Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between Blood Heavy Metal Levels and Predicted 10-Year Risk for A First Atherosclerosis Cardiovascular Disease in the General Korean Population

Background: Atherosclerotic cardiovascular disease (ASCVD) is a preventable type of disease, thus, specifying factors that increase the occurrence of this type of disease is needed. Heavy metals such as cadmium (Cd), lead (Pb), and mercury (Hg) have been suggested as possible factors influencing the development of cardiovascular disease. We aimed to link blood heavy metal levels (Cd, Pb, Hg) with 10-year ASCVD risk scores. Methods: A population of 993 men and 1431 women who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) were included. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations risk prediction model and Korean Risk Prediction Model (KRPM) were used as means for risk prediction. Following multivariate adjustment; blood Cd; Pb; and Hg levels were divided into quartiles for analysis using linear trends estimation and multiple regression models. Results: There was an overall positive trend between blood Cd, Pb, and Hg levels and 10-year ASCVD risk scores; KRPM risk score increasing by quartile for blood Cd (men p < 0.0001, women p = 0.0024), Pb (men p = 0.0097, women p = 0.0330), Hg (men p = 0.0096, women p = 0.0030) rates and pooled cohort equations risk score increasing by quartile for Cd (men p < 0.0001, women p = 0.0034) and Hg (men p = 0.0099, women p = 0.0010) with linear trends. Urban population showed a stronger relationship between blood Cd, Pb, and Hg levels and 10-year ASCVD risk score especially among men with multiple regression analysis. Conclusion: Blood Cd, Pb, and Hg levels are associated with ASCVD risk. Thus, they should be considered while developing preventive measures for ASCVD.
Effects of Melatonin Administration to Pregnant Ewes under Heat-Stress Conditions, in Redox Status and Reproductive Outcome

Heat stress is a known promoter of reactive oxygen species generation, which may compromise pregnancy and foetal development. Melatonin is a pleiotropic molecule that regulates various processes including pregnancy. Thus, it could be used to ameliorate the redox status of pregnant heat-stressed ewes and the outcome of their pregnancy. Sixty-eight ewes participated in the study, which were allocated into two equal groups, i.e., Melatonin (M) and Control (C) group. All ewes were exposed to heat stress from D0 to D120. In both groups, after oestrus synchronization of ewes, rams were introduced to them for mating (D16). In M group, starting with sponges’ insertion (D0), melatonin implants were administered four-fold every 40 days. Pregnancy diagnosis was performed by means of ultrasonography. Daily evaluation of temperature humidity index (THI), rectal temperature, and breathing rate were performed throughout the study. Blood samples were collected repeatedly from D0 until weaning for assaying redox biomarkers. Milk yield was measured thrice during puerperium. The results showed that melatonin administration throughout pregnancy improved the redox status of heat-stressed ewes and increased the mean number and bodyweight of lambs born per ewe, as well as the milk production. Therefore, melatonin may be used as antioxidant regimen in heat-stressed ewes for improving their reproductive traits.
Exhaled Breath Condensate in Disease Monitoring

Collection of exhaled breath condensate (EBC) is a simple, noninvasive way of obtaining samples from the airways. EBC contains a large number of mediators including adenosine, ammonia, hydrogen peroxide, ions, isoprostanes, leukotrienes, nitric oxide-derived products, prostaglandins, etc. Levels of these mediators are influenced by airway diseases, including asthma, chronic obstructive airway diseases (COPD), cystic fibrosis (CF), and bronchiectasis, and modulated by treatment modalities. Furthermore, EBC has other characteristics, such as pH, which is also modulated in airway diseases in relation to disease activity. Although analysis of EBC is a research tool at present, there is accumulating evidence suggesting that detecting and monitoring of biomarkers in EBC may be helpful in diagnosis and follow-up of patients with various pulmonary diseases, not only in research but also in clinical practice. The aim of this review is to describe the most important methodological issues and summarize our current knowledge on the use of EBC analysis for monitoring lung diseases.
Site-Specific Lipidomic Signatures of Sea Lettuce (Ulva spp., Chlorophyta) Hold the Potential to Trace Their Geographic Origin

