Miracle-dz/UniFAR-FTUs huggingface dataset:
Designing and Evaluating Diabetes Education Material for American Indians

This paper describes the methods used to develop and evaluate diabetes education material for American Indians and Alaska Natives living in Washington, Oregon, and Idaho. Reading skills of individuals and readability of a sample of existing diabetic education material were measured. Using the Wide Range Achievement Test to measure reading skills, the authors found that 66% of the sample read at a 5th "grade" or higher level. Readability of a sample of available diabetic education material was found to be, on average, at the 10th "grade" level. Diabetes education booklets targeted to a 5th to 7th "grade" level were developed and assessed for acceptability and compre hension. Final evaluation, using the cloze procedure, showed that 62 % of the target audience under stood the messages in the booklets. A comprehensive assessment process was found to be useful in developing effective diabetes education material for Indian communities.
Nonsense‐mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome

The nonsense‐mediated mRNA decay pathway selects and degrades its targets using a dense network of RNA‐protein and protein–protein interactions. Together, these interactions allow the pathway to collect copious information about the translating mRNA, including translation termination status, splice junction positions, mRNP composition, and 3′UTR length and structure. The core NMD machinery, centered on the RNA helicase UPF1, integrates this information to determine the efficiency of decay. A picture of NMD is emerging in which many factors contribute to the dynamics of decay complex assembly and disassembly, thereby influencing the probability of decay. The ability of the NMD pathway to recognize mRNP features of diverse potential substrates allows it to simultaneously perform quality control and regulatory functions. In vertebrates, increased transcriptome complexity requires balance between these two functions since high NMD efficiency is desirable for maintenance of quality control fidelity but may impair expression of normal mRNAs. NMD has adapted to this challenge by employing mechanisms to enhance identification of certain potential substrates, while using sequence‐specific RNA‐binding proteins to shield others from detection. These elaborations on the conserved NMD mechanism permit more sensitive post‐transcriptional gene regulation but can have severe deleterious consequences, including the failure to degrade pathogenic aberrant mRNAs in many B cell lymphomas.
First estimate of the scale of canonical 5′ splice site GT>GC variants capable of generating wild‐type transcripts

It has long been known that canonical 5′ splice site (5′SS) GT>GC variants may be compatible with normal splicing. However, to date, the actual scale of canonical 5′SSs capable of generating wild‐type transcripts in the case of GT>GC substitutions remains unknown. Herein, combining data derived from a meta‐analysis of 45 human disease‐causing 5′SS GT>GC variants and a cell culture‐based full‐length gene splicing assay of 103 5′SS GT>GC substitutions, we estimate that ~15–18% of canonical GT 5′SSs retain their capacity to generate between 1% and 84% normal transcripts when GT is substituted by GC. We further demonstrate that the canonical 5′SSs in which substitution of GT by GC‐generated normal transcripts exhibit stronger complementarity to the 5′ end of U1 snRNA than those sites whose substitutions of GT by GC did not lead to the generation of normal transcripts. We also observed a correlation between the generation of wild‐type transcripts and a milder than expected clinical phenotype but found that none of the available splicing prediction tools were capable of reliably distinguishing 5′SS GT>GC variants that generated wild‐type transcripts from those that did not. Our findings imply that 5′SS GT>GC variants in human disease genes may not invariably be pathogenic.
Community Structure of Bacteria Associated With Drifting Sargassum horneri, the Causative Species of Golden Tide in the Yellow Sea

