Miracle-dz/UniFAR-FTUs huggingface dataset:
Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients

ABSTRACT Background: The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, e.g., using inulin or iohexol, is laborious and not feasible in daily practice. Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the “true GFR” measured using a gold standard method: iohexol plasma clearance. Methods: Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFRMDRD), Endogenous Creatinine Clearance (GFRECC), and iohexol plasma clearance (GFRiohexol) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay. Results: The eGFRMDRD and GFRECC correlated with the GFRiohexol (R2 = 0.82, P < 0.0001 and R2 = 0.82, P < 0.0001 respectively); however, bias and variability were considerable: the eGFRMDRD overestimated the true GFR with 31 ± 35% (95% limits of agreement: −37% to 100%) and the GFRECC with 37 ± 49% (95% limits of agreement: −59% to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFRiohexol (R2 = 0.90, P < 0.0001) which tended to be better compared with the correlation of eGFRMDRD (P = 0.06) and GFRECC (P = 0.08) with the GFRiohexol. Conclusions: In this pilot study in non-steady-state critically ill sepsis patients, GFR appears to be more accurately reflected by plasma PENK concentrations compared to conventional creatinine-based methods. Therefore, PENK holds promise as an accurate and feasible biomarker to determine kidney function during non-steady-state conditions in the critically ill.
Small Steps in Fitness, Major Leaps in Health for Adults with Intellectual Disabilities.

Physical fitness is positively related to health outcomes like morbidity and all-cause mortality, with minimally required cut-off values to generate those health benefits. Individuals with intellectual disabilities exhibit very low fitness levels well below those cut-off values. Our novel hypothesis is that even among very unfit, older adults with intellectual disabilities, small changes in fitness translate to major changes in health.
Switchable resolution in soft x-ray tomography of single cells

The diversity of living cells, in both size and internal complexity, calls for imaging methods with adaptable spatial resolution. Soft x-ray tomography (SXT) is a three-dimensional imaging technique ideally suited to visualizing and quantifying the internal organization of single cells of varying sizes in a near-native state. The achievable resolution of the soft x-ray microscope is largely determined by the objective lens, but switching between objectives is extremely time-consuming and typically undertaken only during microscope maintenance procedures. Since the resolution of the optic is inversely proportional to the depth of focus, an optic capable of imaging the thickest cells is routinely selected. This unnecessarily limits the achievable resolution in smaller cells and eliminates the ability to obtain high-resolution images of regions of interest in larger cells. Here, we describe developments to overcome this shortfall and allow selection of microscope optics best suited to the specimen characteristics and data requirements. We demonstrate that switchable objective capability advances the flexibility of SXT to enable imaging cells ranging in size from bacteria to yeast and mammalian cells without physically modifying the microscope, and we demonstrate the use of this technology to image the same specimen with both optics.
Development and Psychometric Analysis of the Patient Preferences for Engagement Tool.

BACKGROUND Assessing patients' preferences for engaging in healthcare is needed to inform the planning and delivery of individualized healthcare. Unfortunately, patients are often not engaged in their care to the extent that they would like, leading to patient feelings of disempowerment and frustration. OBJECTIVES The purpose of this study was to (a) develop and (b) psychometrically test the Patient Preferences for Engagement Tool (PPET): A clinical assessment tool that can be used by nursing staff to identify patient preferences for engagement in healthcare. The usability of the PPET was also examined for both nurses and patients participating in the study. METHOD The psychometric evaluation design used content and construct (exploratory and confirmatory factor analysis, known groups comparisons) validity testing and reliability estimation using Cronbach's alpha coefficient. The sample consisted of 308 adult patients aged 18-101 from a Midwestern United States magnet-designated academic medical center. RESULTS Content validity index was at least 0.8 for all but one item. Using a split sample, a six-factor solution was first identified using exploratory factor analysis, and then confirmed using confirmatory factor analysis. Demographic and illness factors were not significant predictors of factor scores. Cronbach's alpha coefficients of all six factors were > 0.7. Both patients and nurses gave high ratings to the tool on effectiveness, efficiency, and satisfaction with use DISCUSSION: The PPET demonstrated acceptable validity and reliability estimates. Assessing patient preferences for engagement gives value to the patient voice and provides an opportunity to have discussions with patients about various ways they can engage in their healthcare. Future research will focus on reducing the number of items on the PPET to construct a clinically useful resource for providers to use to assess patient preferences for healthcare engagement, leading to the development of more personalized care delivery methods.
Systematic scoping review of the concept of ‘genetic identity’ and its relevance for germline modification

