Miracle-dz/UniFAR-FTUs huggingface dataset:
NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8

Enhancing the intracellular labile iron pool (LIP) represents a powerful, yet untapped strategy for driving ferroptotic death of cancer cells. Here, we show that NRF2 maintains iron homeostasis by controlling HERC2 (E3 ubiquitin ligase for NCOA4 and FBXL5) and VAMP8 (mediates autophagosome-lysosome fusion). NFE2L2/NRF2 knockout cells have low HERC2 expression, leading to a simultaneous increase in ferritin and NCOA4 and recruitment of apoferritin into the autophagosome. NFE2L2/NRF2 knockout cells also have low VAMP8 expression, which leads to ferritinophagy blockage. Therefore, deletion of NFE2L2/NRF2 results in apoferritin accumulation in the autophagosome, an elevated LIP, and enhanced sensitivity to ferroptosis. Concordantly, NRF2 levels correlate with HERC2 and VAMP8 in human ovarian cancer tissues, as well as ferroptosis resistance in a panel of ovarian cancer cell lines. Last, the feasibility of inhibiting NRF2 to increase the LIP and kill cancer cells via ferroptosis was demonstrated in preclinical models, signifying the impact of NRF2 inhibition in cancer treatment.
Injuries in Youth Volleyball Players at a National Championship: Incidence, Risk Factors, and Mechanisms of Injury

Objective: To evaluate injury incidence rates, types, mechanisms, and potential risk factors in youth volleyball. Design: Prospective cohort. Setting: 2018 Canadian Youth National Volleyball Tournament. Participants: Thousand eight hundred seventy-six players [466 males, 1391 females, mean age 16.2 years (±1.26)] consented to participate (19.5%). Assessment of Risk Factors: Sex (male/female), age group, position, and underage players. Main Outcome Measures: Players completed a questionnaire (demographic information, injury, and concussion history). Medical attention injuries were recorded by tournament medical personnel through an injury report form (eg, mechanism and type). Injury was defined as any physical complaint seeking onsite medical attention. Concussion was defined using the fifth International Consensus. Injury rates adjusted for cluster by team were calculated by sex. Exploratory multivariable Poisson regression was used to analyze potential risk factors (eg, sex, age group, position, and underage players) for injury, adjusted for cluster by team and offset by athlete exposures (AEs). Results: There were 101 injuries in the 7-day tournament {IRFemale = 6.78 injuries/1000 AEs [95% confidence interval (CI), 5.27-8.72]; IRMale = 4.30 injuries/1000 AEs (95% CI, 2.55-7.24)}. Joint sprain (n = 29, 28.71%) and concussion (n = 26, 25.74%) were the most common. Most concussions were associated with ball-to-head contact (61.5%). There was no statistically significant difference in injury rate by sex (IRRF/M: 1.47; 95% CI, 0.80-2.69). The rates of injury in U14 were higher than U18 (IRRU14: 2.57; 95% CI, 1.11-5.98). Conclusions: Injury rates are high in youth volleyball tournament play, with the highest rates in U14. More research is needed to inform the development of volleyball-specific injury prevention strategies.
NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease

Rationale Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration–derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2–related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.
Acute and Postacute Clinical Characteristics of Coronavirus Disease 2019 in Children in Japan

Background: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. Methods: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. Results: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups 1–4 and 5–11 years of age, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). Conclusions: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.
Rare thermonuclear explosions in short-period cataclysmic variables, with possible application to the nova-like red variable in the Galaxy M31

A very bright nova with a peak luminosity significantly larger than the relevant Eddington luminosity might be initiated by a hydrogen shell flash on a very cold low-mass degenerate dwarf accreting matter from a close low-mass companion which fills its Roche lobe in a system with orbital period 80 minutes to 2 hours. Under appropriate conditions, which are calculated, the mass of accreted matter can be as large as 0.005 M ⊙ when the explosion occurs, and a luminosity larger than the Eddington limit may be generated by the frictional interaction between the matter in a dense common envelope and the interior stellar cores
Balanced crystal orbital overlap population : a tool for analysing chemical bonds in solids

A new tool for analysing theoretically the chemical bonding in solids is proposed. A balanced crystal orbital overlap population (BCOOP) is an energy resolved quantity which is positive for bonding states and negative for antibonding states, hence enabling a distinction between bonding and antibonding contributions to the chemical bond. Unlike the conventional crystal orbital overlap population (COOP), BCOOP handles correctly the situation of crystal orbitals being nearly linear dependent, which is often the case in the solid state. Also, BCOOP is much less basis set dependent than COOP. A BCOOP implementation within the full-potential linear muffin tin orbital method is presented and illustrated for Si, TiC and Ru. Thus, BCOOP is compared to the COOP and crystal orbital Hamilton population (COHP) for systems with chemical bonds ranging from metallic to covalent character.
INTERBAND DIELECTRIC PROPERTIES OF SOLIDS IN AN ELECTRIC FIELD.

