Miracle-dz/UniFAR-FTUs huggingface dataset:
Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis

Abstract Background Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis. Methods An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis. First, airway mucosae from human patients with recurrent tracheal stenosis were analyzed by single-cell RNA sequencing. Canines were then randomly divided into tracheal stenosis, Stent, Stent + Cells, and Stent + Cells + Biogel groups. Autologous airway basal cells of canines in the Stent + Cells and Stent + Cells + Biogel groups were transplanted onto the stenotic airway after modeling. A biogel was coated on the airway prior to basal cell transplantation in the Stent + Cells + Biogel group. After bronchoscopic treatments, canines were followed up for 16 weeks. Results Single-cell RNA sequencing demonstrated packed airway basal cells and an absence of normal airway epithelial cells in patients with RBTS. Autologous airway basal cell transplantation, together with biogel coating, was successfully performed in the canine model. Follow-up observation indicated that survival time in the Stent + Cells + Biogel group was significantly prolonged, with a higher (100%) survival rate compared with the other groups. In terms of pathological and bronchoscopic findings, canines that received autologous basal cell transplantation showed a reduction in granulation hyperplasia as well as airway re-epithelialization with functionally mature epithelial cells. Conclusions Autologous airway basal cell transplantation might serve as a novel regenerative therapy for airway re-epithelialization and inhibit recurrent granulation hyperplasia in benign tracheal stenosis.
Rise and fall of the Nevadaplano

Based on a variety of geologic evidence in eastern Nevada, DeCelles (2004) proposed the late Mesozoic formation of a broad, high plain underlain by thick sialic crust consisting of high-grade metamorphic rocks. Terming this now-exhumed Late Cretaceous–Eocene hinterland metamorphic belt the Nevadaplano, he estimated that its average elevation probably exceeded 3 km (DeCelles 2004, p. 147). Sited in the rain shadow of the thenactive Sierra Nevada volcanic-plutonic arc, the orographic effect on precipitation coupled with limited erosion and active contraction described for the Andes Altiplano and other internally draining high plateaus could explain the presence of a hypothesized ,45–65-km-thick Nevadaplano crust (Wernicke et al. 1996) well into Palaeogene time. Later EW extension and NW-directed shear during Neogene time (Wernicke and Snow 1998; Bennett et al. 2003; Hammond and Thatcher 2004) may reflect divergent asthenospheric flow, resulting in high-temperature thinning of the pre-existing continental lithosphere and collapse of the plateau. The onset of transtension very roughly coincides with overrunning of the East Pacific Rise heat source at ,28 Ma (Atwater 1970; Atwater and Stock 1998). Geologic-structural field relationships and metamorphic thermobarometry of basement rocks, combined with radiometric data, suggest an Eocene to middle Miocene presence of an elevated upland of modest relief in the western Basin and Range, and the Sierra Nevada (Unruh 1991; Chase et al. 1998; Lewis et al. 1999; Wakabayashi and Sawyer 2001; Lee et al. 2009). This widespread peneplain stood high, judging from stable isotope palaeoelevation studies (Horton et al. 2004; Horton and Chamberlain 2006; Mulch et al. 2006; Crowley et al. 2008). Its surface was covered in late Miocene time by a series of lahars, trachyandesites, basaltic lava flows, and associated volcanogenic sediments that extended EW across the ranges for ,200 km; this hinterland was then normal-faulted, uplifted, and dissected by more recent erosion (Jayko 2009; Van Buer et al. 2009).
Radiologist Performance and Reliability of MR Scoring Systems in Perianal Fistulizing Crohn's Disease: Retrospective Analysis in a Real-World Clinical Practice

