Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition

Significance Sickle cell trait has repeatedly been identified as a major human malaria resistance factor. Despite this, the exact mechanism of resistance is unclear. These studies demonstrate how the evolutionarily significant sickle hemoglobin affects Plasmodium falciparum infection success and leads to a better understanding of the molecular basis and pathogenesis of malaria infection. Sickle cell trait (AS) confers partial protection against lethal Plasmodium falciparum malaria. Multiple mechanisms for this have been proposed, with a recent focus on aberrant cytoadherence of parasite-infected red blood cells (RBCs). Here we investigate the mechanistic basis of AS protection through detailed temporal mapping. We find that parasites in AS RBCs maintained at low oxygen concentrations stall at a specific stage in the middle of intracellular growth before DNA replication. We demonstrate that polymerization of sickle hemoglobin (HbS) is responsible for this growth arrest of intraerythrocytic P. falciparum parasites, with normal hemoglobin digestion and growth restored in the presence of carbon monoxide, a gaseous antisickling agent. Modeling of growth inhibition and sequestration revealed that HbS polymerization-induced growth inhibition following cytoadherence is the critical driver of the reduced parasite densities observed in malaria infections of individuals with AS. We conclude that the protective effect of AS derives largely from effective sequestration of infected RBCs into the hypoxic microcirculation.
Sponge dermal membrane morphology: Histology of cell‐mediated particle transport during skeletal growth

The keratose demosponge, Dysidea etheria, secretes a skeletal network of interconnecting spongin fibers and incorporates sand grains and other foreign particles into the fibers. Previous studies showed that foreign particles enhanced fiber growth and increased the stiffness of skeletal fibers. The present study uses light and electron microscopy to study the mechanism of particle incorporation. These histological observations show that particles become engulfed into thickened regions of the mesohyl of the dermal membrane, whereupon ameboid cells contact particles and secrete an electron dense layer of extracellular material onto the particle surface. Within several days, particles are moved towards primary skeletal fibers located at cone‐shaped protuberances on the sponge surface called conules. Particles accumulate at conules and are consolidated by secretion of spongin at the growing fiber apices. The observations suggest that coordinated migration of groups of mesohyl cells control particle transport to conules and that patterns of cell migration are associated with the structural organization of the dermal membrane. Particle transport may be homologous and analogous to spicule transport in other demosponges.
The Role of Macrophages in the Pathogenesis of ALI/ARDS

Despite development in the understanding of the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the underlying mechanism still needs to be elucidated. Apart from leukocytes and endothelial cells, macrophages are also essential for the process of the inflammatory response in ALI/ARDS. Notably, macrophages play a dual role of proinflammation and anti-inflammation based on the microenvironment in different pathological stages. In the acute phase of ALI/ARDS, resident alveolar macrophages, typically expressing the alternatively activated phenotype (M2), shift into the classically activated phenotype (M1) and release various potent proinflammatory mediators. In the later phase, the M1 phenotype of activated resident and recruited macrophages shifts back to the M2 phenotype for eliminating apoptotic cells and participating in fibrosis. In this review, we summarize the main subsets of macrophages and the associated signaling pathways in three different pathological phases of ALI/ARDS. According to the current literature, regulating the function of macrophages and monocytes might be a promising therapeutic strategy against ALI/ARDS.
Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant Treatment in Female Outpatients with Major Depressive Disorder

Objective Some clinical studies have found alterations in the levels of serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) after applying antidepressant treatment in patients with major depressive disorder (MDD). We evaluated the serum BDNF and GDNF levels before and after 12 weeks of antidepressant treatment in MDD outpatients. Methods Serum BDNF and GDNF levels were measured in 23 female MDD outpatients at baseline and after 12 weeks of treatment. The severity of depression was measured with the Hamilton Depression Rating Scale-17 (HAMD-17). Remission of MDD to the treatment was defined as a posttreatment HAMD-17 score of <7. Results Among MDD patients, 19 (82.6%) subjects were in mild to moderate depression. The whole MDD patients had significantly higher serum BDNF and GDNF levels at baseline than those after 12 weeks of antidepressant treatment. The baseline serum BDNF and GDNF levels did not significantly between the remission and nonremission groups. The significant alteration in both BDNF and GDNF levels after antidepressant treatment were observed in patients with remission. Conclusion The present study suggests that the baseline serum BDNF and GDNF levels are higher than the posttreatment levels in some mild-to-moderate MDD outpatients and the significant alteration in BDNF and GDNF level after treatment were observed in patients with remission.
Retrospective analysis of a lactose breath test in a gastrointestinal symptomatic population of Northeast Italy: use of (H2+2CH4) versus H2 threshold

