Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotype and residual enzyme activity in medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency: Are predictions possible?

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) is the most common defect of mitochondrial β‐oxidation. Confirmation diagnostics after newborn screening (NBS) can be performed either by enzyme testing and/or by sequencing of the ACADM gene. Here, we report the results from enzyme testing in lymphocytes with gene variants from molecular analysis of the ACADM gene and with the initial acylcarnitine concentrations in the NBS sample. From April 2013 to August 2019, in 388 individuals with characteristic acylcarnitine profiles suggestive of MCADD the octanoyl‐CoA‐oxidation was measured in lymphocytes. In those individuals with residual activities <50%, molecular genetic analysis of the ACADM gene was performed. In 50% of the samples (195/388), MCADD with a residual activity ranging from 0% to 30% was confirmed. Forty‐five percent of the samples (172/388) showed a residual activity >35% excluding MCADD. In the remaining 21 individuals, MCAD residual activity ranged from 30% to 35%. The latter group comprised both heterozygous carriers and individuals carrying two gene variants on different alleles. Twenty new variants could be identified and functionally classified based on their effect on enzyme function. C6 and C8 acylcarnitine species in NBS correlated with MCAD activity and disease severity. MCADD was only confirmed in half of the cases referred suggesting a higher false positive rate than expected. Measurement of the enzyme function in lymphocytes allowed fast confirmation diagnostics and clear determination of the pathogenicity of new gene variants. There is a clear correlation between genotype and enzyme function underlining the reproducibility of the functional measurement in vitro.
The Effect of Cadmium on GFR Is Clarified by Normalization of Excretion Rates to Creatinine Clearance

Erroneous conclusions may result from normalization of urine cadmium and N-acetyl-β-D-glucosaminidase concentrations ([Cd]u and [NAG]u) to the urine creatinine concentration ([cr]u). In theory, the sources of these errors are nullified by normalization of excretion rates (ECd and ENAG) to creatinine clearance (Ccr). We hypothesized that this alternate approach would clarify the contribution of Cd-induced tubular injury to nephron loss. We studied 931 Thai subjects with a wide range of environmental Cd exposure. For x = Cd or NAG, Ex/Ecr and Ex/Ccr were calculated as [x]u/[cr]u and [x]u[cr]p/[cr]u, respectively. Glomerular filtration rate (GFR) was estimated according to the Chronic Kidney Disease (CKD) Epidemiology Collaboration (eGFR), and CKD was defined as eGFR < 60 mL/min/1.73m2. In multivariable logistic regression analyses, prevalence odds ratios (PORs) for CKD were higher for log(ECd/Ccr) and log(ENAG/Ccr) than for log(ECd/Ecr) and log(ENAG/Ecr). Doubling of ECd/Ccr and ENAG/Ccr increased POR by 132% and 168%; doubling of ECd/Ecr and ENAG/Ecr increased POR by 64% and 54%. As log(ECd/Ccr) rose, associations of eGFR with log(ECd/Ccr) and log(ENAG/Ccr) became stronger, while associations of eGFR with log(ECd/Ecr) and log(ENAG/Ecr) became insignificant. In univariate regressions of eGFR on each of these logarithmic variables, R2 was consistently higher with normalization to Ccr. Our tabular and graphic analyses uniformly indicate that normalization to Ccr clarified relationships of ECd and ENAG to eGFR.
Establishing Pediatric Mouse Models of the Hematopoietic Acute Radiation Syndrome and the Delayed Effects of Acute Radiation Exposure