The wild harvest and aquaculture of Ulva spp. has deserved growing attention in Europe. However, the impact of geographical origin on the biochemical composition of different species and/or strains is yet to be described in detail. Hence, the present study aimed to detect the variability of the lipidome of different species and/or strains of Ulva originating from different geographic locations. We hypothesized that lipidomic signatures can be used to trace the geographic origin post-harvesting of these valuable green seaweeds. Ulva spp. was sampled from eight distinct ecosystems along the Atlantic Iberian coast and Ulva rigida was sourced from an aquaculture farm operating a land-based integrated production site. Results showed significant differences in the lipidomic profile displayed by Ulva spp. originating from different locations, namely, due to different levels of polyunsaturated betaine lipids and galactolipids; saturated betaine lipids and sulfolipids; and some phospholipid species. Overall, a set of 25 site-specific molecular lipid species provide a unique lipidomic signature for authentication and geographic origin certification of Ulva species. Present findings highlight the potential of lipidome plasticity as a proxy to fight fraudulent practices, but also to ensure quality control and prospect biomass for target bioactive compounds.
Injectable Biologics

Abstract Injectable biologics have attracted considerable interest in the field of musculoskeletal medicine. Biologics encompass a broad and diverse group of human tissue–derived therapeutics. The most commonly reported biologics for use in musculoskeletal conditions include platelet-rich plasma, bone marrow aspirate concentrate, mesenchymal stem cells, microfragmented fat, stromal vascular fraction, amniotic membrane–based products, and autologous conditioned serum. The benefits of biologics in tissue healing and regeneration are thought to be derived from their trophic, paracrine, and immunomodulatory functions. The purpose of this review is to define commonly used injectable biologics and to appraise current evidence on its efficacy in the treatment of musculoskeletal disease.
The microbiome of modern microbialites in Bacalar Lagoon, Mexico

Microbialites are highly diverse microbial communities that represent modern examples of the oldest life forms, stromatolites (dated >3.7 Ga). Bacalar Lagoon, in Mexico, harbors the largest freshwater microbialite occurrences of the world; yet diverse anthropogenic activities are changing the oligotrophic conditions of the lagoon. The objective of this work was to perform a spatial exploration of the microbialites of Bacalar Lagoon, analyze their prokaryote diversity, following a high throughput sequencing approach of the V4 region of the 16S rDNA, and correlate to the environmental parameters that influence the structure of these communities. The results indicate the presence of microbialites throughout the periphery of the lagoon. The microbiome of the microbialites is composed primarily of Proteobacteria (40–80%), Cyanobacteria (1–11%), Bacteroidetes (7–8%), Chloroflexi (8–14%), Firmicutes (1–23%), Planctomycetes (1–8%), and Verrucomicrobia (1–4%). Phylogenetic distance analyses suggests two distinct groups of microbialites associated with regions in the lagoon that have differences in their environmental parameters, including soluble reactive silicate (in the north), bicarbonates and available forms of nitrogen (ammonium, nitrates and nitrites) (in the south). These microbialite groups had differences in their microbiome composition associated to strong anthropogenic pressure on water quality (agriculture, landfill leachate, lack of water treatment infrastructure and intensive tourism), which were related to a loss of microbial diversity.
Declining grouper spawning aggregations in Western Province, Solomon Islands, signal the need for a modified management approach

