Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring the association between subjective cognitive decline and frailty: the Hellenic Longitudinal Investigation of Aging and Diet Study (HELIAD)

Abstract Background: Subjective cognitive decline (SCD) refers to self-evaluations of impairment in cognitive functions in the absence of objective deficits. Frailty is a multidimensional syndrome that results in increased vulnerability. Both terms are associated with cognitive decline and increased incidence of dementia. The aim of this study was to explore potential associations between SCD and frailty in elderly individuals. Methods: In this cross-sectional study, we included 1454 participants aged 65 and older from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) study. Individuals with a diagnosis of dementia, mild cognitive impairment, severe anxiety or depression were excluded. SCD were assessed with eighteen questions categorized into cognitive domains. Frailty was assessed according to the Fried definition, the Frailty Index (FI) and the Tilburg Frailty Indicator (TFI). Logistic regression analysis was used to investigate the association. Results: Lower educational level, female sex and low socioeconomic status were found to be associated with frailty and more SCD complaints. Having two or more types of SCD complaints was significantly associated with frailty according to all frailty definitions. All types of SCD complaints were significantly associated with the FI and the TFI. In addition, SCD complaints concerning problems requiring mathematical reasoning had the strongest association with frailty. Conclusion: We found that SCD complaints may be a valid indicator of frailty in cognitively unimpaired older people. We believe that SCD may provide a crucial proactive assessment to detect frailty and to implement programs that will help maintain good health and quality of life during aging.
Probing the impact of nairovirus genomic diversity on viral ovarian tumor domain protease (vOTU) structure and deubiquitinase activity

Post-translational modification of host and viral proteins by ubiquitin (Ub) and Ub-like proteins, such as interferon stimulated gene product 15 (ISG15), plays a key role in response to infection. Viruses have been increasingly identified that contain proteases possessing deubiquitinase (DUB) and/or deISGylase functions. This includes viruses in the Nairoviridae family that encode a viral homologue of the ovarian tumor protease (vOTU). vOTU activity was recently demonstrated to be critical for replication of the often-fatal Crimean-Congo hemorrhagic fever virus, with DUB activity suppressing the type I interferon responses and deISGylase activity broadly removing ISG15 conjugated proteins. There are currently about 40 known nairoviruses classified into fourteen species. Recent genomic characterization has revealed a high degree of diversity, with vOTUs showing less than 25% amino acids identities within the family. Previous investigations have been limited to only a few closely related nairoviruses, leaving it unclear what impact this diversity has on vOTU function. To probe the effects of vOTU diversity on enzyme activity and specificity, we assessed representative vOTUs spanning the Nairoviridae family towards Ub and ISG15 fluorogenic substrates. This revealed great variation in enzymatic activity and specific substrate preferences. A subset of the vOTUs were further assayed against eight biologically relevant di-Ub substrates, uncovering both common trends and distinct preferences of poly-Ub linkages by vOTUs. Four novel X-ray crystal structures were obtained that provide a biochemical rationale for vOTU substrate preferences and elucidate structural features that distinguish the vOTUs, including a motif in the Hughes orthonairovirus species that has not been previously observed in OTU domains. Additionally, structure-informed mutagenesis provided the first direct evidence of a second site involved in di-Ub binding for vOTUs. These results provide new insight into nairovirus evolution and pathogenesis, and further enhances the development of tools for therapeutic purposes.
Effect of Wakame and Carob Pod Snacks on Non-Alcoholic Fatty Liver Disease

Snacks combining different functional ingredients could represent a useful therapeutic strategy against NAFLD. The present study aimed to analyze the effect of two snack formulations based on carob and wakame flour in the treatment for NAFLD in rats. For this purpose, metabolic syndrome was induced in 50 adult rats by a high-fat high-fructose diet over eight weeks. After this period, rats were fed either normal calorie diets supplemented or not with snack A (1/50 wakame/carob pod) and snack B (1/5 wakame/carob pod) for four additional weeks. After sacrifice, liver composition and serum parameters were analyzed. Different pathways of triacylglycerol metabolism in liver were studied including fatty acid oxidation, fatty acid synthesis, triglyceride assembly and release, fatty acid uptake and glucose uptake. Oxidative stress was also measured. Snack treatment, and mainly B snack, reduced liver triacylglycerol levels by increasing fat oxidation. Moreover, this snack reduced oxidative stress. Therefore, this snack formulation could represent an interesting tool useful for fatty liver treatment.
Hypervideo as a tool for communicating Mathematics