Abstract : A general expression for the imaginary part of the one-electron interband dielectric function of a solid in the presence of an electric field is derived. The result is valid for all regions of k-space and explicitly takes into account the variation of the dipole matrix element and effective mass throughout the Brillouin zone. Under certain approximations the finite electric field dielectric function reduces to the convolution of the zero field dielectric function with an Airy function. This result can be used in conjunction with band structure calculations which have already been done in order to predict the line shape of the electroreflectance spectra as a function of electric field. The convolution expression reduces further at non-degenerate critical points, and the forms for the four types of critical points are presented. In certain instances it is possible to unfold the convolution integral and obtain the zero field dielectric function from either the finite field dielectric constant or the electroreflectance data at isolated critical points. (Author)
Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease

Significance The human spleen modulates the retention and elimination of abnormal red blood cells (RBCs) through inter-endothelial slits and erythrophagocytosis, thereby maintaining blood homeostasis. This balance can be severely disrupted by the increased number of aberrant RBCs under certain pathological conditions, such as in sickle cell disease (SCD). Hypoxia in the spleen can lead to severe consequences, as indicated by various degrees of sickling in SCD infants with ASSC. We present a unique, oxygen-mediated spleen-on-a-chip platform to study splenic retention and elimination of RBCs and investigate the homeostatic balance between these functions. Our results provide insights into how splenic sequestration and related crises occur in SCD.
A globally convergent augmented Lagrangian algorithm for optimization with general constraints and simple bounds

The global and local convergence properties of a class of augmented Lagrangian methods for solving nonlinear programming problems are considered. In such methods, simple bound constraints are treated separately from more general constraints and the stopping rules for the inner minimization algorithm have this in mind. Global convergence is proved, and it is established that a potentially troublesome penalty parameter is bounded away from zero.
In vivo protein kinase activity of SnRK1 fluctuates in Arabidopsis rosettes during light-dark cycles

Abstract Sucrose-nonfermenting 1 (SNF1)–related kinase 1 (SnRK1) is a central hub in carbon and energy signaling in plants, and is orthologous with SNF1 in yeast and the AMP-activated protein kinase (AMPK) in animals. Previous studies of SnRK1 relied on in vitro activity assays or monitoring of putative marker gene expression. Neither approach gives unambiguous information about in vivo SnRK1 activity. We have monitored in vivo SnRK1 activity using Arabidopsis (Arabidopsis thaliana) reporter lines that express a chimeric polypeptide with an SNF1/SnRK1/AMPK-specific phosphorylation site. We investigated responses during an equinoctial diel cycle and after perturbing this cycle. As expected, in vivo SnRK1 activity rose toward the end of the night and rose even further when the night was extended. Unexpectedly, although sugars rose after dawn, SnRK1 activity did not decline until about 12 h into the light period. The sucrose signal metabolite, trehalose 6-phosphate (Tre6P), has been shown to inhibit SnRK1 in vitro. We introduced the SnRK1 reporter into lines that harbored an inducible trehalose-6-phosphate synthase construct. Elevated Tre6P decreased in vivo SnRK1 activity in the light period, but not at the end of the night. Reporter polypeptide phosphorylation was sometimes negatively correlated with Tre6P, but a stronger and more widespread negative correlation was observed with glucose-6-phosphate. We propose that SnRK1 operates within a network that controls carbon utilization and maintains diel sugar homeostasis, that SnRK1 activity is regulated in a context-dependent manner by Tre6P, probably interacting with further inputs including hexose phosphates and the circadian clock, and that SnRK1 signaling is modulated by factors that act downstream of SnRK1.
Myrtus communis and Celastrol enriched plant cell culture extracts control together the pivotal role of Cutibacterium acnes and inflammatory pathways in acne

Acne is a multifactorial inflammatory disease of the pilosebaceous unit in which Cutibacterium acnes is one of the main triggers. A strong predominance of C. acnes phylotype IA1 is present in acne skin with higher biofilm organization and virulence, promoting local immuno‐inflammation, especially the Th17 pathway.
UNITED KINGDOM DATABASE STUDY OF INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX) FOR MACULAR EDEMA RELATED TO RETINAL VEIN OCCLUSION