Globally, groupers (Epinephelidae) that form fish spawning aggregations (FSAs) are highly vulnerable to overfishing and often require site-specific approaches to management. Over 5-years (2009–2013), we conducted underwater visual censuses (UVC) at a well-known spawning site at Njari Island, Gizo, Western Province, Solomon Islands, that supports aggregations of squaretail coralgrouper (Plectropomus areolatus), camouflage grouper (Epinephelus polyphekadion) and brown-marbled grouper (E. fuscoguttatus). Findings show that while there were species-specific variations in the duration and timing of the spawning season, aggregation densities peaked from March to June, representing the main spawning season for all three species. For P. areolatus, gonad analysis from samples taken from 2008 to 2011 confirmed reproductive activity in support of density trends observed through UVC. Over the 5-year UVC monitoring period, FSA densities declined for P. areolatus and E. polyphekadion. Conversely, following the first year of monitoring, E. fuscoguttatus densities increased. These inter-specific differences may reflect variable responses to fishing as shown elsewhere, or for example, differences in recruitment success. In response to known declines in FSAs of these species, in 2018 the Solomon Islands government placed a nationwide ban on these species’ harvest and sale between October and January. As this study shows, this ban does not encompass the peak aggregation period at Njari and will offer limited protection to other FSAs of these species that are known to vary in reproductive seasonality across the Solomon Islands. A more biologically meaningful and practical management strategy would be to implement a nationwide ban on the harvest and sale of these groupers each month between full and new moons when these FSAs form consistently throughout the country. Since effective management of FSAs typically requires a combined approach, spatial management that protects both spawning sites and reproductive migratory corridors is warranted.
Alpha-Glucosidase Inhibitor Voglibose Suppresses Azoxymethane-Induced Colonic Preneoplastic Lesions in Diabetic and Obese Mice

Type 2 diabetes mellitus and its related insulin resistance are known to increase the risk of cancer. Anti-diabetic agents can improve insulin resistance and may lead to the suppression of carcinogenesis. This study aimed to investigate the preventive effects of the alpha-glucosidase inhibitor voglibose on the development of azoxymethane-induced colorectal pre-neoplastic lesions in obese and diabetic C57BL/KsJ-db/db mice. The direct effects of voglibose on the proliferation of colorectal cancer cells were also evaluated. Mice were injected with azoxymethane to induce colorectal pre-malignancy and were then administered drinking water with or without voglibose. At the end of the study, the administration of voglibose significantly suppressed the development of colorectal neoplastic lesions. In voglibose-treated mice, serum glucose levels, oxidative stress, as well as mRNA expression of the insulin-like growth factor-1 in the colon mucosa, were reduced. The proliferation of human colorectal cancer cells was not altered by voglibose. These results suggested that voglibose suppressed colorectal carcinogenesis in a diabetes- and obesity-related colorectal cancer model, presumably by improving inflammation via the reduction of oxidative stress and suppressing of the insulin-like growth factor/insulin-like growth factor-1 receptor axis in the colonic mucosa.
Ubiquitin‐Specific Protease 34 Inhibits Osteoclast Differentiation by Regulating NF‐κB Signaling

The ubiquitination and deubiquitination enzymes ensure the stability and proper function of most cellular proteins. Disturbance of either enzyme compromises tissue homeostasis. We recently have identified that the ubiquitin‐specific protease 34 (USP34) contributes to bone formation by promoting osteogenic differentiation of mesenchymal stem cells. However, its role in bone resorption, which couples bone formation, remains unknown. Here we show that knockdown of Usp34 promotes osteoclast differentiation of RAW264.7 cells. Conditional knockout of Usp34 in bone marrow–derived macrophages (BMMs) or in osteoclasts leads to elevated osteoclast function and low bone mass. Mechanically, we identify that USP34 restrains NF‐κB signaling by deubiquitinating and stabilizing the NF‐κB inhibitor alpha (IκBα). Overexpression of IκBα represses osteoclastic hyperfunction of Usp34‐deficient RAW264.7 cells. Collectively, our results show that USP34 inhibits osteoclastogenesis by regulating NF‐κB signaling. © 2020 American Society for Bone and Mineral Research.
A theory-based multi-disciplinary behavioural intervention to promote physical activity and healthy eating in overweight and obese adolescents