Golden tides dominated by Sargassum spp. are occurring at an accelerated rate worldwide. In China, Sargassum has started to bloom in the Yellow Sea and led to tremendous economic losses, but the underlying biological causes and mechanisms are still unclear. Although algae-associated bacteria were suggested to play crucial roles in algal blooms, the profiles of bacteria associated with drifting Sargassum remain unexplored. In this study, the community structures and functions of Sargassum-associated bacteria were analyzed using the high-throughput sequencing data of the V5–V7 hypervariable region of the 16S rRNA gene. Molecular identification revealed that the golden tide analyzed in the Yellow Sea was dominated by a single species, Sargassum horneri. They were a healthy brown color nearshore but were yellow offshore with significantly decreased chlorophyll contents (P < 0.01), which indicates that yellow S. horneri was under physiological stress. The structural and functional analyses of bacterial communities indicated that the drifting S. horneri had an obvious selectivity on their associated bacteria against surrounding seawater. Although the bacterial communities phylogenetically differed between brown and yellow S. horneri (P < 0.01), their dominant functions were all nitrogen and iron transporters, which strongly indicates microbial contribution to blooming of the algal host. For the first time, potential epiphytic and endophytic bacteria associated with Sargassum were independently analyzed by a modified co-vortex method with silica sand. We showed that the composition of dominant endophytes, mainly Bacillus and Propionibacterium, was relatively consistent regardless of host status, whereas the epiphytic operational taxonomic units (OTUs) greatly varied in response to weakness of host status; however, dominant functions were consistent at elevated intensities, which might protect the host from stress related to nitrogen or iron deficiency. Thus, we propose that host physiological status at different intensities of functional demands, which were related to variable environmental conditions, may be a critical factor that influences the assembly of epiphytic bacterial communities. This study provided new insight into the structure and potential functions of associated bacteria with golden tide blooms.
Effects of Sodium-glucose cotransporter 2 inhibitor (dapagliflozin) on food intake and plasma fibroblast growth factor 21 levels in type 2 diabetes patients.

The objective of this study was to investigate whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with type 2 diabetes induced compensatory hyperphagia by reducing fibroblast growth factor 21 (FGF21) secretion. This prospective study was performed in 26 type 2 diabetes patients treated with dapagliflozin (5 mg/day). Hormonal factors associated with glucose metabolism, dietary intakes estimated by brief self-administered diet-history questionnaire (BDHQ), body weight (BW), and body composition were measured at baseline, and 4 and 12 weeks after dapagliflozin. At 12 weeks, HbA1c levels and BW decreased significantly (both p < 0.0001). BMI at baseline was predictive to baseline log10 (FGF21) (p = 0.037). This study showed no change in FGF21, but insulin and glucagon levels decreased significantly (both p < 0.05). Although hyperphagia was found in 10 patients (38.5%), defining hyperphagia as >20% increase in carbohydrate intake, dapagliflozin treatment induced no hyperphagia, when analyzed by all subjects, and there was no significant association between changes in FGF21 levels and carbohydrate intake. On the other hand, a positive correlation between changes in FGF21 levels or carbohydrate intake and BW was observed (both p < 0.005). Taken together, this study demonstrates that the intervention to maintain the reduced levels in FGF21 is beneficial for BW reduction in type 2 diabetes patients treated with SGLT2i.
Flexibility of network materials and the Rigid Unit Mode model: a personal perspective

The Rigid Unit Mode model was initially developed to understand the origin of displacive phase transitions in network silicate structures. Here, we review the successes of the model, and consider how it might apply to a wider range of network structures. This article is part of the theme issue ‘Mineralomimesis: natural and synthetic frameworks in science and technology’.
TCam-2 Cells Deficient for SOX2 and FOXA2 Are Blocked in Differentiation and Maintain a Seminoma-Like Cell Fate In Vivo

