Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Epidemiology and Evolutionary History of Staphylococcus aureus ST45

Staphylococcus aureus ST45 is a major global MRSA lineage with huge strain diversity and a high clinical impact. It is one of the most prevalent carrier lineages but also frequently causes severe invasive disease, such as bacteremia. Little is known about its evolutionary history. In this study, we used whole-genome sequencing to analyze a large collection of 451 diverse ST45 isolates from 6 continents and 26 countries. De novo-assembled genomes were used to understand genomic plasticity and to perform coalescent analyses. ABSTRACT Staphylococcus aureus ST45 is a major global MRSA lineage with huge strain diversity and a high clinical impact. It is one of the most prevalent carrier lineages but also frequently causes severe invasive disease, such as bacteremia. Little is known about its evolutionary history. In this study, we used whole-genome sequencing to analyze a large collection of 451 diverse ST45 isolates from 6 continents and 26 countries. De novo-assembled genomes were used to understand genomic plasticity and to perform coalescent analyses. The ST45 population contained two distinct sublineages, which correlated with the isolates’ geographical origins. One sublineage primarily consisted of European/North American isolates, while the second sublineage primarily consisted of African and Australian isolates. Bayesian analysis predicted ST45 originated in northwestern Europe about 500 years ago. Isolation time, host, and clinical symptoms did not correlate with phylogenetic groups. Our phylogenetic analyses suggest multiple acquisitions of the SCCmec element and key virulence factors throughout the evolution of the ST45 lineage.
Longitudinal Study of Dyadic Adjustment in a Sample of Spanish Fathers

The objectives of this study were to examine the evolution of fathers’ long-term dyadic adjustment after the birth of a child and to analyze their evolution considering related factors. A total of 113 Spanish fathers with a mean age of 35.72 years (SD = 3.84 years) participated. In general, there was a decline in the dyadic adjustment of the fathers until 6–12 months after childbirth, after which their level of adjustment remained stable until 13–24 months. We observed different patterns when analyzing the evolution by subgroups formed based on these different variables, previous experience of paternity, and anxiety. The intrinsic differences between fathers should also be considered because these differences can influence the way in which men face the parental process as well as the evolution of the quality of their relationship with their partner.
Researching Hanabi with CardScript Analysing the rules of collaborative card games

Automated Game Design studies how to support game designers with the iterative process of designing, play testing and adjusting prototypes. But while there are many publications on game design, there are no digital tools for card game design of automated game design accepted as canon by game designers. This thesis focuses on questions game designers might have. We aim to support them by formalising aspects of the prototyping process. We research the mechanics of collaborative card game prototypes and provide tools that give feedback to designers. The design of collaborative games like the award-winning Hanabi forms a new frontier for research in automated game design, because the rules alone do not explain the many ways of how players can collaborate. This project tries to formalise this collaboration and relates it to the mechanics and meta-rules within the game. We present a card game design language and analysis tool called CardScript that aims to help designers express their prototype and informs them on the consequences of the designed mechanics. The tool demonstrates how small adjustments to these game mechanics influence the gameplay and reports back on previously posed designer hypotheses. Ultimately, this can help designers get a better understanding of game mechanics such as collaboration and improve the iterative design process as a whole.
Crucial Role of the C-Terminal Domain of Hfq Protein in Genomic Instability

