Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of a modified renal angina index for AKI prediction in critically ill adults.

BACKGROUND The renal angina index (RAI) is a useful tool for risk-stratification of acute kidney injury (AKI) in critically ill children. We evaluated the performance of a modified adult RAI (mRAI) for the risk-stratification of AKI in critically ill adults. METHODS We used two independent ICU cohorts: 13,965 adult patients from the University of Kentucky (UKY) and 4,789 from UT Southwestern (UTSW). The mRAI included: diabetes, presence of sepsis, mechanical ventilation, pressor/inotrope use, percentage change in SCr in reference to admission SCr (ΔSCr), and fluid overload percentage within the first day of ICU admission. The primary outcome was AKI stage ≥2 at Day 2-7. Performance and reclassification metrics were determined for the mRAI score compared to ΔSCr alone. RESULTS The mRAI score outperformed ΔSCr and readjusted probabilities to predict AKI stage ≥2 at Day 2-7: C-statistic: UKY 0.781 vs. 0.708 (IDI 2.2%) and UTSW 0.766 vs. 0.696 (IDI 1.8%), p<0.001 for both. In the UKY cohort, only 3.3% of patients with mRAI score <10 had the AKI event, while 16.4% of patients with mRAI score of ≥ 10 had the AKI event (NPV 96.8%). Similar findings were observed in the UTSW cohort as part of external validation. CONCLUSIONS In critically ill adults, the adult mRAI score determined within the first day of ICU admission outperformed changes in SCr for the prediction of AKI stage ≥2 at Day 2-7 of ICU stay. The modified adult RAI is a feasible tool for AKI risk-stratification in adult patients in the ICU.
The network structure of schema modes

Abstract A fundamental question in psychotherapy is whether interventions should target client problems (i.e., problem‐focused approaches) or client strengths (i.e., strength‐focused approaches). In this study, we first propose to address this question from a network perspective on schema modes (i.e., healthy or dysfunctional patterns of co‐occurring emotions, cognitions, and behaviours). From this perspective, schema modes mutually influence each other (e.g., healthy modes reduce dysfunctional modes). Recent evidence suggests that changes in modes that are strongly associated to other modes (i.e., central modes) could be associated with greater treatment effects. We therefore suggest research should investigate the relative centrality of healthy and dysfunctional modes. To make an exploratory start, we investigated the cross‐sectional network structure of schema modes in a clinical (comprising individuals diagnosed with paranoid, narcissistic, histrionic, and Cluster C personality disorders) and non‐clinical sample. Results showed that, in both samples, the Healthy Adult was significantly less central than several dysfunctional modes (e.g., Undisciplined Child and Abandoned and Abused Child). Although our study cannot draw causal conclusions, this finding could suggest that weakening dysfunctional modes (compared to strengthening the Healthy Adult) might be more effective in decreasing other dysfunctional modes. Our study further indicates that several schema modes are negatively associated, which could suggest that decreasing one might increase another. Finally, the Healthy Adult was among the modes that most strongly discriminated between clinical and non‐clinical individuals. Longitudinal and experimental research into the network structure of schema modes is required to further clarify the relative influence of schema modes.
From Spark Ignition to Flame Initiation

ABSTRACT The process of spark ignition and the subsequent flame propagation in an internal combustion engine have been investigated. A unique theoretical model which considers the various physical and chemical phenomena associated with the ignition process has been developed. It employs a two-dimensional cylindrical coordinate system and assumes axial and radial symmetry. The model employs also a detailed chemical reaction scheme for a methane-air mixture which contains 29 chemical species and 97 reactions. The thermodynamic and transport properties are evaluated by using statistical thermodynamics and molecular theory approach while including the various energy modes stored in the mixture particles. The appropriate conservation equations are solved numerically by using an integration of the PHOENICS and the CHEMKIN codes. It was concluded from the numerical results that the spark kernel growth can be described as a two-step process. The early short stage (1–5 μs), which involves a pressure wave emission,.
Concentrations of Organic Acids and Soluble Sugars in Juices from Nordic Berries

Comprehensive information was gathered on acid and sugar concentrations of six wild berries (bilberry, lingonberry, cranberry, cloudberry, red raspberry and black crowberry) and five cultivated berries [blackcurrant, whitecurrant, redcurrant, gooseberry (red) and strawberry], all grown in Finland. The main acids of the berry juices were invariably citric and malic acids, even though their concentrations varied widely from one berry to another (2.9-16.2 and 3.3-24.7 g l -1 , respectively). In addition, juices of lingonberry, cranberry, cloudberry and black crowberry contained benzoic acid (0.1-0.7 g l -1 ). The main sugars of the investigated berry juices were fructose (18.0- 57.2 g l -1 ) and glucose (22.2-50.0 g l -1 ). Most of the berries contained also sucrose (0.2-5.1 g l -1 ). The data enable equivalent comparison of Nordic berries and underline the wide variation in their acid and sugar content and so the possibilities for production of numerous organoleptic profiles.
Rac Family Small GTPase 3 Correlates with Progression and Poor Prognosis in Bladder Cancer.

