hepatic transgene expression and reduced toxicity in comparison to canonical AAV therapy.
Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Syndecan-1 is a transmembrane heparan sulfate proteoglycan which is indispensable in the structural and functional integrity of epithelia. Normal hepatocytes display strong cell surface expression of syndecan-1; however, upon malignant transformation, they may lose it from their cell surfaces. In this study, we demonstrate that re-expression of full-length or ectodomain-deleted syndecan-1 in hepatocellular carcinoma cells downregulates phosphorylation of ERK1/2 and p38, with the truncated form exerting an even stronger effect than the full-length protein. Furthermore, overexpression of syndecan-1 in hepatoma cells is associated with a shift of heparan sulfate structure toward a highly sulfated type specific for normal liver. As a result, cell proliferation and proteolytic shedding of syndecan-1 from the cell surface are restrained, which facilitates redifferentiation of hepatoma cells to a more hepatocyte-like phenotype. Our results highlight the importance of syndecan-1 in the formation and maintenance of differentiated epithelial characteristics in hepatocytes partly via the HGF/ERK/Ets-1 signal transduction pathway. Downregulation of Ets-1 expression alone, however, was not sufficient to replicate the phenotype of syndecan-1 overexpressing cells, indicating the need for additional molecular mechanisms. Accordingly, a reporter gene assay revealed the inhibition of Ets-1 as well as AP-1 transcription factor-induced promoter activation, presumably an effect of the heparan sulfate switch.
Analyzing the effects of free water modeling by deep learning on diffusion MRI structural connectivity estimates in glioma patients

Diffusion-weighted MRI makes it possible to quantify subvoxel brain microstructure and to reconstruct white matter fiber trajectories with which structural connectomes can be created. However, at the border between cerebrospinal fluid and white matter, or in the presence of edema, the obtained MRI signal originates from both the cerebrospinal fluid as well as from the white matter partial volume. Diffusion tractography can be strongly influenced by these free water partial volume effects. Thus, including a free water model can improve diffusion tractography in glioma patients. Here, we analyze how including a free water model influences structural connectivity estimates in healthy subjects as well as in brain tumor patients. During a clinical study, we acquired diffusion MRI data of 35 glioma patients and 28 age- and sex-matched controls, on which we applied an open-source deep learning based free water model. We performed deterministic as well as probabilistic tractography before and after free water modeling, and utilized the tractograms to create structural connectomes. Finally, we performed a quantitative analysis of the connectivity matrices. In our experiments, the number of tracked diffusion streamlines increased by 13% for high grade glioma patients, 9.25% for low grade glioma, and 7.65% for healthy controls. Intra-subject similarity of hemispheres increased significantly for the patient as well as for the control group, with larger effects observed in the patient group. Furthermore, inter-subject differences in connectivity between brain tumor patients and healthy subjects were reduced when including free water modeling. Our results indicate that free water modeling increases the similarity of connectivity matrices in brain tumor patients, while the observed effects are less pronounced in healthy subjects. As the similarity between brain tumor patients and healthy controls also increased, connectivity changes in brain tumor patients may have been overestimated in studies that did not perform free water modeling.
Novel Harmicines with Improved Potency against Plasmodium

Harmicines represent hybrid compounds composed of β-carboline alkaloid harmine and cinnamic acid derivatives (CADs). In this paper we report the synthesis of amide-type harmicines and the evaluation of their biological activity. N-harmicines 5a–f and O-harmicines 6a–h were prepared by a straightforward synthetic procedure, from harmine-based amines and CADs using standard coupling conditions, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo [4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) and N,N-diisopropylethylamine (DIEA). Amide-type harmicines exerted remarkable activity against the erythrocytic stage of P. falciparum, in low submicromolar concentrations, which was significantly more pronounced compared to their antiplasmodial activity against the hepatic stages of P. berghei. Furthermore, a cytotoxicity assay against the human liver hepatocellular carcinoma cell line (HepG2) revealed favorable selectivity indices of the most active harmicines. Molecular dynamics simulations demonstrated the binding of ligands within the ATP binding site of PfHsp90, while the calculated binding free energies confirmed higher activity of N-harmicines 5 over their O-substituted analogues 6. Amino acids predominantly affecting the binding were identified, which provided guidelines for the further derivatization of the harmine framework towards more efficient agents.
Structural and functional diversity calls for a new classification of ABC transporters

