Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of psycho-social support by teachers on improving mental health and hope of adolescents in an earthquake-affected district in Nepal: A cluster randomized controlled trial

Introduction Adolescents can be prone to mental health problems such as post-traumatic stress disorder (PTSD) and depression following disasters. School teachers can provide timely psycho-social support that could instill hope and improve mental health among adolescents in a post-earthquake situation in a low-resource setting. This study examined the effect of training for school teachers on psycho-social support on adolescents’ mental health and hope in an earthquake affected district in Nepal. Methods This cluster randomized controlled trial was conducted in 15 schools in Dhading, a severely affected district by the 2015 earthquake in Nepal. The schools were randomized, as a result, 8 were in the intervention group and 7 in the control group. A total of 1,220 adolescents were recruited at baseline of which 605 adolescents belonged to intervention group and 615 to control group. The follow-up rate at 6 months was 83%. This trial was registered with Clinicaltrials.gov with registration number NCT03387007. Results The intervention did not show significant effects for PTSD symptoms (Intervention*time, β = 0.33, p = 0.536), depression symptoms (Intervention*time, β = 0.30, p = 0.249), and hope (Intervention*time, β = -0.23, p = 0.588), among the adolescents at 6 months follow-up. Conclusion The intervention did not improve mental health symptoms and hope among adolescents at 6 months follow-up. More focused and longer training could be necessary to address mental health among adolescents affected by earthquake. Additionally, longer follow-up could be necessary to assess the changes taking place over time. Trial registration ClinicalTrials.gov NCT03387007.
Retinal topography and microhabitat diversity in a group of dragon lizards

The well‐studied phylogeny and ecology of dragon lizards and their range of visually mediated behaviors provide an opportunity to examine the factors that shape retinal organization. Dragon lizards consist of three evolutionarily stable groups based on their shelter type, including burrows, shrubs, and rocks. This allows us to test whether microhabitat changes are reflected in their retinal organization. We examined the retinae of three burrowing species (Ctenophorus pictus, C. gibba, and C. nuchalis), and three species that shelter in rock crevices (C. ornatus, C. decresii, and C. vadnappa). We used design‐based stereology to sample both the photoreceptor array and neurons within the retinal ganglion cell layer to estimate areas specialized for acute vision. All species had two retinal specializations mediating enhanced spatial acuity: a fovea in the retinal center and a visual streak across the retinal equator. Furthermore, all species featured a dorsoventrally asymmetric photoreceptor distribution with higher photoreceptor densities in the ventral retina. This dorsoventral asymmetry may provide greater spatial summation of visual information in the dorsal visual field. Burrow‐dwelling species had significantly larger eyes, higher total numbers of retinal cells, higher photoreceptor densities in the ventral retina, and higher spatial resolving power than rock‐dwelling species. C. pictus, a secondary burrow‐dwelling species, was the only species that changed burrow usage over evolutionary time, and its retinal organization revealed features more similar to rock‐dwelling species than other burrow‐dwelling species. This suggests that phylogeny may play a substantial role in shaping retinal organization in Ctenophorus species compared to microhabitat occupation.
A GDSL Esterase/Lipase Catalyzes the Esterification of Lutein in Bread Wheat

