Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of IL-12p40 and type 1 immunity by Toxoplasma gondii in the absence of the TLR-MyD88 signaling cascade

Toxoplasma gondii is an orally acquired pathogen that induces strong IFN-γ based immunity conferring protection but that can also be the cause of immunopathology. The response in mice is driven in part by well-characterized MyD88-dependent signaling pathways. Here we focus on induction of less well understood immune responses that do not involve this Toll-like receptor (TLR)/IL-1 family receptor adaptor molecule, in particular as they occur in the intestinal mucosa. Using eYFP-IL-12p40 reporter mice on an MyD88-/- background, we identified dendritic cells, macrophages, and neutrophils as cellular sources of MyD88-independent IL-12 after peroral T. gondii infection. Infection-induced IL-12 was lower in the absence of MyD88, but was still clearly above noninfected levels. Overall, this carried through to the IFN-γ response, which while generally decreased was still remarkably robust in the absence of MyD88. In the latter mice, IL-12 was strictly required to induce type I immunity. Type 1 and type 3 innate lymphoid cells (ILC), CD4+ T cells, and CD8+ T cells each contributed to the IFN-γ pool. We report that ILC3 were expanded in infected MyD88-/- mice relative to their MyD88+/+ counterparts, suggesting a compensatory response triggered by loss of MyD88. Furthermore, bacterial flagellin and Toxoplasma specific CD4+ T cell populations in the lamina propria expanded in response to infection in both WT and KO mice. Finally, we show that My88-independent IL-12 and T cell mediated IFN-γ production require the presence of the intestinal microbiota. Our results identify MyD88-independent intestinal immune pathways induced by T. gondii including myeloid cell derived IL-12 production, downstream type I immunity and IFN-γ production by ILC1, ILC3, and T lymphocytes. Collectively, our data reveal an underlying network of immune responses that do not involve signaling through MyD88.
Development of Multiple J-aggregate-gold Nanoparticle Probes for SERRS Multiplexing

Development of multiple J-aggregate-gold nanoparticle probes is necessary to utilize their significantly enhanced Raman scattering for biological diagnostics. As Raman probes have the potential for concurrent imaging of a much higher number of biomarkers than fluorophores, development of the maximum variety of Raman probes is required to take full advantage of their multiplexing. Herein it is reported the decorating of gold nanoparticles with a number of J-aggregate dyes, through development of a negatively charged facilitator assembly and use of an established short chain positive linker. Significantly bright probes were silica encapsulated and demonstrated a notable decrease in fluorescence background. To target these particles to biomarkers, a means of antibody functionalization was explored.
Catalytic metal-based systems for controlled statistical copolymerisation of lactide with a lactone

Polylactide (PLA) is currently considered as a major polymer which could serve as a potential substitute to the widely used petroleum-based plastics. It is typically produced by coordination–insertion polymerisation (Ring-Opening Polymerisation, ROP) of the cyclic ester, lactide (LA), a dimer of lactic acid that is extracted from biomass via biotechnological processing. However, PLA has limitations that hinder its ability to compete with conventional plastics, particularly with regard to its brittle behaviour. Different methodologies have been employed in order to improve the performances of PLA and thereby expand its range of applications. One strategy involves the statistical Ring-Opening coPolymerisation (ROcoP) of LA with another lactone, primarily e-caprolactone (e-CL), which enables the inherent properties of each homopolymer to be incorporated within the same polymer chain. Nevertheless, the difference in the reactivity of LA relative to the lactone comonomer and the occurrence of undesired transesterification creates the challenge of producing a strictly random copolymer. Herein, this review aims to present the variety of metal-based catalysts and/or initiators that target the synthesis of statistical copolymers of LA and lactone, under smooth conditions to ensure the best possible controlled polymerisation process.
Ventricular wall stress and wall shear stress homeostasis predicts cardiac remodeling during pregnancy: A modeling study