Members of the ATP‐binding cassette (ABC) transporter superfamily translocate a broad spectrum of chemically diverse substrates. While their eponymous ATP‐binding cassette in the nucleotide‐binding domains (NBDs) is highly conserved, their transmembrane domains (TMDs) forming the translocation pathway exhibit distinct folds and topologies, suggesting that during evolution the ancient motor domains were combined with different transmembrane mechanical systems to orchestrate a variety of cellular processes. In recent years, it has become increasingly evident that the distinct TMD folds are best suited to categorize the multitude of ABC transporters. We therefore propose a new ABC transporter classification that is based on structural homology in the TMDs.
Influence of Ultraviolet and Oxygen Coupling Aging on Rheological Properties and Functional Group Index of Warm Mix Asphalt Binder

Warm-mixed asphalt (WMA) has the characteristics of low mixing temperature and energy consumption, which makes it more suitable than hot-mixed asphalt for plateau regions (the altitude is above 500 m, and the terrain is relatively flat or has a wide area with certain undulations). However, WMA is subject to severe ultraviolet (UV) aging because the UV radiation in plateau areas is more intense. The asphalt’s aging changes its rheological properties inevitably, and thus degrades the asphalt pavement’s performance. Accordingly, the purpose of this paper is to investigate the effect of UV and oxygen coupling aging on WMA’s rheological properties and functional group index. Temperature and frequency sweep tests were performed with a dynamic shear rheometer. At the same time, the functional group index was used as an indicator to compare the changes in the WMA’s infrared spectrum before and after UV aging. The results showed that WMA’s elasticity increased and its viscosity decreased after aging with UV. Under the condition of UV–oxygen isolation, as the aging period increased, the WMA’s rutting factor increased gradually. The degree of improvement was greater than that under the condition of oxygen isolation. In contrast, the time required for the WMA’s complex shear modulus to recover under the condition of UV–oxygen coupling was delayed. An increase in the peak value of infrared spectrum indicates that the WMA has undergone oxygen aging. The presence and change in the carbonyl group reflects the degree of the WMA’s UV aging, and the UV aging condition had a greater effect on the peak values of the carbonyl and sulfoxide groups.
Violation of Stokes–Einstein and Stokes–Einstein–Debye relations in polymers at the gas-supercooled liquid coexistence

Molecular dynamics simulations are performed on a system of model linear polymers to look at the violations of Stokes–Einstein (SE) and Stokes–Einstein–Debye (SED) relations near the mode coupling theory transition temperature T c at three (one higher and two lower) densities. At low temperatures, both lower density systems show stable gas-supercooled-liquid coexistence whereas the higher density system is homogeneous. We show that monomer density relaxation exhibits SE violation for all three densities, whereas molecular density relaxation shows a weak violation of the SE relation near T c in both lower density systems. This study identifies disparity in monomer mobility and observation of jumplike motion in the typical monomer trajectories resulting in the SE violations. In addition to the SE violation, a weak SED violation is observed in the gas-supercooled-liquid coexisting domains of the lower densities. Both lower density systems also show a decoupling of translational and rotational dynamics in this polymer system.
Remediation of Nickel-Contaminated Soil by Brassica juncea L. cv. T-59 and Effect of the Metal on Some Metabolic Aspects of the Plant

ABSTRACT Among four cultivars of Brassica juncea L. , viz., TM-4, TM-2, RH-30, and T-59, cv. T-59 was relatively more tolerant to nickel (Ni) toxicity based on the growth parameters, seedling vigor index, and metal tolerance index. Nickel application inhibited the activity of the nitrate-assimilating enzyme nitrate reductase in the roots, stem, and leaves, whereas the total organic nitrogen, proline, and activity of a polyamine-metabolizing enzyme, diamine oxidase, increased in this tolerant cultivar (T-59). It accumulated a good amount of Ni from the soil in its root and shoot (i.e., 6.0–6.51 μg Ni g−1 dry weight) during 2 months of cultivation with an 8.0 mM Ni supply in the soil. The data presented in this paper indicate that Ni tolerance and its removal by Indian mustard from subtropical Indian soil is cultivar dependent, possibly due to different genetic and physiological adaptations of the cultivars.