Miracle-dz/UniFAR-FTUs huggingface dataset:
Cooperative genetic networks drive embryonic stem cell transition from naïve to formative pluripotency

In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large‐scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre‐ to post‐implantation epiblast in utero. We identified 496 naïve state‐associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition.
Concomitant thoracoscopic left cardiac sympathectomy and RVOT epicardial ablation of the arrhythmogenic substrate in a patient with Long QT and Brugada syndromes related to uncommon sodium channel beta‐subunit mutation

Any alterations related to generation and/or conduction of action potentials in the cardiac tissue can result in the origin and propagation of cardiac arrhythmias.1 In many cases, heritable mutations in genes that encode heart ion channels are the underlying cause of arrhythmias,2 sometimes in patients with a structurally normal heart. Brugada syndrome (BrS) is now associated with >500 genetic variants of ion channels, but the majority of cases does not have a definite genetic diagnosis.3 Long QT syndrome (LQTS) has a much longer history and is associated with at least 17 genes. Some genetic mutations related to sodium ion currents are in common between the two syndromes. Among them, the most frequent is the alteration of the SCN5A gene, which encodes for the α-subunit of sodium channels; fewer common mutations may relate to the sodium channel β-subunit, such as mutations in the SCN5B gene.1,4 Phenotypic overlaps of the long QT syndrome and Brugada syndrome are already reported in literature.5 We report a case of overlap of Brugada and LQT Syndrome related to uncommon sodium channel β-subunit mutation, treated surgically with a sympathectomy and an epicardial thoracoscopic ablation of the RVOT and anterior RVwall.6 2 CASE REPORT
Effect of steps on dislocations in CVD diamond grown on {001} substrates

Single crystal CVD synthetic diamond samples grown on (001) substrates have been studied using X-ray topography, photoluminescence imaging, cathodoluminescence imaging and transmission electron microscopy. X-ray section topographs sampling a plane very close to the surface of a (010) cross-sectional slice show contrast that is closely correlated with photoluminescence image contrast relating to differences in incorporation of point defects on step risers and terraces during growth. The point defect content is too low to influence X-ray topography contrast and therefore the correlation suggests a difference between the dislocation content for terrace and riser growth. Dislocations imaged in cathodoluminescence have been observed to follow paths that are strongly influenced by step flow during growth. Transmission electron micrographs show [001] dislocations with sections of 60° or edge dislocations in configurations consistent with formation as a result of step flow growth. It is proposed that a passing riser can cause dislocations to switch from [001] to [101] line direction when this minimises the increase in the energy associated with the dislocation as riser growth proceeds. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Episodic processes in moral decisions: Evidence from medial temporal lobe amnesia

Theoretical accounts of moral decision making imply distinct ways in which episodic memory processes may contribute to judgments about moral dilemmas that entail high conflict between a harmful action and a greater good resulting from such action. Yet, studies examining the status of moral judgment in amnesic patients with medial temporal lobe (MTL) lesions have yielded inconsistent results. To examine whether and how episodic processes contribute to high conflict moral decisions, amnesic patients with MTL damage and control participants were asked to judge the moral acceptability of a harmful action across two conditions that differed in the framing of the moral question. We predicted that personal (but not abstract) framing would engage episodic processes involved in mental simulation, yielding a selective impairment in MTL patients in the personal framing condition. This prediction was not confirmed as neither patients nor controls were influenced by the framing of the moral question. With the exception of a patient whose lesion extended into the amygdala bilaterally, patients were less willing than controls to endorse the utilitarian option, rejecting the harmful action despite its beneficial outcome. They also rated actions as emotionally more intense than did controls. These findings suggest that episodic processes involved in mental simulation are necessary to prospectively evaluate action‐outcome contingencies.
Modulation of cigarette smoke extract-induced human bronchial epithelial damage by eucalyptol and curcumin

Smoking is one of the most important leading death cause worldwide. From a toxicological perspective, cigarette smoke serves hazards especially for the human being exposed to passive smoke. Over the last decades, the effects of natural compounds on smoking-mediated respiratory diseases such as COPD, asthma, and lung cancer have been under investigation, as well as the mechanistic aspects of disease progression. In the present study, the protective mechanism of eucalyptol (EUC), curcumin (CUR), and their combination on BEAS-2B cells were investigated in vitro to understand their impact on cell death, oxidative cell injury, and inflammatory response induced by 3R4F reference cigarette extract (CSE). According to the present findings, EUC, CUR, and their combination improved cell viability, attenuated CSE-induced apoptosis, and LC3B expression. Further, CSE-induced oxidative damage and inflammatory response in human bronchial epithelial cells were remarkably reduced by the combination treatment through modification of enzymatic antioxidant activity, GSH, MDA, and intracellular ROS levels as well as nitrite and IL-6 levels. In addition, nuclear translocation of Nrf2, a regulatory protein involved in the indirect antioxidant response, was remarkably up-regulated with the combination pre-treatment. In conclusion, EUC and CUR in combination might be a potential therapeutic against smoking-induced lung diseases through antioxidant and inflammatory pathways and results represent valuable background for future in vivo pulmonary toxicity studies.
Aqueous polymerization of methyl methacrylate initiated by Ce(IV)–alcohol redox systems: Effect of acid concentration and additives