Background: Perianal fistulizing Crohn's disease (CD-PAF) is difficult to treat, and several MR scoring systems have been developed to assess treatment response. Objective: To assess the relationship between CD-PAF MR scoring systems and radiologists' subjective assessment of CD-PAF severity and treatment response on baseline and follow-up pelvic MR. Methods: Retrospective single institution study of consecutive symptomatic patients with CD-PAF patients who underwent pelvic MR before and [≥]3 months after initiating biologic therapy during a 10-year period (December 2011 to December 2021). One of four radiologists interpreted baseline and follow-up MRs. Scoring systems included variables in the modified Van Assche index (mVAI), magnetic resonance novel index for fistula imaging in CD (MAGNIFI-CD), and pediatric MR-based perianal Crohn's disease (PEMPAC) index. For initial and follow-up MR, a 5-point Likert scale assessed severity (1=mild, 3=moderate, 5=marked). On follow-up MR, radiologists evaluated fistula response as 1-improved, 3-stable, or 5-worsened CD-PAF severity. All four study radiologists scored the baseline MR in 20 patients to calculate inter-reader agreement statistics. Interrater reliability was assessed with the Krippendorff coefficient for categorical variables and intraclass correlation coefficient (ICC) for continuous variables. Results: The final cohort included 96 CD-PAF patients (50 men; mean age=33.0 years) with 192 baseline and follow-up MRs. Moderate to substantial agreement was observed among radiologists for MAGNIFI-CD, mVAI, PEMPAC, and Likert scores (ICC: 0.716, 0.756, 0.535, and 0.679 respectively). Individual components of MR scoring systems had Fair to Substantial agreement (Alpha: 0.195 to 0.730). Significant univariate associations were found between MR scoring systems and radiologists' Likert severity assessments (p<0.001, Pearson correlation coefficients [≥]0.820). In patients meeting criteria for change in disease severity (n=17), all scoring systems demonstrated AUC values [≥]0.93. Conclusion: The MR scoring systems for CD-PAF (MAGNIFI-CD, mVAI, and PEMPAC) demonstrated strong associations with radiologists' subjective assessments of severity and treatment response on baseline and follow-up pelvic MR. Inter-reader agreement of these scoring systems outperformed individual MR factors.
Sublethal effects of fenoxycarb on female reproduction in Helicoverpa armigera (Lepidoptera: Noctuidae)

Abstract The cotton bollworm, Helicoverpa armigera (Hünber) (Lepidoptera: Noctuidae), is a polyphagous pest that causes severe damage to economical crops in most parts of the world. The juvenile hormone analogues are a group of insect growth regulators that increase larval ages and disrupt larval development. Moreover, they affect reproductive system in adult insects. In this study, the effects of sublethal doses of fenoxycarb on fecundity, fertility, and longevity parameters, as well as on oocyte size, ecdysteroid titer in ovaries, and expression level of the ultraspiracle (USP), ecdysone receptor (EcR), hormone receptor 3 (HR3), and vitellogenin (Vg) genes in adult female H. armigera, were examined. Feeding on artificial diet containing fenoxycarb (LC10 and LC25) significantly decreased the percentage of larval survival rate, pupation rate, pupal weight, fecundity, fertility, and oviposition period. It also clearly shortened female longevity. Fenoxycarb treatment suppressed the expression of the USP, EcR, and Vg genes in H. armigera but had no effect on the HR3 gene expression level in either pupae or adults. Overall, our results show that using fenoxycarb as a juvenile hormone analogue can reduce reproduction in H. armigera and may work as an alternative to the use of insecticides for controlling this important agricultural pest.
Single and combined effects of dimethoate and malathion on oxidative stress biomarkers in the non-target freshwater mussel Dreissena polymorpha

Abstract This study evaluates the single and combined effects of dimethoate (DI) and malathion (MA) on oxidative stress biomarkers in the freshwater mussel Dreissena polymorpha, estimating the potential harm of these pesticides on aquatic ecosystems. Superoxide dismutase (SOD) and catalase (CAT) activities, and glutathione (GSH) and lipid peroxidation (TBARS) levels were determined in D. polymorpha exposed to sublethal concentrations of DI, MA and a combination of the two during 24 and 96 h periods. The results showed that the GSH levels were decreased but the TBARS levels were increased in all the exposure groups after 24 and 96 h compared to the control. It was observed that SOD activity decreased but CAT activity increased in all the DI exposure groups after 24 h compared to the control. At the end of 96 hours, it was observed that CAT and SOD activities increased again in some exposure groups compared to the control. Exposure time also had an effect on biomarkers in different levels. According to the results, the cytotoxicity of DI and MA combination depended on their concentrations. DI or/ and MA, in sub-lethal concentrations, induced oxidative damages in D. polymorpha. Combined exposure of the pesticides can alter their toxicity and may be evidence of increased toxicity and oxidative stress.
Health taxes in Indonesia: a review of policy debates on the tobacco, alcoholic beverages and sugar-sweetened beverage taxes in the media

Introduction One of the WHO’s ‘best buys’ in controlling non-communicable diseases and their risk factors is to impose health taxes. While the Indonesian political process inhibits the implementation of health tax policy, studies to discuss the issue remain limited. Methods We employed media analysis to document health tax policy dynamics, for example, the changes in policy timeline and key actors’ statements. We conducted an article search in the Open-Source Intelligence database using appropriate terminology on three commodities, for example, tobacco, alcoholic beverages and sugar-sweetened beverages (SSB). Results Throughout the 15 years of implementation (2007–2022), tobacco has received the most policy attention compared with the other two commodities. This is mainly related to the increasing tariff and reforming the tax structure. As Indonesia is a Muslim-majority country, alcohol consumption is low, and a tax on alcoholic beverages was nearly unchanging and lacked media coverage. Ministry of Finance (MoF) officials are key opinion leaders often cited in the media for health taxes. MoF’s support for health taxes is important to pass and implement health taxes. While SSB taxation is emerging, key opinion leaders’ media statements imply policy contestation, leading to delayed implementation. The policy debates on tobacco taxation implied election years as a major challenge for health tax passages. During the political years, anti-health tax arguments emerged from politicians. While the political contestation on SSB concluded that accentuating the health tax arguments in favour of public health generates the strongest opposition against taxation from the industry. Conclusions Politics of tobacco tax implementation are complex—compared with the other two commodities. The political context drives the divided views among policy-makers. Policy recommendations include generating public allies with key religious opinion leaders, continuing capacity building for politicians and Ministry of Health, and generating evidence-based arguments in favour of public health for MoF.
Considerations for modelling a broad food tax in the Philippines and other low-income and middle-income countries

