Miracle-dz/UniFAR-FTUs huggingface dataset:
The Perceived Health Status from Young Adults to Elderly: Results of the MEHM Questionnaire within the CUORE Project Survey 2008–2012

Improving healthy life years requires an effective understanding and management of the process of healthy ageing. Assessing the perceived health status and its determinants is a relevant step in this process. This study explored the potentialities of the Minimum European Health Module (MEHM) to cope with this critical issue. Investigation was conducted on 4798 Italian residents (49.7% women, aged 35–79 years), participating in the CUORE Project Health Examination Survey 2008–2012. The three MEHM questions—perceived health status, chronic morbidity and activity limitations—were examined also in association with living context, seasonality, marital status and level of education. A higher prevalence of health status negative perception was associated with older age (9% and 24% respectively in men and women aged 35–44 years; 46% and 61% respectively in men and women aged 75–79 years). In women, this negative perception was higher than in men in any age group, and reached 50% in the 65–69 age group, 10 years earlier than in men. For both sexes, the level of education had a strong impact on this negative perception (odds ratio 2.32 and 2.72 in men and women respectively), while “living alone” played a greater impact in women than in men. MEHM activity limitations subscale was as much as 30% higher for questionnaires answered during the hottest months. This study identified potential predictors of perceived health status in adults aged 35–79 years, which can be used to target interventions aimed at improving self-perceived health status.
Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study

Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking. Objective: To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA. Methods: Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls without previous cardiovascular events. Peripheral ED, evaluated by flow-mediated pulse amplitude tonometry, was defined by log-transformed reactive hyperemia index (Ln-RHI) values < 0.51. Results: PON-1 activity and PSH concentrations were significantly reduced in RA patients compared to controls. In regression analysis, increased plasma MDA levels were significantly associated with reduced Ln-RHI [B coefficient (95% CI) = −0.003 (−0.005 to −0.0008), p = 0.008] and the presence of peripheral ED (OR (95% CI) = 1.75 (1.06–2.88), p = 0.028). Contrary to our expectations, increased PON-1 activity was significantly associated, albeit weakly, with the presence of ED (OR (95% CI) = 1.00 (1.00–1.01), p = 0.017). Conclusions: In this first evidence of a link between oxidative stress and markers of atherosclerosis, MDA and PON-1 showed opposite associations with peripheral vasodilatory capacity and the presence of ED in RA. Further studies are needed to determine whether this association predicts atherosclerotic events in the RA population.
A novel prognostic index of hepatocellular carcinoma based on immunogenomic landscape analysis

Changes in immune responses to hepatocellular carcinoma (HCC) are closely related to the occurrence, development, and prognosis of this disease. Exploring the role of immune‐related genes (IRGs) in HCC would provide insights into the mechanisms regulating this disease. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) provide a platform for such research, owing to a large number of HCC samples available for comprehensive and systematic immunogenomics analyses. We analyzed the IRGs expression profile and clinical information of patients with HCC based on the TCGA and ICGC database. Potential molecular mechanisms and properties of the screened IRGs were analyzed across multiple databases. And we analyzed the correlation between IRGs, single‐nucleotide polymorphisms, and copy number variation. A novel prognostic index, based on IRGs, was developed using the LASSO Cox regression algorithm, followed by univariate and multivariate Cox regression analyses to analyze the prognostic index. Information in the ICGC database was used to verify the reliability of the prognostic index. A total of 54 differentially expressed IRGs were found to be significantly associated with HCC prognosis, and there is a significant correlation between their expression level and copy number variation. Functional enrichment analyses indicated that the genes play active roles in tumor and immune‐related signaling pathways. In addition, five potential biomarkers namely IRG, MAPK3, HSP90AA1, HSP90AB1, HSPA4, and CDK4, were identified. Finally, a novel prognostic index, based on IRGs (PSMD14, FABP6, ISG20L2, HGF, BIRC5, IL17D, and STC2), was found useful as an independent prognostic factor, not only for prognosis but also to reflect levels of infiltration in a variety of immune cells. Our team conducted a genomics study of IRGs in HCC and screened several clinically significant IRGs, and our model provides an effective approach for stratification and characterization of patients using IRG‐based immunolabeling tools to monitor the prognosis of HCC.
Maladaptive Changes Associated With Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice

Abstract We investigated whether late-life changes in cardiac structure and function were related to high levels of frailty and inflammation in male and female mice. Frailty (frailty index), ventricular structure/function (echocardiography), and serum cytokines (multiplex immunoassay) were measured in 16- and 23-month-old mice. Left ventricular (LV) mass and septal wall thickness increased with age in both sexes. Ejection fraction increased with age in males (60.4 ± 1.4 vs 68.9 ± 1.8%; p < .05) but not females (58.8 ± 2.5 vs 62.6 ± 2.4%). E/A ratios declined with age in males (1.6 ± 0.1 vs 1.3 ± 0.1; p < .05) but not females (1.4 ± 0.1 vs 1.3 ± 0.1) and this was accompanied by increased ventricular collagen levels in males. These changes in ejection fraction (r = 0.52; p = .01), septal wall thickness (r = 0.59; p = .002), E/A ratios (r = −0.49; p = .04), and fibrosis (r = 0.82; p = .002) were closely graded by frailty scores in males. Only septal wall thickness and LV mass increased with frailty in females. Serum cytokines changed modestly with age in both sexes. Nonetheless, in males, E/A ratios, LV mass, LV posterior wall thickness, and septal wall thickness increased as serum cytokines increased (eg, IL-6, IL-3, IL-1α, IL-1β, tumor necrosis factor-α, eotaxin, and macrophage inflammatory protein-1α), while ejection fraction declined with increasing IL-3 and granulocyte-macrophage colony stimulating factor. Cardiac outcomes were not correlated with inflammatory cytokines in females. Thus, changes in cardiac structure and function in late life are closely graded by both frailty and markers of inflammation, but this occurs primarily in males. This suggests poor overall health and inflammation drive maladaptive changes in older male hearts, while older females may be resistant to these adverse effects of frailty.
Targeting IL‐5 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab

Airway hyperresponsiveness (AHR) is a central abnormality in asthma. IL‐5 may modulate AHR in animal models of asthma, but the available data is inconsistent on the impact of targeting IL‐5 pathway against AHR. The difference between targeting IL‐5 or the IL‐5 receptor, α subunit (IL‐5Rα) in modulating AHR remains to be investigated in human airways. The aim of this study was to compare the role of the anti‐IL‐5Rα benralizumab and the anti‐IL‐5 mepolizumab against AHR and to assess whether these agents influence the levels of cAMP.
A Case-Control Study of Meat Mutagens and Colorectal Cancers in Viet Nam

Objective: The aim was to examine the association between heterocyclic amines 2-amino-1-methyl-6-phenylimidazo pyridine (PhIP) and the risk of colorectal cancer (CRC) in Viet Nam. Methods: We performed a case-control study for 512 colorectal cancer patients with the histopathological confirmation and 1,096 hospital controls. We collected information on lifestyle, diet, and cooking methods from participants by trained interviewers using the validated questionnaires. We used data of PhIP concentration in cooked beef analyzed by the LC/MS/MS and cooking questionnaire to estimate the daily intake of PhIP. We divided the estimated amount of PhIP (ng/person/day) into three levels of non-intake (the reference), medium, and high to estimate the Odds ratio and 95% confidence interval (OR, 95%CI). Results: The median intake of PhIP (ng/person/day) was 18ng and 102.8ng for medium and high PhIP intake, respectively. There was a significant association between PhIP intake and the risk of colorectal cancer. The adjusted OR (95%C), high intake vs. non-intake, were 4.89 (3.03, 7.89), p_trend<0.01 for all participants, for men OR (95%C): 5.27 (2.83, 9.81), p_trend<0.01, for women OR (95%C): 4.58 (2.10, 10.01), p_trend<0.01. The significant positive association was also observed for the sub-sites of the colon (proximal and distant) and rectum cancers. Conclusions: We observed the positive association of PhIP contributed from cooked-beef and the development of CRC. Cooking methods related to the occurrence of PhIP and other types of heterocyclic amines in cooked-beef and other meats would be significant investigations.
Electronic Patient Reporting of Adverse Events and Quality of Life: A Prospective Feasibility Study in General Oncology

