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The majority of experiments investigating the immune response to gastrointestinal helminth infection use a single bolus infection. However, in situ individuals are repeatedly infected with low doses. Therefore, to model natural infection, mice were repeatedly infected (trickle infection) with low doses of Trichuris muris. Trickle infection resulted in the slow acquisition of immunity reflected by a gradual increase in worm burden followed by partial expulsion. Flow cytometry revealed that the CD4+ T cell response shifted from Th1 dominated to Th2 dominated, which coincided with an increase in Type 2 cytokines. The development of resistance following trickle infection was associated with increased worm expulsion effector mechanisms including goblet cell hyperplasia, Muc5ac production and increased epithelial cell turn over. Depletion of CD4+ T cells reversed resistance confirming their importance in protective immunity following trickle infection. In contrast, depletion of group 2 innate lymphoid cells did not alter protective immunity. T. muris trickle infection resulted in a dysbiotic mircrobiota which began to recover alpha diversity following the development of resistance. These data establish trickle infection as a robust and informative model for analysis of immunity to chronic intestinal helminth infection more akin to that observed under natural infection conditions and confirms the importance of CD4+ T cell adaptive immunity in host protection.

Infection with soil-transmitted helminths (STH) remains a major burden on global health and agriculture. Our understanding of the immunological mechanisms that govern whether an individual is resistant or susceptible to infection is derived primarily from model infections in rodents. Typically, experimental infections employ an artificially high, single bolus of parasites that leads to rapid expulsion of the primary infection and robust immunity to subsequent challenges. However, immunity is generated slowly, and is only partially effective, with individuals in endemic areas retaining low-level infections throughout their lives. Therefore, there is a gap between traditional model STH systems and observations in the field. Here, we review the immune response to traditional model STH infections in the laboratory. We compare these data to studies of natural infection in humans and rodents in endemic areas, highlighting crucial differences between experimental and natural infection. We then detail the literature to date on the use of \"trickle\" infections to experimentally model the kinetics of natural infection.

Health-related quality of life (HRQOL) is affected by numerous clinical variables, including disease activity, damage, fibromyalgia, depression and anxiety. However, these associations have not yet been described in Mexican patients with systemic lupus erythematosus (SLE). To evaluate the relationship between disease activity, damage, depression and fibromyalgia and HRQOL measured by the LupusQoL-instrument in Mexican patients with SLE. A cross-sectional study was conducted in women fulfilling the 1997 ACR classification criteria for SLE. HRQOL was evaluated using a disease-specific instrument for SLE, the LupusQoL (validated for the Spanish-speaking population). Patients were evaluated clinically to determine the degree of disease activity and damage using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and Systemic Lupus International Collaborating Clinics-Damage Index (SLICC), respectively. Fibromyalgia and depression were assessed using the ACR criteria and the CES-D scale, respectively. The relationship between HRQOL and these variables was measured using Spearman's rank correlation coefficient and linear regression analysis. A total of 138 women with SLE, age 40.3±11 years, disease duration 8.8±6.4 years, with disease activity in 51.4%, depression in 50%, damage in 43% and fibromyalgia in 19.6% were included. Poorer HRQOL correlated with depression (r = -0.61; p< 0.005), fibromyalgia (r = -0.42; p< 0.005), disease activity (r = -0.37; p < 0.005) and damage (r = -0.31; p < 0.005). In the multivariate linear regression analysis, damage (β = -3.756, p<0.005), fibromyalgia (β = -0.920, p<0.005), depression (β = -0.911, p<0.005) and disease activity (β = -0.911, p<0.005) were associated with poor HRQOL. SLE disease activity, damage, fibromyalgia and depression were associated with poor HRQOL in our sample of Mexican SLE patients.

We present the assessment of an entropy projection-correction approach, embedded on a high order discontinuous Galerkin (DG) scheme, as an effective and efficient solution for undertaking under-resolved implicit Large Eddy simulations (iLES) of turbulent transonic/supersonic flows. Combining the L 2 projection of the discrete spatial operators onto the entropy variable space with the residual correction of [1] we achieve an entropy conserving/stable (EC/ES) DG discretization of the convective operators upon suitable choice of the associated numerical flux function. The resulting framework shows an improved robustness which is exploited to tackle iLES on severely under-resolved space discretizations, achieving remarkably accurate solutions even on such coarse computational spaces.

