Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient preferences and experiences regarding thrombopoietin-receptor agonists for immune thrombocytopenia in The Netherlands (TRAPeze Netherlands study)

ABSTRACT Objective: Identify patient experience and preference towards thrombopoietin-receptor agonists (TPO-RAs) in treatment of immune thrombocytopenia (ITP) in the Netherlands. Methods: The Thrombopoietin-Receptor Agonist Patient experience (TRAPeze) survey used a discrete choice experiment (DCE) to elicit patient preferences and a patient burden survey (PBS) to evaluate the clinical and social impact of ITP. TRAPeze collected responses from 6th October to 19th November 2021. Results: Seventy-six respondents completed the DCE: treatment preference appeared to be driven by method of administration (odds ratio [OR] 4.33; 95% confidence interval [CI] 2.88–6.52), frequency of dosing (OR 2.33; 95% CI 1.86–2.92) and drug–food interactions (OR 1.91; 95% CI 1.54–2.37). Respondents preferred therapies delivered orally over subcutaneous injection (OR 4.22; 95% CI 2.76–6.46), dosed once weekly over once daily (OR 2.37; 95% CI 1.58–3.54) and without food restrictions over with restrictions (OR 1.90; 95% CI 1.52–2.38). Sixty-nine respondents completed the DCE and PBS (mean [range] age 53 [19–83] years, 65% female). Seven incomplete PBS responses were excluded from analysis. Respondents were currently, or most recently, receiving eltrombopag (n = 43) or romiplostim (n = 26), of which 30% (n = 21/69) had previously received another TPO-RA. Loss (29%, n = 6/21) and lack (29%, n = 6/21) of response were the most common reasons for switching TPO-RA. Only 28% (n = 18/65) of respondents felt their TPO-RA increased energy levels. Conclusion: Patients preferred therapies delivered orally, dosed less frequently and without food restrictions. QoL of ITP patients on TPO-RAs can be improved; the burden analyses presented can inform future efforts towards this.
Neuronal NADPH oxidase is required for neurite regeneration of Aplysia bag cell neurons

NADPH oxidase (Nox), a major source of reactive oxygen species (ROS), is involved in neurodegeneration after injury and disease. Nox is expressed in both neuronal and non‐neuronal cells and contributes to an elevated ROS level after injury. Contrary to the well‐known damaging effect of Nox‐derived ROS in neurodegeneration, recently a physiological role of Nox in nervous system development including neurogenesis, neuronal polarity, and axonal growth has been revealed. Here, we tested a role for neuronal Nox in neurite regeneration following mechanical transection in cultured Aplysia bag cell neurons. Using a novel hydrogen peroxide (H2O2)‐sensing dye, 5′‐(p‐borophenyl)‐2′‐pyridylthiazole pinacol ester (BPPT), we found that H2O2 levels are elevated in regenerating growth cones following injury. Redistribution of Nox2 and p40phox in the growth cone central domain suggests Nox2 activation after injury. Inhibiting Nox with the pan‐Nox inhibitor celastrol reduced neurite regeneration rate. Pharmacological inhibition of Nox is correlated with reduced activation of Src2 tyrosine kinase and F‐actin content in the growth cone. Taken together, these findings suggest that Nox‐derived ROS regulate neurite regeneration following injury through Src2‐mediated regulation of actin organization in Aplysia growth cones.
The Relative Behavior of Shear Velocity, Bulk Sound Speed, and Compressional Velocity in the Mantle: Implications for Chemical and Thermal Structure

Despite immense progress in imaging seismic velocity anomalies in the mantle over the past 15 years, we still know relatively little about their physical cause. One way to shed some light on this problem is to investigate the relative amplitudes of compressional and shear velocity anomalies in the mantle. Unfortunately, the amplitudes of velocity anomalies can be quite sensitive to the data sets and imaging techniques employed. It is therefore usually meaningless to take two models from the literature and do a simple comparison, In this paper, we consider joint modeling of P and S data sets and compare with some recent results from the literature. Some robust patterns are beginning to emerge which allow us to identify regions of the lower mantle which are anomalous. Such regions seem to be associated with large-scale upwelling in the mantle and may indicate chemical interaction with the core.
ADAMTS12 is a stromal modulator in chronic liver disease

