Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin D and the insulin-like growth factor system: Implications for colorectal neoplasia.

Epidemiological studies have strongly associated lower levels of vitamin D and its metabolites with an increased risk of colorectal cancer (CRC). The action of calcitriol, the active metabolite of vitamin D, is mediated by the vitamin D receptor (VDR) that is present in most tissues. In advanced CRC, VDR expression is lowered. Calcitriol has several antineoplastic effects in CRC: it promotes the G1- phase cycle arrest, lowers vascular endothelial growth factor (VEGF) synthesis, and acts on tumor stromal fibroblasts to limit cell migration and angiogenesis. Hyperinsulinemia and insulin-like growth factors (IGFs) have been implicated in the pathophysiology of CRC. IGF-1 and IGFBP-3 have been the most studied components of the IGF system. Only 1% of the total serum IGF-1 is free and bioactive and 80% of it binds to IGFBP-3. IGF-1 and its receptor IGF-1R are known to induce cell proliferation. Both IGF-1 and IGFBP-3 can favor angiogenesis by increasing the transcription of the VEGF gene. A high serum IGF-1/IGFBP-3 ratio is associated with increased risk for CRC. VDR is a transcription factor for the IGFBP-3 gene, and IGF-1 can increases calcitriol synthesis. Studies examining the effect of vitamin D treatment on serum IGF-1 and IGFBP-3 have not been in agreement since different populations, dosages, and intervention periods have been used. New vitamin D treatment studies that examine CRC should take in account confounding factors such as obesity or VDR genotypes.
Invasive mutualisms and the structure of plant–pollinator interactions in the temperate forests of north‐west Patagonia, Argentina

1 Alien species may form plant–animal mutualistic complexes that contribute to their invasive potential. Using multivariate techniques, we examined the structure of a plant–pollinator web comprising both alien and native plants and flower visitors in the temperate forests of north‐west Patagonia, Argentina. Our main objective was to assess whether plant species origin (alien or native) influences the composition of flower visitor assemblages. We also examined the influence of other potential confounding intrinsic factors such as flower symmetry and colour, and extrinsic factors such as flowering time, site and habitat disturbance. 2 Flowers of alien and native plant species were visited by a similar number of species and proportion of insects from different orders, but the composition of the assemblages of flower‐visiting species differed between alien and native plants. 3 The influence of plant species origin on the composition of flower visitor assemblages persisted after accounting for other significant factors such as flowering time, bearing red corollas, and habitat disturbance. This influence was at least in part determined by the fact that alien flower visitors were more closely associated with alien plants than with native plants. The main native flower visitors were, on average, equally associated with native and alien plant species. 4 In spite of representing a minor fraction of total species richness (3.6% of all species), alien flower visitors accounted for > 20% of all individuals recorded on flowers. Thus, their high abundance could have a significant impact in terms of pollination. 5 The mutualistic web of alien plants and flower‐visiting insects is well integrated into the overall community‐wide pollination web. However, in addition to their use of the native biota, invasive plants and flower visitors may benefit from differential interactions with their alien partners. The existence of these invader complexes could contribute to the spread of aliens into novel environments.
Amylolysis of maize mutant starches

