Miracle-dz/UniFAR-FTUs huggingface dataset:
Tspan8 Drives Melanoma Dermal Invasion by Promoting ProMMP-9 Activation and Basement Membrane Proteolysis in a Keratinocyte-Dependent Manner

Melanoma is the most aggressive skin cancer with an extremely challenging therapy. The dermal-epidermal junction (DEJ) degradation and subsequent dermal invasion are the earliest steps of melanoma dissemination, but the mechanisms remain elusive. We previously identified Tspan8 as a key actor in melanoma invasiveness. Here, we investigated Tspan8 mechanisms of action during dermal invasion, using a validated skin-reconstruct-model that recapitulates melanoma dermal penetration through an authentic DEJ. We demonstrate that Tspan8 is sufficient to induce melanoma cells’ translocation to the dermis. Mechanistically, Tspan8+ melanoma cells cooperate with surrounding keratinocytes within the epidermis to promote keratinocyte-originated proMMP-9 activation process, collagen IV degradation and dermal colonization. This concurs with elevated active MMP-3 and low TIMP-1 levels, known to promote MMP-9 activity. Finally, a specific Tspan8-antibody reduces proMMP-9 activation and dermal invasion. Overall, our results provide new insights into the role of keratinocytes in melanoma dermal colonization through a cooperative mechanism never reported before, and establish for the first time the pro-invasive role of a tetraspanin family member in a cell non-autonomous manner. This work also displays solid arguments for the use of Tspan8-blocking antibodies to impede early melanoma spreading and therefore metastasis.
Characteristics of Serotype 3 Invasive Pneumococcal Disease before and after Universal Childhood Immunization with PCV13 in Massachusetts

Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the impact of PCV13 on serotype 3 IPD incidence and disease characteristics in Massachusetts’ children. Methods: Serotype 3 IPD cases in children <18 years old were identified via enhanced passive surveillance system in Massachusetts. We compared incidence rates and characteristics of IPD cases before and after PCV13. Results: A total of 47 serotype 3 IPD cases were identified from 2002 to 2017; incidence of serotype 3 IPD in the years following PCV13 was 0.19 per 100,000 children compared to 0.21 before PCV 13, incidence rate ratio (IRR) = 0.86 (95% CI 0.47–1.57). The majority (78%) of post-PCV13 serotype 3 IPD cases occurred among fully vaccinated children. Age distribution, clinical syndrome and presence of comorbidities among serotype 3 IPD cases were similar before and after PCV13 introduction. There was no association between the date of the last PCV13 dose and time to IPD to suggest waning of immunity. Conclusions: seven years following PCV 13 we found no significant changes in serotype 3 IPD incidence or disease characteristics in children in Massachusetts.
The Clinical Expression of Hemochromatosis in Oslo, Norway: Excessive Oral Iron Intake May Lead to Secondary Hemochromatosis Even in HFE C282Y Mutation Negative Subjects

Background: The prevalence of hereditary hemochromatosis in Norway is one of the highest reported in the world. However, the clinical presentation in patients with hemochromatosis in Norway seems to be different compared with recent studies elsewhere. The aim of this study was to investigate patients with hemochromatosis in one community hospital in Norway and to study the prevalence of the C282Y mutation. Methods: One hundred and twenty patients were consecutively admitted to one medical department in Oslo. Serum transferrin and ferritin concentrations were measured in all patients, and a percutaneous liver biopsy was obtained in 108 of 120 (90%) patients. Stainable iron (Perls stain) in hepatocytes was graded from 0 to 4+ and fibrosis from 1 to 4. Genotyping for the C282Y and H63D mutation in the HFE gene was performed by PCR-RFLP. Results: Forty-eight (40%) of the patients suffered from tiredness and astenia and 29 (24%) had typical arthropathy. Only 5 of 105 (4.5%) had biopsy confirmed cirrhosis and 5 had diabetes mellitus. Patients referred from a blood bank had significantly less symptoms and signs compared with other patients. Twenty-one of 120 (17.5%) patients were C282Y mutation negative. Seventeen (81%) of these patients (16 women and 1 man) had a history of extensive oral iron intake lasting from 5 to 50 years. When excluding those with extensive oral iron intake (n = 17), 92 of 103 (89%) were homozygous for the C282Y mutation, 7 (7%) were heterozygous including 3 compound heterozygous and 4 (4%) were mutation negative. Conclusions: Only a minority of our patients with hemochromatosis had a far advanced disease at the time of diagnosis (less than 5% had cirrhosis) and hemochromatosis in a majority of the C282Y mutation negative patients was associated with excessive oral iron intake for several years.
A Comparative Study of Cohorts for Children’s Body Mass Index Changes