Medical countermeasures (MCMs) for hematopoietic acute radiation syndrome (H-ARS) should be evaluated in well-characterized animal models, with consideration of at-risk populations such as pediatrics. We have developed pediatric mouse models of H-ARS and delayed effects of acute radiation exposure (DEARE) for efficacy testing of MCMs against radiation. Male and female C57BL/6J mice aged 3, 4, 5, 6, 7 and 8 weeks old (±1 day) were characterized for baseline hematopoietic and gastrointestinal parameters, radiation response, efficacy of a known MCM, and DEARE at six and 12 months after total-body irradiation (TBI). Weanlings (age 3 weeks) were the most radiosensitive age group with an estimated LD50/30 of 712 cGy, while mice aged 4 to 8 weeks were more radioresistant with an estimated LD50/30 of 767–787 cGy. Female weanlings were more radiosensitive than males at 3 and 4 weeks old but became significantly more radioresistant after the pubertal age of 5 weeks. The most dramatic increase in body weight, RBC counts and intestinal circumference length occurred from 3 to 5 weeks of age. The established radiomitigator Neulasta® (pegfilgrastim) significantly increased 30-day survival in all age groups, validating these models for MCM efficacy testing. Analyses of DEARE among pediatric survivors revealed depressed weight gain in males six months post-TBI, and increased blood urea nitrogen at 12 months post-TBI which was more severe in females. Hematopoietic DEARE at six months post-TBI appeared to be less severe in survivors from the 3- and 4-week-old groups but was equally severe in all age groups by 12 months of age. Similar to our other acute radiation mouse models, there was no appreciable effect of Neulasta used as an H-ARS MCM on the severity of DEARE. In summary, these data characterize a pediatric mouse model useful for assessing the efficacy of MCMs against ARS and DEARE in children.
Factors Affecting Changes in the Mental Health of North Korean Refugee Youths: A Three-Year Follow-Up Study

This study identified factors affecting changes in depression of 64 North Korean refugee youths (NKRYs) aged 13 to 23 years (40 female) using follow-up data over a three-year period. We collected intrapersonal factors (emotional regulation strategies, resilience, quality of life) and external factors (psychological and practical support, family adaptation, and cohesion) to understand the preventative and risk factors affecting changes in depression. The trend of depression symptoms significantly increased, and the proportion of people classified as depressed (cut-off score = 21) increased steadily from 45.3% to 59.4% in the third year. In addition, we conducted a panel regression analysis, which showed that individual internal factors had a statistically significant effect on changes in depression. Specifically, expressive suppression of emotions was shown to increase depression over time. Resilience and life satisfaction were significant factors reducing depression in this study. On the other hand, external factors were not significantly related to changes over time in depression of NKRYs. Interventions for NKRYs at risk of depression are necessary and should include ways to enhance resilience and life satisfaction, and foster ego strength by recognizing emotions and promoting healthy emotional expression.
Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone

Over 240 million non-cardiac operations occur each year and are associated with a 15–20% incidence of adverse perioperative cardiovascular events. Unfortunately, preoperative therapies that have been useful for chronic ischemic heart diseases, such as coronary artery revascularization, antiplatelet agents, and beta-blockers have failed to improve outcomes. In a pre-clinical swine model of ischemic heart disease, we showed that daily administration of ubiquinone (coenzyme Q10, CoQ10) enhances the antioxidant status of mitochondria within chronically ischemic heart tissue, potentially via a PGC1α-dependent mechanism. In a randomized controlled trial, among high-risk patients undergoing elective vascular surgery, we showed that NT Pro-BNP levels are an important means of risk-stratification during the perioperative period and can be lowered with administration of CoQ10 (400 mg/day) for 3 days prior to surgery. The review provides background information for the role of oxidant stress and inflammation during high-risk operations and the potential novel application of ubiquinone as a preoperative antioxidant therapy that might reduce perioperative adverse cardiovascular outcomes.
Characterization and Control of Hidden Micro-Oxygenation in the Winery: Wine Racking

