Miracle-dz/UniFAR-FTUs huggingface dataset:
Severe COVID-19 in pregnancy has a distinct serum profile, including greater complement activation and dysregulation of serum lipids

Background Pregnancies complicated by Coronavirus Disease 2019 (COVID-19) are at an increased risk of severe morbidity due to physiologic changes in immunologic, cardiovascular, and respiratory function. There is little is known about how severity of COVID-19 changes protein and metabolite expression in pregnancy. Objective This study aims to investigate the pathophysiology behind various clinical trajectories in pregnant patients diagnosed with COVID-19 using multi-omics profiling. Study design This is a prospective cohort study of 30 pregnant patients at a single tertiary care center. Participants were categorized by severity of COVID-19 disease (control, asymptomatic, mild/moderate, or severe). Maternal serum samples underwent LC-MS-based multiomics analysis for profiling of proteins, lipids, electrolytes, and metabolites. Linear regression models were used to assess how disease severity related to analyte levels. Reactome pathway enrichment analysis was conducted on differential analytes. Results Of 30 participants, 25 had confirmed diagnosis of COVID-19 (6 asymptomatic (one post-infection), 13 mild/moderate (all post-infection), 6 severe), and 5 participants were controls. Severe COVID-19 was associated with distinct profiles demonstrating significant proteomic and lipidomic signatures which were enriched for annotations related to complement and antibody activity. (FDR < 0.05). Downregulated analytes were not significantly enriched but consisted of annotation terms related to lipoprotein activity (FDR > 0.2). Post-infection mild/moderate COVID-19 did not have significantly altered serum protein, metabolite, or lipid metabolite levels compared to controls. Conclusions Pregnancies with severe COVID-19 demonstrate greater inflammation and complement activation and dysregulation of serum lipids. This altered multiomic expression provides insight into the pathophysiology of severe COVID-19 in pregnancy and may serve as potential indicators for adverse pregnancy outcomes.
Exploring the Virtual-Representational-Abstract Instructional Sequence Across the Learning Stages for Struggling Students

In recent years, virtual manipulatives have been explored and used as an alternative to concrete manipulatives in mathematics for students on their own and as part of manipulative-based instructional sequences. Researchers examining virtual manipulative-based instructional sequences tend to focus on students documented with disabilities, as opposed to students at-risk or struggling with mathematics, as well as students’ acquisition of the target skill, despite students experiencing learning in four stages: acquisition, fluency, maintenance, and generalization. This study explored the virtual-representational-abstract (VRA) instructional sequence across four stages of learning for three elementary students struggling in mathematics. In the single-case design study, researchers found a functional relationship between the VRA instructional sequence delivered online via explicit instruction and students’ computational accuracy in their targeted area of mathematics need. Researchers also found limited influence on fluency rate or generalization to word problem accuracy but that students did maintain.
The Mental and Physical Health of the Homeless-Evidence From the National Survey on Psychiatric and Somatic Health of Homeless Individuals (the NAPSHI Study).

BACKGROUND The health status of homeless individuals in Germany has been described incompletely. Mental and somatic illnesses seem to contribute to the high mortality in this cohort. METHODS In this national, multicenter, cross-sectional study, data were collected on the health of 651 homeless individuals in the metropolitan regions of Hamburg, Frankfurt, Leipzig, and Munich metropolitan regions. The lifetime prevalences of physician-diagnosed mental and somatic illnesses were determined with interview-based questionnaires. Furthermore, clinical and laboratory examinations were carried out. Multivariable regressions were performed to identify determinants of health status and access to care. RESULTS High prevalences of both mental and somatic illnesses were confirmed. Particularly, cardiovascular and metabolic diseases were highly prevalent. Evidence for possible unrecognized arterial hypertension and possible unrecognized hypercholesterolemia was found in 27.5% and 15.6% of homeless individuals, respectively. 23.1% of study participants reported having received a diagnosis of a mental illness. Evidence for a possible unrecognized mental illness was found in 69.7%. A history of immigration from another country to Germany was found to be an important determinant of the summed scores for mental, somatic, and possible unrecognized illness. Homeless individuals of non-German origin were more likely to be living without shelter (p = 0.03) and to lack health insurance (p < 0.001). CONCLUSION High prevalence rates for mental and somatic illnesses and limited access to mainstream medical care were found. Homeless individuals appear to receive inadequate care for mental illness. Healthcare programs for homeless individuals in Germany should pay particular attention to homeless migrants.
A human kidney and liver organoid‐based multi‐organ‐on‐a‐chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell‐derived extracellular vesicles