Testicular germ cell tumors (GCTs) are very common in young men and can be stratified into seminomas and non-seminomas. While seminomas share a similar gene expression and epigenetic profile with primordial germ cells, the stem cell population of the non-seminomas, the embryonal carcinoma (EC), resembles malignant embryonic stem cells. Thus, ECs are able to differentiate into cells of all three germ layers (teratomas) and even extra-embryonic-tissue-like cells (yolk-sac tumor, choriocarcinoma). In the last years, we demonstrated that the cellular microenvironment considerably influences the plasticity of seminomas (TCam-2 cells). Upon a microenvironment-triggered inhibition of the BMP signaling pathway in vivo (murine flank or brain), seminomatous TCam-2 cells reprogram to an EC-like cell fate. We identified SOX2 as a key factor activated upon BMP inhibition mediating the reprogramming process by regulating pluripotency, reprogramming and epigenetic factors. Indeed, CRISPR/Cas9 SOX2-deleted TCam-2 cells were able to maintain a seminoma-cell fate in vivo for about six weeks, but after six weeks in vivo still small sub-populations initiated differentiation. Closer analyses of these differentiated clusters suggested that the pioneer factor FOXA2 might be the driving force behind this induction of differentiation, since many FOXA2 interacting genes and differentiation factors like AFP, EOMES, CDX1, ALB, HAND1, DKK, DLK1, MSX1 and PITX2 were upregulated. In this study, we generated TCam-2 cells double-deficient for SOX2 and FOXA2 using the CRISPR/Cas9 technique and xenografted those cells into the flank of nude mice. Upon loss of SOX2 and FOXA2, TCam-2 maintained a seminoma cell fate for at least twelve weeks, demonstrating that both factors are key players in the reprogramming to an EC-like cell fate. Therefore, our study adds an important piece to the puzzle of GCT development and plasticity, providing interesting insights in what can be expected in a patient, when GCT cells are confronted with different microenvironments.
Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions

This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory cytokines but not by vitamin D itself. DBP is the most polymorphic protein known, and different DBP alleles can have substantial impact on its biologic functions. The three most common alleles—Gc1f, Gc1s, Gc2—differ in their affinity with the vitamin D metabolites and have been variably associated with a number of clinical conditions. Although DBP has a number of biologic functions independent of vitamin D, its major biologic function is that of regulating circulating free and total levels of vitamin D metabolites. 25 hydroxyvitamin D (25(OH)D) is the best studied form of vitamin D as it provides the best measure of vitamin D status. In a normal non-pregnant individual, approximately 0.03% of 25(OH)D is free; 85% is bound to DBP, 15% is bound to albumin. The free hormone hypothesis postulates that only free 25(OH)D can enter cells. This hypothesis is supported by the observation that mice lacking DBP, and therefore with essentially undetectable 25(OH)D levels, do not show signs of vitamin D deficiency unless put on a vitamin D deficient diet. Similar observations have recently been described in a family with a DBP mutation. This hypothesis also applies to other protein bound lipophilic hormones including glucocorticoids, sex steroids, and thyroid hormone. However, tissues expressing the megalin/cubilin complex, such as the kidney, have the capability of taking up 25(OH)D still bound to DBP, but most tissues rely on the free level. Attempts to calculate the free level using affinity constants generated in a normal individual along with measurement of DBP and total 25(OH)D have not accurately reflected directly measured free levels in a number of clinical conditions. In this review, we examine the impact of different clinical conditions as well as different DBP alleles on the relationship between total and free 25(OH)D, using only data in which the free 25(OH)D level was directly measured. The major conclusion is that a number of clinical conditions alter this relationship, raising the question whether measuring just total 25(OH)D might be misleading regarding the assessment of vitamin D status, and such assessment might be improved by measuring free 25(OH)D instead of or in addition to total 25(OH)D.
Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens

Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events. In our earlier studies, we made a surprising discovery that peptides derived from structural and non-structural proteins of HCV have substantial amino acid sequence homologies with various proteins of adenoviruses and that immunizing mice with a non-replicating, non-recombinant adenovirus vector leads to induction of a robust cross-reactive cellular and humoral response against various HCV antigens. In this work, we further demonstrate antibody cross-reactivity between Ad and HCV in vivo. We also extend this observation to show that recombinant adenoviruses containing antigens from unrelated pathogens also possess the ability to induce cross-reactive immune responses against HCV antigens along with the induction of transgene antigen-specific immunity. This cross-reactive immunity can (a) accommodate the making of dual-pathogen vaccines, (b) play an important role in the natural course of HCV infection and (c) provide a plausible answer to many unexplained questions regarding immunity to HCV.
A latent class analysis of the co-occurrence of sexual violence, substance use, and mental health in youth