Starches from single and double maize mutants were subjected to enzymatic degradation by porcine pancreatic α-amylase. The maize mutants covered a broad range of macromolecular composition and crystalline structure relative to fractional crystallinity level (from 0.19 to 0.48) and polymorphic type (with various proportions of A-, B- and V-type allomorphs). Regardless of amylose content or crystallinity level, starches with a predominant B-crystalline type were more resistant to amylolysis than others, and initial rates of hydrolysis were lower for B-type than A-type starches. Final hydrolysis extents were less than 35% for predominant B-type starches, 60% for C-type ones and more than 70% for predominant A- or V-type ones. Dangling chains or crystal defects also appeared to increase initial hydrolysis rates, although lower initial rates and final hydrolysis extents were mainly related to the amount of B-type crystallites. Unexpectedly, hydrolysis residues were composed of both amorphous and B-type crystalline regions. These observations suggest that resistance to amylolysis is related to the distribution of B-type crystallites within the granule rather than to the relative proportion of B-type crystallites. Des amidons provenant de mais mutant (simple ou double) sont soumis a une degradation enzymtique par l'α-amylase pancreatique porcine. Les amidons sont de composition et de structure cristalline variables. Les amidons de type B sont plus resistants a l'amylolyse que les autres. Les vitesses initiales d'amylolyse varient en fonction des branchements et des defauts cristallins de l'amidon. La resistance a l'amylolyse est liee a la distribution des cristallites de type B a l'interieur des granules plutot qu'a la proportion des cristallites de type B.
Lipidome Profiles Are Related to Depressive Symptoms and Preterm Birth Among African American Women

African American women have the highest rate of preterm birth (PTB; <37 completed weeks’ gestation) of any racial and ethnic group in the United States (14.1%). Depressive symptoms (DS) have been linked to PTB risk of African American women. We hypothesized that maternal lipidomic profiles are related to prenatal DS and gestational age at birth among African American women. Women were enrolled at 9–25 weeks’ gestation, completed questionnaires, and provided plasma samples. Lipidomic profiles were determined by “shotgun” Orbitrap high-resolution/accurate mass spectrometry. Data were analyzed using SIMCA P+ software. There was a clear separation in the orthogonal projections to latent structures discriminant analysis score plot between women with Center for Epidemiologic Studies Depression Scale (CES-D) scores ≥23 and women with CES-D scores ≤22. Similarly, a clear separation was observed in the model between PTB and full-term birth. Corresponding S-plot, loading plot, and variable importance in projection plot/list were used to identify the lipids responsible for the groupings. Higher levels of specific triglyceride (TG) species and lower levels of specific phosphatidylcholines (PCs) PC(37:1), PC(41:6), and PC(39:3) were associated with PTB. PC PC(37:1) levels were also lower among women with CES-D scores ≥23, pointing toward a possible connection between DS and PTB. Although overweight pregnant women showed higher levels of TGs, the PTB model showed specific TGs unique to PTB. Lipidomic profiles in pregnant African American women are related to DS, and our data suggest a role for specific TGs and PCs in PTB.
Evaluation of inhibitory activity of domestic probiotics for against invasion and infection by Proteus mirabilis in the urinary tract.

INTRODUCTION Approximately 5% of men and 40%-50% of women have experienced urinary tract infections (UTI), which are the most common infectious diseases and nosocomial infections in humans. Proteus mirabilis is susceptible to most antibiotics, but antibiotic treatment usually causes side effects. In this research, lactic acid bacteria (LAB) was assessed for its inhibitory activity against a urinary tract pathogen. METHODOLOGY We studied the effect of pH adjustment, heat, and enzyme treatments on the inhibitory activity of LAB strains and their supernatants, using well-diffusion and co-culture assays. In the cell culture assay, anti-adhesion and anti-invasion activities against P. mirabilis were tested with SV-HUC-1 urothelial cells. RESULTS LAB were able to adhere to the urothelial cells and inhibited P. mirabilis growth. LAB were also able to inhibit P. mirabilis adhesion to or invasion of SV-HUC-1 urothelial cells. Finally, in the competition assay, LAB showed inhibitory effects against P. mirabilis. LAB could also inhibit the invasion of P. mirabilis into urothelial cells. CONCLUSIONS Two LAB strains (PM206 and 229) exhibited antagonistic activity against P. mirabilis adhesion or invasion of urothelial cells in culture. In the future, probiotics may be used in food or urinary tract cleansing and could replace antibiotic treatments.
Gene Trees and Species Trees: Molecular Systematics as One-Character Taxonomy