Transferring wine is a common operation in most of the wineries in the world that depends mainly on the equipment and materials used. These contributions are widely unknown, and their knowledge is of vital importance to controlling the winemaking process. This work presents the results of characterizing the oxygen supply due to the use of hoses of different materials (Butyl Rubber, IIR; Nitrile Butadiene Rubber, NBR; Ethylene Propylene Diene Monomer rubber, EPDM; Ultra-high-molecular-weight polyethylene, UHMW; Natural Rubber, NR), dimensions (DN32; DN50), connectors (DIN 11851, Tri-CLAMP) with gaskets of different materials (NBR; EPDM; Fluorocarbon, FKM/FPM; silicone rubber, Q/VMQ; Polytetrafluoroethylene, PTFE). In addition, the use of different inert gases (N2, CO2, Ar, N2 + CO2 and Ar + CO2) for air purging of hoses and tanks, as well as for ullage blanketing during tank-to-tank racking, and their economic impact were studied. The results indicated that the IIR hoses had the least amount of O2 added to the liquid and that the Tri-clamp connectors were generally more airtight, with the FKM seals standing out. The most recommended inert gas was CO2 when the type of wine allows it, N2 being the most recommended in any case. When all these recommendations were used together the addition of O2 during tank-to-tank racking was drastically reduced.
Comparative external workload analysis based on the new functional classification in cerebral palsy football 7-a-side. A full-season study

ABSTRACT The evolution of functional classification (FT) is important for promoting competitive balance. Technological advances allow the objective monitoring of competitive demands that is required to manage and individualize workloads. Therefore, this study aimed to characterize external workload in all matches from the 2018/2019 season of the CPF7 Spanish National League and to compare demands based on the new FT (FT1, FT2 yFT3) in time-motion (locomotion and speed changes) and accelerometer-based workload (impacts). Statistical analysis was composed of one-way ANOVA with Bonferroni post-hoc and omega partial squared effect size. Differences were found among all FT in total distance, running, high-intensity, sprinting, very high accelerations and decelerations (FT3> FT2> FT1; p < .01; ωp 2= 0.29-to-0.43); and with respect to the highest functional limitation (FT3 = FT2> FT1) in maximum sprinting, moderate-high accelerations and decelerations, total impacts and at very-low intensity (ωp 2= 0.13-to-0.29). In conclusion, FT3 players presented a physical advantage with respect to FT2-FT1 players in competition, especially in high-intensity actions that are crucial in team-sports performance. The present results facilitate designing specific training workloads according to FT, players’ disability and competition demands, being the first approach to characterize match demands with inertial devices based on the new FT.
Treatment and outcome of ulcerative colitis during the first 10 years after diagnosis in a prospectively followed population-based cohort

Abstract Background and aims There is a shortage of studies evaluating the effect of prevalent use of immunomodulators (IMMs) and biologicals on the clinical course of ulcerative colitis (UC) during 10 years. The aim of the present study is to report the use of drugs and surgery as well as mortality in a population based setting. Methods Between 2005 and 2009, we identified 330 patients in all ages (3–86 years) with an incident diagnosis of UC in the County of Uppsala, Sweden. They were followed prospectively and the medical notes were retrospectively analysed with special reference to the use of drugs, surgery and mortality. Results Median follow-up was 11.2 years (inter-quartile range 10.2–12.7). Out of the 330 patients, 298 (90.3%) could be followed for at least 10 years or until death. The cumulative exposure to different drugs was as follows: 5-ASA 96.6%, steroids 73.3%, IMMs 35.4% and biologicals 11.4%. Fourteen patients (4.6%) needed a colectomy during the observation time. Overall mortality in 10 years was 7% (23/330) whereof three patients died as a consequence of the disease or its treatment. Three patients (0.9%) were diagnosed with colonic cancer of whom two also had sclerosing cholangitis. Conclusions A frequent use of IMMs and biologicals during 10 years, can result in a low need for colectomy without increased mortality compared to previous reports.
Spatiotemporal Dynamics of Highly Pathogenic Avian Influenza Subtype H5N8 in Poultry Farms, South Korea