Supplemental Digital Content is Available in the Text. A database study of dexamethasone implant in retinal vein occlusion found a comparable safety and efficacy outcomes to clinical trial results. The probability of intraocular pressure elevation increases with repeat injections and in phakic versus pseudophakic eyes. Purpose: To study the treatment patterns, visual outcomes and safety profile of intravitreal dexamethasone implant (IDI) used for the treatment of macular edema secondary to retinal vein occlusion. Methods: Up to 2 years of routinely collected anonymized data within electronic medical record systems were remotely extracted from 16 centers. The outcome measures include visual outcome, number of injections, and safety measures, including the rate of intraocular pressure (IOP) rise, frequency of IOP-lowering medication usage, and cataract surgery rates. Results: The study included 688 eyes (44.4%) with central retinal vein occlusion and 862 eyes (55.6%) with branch retinal vein occlusion; 1,250 eyes (80.6%) were treatment naive and 28% (275/989) had high IOP or were on IOP-lowering medications before IDI use. It was found that 31% (476) of eyes received two injections, and 11.7% (182) and 3.7% (58) of eyes received three and four injections, respectively. The mean baseline Snellen visual acuity improved from 20/125 to 20/40 after the first injection. The probability of cataract surgery was 15% at 24 months. The proportion of eyes with ≥10 mmHg change from baseline was higher in phakic (14.2%) compared with pseudophakic eyes (5.4%, P = 0.004). Three eyes required IOP filtering surgery (0.2%). Conclusion: The visual results of IDI in eyes with macular edema secondary to retinal vein occlusion in the real world are comparable to those of clinical trial setting. Increased IOP in eyes with preexisting ocular hypertension or glaucoma can be controlled with additional medical treatment. Intraocular pressure rise with IDI may be more frequent in phakic than in pseudophakic eyes.
Epidemiology and Economic Burden of Acute Infectious Gastroenteritis Among Adults Treated in Outpatient Settings in US Health Systems

INTRODUCTION: Acute infectious gastroenteritis (AGE) is a common reason for outpatient visits and hospitalizations in the United States. This study aimed to understand the demographic and clinical characteristics, common pathogens detected, health care resource utilization (HRU), and cost among adult outpatients with AGE visiting US health systems. METHODS: A retrospective cohort study was conducted using one of the largest hospital discharge databases (PINC AI Healthcare Database) in the United States. Adult patients (aged ≥18 years) with a principal diagnosis of AGE during an outpatient visit between January 1, 2016, and June 30, 2021, were included. Pathogen detection analysis was performed in those with microbiology data available. RESULTS: Among 248,896 patients, the mean age was 44.3 years (range 18–89+ years), 62.9% were female, and 68.5% were White. More than half (62.0%) of the patients did not have any preexisting comorbidity, and only 18.3% underwent stool workup at the hospital. Most patients (84.7%) were seen in the emergency department, and most (96.4%) were discharged home. Within 30 days of discharge, 1.0% were hospitalized, and 2.8% had another outpatient visit due to AGE. The mean cost of the index visit plus 30-day AGE-related follow-up was $1,338 per patient, amounting to $333,060,182 for the total study population. Among patients with microbiology data available (n = 12,469), common pathogens detected were Clostridioides difficile (32.2%), norovirus (6.3%), and Campylobacter spp. (4.0%). DISCUSSION: AGE is a common and costly disease affecting adults of all ages and more females than males, including individuals with or without baseline conditions in a hospital-based outpatient setting. C. difficile was the most common pathogen detected.
Stellar winds in molecular clouds

Strong stellar winds from O stars may dominate the evolution of compact H II regions in molecular clouds. For a cloud with density 10/sup 5/ cm/sup -3/, the pressure-driven bubble expands to about 0.2 pc radius in 10/sup 4/ yr, after which time the interior cools and wind momentum continues to drive the shell. Grains accumulate in a shell outside the bubble, radiating the star's UV Luminosity in the far-IR. The radio appearance of the H II shell should resemble a typical compact H II region, although the interpretation of its spectrum is slightly modified by the shell-like, rather than spherical, geometry. The hot interior cavity could possibly be distinguished by the detection of 3--4 keV X-rays or by the observation of their effects on the ionization stages of the H II region through IR lines of (Ar III), (S IV), (Ne III), or (ArV). When the star explodes after several million years, the initial expansion of the supernova remnant will differ from that expected for a homogeneous medium, and the IR emission will be dramatically altered.
Testing and Estimation for a Circular Stationary Model

