Miracle-dz/UniFAR-FTUs huggingface dataset:
Methods for Assessing Longitudinal Biomarkers of Time-to-Event Outcomes in CKD: A Simulation Study.

BACKGROUND AND OBJECTIVES Identifying novel biomarkers is critical to advancing diagnosis and treatment of CKD, but relies heavily on the statistical methods used. Inappropriate methods can lead to both false positive and false negative associations between biomarkers and outcomes. This study assessed accuracy of methods using computer simulations and compared biomarker association estimates in the NEPhrotic syndrome sTUdy NEtwork (NEPTUNE), a prospective cohort study of patients with glomerular disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We compared three methods for analyzing repeatedly measured biomarkers in proportional hazards models: (1) time-invariant average, that averages values over all follow-up and uses the average as a baseline covariate, (2) time-varying last observation carried forward (LOCF), that assumes the covariate is unchanged until the next observed value, and (3) time-varying cumulative average, that updates the average using values at or before each measurement. RESULTS Under both true mechanisms of LOCF and cumulative average, simulation results showed the time-invariant average method often gave extremely inaccurate results. When LOCF was the true association mechanism, the cumulative average method often gave overestimated association estimates that were further away from the null. When cumulative average was the true mechanism, LOCF always underestimated the associations, i.e., closer to the null. In NEPTUNE, compared with the LOCF or cumulative average methods, hazard ratios estimated from the time-invariant average method were always higher. CONCLUSIONS Different analytic methods resulted in markedly different results. Using the time-invariant average produces inaccurate association estimates, whereas other methods can estimate additive (cumulative average) or instantaneous (LOCF) associations depending on the hypothesized underlying association mechanism and research question.
Factors predicting long-term survival of patients with sepsis on arrival at the emergency department

Abstract Predicting long-term outcomes after sepsis is important when caring for patients with this condition. The purpose of the present study was to develop models predicting long-term mortality of patients with sepsis, including septic shock. Retrospective data from 446 patients with sepsis (60.8% men; median age, 71 years) treated at a single university-affiliated tertiary care hospital over 3 years were reviewed. Binary logistic regression was used to identify factors predicting mortality at 180 and 365 days after arrival at the emergency department. Long-term prognosis scores for the 180- and 365-day models were calculated by assigning points to variables according to their β coefficients. The 180- and 365-day mortality rates were 40.6% and 47.8%, respectively. Multivariate analysis identified the following factors for inclusion in the 180- and 365-day models: age ≥65 years, body mass index ≤18.5 kg/m2, hemato-oncologic diseases as comorbidities, and ventilator care. Patients with scores of 0 to ≥3 had 180-day survival rates of 83.8%, 70.8%, 42.3%, and 25.0%, respectively, and 365-day survival rates of 72.1%, 64.6%, 36.2%, and 15.9%, respectively (all differences P < .001; log-rank test). The areas under the receiver operating characteristic curves of the 180- and 365-day models were 0.713 (95% confidence interval [CI] 0.668–0.756, P < .001) and 0.697 (95% CI 0.650–0.740, P < .001), respectively. These long-term prognosis models based on baseline patient characteristics and treatments are useful for predicting the 6- and 12-month mortality rates of patients with sepsis.
Combining non‐invasive brain stimulation with functional magnetic resonance imaging to investigate the neural substrates of cognitive aging

As aging population is increasing, new methodologies to apprehend and enhance the mechanisms related to optimal brain function in advancing age become urgent. This review describes how the combined use of non‐invasive brain stimulation (NIBS) with functional magnetic resonance imaging (fMRI) provides novel experimental data on the putative neurophysiological mechanisms underlying inter‐individual differences in cognitive status among older adults, also further illuminating our understanding of theoretical models proposed within the cognitive neuroscience of aging literature. In addition, it explores published evidence of how this combined procedure entails the capacity to modify the activity and connectivity of specific brain networks in older adults, potentially leading to improvements in cognitive function and other measures reflecting mental health status. Although additional research is needed, combining NIBS with fMRI might provide innovative understanding of how fundamental brain plasticity mechanisms operate in advancing age, a knowledge that may be eventually used to refine more individually tailored approaches to promote brain health in aged populations.
Optical simulation study on the spatial resolution of a thick monolithic PET detector