Background Lactose malabsorption is normally evaluated by measuring exhaled H2 produced by intestinal flora, from unabsorbed lactose. However, differing microbiome composition can lead to the production of CH4 instead of H2; hence, some authors challenge the H2 method sensitivity and favor the evaluation of both intestinal gases. Aim To compare different approaches to usage of a lactose breath test for lactose malabsorption diagnosis, after medical evaluation of gastrointestinal symptoms. Methods In a retrospective observational study, we compared the 2 approaches in a population of 282 subjects in Northern Italy. Following oral lactose administration, exhaled samples were harvested every 30 minutes for 4 hours and prepared for H2 and CH4 analysis. Basal gas levels were subtracted from H2 and CH4 ppm and values at 4 hours and peaks were considered for analysis. Results Applying the standard methodology, which takes separately into consideration H2 and CH4 produced in the intestinal lumen, the results indicated that 11.7% of the patients were diagnosed “positive” for hypolactasia, differently from what was expected. Conversely, taking into consideration the sum of H2 and CH4, the percentage increased to 62.8%, closer to the expected one. No significant differences were found when comparing the 2 groups for age, gender, or symptoms. The sizable difference between the 2 approaches is likely linked to gut microbiome variability, and consequently the different production of the 2 gases, in the population. Conclusion The threshold normally used for lactose breath test should be reconsidered and changed, merging H2 and CH4 stoichiometric values to increase sensitivity.
Coded Caching Gains for Cache-less Users Eleftherios Lampiris

The work identifies the performance limits of the multiple-input single-output broadcast channel where cacheaided users coincide with users that do not have caches. The main contribution is a new algorithm that employs perfect matchings on a bipartite graph to offer full multiplexing as well as full coded-caching gains to both cache-aided as well as cache-less users. This performance is shown to be within a factor of at most 3 from the optimal, under the assumption of linear oneshot schemes. An interesting outcome is the following: starting from a singlestream centralized coded caching setting with normalized cache size γ, then every addition of an extra transmit antenna allows for the addition of approximately 1/γ extra cache-less users, at no added delay costs. For example, starting from a single-stream coded caching setting with γ = 1/100, every addition of a transmit antenna, allows for serving approximately an additional 100 more cache-less users, without any increase in the overall delay. Finally the work reveals the role of multiple antennas in removing the penalties typically associated to cache-size unevenness, as it shows that the performance in the presence of both cache-less and cache-aided users, matches the optimal (under uncoded cache placement) performance of the corresponding symmetric case where the same cumulative cache volume is split evenly across all users.
Pregnancy-induced growth of a spinal hemangioblastoma: presumed mechanisms and their implications for therapeutic approaches

Hemangioblastomas are benign tumors of the central nervous system (CNS) that may occur either sporadically or as part of von Hippel–Lindau (VHL) disease, in which they coexist with a series of other tumors outside the CNS. Because of their low mitosis rate, hemangioblastomas usually have slow-growing and late manifestations, but may cause sudden neurological symptoms if tumor hemorrhage occurs. Few studies have evaluated the impact of pregnancy on the evolution of hemangioblastomas. Some authors have reported tumor growth in women with VHL disease, but no such association was observed by others. The influence of pregnancy on sporadic hemangioblastomas remains largely unexplored. We report here the case of a pregnant woman whose first manifestation of sporadic spinal hemangioblastoma was life-threatening, rapidly progressive dysautonomia. In addition, we discuss the role of pregnancy in the triggering of symptoms, as well as the possibility of medically indicated delivery for the management of these tumors.
CXCL13 produced by macrophages due to Fli1 deficiency may contribute to the development of tissue fibrosis, vasculopathy and immune activation in systemic sclerosis