Reconstruction of phylogenies from molecular data has become an important and increasingly common approach in systematics. The product of such studies is a gene tree, hypoth- esizing relationships among genes or genomes. This gene tree may be fundamentally incongruent with the true species phylogeny, due to various biological phenomena such as introgression, lineage sorting, or mistaken orthology. In such circumstances all of the gene tree characters defining the relationships of molecular taxa (haplotypes) may be necessarily correlated, and the gene or genome may behave as a single species tree character. In these circumstances robustness of the gene hypoth- esis is meaningless as a measure of confidence in the species phylogenetic hypothesis. Incongruence between a phylogenetic hypothesis based on numerous, presumably independent, non-molecular characters and a single gene tree should not be assumed to be due to noise in non-molecular data. As with other characters, a character phylogeny, in this case a gene tree, can be tested best by a parsimony analysis in which other characters are included. If independence of molecular characters is assumed, then each is an equivalent phylogenetic hypothesis, as is each non-molecular character, leading to the suggestion that direct combination is appropriate. Swamping becomes an issue when a large molecular data set may be behaving as a single character. To alleviate this problem, a gene tree may be treated as a single multistate character, either ordered or unordered, and included with non-molecular data to obtain a globally parsimonious result. An example is given using published molecular and non-molecular data from the Asteraceae.
Whole-slide image analysis of the tumor microenvironment identifies low B-cell content as a predictor of adverse outcome in patients with advanced-stage classical Hodgkin lymphoma treated with BEACOPP

Asubset of patients with advanced-stage classical Hodgkin lymphoma (cHL) relapse or progress following standard treatment. Given their dismal prognosis, identifying this group of patients upfront represents an important medical need. While prior research has identified characteristics of the tumor microenvironment, which are associated with cHL outcomes, biomarkers that are developed and validated in this high-risk group are still lacking. Here, we applied wholeslide image analysis (WSI), a quantitative, large-scale assessment of tumor composition that utilizes conventional histopathology slides. We conducted WSI on pre-treatment biopsies from 340 patients with advanced-stage cHL enrolled in the HD12 and HD15 trials of the German Hodgkin Study Group (GHSG), and tested our results in a validation cohort of 147 advanced-stage cHL patients within the GHSG HD18 trial. All patients were treated with BEACOPP-based regimens. By quantifying T cells, B cells, Hodgkin and Reed-Sternberg cells and macrophages with WSI, 80% of all cells in the tumor tissue were identified. Crucially, low B-cell count was associated with significantly reduced progression-free survival and overall survival, while the content of T cells, macrophages and Hodgkin and Reed-Sternberg cells was not associated with the risk of progression or relapse in the study cohort. We further validated low Bcell content as a prognostic factor for progression-free survival and overall survival in the validation cohort and demonstrated the good interobserver agreement of WSI. WSI may represent a key tool for risk stratification of advanced-stage cHL and can easily be added to the standard diagnostic histopathology work-up.
Using Virtual Agents and Activity Monitors to Autonomously Track and Assess Self-Determined Physical Activity Among Young Children: A 6-Week Feasibility Field Study

The majority of youth fail to get the recommended amount of physical activity (PA), and there is a precipitous decline in PA among children as they get older. Guided by self-determination theory and social cognitive theory, we designed an interactive, mixed reality PA intervention for 6-10-year-old children. Capitalizing on the features of consumer-grade interactive communication technologies, the intervention features a kiosk-based system that houses a virtual agent programmed to encourage children to set self-determined PA goals. This intervention aims to resolve many practical challenges in designing and administering a personalized, intrinsically motivated PA intervention for this age group. We pilot tested the feasibility of this kiosk across 6 weeks with n = 42 child/parent dyads. The kiosk tracked and logged children's daily PA and engagement with the intervention without having to rely on human reporting, provided tailored evaluation and feedback whenever children requested it, informed parents about their child's PA progress, and employed a virtual agent (a dog) to offer social support to children. The virtual agent prompted users to set PA goals, and as children met these goals over time, their personalized dog became happier, more fit, and better at tricks. Each time a child engaged with the kiosk the system automatically sent a text message to his/her parent with details about the child's PA progress. The current study demonstrated the kiosk's feasibility in the field over 6 weeks, illustrating the potential of using interactive technologies as tools for disseminating self-sufficient, and truly self-determined health interventions for children at scale.
A novel training-free recognition method for SSVEP-based BCIs using dynamic window strategy

