Miracle-dz/UniFAR-FTUs huggingface dataset:
Diurnal Physical Activity Patterns across Ages in a Large UK Based Cohort: The UK Biobank Study

The ability of individuals to engage in physical activity is a critical component of overall health and quality of life. However, there is a natural decline in physical activity associated with the aging process. Establishing normative trends of physical activity in aging populations is essential to developing public health guidelines and informing clinical perspectives regarding individuals’ levels of physical activity. Beyond overall quantity of physical activity, patterns regarding the timing of activity provide additional insights into latent health status. Wearable accelerometers, paired with statistical methods from functional data analysis, provide the means to estimate diurnal patterns in physical activity. To date, these methods have been only applied to study aging trends in populations based in the United States. Here, we apply curve registration and functional regression to 24 h activity profiles for 88,793 men (N = 39,255) and women (N = 49,538) ages 42–78 from the UK Biobank accelerometer study to understand how physical activity patterns vary across ages and by gender. Our analysis finds that daily patterns in both the volume of physical activity and probability of being active change with age, and that there are marked gender differences in these trends. This work represents the largest-ever population analyzed using tools of this kind, and suggest that aging trends in physical activity are reproducible in different populations across countries.
Vaccination against PD-L1 with IO103 a Novel Immune Modulatory Vaccine in Basal Cell Carcinoma: A Phase IIa Study

Simple Summary Basal cell carcinoma is the most common skin cancer and new treatments for patients with widespread and numerous tumors are lacking. In a previous study treating patients with multiple myeloma with a peptide vaccine called IO103 against an immune checkpoint molecule called programmed death ligand 1, two cases of basal cell carcinoma regressed. The aim of the present study was to assess the effect of vaccination with IO103 in ten patients with basal cell carcinoma. Patients were vaccinated with Montanide as adjuvant up to nine times during six months. Regression in tumor size of at least 30% was seen in five of 18 tumors, two of which showed complete regression. Vaccinations resulted in immune responses against the vaccine in blood samples from nine of ten patients and in skin samples from five of nine patients. The findings suggest that the vaccine may be effective against some basal cell carcinomas. Abstract Antitumor activity of immune checkpoint blocking antibodies against programmed death 1 (PD-1) in basal cell carcinoma (BCC) has been described. IO103 is a peptide vaccine against the major PD-1 ligand PD-L1. A phase IIa study of vaccination with IO103 and Montanide adjuvant was conducted in patients with resectable BCC (NCT03714529). Vaccinations were given six times every 2 weeks (q2w), followed by three vaccines q4w in responders. Primary endpoints were clinical responses of target tumors, change in target tumor size and immune responses to the vaccine. Secondary endpoint was safety. One tumor per patient was designated target tumor and biopsied twice during the course of vaccination. Synchronous non-target BCCs were not biopsied during vaccinations. Ten patients were vaccinated (six patients received six vaccinations and four patients received nine vaccinations). A partial response (PR) was seen in two target tumors. Two complete responses (CR) and one PR were observed in eight non-target tumors in four patients. No tumors progressed. Related adverse events were grade 1 and reversible. Immune responses against IO103 were induced in blood samples from nine of ten and skin-infiltrating lymphocytes from five of the nine patients. The regressions seen in non-target tumors suggest that IO103 may be effective against a subtype of BCC.
Social Networks, Trust, and Disaster-Risk Perceptions of Rural Residents in a Multi-Disaster Environment: Evidence from Sichuan, China