Highly pathogenic avian influenza (HPAI), a zoonotic disease, is a major threat to humans and poultry health worldwide. In January 2014, HPAI virus subtype H5N8 first infected poultry farms in South Korea, and 393 outbreaks, overall, were reported with enormous economic damage in the poultry industry. We analyzed the spatiotemporal distribution of HPAI H5N8 outbreaks in poultry farms using the global and local spatiotemporal interaction analyses in the first (January to July 2014) and second (September 2014 to June 2015) outbreak waves. The space–time K-function analyses revealed significant interactions within three days and in an over-40 km space–time window between the two study periods. The excess risk attributable value (D0) was maintained despite the distance in the case of HPAI H5N8 in South Korea. Eleven spatiotemporal clusters were identified, and the results showed that the HPAI introduction was from the southwestern region, and spread to the middle region, in South Korea. This spatiotemporal interaction indicates that the HPAI epidemic in South Korea was mostly characterized by short period transmission, regardless of the distance. This finding supports strict control strategies such as preemptive depopulation, and poultry movement tracking. Further studies are needed to understand HPAI disease transmission patterns.
Micromorphological Characteristics of Compression Wood Degradation in Waterlogged Archaeological Pine Wood

Summary The degradation characteristics of waterlogged archaeological compression wood excavated in South Korea were examined by transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Degradation of Pinus compression wood occurred mainly in the inner part of the S2 layer. In contrast, the outer part of the S2 layer remained relatively intact. CLSM and TEM showed the erosion type of bacterial attack to be dominant in the secondary cell walls of both severe and mild compression wood. However, in some cases the middle lamella was also degraded, which suggests that other forms of microbial attacks, such as bacterial tunnelling, were also present. Bacterial erosion in the severe compression wood was mainly confined to the inner part of the S2 layer whereas in the mild compression wood it also extended into the outer part of the S2 and the S1 layer. The extent of erosion correlated to the differences in the amount and distribution of lignin, particularly in the outer S2 layer between the severe and mild compression wood cells. These features are compared with the degradation of normal Pinus wood.
Comparative study of phacoemulsification parameters with and without nitinol filament nuclear disassembly

Nitinol filament nuclear disassembly reduced phacoemulsification energy and significantly reduced phacoemulsification and irrigation/aspiration time in eyes undergoing cataract surgery compared with conventional lens fragmentation in a private practice setting. Purpose: The purpose of this study was to evaluate the impact of nitinol microfilament lens disassembly using the miLOOP device on phacoemulsification parameters in routine cataract surgery. Setting: Private practice in Cleveland, Ohio. Design: Retrospective comparative consecutive case series. Methods: A chart review of consecutive cataract surgery cases in a single center operated by a single surgeon was conducted. Eyes were grouped by whether they underwent nitinol filament nuclear disassembly. Phacoemulsification energy, phacoemulsification time, and irrigation/aspiration (I/A) recorded during the operation were compared. Bilateral eyes were included only if the contralateral eye was in the opposite group. Results: A total of 212 eyes in 131 patients were eligible for analysis, including 81 subjects with both eyes. Most eyes (93%) had grade 2+ or 3+ nuclear sclerotic cataracts. A total of 102 eyes (48%) underwent nitinol filament nuclear disassembly preceding phacoemulsification. For all eyes, there was a 16% reduction in phacoemulsification energy, with a larger drop in grade 3+ eyes (−22%). Phacoemulsification and I/A times also reduced significantly (−19% and −37%, respectively, P < .02). Conclusions: Nitinol microfilament nuclear disassembly reduced total phacoemulsification energy and time during cataract surgery, particularly in severe cataracts.
Levels of Physical Activity and Mental Health in Adolescents in Ireland