The discovery of an apoplastic enzyme responsible for esterifying carotenoids that is unexpectedly spatially separated from its plastidic substrate, lutein, affords new ways to biofortify crops. Xanthophylls are a class of carotenoids that are important micronutrients for humans. They are often found esterified with fatty acids in fruits, vegetables, and certain grains, including bread wheat (Triticum aestivum). Esterification promotes the sequestration and accumulation of carotenoids, thereby enhancing stability, particularly in tissues such as in harvested wheat grain. Here, we report on a plant xanthophyll acyltransferase (XAT) that is both necessary and sufficient for xanthophyll esterification in bread wheat grain. XAT contains a canonical Gly-Asp-Ser-Leu (GDSL) motif and is encoded by a member of the GDSL esterase/lipase gene family. Genetic evidence from allelic variants of wheat and transgenic rice (Oryza sativa) calli demonstrated that XAT catalyzes the formation of xanthophyll esters. XAT has broad substrate specificity and can esterify lutein, β-cryptoxanthin, and zeaxanthin using multiple acyl donors, yet it has a preference for triacylglycerides, indicating that the enzyme acts via transesterification. A conserved amino acid, Ser-37, is required for activity. Despite xanthophylls being synthesized in plastids, XAT accumulated in the apoplast. Based on analysis of substrate preferences and xanthophyll ester formation in vitro and in vivo using xanthophyll-accumulating rice callus, we propose that disintegration of the cellular structure during wheat grain desiccation facilitates access to lutein-promoting transesterification.
The Involvement of the Banana F-Box Protein MaEBF1 in Regulating Chilling-Inhibited Starch Degradation through Interaction with a MaNAC67-Like Protein

Low-temperature storage is a common strategy for preserving and transporting vegetables and fruits. However, many fruits are hypersensitive to chilling injury, including bananas. In the present study, storage conditions of 11 °C delayed the ripening of Fenjiao (Musa ABB Pisang Awak) banana, and the pulp could be softened after ethephon treatment. Storage conditions of 7 °C prevented fruit from fully softening, and fruit contained a significantly higher starch content and lower soluble sugar content. MaEBF1, a critical gene component in the ethylene signaling pathway, was repressed during ripening after fruit had been stored for 12 days at 7 °C. The expression of a series of starch degradation-related genes and a MaNAC67-like gene were also severely repressed. Both MaEBF1 and MaNAC67-like genes were ethylene-inducible and localized in the nucleus. MaNAC67-like protein was able to physically bind to the promoter of genes associated with starch degradation, including MaBAM6, MaSEX4, and MaMEX1. Yeast two-hybrid, GST-pull down, and BiFC assays showed that MaEBF1 interacted with the MaNAC67-like protein, and their interaction further activated the promoters of MaBAM6 and MaSEX4. The current study indicates that MaNAC67-like is a direct regulator of starch degradation and potential for involvement in regulating chilling-inhibited starch degradation by interacting with the ethylene signaling components in banana fruit. The present work paves the way for further functional analysis of MaEBF1 and MaNAC67-like in banana, which will be useful for understanding the regulation of banana starch metabolism and fruit ripening.
Precision medicine in severe pediatric asthma: opportunities and challenges

Purpose of review Severe pediatric asthma exerts a substantial burden on patients, their families and society. This review provides an update on the latest insights and needs regarding the implementation of precision medicine in severe pediatric asthma. Recent findings Biologicals targeting underlying inflammatory pathways are increasingly available to treat children with severe asthma, holding the promise to enable precision medicine in this heterogeneous patient population with high unmet clinical needs. However, the current understanding of which child would benefit from which type or combination of biologicals is still limited, as most evidence comes from adult studies and might not be generalizable to the pediatric population. Studies in pediatric severe asthma are scarce due to the time-consuming effort to diagnose severe asthma and the challenge to recruit sufficient study participants. The application of innovative systems medicine approaches in international consortia might provide novel leads for – preferably noninvasive – new biomarkers to guide precision medicine in severe pediatric asthma. Summary Despite the increased availability of targeted treatments for severe pediatric asthma, clinical decision-making tools to guide these therapies are still lacking for the individual pediatric patient.
Headgroup Structure and Cation Binding in Phosphatidylserine Lipid Bilayers.