Individual perception of disaster risk is not only the product of individual factors, but also the product of social interactions. However, few studies have empirically explored the correlations between rural residents’ flat social networks, trust in pyramidal channels, and disaster-risk perceptions. Taking Sichuan Province—a typical disaster-prone province in China—as an example and using data from 327 rural households in mountainous areas threatened by multiple disasters, this paper measured the level of participants’ disaster-risk perception in the four dimensions of possibility, threat, self-efficacy, and response efficacy. Then, the ordinary least squares method was applied to probe the correlations between social networks, trust, and residents’ disaster-risk perception. The results revealed four main findings. (1) Compared with scores relating to comprehensive disaster-risk perception, participants had lower perception scores relating to possibility and threat, and higher perception scores relating to self-efficacy and response efficacy. (2) The carrier characteristics of their social networks significantly affected rural residents’ perceived levels of disaster risk, while the background characteristics did not. (3) Different dimensions of trust had distinct effects on rural residents’ disaster-risk perceptions. (4) Compared with social network variables, trust was more closely related to the perceived level of disaster risks, which was especially reflected in the impact on self-efficacy, response efficacy, and comprehensive perception. The findings of this study deepen understanding of the relationship between social networks, trust, and disaster-risk perceptions of rural residents in mountainous areas threatened by multiple disasters, providing enlightenment for building resilient disaster-prevention systems in the community.
Assessing the Involvement of Selected Phenotypes of Pseudomonas simiae PICF7 in Olive Root Colonization and Biological Control of Verticillium dahliae

Pseudomonas simiae PICF7 is an indigenous inhabitant of the olive (Olea europaea L.) rhizosphere/root endosphere and an effective biocontrol agent against Verticillium wilt of olive (VWO), caused by the soil-borne fungus Verticillium dahliae. This study aimed to evaluate the potential involvement of selected phenotypes of strain PICF7 in root colonization ability and VWO biocontrol. Therefore, a random transposon-insertion mutant bank of P. simiae PICF7 was screened for the loss of phenotypes likely involved in rhizosphere/soil persistence (copper resistance), root colonization (biofilm formation) and plant growth promotion (phytase activity). Transposon insertions in genes putatively coding for the transcriptional regulator CusR or the chemotaxis protein CheV were found to affect copper resistance, whereas an insertion in fleQ gene putatively encoding a flagellar regulatory protein hampered the ability to form a biofilm. However, these mutants displayed the same antagonistic effect against V. dahliae as the parental strain. Remarkably, two mutants impaired in biofilm formation were never found inside olive roots, whereas their ability to colonize the root exterior and to control VWO remained unaffected. Endophytic colonization of olive roots was unaltered in mutants impaired in copper resistance and phytase production. Results demonstrated that the phenotypes studied were irrelevant for VWO biocontrol.
HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges

Several investigations have been published on Hepatitis Delta Virus (HDV) infection in recent years, from which we have drawn the salient data to provide readers with useful information to improve their knowledge on the subject. HDV genotypes 5–8 have been recently imported to Western countries from central Africa, whose clinical relevance deserves further investigation. Ongoing HDV replication has been identified as an independent predictor of progression to cirrhosis and HCC for patients with HDV chronic hepatitis (HDV-CH). Long-term treatments of HDV-CH with standard or pegylated interferon alfa (peg-IFN-α) have all been unsatisfactory, leading to a sustained virological response (SVR) only in 20–30% of patients treated, faced with a poor tolerability and frequent serious adverse reactions; the addition of HBV nucleo(s)tide analogues to peg-IFN- α did not improve the rate of SVR. The improved knowledge of the HDV life cycle has allowed the development of direct acting agents towards key-points of the HDV life cycle, namely bulevirtide, lonafarnib and nucleic acid polymers. Preliminary data have shown that these drugs are more effective than interferon-based therapies, but adverse reactions are also common, which however seem toned down in combination therapy with other antivirals.
The Claudin-Low Subtype of High-Grade Serous Ovarian Carcinoma Exhibits Stem Cell Features