ABSTRACT The purpose of this study is to examine how the body mass index changes over time and to determine whether there is a difference between the cohorts. For these purposes, we used latent growth curve modeling and multi-group analysis involving 2,250 students (first-grade cohort panel data) and 2,094 students (fourth-grade cohort panel data) who participated in the Korean Children and Youth Panel Survey. Major findings are as follows. 1) The trajectories of body mass index were different by the cohort. Specifically, children’s body mass index has become more serious in recent generation. 2) Multi-group analysis showed that the trajectories of body mass index and its predictors were varied by the cohort. Specifically, self-esteem, abuse, sedentary lifestyle, and study time explained the cohort effect. These findings suggest that the social environment intervention is needed for the physical health of children.
Deepwater Exchange Processes in the Saguenay Fjord

Evidence is presented showing that the deep waters in the Saguenay Fjord are flushed at a rate that appears to be significantly higher than other sill fjords with comparable bathymetry. Interval waves in the St. Lawrence estuary, with magnitudes of up to 60 m, provide a mechanism for bringing up dense water, semidiurnally, to the level of the seaward sill. Providing the density of the deep water in the fjord's outer basin is less than that at sill depth, a density flow develops and descends into the basin. Estimates of volume and kinetic energy fluxes of the plume suggest that, by itself, this is insufficient to explain the high flushing rates observed. Other processes, such as internal waves, which must be operative in carrying energy into the deep basin, are discussed. Key words: estuaries, sill fjords, mixing, circulation, coastal
Imperfect transparency and camouflage in glass frogs

Significance Transparency is one of the most intuitive forms of camouflage, where predators see straight through their prey as if it were not there. Glass frogs are a classic example of animal transparency and are well known for their transparent ventral skin, through which the internal organs can be clearly seen. The efficacy of transparency on land, however, has been controversial. We found that under natural conditions these frogs are better described as translucent and that translucency acts as modifiable camouflage. Differences in the degree of translucency over the frog act to disguise the frog’s outline and highlight the potential of “edge diffusion” as a form of camouflage, making glass frog camouflage distinct from both transparency and active color change. Camouflage patterns prevent detection and/or recognition by matching the background, disrupting edges, or mimicking particular background features. In variable habitats, however, a single pattern cannot match all available sites all of the time, and efficacy may therefore be reduced. Active color change provides an alternative where coloration can be altered to match local conditions, but again efficacy may be limited by the speed of change and range of patterns available. Transparency, on the other hand, creates high-fidelity camouflage that changes instantaneously to match any substrate but is potentially compromised in terrestrial environments where image distortion may be more obvious than in water. Glass frogs are one example of terrestrial transparency and are well known for their transparent ventral skin through which their bones, intestines, and beating hearts can be seen. However, sparse dorsal pigmentation means that these frogs are better described as translucent. To investigate whether this imperfect transparency acts as camouflage, we used in situ behavioral trials, visual modeling, and laboratory psychophysics. We found that the perceived luminance of the frogs changed depending on the immediate background, lowering detectability and increasing survival when compared to opaque frogs. Moreover, this change was greatest for the legs, which surround the body at rest and create a diffuse transition from background to frog luminance rather than a sharp, highly salient edge. This passive change in luminance, without significant modification of hue, suggests a camouflage strategy, “edge diffusion,” distinct from both transparency and active color change.
Technology-Dependent Pediatric Inpatients at Children's Versus Nonchildren's Hospitals.