The intrinsic spatial resolution of clinical positron emission tomography (PET) detectors is ~3–4 mm. A further improvement of the resolution using pixelated detectors will not only result in a prohibitive cost, but is also inevitably accompanied by a strong degradation of important performance parameters like timing, energy resolution and sensitivity. Therefore, it is likely that future generation high resolution PET detectors will be based on continuous monolithic scintillation detectors. Monolithic detectors have attractive properties to reach superior 3D spatial resolution while outperforming pixelated detectors in timing, energy resolution and sensitivity. In this work, optical simulations including an advanced surface reflection model, allow us to investigate the influence of three parameters on the spatial resolution: silicon photomultiplier (SiPM) pixel size, photon detection efficiency (PDE) and the number of channels used to read out the SiPM array. A lutetium-yttrium oxyorthosilicate (LYSO) crystal with dimensions 50 × 50 × 16 mm3 coupled to an SiPM array is calibrated and a nearest neighbor (NN) algorithm is used to position events. Findings show that the tested parameters affect the spatial resolution resulting in 0.40–0.66 mm full width at half maximum (FWHM). Best resolution could be obtained with smaller SiPM pixels, higher PDE, and an individual channel readout. However, it was shown that combining channels by adding their signals can significantly reduce the amount of readout channels while having small or no significant impact on the resolution. The mean depth of interaction (DOI) estimation error is 1.6 mm. This study demonstrates the ultimate spatial resolution that can be obtained with this detector without being constrained by practical limitations of experimental setups. In the future these optical simulations may be used as a more precise and fast method to obtain calibration data for real monolithic detectors.
Loss of Peter Pan (PPAN) Affects Mitochondrial Homeostasis and Autophagic Flux

Nucleolar stress is a cellular response to inhibition of ribosome biogenesis or nucleolar disruption leading to cell cycle arrest and/or apoptosis. Emerging evidence points to a tight connection between nucleolar stress and autophagy as a mechanism underlying various diseases such as neurodegeneration and treatment of cancer. Peter Pan (PPAN) functions as a key regulator of ribosome biogenesis. We previously showed that human PPAN localizes to nucleoli and mitochondria and that PPAN knockdown triggers a p53-independent nucleolar stress response culminating in mitochondrial apoptosis. Here, we demonstrate a novel role of PPAN in the regulation of mitochondrial homeostasis and autophagy. Our present study characterizes PPAN as a factor required for maintaining mitochondrial integrity and respiration-coupled ATP production. PPAN interacts with cardiolipin, a lipid of the inner mitochondrial membrane. Down-regulation of PPAN enhances autophagic flux in cancer cells. PPAN knockdown promotes recruitment of the E3-ubiquitin ligase Parkin to damaged mitochondria. Moreover, we provide evidence that PPAN knockdown decreases mitochondrial mass in Parkin-expressing cells. In summary, our study uncovers that PPAN knockdown is linked to mitochondrial damage and stimulates autophagy.
Trends and changes in the knowledge of mother-to-child transmission means of HIV among Vietnamese women aged 15–49 years and its associated factors: findings from the Multiple Indicator Cluster Surveys, 2000–2014

ABSTRACT This study aims to characterize trends and changes in the prevalence of knowledge of mother-to-child transmission (MTCT) means of HIV as well as to identify its associated socioeconomic factors among Vietnamese women. This is a repeated cross-sectional study using data from the Vietnam Multiple Indicator Cluster Surveys 2000, 2006, 2011 and 2014. We found that a slow increase was found in the trend of adequate knowledge of HIV transmission means from mother to child among women between 2000 and 2014 (41.81% in 2000, 45.66% in 2006, 49.58% in 2011, and 46.83% in 2014). Most women knew that HIV could be transmitted during pregnancy, however, more than half of women did not know all three ways of MTCT. Socioeconomic factors including age, ethnicity, education level, and economic status as factors that affected full knowledge of MTCT means. The study helps to design public health programs to raise 15–49-year-old women’s knowledge in HIV transmission means from mother to child as well as can provide a quite strong case for policy adaptation to improve women’s health in the time to come.
Maternal Satisfaction with Healthcare after Perinatal Loss in Monochorionic Twin Pregnancy