Bladder cancer (BC) is a common genitourinary malignancy worldwide. However, the molecular pathogenesis of BC remains unclear. The current study conducted bioinformatic analyses to discover key genes involved in BC progression. A total of 375 differentially expressed genes (DEGs) were screened in the GEO database and The Cancer Genome Atlas (TCGA) database, which were further evaluated by the core level in the protein-protein interaction network. RAC3 (Rac family small GTPase 3), one of the top hub genes, was focused on for its gene expression and prognostic value in BC. Immunohistochemical assays indicated elevated RAC3 levels in BC tissues compared with normal tissues. Overexpression of RAC3 expression was closely associated with poor differentiation (p = 0.035), advanced TNM stage (p = 0.014), lymph metastasis (p = 0.033), and recurrence (p < 0.001). Kaplan-Meier and Cox proportional hazards analyses demonstrated that high RAC3 expression indicated poor survival of BC patients, which could serve as an independent prognostic factor for overall survival (HR = 3.159, p = 0.023) and disease-free survival (HR = 4.633, p = 0.002). Moreover, bioinformatic analyses indicated that RAC3 might be correlated with malignant phenotypes and immune infiltration of BC. Taken together, RAC3 could be a novel prognostic biomarker for BC.
SARS-CoV2 Infection in Children with Liver Transplant and Native Liver Disease: An International Observational Registry Study.

OBJECTIVE Increased mortality risk due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. METHODS In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. RESULTS Patients with LD were more likely to require admission (70% vs 43% LT, p = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, p = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and one patient died. Bivariable logistic-regression analysis found that patients with non-alcoholic fatty liver disease (NAFLD) (OR 5.6, p = 0.02) and LD (OR 6.1, p = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). CONCLUSIONS Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.
Osmolality of Commonly Used Oral Medications in the Neonatal Intensive Care Unit.

OBJECTIVE The administration of hyperosmolar oral products in neonates has been associated with gastrointestinal complications. The American Academy of Pediatrics recommends a maximum osmolality of 450 mOsm/kg for formulas and enteral nutrition for term infants, and recent studies reported intolerance to enteral nutrition with osmolality above 500 mOsm/kg in low birthweight infants. The osmolality of medications administered to neonates is often not available in the literature or from manufacturers. The purpose of this study was to determine the osmolality of oral medications commonly administered to neonates in the NICU. METHODS Fifty-two oral medications were chosen for this study, including solutions, suspensions, syrups, elixirs, and intravenous solutions administered orally. The osmolality of each medication was measured in triplicate by using freezing point depression. RESULTS Thirty-seven of the 43 medications with measurable values (86.1%) had an osmolality greater than 500 mOsm/kg, and 6 medications (14%) had an osmolality less than 500 mOsm/kg. Nine medications did not result in a value. CONCLUSIONS Our study provides osmolality data on oral medications commonly used in neonates with most oral medications having an osmolality greater than 500 mOsm/kg.
N(6)‐methyladenosine‐binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay

N6‐methyladenosine (m6A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B‐cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m6A modification in human NPC biopsies, patient‐derived xenograft tissues, and cells at different EBV infection stages. m6A‐modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m6A‐dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post‐transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m6A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV‐associated cancers.
Decompensation in Direct-Acting Antiviral Cured Hepatitis C Virus Compensated Patients With Clinically Significant Portal Hypertension: Too Rare to Warrant Universal Β-Blocker Therapy