BACKGROUND AND OBJECTIVE Technology-dependent children (TDC) are admitted to both children's hospitals (CHs) and nonchildren's hospitals (NCHs), where there may be fewer pediatric-specific specialists or resources. Our objective was to compare the characteristics of TDC admitted to CHs versus NCHs. METHODS This was a multicenter, retrospective study using the 2012 Kids' Inpatient Database. We included patients aged 0 to 18 years with a tracheostomy, gastrostomy, and/or ventricular shunt. We excluded those who died, were transferred into or out of the hospital, had a length of stay (LOS) that was an extreme outlier, or had missing data for key variables. We compared patient and hospital characteristics across CH versus NCH using χ2 tests and LOS and cost using generalized linear models. RESULTS In the final sample of 64 521 discharges, 55% of discharges of TDC were from NCHs. A larger proportion of those from CHs had higher disease severity (55% vs 49%; P < .001) and a major surgical procedure during hospitalization (28% vs 24%; P < .001). In an adjusted generalized linear model, the mean LOS was 4 days at both hospital types, but discharge from a CH was associated with a higher adjusted mean cost ($16 754 vs $12 023; P < .001). CONCLUSIONS Because the majority of TDC are hospitalized at NCHs, future research on TDC should incorporate NCH settings. Further studies should investigate if some may benefit from regionalization of care or earlier transfer to a CH.
Tumour Necrosis Factor Alpha and Its Promoter Polymorphisms' Role in the Phenotypic Expression of Hemochromatosis

Background: The majority of hemochromatosis patients are homozygous for the HFE-C282Y mutation. However, less than half of C282Y homozygous subjects identified by population screening studies actually develop the disease. The cytokine TNF- ! is implicated in the regulation of iron metabolism at different levels. Our aim was to study the role of TNF- ! and its promoter polymorphisms in the phenotypic expression of hemochromatosis in individuals with and without the C282Y mutation. Methods: We studied 4 groups of 10 subjects each: ( 1 ) C282Y homozygotes without clinical hemochromatosis; ( 2 ) C282Y homozygotes with hemochromatosis; ( 3 ) secondary hemochromatosis (without C282Y mutation); and ( 4 ) controls. Groups were age-matched and sex-matched. Peripheral blood mononuclear cells (PBMC) were stimulated with lipopolysaccharide (LPS) and the release of TNF- ! was measured. Additionally, the G/A polymorphisms at position -238 and -308 of the TNF- ! gene were determined by PCR and RFLP analysis in 178 hemochromatosis patients and 41 controls. Results: TNF- ! production from PBMC at 8 and 24 r h after increasing concentrations of LPS stimulation were similar in the four groups. The prevalence of TNF- ! polymorphisms was similar in patients and controls. The prevalences of cirrhosis, siderosis, median s-ferritin and median ALT values were similar in patients with and without the TNF- ! polymorphisms. Conclusions: Neither TNF- ! released from PBMC nor the presence of TNF- ! polymorphisms seem to be associated with disease manifestation in hemochromatosis.
Long-term Course in Collagenous Colitis and the Impact of Bile Acid Malabsorption and Bile Acid Sequestrants on Histopathology and Clinical Features

Background: Bile acid malabsorption is common in collagenous colitis, although long-term follow-up data on the impact of bile acids are limited. The aim was to study whether bile acid malabsorption is a permanent finding, with an impact on histopathology and clinical features in collagenous colitis. Methods:
Contributions of HOX genes to cancer hallmarks: Enrichment pathway analysis and review