Abstract Purpose: The purpose of this study was to understand co-occurrence of sexual violence, substance use, and mental health in youth and see if there are differences in experiences among sexual identities, races, and genders. Methods: The 2017 Youth Risk Behavior Survey sampled 14,638 high school students. Latent class analysis was used to understand the relationship between incidence of sexual violence, substance use, and depression and suicidality in a nationally representative sample. The model controlled for demographic and bullying covariates. Results: A four-class solution provided optimal fit. Classes were low risk (51.8%); low violence, frequent substance use, and high depression and suicidal ideation (29.7%); experienced violence and moderate mental health issues(5.1%); and some violence, high substance use, and high depression and suicidal ideation (13.4%). Youth who identified as sexual minority youth were almost 2.5–5 times more likely to be in the three higher risk classes than their heterosexual peers. Those who identified as “I don’t know” were almost 3 times more likely to be in the three higher risk classes than heterosexual youth. Multiracial youth had higher likelihood of being in the three riskier classes compared to Caucasian youth. Females were 2.5 and 3 times more likely to be in the low violence and some violence classes compared to males. Conclusion: The study’s finding distinct classes of co-occurring behavioral and mental health outcomes fill gaps in the current literature and informs practitioners that LGB youth and bi/multiracial youth were at an elevated risk of co-occurring victimization, substance use, and mental health problems.
Patient and Public Involvement and Engagement in a doctoral research project exploring self‐harm in older adults

The contribution of involving patients and public in health research is widely reported, particularly within mental health research. Less is written about such contributions to doctoral research. The research focus of this doctoral research, self‐harm in older adults, was put forward by a Patient Public Involvement Engagement (PPIE) group, who contributed to its development.
Promoting Increased Use of Ear Protectors in Noise Through Information Feedback

Workers in a noisy department of a metal fabrication plant took hearing tests before and at the end of their workshifts to ascertain the extent of temporary hearing losses that occurred with and without earplugs being worn. This information was fed back to individual workers as a means for motivating greater use of ear protectors issued for hearing conservation purposes. Subsequent observations of earplug users in this department for 5 months showed a steady increase, attaining a level of 85 -90%. No more than 10% of the workers in another noisy department in the same plant, serving as a control group, wore earplugs over the same 5-month period after being given a standard lecture on hearing conservation in noise, later augmented by disciplinary threats. The effectiveness of the feedback technique in promoting earplug usage was explained as a two-stage process involving individual reinforcement, and subsequent group adoption of new norms for accepted behavior.
Knockdown of NANOG Reduces Cell Proliferation and Induces G0/G1 Cell Cycle Arrest in Human Adipose Stem Cells

The core components of regenerative medicine are stem cells with high self-renewal and tissue regeneration potentials. Adult stem cells can be obtained from many organs and tissues. NANOG, SOX2 and OCT4 represent the core regulatory network that suppresses differentiation-associated genes, maintaining the pluripotency of mesenchymal stem cells. The roles of NANOG in maintaining self-renewal and undifferentiated status of adult stem cells are still not perfectly established. In this study we define the effects of downregulation of NANOG in maintaining self-renewal and undifferentiated state in mesenchymal stem cells (MSCs) derived from subcutaneous adipose tissue (hASCs). hASCs were expanded and transfected in vitro with short hairpin Lentivirus targeting NANOG. Gene suppressions were achieved at both transcript and proteome levels. The effect of NANOG knockdown on proliferation after 10 passages and on the cell cycle was evaluated by proliferation assay, colony forming unit (CFU), qRT-PCR and cell cycle analysis by flow-cytometry. Moreover, NANOG involvement in differentiation ability was evaluated. We report that downregulation of NANOG revealed a decrease in the proliferation and differentiation rate, inducing cell cycle arrest by increasing p27/CDKN1B (Cyclin-dependent kinase inhibitor 1B) and p21/CDKN1A (Cyclin-dependent kinase inhibitor 1A) through p53 and regulate DLK1/PREF1. Furthermore, NANOG induced downregulation of DNMT1, a major DNA methyltransferase responsible for maintaining methylation status during DNA replication probably involved in cell cycle regulation. Our study confirms that NANOG regulates the complex transcription network of plasticity of the cells, inducing cell cycle arrest and reducing differentiation potential.
Treatment of established osteoporosis: a systematic review and cost-utility analysis.