Phosphatidylserine (PS) is a negatively charged lipid type commonly found in eukaryotic membranes, where it interacts with proteins via nonspecific electrostatic interactions as well as via specific binding. Moreover, in the presence of calcium ions, PS lipids can induce membrane fusion and phase separation. Molecular details of these phenomena remain poorly understood, partly because accurate models to interpret the experimental data have not been available. Here we gather a set of previously published experimental NMR data of C-H bond order parameter magnitudes, |S CH |, for pure PS and mixed PS:PC (phosphatidylcholine) lipid bilayers, and augment this data set by measuring the signs of S CH in the PS headgroup using S-DROSS solid-state NMR spectroscopy. The augmented data set is then used to assess the accuracy of the PS headgroup structures in, and the cation binding to, PS-containing membranes in the most commonly used classical molecular dynamics (MD) force fields including CHARMM36, Lipid17, MacRog, Slipids, GROMOS-CKP, Berger, and variants. We show large discrepancies between different force fields, and that none of them reproduces the NMR data within experimental accuracy. However, the best MD models can detect the most essential differences between PC and PS headgroup structures. The cation binding affinity is, in line with our previous results for PC lipids, not captured correctly by any of the PS force fields. Moreover, the simulated response of PS headgroup to bound ions can differ from experiments even qualitatively. The collected experimental dataset and simulation results will pave the way for development of lipid force fields that correctly describe the biologically relevant negatively charged membranes and their interactions with ions. This work is part of the NMRlipids open collaboration project (nmrlipids.blogspot.fi).
The subcortical maternal complex protein Nlrp4f is involved in cytoplasmic lattice formation and organelle distribution

ABSTRACT In mammalian oocytes and embryos, the subcortical maternal complex (SCMC) and cytoplasmic lattices (CPLs) are two closely related structures. Their detailed compositions and functions remain largely unclear. Here, we characterize Nlrp4f as a novel component associated with the SCMC and CPLs. Disruption of maternal Nlrp4f leads to decreased fecundity and delayed preimplantation development in the mouse. Lack of Nlrp4f affects organelle distribution in mouse oocytes and early embryos. Depletion of Nlrp4f disrupts CPL formation but does not affect the interactions of other SCMC proteins. Interestingly, the loss of Khdc3 or Tle6, two other SCMC proteins, also disrupts CPL formation in mouse oocytes. Thus, the absence of CPLs and aberrant distribution of organelles in the oocytes caused by disruption of the examined SCMC genes, including previously reported Zbed3, Nlrp5, Ooep and Padi6, indicate that the SCMC is required for CPL formation and organelle distribution. Consistent with the role of the SCMC in CPL formation, the SCMC forms before CPLs during mouse oogenesis. Together, our results suggest that the SCMC protein Nlrp4f is involved in CPL formation and organelle distribution in mouse oocytes. Summary: Nlrp4f is identified as a novel component of the subcortical maternal complex that is required for organelle distribution and cytoplasmic lattice formation, and is probably involved in mouse preimplantation development and female fertility.
Editor's Note: LOX-Mediated Collagen Cross-linking Is Responsible for Fibrosis-Enhanced Metastasis.

The editors were made aware of concerns regarding [this article][1] ([1][2]). An internal review by the editors determined that lanes 2–4 of the pSMAD2 Western blot image in Supplementary Fig. S3C are identical to the LOX Western blot image in Supplementary Fig. S3D. 1. 1. [↵][3]1. Cox TR
The pharmacotherapeutic management of pediatric Crohn’s disease

ABSTRACT Introduction: Crohn’s disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract. The aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and if possible, achieve mucosal healing. Areas covered: This review summarizes evidence for the various therapeutic options in the treatment of children with CD. Exclusive enteral nutrition, corticosteroids, and biologics may be used for induction of remission. Immunomodulators (thiopurines, methotrexate) and biologics (infliximab, adalimumab) may be employed for maintenance of remission to prevent flares of disease and avoid chronic steroid use. In cases of fibrotic disease, intestinal perforations, or medically refractory, surgery may be the best therapeutic option. Expert opinion: Exclusive enteral nutrition, corticosteroids, and biologics (including anti-TNF inhibitors) may be used for induction of remission in patients with active flare of their disease. Immunomodulators and TNF inhibitors may be used for maintenance of remission. Early use of anti-TNF inhibitors in patients with moderate to severe CD may improve efficacy and prevent penetrating complications of disease. While pediatric data is limited, newer biologics, such as vedolizumab and ustekinumab, are used off-label in anti-TNF refractory disease.
Tubulin mutations in brain development disorders: Why haploinsufficiency does not explain TUBA1A tubulinopathies