CXCL13, a chemokine for B cells, follicular T cells, T helper 17 cells, and regulatory T cells, is reported to contribute to the development of systemic sclerosis (SSc), reflecting aberrant activation of immune system. To better understand the role of CXCL13 in SSc, we investigated the influence of Fli1 deficiency, a potential predisposing factor of this disease, on CXCL13 expression and assessed the clinical correlation of serum CXCL13 levels by multivariate regression analysis. Haploinsufficient loss of Fli1 remarkably induced CXCL13 expression in murine peritoneal macrophages, while gene silencing of FLI1 did not affect the expression of CXCL13 in human dermal fibroblasts and human dermal microvascular endothelial cells. Serum CXCL13 levels were elevated in SSc patients compared with healthy controls and correlated positively with skin score and negatively with pulmonary function test results. SSc patients with elevated serum CXCL13 levels had longer disease duration, diffuse cutaneous involvement, interstitial lung disease (ILD), heart involvement, pulmonary arterial hypertension, Raynaud's phenomenon, pitting scars, digital ulcers, telangiectasia, and high serum IgG levels more frequently than the other patients. In particular, serum CXCL13 levels were associated with ILD and digital ulcers by multivariate regression analysis. Taken together, these results indicate that CXCL13 expression is upregulated by Fli1 deficiency in macrophages, potentially contributing to the development of tissue fibrosis, vasculopathy and immune activation in SSc, especially ILD and digital ulcers.
Are we choosing the right flagships? The bird species and traits Australians find most attractive

Understanding what people like about birds can help target advocacy for bird conservation. However, testing preferences for characteristics of birds is methodologically challenging, with bias difficult to avoid. In this paper we test whether preferred characteristics of birds in general are shared by the individual bird species the same people nominate as being those they consider most attractive. We then compare these results with the birds which appear most frequently in the imagery of conservation advocates. Based on a choice model completed by 638 general public respondents from around Australia, we found a preference for small colourful birds with a melodious call. However, when the same people were asked which five birds they found most attractive, 48% named no more than three, mostly large well-known species. Images displayed by a leading Australian bird conservation organisation also favoured large colourful species. The choice model results suggest conservation advocates can promote a much wider range of bird types as flagships, particularly smaller species that might otherwise be neglected.
Vitamin D Deficiency and Its Relationship with Child-Pugh Class in Patients with Chronic Liver Disease

Abstract Background and Aims: Skeletal manifestation in liver diseases represents the minimally scrutinized part of the disease spectrum. Vitamin D deficiency has a central role in developing hepatic osteodystrophy in patients with chronic liver disease. This study aimed to investigate vitamin D levels and their relationship with disease advancement in these patients. Methods: Vitamin D levels were checked in 125 chronic liver disease patients. The patients were classified in three stages according to Child-Pugh score: A, B and C. The relationship of vitamin D levels with Child-Pugh score and other variables in the study was assessed by the contingency coefficient. Correlation and logistic regression analyses were also carried out to find additional predictors of low vitamin D levels. Results: Among the patients, 88% had either insufficient or deficient stores of vitamin D, while only 12% had sufficient vitamin D levels (p >0.05). Vitamin D levels were notably related to Child-Pugh class (contingency coefficient = 0.5, p <0.05). On univariate and multinomial regression analyses, age, female sex, MELD and Child-Pugh class were predictors of low vitamin D levels. Age, model of end-stage liver disease score and Child-Pugh score were negatively correlated to vitamin D levels (p <0.05). Conclusions: Vitamin D deficiency is notably related to age, female sex and model of end-stage liver disease score, in addition to Child-Pugh class of liver cirrhosis. Vitamin D levels should be routinely checked in patients with advanced liver cirrhosis (Child-Pugh class B and C) and this deficiency must be addressed in a timely manner to improve general well-being of cirrhotic patients.
Coupled Dictionary Learning for Multi-Contrast MRI Reconstruction

Medical imaging tasks often involve multiple contrasts, such as T1-and T2-weighted magnetic resonance imaging (MRI) data. These contrasts capture information associated with the same underlying anatomy and thus exhibit similarities. In this paper, we propose a Coupled Dictionary Learning based multi-contrast MRI reconstruction (CDLMRI) approach to leverage an available guidance contrast to restore the target contrast. Our approach consists of three stages: coupled dictionary learning, coupled sparse denoising, and k-space consistency enforcing. The first stage learns a group of dictionaries that capture correlations among multiple contrasts. By capitalizing on the learned adaptive dictionaries, the second stage performs joint sparse coding to denoise the corrupted target image with the aid of a guidance contrast. The third stage enforces consistency between the denoised image and the measurements in the k-space domain. Numerical experiments on the retrospective under-sampling of clinical MR images demonstrate that incorporating additional guidance contrast via our design improves MRI reconstruction, compared to state-of-the-art approaches.
AFLOW-CHULL: Cloud-Oriented Platform for Autonomous Phase Stability Analysis