Abstract Mesenchymal stromal cell (MSC)‐derived small extracellular vesicles (sEVs) show therapeutic potential in multiple disease models, including kidney injury. Clinical translation of sEVs requires further preclinical and regulatory developments, including elucidation of the biodistribution and mode of action (MoA). Biodistribution can be determined using labelled sEVs in animal models which come with ethical concerns, are time‐consuming and expensive, and may not well represent human physiology. We hypothesised that, based on developments in microfluidics and human organoid technology, in vitro multi‐organ‐on‐a‐chip (MOC) models allow us to study effects of sEVs in modelled human organs like kidney and liver in a semi‐systemic manner. Human kidney‐ and liver organoids combined by microfluidic channels maintained physiological functions, and a kidney injury model was established using hydrogenperoxide. MSC‐sEVs were isolated, and their size, density and potential contamination were analysed. These sEVs stimulated recovery of the renal epithelium after injury. Microscopic analysis shows increased accumulation of PKH67‐labelled sEVs not only in injured kidney cells, but also in the unharmed liver organoids, compared to healthy control conditions. In conclusion, this new MOC model recapitulates therapeutic efficacy and biodistribution of MSC‐sEVs as observed in animal models. Its human background allows for in‐depth analysis of the MoA and identification of potential side effects.
Predictive Factors of Outcome in Cases of Out-of-hospital Cardiac Arrest Due to Traffic Accident Injuries in Thailand; a National Database Study

Introduction: Traffic accident injury is one of the global leading causes of death and an important public health problem. This study aimed to evaluate the predictive factors of return of spontaneous circulation (ROSC) at the scene in out-of-hospital cardiac arrest (OHCA) due to traffic accidents. Methods : This retrospective cross-sectional study was conducted on cases of OHCA due to traffic accident, who were resuscitated at the scene by emergency medical services (EMS) in Bankok, Thiland, from January 1, 2020, to December 31, 2020 (1 year). Patients were divided into two groups of with and without ROSC and independent predictive factors of outcome were evaluated. Results : 2400 OHCA cases met the inclusion criteria, among them, 1728 (72.0%) achieved ROSC at the scene. Facial injury (adjusted OR = 2.17, 95%CI: 1.37–3.44, p = 0.001); prehospital airway management using bag valve mask (adjusted OR = 1.69, 95%CI: 1.21–2.34, p = 0.002), and endotracheal tube (adjusted OR = 3.88, 95%CI: 1.84–8.18, p <0.001); and prehospital fluid therapy using normal saline (adjusted OR = 4.24, 95%CI: 3.12–5.77, p <0.001), ringer lactate (adjusted OR = 5.13, 95%CI: 3.47–7.61, p <0.001), and other solutions (adjusted OR = 5.25, 95%CI: 2.16–12.8, p <0.001) were independent predictive factors of ROSC at the scene in OHCA due to traffic accidents. Conclusion : Based on the findings, the rate of ROSC at the scene for cases with OHCA due to traffic accidents, serviced by EMS was high, i.e., 72%, and three independent predictive factors of ROSC at the scene were facial injury, prehospital airway management, and prehospital fluid management.
Impact of Antithrombin Activity Levels Following Recombinant Antithrombin Gamma Therapy in Patients with Sepsis-Induced Disseminated Intravascular Coagulation