EU legislation prohibits clinical trials that modify germ line ‘genetic identity’. ‘Genetic identity’ however, is left undefined. This study aims to identify the use of the term ‘genetic identity’ in academic literature, and investigate its relevance for debates on genetic modification. A total of 616 articles that contained the term were identified. Content analysis revealed that the term was used in various and contradicting ways and a clear understanding of the term is lacking. This review demonstrates that the EU legislation is open to interpretation, because of the diversity of meaning with which ‘genetic identity’ is currently used. Because of the diversity of meaning with which ‘genetic identity’ is used and understood, further reflection is needed. This requires further medical, legal, ethical and social debate and a coordinated response at both a European and a global level.
Impact of ZnO Addition on Er3+ Near-Infrared Emission, the Formation of Ag Nanoparticles, and the Crystallization of Sodium Fluorophosphate Glass

The impact of the progressive addition of ZnO up to 5 mol% on the thermal, structural, and optical properties of Er3+-doped phosphate glasses within the system NaPO3-NaF-ZnO-Ag2O is discussed. The glass network was found to depolymerize upon the addition of ZnO. This promotes a slight increase in the intensity of the emission at 1.5 µm as well as enhances the silver ions clustering ability under the heat treating. The Ag-nanoparticles formed after moderate heat-treatment can further enhance the emission at 1.5 µm, whereas an excessive amount of the clusters leads to the opposite effect. The addition of ZnO helps to slightly increase the glass ability of the system. The crystallization behavior study revealed that surface crystallization is observed for all the glasses. It is found that even a small ZnO addition changes the crystalline phases formed after devitrification. Moreover, the addition of ZnO decreases the crystallization tendency of the glass.
Plasma metabolomics of the time resolved response to Opisthorchis felineus infection in an animal model (golden hamster, Mesocricetus auratus)

Background Opisthorchiasis is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. Opisthorchiasis can lead to severe hepatobiliary morbidity and is classified as a carcinogenic agent. Here we investigate the time-resolved metabolic response to Opisthorchis felineus infection in an animal model. Methodology Thirty golden hamsters were divided in three groups: severe infection (50 metacercariae/hamster), mild infection (15 metacercariae/hamster) and uninfected (vehicle-PBS) groups. Each group consisted of equal number of male and female animals. Plasma samples were collected one day before the infection and then every two weeks up to week 22 after infection. The samples were subjected to 1H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical modelling. Principal findings The time-resolved study of the metabolic response to Opisthorchis infection in plasma in the main lines agrees with our previous report on urine data. The response reaches its peak around the 4th week of infection and stabilizes after the 10th week. Yet, unlike the urinary data there is no strong effect of the gender in the data and the intensity of infection is presented in the first two principal components of the PCA model. The main trends of the metabolic response to the infection in blood plasma are the transient depletion of essential amino acids and an increase in lipoprotein and cholesterol concentrations. Conclusions The time resolved metabolic signature of Opisthorchis infection in the hamster’s plasma shows a coherent shift in amino acids and lipid metabolism. Our work provides insight into the metabolic basis of the host response on the helminth infection.
Numerical simulation of atmospheric CO2 concentration and flux over the Korean Peninsula using WRF-VPRM model during Korus-AQ 2016 campaign