Introduction: The analysis of patients’ satisfaction with healthcare is recognised as being useful in the evaluation of health outcomes and perceived quality of care. Little is known, however, about how the psychological status of women who experience perinatal complications may affect their perceived satisfaction with care. Methods: We assessed healthcare satisfaction in 52 women who had undergone intrauterine surgery during a complicated monochorionic twin pregnancy and examined the influence that fetal loss and sociodemographic, clinical, and psychological factors had on the degree of satisfaction. Data were gathered in an individual interview and through the administration of the Medical Patient Satisfaction Questionnaire, Beck Depression Inventory, and State–Trait Anxiety Inventory. Relationships between variables were analysed using a chi-square test, Spearman’s rho, Student’s t test, and the Mann–Whitney U test, in accordance with the metric nature of the variables and the assumptions fulfilled. Results: Age and level of education were not associated with the degree of healthcare satisfaction. Negative but non-significant correlations were observed between the level of satisfaction and symptoms of anxiety and depression. Satisfaction with healthcare was high in the sample as a whole, although it was significantly higher among women who had not experienced fetal loss. There were no differences in satisfaction with services involving direct contact with medical staff, whereas satisfaction with indirect services was lower among women who had experienced perinatal loss. Conclusions: Due to the unique characteristics of this population, specialised care teams of both professional healthcare and indirect services are needed. Although administrative aspects of healthcare are regarded as being of secondary importance, this may not be the case with more vulnerable populations.
Effects of Vitamin D Supplementation on Body Composition and Metabolic Risk Factors in Men: A Randomized Controlled Trial

Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial. We included 200 healthy men with serum 25-hydroxyvitamin D (25(OH) D) levels <75 nmol/L. Subjects received 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were metabolic markers, anthropometric measures, and body composition assessed by Dual-energy X-ray absorptiometry. One-hundred and ninety-two men completed the study. We found a significant treatment effect on fasting glucose/fasting insulin ratio (−5.3 (−10.4 to −0.2), p = 0.040), whereas we observed no significant effect on the remaining outcome parameters. In subgroup analyses of men with baseline 25(OH)D levels <50 nmol/L (n = 80), we found a significant effect on waist circumference (1.6 (0.3 to 2.9) cm, p = 0.012), waist-to-hip ratio (0.019 (0.002 to 0.036), p = 0.031), total body fat (0.029 (0.004 to 0.055) %, p = 0.026), and android fat (1.18 (0.11 to 2.26) %, p = 0.010). In middle-aged healthy men, vitamin D treatment had a negative effect on insulin sensitivity. In vitamin D deficient men, vitamin D has an unfavorable effect on central obesity and body composition.
Moving from Empirical to Rational Vaccine Design in the ‘Omics’ Era

An ideal vaccine provides long lasting protection against a pathogen by eliciting a well-rounded immune response which engages both innate and adaptive immunity. However, we have a limited understanding of how components of innate immunity, antibody and cell-mediated adaptive immunity interact and function together at a systems level. With advances in high-throughput ‘Omics’ methodologies it has become possible to capture global changes in the host, at a cellular and molecular level, that are induced by vaccination and infection. Analysis of these datasets has shown the promise of discovering mechanisms behind vaccine mediated protection, immunological memory, adverse effects as well as development of more efficient antigens and adjuvants. In this review, we will discuss how systems vaccinology takes advantage of new technology platforms and big data analysis, to enable the rational development of better vaccines.
Epigenetic silencing of a multifunctional plant stress regulator