Adamalysins, a family of metalloproteinases containing a disintegrin and metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTSs), belong to the matrisome and play important roles in various biological and pathological processes, such as development, immunity and cancer. Using a liver cancer dataset from the International Cancer Genome Consortium, we developed an extensive in silico screening that identified a cluster of adamalysins co‐expressed in livers from patients with hepatocellular carcinoma (HCC). Within this cluster, ADAMTS12 expression was highly associated with recurrence risk and poorly differentiated HCC signatures. We showed that ADAMTS12 was expressed in the stromal cells of the tumor and adjacent fibrotic tissues of HCC patients, and more specifically in activated stellate cells. Using a mouse model of carbon tetrachloride‐induced liver injury, we showed that Adamts12 was strongly and transiently expressed after a 24 h acute treatment, and that fibrosis was exacerbated in Adamts12‐null mice submitted to carbon tetrachloride‐induced chronic liver injury. Using the HSC‐derived LX‐2 cell line, we showed that silencing of ADAMTS12 resulted in profound changes of the gene expression program. In particular, genes previously reported to be induced upon HSC activation, such as PAI‐1, were mostly down‐regulated following ADAMTS12 knock‐down. The phenotype of these cells was changed to a less differentiated state, showing an altered actin network and decreased nuclear spreading. These phenotypic changes, together with the down‐regulation of PAI‐1, were offset by TGF‐β treatment. The present study thus identifies ADAMTS12 as a modulator of HSC differentiation, and a new player in chronic liver disease.
Delayed melatonin circadian timing, lower melatonin output and sleep disruptions in myopic, or short-sighted, children.

STUDY OBJECTIVES This study investigated the differences in melatonin circadian timing and output, sleep characteristics, and cognitive function in myopic and non-myopic (or emmetropic) children, age 8-15 years. METHODS 26 myopes [refractive error (mean ± standard error mean) -2.06 ± 0.23 dioptres] and 19 emmetropes (-0.06 ± 0.04 dioptres), aged 11.74 ± 2.31 years were recruited. Circadian timing was assessed using salivary dim light melatonin onset (DLMO), collected half-hourly for 7 hours, beginning 5 hours before and finishing 2 hours after individual average sleep onset in a sleep laboratory. Nocturnal melatonin output was assessed via aMT6s levels from urine voids collected from 05:30 pm and until 8:00 am the following morning. Actigraphy-derived objective sleep timing were acquired for a week prior to the sleep laboratory visit. Cognitive assessments of sustained attention (using Psychomotor Vigilance Task or PVT) and working memory (using digit spans) were performed on the night of sleep laboratory. RESULTS Myopic children (9:07 pm ± 14 min) exhibited a DLMO phase-delay of 1 hr 8 min compared to emmetropes (7:59 pm ± 13 min), p=0.002. aMT6s melatonin levels were significantly lower among myopes (18.70 ± 2.38) than emmetropes (32.35 ± 6.93, p=0.001). Myopes also exhibited significantly delayed sleep onset, delayed wake-up time, poor and reduced sleep, and more evening-type diurnal preference than emmetropes (all p<0.05). Finally, myopes showed a slower reaction time in the PVT (p<0.05), but not digit span tasks at night. CONCLUSION These findings suggest a potential association between circadian rhythm dysfunction and myopia in children.
Molecular epidemiology of infectious bursal disease virus in the Near East and Persian Gulf regions

ABSTRACT Infectious bursal disease virus (IBDV) is a ubiquitous immunosuppressive pathogen which is a severe burden to the poultry industry. Due to frequent mutation and reassortment events, its double-stranded, bi-segmented RNA genome displays a considerable heterogeneity, which in turn produces profound differences in antigenicity and pathogenicity. In recent years, the investigation of IBDV epidemiology has greatly benefited from the proposal of multiple phylogenetic classification systems which prompted the execution of molecular surveys all over the world, producing a wealth of standardized and easily sharable data. The present epidemiological survey was conducted in six Near East and Persian Gulf countries to characterize the field IBDVs circulating in the region. Ninety-three broiler flocks, immunized with different vaccination protocols, were investigated over a one-year period by collecting eight individual bursal samples at a time. Using molecular assays targeting both genome segments, field IBDVs belonging to four genotypes were detected from 42 flocks across all investigated countries. While traditional very virulent IBDVs (genotype A3B2) represented a minority, multiple atypical IBDV genotypes (A3B1, A4B1 and A6B1) were found to circulate in most of the region. Many of the detected strains were related to sequences from other continents, supporting the involvement of the Near and Middle East in complex networks of viral spreading. The obtained results, combined with the available literature, allowed us to update the epidemiological picture, hopefully favouring the identification of epidemiological threats and the planning of effective monitoring and control strategies. RESEARCH HIGHLIGHTS Different field IBDVs were found to circulate in the Near and Middle East. Multiple atypical genotypes (A3B1, A4B1, A6B1) were found to circulate extensively. Traditional very virulent IBDVs (A3B2) were a minority of the detected strains. Viral exchanges can be hypothesized between the region and different continents.
Dynamics of ribosome composition and ribosomal protein phosphorylation in immune signaling in Arabidopsis thaliana