We conducted regional scale CO2 simulations using the Weather Research and Forecasting model (WRF) coupled with the Vegetation Photosynthesis and Respiration Model (VPRM). We contrasted simulated concentrations with column, ground and aircraft observations during the Korea-United States Air Quality (KORUS-AQ) 2016 field campaign. Overall, WRF-VPRM slightly underestimates CO2 concentrations at ground and column monitoring sites, but it significantly underestimates at an inland tower measurement site, especially within the stable (nocturnal) boundary layer in nighttime. The model successfully captures the airborne vertical profiles but showed a large offset within the planetary boundary layer (PBL) in the areas surrounding Seoul and around the Taeahn point source emissions in the west coastal area of the Korean Peninsula. A case study flight intended to capture Chinese influence observed no clear signals of long-range transport of CO2, due mainly to the much larger magnitude of background CO2 concentrations. The calculated Net Ecosystem Exchange (NEE) with flux measurements at a tower site in the South Korean Peninsula has also been evaluated comparing with CO2 flux measurements at a flux tower site, resulting in the underestimation by less than a factor of 1.
Cellular diversity and lineage trajectory: insights from mouse single cell transcriptomes

ABSTRACT Single cell RNA-sequencing (scRNA-seq) technology has matured to the point that it is possible to generate large single cell atlases of developing mouse embryos. These atlases allow the dissection of developmental cell lineages and molecular changes during embryogenesis. When coupled with single cell technologies for profiling the chromatin landscape, epigenome, proteome and metabolome, and spatial tissue organisation, these scRNA-seq approaches can now collect a large volume of multi-omic data about mouse embryogenesis. In addition, advances in computational techniques have enabled the inference of developmental lineages of differentiating cells, even without explicitly introduced genetic markers. This Spotlight discusses recent advent of single cell experimental and computational methods, and key insights from applying these methods to the study of mouse embryonic development. We highlight challenges in analysing and interpreting these data to complement and expand our knowledge from traditional developmental biology studies in relation to cell identity, diversity and lineage differentiation. Summary: This Spotlight provides key insights into the lineage specification and developmental trajectory in mouse embryonic development from the perspective of the single cell transcriptome.
Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index

Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of β-hydroxybutyrate (β-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: β-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R2 = 0.996, 0.994, and 0.994 for β-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for β-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 to ≤0.001). Age- and sex-adjusted multivariable linear regression analysis revealed that total ketone bodies and β-HB were associated directly with free fatty acids (FFAs) and T2DM and inversely with triglycerides and insulin resistance as measured by the Lipoprotein Insulin Resistance Index. Conclusions: Concentrations of the three main ketone bodies can be determined by NMR with good clinical performance, are elevated in T2DM and are inversely associated with triglycerides and insulin resistance.
Identification of naturally originated molecules as γ-aminobutyric acid receptor antagonist

Abstract γ-aminobutyric acid, being a principle neuromediator in humans controlling the inhibition signals, acts on the ligand-gated pentameric type A receptors to transmit their response. Any dysfunction of these receptors leads to neurological disorders and mental illness. Benzodiazepine has been used extensively for the treatment of these disorders, which shows its effect by reducing the threshold concentration of γ-aminobutyric acid required to activate the receptor. Being a central nervous system depressant, benzodiazepine is also a common substance of abuse along with other recreational drugs that show affinity towards the benzodiazepine binding site. Flumazenil is considered the first line of treatment for the overdose of these substances, which competes with them to bind with the receptor having a higher binding affinity towards the receptor. Like most of the synthetic drugs, Flumazenil also has some side-effects associated with it. Here we focus our work towards finding specific naturally originated antagonist of the benzodiazepine binding site to suggest an alternative for Flumazenil by performing various computational analysis like docking experiments followed by simulations and molecular mechanics poisson-boltzmann surface area analysis. Molecular docking experiments filtered out four ligand molecules specific for the benzodiazepine binding site, namely, ligand-1,7,9 and 17. Further, molecular dynamics simulations showed ligand-17 to have stable conformation in the binding site as well as a lower binding free energy as compared to Flumazenil. Due to its natural origin, ligand-17 is supposed to have lower side effects; therefore, its backbone can be further explored to develop specific antagonists of benzodiazepines. Communicated by Ramaswamy H. Sarma Graphical Abstract
A Targeted Genetic Association Study of the Rare Type of Osteomyelitis

Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic ≥0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype.
Deep Learning‐Based Single‐Cell Optical Image Studies

Optical imaging technology that has the advantages of high sensitivity and cost‐effectiveness greatly promotes the progress of nondestructive single‐cell studies. Complex cellular image analysis tasks such as three‐dimensional reconstruction call for machine‐learning technology in cell optical image research. With the rapid developments of high‐throughput imaging flow cytometry, big data cell optical images are always obtained that may require machine learning for data analysis. In recent years, deep learning has been prevalent in the field of machine learning for large‐scale image processing and analysis, which brings a new dawn for single‐cell optical image studies with an explosive growth of data availability. Popular deep learning techniques offer new ideas for multimodal and multitask single‐cell optical image research. This article provides an overview of the basic knowledge of deep learning and its applications in single‐cell optical image studies. We explore the feasibility of applying deep learning techniques to single‐cell optical image analysis, where popular techniques such as transfer learning, multimodal learning, multitask learning, and end‐to‐end learning have been reviewed. Image preprocessing and deep learning model training methods are then summarized. Applications based on deep learning techniques in the field of single‐cell optical image studies are reviewed, which include image segmentation, super‐resolution image reconstruction, cell tracking, cell counting, cross‐modal image reconstruction, and design and control of cell imaging systems. In addition, deep learning in popular single‐cell optical imaging techniques such as label‐free cell optical imaging, high‐content screening, and high‐throughput optical imaging cytometry are also mentioned. Finally, the perspectives of deep learning technology for single‐cell optical image analysis are discussed. © 2020 International Society for Advancement of Cytometry
Would you like to participate in this trial? The practice of informed consent in intrapartum research in the last 30 years

Background Informed consent is the cornerstone of the ethical conduct and protection of the rights and wellbeing of participants in clinical research. Therefore, it is important to identify the most appropriate moments for the participants to be informed and to give consent, so that they are able to make a responsible and autonomous decision. However, the optimal timing of consent in clinical research during the intrapartum period remains controversial, and currently, there is no clear guidance. Objective We aimed to describe practices of informed consent in intrapartum care clinical research in the last three decades, as reported in uterotonics for postpartum haemorrhage prevention trials. Methods This is a secondary analysis of the studies included in the Cochrane review entitled “Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis” published in 2018. All the reports included in the Cochrane network meta-analysis were eligible for inclusion in this analysis, except for those reported in languages other than English, French or Spanish. We extracted and synthesized data on the time each of the components of the informed consent process occurred. Results We assessed data from 192 studies, out of 196 studies included in the Cochrane review. The majority of studies (59.9%, 115 studies) reported that women were informed about the study, without specifying the timing. When reported, most studies informed women at admission to the facility for childbirth. Most of the studies reported that consent was sought, but only 59.9% reported the timing, which in most of the cases, was at admission for childbirth. Among these, 32 studies obtained consent in the active phase of labour, 17 in the latent phase and in 10 studies the labour status was unknown. Women were consented antenatally in 6 studies and in 8 studies the consent was obtained indistinctly during antenatal care or at admission. Most of the studies did not specified who was the person who sought the informed consent. Conclusion Practices of informed consent in trials on use of uterotonics for prevention of postpartum haemorrhage showed variability and substandard reporting. Informed consent sought at admission for childbirth was the most frequent approach implemented in these trials.