Recombinant antithrombin gamma (rAT) is reported as an effective drug for patients with disseminated intravascular coagulation (DIC) in Japan. As the appropriate dose and targeted AT activity remain unknown, this study aimed to determine these aspects for sepsis-induced DIC. Thirty-one patients with septic shock and DIC with AT levels <70% were treated with rAT between May 2018 and December 2020. The recovery rates from DIC were 32.2% and 63.3% on day 3 and 5 post administration, respectively. Recovery and survival rates were significantly higher in patients who achieved AT activity ≥70% or 80% on day 3 post administration. Receiver operating characteristic curve analysis revealed that the cutoff values of post-treatment AT activity on day 3 for 28-day survival and 5-day recovery from DIC were 79.5% and 81.5%, respectively. Patients who did not achieve AT activity ≥80% on day 3 presented a lower base level of AT activity and lower dose supplementation. Our results suggest that targeted AT activity should be at least 70%, and ideally 80%, and sufficient doses to maintain this activity are required to achieve better outcomes.
Dual-Beam Photothermal Spectroscopy Employing a Mach–Zehnder Interferometer and an External Cavity Quantum Cascade Laser for Detection of Water Traces in Organic Solvents

We report on a mid-infrared (mid-IR) photothermal spectrometer for liquid-phase samples for the detection of water in organic solvents, such as ethanol or chloroform, and in complex mixtures, such as jet fuel. The spectrometer is based on a Mach–Zehnder interferometer (MZI) employing a He-Ne laser, a mini-flow cell with two embedded channels placed in the interferometer’s arms, and a tunable external cavity quantum cascade laser (EC-QCL) for selective analyte excitation in a collinear arrangement. In this study, the bending vibration of water in the spectral range 1565–1725 cm–1 is targeted. The interferometer is locked to its quadrature point (QP) for most stable and automated operation. It provides a linear response with respect to the water content in the studied solvents and photothermal analyte spectra, which are in good agreement with FTIR absorbance spectra. The method is calibrated and validated against coulometric Karl Fischer (KF) titration, showing comparable performance and sensitivity. Limits of detection (LODs) for water detection in the single-digit ppm range were obtained for chloroform and jet fuel due to their low background absorption, whereas lower sensitivity has been observed for water detection in ethanol due to pronounced background absorption from the solvent. In contrast to KF titration, which requires toxic reagents and produces waste, the developed method works reagent-free. It can be applied in an online format in the chemical industry as well as for fuel quality control, being industrial applications where traces of water need to be accurately determined, preferably in real-time. It thus holds great promise as a green alternative to the offline KF titration method, which is the current standard method for this application.
Indirect contact with nature, lifestyle, and mental health outcomes during mandatory hotel quarantine in Hong Kong

Abstract Background During the pandemic of COVID-19 Hong Kong lead one of the world’s longest and most stringent quarantine measures. Aims To examine cross-sectionally (i) the relationship between the duration of mandatory hotel quarantine and mental health outcomes; (ii) whether indirect contact with nature and lifestyle factors (i.e. diet, sleep, exercises, social support, and sense of meaning), mitigated this relationship. Methods A group of 248 participants under 14 or 21-d mandatory hotel quarantine in Hong Kong completed an online questionnaire that included quarantine and lifestyle-related questions, as well as mental health outcome measures. Results For those under a 21-d quarantine, there was a significant effect of the week of quarantine on the level of depressive symptoms (Patient Health Questionnaire-4), which peaked in Week 2. Worse quality of sleep, a lower sense of meaning, and a longer set (but not completed) duration of quarantine were predictors of worse mental health outcomes. The positive relationship between the day of quarantine and the level of perceived stress was moderated by the indirect contact with nature. Conclusion The results shed light on the potential negative impact of prolonged periods of quarantine on mental health outcomes and the possible protective factors.
Measuring omega(0) using cluster evolution