Polymerization of methyl methacrylate (MMA) initiated by ceric ammonium nitrate in combination with alcohols, isopropyl and, isobutyl alcohol, has been studied in aqueous nitric acid. The effect of nitric acid and nitrate ion concentrations on the initial rate of polymerization as well as on that of ceric ion consumption and on polymer molecular weight has been investigated. The rate of polymerization initially rapidly to a maximum with increasing nitric acid concentration at constant nitrate ion concentration, and then, decreased at higher acid concentrations. The rate of ceric ion consumption increased on increasing the acid concentration. A fall in both the rates was observed as the nitrate ion concentration increased, and when acid concentration was kept constant. Average-molecular weights decreased with increasing the acid concentration; whereas they increased with increasing that of nitrate ion. The effect of certain water-miscible organic solvents has also been studied. Both the rates increased in their presence, whereas the molecular weight underwent a decrease
Trends, structural changes, and assessment of time series models for forecasting hospital discharge due to death at a Mexican tertiary care hospital

Background Data on hospital discharges can be used as a valuable instrument for hospital planning and management. The quantification of deaths can be considered a measure of the effectiveness of hospital intervention, and a high percentage of hospital discharges due to death can be associated with deficiencies in the quality of hospital care. Objective To determine the overall percentage of hospital discharges due to death in a Mexican tertiary care hospital from its opening, to describe the characteristics of the time series generated from the monthly percentage of hospital discharges due to death and to make and evaluate predictions. Methods This was a retrospective study involving the medical records of 81,083 patients who were discharged from a tertiary care hospital from April 2007 to December 2019 (first 153 months of operation). The records of the first 129 months (April 2007 to December 2017) were used for the analysis and construction of the models (training dataset). In addition, the records of the last 24 months (January 2018 to December 2019) were used to evaluate the predictions made (test dataset). Structural change was identified (Chow test), ARIMA models were adjusted, predictions were estimated with and without considering the structural change, and predictions were evaluated using error indices (MAE, RMSE, MAPE, and MASE). Results The total percentage of discharges due to death was 3.41%. A structural change was observed in the time series (March 2009, p>0.001), and ARIMA(0,0,0)(1,1,2)12 with drift models were adjusted with and without consideration of the structural change. The error metrics favored the model that did not consider the structural change (MAE = 0.63, RMSE = 0.81, MAPE = 25.89%, and MASE = 0.65). Conclusion Our study suggests that the ARIMA models are an adequate tool for future monitoring of the monthly percentage of hospital discharges due to death, allowing us to detect observations that depart from the described trend and identify future structural changes.
Experience of implementing and delivering group consultations in UK general practice: a qualitative study

Background Group consultations are a relatively new concept in UK primary care and are a suggested solution to current workload pressures in general practice. Little is known about the experience of implementing and delivering this approach from staff and organisational perspectives. Aim To explore the experience of implementing and delivering group consultations in general practice. Design and setting Qualitative telephone interview study. Method Topic guides explored the perspectives and experiences of general practice staff on the implementation and delivery of group consultations. Data analysis adopted principles of the Framework Method underpinned by Normalisation Process Theory. Results Interviews were conducted with 8 GPs, 8 practice nurses, 1 nurse associate, 1 practice pharmacist, 1 deputy practice manager, and 1 healthcare assistant. Four themes were identified: sense making of group consultations; the work associated with initiating group consultations; the experiences of operationalising group consultations; and sustaining change. Group consultations made sense to participants as a mechanism to reduce burden on primary care, enhance multidisciplinary working, and provide patient-centred care. Implementation required strong leadership from a ‘champion’, and a facilitator had a pivotal role in operationalising the approach. The associated workload was often underestimated. Barriers to embedding change included achieving whole practice buy-in, competing practice priorities, and system-level flexibility. Conclusion General practice clinicians enjoyed group consultations, yet significant work is required to initiate and sustain the approach. An implementation plan considering leadership, roles and responsibilities, and wider organisational support is required at the outset. Further research or evaluation is needed to measure process outcomes.
Viral evolution sustains a dengue outbreak of enhanced severity