G-rich DNA repeats that can form G-quadruplex structures are prevalent in bacterial genomes and are frequently associated with regulatory regions of genes involved in virulence, antigenic variation, and antibiotic resistance. These sequences are also inherently mutagenic and can lead to changes affecting cell survival and adaptation. Transcription of the G-quadruplex-forming repeat (G3T)n in E. coli, when mRNA comprised the G-rich strand, promotes G-quadruplex formation in DNA and increases rates of deletion of G-quadruplex-forming sequences. The genomic instability of G-quadruplex repeats may be a source of genetic variability that can influence alterations and evolution of bacteria. The DNA chaperone Hfq is involved in the genetic instability of these G-quadruplex sequences. Inactivation of the hfq gene decreases the genetic instability of G-quadruplex, demonstrating that the genomic instability of this regulatory element can be influenced by the E. coli highly pleiotropic Hfq protein, which is involved in small noncoding RNA regulation pathways, and DNA organization and packaging. We have shown previously that the protein binds to and stabilizes these sequences, increasing rates of their genomic instability. Here, we extend this analysis to characterize the role of the C-terminal domain of Hfq protein in interaction with G-quadruplex structures. This allows to better understand the function of this specific region of the Hfq protein in genomic instability.
The Role of Proteostasis Derailment in Cardiac Diseases

The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing and changes in lifestyle. Prevailing theories about the mechanisms of cardiac disease onset feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of the protein quality control as central factors. In the heart, loss of protein patency, due to flaws in design (genetically) or environmentally-induced wear and tear, may overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac disease onset.
Can Additional Patient Information Improve the Diagnostic Performance of Deep Learning for the Interpretation of Knee Osteoarthritis Severity

The study compares the diagnostic performance of deep learning (DL) with that of the former radiologist reading of the Kellgren–Lawrence (KL) grade and evaluates whether additional patient data can improve the diagnostic performance of DL. From March 2003 to February 2017, 3000 patients with 4366 knee AP radiographs were randomly selected. DL was trained using knee images and clinical information in two stages. In the first stage, DL was trained only with images and then in the second stage, it was trained with image data and clinical information. In the test set of image data, the areas under the receiver operating characteristic curve (AUC)s of the DL algorithm in diagnosing KL 0 to KL 4 were 0.91 (95% confidence interval (CI), 0.88–0.95), 0.80 (95% CI, 0.76–0.84), 0.69 (95% CI, 0.64–0.73), 0.86 (95% CI, 0.83–0.89), and 0.96 (95% CI, 0.94–0.98), respectively. In the test set with image data and additional patient information, the AUCs of the DL algorithm in diagnosing KL 0 to KL 4 were 0.97 (95% confidence interval (CI), 0.71–0.74), 0.85 (95% CI, 0.80–0.86), 0.75 (95% CI, 0.66–0.73), 0.86 (95% CI, 0.79–0.85), and 0.95 (95% CI, 0.91–0.97), respectively. The diagnostic performance of image data with additional patient information showed a statistically significantly higher AUC than image data alone in diagnosing KL 0, 1, and 2 (p-values were 0.008, 0.020, and 0.027, respectively). The diagnostic performance of DL was comparable to that of the former radiologist reading of the knee osteoarthritis KL grade. Additional patient information improved DL diagnosis in interpreting early knee osteoarthritis.
Back to the future of academic anaesthesia: publication outputs of UK anaesthetists

1Honorary Consultant, Departments of Anaesthesia andCritical CareMedicine, University Hospitals BirminghamNHS Trust, Birmingham, UK 2Associate Clinical Professor,WarwickMedical School, University ofWarwick,Warwick, UK 3Consultant, Department of Anaesthesia,WythenshaweHospital, Manchester University NHS Foundation Trust, Manchester, UK 4 Senior Clinical Lecturer, LancasterMedical School, Faculty of Health andMedicine, Lancaster University, Lancaster, UK
Do primates flexibly use spatio-temporal cues when foraging?