Pregnancy is a unique and dynamic process characterized by significant changes in the maternal cardiovascular system that are required to satisfy the increased maternal and fetal metabolic demands. Profound structural and hemodynamic adaptations occur during healthy pregnancy that allows the mother to maintain healthy hemodynamics and provide an adequate uteroplacental blood circulation to ensure physiological fetal development. Investigating these adaptations is crucial for understanding the physiology of pregnancy and may provide important insights for the management of high‐risk pregnancies. However, no previous modeling studies have investigated the maternal cardiac structural changes that occur during gestation. This study, therefore, had two aims. The first was to develop a lumped parameter model of the whole maternal circulation that is suitable for studying global hemodynamics and cardiac function at different stages of gestation. The second was to test the hypothesis that myofiber stress and wall shear stress homeostasis principles can be used to predict cardiac remodeling that occurs during normal pregnancy. Hemodynamics and cardiac variables predicted from simulations with and without controlled cardiac remodeling algorithms were compared and evaluated with reference clinical data. While both models reproduced the hemodynamic variations that arise in pregnancy, importantly, we show that the structural changes that occur with pregnancy could be predicted by assuming invariant homeostatic “target” values of myocardial wall stress and chamber wall shear stress.
Comparative Genomics Reveals Recent Adaptive Evolution in Himalayan Giant Honeybee Apis laboriosa

Abstract The Himalayan giant honeybee, Apis laboriosa, is the largest individual honeybee with major ecological and economic importance in high-latitude environments. However, our understanding of its environmental adaptations is circumscribed by the paucity of genomic data for this species. Here, we provide a draft genome of wild A. laboriosa, along with a comparison to its closely related species, Apis dorsata. The draft genome of A. laboriosa based on the de novo assembly is 226.1 Mbp in length with a scaffold N50 size of 3.34 Mbp, a GC content of 32.2%, a repeat content of 6.86%, and a gene family number of 8,404. Comparative genomics analysis revealed that the genes in A. laboriosa genome have undergone stronger positive selection (2.5 times more genes) and more recent duplication/loss events (6.1 times more events) than those in the A. dorsata genome. Our study implies the potential molecular mechanisms underlying the high-altitude adaptation of A. laboriosa and will catalyze future comparative studies to understand the environmental adaptation of modern honeybees.
A Systematic Review and Meta-Analysis of the Relationship Between the Radiation Absorbed Dose to the Thyroid and Response in Patients Treated with Radioiodine for Graves' Disease

Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08–1.14] and OR = 1.09 [CI 1.06–1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120–180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17–5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose–response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments.
Radiomics in Oncology: A Practical Guide

Radiomics refers to the extraction of mineable data from medical imaging and has been applied within oncology to improve diagnosis, prognostication, and clinical decision support, with the goal of delivering precision medicine. The authors provide a practical approach for successfully implementing a radiomic workflow from planning and conceptualization through manuscript writing. Applications in oncology typically are either classification tasks that involve computing the probability of a sample belonging to a category, such as benign versus malignant, or prediction of clinical events with a time-to-event analysis, such as overall survival. The radiomic workflow is multidisciplinary, involving radiologists and data and imaging scientists, and follows a stepwise process involving tumor segmentation, image preprocessing, feature extraction, model development, and validation. Images are curated and processed before segmentation, which can be performed on tumors, tumor subregions, or peritumoral zones. Extracted features typically describe the distribution of signal intensities and spatial relationship of pixels within a region of interest. To improve model performance and reduce overfitting, redundant and nonreproducible features are removed. Validation is essential to estimate model performance in new data and can be performed iteratively on samples of the dataset (cross-validation) or on a separate hold-out dataset by using internal or external data. A variety of noncommercial and commercial radiomic software applications can be used. Guidelines and artificial intelligence checklists are useful when planning and writing up radiomic studies. Although interest in the field continues to grow, radiologists should be familiar with potential pitfalls to ensure that meaningful conclusions can be drawn. Online supplemental material is available for this article. Published under a CC BY 4.0 license.
Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study