Nonselective β-blockers improve decompensation-free survival in viremic hepatitis C virus compensated cirrhotic patients with clinically significant portal hypertension, but their protective role after sustained virological response by direct-acting antiviral (DAA) is undefined. We evaluated the incidence of decompensation in DAA-cured Child-A patients without high-risk varices. During the 49-month (12–60) follow-up, only one of 148 patients decompensated (ascites), with a 4-year cumulative risk of 1%, but decompensation was associated with hepatocellular carcinoma. The risk of decompensation in DAA cured hepatitis C virus compensated Child-A cirrhotic patients with clinically significant portal hypertension but without high-risk varices is negligible; thus, questioning the need for nonselective β-blocker treatment in this setting (see Visual abstract, Supplemental Digital Content, 1, http://links.lww.com/AJG/B861).
Incidence, duration and risk factors associated with delayed and missed diagnostic opportunities related to tuberculosis: a population-based longitudinal study

Objectives Missed opportunities to diagnose tuberculosis are costly to patients and society. In this study, we (1) estimate the frequency and duration of diagnostic delays among patients with active pulmonary tuberculosis and (2) determine the risk factors for experiencing a diagnostic delay. Design A retrospective cohort study of patients with tuberculosis using longitudinal healthcare encounters prior to diagnosis. Setting Commercially insured enrollees from the Commercial Claims and Encounters or Medicare Supplemental IBM Marketscan Research Databases, 2001–2017. Participants All patients diagnosed with, and receiving treatment for, pulmonary tuberculosis, enrolled at least 365 days prior to diagnosis. Primary and secondary outcome measures We estimated the number of visits with tuberculosis-related symptoms prior to diagnosis that would be expected to occur in the absence of delays and compared this estimate to the observed pattern. We computed the number of visits representing a delay and used a simulation-based approach to estimate the number of patients experiencing a delay, number of missed opportunities per patient and duration of delays (ie, time between diagnosis and earliest missed opportunity). We also explored risk factors for missed opportunities. Results We identified 3371 patients diagnosed and treated for active tuberculosis that could be followed up for 1 year prior to diagnosis. We estimated 77.2% (95% CI 75.6% to 78.7%) of patients experienced at least one missed opportunity; of these patients, an average of 3.89 (95% CI 3.65 to 4.14) visits represented a missed opportunity, and the mean duration of delay was 31.66 days (95% CI 28.51 to 35.11). Risk factors for delays included outpatient or emergency department settings, weekend visits, patient age, influenza season presentation, history of chronic respiratory symptoms and prior fluoroquinolone use. Conclusions Many patients with tuberculosis experience multiple missed diagnostic opportunities prior to diagnosis. Missed opportunities occur most commonly in outpatient settings and numerous patient-specific, environment-specific and setting-specific factors increase risk for delays.
Combining ecstasy and ethanol: higher risk for toxicity? A review

Abstract Ecstasy use is commonly combined with ethanol consumption. While combination drug use in general is correlated with a higher risk for toxicity, the risk of the specific combination of ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) and ethanol is largely unknown. Therefore, we have reviewed the literature on changes in MDMA pharmacokinetics and pharmacodynamics due to concurrent ethanol exposure in human, animal and in vitro studies. MDMA pharmacokinetics appear unaffected: the MDMA blood concentration after concurrent exposure to MDMA and ethanol was comparable to lone MDMA exposure in multiple human placebo-controlled studies. In contrast, MDMA pharmacodynamics were affected: locomotor activity increased and body temperature decreased after concurrent exposure to MDMA and ethanol compared to lone MDMA exposure. Importantly, these additional ethanol effects were consistently observed in multiple animal studies. Additional ethanol effects have also been reported on other pharmacodynamic aspects, but are inconclusive due to a low number of studies or due to inconsistent findings. These investigated pharmacodynamic aspects include monoamine brain concentrations, neurological (psychomotor function, memory, anxiety, reinforcing properties), cardiovascular, liver and endocrine effects. Although only a single or a few studies were available investigating these aspects, most studies indicated an aggravation of MDMA-induced effects upon concurrent ethanol exposure. In summary, concurrent ethanol exposure appears to increase the risk for MDMA toxicity. Increased toxicity is due to an aggravation of MDMA pharmacodynamics, while MDMA pharmacokinetics is largely unaffected. Although a significant attenuation of the MDMA-induced increase of body temperature was observed in animal studies, its relevance for human exposure remains unclear.
Assessment of Carbohydrate Availability, Fermentability, and Food Energy Value in Humans Using Measurements of Breath Hydrogen

Abstract Measurements in humans of their breath hydrogen is sometimes used to assess the availability, fermentability, and food energy value of carbohydrates that, to an unknown extent, resists small intestinal digestion and fermentation in the large intestine. Here I outline that the method is utterly flawed and conclude that it is unsuitable for making claims as to the availability, fermentability, and food energy value of carbohydrates. More traditional methods, although more demanding of time and effort, can be used. Otherwise further development of methodology is essential to avoid undue risk of bias.
Development and Testing of Thrombolytics in Stroke

Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies in vitro and in vivo.
Audiological and Surgical Outcomes of Pediatric Cochlear Implantation in Mondini's Dysplasia: Our Experience.