Objective. Filter bank canonical correlation analysis (FBCCA) is a widely-used classification approach implemented in steady-state visual evoked potential (SSVEP)–based brain computer interfaces (BCIs). However, conventional detection algorithms for SSVEP recognition problems, including the FBCCA, were usually based on ‘fixed window’ strategy. That’s to say, these algorithms always analyze data with fixed length. This study devoted to enhance the performance of SSVEP-based BCIs by designing a new dynamic window strategy which automatically finds an optimal data length to achieve higher information transfer rate (ITR). Approach. The main purpose of ‘dynamic window’ is to minimize the required data length while maintaining high accuracy. This study projected the correlation coefficients of FBCCA into probability space by softmax function and built a hypothesis testing model, which took risk function as evaluation of classification result’s ‘credibility’. In order to evaluate the superiority of this approach, FBCCA with fixed data length (FBCCA-FW) and spatial temporal equalization dynamic window (STE-DW) were implemented for comparison. Main results. Fourteen healthy subjects’ results were concluded by a 40-target online SSVEP-based BCI speller system. The results suggest that this proposed approach significantly outperforms STE-DW and FBCCA-FW in terms of accuracy and ITR. Significance. By incorporating the fundamental ideas of FBCCA and dynamic window strategy, this study proposed a new training-free dynamical optimization algorithm, which significantly improved the performance of online SSVEP-based BCI systems.
What is the best clinical approach to recurrent/refractory osteosarcoma?

ABSTRACT Introduction: Osteosarcoma is the most common malignant bone tumor. It is currently treated with pre-and postoperative chemotherapy, associated with surgical resection of the tumor. Area covered: Relapses occur in about one in three patients presenting with localized disease, and three in four of those with metastases at diagnosis. Relapsing disease carries a very poor prognosis, with 5-year survival rates ranging between 13% and 40%. Expert opinion: Patients with unilateral lung involvement or solitary lung metastases and a recurrence-free interval (RFI) longer than 24 months have a better prognosis, and could be managed with surgical resection and close observation. Complete surgical resection of all sites of disease remains essential to survival: patients unable to achieve complete remission have a catastrophic overall survival rate. The role of second-line chemotherapy is not at all clear, and no controlled studies are available on this topic. It is worth considering for patients unable to achieve complete surgical remission, and those with multiple metastases and/or a RFI <24 months. Given their dismal prognosis, patients with multiple sites of disease not amenable to complete surgical resection should also be considered for innovative therapeutic approaches.
Allocation of Resources to Sex Functions in Flowering Plants

The study of allocation of resources offers the possibility of understanding the pressures of natural selection on reproductive functions. In allocation studies, theoretical predictions are generated and the assumptions as well as the predictions can be tested in the field. Here, we review some of the theoretical models, and discuss how much biological reality can be included in them, and what factors have been left out. We also review the empirical data that have been generated as tests of this body of theory. There are many problems associated with estimating reproductive resources, and also with testing how allocation of these resources affects reproductive and other components of fitness, and we assess how important these may be in allowing empirical results to be interpreted. Finally, we discuss the relevance of resource allocation patterns to the evolution of unisexual flowers, both at the level of individual plants (monoecy, andro- and gynomonoecy) and at the population level (dioecy).
CAR-T and ibrutinib vs CLL: sequential or simultaneous?