The evolution of the galaxy cluster abundance depends sensitively on the value of the cosmological density parameter, Omega_0. Recent ASCA data are used to quantify this evolution as measured by the X-ray temperature function. A chi^2 minimisation fit to the cumulative temperature function, as well as a maximum likelihood estimate (which requires additional assumptions about cluster luminosities), lead to the estimate Omega_0 \approx 0.45+/-0.2 (1-sigma statistical error). Various systematic uncertainties are considered, none of which enhance significantly the probability that Omega_0=1. These conclusions hold for models with or without a cosmological constant. The statistical uncertainties are at least as large as the individual systematic errors that have been considered here, suggesting that additional temperature measurements of distant clusters will allow an improvement in this estimate. An alternative method that uses the highest redshift clusters to place an upper limit on Omega_0 is also presented and tentatively applied, with the result that Omega_0=1 can be ruled out at the 98 per cent confidence level. Whilst this method does not require a well-defined statistical sample of distant clusters, there are still modelling uncertainties that preclude a firmer conclusion at this time.
A kernel method of estimating structured nonparametric regression based on marginal integration

SUMMARY We define a simple kernel procedure based on marginal integration that estimates the relevant univariate quantity in both additive and multiplicative nonparametric regression. Nonparametric regression is frequently used as a preliminary diagnostic tool. It is a convenient method of summarising the relationship between a dependent and a univariate independent variable. However, when the explanatory variables are multidimensional, these methods are less satisfactory. In particular, the rate of convergence of standard estimators is poorer, while simple plots are not available to aid model selection. There are a number of simplifying structures that have been used to avoid these problems. These include the regression tree structure of Gordon & Olshen (1980), the projection pursuit model of Friedman & Stuetzle (1981), semiparametric models such as considered
Discovery of RUF6 ncRNA–interacting proteins involved in P. falciparum immune evasion

An RNA-directed proteomic discovery (ChIRP-MS) protocol is used to identify in vivo RUF6 ncRNA–protein interactions that sustain virulence genes in the human malaria parasite, Plasmodium falciparum. Non-coding RNAs (ncRNAs) are emerging regulators of immune evasion and transmission of Plasmodium falciparum. RUF6 is an ncRNA gene family that is transcribed by RNA polymerase III but actively regulates the Pol II–transcribed var virulence gene family. Understanding how RUF6 ncRNA connects to downstream effectors is lacking. We developed an RNA-directed proteomic discovery (ChIRP-MS) protocol to identify in vivo RUF6 ncRNA–protein interactions. The RUF6 ncRNA interactome was purified with biotinylated antisense oligonucleotides. Quantitative label-free mass spectrometry identified several unique proteins linked to gene transcription including RNA Pol II subunits, nucleosome assembly proteins, and a homologue of DEAD box helicase 5 (DDX5). Affinity purification of Pf-DDX5 identified proteins originally found by our RUF6-ChIRP protocol, validating the technique’s robustness for identifying ncRNA interactomes in P. falciparum. Inducible displacement of nuclear Pf-DDX5 resulted in significant down-regulation of the active var gene. Our work identifies a RUF6 ncRNA–protein complex that interacts with RNA Pol II to sustain the var gene expression, including a helicase that may resolve G-quadruplex secondary structures in var genes to facilitate transcriptional activation and progression.
SL(3) Chern-Simons Higher Spin and Open Toda Chain Theories

We begin from the SL(3) Chern-Simons higher spin theory, which contains the first-order formulation of Einstein gravity theory in three dimensions. Then the dimensional reduction in this Chern-Simons theory gives the SL(3) reparametrization invariant Schwarzian theory, which is the boundary theory of an interacting theory between the spin-2 and spin-3 fields at the infrared or massless limit. We show that the Lorentzian SL(3) Schwarzian theory is dual to the integrable model, SL(3) open Toda chain theory. Finally, we demonstrate the application of open Toda chain theory from the SL(2) case. The numerical result confirms that the SYK model in the holographic limit, $N\gg\beta J\gg 1$, where $N$ is the number of Majorana fermion fields, $\beta$ is the inverse temperature, and $J$ is the coupling constant, and the JT gravity theory with a constant boundary dilaton should be integrable and not have the random matrix spectrum by computing the spectral form factor.
Characteristics and difference of respiratory diseases in Korean adults aged ≥40 years: A cross‐sectional study

National big data pertaining to the status of common respiratory diseases is essential to devising appropriate policies to promote proper treatment and prevention of respiratory diseases amid the prolonged coronavirus disease 2019 (COVID‐19) pandemic. The aim of this study is to investigate the prevalence of common respiratory diseases and their association with sociodemographic characteristics, comorbidities, and medical history using 11 years (2008–2018) of the Korea National Health and Nutrition Examination Survey (KNHANES) data, ultimately to present foundational data for policy decision making and disease prevention measures.
Trajectories of Cognition and Daily Functioning Before and After Incident Diabetes.