OBJECTIVES Aim of present study is to compare audiological and surgical outcomes in prelingual deaf children with Mondini's dysplasia (MD) and those with normal inner ear anatomy. MATERIALS AND METHODS Retrospective data was collected from Jan 2008 to Dec 2016. Children with bony IEM other than MD, syndromic association, multiple disabilities, those lost to follow up, and perilingual or postlingual deafness were excluded from study. Audiological outcomes for auditory perception (CAP score) and speech intelligibility (SIR score) was noted for a follow up period of 1 year. RESULTS Mean age at implantation was 2.8 years (Range of 2 to 6 years). 2 patients had intraoperative CSF ooze which was controlled intraoperatively by conservative measures. Post operative facial nerve function was normal in all patients. None of the patient in either group had any complications at one year of follow up period. There was statistically significant improvement in CAP - SIR score in Group A at 6 - 12 months compared to pretreatment. There was no statistically significant difference between the 2 groups in terms of CAP - SIR score at 6 - 12 months. CONCLUSION The study stresses the fact that cochlear implantation can be safely performed in children with MD although there is a risk of intraoperative CSF leak which can be controlled intraoperatively. Cochlear implantation in children with MD has good surgical, auditory and speech outcomes at par with children with normal bony inner ear anatomy.
Transferrin-mediated iron sequestration suggests a novel therapeutic strategy for controlling Nosema disease in the honey bee, Apis mellifera

Nosemosis C, a Nosema disease caused by microsporidia parasite Nosema ceranae, is a significant disease burden of the European honey bee Apis mellifera which is one of the most economically important insect pollinators. Nevertheless, there is no effective treatment currently available for Nosema disease and the disease mechanisms underlying the pathological effects of N. ceranae infection in honey bees are poorly understood. Iron is an essential nutrient for growth and survival of hosts and pathogens alike. The iron tug-of-war between host and pathogen is a central battlefield at the host-pathogen interface which determines the outcome of an infection, however, has not been explored in honey bees. To fill the gap, we conducted a study to investigate the impact of N. ceranae infection on iron homeostasis in honey bees. The expression of transferrin, an iron binding and transporting protein that is one of the key players of iron homeostasis, in response to N. ceranae infection was analysed. Furthermore, the functional roles of transferrin in iron homeostasis and honey bee host immunity were characterized using an RNA interference (RNAi)-based method. The results showed that N. ceranae infection causes iron deficiency and upregulation of the A. mellifera transferrin (AmTsf) mRNA in honey bees, implying that higher expression of AmTsf allows N. ceranae to scavenge more iron from the host for its proliferation and survival. The suppressed expression levels of AmTsf via RNAi could lead to reduced N. ceranae transcription activity, alleviated iron loss, enhanced immunity, and improved survival of the infected bees. The intriguing multifunctionality of transferrin illustrated in this study is a significant contribution to the existing body of literature concerning iron homeostasis in insects. The uncovered functional role of transferrin on iron homeostasis, pathogen growth and honey bee’s ability to mount immune responses may hold the key for the development of novel strategies to treat or prevent diseases in honey bees.
Letter to the editor: Excess all-cause mortality during second wave of COVID-19 – the Polish perspective

Bulgaria, Czech Republic, Poland and Romania are not part of the European monitoring of excess mortality for public health action (EuroMOMO) network, which means that their data are not included in the periodic z-score reports. However, Eurostat information for November 2020 [2,3] revealed that these four countries, with a total population of 75 million, were among the seven with highest excess mortality in the European Union (EU). The increase in the number of deaths for all causes, compared with 2016–2019, exceeded 50% in Romania, 75% in the Czech Republic and 90% in Bulgaria. Poland, with a 97% increase, had the highest excess mortality among all EU countries in November 2020. Other countries with over 50% increase include Belgium, Hungary and Slovenia, which means that six of seven countries with highest excess mortality lie in Central and Eastern Europe. In September 2020, Poland followed the Czech Republic (45% vs 53% increase). The Eurostat overview for December 2020 shows lower rates of excess mortality but confirms the discrepancies between different areas in Europe [4].