PURPOSE: Adverse event (AE) reporting is essential in clinical trials. Clinician interpretation can result in under-reporting; therefore, the value of patient self-reporting has been recognized. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for direct patient AE reporting. A nonrandomized prospective cohort feasibility study aimed to explore the compliance and acceptability of an electronic (Internet or telephone) system for collecting patient self-reported AEs and quality of life (QOL). METHODS: Oncology patients undergoing treatment (chemotherapy, targeted agents, hormone therapy, radiotherapy, and/or surgery) at 2 hospitals were sent automated weekly reminders to complete PRO-CTCAE once a week and QOL (for a maximum of 12 weeks). Patients had to speak/understand English and have access to the Internet or a touch-tone telephone. Primary outcome was compliance (proportion of expected questionnaires), and recruitment rate, attrition, and patient/staff feedback were also explored. RESULTS: Of 520 patients, 249 consented (47.9%)—mean age was 62 years, 51% were male, and 70% were married—and 230 remained on the study at week 12. PRO-CTCAE was completed at 2,301 (74.9%) of 3,074 timepoints and QOL at 749 (79.1%) of 947 timepoints. Individual weekly/once every 4 weeks compliance reduced over time but was more than 60% throughout. Of 230 patients, 106 (46.1%) completed 13 or more PRO-CTCAE, and 136 (59.1%) of 230 patients completed 4 QOL questionnaires. Most were completed on the Internet (82.3%; mean age, 60.8 years), which was quicker, but older patients preferred the telephone option (mean age, 70.0 years). Positive feedback was received from patients and staff. CONCLUSION: Self-reporting of AEs and QOL using an electronic home-based system is feasible and acceptable. Implementation of this approach in cancer clinical trials may improve the precision and accuracy of AE reporting.
Chromosome‐level de novo genome assembly of Sarcophaga peregrina provides insights into the evolutionary adaptation of flesh flies

Sarcophaga peregrina is considered to be of great ecological, medical and forensic significance, and has unusual biological characteristics such as an ovoviviparous reproductive pattern and adaptation to feed on carrion. The availability of a high‐quality genome will help to further reveal the mechanisms underlying these charcateristics. Here we present a de novo‐assembled genome at chromosome scale for S. peregrina. The final assembled genome was 560.31 Mb with contig N50 of 3.84 Mb. Hi‐C scaffolding reliably anchored six pseudochromosomes, accounting for 97.76% of the assembled genome. Moreover, 45.70% of repeat elements were identified in the genome. A total of 14,476 protein‐coding genes were functionally annotated, accounting for 92.14% of all predicted genes. Phylogenetic analysis indicated that S. peregrina and S. bullata diverged ~ 7.14 million years ago. Comparative genomic analysis revealed expanded and positively selected genes related to biological features that aid in clarifying its ovoviviparous reproduction and carrion‐feeding adaptations, such as lipid metabolism, olfactory receptor activity, antioxidant enzymes, proteolysis and serine‐type endopeptidase activity. Protein‐coding genes associated with ovoviparity, such as yolk proteins, transferrin and acid sphingomyelinase, were identified. This study provides a valuable genomic resource for S. peregrina, and sheds insight into further revealing the underlying molecular mechanisms of adaptive evolution.
Clinical Features of Plasmablastic Lymphoma: Case Series From an Asian Tertiary Cancer Center and Literature Review