OBJECTIVE The temporal pattern of cognitive and functional change before and after incident diabetes remains unknown. RESEARCH DESIGN AND METHODS Data from wave 2 to wave 9 (2004-2018) of the English Longitudinal Study of Ageing were used. Global cognition (assessed by orientation, memory, and executive function) and daily functioning (calculated as the sum of impaired basic and instrumental activities of daily living) were measured in each wave. Incident diabetes was defined as glycated hemoglobin A1c ≥6.5% (47.5 mmol/mol), self-reported doctor diagnosis of diabetes, or glucose-lowering medication use during follow-up. RESULTS Among the 6,342 participants (mean age 65.0 years, 57.8% women) included, 576 participants (9.1%) with incident diabetes were identified during a median follow-up of 13.3 years. The annual rates of change in global cognition (β = -0.035 SD/year; 95% CI -0.054 to -0.015), orientation (-0.031 SD/year; -0.060 to -0.002), memory (-0.016 SD/year; -0.029 to -0.003), and executive function (-0.027 SD/year; -0.042 to -0.013) were accelerated after diabetes diagnosis compared with before the event. The postdiabetes annual changes in daily functioning (0.093 points/year; 95% CI 0.056-0.131) were also accelerated compared with the prediabetes diagnosis. However, the rate of cognitive and functional decline before the diabetes diagnosis in participants with future incident diabetes was similar to the rate in participants without diabetes. Also, no significant acute change was observed during its onset. CONCLUSIONS Incident diabetes is associated with accelerated cognitive and functional decline after, but not before, the event. We suggest careful monitoring for cognitive and physical dysfunction after a diabetes diagnosis.
Holographic entanglement entropies for Schwarzschild and Reisner-Nordström black holes in asymptotically Minkowski spacetimes

The holographic entanglement entropies (HEE) associated with four dimensional Schwarzschild and Reisner-Nordstrom black holes in asymptotically Minkowski spacetimes are investigated. Unlike the cases of asymptotically AdS spacetimes for which the boundaries are always taken at (timelike) conformal infinities, we take the boundaries at either large but finite radial coordinate (far boundary) or very close to the black hole event horizons (near horizon boundary). The reason for such choices is that such boundaries are similar to the conformal infinity of AdS spacetime in that they are all timelike, so that there may be some hope to define dual systems with ordinary time evolution on such boundaries. Our results indicate that, in the case of far boundaries, the leading order contribution to the HEEs come from the background Minkowski spacetime, however, the next to leading order contribution which arises from the presence of the black holes is always proportional to the black hole mass, which constitutes a version of the first law of the HEE for asymptotically flat spacetimes, and the higher order contributions are always negligibly small. In the case of near horizon boundaries, the leading order contribution to the HEE is always proportional to the area of the black hole event horizon, and the case of extremal RN black hole is distinguished from the cases of non-extremal black holes in that the minimal surface defining the HEE is completely immersed inside the boundary up to the second order in the perturbative expansion.
EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B

Background Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB. Methods In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50–800 mg and multiple ascending doses of 200–800 mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200–800 mg or placebo for 28 days. Results EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600 mg after single doses and up to 400 mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (Ctrough) approximately 20-fold above the protein-adjusted 50% effective concentration (EC50) for the dose range. Mean change in HBV RNA from baseline to Day 28 was −2.03, −1.67, −1.87, and −0.58 log U/mL in the 200 mg, 400 mg, 800 mg, and placebo CHB groups, respectively. Conclusions EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.