The central regulator of the ethylene (ET) signaling pathway, which controls a plethora of developmental programs and responses to environmental cues in plants, is ETHYLENE-INSENSITIVE2 (EIN2). Here we identify a chromatin-dependent regulatory mechanism at EIN2 requiring two genes: ETHYLENE-INSENSITIVE6 (EIN6), which is a H3K27me3 demethylase also known as RELATIVE OF EARLY FLOWERING6 (REF6), and EIN6 ENHANCER (EEN), the Arabidopsis homolog of the yeast INO80 chromatin remodeling complex subunit IES6 (INO EIGHTY SUBUNIT). Strikingly, EIN6 (REF6) and the INO80 complex redundantly control the level and the localization of the repressive histone modification H3K27me3 and the histone variant H2A.Z at the 5’ untranslated region (5’UTR) intron of EIN2. Concomitant loss of EIN6 (REF6) and the INO80 complex shifts the chromatin landscape at EIN2 to a repressive state causing a dramatic reduction of EIN2 expression. These results uncover a unique type of chromatin regulation which safeguards the expression of an essential multifunctional plant stress regulator.
Metabolomic profiling of blood plasma in patients with primary brain tumours: Basal plasma metabolites correlated with tumour grade and plasma biomarker analysis predicts feasibility of the successful statistical discrimination from healthy subjects – a preliminary study

The brain tumours represent a complex tissue that has its own characteristic metabolic features and is interfaced with the whole organism. We investigated changes in basal blood plasma metabolites in the presence of primary brain tumour, their correlation with tumour grade, as well as the feasibility of statistical discrimination based on plasma metabolites. Together 60 plasma samples from patients with clinically defined glioblastoma, meningioma, oligodendrioglioma, astrocytoma, and non‐specific glial tumour and plasma samples from 28 healthy volunteers without any cancer history were measured by NMR spectroscopy. In blood plasma of primary brain tumour patients, we found significantly increased levels of glycolytic metabolites glucose and pyruvate, and significantly decreased level of glutamine and also metabolites participating in tricarboxylic acid (TCA) cycle, citrate and succinate, when compared with controls. Further, plasma metabolites levels: tyrosine, phenylalanine, glucose, creatine and creatinine correlated significantly with tumour grade. In general, observed changes are parallel to the biochemistry expected for tumourous tissue and metabolic changes in plasma seem to follow the similar rules in all primary brain tumours, with very subtle variations among tumour types. Only two plasma metabolites tyrosine and phenylalanine were increased exclusively in blood plasma of patients with glioblastoma. Based on metabolite levels, an excellent discrimination between plasma from patient's tumours and controls was attainable. The metabolites creatine, pyruvate, glucose, formate, creatinine and citrate were of the highest discriminatory power.
Improved Reference Genome Sequence of Coccidioides immitis Strain WA_211, Isolated in Washington State

Coccidioides fungi are widely distributed in the American continents, with an expanding western range documented by a recently discovered cryptic population of Coccidioides immitis in Washington State. The assembled and annotated reference genome sequence of the soil-derived C. immitis strain WA_211 will support population and functional genomics studies. ABSTRACT Coccidioides fungi are widely distributed in the American continents, with an expanding western range documented by a recently discovered cryptic population of Coccidioides immitis in Washington State. The assembled and annotated reference genome sequence of the soil-derived C. immitis strain WA_211 will support population and functional genomics studies.
Trends and Correlates of Overweight among Pre-School Age Children, Adolescent Girls, and Adult Women in South Asia: An Analysis of Data from Twelve National Surveys in Six Countries over Twenty Years