Abstract In plants, the detection of microbe-associated molecular patterns (MAMPs) induces primary innate immunity by the activation of mitogen-activated protein kinases (MAPKs). We show here that the MAMP-activated MAPK MPK6 not only modulates defense through transcriptional regulation but also via the ribosomal protein translation machinery. To understand the effects of MPK6 on ribosomes and their constituent ribosomal proteins (RPs), polysomes, monosomes and the phosphorylation status of the RPs, MAMP-treated WT and mpk6 mutant plants were analysed. MAMP-activation induced rapid changes in RP composition of monosomes, polysomes and in the 60S ribosomal subunit in an MPK6-specific manner. Phosphoproteome analysis showed that MAMP-activation of MPK6 regulates the phosphorylation status of the P-stalk ribosomal proteins by phosphorylation of RPP0 and the concomitant dephosphorylation of RPP1 and RPP2. These events coincide with a significant decrease in the abundance of ribosome-bound RPP0s, RPP1s and RPP3s in polysomes. The P-stalk is essential in regulating protein translation by recruiting elongation factors. Accordingly, we found that RPP0C mutant plants are compromised in basal resistance to Pseudomonas syringae infection. These data suggest that MAMP-induced defense also involves MPK6-induced regulation of P-stalk proteins, highlighting a new role of ribosomal regulation in plant innate immunity.
Mental and Physical Health-Related Cannabis Motives Mediate the Relationship between Childhood Trauma and Problematic Cannabis Use over Time among Emerging Adult Cannabis Users

Abstract Background While growing evidence has identified mental and physical health-related cannabis use motives as significant mechanisms between childhood trauma and problematic cannabis use (PCU) for emerging adults (EA), there is a need to understand the longitudinal stability of these pathways and how they impact PCU as cannabis users age into later adulthood. Methods The current study extends an analysis examining the impact of childhood trauma (e.g., emotional abuse, sexual abuse) on multiple indicators of PCU through a range of cannabis use motives. 339 medical cannabis patient and non-patient EA users from the Los Angeles area were sampled at baseline (mean age = 21.23; SD = 2.48). The present analysis used four waves of follow-up data collected from 2016 to 2018 (W3, W4) and 2019-2020 (W5, W6). Results Use of cannabis to cope with nausea, sleep, pain, and emotional distress mediated the relationships between some types of childhood abuse and PCU at W4, though most associations attenuated by later adulthood (W6). Specifically, greater emotional distress and nausea motives were associated with greater PCU in models of emotional abuse and neglect and sexual abuse, with emotional distress continuing to mediate at W6. Conversely, sleep and pain motives were associated with lower PCU in models for emotional neglect. Conclusions Mental and physical health-related motives reflect potential intervenable factors that predict PCU in emerging adulthood among EA cannabis users with histories of childhood trauma. Results highlight the importance of and value for assessing a wide range of motives and PCU outcomes to target and address areas for intervention.
PSEM_2D: A physically based model of erosion processes at the plot scale