Background: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study’s hypothesis was that certain treatments are associated with lower COVID-19 mortality. Methods: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19–related pharmacologic and organ support treatments. The outcome was in-hospital mortality. Results: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score–matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score–matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). Conclusions: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients. In a retrospective cohort consisting of 2,070 critically ill COVID-19 patients treated in six hospitals, multivariable regression analysis showed lower in-hospital mortality associated with apixaban, aspirin, or enoxaparin treatment. Propensity score–matching analyses demonstrated lower mortality for patients receiving apixaban (27% [96 of 360] vs. 37% [133 of 360]), aspirin (26% [121 of 473] vs. 30% [140 of 473]), or enoxaparin (25% [87 of 347] vs. 34% [117 of 347]) compared to matched controls. Supplemental Digital Content is available in the text.
Ammonia impairs tight junction barriers by inducing mitochondrial dysfunction in Caco‐2 cells

Ammonia is one of the major metabolites produced by intestinal microorganisms; however, its role in intestinal homeostasis is poorly understood. The present study investigated the regulation of intestinal tight junction (TJ) proteins by ammonia and the underlying mechanisms in human intestinal Caco‐2 cells. Ammonia (15, 30, and 60 mM) increased the permeability of the cells in a dose‐dependent manner, as indicated by reduced transepithelial electrical resistance and increased dextran flux. Immunoblot and immunofluorescence analyses revealed that the ammonia‐induced increase in TJ permeability reduced the membrane localization of TJ proteins such as zonula occludens (ZO)1, ZO2, occludin, claudin‐1, and claudin‐3. DNA microarray analysis identified a biological pathway “response to reactive oxygen species” enriched by ammonia treatment, indicating the induction of oxidative stress in the cells. Ammonia treatment also increased the malondialdehyde content and decreased the ratio of reduced to oxidized glutathione. Meanwhile, ammonia treatment‐induced mitochondrial dysfunction, as indicated by the downregulation of genes associated with the electron transport chain, reduction of the cellular ATP, NADH, and tricarboxylic acid cycle intermediate content, and suppression of the mitochondrial membrane potential. In contrast, N‐acetyl cysteine reversed the ammonia‐induced impairment of TJ permeability and structure without affecting the mitochondrial parameters. Collectively, ammonia impaired the TJ barrier by increasing oxidative stress in Caco‐2 cells. A mitochondrial dysfunction is possibly an event preceding ammonia‐induced oxidative stress. The findings of this study could potentially improve our understanding of the interplay between intestinal microorganisms and their hosts.
Automatic measurement of axial vertebral rotation in 3D vertebral models

Axial Vertebral Rotation (AVR) is a significant indicator of adolescent idiopathic scoliosis (AIS). A host of methods are provided to measure AVR on coronal plane radiographs or 3D vertebral model. This paper provides a method of automatic AVR measurement in 3D vertebral model that is based on point cloud segmentation neural network and the tip of the spinous process searching algorithm. An improved PointNet using multi-input and attention mechanism named Multi-Input PointNet is proposed, which can segment the upper and lower endplates of the vertebral model accurately to determine the transverse plane of vertebral model. An algorithm is developed to search the tip of the spinous process according to the special structure of vertebrae. AVR angle is measured automatically using the midline of vertebral model and projection of y-axis on the transverse plane of vertebral model based on points obtained above. We compare automatic measurement results with manual measurement results on different vertebral models. The experiment shows that automatic results can achieve accuracy of manual measurement results and the correlation coefficient of them is 0.986, proving our automatic AVR measurement method performs well.
Generous hosts: Growth of 'Candidatus Liberibacter asiaticus' in Madagascar periwinkle (Catharanthus roseus) highlights its nutritional needs.