The neuronal cytoskeleton performs incredible feats during nervous system development. Extension of neuronal processes, migration, and synapse formation rely on the proper regulation of microtubules. Mutations that disrupt the primary α‐tubulin expressed during brain development, TUBA1A, are associated with a spectrum of human brain malformations. One model posits that TUBA1A mutations lead to a reduction in tubulin subunits available for microtubule polymerization, which represents a haploinsufficiency mechanism. We propose an alternative model for the majority of tubulinopathy mutations, in which the mutant tubulin polymerizes into the microtubule lattice to dominantly “poison” microtubule function. Nine distinct α‐tubulin and ten β‐tubulin genes have been identified in the human genome. These genes encode similar tubulin proteins, called isotypes. Multiple tubulin isotypes may partially compensate for heterozygous deletion of a tubulin gene, but may not overcome the disruption caused by missense mutations that dominantly alter microtubule function. Here, we describe disorders attributed to haploinsufficiency versus dominant negative mechanisms to demonstrate the hallmark features of each disorder. We summarize literature on mouse models that represent both knockout and point mutants in tubulin genes, with an emphasis on how these mutations might provide insight into the nature of tubulinopathy patient mutations. Finally, we present data from a panel of TUBA1A tubulinopathy mutations generated in yeast α‐tubulin that demonstrate that α‐tubulin mutants can incorporate into the microtubule network and support viability of yeast growth. This perspective on tubulinopathy mutations draws on previous studies and additional data to provide a fresh perspective on how TUBA1A mutations disrupt neurodevelopment.
From habitat use to social behavior: natural history of a voiceless poison frog, Dendrobates tinctorius

Descriptive studies of natural history have always been a source of knowledge on which experimental work and scientific progress rely. Poison frogs are a well-studied group of small Neotropical frogs with diverse parental behaviors, distinct calls, and bright colors that warn predators about their toxicity; and a showcase of advances in fundamental biology through natural history observations. The dyeing poison frog, Dendrobates tinctorius, is emblematic of the Guianas region, widespread in the pet-trade, and increasingly popular in research. This species shows several unusual behaviors, such as the lack of advertisement calls and the aggregation around tree-fall gaps, which remain poorly described and understood. Here, we summarize our observations from a natural population of D. tinctorius in French Guiana collected over various field trips between 2009 and 2017; our aim is to provide groundwork for future fundamental and applied research spanning parental care, animal dispersal, disease spread, habitat use in relation to color patterns, and intra specific communication, to name a few. We report sex differences in habitat use and the striking invasion of tree-fall gaps; describe their courtship and aggressive behaviors; document egg development and tadpole transport; and discuss how the knowledge generated by this study could set the grounds for further research on the behavior, ecology, and conservation of this species.
Homologous Regulation of Mu Opioid Receptor Recycling by Gβγ, Protein Kinase C, and Receptor Phosphorylation

Membrane trafficking and receptor signaling are two fundamental cellular processes that interact constantly. Although how trafficking regulates signaling is well studied, how signaling pathways regulate trafficking is less well understood. Here, we use the mu opioid receptor (MOR), the primary target for opioid analgesics, to define a signaling pathway that dynamically regulates postendocytic receptor recycling. By directly visualizing individual MOR recycling events, we show that agonist increases MOR recycling. Inhibition of Gβγ, phospholipase C, or protein kinase C mimicked agonist removal, whereas activation of Gβγ increased recycling even after agonist removal. Phosphorylation of serine 363 on the C-terminal tail of MOR was required and sufficient for agonist-mediated regulation of MOR recycling. Our results identify a feedback loop that regulates MOR recycling via Gβγ, protein kinase C, and receptor phosphorylation. This could serve as a general model for how signaling regulates postendocytic trafficking of G protein–coupled receptors. SIGNIFICANCE STATEMENT G protein–coupled receptor (GPCR) localization in the endosome is being increasingly recognized as an important and distinct component of GPCR signaling and physiology. This study identifies a G protein–dependent and protein kinase C–dependent signaling pathway that dynamically regulates the endosomal localization of the mu opioid receptor, the primary target of opioid analgesics and abused drugs. This pathway could provide a mechanism to manipulate spatial encoding of opioid signaling and physiology.
Extended Duration of Dual‐Antiplatelet Therapy After Percutaneous Coronary Intervention: How Long Is Too Long?