This paper presents the development and first applications of the Plot Soil Erosion Model 2D (PSEM_2D). Infiltration is computed using a Green and Ampt model, overland flow is computed using the depth‐averaged two‐dimensional unsteady flow equations (Saint Venant equations), and soil erosion is computed by combining the equation of mass conservation of sediment and a detachment‐transport coupling model for erosion by runoff. A shear stress approach is used to determine the transport capacity. The formation of a covering cohesionless layer as a result of depositing sediment and action of rainfall impact before runoff is considered. The erosion processes involved are rainfall and runoff detachment of original soil, rainfall redetachment, and overland flow entrainment of sediment from the deposited layer, and deposition. The model uses a single representative particle size. Complex rainfall events on natural slopes can be simulated. The accuracy of the predictions for erosion of planar surfaces is tested by comparison with observed data obtained from experiments and with an analytical solution. Good agreement between the calculated results and measured data was found. A sensitivity analysis was also performed. Limitations related to the description of overland flow on plane soil surface are pointed out. Finally, an application to a nonplanar natural surface of 75 m2 illustrated the distribution of erosion and sedimentation over the plot.
Magmatic flow paths and palaeomagnetism of the Miocene Stoddard Mountain laccolith, Iron Axis region, Southwestern Utah, USA

Abstract The Stoddard Mountain laccolith is part of a complex of Early Miocene laccoliths intruded along the western edge of the Colorado Plateau in the Iron Axis region of Southwestern Utah. Most Colorado Plateau laccoliths (e.g. Henry and La Sal Mountains) are considered to be fed by a central axial feeder system. However, detailed mapping in the Iron Axis region suggests that the Stoddard Mountain laccolith was fed laterally from the west. Structural and field data suggest the quartz monzonitic magma initially migrated laterally eastward at ∼1 km depth as a sill before spreading laterally north-south where it inflated to ∼1–1.5 km thickness. To test the model of a lateral feeder system, data were collected from 32 palaeomagnetic sites and 76 AMS stations (763 accepted specimens) sampled over the ∼54 km2 exposed part of the N-S oval-shaped laccolith. The in situ AMS fabrics, inferred to correlate with magmatic fabrics, typically show NE trending lineations in the north and S-SE trending lineations in the south part of the intrusion. The palaeomagnetic data are interpreted to indicate a very minimal amount of post-emplacement deformation of the intrusion. The overall lack of westerly-directed and steep magnetic lineations argues against emplacement via a central axial feeder system.
The sesquiterpene lactone mix: A review of past, present and future aspects

The sesquiterpene lactones (SLs) are secondary plant metabolites, which are widespread in the Compositae/Asteraceae plant family. The first SLs were detected more than 100 years ago, and allergic contact dermatitis from Compositae has been reported since the beginning of the 1900s, but it was not until the late 1960s and early 1970s that a collaboration between dermatologists, chemists and botanists led to the detection of SLs as the main allergens of Compositae plants. In the 1980s, the SL mix, consisting of equimolar amounts of alantolactone, costunolide and dehydrocostus lactone, was developed as a screening agent for Compositae sensitisation. Today, after inclusion of SL mix in the baseline series, the mean prevalence of reactions in Europe is around 1%, and in North America 0.8%. In countries outside Europe and North America, the prevalence ranges between 0% and 10.7%. The detection rate of SL mix is lower than that of some plant extracts, and ideally, SL mix should be supplemented with a mix of SLs from locally prevalent allergenic plants. The prevalence of positive reactions to SL mix suggests continued baseline testing in most European countries, North America, New Zealand, Australia and probably some Chinese centres.
Microbisporicin (NAI-107) protects Galleria mellonella from infection with Neisseria gonorrhoeae