Authors' conclusions Cost-effective scenarios for several interventions in the management of established osteoporosis were identified. Costeffectiveness ratios decrease with age. At age 50 years, only HRT and calcium plus vitamin D were cost-effective (assuming that the agent would decrease the risk of appendicular fractures at this age). At age 80 years, HRT, calcium with or without vitamin D, alfacalcidol, alendronate and bisphosphonate were all cost-effective.
Modification of the Raman Spectra in Graphene-Based Nanofluids and Its Correlation with Thermal Properties

It is well known that by dispersing nanoparticles in a fluid, the thermal conductivity of the resulting nanofluid tends to increase with the concentration of nanoparticles. However, it is not clear what the mechanism behind this phenomenon is. Raman spectroscopy is a characterization technique connecting the molecular and macroscopic world, and therefore, it can unravel the puzzling effect exerted by the nanomaterial on the fluid. In this work, we report on a comparative study on the thermal conductivity, vibrational spectra and viscosity of graphene nanofluids based on three different amides: N, N-dimethylacetamide (DMAc); N, N-dimethylformamide (DMF); and N-methyl-2-pyrrolidinone (NMP). A set of concentrations of highly stable surfactant-free graphene nanofluids developed in-house was prepared and characterized. A correlation between the modification of the vibrational spectra of the fluids and an increase in their thermal conductivity in the presence of graphene was confirmed. Furthermore, an explanation of the non-modification of the thermal conductivity in graphene-NMP nanofluids is given based on its structure and a peculiar arrangement of the fluid.
Phytochemical and Biological Activities in Limonium Species Collected in Different Biotopes of Tunisia

A particular interest is nowadays given to natural antioxidants occurring in foods which can reduce the risk of several diseases through their protective effect. The genus Limonium is widely distributed in different salt regions of Tunisia and known in traditional medicine for the presence of highly effective viral and bacterial replication inhibitors. Limonium leaves have possible beneficial effects on human health for their antioxidant activities and free radical scavenging abilities. To exploit the potential of plants from extreme environments as new sources of natural antioxidants, we studied the extracts from leaves of eight Limonium species growing in extreme environments in Tunisia. Antioxidant molecules (polyphenols, flavonoids, flavonols, ascorbate, tocopherols), in vitro (DPPH, ORAC) and ex vivo antioxidant potential on human erythrocytes, antioxidant enzymes activities (superoxide dismutase, peroxidases, glutathione reductase) were evaluated to identify the species with the best antioxidant capacity. The results showed variability among the species considered in function of the environmental conditions of their natural biotopes, as for the antioxidants measured. In particular, L. vulgare from Oued Rane biotope, characterized by dryness and high temperatures, was the species with the highest enzymatic activity and antioxidant capacity, making it interesting as possible edible halophyte plant or as food complement.
Taking vertebroplasty to a new level or making a mountain out of a molehill?

Several recent publications, including the article by Dublin et al in this issue of the AJNR, have reported restoration of height of fractured vertebral bodies treated with vertebroplasty ([1][1], [2][2]) and kyphoplasty ([3][3], [4][4]). From my own experience with the procedures and perusal of the