Miracle-dz/UniFAR-FTUs huggingface dataset:
UNIVERSIDADE FEDERAL DO ESPÍRITO SANTO CENTRO DE CIÊNCIAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM DOENÇAS INFECCIOSAS

Background: A new interferon-γ release assay, QuantiFERON-TB (QFT) test, poses as an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Here, we compared the performance of QFT with tuberculin skin test (TST) measured at two different cut-off points among primary health care workers (HCW) in Brazil. Methods: A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both ≥5mm and ≥10 mm as cut-off points. Results: We enrolled 632 HCWs. When the cut-off value of ≥10 mm was used, agreement between QFT and TST was 69% (k=0.31), and when the cut-off of ≥5 mm was chosen, the agreement was 57% (k=0.22). We investigated possible factors of discordance of TST vs QFT. Compared to the TST-/QFT– group, the risk factors identified for discordance at the TST+/QFTgroup when the TST cut-off of ≥5 mm was used were age between 41-45 [OR=2.70; CI 95%: 1.32-5.51] and 46-64 [OR=2.04; CI 95%: 1.05-3.93], BCG scar [OR=2.72; CI 95%: 1.40-5.25], and having worked only in primary health care [OR=2.30; CI 95%: 1.09-4.86]. On the other hand, for the cut-off of ≥10 mm BCG scar [OR=2.26; CI 95%: 1.03-4.91], being a household contact of a TB patient [OR=1.72; CI 95%: 1.01-2.92] and having had a previous TST [OR=1.66; CI 95%: 1.05-2.62], were significant. Interestingly, discordance observed at the TST-/QFT+ group showed no statistically significant association with any of the variables regardless of TST cut-off value used. Conclusions: Although we identified BCG vaccination to contribute to the discordance in spite of TST cut-offs, the current Brazilians recommendation for the initiation of LTBI treatment, based on TST, should not be changed, based on QFT limitations and decreased accuracy of the method.
Metabolomics of small extracellular vesicles derived from isocitrate dehydrogenase 1-mutant HCT116 cells collected by semi-automated size exclusion chromatography

Cancer-derived small extracellular vesicles (sEVs) are multifunctional particles with a lipid bilayer structure that are involved in cancer progression, such as malignant proliferation, distant metastasis, and cancer immunity evasion. The separation protocol used to isolate sEVs is an important process and thus, several have been developed, including ultracentrifugation (UC), size exclusion chromatography (SEC), and affinity purification using antibodies against sEV surface antigens. However, the effects of different separation methods on sEV components have not been adequately examined. Here, we developed a semi-automated system for collecting sEVs by combining SEC and preparative high-performance liquid chromatography and applied it to metabolome analysis. The developed SEC system could recover sEVs more efficiently and non-destructively than UC, suggesting that it is an appropriate recovery method for metabolic analysis and reflects biological conditions. Furthermore, using the developed SEC system, we performed metabolome analysis of sEVs from isocitrate dehydrogenase 1 (IDH)-mutated human colon HCT116 cells, which produce the oncogenic metabolite, 2-hydroxyglutaric acid (2-HG). IDH1-mutated HCT116 cells released significantly more sEVs than wild-type (WT) cells. The metabolomic profiles of IDH1 mutant and WT cells showed distinct differences between the cells and their sEVs. Notably, in IDH mutant cells, large amounts of 2-HG were detected not only in cells, but also in sEVs. These results indicate that the SEC system we developed has wide potential applications in sEVs research.
Exaggerated exercise pressor reflex in male UC Davis type 2 diabetic rats is due to the pathophysiology of the disease and not aging