ABSTRACT Due to the increasing incidence of antibiotic-resistant bacterial pathogens, the need for the development of alternative compounds is of utmost importance. Bacteriocins are considered a promising alternative to antibiotics. In this study, we determined the in vitro activities of 65 bacteriocins from the PARAGEN collection along with microbisporicin (NAI-107) against 14 WHO reference isolates of Neisseria gonorrhoeae, one isolate of Neisseria meningitidis, and four commensal Neisseria spp. The initial screening of the bacteriocins was carried out using a spot-on-lawn assay wherein 12 bacteriocins (12/66) showed a zone of inhibition against the WHO-P N. gonorrhoeae isolate. Four bacteriocins (4/12), Garvicin KS (GarKS) (ABC), lacticin (lcn) Q, lcn Z, and NAI-107, demonstrated higher activity, and minimum inhibitory concentrations (MICs) using agar dilutions were determined for 19 Neisseria spp. GarKS (ABC), lcn Q, and lcn Z had an MIC range of 4–16 µg/mL, whereas NAI-107 had an MIC range of <0.25 to 2 µg/mL. Using an in vivo Galleria mellonella model, we determined the efficacy of GarKS (ABC), lcn Z, and NAI-107. GarKS (ABC) and lcn Z displayed no in vivo toxicity but showed no in vivo activity against WHO-P N. gonorrhoeae. In contrast, NAI-107 was as effective as ceftriaxone and significantly increased the survival rate of WHO-P N. gonorrhoeae-infected G. mellonella larvae. In conclusion, NAI-107 exhibited potent in vitro and in vivo activities against N. gonorrhoeae. To our knowledge, this is the first study to demonstrate that NAI-107 possesses anti-gonococcal activity in vivo. IMPORTANCE We screened 66 bacteriocins to see if they exhibited anti-gonococcal activity. We found 12 bacteriocins with anti-gonococcal effects, and 4 bacteriocins showed higher anti-gonococcal activity. Three bacteriocins, lacticin Z, lacticin Q, and Garvicin KS (ABC), showed in vitro anti-gonococcal activity but no in vivo inhibitory effects against the Neisseria gonorrhoeae (WHO-P) isolate. On the other hand, NAI-107 showed in vivo anti-gonococcal activity. The findings suggest that NAI-107 is a promising alternative to treat gonorrhea infections. We screened 66 bacteriocins to see if they exhibited anti-gonococcal activity. We found 12 bacteriocins with anti-gonococcal effects, and 4 bacteriocins showed higher anti-gonococcal activity. Three bacteriocins, lacticin Z, lacticin Q, and Garvicin KS (ABC), showed in vitro anti-gonococcal activity but no in vivo inhibitory effects against the Neisseria gonorrhoeae (WHO-P) isolate. On the other hand, NAI-107 showed in vivo anti-gonococcal activity. The findings suggest that NAI-107 is a promising alternative to treat gonorrhea infections.
Correction to:The first recent case of Cimex hemipterus (Hemiptera: Cimicidae) with super-kdr mutations in the Republic of Korea

With the increase in international travel and trade, in conjunction with the development of insecticide resistance, infestations of Cimex lectularius (L.) and Cimex hemipterus (F.) (Hemiptera: Cimicidae) have resurged globally in the last 2 decades. Recently, it was reported that C. hemipterus was also found in temperate regions, indicating the possibility of its expansion outside tropical regions. Cimex hemipterus has not been officially recorded in Korea since its initial description in 1934. Here, we report the first recent case of C. hemipterus in Korea based on morphological and molecular identification. Partial sequencing of the voltage-sensitive sodium channel gene revealed super-kdr mutations (M918I and L1014F) that are associated with pyrethroid resistance. This case report serves as a warning to intensify the bed bug surveillance system in Korea regarding the presence of C. hemipterus and to prepare effective alternative insecticides for pyrethroids.
Relationship Between Nociplastic Pain Involvement and Medication Use, Symptom Relief, and Adverse Effects Among People Using Medical Cannabis for Chronic Pain

Objectives: Cannabis is increasingly being used for chronic pain management, but cannabis’ effects remain poorly characterized in chronic nociplastic pain (NPP), which is posited to be caused by disturbances in nervous system pain processing. In this cross-sectional study (n=1213), we used the 2011 Fibromyalgia (FM) Survey Criteria as a surrogate measure for degree of NPP among individuals using medical cannabis for chronic pain. Methods: Using a quartile-split, we investigated associations between the degree of NPP and medication use, cannabis use characteristics, and symptom relief. Continuous variables were assessed using one-way analysis of variance and categorical variables with Pearson χ2 test and binomial logistic regression for calculation of odds ratios. Results: Participants were predominately female (59%), with a mean ± SD age of 49.4±13.6 years. Higher FM scores were associated with less self-reported improvement in pain and health since initiating medical cannabis use, as well as more cannabis-related side effects. Paradoxically, higher FM scores were also associated with higher usage of concomitant medication use (including opioids and benzodiazepines) but also with substituting cannabis for significantly more medication classes, including opioids and benzodiazepines. Discussion: This article presents evidence that individuals in higher NPP quartiles have higher analgesic intake, higher odds of substituting cannabis for medications, higher side effect burden, and lower therapeutic effect from cannabis. These seemingly contradictory findings may reflect higher symptom burden, polypharmacy at baseline, or that NPP may be challenging to treat with cannabis. Further research is necessary to further explain cannabinoid effects in NPP.