In this issue of Blood, Gauthier and colleagues present the results of a pilot study evaluating the safety and feasibility of administrating ibrutinib concurrently with CD3zeta, 4-1BB-signaling anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory chronic lymphocytic leukemia (CLL). 1 Minimal residual disease (MRD) assessment was performed on bone marrow (BM) at an early time point (4 weeks) following CAR T-cell infusion. The study enrolled 19 CLL patients, one of whom died 4 days after infusion from a presumed ibrutinib-related cardiac arrhythmia during grade 2 cytokine release syndrome (CRS). At the 4-week time point, 15 of the remaining 18 patients responded, with 4 patients achieving a complete response. Remarkably, 11 patients had undetectable BM MRD as measured by IGH sequencing. One-year progression-free survival (PFS) of the 18 evaluable patients was 38%. The authors compared these results to 19 CLL patients who were previously treated with a very similar regimen but without concurrent ibrutinib2 and found that severity of CRS was lower with concomitant ibrutinib, but PFS was unchanged.
THE FUNGUS‐ALGA ASSOCIATION IN THE LECANORACEAE: AN ULTRASTRUCTURAL STUDY

Summary Electron micrographs of four lichen species of the Lecanoraceae were examined. The contact between the symbionts ranges from active penetration of the algal cell wall by fungal haustoria in a supposedly primitive growth-form, through intermediate stages, to a kind of hyphal entrapment in an advanced form. Penetration beyond the plasma membrane of intact algal cells has not been observed. Whereas penetrations may occur in all the algal cells composing the algal layer of the primitive thallus, in the more advanced growth-forms, only those cells which have reached a certain stage of their life cycle are attacked.
Experimental studies on some aspects of toxicological effects of gas phase cigarette smoke (GPCS)

We have studied the toxicological effects of gas phase cigarette smoke (GPCS) on: 1) lecithin-formed liposome lipid peroxidation; 2) the liposomal membrane fluidity; 3) conformation changes of rat lung cell membrane proteins; and 4) respiratory burst of human polymorphonuclear leukocytes. The results of these investigations suggested that by stimulating lipid peroxidation, GPCS can cause changes of membrane fluidity and alterations of membrane protein conformations as well as damages to membrane-bound enzymes. We conclude that oxidative damage to cells and tissues is an important toxicological property of GPCS.
Loss of forb diversity in relation to nitrogen deposition in the UK: regional trends and potential controls

In this study we investigate the impact of nitrogen (N) deposition on the diversity of three different vegetation functional groups – forbs, grasses and mosses – using a field survey of acid grasslands across Great Britain. Our aim is to identify the vegetation types that are most vulnerable to enhanced N deposition, and to shed light on the mechanisms that may be driving N‐initiated species changes in the UK. Sixty‐eight randomly selected grasslands belonging to the UK National Vegetation Classification group U4 (Festuca ovina–Agrostis capillaris–Galium saxatile grassland) were studied along a gradient of atmospheric N deposition ranging from 6 to 36 kg N ha−1 yr−1. At each site, vegetation was surveyed and samples were taken from the topsoil and subsoil. Aboveground plant material was collected from three species: a forb, grass and moss. Both the species richness and cover of forbs declined strongly with increasing N deposition, from greater than eight species/20% cover per m2 quadrat at low levels of N to fewer than two species/5% cover at the highest N deposition levels. Grasses showed a weak but significant decline in species richness, and a trend toward increasing cover with increasing N input. Mosses showed no trends in either species richness or cover. Most of the decline in plant species richness could be accounted for by the level of ammonium deposition. Soil KCl‐extractable ammonium concentration showed a significant positive correlation with N input, but there was no relationship between N deposition and extractable nitrate. In the soil O/A horizon, there was no relationship between N deposition and %N, and only a very weak positive relationship between the level of N deposition and the C : N ratio. Finally, in the vegetation, there was no relationship between N deposition and either shoot tissue N concentration or N : P ratio for any of the three reference species. Combining our regional survey with the results of published N‐addition experiments provides compelling evidence that there has been a significant decline in the species richness and cover of forbs across Great Britain, and that the primary cause is competition due to an increase in the cover of grasses in response to enhanced deposition of reactive N, primarily NH4+.