Foraging in seasonal environments can be cognitively demanding. Comparative studies have associated large brain size with a frugivorous diet. We investigated the ability of three semi-free-ranging primate species with different degrees of frugivory (Ntrials: Macaca tonkeana = 419, Macaca fascicularis = 197, Sapajus apella = 346) in developing a mental representation of the spatio-temporal distribution of food using foraging experiments. Forty-two boxes were fixed on trees, and each week (“season”), some of them were filled with fruits which were either highly preferred, or less preferred. Spatial (geometrical panels) and temporal (peel skin of the available fruit) cues were present at each season to indicate where (food location), what (which food) was available, and when. To test the flexible use of the cues in primate foraging behaviour, we first removed the spatial and temporal cues one at a time, and then, we manipulated the “seasonal” order of the available fruit. We compared the foraging performances in the absence and the presence of the cues and during the usual and unusual seasonal order. The average proportion of baited boxes chosen by the subjects in presence of both cues was high (between 73% and 98%) for all species. The primates seemed to remember the spatio-temporal food availability (or used other cues) because no difference was found between trials with or without our spatial and temporal cues. When the usual seasonal pattern was changed, they flexibly adjusted the feeding choice by using the provided temporal cues. We discuss these results also in view of a possible experimental bias.
Rapid Weight Gain, Infant Feeding Practices, and Subsequent Body Mass Index Trajectories: The CALINA Study

We aimed to study growth patterns according to rapid weight gain (RWG) and infant feeding practices during the first 120 days and whether infant feeding practices mediated the association between RWG in the first semester of life and subsequent body mass index (BMI) z-score in children from age 1 to 6. (1) Methods: 862 children from the Growth and Feeding during Lactation and Early Childhood in Children of Aragon study (CALINA in Spanish) were examined. Repeated-measures ANOVA analyses were conducted to assess growth trajectories according to RWG and type of feeding practice. The product of coefficients mediation method was used to assess the potential contribution of infant feeding practices to the association between RWG and BMI z-score. Mediation models were conducted using IBM SPSS-PROCESS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. (2) Results: BMI and weight z-score trajectories were significantly higher in the RWG group and the formula-fed group. No significant differences were found regarding height. Infant feeding practices did not mediate the association between RWG and BMI z-score but were associated with BMI at 6 years. (3) Conclusions: Infant feeding practices and RWG determine different growth trajectories of BMI and weight during childhood. Although infant feeding practices did not mediate the association between early RWG and BMI later in life, formula feeding is independently related to higher BMI growth patterns later in childhood.
Large Animal Models of Heart Failure: Reduced vs. Preserved Ejection Fraction

Simple Summary Human heart failure (HF) is a complex clinical syndrome that can be caused by a variety of diseases. While long-term high blood pressure and heart attacks are major contributing factors, there can be many diseases of the heart and circulation that contribute to the development of HF. Although there have been salutary improvements in the medical management of HF over the last 30 years, ongoing ill effects of living with the syndrome and the persistently high death rates mean there is an irrefutable need for new and improved treatment options. Well-characterized animal models have contributed, and continue to contribute, much to the advancement of clinical care. This review will summarize the main large animal models of HF developed to date. Studies utilizing these large animal models are an essential step leading to the development of novel pharmaceutical and device-based therapies before they can undergo definitive clinical trials. This review will discuss the various benefits of different large animal models of HF and highlight some key deficiencies to date. There is clearly a need for ongoing development of clinically relevant large animal models of HF. Abstract Heart failure (HF) is the final common end point of multiple metabolic and cardiovascular diseases and imposes a significant health care burden worldwide. Despite significant improvements in clinical management and outcomes, morbidity and mortality remain high and there remains an indisputable need for improved treatment options. The pathophysiology of HF is complex and covers a spectrum of clinical presentations from HF with reduced ejection fraction (HFrEF) (≤40% EF) through to HF with preserved EF (HFpEF), with HFpEF patients demonstrating a reduced ability of the heart to relax despite an EF maintained above 50%. Prior to the last decade, the majority of clinical trials and animal models addressed HFrEF. Despite growing efforts recently to understand underlying mechanisms of HFpEF and find effective therapies for its treatment, clinical trials in patients with HFpEF have failed to demonstrate improvements in mortality. A significant obstacle to therapeutic innovation in HFpEF is the absence of preclinical models including large animal models which, unlike rodents, permit detailed instrumentation and extensive imaging and sampling protocols. Although several large animal models of HFpEF have been reported, none fulfil all the features present in human disease and few demonstrate progression to frank decompensated HF. This review summarizes well-established models of HFrEF in pigs, dogs and sheep and discusses attempts to date to model HFpEF in these species.
The study of selected components of grape and fruit wines