Population genetic research has evolved, focusing on selection processes using single nucleotide polymorphisms (SNP) genotyping techniques to study crop traits and domestication. This study explores the adaptation process of three neotropical palms of Acrocomia , a genus that has high potential for oil extraction. Our research focused on their genetic structure, evolutionary significance, and implications of the selection signatures for breeding efforts. We employed genotyping-by-sequencing (GBS) focusing on outlier SNP markers to identify adaptive genes in A. aculeata , A. totai , and A. intumescens across their entire distributions. Our results reveal two major gene pools in A. aculeata : a Central American group and a South American group, mainly influenced by dispersal and biogeographic barriers. Putative selective signatures were identified in candidate genes associated with traits related to oil biosynthesis, pathogen resistance, and adaptation to environmental stress like drought tolerance. A. totai exhibited a pronounced genetic structure influenced by distinct biomes, suggesting recent diversification driven by climatic and geological factors, particularly within the Pantanal biome. A. intumescens displays genetic structuring shaped by the endemic process of biogeographic barriers within the Caatinga biome . Correlations between allele frequencies and climatic variables highlight adaptation to diverse environments, with the annual mean temperature and precipitations being one of the most influential. Candidate genes associated with fatty acid and carotenoid biosynthesis, as well as pathogen resistance and drought tolerance, indicate targets for future breeding studies. Despite the challenges associated with reduced representation sequencing, this study highlights the potential for gene discovery in Acrocomia , offering promising targets to enhance oil yield productivity. Future efforts should prioritize whole-genome sequencing and genotype-environment interaction studies to realize the full potential of Acrocomia spp. in sustainable oil production.

Objectives Ultrasound (US) evaluation is recognized as pivotal in assessing the risk of malignancy (RoM) of thyroid nodules (TNs). Recently, various US-based risk-classification systems (Thyroid Imaging and Reporting Data Systems [TIRADSs] have been developed. An important ongoing project concerns the creation of an international system (I-TIRADS) using unique terminology. Since online tool allow clinicians and patients to stratify the RoM of any TN, the role of computer scientist (CS) should be relevant. This study explored the performance of CS in assessing TNs across the TIRADS categories. Methods The most diffused TIRADSs (i.e., ACR, EU, and K) were considered. Three-hundred scenarios were created. A CS was asked to assess the 300 TNs according to ACR-, EU-, and K-TIRADS. These data were compared with that of clinicians. The inter-observer agreement was estimated with Cohen kappa (κ). Word-cloud plots were used to graph the US descriptors with disagreement. Results The correspondence of the CS’s assessment with the physicians was 100%, 81%, and 43%, using ACR-, EU-, and K-TIRADS, respectively. The CS was unable to classify 19/100 TNs according to EU-TIRADS and 15/100 TNs according to K-TIRADS. The inter-observer agreement between CS and physicians was excellent for ACR-TIRADS (κ = 1), moderate for EU-TIRADS (κ = 0.56), and fair for K-TIRADS (κ = 0.22). Among the non-concordant cases, 16/22 descriptors for EU-TIRADS and 18/18 descriptors for K-TIRADS were found. Conclusion CSs are confident with the ACR-TIRADS lexicon and structure while not with EU- and K-TIRADS, probably because they are pattern-based systems requiring medical training.