Background Plasmablastic lymphoma (PBL) is an aggressive subtype of mature B-cell non-Hodgkin lymphoma. Given its rarity, there remains a lack of clinicopathological data to guide its management, particularly on Asian patients. Methods We conducted a retrospective chart review of 10 patients diagnosed with PBL at the National Cancer Centre Singapore and performed a literature review of similar studies on Asian cohorts. Results Most patients were male (n = 9), with median age at diagnosis of 55 years (range, 33 - 91 years). Seven (70%) patients were considered to be immunocompromised. In the overall cohort, the median overall survival (OS) was 19.4 months with 5-year survival estimates given at 60% and 36% for OS and progression-free survival (PFS), respectively. At diagnosis, patients with HIV/AIDS (n = 5) were younger compared to others (median, 43 vs. 61 years; P = 0.0278), had greater number of nodal site involvement (median, 6 vs. 0; P = 0.0333), and higher international prognostic index (IPI) scores (P = 0.034 for trend). Amongst different chemotherapy used, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH)-based regimens (n = 6) elicited prominent complete response rates (83%) and led to durable responses even in the setting of advanced stage, high-risk IPI score and immunodeficiency. Conclusions In conclusion, our study describes the features of PBL in an Asian cohort and highlights disease features unique to HIV-associated PBL.
2.4 Synaptic Vesicle Associated Proteins and Schizophrenia

There is increasing evidence implicating proteins associated with the synaptic vesicle, a presynaptic organelle that is essential for neurotransmission and synaptic connectivity, to schizophrenia. This chapter reviews the postmortem, genetic, and behavioral data, examines the trends and their relevance. List of Abbreviations: GABA, gamma aminobutyric acid; MAPK, mitogen-activated protein kinase; . 4 Synaptic vesicle associated proteins and schizophrenia SNARE, soluble N-ethylmaleimide-sensitive fusion attachment protein receptor; SNP, single nucleotide polymorphism
Analysis of a second Drosophila Cornichon Protein

Cornichon proteins represent a highly conserved protein family of cargo receptors mediating efficient endoplasmic reticulum (ER) export of numerous transmembrane proteins in all eukaryotes analyzed so far. Drosophila possesses two cornichon genes: cornichon and cornichon-related (cnir). The former is well known for its function in establishment of dorsoventral polarity in the oocyte. This process relies on ER export and processing of the TGFa ligand Gurken and its transport to the oocyte surface. The function of Cnir has not been studied so far and is the subject of this thesis. Phylogentic analysis showed that Cnir represents a putative ortholog of the human Cornichon homolog 4 (CNIH4). A precise deletion of the cnir gene was generated through ends-out targeting via homologous recombination. The cnir mutants are viable but have an increased mortality throughout development and adult life. Furthermore cnir mutant flies display a strong locomotor defect, as well as a reduced sensitivity towards ethanol. Analysis via rescue experiments demonstrated that Cnir function is required in neurons for restoration of locomotor behavior. Using GFP tagged proteins, Cnir was found to putatively localize to the endoplasmic reticulum, supporting a conserved role as cargo receptor. A double mutant for both Drosophila Conrichon proteins was generated and its clonal analysis, as well as crossing genetics, indicate no functional redundancy in the soma. This suggests a selectivity of Cornichon proteins towards specific cagro pools. The putative Cnir ortholog CNIH4 has been shown to interact with the three major families of G protein coupled receptors (GPCRs) and is involved in their trafficking. GPCRs represent the largest superfamily of cell surface receptors and regulate almost every physiological and cellular process, making their trafficking an important flied of study. Locomotor impairment and Parkinson’s disease have been linked to perturbation of dopaminergic pathways in fly and vertebrates. Furthermore, ethanol sensitivity is associated with altered cAMP levels downstream of GPCR signaling. Therefore, locomotor impairment and reduced ethanol sensitivity of cnir mutants might be linked to inefficient GPCR trafficking and thus reduced signaling levels.
Surveillance of Esophageal Cancer in the Republic of Uzbekistan from 2000 to 2018