Self-determination theory and goal setting theory have been independently shown to explain motivation underpinning behaviour engagement, yet no studies to date have combined the two theories in an intervention targeting overweight and obese adolescents. The current study sought to integrate these two theories within the context of a broader study, the Curtin University’s Activity, Food and Attitudes Program (CAFAP). The multidisciplinary family-based intervention aimed to enhance adolescent engagement in physical activity and healthy eating behaviours and was delivered to seven cohorts across three community settings in metropolitan and regional Western Australia using a staggered cohort entry, waitlist controlled design with post-program assessment and follow-up at 3, 6, and 12 months. Effects of the intervention and mechanisms underlying behaviour change were explored in relation to the novel approach of training a multi-disciplinary team of instructors and parents of overweight and obese adolescents to demonstrate needsupportive behaviours. Fifty six adolescent/parent pairs attended the intervention and analyses were conducted from the final sample of 34 participants providing adequate data at 12-month follow-up. One-way repeated measures ANOVAs and mediation analyses were conducted to determine changes in outcomes following intervention in relation to adolescent variables of autonomous motivation (for physical activity and healthy eating), perceived parent support (for physical activity and healthy eating), psychological outcomes (health-related quality of life and depressive symptoms), behavioural outcomes (self-report and accelerometer-based physical activity; intake of junk food and fruit and vegetable serves), and parent variables of autonomous motivation to support adolescent behaviour engagement (physical activity and
Clinical Role of Serum Interleukin-17A in the Prediction of Refractory Mycoplasma pneumoniae Pneumonia in Children

Background Mycoplasma pneumoniae pneumonia (MPP) is a common community-acquired pneumonia (CAP) in children, which may become refractory MPP (RMPP) to treatment. Objective The purpose of this study was to evaluate the clinical utility of measuring serum interleukin (IL)-17A to predict RMPP. Patients and Methods A retrospective clinical study at a single pediatric center included a review of the medical records of all children hospitalized for CAP between November 2015 and October 2019. The diagnosis of MPP was based on clinical presentation, chest radiography, and measurement of serum anti-Mycoplasma immunoglobulin IgM antibody titer using the microparticle agglutination method or sputum samples for Mycoplasma pneumoniae by PCR. Serum levels of IL-18 and IL-17A were determined by ELISA. Results Of the 625 children diagnosed with CAP, there were 154 children with MPP and without underlying diseases who were divided into a non-refractory MPP (NRMPP) group (n = 109) and a RMPP group (n = 45). The RMPP group had a higher incidence of tachypnea, cyanosis, hypoxia, segmental or lobar pneumonia, pleural effusion, and a longer period of hospitalization compared with NRMPP group (all P-values < 0.05). A serum IL-17A level above 10.8 pg/mL was a predictor for RMPP: area under the curve (AUC) 0.822; standard error (SE) 0.039; 95% confidence interval (CI) 0.746–0.897; diagnostic sensitivity and specificity of 77.8% and 77.1%, respectively. An LDH level above 436.5 IU/L and an IL-18 level above 464.5 pg/mL were the second most useful markers for RMPP: AUC 0.775, 0.775; SE 0.038, 0.039; 95% CI 0.700–0.850, 0.698–0.852; sensitivity 77.8%, 82.2%; specificity 62.4%, 59.6%; respectively. Conclusion This preliminary study of MPP in a pediatric population has shown that measurement of serum IL-17A may be a useful marker for the predictor of RMPP.
Human Papillomavirus E6/E7 Expression in Preeclampsia-Affected Placentae