Introduction: Studies in humans and animals have found that type 2 diabetes mellitus (T2DM) exaggerates the blood pressure (BP) response to exercise, which increases the risk of adverse cardiovascular events such as heart attack and stroke. T2DM is a chronic disease that, without appropriate management, progresses in severity as individuals grow older. Thus, it is possible that aging may also exaggerate the BP response to exercise. Therefore, the purpose of the current study was to determine the effect of the pathophysiology of T2DM on the exercise pressor reflex independent of aging. Methods: We compared changes in peak pressor (mean arterial pressure; ΔMAP), BP index (ΔBPi), heart rate (ΔHR), and HR index (ΔHRi) responses to static contraction, intermittent contraction, and tendon stretch in UCD-T2DM rats to those of healthy, age-matched Sprague Dawley rats at three different stages of the disease. Results: We found that the ΔMAP, ΔBPi, ΔHR, and ΔHRi responses to static contraction were significantly higher in T2DM rats (ΔMAP: 29 ± 4 mmHg; ΔBPi: 588 ± 51 mmHg•s; ΔHR: 22 ± 5 bpm; ΔHRi: 478 ± 45 bpm•s) compared to controls (ΔMAP: 10 ± 1 mmHg, p < 0.0001; ΔBPi: 121 ± 19 mmHg•s, p < 0.0001; ΔHR: 5 ± 2 bpm, p = 0.01; ΔHRi: 92 ± 19 bpm•s, p < 0.0001) shortly after diabetes onset. Likewise, the ΔMAP, ΔBPi, and ΔHRi to tendon stretch were significantly higher in T2DM rats (ΔMAP: 33 ± 7 mmHg; ΔBPi: 697 ± 70 mmHg•s; ΔHRi: 496 ± 51 bpm•s) compared to controls (ΔMAP: 12 ± 5 mmHg, p = 0.002; ΔBPi: 186 ± 30 mmHg•s, p < 0.0001; ΔHRi: 144 ± 33 bpm•s, p < 0.0001) shortly after diabetes onset. The ΔBPi and ΔHRi, but not ΔMAP, to intermittent contraction was significantly higher in T2DM rats (ΔBPi: 543 ± 42 mmHg•s; ΔHRi: 453 ± 53 bpm•s) compared to controls (ΔBPi: 140 ± 16 mmHg•s, p < 0.0001; ΔHRi: 108 ± 22 bpm•s, p = 0.0002) shortly after diabetes onset. Discussion: Our findings suggest that the exaggerated exercise pressor reflex and mechanoreflex seen in T2DM are due to the pathophysiology of the disease and not aging.
Seroprevalence of viral transfusion transmitted infections among blood donors at a government hospital blood bank in central India

Background: Blood transfusion service is a sensitive issue as it is covered by ‘Drug and Cosmetics Act’ and has legal implications. Strict criteria are followed while selecting a donor so that proper blood free of all pathogens is available for recipient. Objectives: To study seroprevalence of viral transfusion transmitted major infections (HIV, HBC and HCV) among blood donors at a tertiary care government hospital blood bank in central India and to compare positivity of serum markers of these infections in voluntary and replacement donors. Methodology: Present study was conducted over a period of four and half year (January 2010 to June 2014). Total number of donors screened during this period was 43190. Samples were tested for HIV, HBV and HCV, and retested if found positive by third generation ELISA tests. Comparative analysis was done using Chi-square for linear trend. Comparison between prevalence rates among voluntary and replacement donors was done using Chi-square tests using STATA version 10.0. Results: Of total 43190 donors, 23662 (54.7%) were voluntary and 19528 (45.3%) were replacement donors. Male donors predominated, 40490 (93.7%) male and female 2701 (6.3%). Average seropositivity of HIV, HBsAg and anti-HCV was 0.30%, 1.18% and 0.16% among all donors. Significant difference (p <0.001) in the seropositivity of HIV and HBsAg were seen between voluntary and replacement donors. Seroprevalence of HIV, HBsAg and HCV were 0.22%, 0.09%, 0.14% and 0.42%, 2.5%, 0.21% in VBD and RBD respectively. Conclusion: Comparing a retrospective data over a long period showed decreasing trend in seroprevalence of HIV, HBsAg and anti-HCV. Study results reflect prevalence of these infections in the healthy population and warrant measures that should be taken to detect these infections.
Spectroscopic technologies and data fusion: Applications for the dairy industry