ABSTRACT Compared to the previous 2013–2014 outbreak, dengue 2016–2017 outbreak in New Caledonia was characterized by an increased number of severe forms associated with hepatic presentations. In this study, we assessed the virological factors associated with this enhanced severity. Whole-genome sequences were retrieved from dengue virus (DENV)-1 strains collected in 2013–2014 and from severe and non-severe patients in 2016–2017. Fitness, hepatic tropism and cytopathogenicity of DENV 2016–2017 strains were compared to those of 2013–2014 strains using replication kinetics in the human hepatic cell line HuH7. Whole-genome sequencing identified four amino acid substitutions specific to 2016–2017 strains and absent from 2013–2014 strains. Three of these mutations occurred in predicted T cell epitopes, among which one was also a B cell epitope. Strains retrieved from severe forms did not exhibit specific genetic features. DENV strains from 2016–2017 exhibited a trend towards reduced replicative fitness and cytopathogenicity in vitro compared to strains from 2013–2014. Overall, the 2016–2017 dengue outbreak in New Caledonia was associated with a viral genetic evolution which had limited impact on DENV hepatic tropism and cytopathogenicity. These mutations, however, may have modified DENV strains antigenicity, altering the anti-DENV immune response in some patients, in turn favoring the development of severe forms. Trial registration: ClinicalTrials.gov identifier: NCT04615364.
90K predicts the prognosis of glioma patients and enhances tumor lysate-pulsed DC vaccine for immunotherapy of GBM in vitro

Objectives: This study aimed to investigate the relationship between 90K expression with glioma malignancy and prognosis. Additionally, the enhancement effect of 90K in the Dendritic cell (DC) vaccine for Immunotherapy of glioblastoma (GBM) was evaluated in vitro. Methods: The expression of 90K protein in glioma tissues was detected by western blot. The relationship between the 90K expression and the tumor grade as well as the prognosis of patients was further analyzed by mining TCGA and CGGA database. The concentration of IL-12p70 and IL-10 was detected by ELISA. T lymphocyte proliferation and lethal effect of cytotoxic T cell (CTL) were detected by CCK-8. Results: The expression of 90K was significantly higher in glioma than normal tissue and increased with tumor grade (P< 0.05). Higher 90K expression was observed in IDH wildtype glioma than IDH mutant and predicted worse overall survival for glioma patients. The concentration of IL-12p70 and IFN-γ was the highest in the Apoptosis U251-90K-DC group, in which group the ability to kill U251 cells by CTL was also the strongest. Conclusion: 90K was a useful biomarker for glioma malignancy and patient prognosis. The appearance of 90K enhanced the effect of Apoptosis U251-DC vaccine for immunotherapy of GBM.
Effects of Home-Delivered Meals on Older People’s Protein Intake, Physical Performance, and Health-Related Quality of Life: The Power Meals Randomized Controlled Trial

Abstract This trial examined the effectiveness of an 8-week home meal service on protein and other nutrient intake, physical performance (PP) and health related quality of life (HRQoL) among older people living at home (≥65 years; home care clients, caregivers and care recipients). Participants were randomized into three groups; (1) protein-rich meal, snack, and bread (INT1), (2) regular meal (INT2) and (3) control group. Nutrient intake was assessed with 3-day food diaries, PP with Short Physical Performance Battery (SBBP) and HRQoL with 15 dimensional Health-related quality of life instrument. Total of 67 (59.7% women, mean age 78.2 years) participants (n = 22 INT1, n = 24 INT2, n = 21 CG) completed the trial. At baseline, mean protein intake was 0.92 (SD 0.32) g/kg adjusted body weight (aBW)/d. At 8 weeks, protein-rich home meal service in INT1 increased protein intake (+ 0.11 (95%CI −0.01 to 0.21) g/kg aBW/d, 9.4 (95%CI 1.0 to 17.8) g/d) compared to other groups. It also increased calcium intake (+169.9 (95%CI 26 to 314) mg/d) and improved results in Sit-to-Stand Test (-4.8 (95%CI −6.8 to −2.7) sec) in INT1 compared to CG. Both home meal services increased saturated fat intake (INT1; 4.6 (95%CI 1.0–8.2) g/d, INT2;7.8 (95%CI 1.9 to 13.7)g/d) and decreased salt intake (INT1;-2330.9 (95%CI −2998 to -1664) mg/d, INT2; −2371.9 (95%CI −3399 to -1345) mg/d) compared to CG. There was no effect on overall HRQoL.
Surface Stickiness of Drops of Carbohydrate and Organic Acid Solutions During Convective Drying: Experiments and Modeling