On the World Wide Web, hypertext has provided a powerful mechanism for integrating multimedia as information based on text augmented with image, sound and video elements. However, a broader basis is necessary to structure and integrate a video-centric medium, where the notion of hyperlinks must be redefined to consider the spatial and temporal aspects of video. New interaction paradigms must be developed to navigate in a hyperlinked network, video-driven content called Hypervideo. This work is devoted to the exploring of the mechanisms that allows us to construct this new kind of video-centered presentation making possible enriched forms of navigation, in special, allowing a real navigation through the video. Integrating the temporal dimension on a presentation has been determinant for this purpose. We will study hypervideo particular features, potential uses, tools for its development and production process. In what concerns to potential uses, we will focus on the communication of mathematical concepts. We present in chapter 2 the problematic of communicating Mathematics and we introduce Mathematical Visualization as a technique that can help students on the understanding of abstract ideas. Graphics and video images have been a medium for presenting these visualization results. However, specially in the case of video images, if they are seen in a passive way, their content is not optimally absorbed by the student as its does not provide him time to reflect. This reflection time is essential when trying to understand abstracts concepts. We present hypervideo as a better way to see video images than with VCR. We will explore it as a powerful tool to teach mathematics using the power that video images already have and enriching this content with additional information provided by text, still images, animation and many other kind of media. We present in chapter 3 a general hypermedia model and then our hypervideo model, as a special case of the first one. We will discuss some of the tools that allow constructing this sort of presentation but we will focus on SMIL (pronounced “smile”), Synchronized Multimedia Integration Language. This language is presented in chapter 4. It became a W3C recommendation on 15th June 1998 and has been developed by the SYMM working Group that includes Netscape, Real Networks, Philips, Digital Equipment and others. We present some of the advantages of SMIL as, for example, support for adaptive and independent content. We will also describe some of the players that already support this language like RealPlayer, Grins and QuickTime. In chapter 5, we present the problematic of producing a very new hypermedia product and try to give some general steps when producing a hypervideo. We present, as our
Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems

Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related cancer, and hepatocellular carcinoma. With this focus, we appraised the clinical advantages and drawbacks of metallic, polymeric, and lipid-based nanosystems, such as low invasiveness, low toxicity to the surrounding healthy tissues, high precision, deeper tissue penetration, and dosage adjustment in a real-time setting. Particularly recognizing the increased complexity and multimodality in this area, multifunctional hybrid nanoparticles, comprising different nanomaterials and functionalized with targeting moieties and/or anticancer drugs, present the best characteristics for theranostics. Several examples, focusing on their design, composition, imaging and treatment modalities, and in vitro and in vivo characterization, are detailed herein. Briefly, all studies followed a common trend in the design of these theranostics modalities, such as the use of materials and/or drugs that share both inherent imaging (e.g., contrast agents) and therapeutic properties (e.g., heating or production reactive oxygen species). This rationale allows one to apparently overcome the heterogeneity, complexity, and harsh conditions of tumor microenvironments, leading to the development of successful targeted therapies.
Compliance and Practical Utility of Continuous Wearing of activPAL™ in Adolescents.

PURPOSE The aim of this study was to examine the factors that influence compliance and practical utility of a continuous wear protocols for activPAL™ among adolescents. METHODS Seven hundred and fifty-five (11-18 y; 50.6% girls) students wore the waterproof activPAL™ for 7 consecutive days. The effects of factors such as weather and practical strategies on compliance were assessed. Students were asked to note reasons for removing it in a log. After the 7-day period, students anonymously completed a practical utility questionnaire. RESULTS The final sample used to analyze compliance contained 588 available data points; 72.4% met the validity criteria, which were ≥4 valid days. Rainfall was inversely associated with total wear time, whereas using alcohol pads and cartoon stickers during the application were positively associated with total wear time. Sweating (25.2%) and skin irritation (39.0%) were the most reasons for 290 removal episodes by 235 students. The 131 questionnaires showed that 80.1% regarded the continuous wear period as too long and encountered problems, and 55% would rather not wear it again. CONCLUSION Rainy weather affected girls' compliance with the continuous wear protocol for activPAL™. Skin irritation and sweat-induced inadvertent drops caused removal. Future studies should investigate more user-friendly protocols.
Do GPs use motivational interviewing skills in routine consultations with patients living with mental-physical multimorbidity? An observational study of primary care in Scotland

Objectives To examine whether motivational interviewing is used by GPs in consultations with patients living with mental-physical multimorbidity. Methods Secondary analysis of selected videos from an existing database of routine general practice consultations with adult patients in Glasgow, Scotland. Consultations involving patients with mental-physical multimorbidity were selected and coded using the Motivational Interviewing Treatment Integrity (MITI) coding system. Results Sixty consultations were coded involving 32 GPs across 16 practices. Mean consultation length was 9.9 min. On average GPs asked 1.7 questions per minute and offered 1.2 pieces of information per minute. Using the MITI, five GPs met beginner proficiency for the relational global qualities of partnership and empathy; however, none of the GPs met beginner proficiency for the technical global rating of efforts made to encourage patients to discuss behaviour change. Simple reflections were observed in 67% of consultations and complex reflections in 28% of consultations. Confrontation, a technique inconsistent with motivational interviewing, was observed in 18% of consultations. Discussion MI was not evident in these consultations with patients living with mental-physical multimorbidity. This study provides information about the baseline motivational interviewing-consistent skills of GPs working with multimorbid patients and may be helpful in informing motivational interviewing training efforts and future research.
Accuracy of Intraoperative Computed Tomography in Deep Brain Stimulation—A Prospective Noninferiority Study