Overweight has become a global pandemic and is associated with a rise in diet-related non-communicable diseases and associated co-morbidities. Most of the world’s undernourished people live in South Asia, yet the number of overweight and obese individuals in this region is growing. This study explores trends and correlates of overweight among pre-school age children, adolescent girls, and adult women in South Asia. Using pooled data from 12 national surveys in six countries, generalized linear mixed models were run to analyze relationships. Overweight children had significantly higher odds than non-overweight children of having an overweight mother (Adjusted Odds Ratio: 1.34, p < 0.01). Overweight adolescent girls were more likely to come from a wealthier household (Adjusted Prevalence Ratio (APR): 2.46, p < 0.01) in an urban area (1.74, p < 0.01), and have formal education (1.22, p < 0.01), compared to non-overweight girls. Similar relationships were seen among overweight vs. non-overweight adult women. In Bangladesh, India, and Nepal, overweight among girls and women increased over time, while differentials associated with household wealth, urban residence, and formal education attenuated over time. Overweight and obesity are becoming more prevalent across South Asia in a context of persisting undernutrition. Once a condition of the wealthier, more educated and urban, rates of overweight are increasing among poorer, less educated, and rural women. This requires immediate attention to ‘multi-use’ policies and programmes.
'hagis', an R Package Resource for Pathotype Analysis of Phytophthora sojae Populations Causing Stem and Root Rot of Soybean.

Phytophthora sojae is a significant pathogen of soybean worldwide. Pathotype surveys for Phytophthora sojae are conducted to monitor resistance gene efficacy and determine if new resistance genes are needed. Valuable measurements for pathotype analysis include the distribution of susceptible reactions, pathotype complexity, pathotype frequency, and diversity indices for pathotype distributions. Previously the Habgood-Gilmour Spreadsheet (HaGiS), written in Microsoft® Excel, was used for data analysis. However, the growing popularity of the R programming language in plant pathology and desire for reproducible research made HaGiS a prime candidate for conversion into an R package. Here we report on the development and use of an R package, 'hagis', that can be used to produce all outputs from the HaGiS Excel sheet for P. sojae or other gene-for-gene pathosystem studies.
The effects of eccentric phase duration on concentric outcomes in the back squat and bench press in well-trained males

ABSTRACT The velocity and magnitude in which the eccentric phase of an exercise is completed directly affects performance during the concentric phase. Therefore, the purpose of this research was to investigate the effects of eccentric phase duration on concentric outcomes at 60% and 80% of one-repetition maximum (1RM) in the squat and bench press. Sixteen college-aged, resistance-trained males completed 1RM testing, established normative eccentric durations, and performed fast (0.75 times normative) and slow (2.0 times normative) metronome-controlled eccentric duration repetitions. Outcome measures assessed during the concentric phase were: average concentric velocity (ACV), peak concentric velocity (PCV), rating of perceived exertion (RPE), range of motion (ROM), and barbell path. Eccentric duration was significantly and inversely correlated with ACV at 60% (r = −0.408, p = 0.004) and 80% (r = −0.477, p = 0.001) of 1RM squat. At 60% of 1RM squat, both fast and slow eccentric conditions produced greater (p < 0.001) PCV than normative duration with fast also producing greater PCV than slow (p = 0.044). Eccentric duration had no impact on RPE, ROM, or barbell path. Our results report for the first time that resistance-trained males performing a deliberately faster eccentric phase may enhance their own squat and bench press performance.
Chlorin e6-Loaded PEG-PCL Nanoemulsion for Photodynamic Therapy and In Vivo Drug Delivery

We fabricated poly (ethylene glycol)-block-polycaprolactone (PEG-b-PCL) nanoemulsion for drug delivery and photodynamic therapy. PEG-b-PCL effectively stabilized the interface between water and soybean oil, and the resulting nanoemulsion was about 220.3 nm in diameter with spherical shape. For photodynamic therapy (PDT), chlorin e6 (Ce6) was loaded into the nanoemulsion as a photosensitizer (PS). These chlorin e6-loaded PEG-PCL nanoemulsions (Ce6-PCL-NEs) showed efficient cellular uptake and, upon laser irradiation, generated singlet oxygen to kill tumor cells. Particularly, Ce6-PCL-NEs showed prolonged blood circulation and about 60% increased tumor accumulation compared to free Ce6 after intravenous injection to 4T1 tumor-bearing mice. These results demonstrate the promising potential of Ce6-PCL-NEs for efficient PDT and in vivo drug delivery to tumor tissue.