Abstract Drying kinetics of low molecular weight sugars such as fructose, glucose, sucrose and organic acid such as citric acid and high molecular weight carbohydrate such as maltodextrin (DE 6) were determined experimentally using single drop drying experiments as well as predicted numerically by solving the mass and heat transfer equations. The predicted moisture and temperature histories agreed with the experimental ones within 6% average relative (absolute) error and average difference of ± 1°C, respectively. The stickiness histories of these drops were determined experimentally and predicted numerically based on the glass transition temperature (T g ) of surface layer. The model predicted the experimental observations with good accuracy. A nonsticky regime for these materials during spray drying is proposed by simulating a drop, initially 120 µm in diameter, in a spray drying environment.
Synchrotron phase‐contrast imaging applied to the anatomical study of the hand and its vascularization

Microscopic anatomical study of the hand requires difficult or destructive dissection techniques for each anatomical structure. Synchrotron phase‐contrast imaging (sPCI) allows us to study precisely, at a microscopic resolution and in a nondestructive approach, the soft tissues and bone structures within a single 3D image. Therefore, we aimed to assess the capacity of sPCI to study the arterial anatomy of the hand and digits in human cadavers for anatomical purposes. A non‐injected hand from an embalmed body was imaged using sPCI at 21‐µm pixel size. The vascularization and innervation of the hands were virtually reconstructed at 84‐µm resolution, and the medial neurovascular bundle of the third digit at 21 µm. The thinner‐most distal structures were observed and reported. The diameter and thickness of the vascular and neural structures were defined on 2D computed tomographic axial projections, and using a granulometry method coupled to the 3D reconstructions. The vascularization of the hand was visible from the radial and ulnar arteries to the distal digital transverse anastomoses. The thinnest structure observed was the anastomotic arterial network around the proper palmar digital nerve. The latter emerged from the proper palmar digital artery and vascularized the nerve around its whole length and circumference. The perineural arterioles individualizable at this resolution had a diameter of 66–309 µm. In conclusion, sPCI allows both the arterial and neural anatomy of the hand to be studied at the same time, as well as the anatomical interactions between both networks. It facilitates the study of structures that have different sizes, diameters, thickness, and histological origin with great precision, in a noninvasive way, and using a single technique.
Image similarity‐based cardiac rhythm device identification from X‐rays using feature point matching

Identifying the manufacturer and the type of cardiac implantable electronic devices (CIEDs) is important in emergent clinical settings. Recent studies have illustrated that artificial neural network models can successfully recognize CIEDs from chest X‐ray images. However, all existing methods require a vast amount of medical data to train the classification model. Here, we have proposed a novel method to retrieve an identical CIED image from an image database by employing the feature point matching algorithm.
eHealth Applications to Support Independent Living of Older Persons: Scoping Review of Costs and Benefits Identified in Economic Evaluations

Background eHealth applications are constantly increasing and are frequently considered to constitute a promising strategy for cost containment in health care, particularly if the applications aim to support older persons. Older persons are, however, not the only major eHealth stakeholder. eHealth suppliers, caregivers, funding bodies, and health authorities are also likely to attribute value to eHealth applications, but they can differ in their value attribution because they are affected differently by eHealth costs and benefits. Therefore, any assessment of the value of eHealth applications requires the consideration of multiple stakeholders in a holistic and integrated manner. Such a holistic and reliable value assessment requires a profound understanding of the application’s costs and benefits. The first step in measuring costs and benefits is identifying the relevant costs and benefit categories that the eHealth application affects. Objective The aim of this study is to support the conceptual phase of an economic evaluation by providing an overview of the relevant direct and indirect costs and benefits incorporated in economic evaluations so far. Methods We conducted a systematic literature search covering papers published until December 2019 by using the Embase, Medline Ovid, Web of Science, and CINAHL EBSCOhost databases. We included papers on eHealth applications with web-based contact possibilities between clients and health care providers (mobile health apps) and applications for self-management, telehomecare, telemedicine, telemonitoring, telerehabilitation, and active healthy aging technologies for older persons. We included studies that focused on any type of economic evaluation, including costs and benefit measures. Results We identified 55 papers with economic evaluations. These studies considered a range of different types of costs and benefits. Costs pertained to implementation activities and operational activities related to eHealth applications. Benefits (or consequences) could be categorized according to stakeholder groups, that is, older persons, caregivers, and health care providers. These benefits can further be divided into stakeholder-specific outcomes and resource usage. Some cost and benefit types have received more attention than others. For instance, patient outcomes have been predominantly captured via quality-of-life considerations and various types of physical health status indicators. From the perspective of resource usage, a strong emphasis has been placed on home care visits and hospital usage. Conclusions Economic evaluations of eHealth applications are gaining momentum, and studies have shown considerable variation regarding the costs and benefits that they include. We contribute to the body of literature by providing a detailed and up-to-date framework of cost and benefit categories that any interested stakeholder can use as a starting point to conduct an economic evaluation in the context of independent living of older persons.