Clinical response to deep brain stimulation (DBS) strongly depends on the appropriate placement of the electrode in the targeted structure. Postoperative MRI is recognized as the gold standard to verify the DBS‐electrode position in relation to the intended anatomical target. However, intraoperative computed tomography (iCT) might be a feasible alternative to MRI.
NEW LOSS FROM AN OLD PROBLEM: HOW COUNSELORS CAN ASSIST PERSONS WITH POSTPOLIO SYNDROME

For many persons who were diagnosed with polio years ago, late effect symptoms were not anticipated. They believed they had gone through the more severe ramifications of the illness and were unaware that additional problems could occur. Currently, there are hundreds of thousands of persons in the United States who are experiencing significant difficulties with old symptoms and are also developing new physical and emotional difficulties. Unfortunately, little research has looked at the ways counselors can assist this population.Therefore, the purposes of this study were to identify the physical and emotional problems confronting persons with postpolio and to help counselors gain an understanding of issues they feel might be most appropriate to address in therapy sessions.
Hand hygiene compliance and accuracy in a university dental teaching hospital

Objective This study aimed to evaluate compliance with guidelines on hand hygiene by examining five handwashing categories in postgraduate year (PGY) dentists at a university teaching hospital and to evaluate the accuracy rates of handwashing. Methods Through direct observation, trained PGY dentists were monitored throughout their daily care routine of before contact with patients, before using an instrument, after contact with patients, upon direct exposure to patients’ fluids, and while touching the patients’ surrounding area. Hand hygiene opportunities were considered complete in each category. A total of 16,597 hand hygiene opportunities across 37 individuals were observed from July to October 2012 and from September to October 2013. Results The overall handwashing compliance rate was 34.7%. The handwashing compliance rate was higher during work in oral surgery services (92.8%) than during work in general clinical practice (34.2%). The accuracy rate of handwashing was also higher during work in oral surgery services (87.5%) than during work in general clinical practice (51.0%). Similar results were obtained across all five handwashing categories. Conclusions Handwashing compliance and accuracy rates are low in PGY dentists. More education and continuous monitoring are suggested to improve handwashing compliance, as well as the correct handwashing procedures for dentists.
Cellular Volume and Matrix Stiffness Direct Stem Cell Behavior in a 3D Microniche

The central question addressed in this study is whether cells with different sizes have different responses to matrix stiffness. We used methacrylated hyaluronic acid (MeHA) hydrogels as the matrix to prepare an in vitro 3D microniche in which the single stem cell volume and matrix stiffness can be altered independently from each other. This simple approach enabled us to decouple the effects of matrix stiffness and cell volume in 3D microenvironments. Human mesenchymal stem cells (hMSCs) were cultured in individual 3D microniches with different volumes (2800, 3600, and 6000 μm3) and stiffnesses (5, 12, and 23 kPa). We demonstrated that cell volume affected the cellular response to matrix stiffness. When cells had an optimal volume, cells could form clear stress fibers and focal adhesions on soft, intermediate, or stiff matrix. In small cells, stress fiber formation and YAP/TAZ localization were not affected by stiffness. This study highlights the importance of considering cellular volume and substrate stiffness as important cues governing cell–matrix interactions.
Prevalence of Hepatitis B and Hepatitis D Virus Infections in the United States, 2011-2016.

In the U.S. household population aged 18 years (2011-2016), prevalence of hepatitis B surface antigen (HBsAg) was 0.36% overall, and was highest in non-Hispanic Asians (3.4%). Among adult HBsAg-carriers, 42% (95% confidence interval: 29%-56%) had antibodies to hepatitis D virus (anti-HDV). Routine anti-HDV testing should be performed for HBsAg-carriers.
Dysregulated IL-1&bgr;-GM-CSF Axis in Acute Rheumatic Fever That Is Limited by Hydroxychloroquine