A priori prediction of phase stability of materials is a challenging practice, requiring knowledge of all energetically competing structures at formation conditions. Large materials repositories-housing properties of both experimental and hypothetical compounds-offer a path to prediction through the construction of informatics-based, ab initio phase diagrams. However, limited access to relevant data and software infrastructure has rendered thermodynamic characterizations largely peripheral, despite their continued success in dictating synthesizability. Herein, a new module is presented for autonomous thermodynamic stability analysis, implemented within the open-source, ab initio framework AFLOW. Powered by the AFLUX Search-API, AFLOW-CHULL leverages data of more than 1.8 million compounds characterized in the AFLOW.org repository, and can be employed locally from any UNIX-like computer. The module integrates a range of functionality: the identification of stable phases and equivalent structures, phase coexistence, measures for robust stability, and determination of decomposition reactions. As a proof of concept, thermodynamic characterizations have been performed for more than 1300 binary and ternary systems, enabling the identification of several candidate phases for synthesis based on their relative stability criterion-including 17 promising C15 b-type structures and 2 half-Heuslers. In addition to a full report included herein, an interactive, online web application has been developed showcasing the results of the analysis and is located at aflow.org/aflow-chull .
Strategic Processing of Chinese Young English Language Learners in an International Standardized English Language Test

Strategic competence is acknowledged to be able to explain variations in language test performance. Research with adult language test-takers has shown that strategic competence has dual components: strategic knowledge and strategic processing. Of the two components, strategic processing, which is state-like, unstable, and tends to fluctuate from contexts to contexts, is more closely related to language test performance. To date, none of the existing studies investigates strategic processing with children English language learners (ELLs) and explores the relationship between strategic processing in all the four skills of language learning and the test performance. Addressing these gaps, the current study examined the nature of strategic processing in listening, reading and writing, and speaking of 138 Chinese young ELLs in an international standardized English language test – Cambridge Young Learners English Tests – Flyers test. The three questionnaires regarding strategic processing were administered to the participants immediately following the completion of the test. The confirmatory factor analyses verified that the strategic processing construct in the four skills comprised of a cognitive and a metacognitive dimensions, which resembles the strategic processing of the adult language test-takers. The participants adopted significantly more metacognitive than cognitive strategies consistently in the three sections of the test, possibly due to the status of the test. Both cognitive and metacognitive strategic processing were moderately related to the test performance, explaining from 7 to 31% of the variance in the total shields of the test. Across the four skills, high-performing test-takers used both cognitive and metacognitive strategies more frequently than the moderate- and low-performing test-takers, even though whether such differences were due to their richer strategic knowledge or processing skills was unknown. The study contributes to strategic processing in language testing literature and also provides practical implications for English trainers of the young ELLs in China.
Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Paraoxonase-1 (PON1) is a high-density lipoprotein-associated esterase and is speculated to play a role in several human diseases including diabetes mellitus and atherosclerosis. Low PON1 activity has been associated with increased risk of major cardiovascular events, therefore a variety of studies have been conducted to establish the cardioprotective properties and clinical relevance of PON1. The major aim of this review was to highlight the important studies and to subsequently assess if PON1 has clinical relevance. A review of the literature showed that there is currently insufficient data to suggest that PON1 has clinical relevance. It is our opinion that robust studies are required to clarify the clinical relevance of PON1.
Coagulation factor 9-deficient mice are protected against dextran sulfate sodium-induced colitis

ABSTRACT Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolism. Interestingly, IBD occurs less frequently in patients with inherited bleeding disorders. Therefore, we analyzed whether F9-deficiency is protective against the onset of acute colitis in a genetic hemophilia B mouse model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, F9-deficient mice were protected from body-weight loss and had a reduced disease activity score. We detected decreased colonic myeloperoxidase activity and decreased CXCL1 levels in DSS-treated F9-deficient mice compared with wild-type (WT) littermate controls, indicating decreased neutrophil infiltration. Remarkably, we identified expression of coagulation factor IX (FIX) protein in small intestinal epithelial cells (MODE-K). In epithelial cell cultures, cellular FIX protein expression was increased following stimulation with the bacterial Toll-like receptor agonists lipopolysaccharide, macrophage-activating lipopeptide-2 and Pam3CSK4. Thus, we revealed a protective role of F9-deficiency in DSS-induced colitis and identified the intestinal epithelium as a site of ectopic FIX. This article has an associated First Person interview with the first author of the paper. Summary: Since IBD incidence is less frequent in patients with inherited bleeding disorders, we explored and demonstrated that F9-deficiency is protective against DSS-induced acute colitis in a hemophilia B mouse model.