Simple Summary Here, we identified and characterized a claudin-low subtype of high-grade serous ovarian cancer. This rare variant of undifferentiated neoplasm shares transcriptional features with the homonym subtype of breast cancer, including low epithelial differentiation, high mesenchymal signature, and enrichment for stem cell features. Since the claudin-low transcriptional signature is associated with poor prognosis, we believe that the identification of the claudin-low molecular profile may have important clinical implications, paving the way for personalized medicine in ovarian cancer patients. Abstract Claudin-low cancer (CL) represents a rare and biologically aggressive variant of epithelial tumor. Here, we identified a claudin-low molecular profile of ovarian high-grade serous carcinoma (HGSOC), which exhibits the main characteristics of the homonym breast cancer subtype, including low epithelial differentiation and high mesenchymal signature. Hierarchical clustering and a centroid based algorithm applied to cell line collection expression dataset labeled 6 HGSOC cell lines as CL. These have a high energy metabolism and are enriched in CD44+/CD24− mesenchymal stem-like cells expressing low levels of cell-cell adhesion molecules (claudins and E-Cadherin) and high levels of epithelial-to-mesenchymal transition (EMT) induction transcription factors (Zeb1, Snai2, Twist1 and Twist2). Accordingly, the centroid base algorithm applied to large retrospective collections of primary HGSOC samples reveals a tumor subgroup with transcriptional features consistent with the CL profile, and reaffirms EMT as the dominant biological pathway functioning in CL-HGSOC. HGSOC patients carrying CL profiles have a worse overall survival when compared to others, likely to be attributed to its undifferentiated/stem component. These observations highlight the lack of a molecular diagnostic in the management of HGSOC and suggest a potential prognostic utility of this molecular subtyping.
Green Nanocoatings Based on the Deposition of Zirconium Oxide: The Role of the Substrate

Herein, the influence of the substrate in the formation of zirconium oxide monolayer, from an aqueous hexafluorozirconic acid solution, by chemical conversion and by electro-assisted deposition, has been approached. The nanoscale dimensions of the ZrO2 film is affected by the substrate nature and roughness. This study evidenced that the mechanism of Zr-EAD is dependent on the potential applied and on the substrate composition, whereas conversion coating is uniquely dependent on the adsorption reaction time. The zirconium oxide based nanofilms were more homogenous in AA2024 substrates if compared to pure Al grade (AA1100). It was justified by the high content of Cu alloying element present in the grain boundaries of the latter. Such intermetallic active sites favor the obtaining of ZrO2 films, as demonstrated by XPS and AFM results. From a mechanistic point of view, the electrochemical reactions take place simultaneously with the conventional chemical conversion process driven by ions diffusion. Such findings will bring new perspectives for the generation of controlled oxide coatings in modified electrodes used, as for example, in the construction of battery cells; in automotive and in aerospace industries, to replace micrometric layers of zinc phosphate by light-weight zirconium oxide nanometric ones. This study is particularly addressed for the reduction of industrial waste by applying green bath solutions without the need of auxiliary compounds and using lightweight ceramic materials.
Chemically Defined Xeno- and Serum-Free Cell Culture Medium to Grow Human Adipose Stem Cells

Adipose tissue is an abundant source of stem cells. However, liposuction cannot yield cell quantities sufficient for direct applications in regenerative medicine. Therefore, the development of GMP-compliant ex vivo expansion protocols is required to ensure the production of a “cell drug” that is safe, reproducible, and cost-effective. Thus, we developed our own basal defined xeno- and serum-free cell culture medium (UrSuppe), specifically formulated to grow human adipose stem cells (hASCs). With this medium, we can directly culture the stromal vascular fraction (SVF) cells in defined cell culture conditions to obtain hASCs. Cells proliferate while remaining undifferentiated, as shown by Flow Cytometry (FACS), Quantitative Reverse Transcription PCR (RT-qPCR) assays, and their secretion products. Using the UrSuppe cell culture medium, maximum cell densities between 0.51 and 0.80 × 105 cells/cm2 (=2.55–4.00 × 105 cells/mL) were obtained. As the expansion of hASCs represents only the first step in a cell therapeutic protocol or further basic research studies, we formulated two chemically defined media to differentiate the expanded hASCs in white or beige/brown adipocytes. These new media could help translate research projects into the clinical application of hASCs and study ex vivo the biology in healthy and dysfunctional states of adipocytes and their precursors. Following the cell culture system developers’ practice and obvious reasons related to the formulas’ patentability, the defined media’s composition will not be disclosed in this study.
Tear Film Break-Up Time and Dry Eye Disease Severity in a Large Norwegian Cohort