Increasing consumer awareness, scale of manufacture, and demand to ensure safety, quality and sustainability have accelerated the need for rapid, reliable, and accurate analytical techniques for food products. Spectroscopy, coupled with Artificial Intelligence-enabled sensors and chemometric techniques, has led to the fusion of data sources for dairy analytical applications. This article provides an overview of the current spectroscopic technologies used in the dairy industry, with an introduction to data fusion and the associated methodologies used in spectroscopy-based data fusion. The relevance of data fusion in the dairy industry is considered, focusing on its potential to improve predictions for processing traits by chemometric techniques, such as principal component analysis (PCA), partial least squares regression (PLS), and other machine learning algorithms.
Staged open reduction and internal fixation with double-locking plates to treat bilateral distal femur periprosthetic fractures after total knee arthroplasty: A case report

Background The incidence of periprosthetic fractures after total knee arthroplasty (TKA) increases in parallel with the number of procedures. Comminuted fractures along the primary fracture line extending to the edge of the prosthesis are challenging, and bilateral fractures are rarely reported, especially with open injuries. Case presentation A 65-year-old female had undergone bilateral TKA in our hospital 5 years before admission. She was admitted with a traumatic bilateral Rorabeck type II B distal femur periprosthetic fracture (closed right, open left, Gustilo II) and was treated with bilateral staged open reduction and internal fixation (ORIF) with double-locking plates. The patient experienced a prolonged delayed fracture union and finally healed around 21 months postoperatively. The function was satisfactory after 4 years of follow-up. Conclusion ORIF with double-locking plates can be used to treat Rorabeck II B periprosthetic fracture where the primary fracture line extends beyond the edge of the prosthesis; however, there may be delayed healing or nonunion. Patients need to undergo long-term rehabilitation and endure long disability times and require good rehabilitation nursing care. Once they achieve bone healing, the treatment achieves bone preservation and substantial prosthesis survival.
Fibroblast growth factor 23 is independently associated with renal magnesium handling in patients with chronic kidney disease

Background Disturbances in magnesium homeostasis are common in patients with chronic kidney disease (CKD) and are associated with increased mortality. The kidney is a key organ in maintaining normal serum magnesium concentrations. To this end, fractional excretion of magnesium (FEMg) increases as renal function declines. Despite recent progress, the hormonal regulation of renal magnesium handling is incompletely understood. Fibroblast Growth Factor 23 (FGF23) is a phosphaturic hormone that has been linked to renal magnesium handling. However, it has not yet been reported whether FGF23 is associated with renal magnesium handling in CKD patients. Methods The associations between plasma FGF23 levels, plasma and urine magnesium concentrations and FEMg was investigated in a cross-sectional cohort of 198 non-dialysis CKD patients undergoing renal biopsy. Results FGF23 was significantly correlated with FEMg (Pearson’s correlation coefficient = 0.37, p<0.001) and urinary magnesium (-0.14, p=0.04), but not with plasma magnesium. The association between FGF23 and FEMg remained significant after adjusting for potential confounders, including estimated glomerular filtration rate (eGFR), parathyroid hormone and 25-hydroxyvitamin D. Conclusions We report that plasma FGF23 is independently associated with measures of renal magnesium handling in a cohort of non-dialysis CKD patients. A potential causal relationship should be investigated in future studies.
Methylone, a rapid acting entactogen with robust anxiolytic and antidepressant-like activity