The benefits of physical activity for the physical health of individuals are well documented. Less is known about the benefits of physical activity for mental health. This paper explores the associations between physical activity and positive mental health and mental health problems. The paper utilises data collected from a representative sample of 10–17-year-old adolescents in Ireland. Physical activity in the study is measured using moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA). Mental health was measured using the Cantril Leader of Life Satisfaction, the WHO-5 index, Mental Health Inventory (MHI-5) and the Health Behaviour in School-Aged Children (HBSC) Symptom Checklist (HBSC-SCL). Data were analysed using bivariate (Pearson Correlation, t-test, one-way ANOVA) and multivariate (two-way ANOVA, ordinary least squares (OLS) regressions) analyses. In total, 8636 adolescents were included in this analysis. Higher participation in physical activity was associated with higher scores on the positive mental health indicators and lower scores on the mental health problems indicators. When modelled together, VPA was a stronger predictor of mental health than MVPA, especially in girls. For example, standardised beta coefficients for predicting MHI-5 were −0.09 for MVPA (p < 0.001) and −0.13 for VPA (p < 0.001) To our knowledge, this is the first study that looks at levels of physical activity as well as both positive mental health and mental health problems. The study highlights the need to encourage and enable adolescents, and especially girls, to participate in vigorous exercising as way of promoting positive mental health.
Links between inflammation, mood, and physical function among older adults with HIV.

OBJECTIVES People living with HIV (PLWH) treated with antiretrovirals have lifespans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multi-morbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH ages 54 to 78 years. METHODS Participants provided blood samples for serum cytokines and C-reactive protein (CRP), completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors. RESULTS Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (ß=0.22, t(126)=2.71, p=0.008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted OR=1.72, 95% CI=1.01 to 2.93) and reported worse physical function (ß= -0.23, t(129)= -2.64, p=0.009) and more cognitive complaints (ß= -0.20, t(129)= -2.16, p=0.03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; six-month fall history was not significantly related to inflammatory markers. DISCUSSION Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.
The Psychological Impact of Strict and Prolonged Confinement on Business Students during the COVID-19 Pandemic at a Spanish University

The study was carried out to examine the situation of university students from one month after the beginning of a very strict confinement process in Spain during the COVID-19 pandemic. Students responded to a survey which included the 7-item Generalized Anxiety Disorder Scale (GAD-7) together with other questions relating to their general well-being from the European Quality of Life Survey (EQLS). A total of 198 university students answered the web-based survey. The questionnaire was generated using Microsoft Forms and was explained and distributed online. The results indicated that around 18.7% of students were suffering from severe anxiety and 70.2% were suffering either mild or moderate anxiety at this point of the strict confinement process. The findings show that when emotional well-being (quality of sleep, the perception of feeling fear, death of a relative) is reduced and material well-being is negatively affected (income level) anxiety levels are increased. On the other hand, the results show that having good interpersonal relationships with family members and taking care of personal development (routines and habits that make them feel good) help reduce anxiety levels. The female students in the sample also suffered higher levels of anxiety than males during strict confinement.
Effect of statin treatment in patients with acute myocardial infarction with prediabetes and type 2 diabetes mellitus

Supplemental Digital Content is available in the text Abstract Studies comparing long-term clinical outcomes of statin treatment between acute myocardial infarction (AMI) patients with prediabetes and those with type 2 diabetes mellitus (T2DM) after successful percutaneous coronary intervention (PCI) with the newer-generation drug-eluting stents (DESs) are limited. We compared 2-year clinical outcomes between these patients. A total of 11,962 AMI patients were classified as statin users (n = 10,243) and statin nonusers (n = 1719). Thereafter, statin users and nonusers were further divided into the normoglycemia, prediabetes, and T2DM groups. The major outcome was the occurrence of major adverse cardiac event (MACE) defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat coronary revascularization. After statin treatment, the cumulative incidences of MACE (P = .314), all-cause death, cardiac death (CD), Re-MI, and any repeat revascularization were similar between the prediabetes and T2DM groups. However, the cumulative incidences of MACE (P = .025) and all-cause death (P = .038) in the prediabetes group and those of MACE (P = .001), all-cause death (P = .009), and CD (P = .048) in the T2DM group were significantly higher than those in the normoglycemia group. Moreover, in all the 3 glycemic groups, the cumulative incidences of MACE, all-cause death, and CD were significantly higher among statin nonusers than among statin users. This study revealed that AMI patients with prediabetes had worse clinical outcomes than those with normoglycemia and comparable to those with T2DM after 2-year statin treatment. However, further studies are warranted to confirm the current findings.