Homeobox genes function as master regulatory transcription factors during development, and their expression is often altered in cancer. The HOX gene family was initially studied intensively to understand how the expression of each gene was involved in forming axial patterns and shaping the body plan during embryogenesis. More recent investigations have discovered that HOX genes can also play an important role in cancer. The literature has shown that the expression of HOX genes may be increased or decreased in different tumors and that these alterations may differ depending on the specific HOX gene involved and the type of cancer being investigated. New studies are also emerging, showing the critical role of some members of the HOX gene family in tumor progression and variation in clinical response. However, there has been limited systematic evaluation of the various contributions of each member of the HOX gene family in the pathways that drive the common phenotypic changes (or “hallmarks”) and that underlie the transformation of normal cells to cancer cells. In this review, we investigate the context of the engagement of HOX gene targets and their downstream pathways in the acquisition of competence of tumor cells to undergo malignant transformation and tumor progression. We also summarize published findings on the involvement of HOX genes in carcinogenesis and use bioinformatics methods to examine how their downstream targets and pathways are involved in each hallmark of the cancer phenotype.
Habitat structure, stress and plumage development

Past studies have demonstrated that birds’ perceived risk of predation is influenced by habitat structure, notably the availability of a refuge and the location of food. Thus apparently dangerous habitats, such as those without a refuge, may act as stressors to birds. We test the hypothesis that habitat structure influences stress by manipulating cover availability and food location in European starlings, Sturnus vulgaris, housed in large flight aviaries during moult. We use degree of fluctuating asymmetry (FA) and the number of fault bars in primary feathers to measure stress. The manipulations had no effect on the overall timing or rate of moult, or on the final size and shape of the wings. However, birds from aviaries with cover had lower levels of FA and fewer faults than birds from aviaries without cover. Food location also influenced FA, with birds from aviaries with food located near to cover having lower levels of asymmetry; however, this effect was weak and transitory, only influencing the first primary growth during moult. Food location did not influence the number of fault bars. These results indicate that manipulations of habitat structure can influence stress. Although plumage development may be influenced by perceived risk of predation per se, the possible role of other proximate determinants of plumage abnormalities such as changes in feeding patterns, activity levels, and incidence of mechanical damage are also considered.
Acute Effects of a Short Bout of Physical Activity on Cognitive Function in Sport Students

Physical activity is a promising intervention to restore cognitive function after prolonged sedentary periods. However, little is known about the effect of short physical activity bouts on cognition especially among individuals that are used to physical activity. Therefore, the goal of the present study was to assess the impact of a single ten-minute physical activity bout on the cognitive domain of visual attention compared to sedentary behavior in a population of physically active sport students. Using a randomized controlled design, 51 healthy and physically active sport students [mean age: 22.3 (SD: 2.0) years, 33.3% female] were allocated to one of the following interventions in the break of a two-hour study course: physical activity group (running for ten minutes) and sedentary control group. Visual attention was measured post-intervention using a modified trail making test. Pre-, post-, and 30 min after intervention, perceived attention, and affective states were measured. Between-group comparisons were used to analyze whether visual attention and/or changes in perceived attention or affective states differed between groups. The physical activity group showed significantly higher visual attention post-intervention compared with the sedentary control group, p = 0.003, d = 0.89. Perceived attention, p = 0.006, d = 0.87, and arousal, p < 0.001, d = 1.68, showed a significantly larger pre- and post-intervention increase in the physical activity group compared with the sedentary control group, which was not evident 30 min after intervention. A single ten-minute running intervention in study breaks might help to restore the basal visual attentional domain of cognition after prolonged sedentary periods more effectively compared with common sedentary behavior in breaks between study lessons.
Generalizability of Results From Dyadic Data: Participation of One Versus Two Members of a Romantic Couple Is Associated With Breakup Likelihood

With a growing body of relationship research relying on dyadic data (i.e., in which both members of a couple are participants), researchers have raised questions about whether such samples are representative of the population or unique in important ways. In this research, we used two large data sets (Study 1: n = 5,118; Study 2: n = 5,194) that included participants with and without a romantic partner participating to examine if co-participation status has substantive relationship implications. Results showed that co-participation status predicted breakup even after controlling for other known predictors such as satisfaction, although the effect weakened over time (Study 2). There was also tentative evidence that factors such as conflict may be differentially related to breakup among couples in which one versus both partners participated. These findings raise caution in interpreting effects found in dyadic studies and highlight the need to be mindful of potential bias in recruitment.
Uncrossable and undilatable lesions—A practical approach to optimizing outcomes in PCI