Fiscal policies to improve diet are a promising strategy to address the increasing burden of non-communicable disease, the leading cause of death globally. Sugar-sweetened beverage taxes are the most implemented type of fiscal policy to improve diet. Yet taxes on food, if appropriately structured and applied across the food supply, may support a larger population-level shift towards a healthier diet. Designing these policies and guiding them through the legislative process requires evidence. Equity-oriented cost-effectiveness analyses that estimate the distribution of potential health and economic gains can provide this critical evidence. Taxes on less healthy foods are rarely modelled in low-income and middle-income countries. We describe considerations for modelling the effect of a food tax, which can provide guidance for food tax policy design. This includes describing issues related to the availability, reliability and level of detail of national data on dietary habits, the nutrient content of foods and food prices; the structure of the nutrient profile model; type of tax; tax rate; pass-through rate and price elasticity. Using the Philippines as an example, we discuss considerations for using existing data to model the potential effect of a tax, while also taking into account the political and food policy context. In this way, we provide a modelling framework that can help guide policy-makers and advocates in designing a food policy to improve the health and well-being of future generations in the Philippines and elsewhere.
Tomographic imaging of the shallow crustal structure of the East Pacific Rise at 9°30′N

Compressional wave travel times from a seismic tomography experiment at 9°30′N on the East Pacific Rise are analyzed by a new tomographic method to determine the three-dimensional seismic velocity structure of the upper 2.5 km of oceanic crust within a 20×18 km2 area centered on the rise axis. The data comprise the travel times and associated uncertainties of 1459 compressional waves that have propagated above the axial magma chamber. A careful analysis of source and receiver parameters, in conjunction with an automated method of picking P wave onsets and assigning uncertainties, constrains the prior uncertainty in the data to 5 to 20 ms. The new tomographic method employs graph theory to estimate ray paths and travel times through strongly heterogeneous and densely parameterized seismic velocity models. The nonlinear inverse method uses a jumping strategy to minimize a functional that includes the penalty function, horizontal and vertical smoothing constraints, and prior model assumptions; all constraints applied to model perturbations are normalized to remove bias. We use the tomographic method to reject the null hypothesis that the axial seismic structure is two-dimensional. Three-dimensional models reveal a seismic structure that correlates well with cross- and along-axis variations in seafloor morphology, the location of the axial summit caldera, and the distribution of seafloor hydrothermal activity. The along-axis segmentation of the seismic structure above the axial magma chamber is consistent with the hypothesis that mantle-derived melt is preferentially injected midway along a locally linear segment of the rise and that the architecture of the crustal section is characterized by an en echelon series of elongate axial volcanoes approximately 10 km in length. The seismic data are compatible with a 300- to 500-m-thick thermal anomaly above a midcrustal melt lens; such an interpretation suggests that hydrothermal fluids may not have penetrated this region in the last 103 years. Asymmetries in the seismic structure across the rise support the inferences that the thickness of seismic layer 2 and the average midcrustal temperature increase to the west of the rise axis. These anomalies may be the result of off-axis magmatism; alternatively, the asymmetric thermal anomaly may be the consequence of differences in the depth extent of hydrothermal cooling.
Sensorimotor brain-computer interface performance depends on signal-to-noise ratio but not connectivity of the mu rhythm in a multiverse analysis of longitudinal data