Abstract Study Objectives Objective sleep impairments in insomnia disorder (ID) are insufficiently understood. The present study evaluated whether whole-night sleep stage dynamics derived from polysomnography (PSG) differ between people with ID and matched controls and whether sleep stage dynamic features discriminate them better than conventional sleep parameters. Methods Eighty-eight participants aged 21–70 years, including 46 with ID and 42 age- and sex-matched controls without sleep complaints, were recruited through www.sleepregistry.nl and completed two nights of laboratory PSG. Data of 100 people with ID and 100 age- and sex-matched controls from a previously reported study were used to validate the generalizability of findings. The second night was used to obtain, in addition to conventional sleep parameters, probabilities of transitions between stages and bout duration distributions of each stage. Group differences were evaluated with nonparametric tests. Results People with ID showed higher empirical probabilities to transition from stage N2 to the lighter sleep stage N1 or wakefulness and a faster decaying stage N2 bout survival function. The increased transition probability from stage N2 to stage N1 discriminated people with ID better than any of their deviations in conventional sleep parameters, including less total sleep time, less sleep efficiency, more stage N1, and more wake after sleep onset. Moreover, adding this transition probability significantly improved the discriminating power of a multiple logistic regression model based on conventional sleep parameters. Conclusions Quantification of sleep stage dynamics revealed a particular vulnerability of stage N2 in insomnia. The feature characterizes insomnia better than—and independently of—any conventional sleep parameter.

Critically ill patients and patients with haematological cancer are HIV-negative populations at high risk of invasive fungal infections. In intensive-care units, candidaemia and intra-abdominal candidiasis predominate, but aspergillosis has emerged as a lethal, under-recognised cause of pneumonia. In patients with haematological malignancies or who have undergone stem-cell transplantations, pulmonary disease due to aspergillus and other mould diseases predominate. In this Series paper, we provide an update on risk assessment, new diagnostic strategies, and therapeutic approaches. New concepts have emerged for use of risk prediction rules and an evidence base now exists for inclusion of biomarkers (eg, galactomannan, 1,3-β-D-glucan, and PCR assays for Aspergillus spp) into early diagnostic and therapeutic strategies. Imaging techniques remain helpful for early diagnosis of pulmonary mould diseases, with PET techniques offering potential improvements in diagnostic specificity and evaluation of clinical response. Echinocandins and triazoles have been validated extensively for prophylaxis, empirical therapy, and targeted therapy, but an increase in intrinsically resistant fungi and emergence of secondary resistance as a result of drug-induced selection pressure are of major concern. Echinocandins remain a major component of treatment of invasive candidiasis and new triazoles are the best alternative for prophylaxis and therapy of invasive aspergillosis.

An account of work performed at the UNA laboratories since 1992 on the detection and description of interlaminar glial processes, is presented. The incidental observation (serendipity) of longer than expected glial processes in the superficial layers of the cerebral cortex in hemiparkinsonian Cebus apella monkeys, was expanded afterwards to cover the largest possible sampling of representatives of mammalian orders and species, as well as in experimental and pathological conditions, in human and non-human primates. The term interlaminar was coined to differentiate these processes from the classical astroglial stellate, intralaminar ones. Such account grew to the point of inspiring, on speculative grounds, possible roles in the organization of the cerebral cortex. Interlaminar glial processes represent an essentially primate characteristic, affected by neuropathological conditions such as DS and AD and experimental procedures affecting normal sensory input, suggesting thalamic involvement in their normal expression. Their ontogenetic development, phylogenetic evolution and aging changes are described.

Because of their high photon flux, x-ray free-electron lasers (FEL) allow to resolve the structure of individual nanoparticles via coherent diffractive imaging (CDI) within a single x-ray pulse. Since the inevitable rapid destruction of the sample limits the achievable resolution, a thorough understanding of the spatiotemporal evolution of matter on the nanoscale following the irradiation is crucial. We present a technique to track x-ray induced structural changes in time and space by recording two consecutive diffraction patterns of the same single, free-flying nanoparticle, acquired separately on two large-area detectors opposite to each other, thus examining both the initial and evolved particle structure. We demonstrate the method at the extreme ultraviolet (XUV) and soft x-ray Free-electron LASer in Hamburg (FLASH), investigating xenon clusters as model systems. By splitting a single XUV pulse, two diffraction patterns from the same particle can be obtained. For focus intensities of about 2 × 10 12  W cm −2 we observe still largely intact clusters even at the longest delays of up to 650 picoseconds of the second pulse, indicating that in the highly absorbing systems the damage remains confined to one side of the cluster. Instead, in case of five times higher flux, the diffraction patterns show clear signatures of disintegration, namely increased diameters and density fluctuations in the fragmenting clusters. Future improvements to the accessible range of dynamics and time resolution of the approach are discussed.