Uncrossable lesions are those that cannot be crossed with a balloon after successful guidewire crossing. These lesions are challenging and are commonly encountered in tortuous and calcified arteries as well as chronic total occlusions. They are the second most common barrier to successful PCI in CTO intervention after inability to cross the CTO segment with a guidewire. Procedures involving balloon uncrossable lesions during routine and CTO PCI utilise longer procedural times, radiation dose and contrast volumes with a lower likelihood of procedural success. In this article, we describe a pragmatic approach of managing balloon uncrossable lesions utilising the most contemporary equipment available in an algorithmic fashion beginning with simple, cost effective techniques right up to complex strategies for advanced operators. In addition, some of these lesions, even when crossed by any technique, they may remain difficult to dilate and prepare for stent insertion. We describe an approach of how to manage these undilatable lesions.
Enhanced microbial degradation of irradiated cellulose under hyperalkaline conditions

ABSTRACT Intermediate-level radioactive waste includes cellulosic materials, which under the hyperalkaline conditions expected in a cementitious geological disposal facility (GDF) will undergo abiotic hydrolysis forming a variety of soluble organic species. Isosaccharinic acid (ISA) is a notable hydrolysis product, being a strong metal complexant that may enhance the transport of radionuclides to the biosphere. This study showed that irradiation with 1 MGy of γ-radiation under hyperalkaline conditions enhanced the rate of ISA production from the alkali hydrolysis of cellulose, indicating that radionuclide mobilisation to the biosphere may occur faster than previously anticipated. However, irradiation also made the cellulose fibres more available for microbial degradation and fermentation of the degradation products, producing acidity that inhibited ISA production via alkali hydrolysis. The production of hydrogen gas as a fermentation product was noted, and this was associated with a substantial increase in the relative abundance of hydrogen-oxidising bacteria. Taken together, these results expand our conceptual understanding of the mechanisms involved in ISA production, accumulation and biodegradation in a biogeochemically active cementitious GDF.
“I’ll work out tomorrow”: The Procrastination in Exercise Scale

Exercise procrastination (i.e. the voluntary delay of intended exercise) represents a novel, reasoned route to self-regulatory failure in physical activity. This study sought to develop and evaluate a scale to measure exercise procrastination and assess its relationship with self-reported physical activity. Two surveys were administered to community samples (n = 270, 279). In both samples, the Procrastination in Exercise Scale was positively correlated with general procrastination and predicted lower physical activity after controlling for intentions and general procrastination. Exercise procrastination appears to be a common phenomenon, and better understanding its role in physical activity may lead to novel intervention approaches.
Characterization of Chenopodin Isoforms from Quinoa Seeds and Assessment of Their Potential Anti-Inflammatory Activity in Caco-2 Cells

Several food-derived molecules, including proteins and peptides, can show bioactivities toward the promotion of well-being and disease prevention in humans. There is still a lack of information about the potential effects on immune and inflammatory responses in mammalian cells following the ingestion of seed storage proteins. This study, for the first time, describes the potential immunomodulation capacity of chenopodin, the major protein component of quinoa seeds. After characterizing the molecular features of the purified protein, we were able to separate two different forms of chenopodin, indicated as LcC (Low charge Chenopodin, 30% of total chenopodin) and HcC (High charge Chenopodin, 70% of total chenopodin). The biological effects of LcC and HcC were investigated by measuring NF-κB activation and IL-8 expression studies in undifferentiated Caco-2 cells. Inflammation was elicited using IL-1β. The results indicate that LcC and HcC show potential anti-inflammatory activities in an intestinal cell model, and that the proteins can act differently, depending on their structural features. Furthermore, the molecular mechanisms of action and the structural/functional relationships of the protein at the basis of the observed bioactivity were investigated using in silico analyses and structural predictions.