T hemost recent American College of Cardiology/American Heart Association guidelines on duration of dualantiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) give a class I recommendation to continue DAPT for at least 12 months after an acute coronary syndrome (ACS) and at least 6 months after revascularization in the setting of stable ischemic heart disease. These guidelines also give a class IIb recommendation for continuation of DAPT beyond 6 and 12 months in patients with stable ischemic heart disease and ACS, respectively, if these patients have tolerated DAPT without a bleeding event and are at low risk for bleeding in the future. However, they do not provide any guidance with respect to how long DAPT should be continued and leave it to the clinician to discuss the risks versus benefits with the patient and individualize antiplatelet therapy. Therefore, in clinical practice, we often see patients on DAPT several years after a PCI as they are instructed by their providers to never discontinue them. In fact, given how much the importance of taking DAPT in the early period after PCI is emphasized, patients at times are uncomfortable stopping the second antiplatelet agent at any time. The lack of a clear recommendation is not surprising, despite multiple recent randomized controlled trials evaluating differing durations of extended DAPT given several evolving factors and the overall risk/benefits of DAPT. Guidelines commenting on DAPT duration have largely included trials using clopidogrel and early-generation stents. The advent of more potent P2Y12 inhibitors, such as prasugrel and ticagrelor, has reduced major adverse cardiovascular events, but at the cost of increased bleeding. On the other hand, the newer-generation DESs, with their thinner stent struts, a more biocompatible polymer, and favorable drugeluting characteristics, have considerably decreased the risk of stent thrombosis, particularly late stent thrombosis. Although extended DAPT duration has been associated with reduction in recurrent myocardial infarction (MI) and cardiovascular death, there are statistically significant increases in major bleeding events. With the increased recognition of bleeding events and advancements in DES technology, it has been hypothesized that shorter durations of DAPT may be more appropriate. The European and American College of Cardiology/American Heart Association guidelines have already reduced the minimum absolutely required duration of DAPT by incorporating short DAPT into their recommendations. However, the question about the value of extended DAPT duration in selected patients still remains to be answered. To our knowledge, there are 4 randomized controlled trials that have compared the efficacy and bleeding outcomes of standard 12-month therapy versus extended-duration DAPT (>24 months), which are listed below:
Dietary patterns of bank employees and their association with socioeconomic, behavioral and labor factors

This paper aimed to evaluate food consumption of bank employees and its association with socioeconomic, behavioral and labor factors. This is a cross-sectional study with 515 bank employees. To evaluate food consumption, a semi-quantitative food frequency questionnaire was used. The analysis of main components with Varimax rotation was used to determine the dietary patterns. Three dietary patterns were identified: “vegetables, fruits, cereals and tubers”, “sweets and snacks” and “traditional and protein”. We found that individuals who did not consume sweeteners were more likely to adhere to the “vegetables, fruits, cereals and tubers” pattern and were less likely to adhere to the “sweets and snacks” and “traditional and protein” patterns. Bank employees who rarely ate in restaurants were three times more likely to adhere to the “sweets and snacks” pattern. However, those who used to consume industrialized seasoning and those who reported receiving low social support were, respectively, 2.3 and 1.5 times more likely to adhere to the “traditional and protein” pattern. We can conclude that food consumption of bank employees is not related to the sociodemographic conditions of these individuals, and behavior and perception of social support received is associated with these dietary patterns.