Background: Differences in the geographical distributions of esophageal cancer (EC) are associated with environmental influences and genetic risk factors. The inhabitants of the Republic of Uzbekistan are at high-risk for EC; however, detailed epidemiological data regarding the dynamics of EC are not available. Methods: To address this gap in our knowledge, here we reviewed trends in the incidence of EC in Uzbekistan from 2000 through 2018. We acquired the epidemiological data for 17,144 patients with EC from the national epidemiological data base of Uzbekistan. Results: The mean incidence (per 100,000 persons) during the study period was 2.8, which peaked at 3.9 in 2007 and decreased below 2.5 in 2014 and thereafter. The incidence was highest for patients aged 61 years to 70 years (37.5%). Among patients with EC, 13,331 (80.0%) and 3,333 (20.0%) were diagnosed with squamous cell carcinoma or adenocarcinoma, respectively. The incidences of patients with EC with adenocarcinoma were 0.6 from 2010–2018 and 0.4 from 2000 to 2009. The majority of patients were diagnosed with stage III EC, which was associated with a 5-year survival rate that increased from approximately 15% (2000–2009) and plateaued at approximately 25% (2012–2018). Conclusions: We conclude that preventing the progression of EC to stage III is required to improve the prognosis of patients with EC who reside in Uzbekistan.
Characteristics and outcomes of a cohort of COVID-19 patients in the Province of Reggio Emilia, Italy

This is a population-based prospective cohort study on archive data describing the age- and sex-specific prevalence of COVID-19 and its prognostic factors. All 2653 symptomatic patients tested positive for SARS-CoV-2 from February 27 to April 2, 2020 in the Reggio Emilia province, Italy, were included. COVID-19 cumulative incidence, hospitalization and death rates, and adjusted hazard ratios (HR) with 95% confidence interval (95% CI) were calculated according to sociodemographic and clinical characteristics. Females had higher prevalence of infection than males below age 50 (2.61 vs. 1.84 ‰), but lower in older ages (16.49 vs. 20.86 ‰ over age 80). Case fatality rate reached 20.7% in cases with more than 4 weeks follow up. After adjusting for age and comorbidities, men had a higher risk of hospitalization (HR 1.4 95% CI 1.2 to 1.6) and of death (HR 1.6, 95% CI 1.2 to 2.1). Patients over age 80 compared to age < 50 had HR 7.1 (95% CI 5.4 to 9.3) and HR 27.8 (95% CI 12.5 to 61.7) for hospitalization and death, respectively. Immigrants had a higher risk of hospitalization (HR 1.3, 95% CI 0.99 to 1.81) than Italians and a similar risk of death. Risk of hospitalization and of death were higher in patients with heart failure, arrhythmia, dementia, coronary heart disease, diabetes, and hypertension, while COPD increased the risk of hospitalization (HR 1.9, 95% CI 1.4 to 2.5) but not of death (HR 1.1, 95% CI 0.7 to 1.7). Previous use of ACE inhibitors had no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34). Identified susceptible populations and fragile patients should be considered when setting priorities in public health planning and clinical decision making.
Ciprofloxacin-Collagen-Based Materials with Potential Oral Surgical Applications

We report in this paper the synthesis and characterization of a new collagen-based material. This material was obtained in a spongy form and was functionalized with an antibiotic, ciprofloxacin. The targeted applications of these kind of materials concern the post-operative prophylaxis. The in vitro tests (antimicrobial, cytotoxic, drug release) showed that sponges with a concentration of 0.75 g of ciprofloxacin per gram of collagen could be beneficial for the desired applications.
Up in the Air: Evidence of Dehydration Risk and Long-Haul Flight on Athletic Performance

The microclimate of an airline cabin consists of dry, recirculated, and cool air, which is maintained at lower pressure than that found at sea level. Being exposed to this distinctive, encapsulated environment for prolonged durations, together with the short-term chair-rest immobilization that occurs during long-haul flights, can trigger distinct and detrimental reactions to the human body. There is evidence that long-haul flights promote fluid shifts to the lower extremity and induce changes in blood viscosity which may accelerate dehydration, possibly compromising an athlete’s potential for success upon arrival at their destination. Surprisingly, and despite several recent systematic reviews investigating the effects of jet lag and transmeridian travel on human physiology, there has been no systematic effort to address to what extent hypohydration is a (health, performance) risk to travelers embarking on long journeys. This narrative review summarizes the rationale and evidence for why the combination of fluid balance and long-haul flight remains a critically overlooked issue for traveling persons, be it for health, leisure, business, or in a sporting context. Upon review, there are few studies which have been conducted on actual traveling athletes, and those that have provide no real evidence of how the incidence rate, magnitude, or duration of acute dehydration may affect the general health or performance of elite athletes.