Introduction Selective serotonin reuptake inhibitor (SSRI) antidepressants represent first-line pharmacological treatment for a variety of neuropsychiatric illnesses, including major depressive disorder (MDD), anxiety, and post-traumatic stress disorder (PTSD), which show high rates of comorbidity. SSRIs have a delayed onset of action. Most patients do not show significant effects until 4–8 weeks of continuous treatment, have impairing side effects and as many as 40% of patients do not respond. Methylone (3,4-methylenedioxy-N-methylcathinone; MDMC, βk-MDMA, M1) is a rapid-acting entactogen that showed significant benefit in a clinical case series of PTSD patients and was well-tolerated in two Phase 1 studies of healthy volunteers. Based on these early observations in humans, in the current study we tested the hypothesis that methylone has antidepressant-like and anxiolytic effects in preclinical tests. Methods For all studies, 6–8-week-old male Sprague Dawley rats (N = 6–16) were used. We employed the Forced Swim Test (FST), a classic and widely used screen for antidepressants, to explore the effects of methylone and to probe dose-response relationships, durability of effect, and potential interactions with combined SSRI treatment. We compared the effect of methylone with the prototypical SSRI fluoxetine. Results Three doses of fluoxetine (10 mg/kg) given within 24 h before FST testing caused a 50% reduction in immobility compared with controls that lasted less than 24 h. In contrast, a single dose of methylone (5–30 mg/kg) administered 30 min prior to testing produced a rapid, robust, and durable antidepressant-like response in the FST, greater in magnitude than fluoxetine. Immobility was reduced by nearly 95% vs. controls and effects persisted for at least 72 h after a single dose (15 mg/kg). Effects on swimming and climbing behavior in the FST, which reflect serotonergic and noradrenergic activity, respectively, were consistent with studies showing that methylone is less serotoninergic than MDMA. Fluoxetine pretreatment did not change methylone’s antidepressant-like effect in the FST, suggesting the possibility that the two may be co-administered. In addition, methylone (5–30 mg/kg) exhibited anxiolytic effects measured as increased time spent in the center of an open field. Discussion Taken together, and consistent with initial clinical findings, our study suggests that methylone may have potential for treating depression and anxiety.
Association between sleep duration and myopia among Chinese children during the COVID-19 pandemic: A cross-sectional study

Background The studies on the association between sleep duration and myopia are limited, and the evidence is inconsistent. This study aimed to evaluate the association between sleep duration and myopia, cycloplegic spherical equivalent (SE) and axial length (AL) among Chinese children during the Corona Virus Disease 2019 (COVID-19) pandemic. Methods The study was a cross-sectional study on Chinese children aged 6–18 years. The comprehensive ophthalmic examinations for children included cycloplegic SE, AL, and standardized questionnaires. The questionnaire included sleep duration, parental myopia, outdoor time, and continuous near work duration without breaks. Myopia was defined as SE ≤-0.50 diopters (D). Results A total of 1,140 children were included in the analyses, with 84.7% of myopic children and 74.4% of children's daily sleep duration being more than 8 h/d. In univariate regression analysis, compared with sleep duration < 8 h/d, children with sleep duration of 8–9 and >9 h/d were less myopia (p < 0.01 for all), and had less myopic SE (p < 0.01 for all), and shorter AL (p < 0.01 for all). After adjusting for age, gender, parental myopia, outdoor time, and continuous near work duration without breaks, sleep duration was not associated with myopia, cycloplegic SE, and AL (p > 0.05 for all). Conclusions This study showed sleep duration was related to myopia, cycloplegic SE, and AL among Chinese children during the COVID-19 pandemic-related lifestyles, but no independent association.
Pre-pregnancy BMI was associated with gestational depressive phenotypes in a population of 12,099 women in Chongqing, China

Objective To investigate the association between pre-pregnancy body mass index (BMI) and gestational depressive phenotypes. Methods The pregnant women receiving the first prenatal examination (4th –13th week of gestation) in Chongqing Health Center for Women and Children were recruited between February 2020 and September 2021. Depressive phenotypes was assessed by the Patient Health Questionnaire (PHQ-9) and the Symptom Checklist 90 (SCL-90) scale at recruitment. Pre-pregnancy weight and height were self-reported by the participants. Demographic and obstetric characteristics were obtained from the hospital information system. The association between pre-pregnancy BMI and the scores of PHQ-9 or SCL-90 scale was investigated by uni-variate analysis with Kruskal-Wallis test and by multi-variate analysis with linear regression model with adjustment of age, parity, smoking, alcohol consumption, and assisted reproduction. The association between pre-pregnancy BMI and PHQ-9 or SCL-90 diagnosed depressive phenotypes was analyzed by Chi-square test and logistic regression respectively. Results A total of 12,099 pregnant women were included, where 100% of them filled out the PHQ-9 scale and 99.6% filled out the SCL-90 scale, and 47.26% and 4.62% of the pregnant women had depressive phenotypes, respectively. Women with higher pre-pregnancy BMI had lower depressive phenotypes scores during pregnancy. Multivariable analysis of the PHQ-9 scale showed that overweight/obese subjects had a higher incidence of depressive phenotypes compared with subjects with normal BMI (OR=0.803, 95% CI [0.723, 0.892]). In a stratified analysis assessed by the PHQ-9, women who were overweight/obese prior to pregnancy were less likely to develop depressive phenotypes during pregnancy than women who were normal weight prior to pregnancy, regardless of whether they were nulliparous (OR=0.795, 95%CI[0.696,0.908]) or multiparous (OR=0.809, 95%CI[0.0.681,0.962]), while in the three age groups of 25-29 years, 30-34 years and ≥35 years, pre-pregnancy overweight/obesity were associated with lower risk of gestational depressive phenotypes. However, analysis of the SCL-90 scale showed no statistical association between depressive symptom and BMI. No substantial interaction was observed between BMI and parity or age. Conclusions Increased pre-pregnancy BMI may be associated with reduced risk of gestational depressive phenotypes in Chinese women. Independent studies are warranted to validate the findings of the present study.
Varieties and ensiling: Impact on chemical composition, fermentation quality and bacterial community of alfalfa