Abstract : Tests are conducted for x, a random vector having a p-variate normal distribution with a mean vector and specifically defined covariance matrix. On the basis of N independent observations on x, likelihood ratio tests of various hypotheses are considered. Tests are made (1) for symmetries in the covariance structure and (2) for means given that the covariance matrix is circular; (3) other tests enable means and covariances to be investigated simultaneously. Large sample results are obtained for both the central and noncentral cases. The structure of symmetry and circularity offers a more general model than that of the intra-class correlation or sphericity models previously considered. (Author)
Pentacene thin film transistors on inorganic dielectrics: Morphology, structural properties, and electronic transport

The structural and transport properties of evaporated pentacene organic thin film transistors (TFTs) are reported, and they show the influence of the deposition conditions with different inorganic dielectrics. Dielectrics compatible with large area fabrication were explored to facilitate low cost electronics on glass or flexible plastic substrates. X-ray diffraction and atomic force microscopy show a clear correlation between the morphology and the structure of the highly polycrystalline films for all dielectrics investigated. The roughness of the dielectric has a distinct influence on the morphology and the structural properties, whereas the films on smooth thermal oxide are in general highly ordered and independent of the deposition conditions. The ordered films exhibit a “thin film” and a bulk phase, and the bulk phase volume fraction increases with the deposition temperature and the film thickness. Careful control of the deposition conditions gives virtually identical films on thermal oxide and silico.
Iterative learning control of SOFC based on ARX identification model

This paper presents an application of iterative learning control (ILC) technique to the voltage control of solid oxide fuel cell (SOFC) stack. To meet the demands of the control system design, an autoregressive model with exogenous input (ARX) is established. Firstly, by regulating the variation of the hydrogen flow rate proportional to that of the current, the fuel utilization of the SOFC is kept within its admissible range. Then, based on the ARX model, three kinds of ILC controllers, i.e. P-, PI-and PD-type are designed to keep the voltage at a desired level. Simulation results demonstrate the potential of the ARX model applied to the control of the SOFC, and prove the excellence of the ILC controllers for the voltage control of the SOFC.
Evaluating associations between level of trauma care and outcomes of patients with specific severe injuries: A systematic review and meta-analysis

Top levels of trauma care are associated with improved survival for major trauma patients. This has been reproduced when combining populations with specific injuries. See link below. #major trauma center #critical care #outcome assessment BACKGROUND Trauma networks have multiple designated levels of trauma care. This classification parallels concentration of major trauma care, creating innovations and improving outcome measures. OBJECTIVES The objective of this study is to assess associations of level of trauma care with patient outcomes for populations with specific severe injuries. METHODS A systematic literature search was conducted using six electronic databases up to April 19, 2022 (PROSPERO CRD42022327576). Studies comparing fatal, nonfatal clinical, or functional outcomes across different levels of trauma care for trauma populations with specific severe injuries or injured body region (Abbreviated Injury Scale score ≥3) were included. Two independent reviewers included studies, extracted data, and assessed quality. Unadjusted and adjusted pooled effect sizes were calculated with random-effects meta-analysis comparing Level I and Level II trauma centers. RESULTS Thirty-five studies (1,100,888 patients) were included, of which 25 studies (n = 443,095) used for meta-analysis, suggesting a survival benefit for the severely injured admitted to a Level I trauma center compared with a Level II trauma center (adjusted odds ratio [OR], 1.15; 95% confidence interval [CI], 1.06–1.25). Adjusted subgroup analysis on in-hospital mortality was done for patients with traumatic brain injuries (OR, 1.23; 95% CI, 1.01–1.50) and hemodynamically unstable patients (OR, 1.09; 95% CI, 0.98–1.22). Hospital and intensive care unit length of stay resulted in an unadjusted mean difference of −1.63 (95% CI, −2.89 to −0.36) and −0.21 (95% CI, −1.04 to 0.61), respectively, discharged home resulted in an unadjusted OR of 0.92 (95% CI, 0.78–1.09). CONCLUSION Severely injured patients admitted to a Level I trauma center have a survival benefit. Nonfatal outcomes were indicative for a longer stay, more intensive care, and more frequently posthospital recovery trajectories after being admitted to top levels of trauma care. Trauma networks with designated levels of trauma care are beneficial to the multidisciplinary character of trauma care. LEVEL OF EVIDENCE Systematic review and meta-analysis; Level III.