Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation in outcomes with extracorporeal membrane oxygenation in the era of coronavirus: A multicenter cohort evaluation

Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients with coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome unresponsive to other interventions. However, a COVID-19 infection may result in a differential tolerance to both medical treatment and ECMO management. The aim of this study was to compare outcomes (mortality, organ failure, circuit complications) in patients on ECMO with and without COVID-19 infection, either by venovenous (VV) or venoarterial (VA) cannulation. This is a multicenter, retrospective analysis of a national database of patients placed on ECMO between May 2020 and January 2022 within the United States. Nine-hundred thirty patients were classified as either Pulmonary (PULM, n = 206), Cardiac (CARD, n = 279) or COVID-19 (COVID, n = 445). Patients were younger in COVID groups: PULM = 48.4 ± 15.8 years versus COVID = 44.9 ± 12.3 years, p = 0.006, and CARD = 57.9 ± 15.4 versus COVID = 46.5 ± 11.8 years, p < 0.001. Total hours on ECMO were greatest for COVID patients with a median support time two-times higher for VV support (365 [101, 657] hours vs 183 [63, 361], p < 0.001), and three times longer for VA support (212 [99, 566] hours vs 70 [17, 159], p < 0.001). Mortality was highest for COVID patients for both cannulation types (VA-70% vs 51% in CARD, p = 0.041, and VV-59% vs PULM-42%, p < 0.001). For VA supported patients hepatic failure was more often seen with COVID patients, while for VV support renal failure was higher. Circuit complications were more frequent in the COVID group as compared to both CARD and PULM with significantly higher circuit change-outs, circuit thromboses and oxygenator failures. Anticoagulation with direct thrombin inhibitors was used more often in COVID compared to both CARD (31% vs 10%, p = 0.002) and PULM (43% vs 15%, p < 0.001) groups. This multicenter observational study has shown that COVID patients on ECMO had higher support times, greater hospital mortality and higher circuit complications, when compared to patients managed for either cardiac or pulmonary lesions.
Cardiogenic shock due to yew poisoning rescued by VA-ECMO: case report and literature review

ABSTRACT Ingestion of leaves of the European yew tree (Taxus baccata) can result in fatal cardiac arrhythmias and acute cardiogenic shock. This cardiotoxicity derives from taxine alkaloids that block cardiac voltage-gated sodium and calcium channels. Prompt initiation of venoarterial extracorporeal membrane oxygenation is essential to bridge these critically ill patients to recovery, as there is no antidote available. We here report a 39-year old patient with toxic cardiogenic shock after yew poisoning, who was successfully rescued by venoarterial extracorporeal membrane oxygenation and had a full neurological recovery. This report emphasizes the role of intoxications as reversible causes of cardiac arrest and adds further evidence to the body of existing literature thus encouraging the early use of venoarterial extracorporeal membrane oxygenation in patients with yew poisoning and cardiogenic shock.
Personalized ablation vs. conventional ablation strategies to terminate atrial fibrillation and prevent recurrence

Abstract Aims The long-term success rate of ablation therapy is still sub-optimal in patients with persistent atrial fibrillation (AF), mostly due to arrhythmia recurrence originating from arrhythmogenic sites outside the pulmonary veins. Computational modelling provides a framework to integrate and augment clinical data, potentially enabling the patient-specific identification of AF mechanisms and of the optimal ablation sites. We developed a technology to tailor ablations in anatomical and functional digital atrial twins of patients with persistent AF aiming to identify the most successful ablation strategy. Methods and results Twenty-nine patient-specific computational models integrating clinical information from tomographic imaging and electro-anatomical activation time and voltage maps were generated. Areas sustaining AF were identified by a personalized induction protocol at multiple locations. State-of-the-art anatomical and substrate ablation strategies were compared with our proposed Personalized Ablation Lines (PersonAL) plan, which consists of iteratively targeting emergent high dominant frequency (HDF) regions, to identify the optimal ablation strategy. Localized ablations were connected to the closest non-conductive barrier to prevent recurrence of AF or atrial tachycardia. The first application of the HDF strategy had a success of >98% and isolated only 5–6% of the left atrial myocardium. In contrast, conventional ablation strategies targeting anatomical or structural substrate resulted in isolation of up to 20% of left atrial myocardium. After a second iteration of the HDF strategy, no further arrhythmia episode could be induced in any of the patient-specific models. Conclusion The novel PersonAL in silico technology allows to unveil all AF-perpetuating areas and personalize ablation by leveraging atrial digital twins.
Experimental studies on androgen administration in animal models: current and future perspectives