Serving as a channel for communication with locked-in patients or control of prostheses, sensorimotor brain-computer interfaces (BCIs) decode imaginary movements from the recorded activity of the user’s brain. However, many individuals remain unable to control the BCI, and the underlying mechanisms are not clear yet. The user’s BCI performance was previously shown to correlate with the resting-state signal-to-noise ratio (SNR) of the mu rhythm and the phase synchronization (PS) of the mu rhythm between sensorimotor areas. Yet, these predictors of performance were primarily evaluated in a single BCI session, while the longitudinal aspect remains rather uninvestigated. In addition, different analysis pipelines were used for the estimation of PS in source space, potentially hindering the reproducibility of the results. To systematically address these issues, we performed an extensive validation of the relationship between pre-stimulus SNR, PS, and session-wise BCI performance using a publicly available dataset of 62 human participants performing up to 11 sessions of BCI training. We combined 24 pipelines for source space analysis and three PS measures in a multiverse analysis to investigate how robust the observed effects were to the selection of the pipeline. Our results show that SNR had a between- and within-subject effect on BCI performance for the majority of the pipelines. In contrast, the effect of phase synchronization on BCI performance was less robust to the selection of the pipeline and became non-significant after controlling for SNR. Taken together, our results demonstrate that changes in neuronal connectivity within the sensorimotor system are not critical for learning to control a BCI, and interventions that increase the SNR of the mu rhythm might lead to improvements in the user’s BCI performance.
Pulsed ultrasound modulates the cytotoxic effect of cisplatin and doxorubicin on cultured human retinal pigment epithelium cells (ARPE-19)

Objective Pulsed ultrasound has been proposed as a tool to enhance ocular drug delivery, but its effects on drug potency are not well understood. Doxorubicin-HCl and cisplatin are two drugs commonly used to treat ocular melanoma. We report the effects of pulsed ultrasound on the cytotoxicity of doxorubicin-HCl and cisplatin in vitro. Methods Cultured human retinal pigment epithelium cells (ARPE-19) cells were treated with doxorubicin-HCl or cisplatin in the presence or absence of ultrasound. MTT and Trypan blue assays were performed at 24 and 48 hours post-treatment to assess cell metabolism and death. Results Cells treated with ultrasound plus doxorubicin-HCl demonstrated a significant decrease in metabolism compared to cells treated with doxorubicin-HCl alone. In contrast, cells treated with ultrasound plus cisplatin exhibited a significant increase in metabolism compared to cells treated with cisplatin alone at 48-hours. Cells treated with cisplatin pre-treated with ultrasound (US-Cis) exhibited a significant decrease in metabolism. Cell death was similar in doxorubicin- and cisplatin-treated cells with and without ultrasound. Conclusion Pulsed ultrasound enhances the cytotoxicity of doxorubicin-HCl at 24- and 48-hours post-treatment but abrogates cisplatin toxicity 48-hours post-treatment. This suggests ultrasound modulates cell-drug interactions in a drug-specific manner. These findings may influence the future development of ultrasound-assisted ocular drug delivery systems.
DNA Transposons favour de novo transcript emergence through enrichment of transcription factor binding motifs

De novo genes emerge from non-coding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORFs emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome. In this study we searched for de novo transcripts by using newly assembled genomes and transcriptomes of seven inbred lines of Drosophila melanogaster, originating from six European and one African population. This setup allowed us to detect line specific de novo transcripts, and compare them to their homologous non-transcribed regions in other lines, as well as genic and intergenic control sequences. We studied the association with transposable elements and the enrichment of transcription factor motifs upstream of de novo emerged transcripts and compared them with regulatory elements. We found that de novo transcripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with high CpG islands and regions of TEs activity. Moreover, upstream regions of de novo transcripts are highly enriched with regulatory motifs. Such motifs abound in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstream de novo transcripts than upstream their non-transcribed homologs. Overall, our study demonstrates that TEs insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families.
Default mode network shows distinct emotional and contextual responses yet common effects of retrieval demands across tasks

The default mode network (DMN) lies towards the heteromodal end of the principal gradient of intrinsic connectivity, maximally separated from sensory-motor cortex. It supports memory-based cognition, including the capacity to retrieve conceptual and evaluative information from sensory inputs, and to generate meaningful states internally; however, the functional organisation of DMN that can support these distinct modes of retrieval remains unclear. We used fMRI to examine whether activation within subsystems of DMN differed as a function of retrieval demands, or the type of information to be retrieved, or both. In a picture association task, participants retrieved two types of semantic features about contexts and emotions: in the generate phase, these associations were retrieved from a novel picture, while in a switch phase, participants retrieved a new association for the same image. Semantic context and emotion trials were associated with dissociable DMN subnetworks, indicating that a key dimension of DMN organisation relates to the type of information being accessed. The fronto-temporal and medial temporal DMN showed a preference for emotional and contextual associations, respectively. Relative to the generate phase, the switch phase recruited clusters closer to the heteromodal apex of the principal gradient – a cortical hierarchy separating unimodal and heteromodal regions. There were no differences in this effect between association types. Instead, memory switching was associated with a distinct subnetwork associated with controlled internal cognition. These findings delineate distinct patterns of DMN recruitment for different kinds of associations yet common responses across tasks that reflect retrieval demands. Key points Retrieval of contextual and emotional features relies on distinct default mode subnetworks. Novelty of visual input has an equivalent effect across default mode subnetworks. Secondary associations retrieved from re-presented pictures activate heteromodal end of the principal gradient.