Introduction Six species of alfalfa commonly found in northern China were collected in the present study. Methods The chemical composition and epiphytic microbial communities during the ensiling were analyzed; and their effects on fermentation quality and silage bacterial communities were assessed. The effects of physicochemical characteristics of alfalfa on the bacterial community were also investigated in terms of nutritional sources of microbial growth and reproduction. Results and discussion The results showed that the chemical composition was significantly different in various alfalfa varieties, yet, the dominant genera attached to each variety of alfalfa was similar, except for pantoea (p<0.05). After ensiling, both the fermentation quality and microbial community changed obviously (p<0.05). Specifically, ZM2 had lower pH and ammonia nitrogen (NH3-N) content but higher LA content than other varieties of alfalfa silage. Beneficial bacteria such as Lentilactobacillus and Lactiplantibacillus were predominant in ZM2, which accounted for the higher fermentation quality. Significant correlations between the chemical composition of silage, fermentation quality and bacterial communities composition were observed. Moreover, variations in bacteria community structure during the fermentation of alfalfa were mainly influenced by water-soluble carbohydrates (36.79%) and dry matter (21.77%). Conclusion In conclusion, this study revealed the influence of chemical composition on microbial community and fermentation quality, laying the groundwork for future studies on high-quality silage.
Long term complications following elbow-based autogenous haemodialysis access: studies on high flow and hand ischemia

Patients with kidney failure who become dependent on haemodialysis will often develop an arteriovenous fistula (AVF), a negative effect of which being the occurrence of complications after a few years. This doctoral research project focusses on two long-term complications related to AVFs. The first long-term complication this dissertation focusses on is a high blood flow (high flow access (HFA)) which may lead to excessive burdening of the heart. Surgical banding for HFA, a method often applied in the past, is shown to be less effective than presumed. The recurrence rate of HFA is 50% after 1 year of follow-up. Revision using distal inflow (RUDI), a new technique, appears to be much more successful, as the recurrence rate is only 16% after 1 year of follow-up. A second complication this dissertation focusses on is a severely reduced perfusion of the hand (haemodialysis access-induced distal ischaemia (HAIDI)). Generalised arteriosclerosis and increased arterial stiffness are found to largely contribute to HAIDI. Another cause of HAIDI is ‘loss’ of blood pressure through ‘side’ veins around the AVF which are not punctured for dialysis. Knotting these ‘side’ veins is found to be an effective treatment method.
Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: An individual-level analysis within 13 months in the ORCHESTRA cohort

Short summary We investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months. Background Persistence of vaccine immunization is key for COVID-19 prevention. Methods We investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements. Results We observed a progressively decreasing difference in serologic levels from <30 days to 210–240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference [95% confidence interval (CI) 0.78–0.85]. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07–1.10) and 1.04 (95% CI 1.03–1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56–1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75–0.92) and mixed vaccines (RR 0.61, 95% CI 0.51–0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40–0.54). Conclusions Age, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.