Purpose of review This review aims to report the most recent (2020–2022) experimental scientific studies conducted on animal models, in order to highlight the relevant findings on the adverse effects related to androgen administration. Recent findings Forty-one studies published between January 2020 and July 2022 were selected. The majority of studies investigated the effects of one androgen, whereas only four studies analyzed the effects of two drugs. Nandrolone decanoate was the most investigated drug (20 articles), boldenone was tested in 8 articles, testosterone and stanozolol were used in 7 articles each, 17b-trenbolone, metandienone, and oxandrolone were tested in 1 article each. The articles clarify the adverse effects of androgen administration on the heart, brain, kidney, liver, reproductive and musculoskeletal systems. Summary The main findings of this review highlight that androgen administration increases inflammatory mediators, altering different biochemical parameters. The results concerning the reversibility of the adverse effects are controversial: on the one hand, several studies suggested that by stopping the androgen administration, the organs return to their initial state; on the other hand, the alteration of different biochemical parameters could generate irreversible organ damage. Moreover, this review highlights the importance of animal studies that should be better organized in order to clarify several important aspects related to androgen abuse to fill the gap in our knowledge in this research field.
Measurement Properties of the Health Literacy Questionnaire in the Understanding Multiple Sclerosis Massive Open Online Course Cohort: A Rasch Analysis

Background: Online health education and other electronic health improvement strategies are developing rapidly, highlighting the growing need for valid scales to assess health literacy (HL). One comprehensive HL scale is the Health Literacy Questionnaire (HLQ), but little is known about its measurement properties in online health education cohorts. Objective: The purpose of this study was to determine if the multidimensional HLQ is an appropriate tool to measure HL in a cohort of Understanding Multiple Sclerosis (MS) online course enrollees. Methods: Participants who enrolled in the first two open enrollments of the Understanding MS online course completed the HLQ (N = 1,182) in an online survey prior to beginning course materials. We used Rasch analysis to assess the measurement properties of the HLQ. Key Results: The nine Domains of the HLQ each had ordered category function and a good fit with the Rasch model. Each domain was one-dimensional and exhibited good internal consistency and reliability. None of the 44 individual items of the HLQ demonstrated item bias or local dependency. However, while the overall fit was good, few measurement gaps were identified in this cohort for participants in each of the nine Domains, meaning that the HLQ may have low measurement precision in some participants. Conclusion: Our analysis of the HLQ indicated acceptable measurement properties in a cohort of Understanding MS online course enrollees. Although reliable information on nine separate constructs of HL was obtainable in the current study indicating that the HLQ can be used in similar cohorts, its limitations must be also considered. [HLRP: Health Literacy Research and Practice. 2022;6(3):e200–e212. ] Plain Language Summary: In this study, we have shown that the HLQ is suitable for measuring HL in an online public health educational platforms for chronic diseases including multiple sclerosis. This finding adds to the evidence that the HLQ can be widely used in measuring HL in different settings, populations, and health educational platforms.
Punishment of ethanol choice in rhesus monkeys

A defining characteristic of individuals diagnosed with alcohol use disorder (AUD) is that negative outcomes related to drinking do not lead them to reduce their alcohol use. In rodent models of AUD, this characteristic has been studied by adding the bitter tastant quinine to an ethanol solution. In this study, we extended this approach to a nonhuman primate model in which the ability of quinine to decrease the choice of a 4% ethanol solution vs. water was measured. Five adult female rhesus monkeys with 7.3 years of experience drinking ethanol were given access to a 4% ethanol solution and water for 3 h per day. When ethanol choice was stable, a single quinine concentration (0.03–5.6g/L) was added to the ethanol solution for 1 day until a quinine concentration-effect curve was generated. After determining the quinine concentration that reduced ethanol choice by half (the quinine EC50), the relative reinforcing strength of ethanol was manipulated by adding quinine or sucrose to the water alternative depending on the monkey’s baseline choice. Adding quinine to ethanol produced a concentration-dependent decrease in ethanol choice and intake. Importantly, water intake increased, indicating an effect on response allocation rather than simply a decrease in fluid consumption. Consistent with this conclusion, the addition of quinine or sucrose to the water alternative resulted in predictable increases and decreases, respectively, in ethanol choice. These studies establish a model of punishment of ethanol choice in nonhuman primates that can be used to understand the contextual, biologic and pharmacologic factors that influence sensitivity to the punishment of alcohol drinking.
Population Pharmacokinetic Modeling and Simulation of Rifapentine Supports Concomitant Antiretroviral Therapy with Efavirenz and Non-Weight Based Dosing