‛Candidatus Liberibacter asiaticus', the putative causal agent of citrus greening is not available in pure culture yet. In addition to trees of citrus and citrus relatives, ‛Ca. L. asiaticus' can grow in Madagascar periwinkle (Catharanthus roseus). Using GC-MS, we compared the phloem sap composition in sweet orange ‛Valencia' (Citrus sinensis) and periwinkle plants after the infection with ‛Ca. L. asiaticus'. Interestingly, in contrast to our previous studies of total leaf metabolites, we found that, compared to uninfected phloem sap, we found that the organic acids implicated in the TCA cycle including citrate, isocitrate, succinate, fumarate, and malate were reduced significantly in the infected phloem saps of both species. As a result of the reduction of organic acids content, the pH of infected phloem saps was increased. We hypothesize that the bacterial growth induces the mitochondrial TCA cycle in parenchyma cells to produce more of these compounds to be used as a bacterial carbon source. Once these compounds reach a low level in the phloem sap, the bacterium may send a signal, yet to be identified, to initiate a feedback loop to further induce the TCA cycle. Phloem blockage might be another reason behind the reduced the translocation of TCA cycle intermediates within the phloem. The net result, localized availability of organic acids likely benefits the bacterial growth and may explain the unequal distribution of 'Ca L. asiaticus' within infected trees. These findings may help in designing media for the pure culturing of ‛Ca. L. asiaticus'.
Rapid detection of peach shoot blight caused by Phomopsis amygdali utilizing a new target gene identified from genome sequences within loop-mediated isothermal amplification.

Peach shoot blight (PSB) caused by Phomopsis amygdali is a serious threat to the healthy development of the peach industry and leads to 30-50 % damage to peach production in southern China. In this study, loop-mediated isothermal amplification (LAMP) technology was used to detect the P. amygdali target of a gene of GME6801 that was unique in the whole genome of the pathogen compared with that of Diaporthe (Phomopsis) longicolla TWH P74, Fusurium graminearum PH-1, Colletotrichum gloeosporioides SMCG1 and Magnaporthe oryzae 70-15. Blast comparison of this gene sequence in NCBI database showed that no homologous sequences were found. Therefore, the gene sequence of GME6801 was used to design two pairs of LAMP primers and one pair of PCR primers. The results showed that both of primer sets were specific to the 15 strains of P. amygdali, and the other 15 fungal strains presented negative reactions, similar to the control. In addition, 50 pg of genomic DNA of P. amygdali in a 25 μl reaction system could be detected by LAMP assay which was 100 times more sensitive than PCR. Furthermore, the GME6801 LAMP assay was used to detect artificially inoculated twigs of the pathogen, disease twigs within significantly symptomatic PSB in the field and healthy twigs in the same orchard, with the detection rates of 100%, 75% and 20.8%, respectively. However, the detection rates of conventional PCR were separately 100%, 62.5% and 16.7%. The results indicated that GME6801-based LAMP could be used for P. amygdali detection as its specificity, sensitivity and simplicity. This study provides a rapid experimental basis for the identification and prediction of P. amygdali that causes PSB and is beneficial for precise prevention and control of the disease.
Solution-Processed Hybrid Graphene Flake/2H-MoS2 Quantum Dot Heterostructures for Efficient Electrochemical Hydrogen Evolution

We designed solution-processed, flexible hybrid graphene flake/2H-MoS2 quantum dot (QD) heterostructures, showing enhanced electrocatalytic activity for the hydrogen evolution reaction (HER) with respect to their native individual components. The 2H-MoS2 QDs are produced through a scalable, environmentally friendly, one-step solvothermal approach from two-dimensional (2D) 2H-MoS2 flakes obtained by liquid phase exfoliation (LPE) of their bulk counterpart in 2-Propanol. This QDs synthesis avoids the use of high boiling point and/or toxic solvents. Graphene flakes are produced by LPE of graphite in N-Methyl-2-pyrrolidone. The electrochemical properties of 2H-MoS2 QDs and their HER-favorable chemical and electronic coupling with graphene enable to reach current density of 10 mA/cm² at an overpotential of 136 mV, surpassing the performances of graphene flake/2H-MoS2 (1T-MoS2) flake heterostructures. Our approach provides a shortcut, viable and cost-effective method for enhancing the 2D materials electrocataly.