Background: Acute rheumatic fever (ARF) and rheumatic heart disease are autoimmune consequences of group A streptococcus infection and remain major causes of cardiovascular morbidity and mortality around the world. Improved treatment has been stymied by gaps in understanding key steps in the immunopathogenesis of ARF and rheumatic heart disease. This study aimed to identify (1) effector T cell cytokine(s) that might be dysregulated in the autoimmune response of patients with ARF by group A streptococcus, and (2) an immunomodulatory agent that suppresses this response and could be clinically translatable to high-risk patients with ARF. Methods: The immune response to group A streptococcus was analyzed in peripheral blood mononuclear cells from an Australian Aboriginal ARF cohort by a combination of multiplex cytokine array, flow cytometric analysis, and global gene expression analysis by RNA sequencing. The immunomodulatory drug hydroxychloroquine was tested for effects on this response. Results: We found a dysregulated interleukin-1&bgr;-granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine axis in ARF peripheral blood mononuclear cells exposed to group A streptococcus in vitro, whereby persistent interleukin-1&bgr; production is coupled to overproduction of GM-CSF and selective expansion of CXCR3+CCR4−CCR6− CD4 T cells. CXCR3+CCR4−CCR6− CD4 T cells are the major source of GM-CSF in human CD4 T cells and CXCL10, a CXCR3 ligand and potent T helper 1 chemoattractant, was elevated in sera from patients with ARF. GM-CSF has recently emerged as a key T cell-derived effector cytokine in numerous autoimmune diseases, including myocarditis, and the production of CXCL10 may explain selective trafficking of these cells to the heart. We provide evidence that interleukin-1&bgr; amplifies the expansion of GM-CSF-expressing CD4 T cells, which is effectively suppressed by hydroxychloroquine. RNA sequencing showed shifts in gene expression profiles and differentially expressed genes in peripheral blood mononuclear cells derived from patients at different clinical stages of ARF. Conclusions: Given the safety profile of hydroxychloroquine and its clinical pedigree in treating autoimmune diseases such as rheumatoid arthritis, where GM-CSF plays a pivotal role, we propose that hydroxychloroquine could be repurposed to reduce the risk of rheumatic heart disease after ARF.
Vitamin D Is Inversely Related to Obesity: Cross-Sectional Study in a Small Cohort of Serbian Adults

Abstract Objective: Vitamin D (vitD) mediates numerous health conditions other than bone health and mineralization. Its role in cardiometabolic condition is still inconclusive. Methods: We conducted a cross-sectional study in 87 apparently healthy Serbian adults. We assessed their dietary intake, anthropometric and biochemical parameters, blood pressure, and vitD status (as serum 25-hydroxyvitamin D, 25(OH)D). Unexpectedly, the status was significantly higher in January than in July. Therefore, we pooled the data from two time points, to enhance the statistical power for carrying out association analyses. We employed linear regression models to evaluate the associations between vitD status and the obesity biomarkers of serum lipids and blood pressure. Results: Mean vitD intake of 3.85 ± 4.71 μg in the cohort was below recommended. Of the subjects in the pooled cohort, 60.58% were vitD deficient (with serum 25(OH)D below 50 nmol/L), with the majority of them being women who were overweight. VitD status tended to be inversely related to percent body fat and waist/height ratio in the crude regression model. After age and gender adjustment, the status was significantly related to waist circumference, waist/height ratio, and waist/hip ratio (β = –0.116, 95% confidence interval [CI]: –0.206, –0.025, β = –0.001, 95% CI: –0.001, 0.000, and β = –0.001, 95% CI: –0.001, 0.000, respectively). These associations remained only within women. Fully adjusted models supported the notion of vitD being independently associated with central adiposity, regardless of age, gender, and total obesity. Conclusions: In apparently healthy adults with low vitD intake, vitD status was inversely associated with obesity parameters, pronouncedly in women. Our data support the need for development and implementation of public health policies on increasing vitD intake also as part of obesity management strategies.
‘I saw it as a second chance’: A qualitative exploration of experiences of treatment failure and regimen change among people living with HIV on second- and third-line antiretroviral therapy in Kenya, Malawi and Mozambique

ABSTRACT Increasing numbers of people living with HIV (PLHIV) in sub-Saharan Africa are experiencing failure of first-line antiretroviral therapy and transitioning onto second-line regimens. However, there is a dearth of research on their treatment experiences. We conducted in-depth interviews with 43 PLHIV on second- or third-line antiretroviral therapy and 15 HIV health workers in Kenya, Malawi and Mozambique to explore patients’ and health workers’ perspectives on these transitions. Interviews were audio-recorded, transcribed and translated into English. Data were coded inductively and analysed thematically. In all settings, experiences of treatment failure and associated episodes of ill-health disrupted daily social and economic activities, and recalled earlier fears of dying from HIV. Transitioning onto more effective regimens often represented a second (or third) chance to (re-)engage with HIV care, with patients prioritising their health over other aspects of their lives. However, many patients struggled to maintain these transformations, particularly when faced with persistent social challenges to pill-taking, alongside the burden of more complex regimens and an inability to mobilise sufficient resources to accommodate change. Efforts to identify treatment failure and support regimen change must account for these patients’ unique illness and treatment histories, and interventions should incorporate tailored counselling and social and economic support.