The Brief Rifapentine–Isoniazid Efficacy for TB Prevention/A5279 trial demonstrated a 1-month daily regimen of rifapentine and isoniazid was noninferior to 9 months of isoniazid alone for preventing TB in persons living with HIV (PLWH). Our objective was to evaluate rifapentine pharmacokinetics in trial participants receiving antiretroviral therapy (ART) and perform simulations to compare weight-based rifapentine dosing with a standard, fixed dose. ABSTRACT The Brief Rifapentine–Isoniazid Efficacy for TB Prevention/A5279 trial demonstrated a 1-month daily regimen of rifapentine and isoniazid was noninferior to 9 months of isoniazid alone for preventing TB in persons living with HIV (PLWH). Our objective was to evaluate rifapentine pharmacokinetics in trial participants receiving antiretroviral therapy (ART) and perform simulations to compare weight-based rifapentine dosing with a standard, fixed dose. Nonlinear mixed effect modeling was used to estimate rifapentine and 25-desacetyl rifapentine population pharmacokinetic characteristics. The pharmacokinetic model was validated using a nonparametric bootstrap and visual predictive checks. Monte Carlo simulations were performed to compare weight-based and fixed dose regimens. Rifapentine and 25-desacetyl rifapentine concentrations (347 of each; 185 participants) were each described with a one-compartment model with one-way conversion between rifapentine and 25-desacetyl rifapentine. The absorption rate was nearly doubled in fed versus fasting states. Rifapentine clearance was increased 31% in those receiving efavirenz (EFV)-based versus nevirapine-based ART. Metabolite clearance was allometrically scaled with fat-free mass. Simulations showed lower rifapentine exposures with weight-based compared with fixed dosing. With 10 mg/kg weight-based regimens, 26% and 62% of simulated exposures in <35 kg and 35-45 kg weight classes were above target (AUC0 to 24 h of 257 mg*hr/L); 85% of simulated exposures across all weight classes with fixed dosing were above target. These data support fixed dosing with rifapentine 600 mg daily for TB prevention regardless of weight for PLWH 13 years or older receiving the 4-week regimen and no need for dose adjustment when given with EFV-based ART. Clinical Trials Registration. NCT01404312.
Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration

Abstract EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1 R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.
Old open clusters as key tracers of Galactic chemical evolution II. Iron and elemental abundances in NGC 2324, NGC 2477, NGC 2660, NGC 3960, and Berkeley 32

Aims. To constrain the formation and chemical evolution of the Galactic disk, we surveyed open clusters of different ages, metal contents, and distances from the Galactic centre. We employed FLAMES on VLT-UT2 to collect UVES spectra of five to ten giant stars in each of the selected clusters and used them to derive the iron abundance and the detailed chemical composition. Methods. Equivalent widths were measured and abundance analysis was performed using the MOOG code and Kurucz model atmospheres on all stars considered as cluster members on the basis of their radial velocity. Results. We derived the atmospheric parameters and the Fe abundance for NGC 2324 and NGC 2477 (average [Fe/H] = -0.17 with rms 0.05 dex, and +0.07 with rms 0.03 dex, respectively), two clusters never analyzed using high resolution spectra. We also derived the abundances of Mg, Al, Ca, Si, Ti, Cr, Ni, and Ba for these two clusters and for NGC 2660, NGC 3960, and Berkeley 32, whose atmospheric parameters and metallicities were measured in a previous paper. We determined the reddening values for the five clusters, based on the spectroscopic temperatures, literature photometry, and a colour-temperature relation. Conclusions. All clusters show solar-scaled abundances for α - and Fe-peak elements, while [Na/Fe] appears slightly enhanced and [Ba/Fe] significantly enhanced. Our findings were compared to thin-disk stars and other open clusters, and no significant deviation from the standard behavior was found.
The prevalence of comorbidity in the lung cancer screening population: A systematic review and meta-analysis