This study evaluated to what extent tear film break-up time (TFBUT) could discriminate pathological scores for other clinical tests and explore the associations between them. Dry eye patients (n = 2094) were examined for ocular surface disease index (OSDI), tear film osmolarity (Osm), TFBUT, blink interval, ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test, meibomian expressibility, meibomian quality, and meibomian gland dysfunction. The results were grouped into eight levels of break-up time (≤2, ≥3, ≤5, ≥6, ≤10, ≥11, ≤15, and ≥16) with or without sex stratification. Receiver-operating characteristic curve (ROC) analysis and Pearson’s correlation coefficients were used to study TFBUT’s discriminative power and the associations among the tests, respectively. Above and below each TFBUT’s cut-off, all of the parameters indicated significant difference between groups, except OSDI (cut-off 15 s) and Osm (cut-offs 5 s–15 s). At TFBUT cut-off of 2 s, sex difference could be detected for OSDI, Osm, and OSS. OPI presented the strongest discriminative power and association with TFBUT in sharp contrast to Osm, holding the poorest discriminative power with no significant correlation. The remaining parameters were within the poor to very poor categories, both with regard to discrimination and correlation. In conclusion, patients with lower TFBUT presented with more severe DED parameters at all four defined cut-off values.
Monetite (CaHPO4) Synthesis in Ethanol at Room Temperature

A straightforward process was developed to synthesize monetite (CaHP0 4 , dicalcium phosphate anhydrous) powders at room temperature (21°±1°C) in ethanol solutions. The process reported here constitutes an alternative to well-publicized monetite synthesis procedures based on the dehydration of brushite (CaHP0 4 .2H 2 0, dicalcium phosphate dihydrate) powders either in acidic, hot (70°-95°C) aqueous solutions or in drying ovens (200°-225°C). Submicrometer monetite powders were synthesized in ethanol (ethyl alcohol) solutions containing small aliquots of concentrated H 3 PO 4 (orthophosphoric acid, 85%). Precipitated CaCO 3 (calcium carbonate, calcite form) powders with submicrometer particles were simply stirred in the above solutions in glass bottles for 3 h. The starting Ca/P molar ratio in the synthesis bottles was 0.50. Monetite powders obtained with a stacked-nanosheets particle texture did not contain any unreacted CaC0 3 . Monetite powders were also found to have the ability to completely transform into apatitic (apatite-like) calcium phosphate powders when soaked in calcium-containing saline solutions (i.e., 142 mM Na + , 5 mM K + , and 50 mM Ca 2+ in water) for 6 days at 37°C.
Sleep and the General Behavior of Infants and Parents during the Closure of Schools as a Result of the COVID-19 Pandemic: Comparison with 2019 Data

This study compared cross-sectional data from online surveys describing the sleep behavior of infants and caregivers in March 2020 (the school closure period during the early stages of the COVID-19 pandemic; n = 295, 23.8 ± 3.8 months old) and March 2019 (before the pandemic; n = 2017, 24.2 ± 3.8 months old). In comparing those two points in time, no significant differences were found in wake-up times (2019: 7:19 ± 0:46 am vs. 2020: 7:18 ± 0:47 am, p = 0.289), bedtimes (21:01 ± 0:48 pm vs. 21:04 ± 0:53 pm, p = 0.144), or nocturnal sleep times (593.7 ± 43.9 min vs. 588.1 ± 50.3 min, p = 0.613). Regarding the caregivers, in 2020, wake-up times (2019: 6:46 ± 0:50 am vs. 2020: 6:39 ± 0:50 am, p = 0.017) and bedtimes (22:53 ± 1:17 pm vs. 22:42 ± 1:04 pm, p = 0.016) became significantly earlier compared to 2019. Among infants staying at home, total sleep time and percentage of outdoor play decreased significantly, and media use increased significantly in 2020. Lower levels of exercise and more frequent media viewing may have caused prolonged sleep latency in these children. The percentage of caregivers responding with “negative childcare feelings” was significantly higher in the group with less than three nursery school attendance days. Caregivers and infants staying at home are a high-risk group during the pandemic.
Evidence for the Contribution of Gut Microbiota to Age-Related Anabolic Resistance