Whether HPV is causative of pregnancy complications is uncertain. E6 and E7 affect functions underling preeclampsia (PET) in cultured trophoblasts, but whether E6 and E7 is produced in the placenta is uncertain. Here, we investigated whether E6/E7 was expressed in the placentae from pregnancies with PET, other pregnancy complications (fetal growth restriction (FGR) and diabetes mellitus), and uncomplicated pregnancies. Placental tissues collected from two geographical locations were subjected to RNAscope analyses of high- and low- risk E6/E7, and individual HPV types identified using an HPV array. High-risk E6/E7 expression was increased in both PET cohorts, (81% and 86% of patients positive for high-risk HPV DNA compared to 13% of control patients). Various HPV types were identified. Although HPV 18 was the most frequent in all cohorts, the majority of individuals had multiple HPV types (55% of the PET compared to 25% of the control cohort). Further evidence that E6 and E7 is present early when placental pathology underlying preeclampsia is established, is provided with the finding of high-risk E6/E7 in the first-trimester placenta anchoring trophoblast. In conclusion, E6/E7 expression and multiple HPV types were frequent in placentae from preeclampsia-complicated pregnancies.
Natural History of Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a scarred ventricular myocardium with a distinctive propensity to ventricular arrhythmias (VAs) and sudden cardiac death, especially in young athletes. Arrhythmogenic right ventricular cardiomyopathy (ARVC) represents the best characterized variant of AC, with a peculiar genetic background, established diagnostic criteria and management guidelines; however, the identification of nongenetic causes of the disease, combined with the common demonstration of biventricular and left-dominant forms, has led to coin the term of “arrhythmogenic cardiomyopathy”, to better define the broad spectrum of the disease phenotypic expressions. The genetic basis of AC are pathogenic mutations in genes encoding the cardiac desmosomes, but also non-desmosomal and nongenetic variants were reported in patients with AC, some of which showing overlapping phenotypes with other non-ischemic diseases. The natural history of AC is characterized by VAs and progressive deterioration of cardiac performance. Different phases of the disease are recognized, each characterized by pathological and clinical features. Arrhythmic manifestations are age-related: Ventricular fibrillation and SCD are more frequent in young people, while sustained ventricular tachycardia is more common in the elderly, depending on the different nature of the myocardial lesions. This review aims to address the genetic basis, the clinical course and the phenotypic variants of AC.
Body of Evidence: Do Autopsy Findings Impact Medical Malpractice Claim Outcomes?

Supplemental digital content is available in the text. Objective Clinicians may hesitate to advocate for autopsies out of concern for increased malpractice risk if the pathological findings at time of death differ from the clinical findings. We aimed to understand the impact of autopsy findings on malpractice claim outcomes. Methods Closed malpractice claims with loss dates between 1995 and 2015 involving death related to inpatient care at 3 Harvard Medical School hospitals were extracted from a captive malpractice insurer’s database. These claims were linked to patients’ electronic health records and their autopsy reports. Using the Goldman classification system, 2 physician reviewers blinded to claim outcome determined whether there was major, minor, or no discordance between the final clinical diagnoses and pathologic diagnoses. Claims were compared depending on whether an autopsy was performed and whether there was major versus minor/no clinical-pathologic discordance. Primary outcomes included percentage of claims paid through settlement or plaintiff verdict and the amount of indemnity paid, inflation adjusted. Results Of 293 malpractice claims related to an inpatient death that could be linked to patients’ electronic health records, 89 claims (30%) had an autopsy performed by either the hospital or medical examiner. The most common claim allegation was an issue with clinician diagnosis, which was statistically less common in the autopsy group (18% versus 38%, P = 0.001). There was no difference in percentage of claims paid whether an autopsy was performed or not (42% versus 41%, P = 0.90) and no difference in median indemnity of paid claims after adjusting for number of defendants ($1,180,537 versus $906,518, P = 0.15). Thirty-one percent of claims with hospital autopsies performed demonstrated major discordance between autopsy and clinical findings. Claims with major clinical-pathologic discordance also did not have a statistically significant difference in percentage paid (44% versus 41%, P > 0.99) or amount paid ($895,954 versus $1,494,120, P = 0.10) compared with claims with minor or no discordance. Conclusions Although multiple factors determine malpractice claim outcome, in this cohort, claims in which an autopsy was performed did not result in more paid outcomes, even when there was major discordance between clinical and pathologic diagnoses.