Objective Comorbidity is associated with adverse outcomes for all lung cancer patients, but its burden is less understood in the context of screening. This review synthesises the prevalence of comorbidities among lung cancer screening (LCS) candidates and summarises the clinical recommendations for screening comorbid individuals. Methods We searched MEDLINE, EMBASE, EBM Reviews, and CINAHL databases from January 1990 to February 2021. We included LCS studies that reported a prevalence of comorbidity, as a prevalence of a particular condition, or as a summary score. We also summarised LCS clinical guidelines that addressed comorbidity or frailty for LCS as a secondary objective for this review. Meta-analysis was used with inverse-variance weights obtained from a random-effects model to estimate the prevalence of selected comorbidities. Results We included 69 studies in the review; seven reported comorbidity summary scores, two reported performance status, 48 reported individual comorbidities, and 12 were clinical guideline papers. The meta-analysis of individual comorbidities resulted in an estimated prevalence of 35.2% for hypertension, 23.5% for history of chronic obstructive pulmonary disease (COPD) (10.7% for severe COPD), 16.6% for ischaemic heart disease (IHD), 13.1% for peripheral vascular disease (PVD), 12.9% for asthma, 12.5% for diabetes, 4.5% for bronchiectasis, 2.2% for stroke, and 0.5% for pulmonary fibrosis. Conclusions Comorbidities were highly prevalent in LCS populations and likely to be more prevalent than in other cancer screening programmes. Further research on the burden of comorbid disease and its impact on screening uptake and outcomes is needed. Identifying individuals with frailty and comorbidities who might not benefit from screening should become a priority in LCS research.
Interplay between abiotic and microbial biofilm‐mediated processes for travertine formation: Insights from a thermal spring (Piscine Carletti, Viterbo, Italy)

Active hydrothermal travertine systems are ideal environments to investigate how abiotic and biotic processes affect mineralization mechanisms and mineral fabric formation. In this study, a biogeochemical characterization of waters, dissolved gases, and microbial mats was performed together with a mineralogical investigation on travertine encrustations occurring at the outflow channel of a thermal spring. The comprehensive model, compiled by means of TOUGHREACT computational tool from measured parameters, revealed that mineral phases were differently influenced by either abiotic conditions or microbially driven processes. Microbial mats are shaped by light availability and temperature gradient of waters flowing along the channel. Mineralogical features were homogeneous throughout the system, with euhedral calcite crystals, related to inorganic precipitation induced by CO2 degassing, and calcite shrubs associated with organomineralization processes, thus indicating an indirect microbial participation to the mineral deposition (microbially influenced calcite). The microbial activity played a role in driving calcite redissolution processes, resulting in circular pits on calcite crystal surfaces possibly related to the metabolic activity of sulfur‐oxidizing bacteria found at a high relative abundance within the biofilm community. Sulfur oxidation might also explain the occurrence of gypsum crystals embedded in microbial mats, since gypsum precipitation could be induced by a local increase in sulfate concentration mediated by S‐oxidizing bacteria, regardless of the overall undersaturated environmental conditions. Moreover, the absence of gypsum dissolution suggested the capability of microbial biofilm in modulating the mobility of chemical species by providing a protective envelope on gypsum crystals.
Empirical antimicrobial therapy for bloodstream infections not compliant with guideline was associated with discordant therapy, which predicted poorer outcome even in a low resistance environment

Abstract Objectives To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome. Methods A retrospective observational study including patients aged 18 years admitted to a university hospital in central Norway with positive blood culture in 2019. Results We included 756 BSI episodes in our analysis. Empirical antimicrobial therapy was in accordance with the national guideline in 534 (70.6%), and not in accordance in 190 (25.1%) of the BSI episodes. There was a statistically significant association between compliance with the national guideline and concordant empirical antimicrobial therapy (p = .001). De-escalation of antimicrobial therapy was possible but not done in 217 (31.1%) of the BSI episodes. Variables identified as independent predictors of discordant empirical antimicrobial therapy included hospital department, type of empirical antimicrobial regimen, bacterial species, and AMR. Independent predictors of intra-hospital case fatality rate were coverage of empirical antimicrobial therapy, CCI-score, SAPS-II score, site of infection, and type of empirical antimicrobial regimen. Furthermore, the intra-hospital and long-term unadjusted all-cause case fatality rates were increased (p < .001, log-rank test for overall difference in survival) for the patients who received discordant empirical antimicrobial therapy. Conclusion Our study shows that empirical antimicrobial therapy initiated in accordance with national guideline recommendations increases the likelihood of receiving concordant therapy. Discordant empirical antimicrobial therapy was associated with poorer outcomes, even in a setting with low AMR prevalence.