Globally, people 65 years of age and older are the fastest growing segment of the population. Physiological manifestations of the aging process include undesirable changes in body composition, declines in cardiorespiratory fitness, and reductions in skeletal muscle size and function (i.e., sarcopenia) that are independently associated with mortality. Decrements in muscle protein synthetic responses to anabolic stimuli (i.e., anabolic resistance), such as protein feeding or physical activity, are highly characteristic of the aging skeletal muscle phenotype and play a fundamental role in the development of sarcopenia. A more definitive understanding of the mechanisms underlying this age-associated reduction in anabolic responsiveness will help to guide promyogenic and function promoting therapies. Recent studies have provided evidence in support of a bidirectional gut-muscle axis with implications for aging muscle health. This review will examine how age-related changes in gut microbiota composition may impact anabolic response to protein feeding through adverse changes in protein digestion and amino acid absorption, circulating amino acid availability, anabolic hormone production and responsiveness, and intramuscular anabolic signaling. We conclude by reviewing literature describing lifestyle habits suspected to contribute to age-related changes in the microbiome with the goal of identifying evidence-informed strategies to preserve microbial homeostasis, anabolic sensitivity, and skeletal muscle with advancing age.
Alternative Friendships to Improve Men’s Health Status. The Impact of the New Alternative Masculinities’ Approach

Background: Men who develop behaviors connected with the model of hegemonic masculinity present several health problems. Previous research has shown the types of problems that men commonly suffer in this regard such as chronic diseases, dietary disorders, and traffic accidents. To combat and overcome this situation, several campaigns, policies and recommendations have been undertaken, and consequently, their influence has been analyzed. However, there have been few investigations into the role of men’s friendship in the reduction of these physical health problems. The findings presented in this article are focused on this issue, illustrating the impact of male friendship on the shaping of healthy behaviors. Methods: Drawing upon a qualitative-based methodology articulated in a case study of the Men in Dialogue association, located in Spain, the study has followed the premises of the communicative approach, a total of 15 structured online open-ended questionnaires have been performed and analyzed. The median age of the participants is 37.5 years. Results: The findings show how men involved in Men in Dialogue are promoting a kind of masculine friendship that is improving men’s emotional well-being and, consequently, their physical health.
DNA or Protein Methylation-Dependent Regulation of Activator Protein-1 Function

Epigenetic regulation and modification govern the transcriptional mechanisms that promote disease initiation and progression, but can also control the oncogenic processes, cell signaling networks, immunogenicity, and immune cells involved in anti-inflammatory and anti-tumor responses. The study of epigenetic mechanisms could have important implications for the development of potential anti-inflammatory treatments and anti-cancer immunotherapies. In this review, we have described the key role of epigenetic progression: DNA methylation, histone methylation or modification, and protein methylation, with an emphasis on the activator protein-1 (AP-1) signaling pathway. Transcription factor AP-1 regulates multiple genes and is involved in diverse cellular processes, including survival, differentiation, apoptosis, and development. Here, the AP-1 regulatory mechanism by DNA, histone, or protein methylation was also reviewed. Various methyltransferases activate or suppress AP-1 activities in diverse ways. We summarize the current studies on epigenetic alterations, which regulate AP-1 signaling during inflammation, cancer, and autoimmune diseases, and discuss the epigenetic mechanisms involved in the regulation of AP-1 signaling.
Oral Health Status and the Impact on Oral Health-Related Quality of Life among the Institutionalized Elderly Population: A Cross-Sectional Study in an Area of Southern Italy

Abstract Background: The objectives of this study were to describe the oral health status in the institutionalized geriatric population in an area of southern Italy and to identify the impact of oral health on the Oral Health Related Quality of Life (OHRQoL). Methods: Data were collected from individuals aged ≥60 years in randomly selected Calabrian long-term care facilities. The dental health status was assessed recording the decayed, missing, or filled dental elements due to the carious lesions (DMFT) index, the presence of visible dental plaque, and the gingival condition. The influence of the dental health status on the self-perceived value of life was assessed using the Geriatric Oral Health Assessment Index (GOHAI). Results: Among the 344 elderly individuals included, 18.4% reported frequent tooth-brushing, and only 39.9% reported the need of dental care. The DMFT index was 26.4. Less than a third of the participants had a GOHAI score of ≤50 which is suggestive of highly compromised OHRQoL. The GOHAI score was significantly better for elderly individuals with no self-perceived need of dental care and with a lower DMFT index. Conclusions: The burden of oral conditions among residents in long-term care facilities was considerable, with a high prevalence of missing teeth and dentures. Strategies targeting care providers are needed.