This study aimed to compare chemical properties, in terms of the content of volatile substances, antioxidant compounds, and antioxidant activity (AOA), in samples of fruit and grape wines. For this purpose, the following types of wine were selected, namely fruit wines (apple, strawberry, and elderberry) and grape wines (Müller-Thurgau, St. Lawrence Rosé, and Blue Portugal). Basic analyses of fruit and grape wines were conducted by using the ALPHA method and volatile substances in wines were determined by the GS/MC method. The antioxidant content and AOA were estimated by spectrophotometry, using two types of DPPH method. The results of the experiment showed that the highest values of antioxidant compounds (anthocyanins and flavanols) were found in the samples of Blue Portugal wine and elderberry wine. Significant differences were determined among the wines in antioxidant content, which may have been influenced by the production technology. The results showed that the alcohol content of the wines ranged from 10.99% to 19.49% vol. The highest alcohol content was measured in the elderberry wine samples and the lowest in those of the apple wine. The strawberry wine had the highest titratable acid content, which corresponded to a pH of 3.38. The lowest content was measured in the apple wine samples. Due to the higher acid content of the strawberry wine, a higher residual sugar level of 46.9 g.L -1 was obtained. We noted that the red fruit wines contained a higher proportion of valuable bioactive substances than white grape wines. Wines with superior sensory properties did not contain higher levels of antioxidants or higher AOA. The research results can provide a helpful reference for the widespread use of grape and fruit wines in medical, nutritional, and other fields.
Optimization of Vancomycin Dosing Regimen in Cancer Patients using Pharmacokinetic/Pharmacodynamic Modeling

Gram‐positive bacterial infections are considered one of the major causes of mortality and morbidity in patients with cancer. Hence, the challenge lies in regulating the pervasive use of vancomycin in the management of infections facing such patients due to the anomalous vancomycin pharmacokinetics (PKs) and pharmacodynamics (PDs). Inappropriate vancomycin exposure is associated with toxicity, pathogen resistance, and therapeutic failure.
The Development of Stabilised Clay-Hemp Building Material for Sustainability and Low Carbon Use

This paper reports on stabilised clay-hemp building material for sustainability and low carbon use. Ground Granulated Blast-furnace Slag (GGBS) was used as a partial substitute for conventional stabiliser (lime or Portland cement) to stabilise Lower Oxford Clay (LOC) incorporating industrial hemp. The development of stabilised clay-hemp building material is expected to underpin the potential of commercial production of non-fired stabilised hemp walls, hemp blocks and hemp bricks, with a potential to offer an environmentally friendly alternative to traditional concrete, fired clay bricks and cement bricks. The parameters considered in this study are: material characterisation, unconfined compressive strength, linear expansion and cost. The 50-day linear expansion results for the test specimens showed that the maximum overall expansion rate for all the stabilised mixtures was 2%. The expansion behaviour of all stabilised clay-hemp material was significantly reduced with the presence of GGBS. The cost analysis results showed that the stabilised clay-hemp material manufactured with lime – GGBS system had the lowest net present value.
A dose‐dense short‐term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high‐risk Burkitt lymphoma or high‐grade B‐cell lymphoma: safety and efficacy results of the “CARMEN” phase II trial

A few prospective trials in HIV‐positive patients with Burkitt lymphoma (BL) or high‐grade B‐cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose‐dense, short‐term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36‐day polychemotherapy induction followed by high‐dose cytarabine‐based consolidation and response‐tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)‐ conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV‐positive adults (median age 42, range 26–58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double‐hit lymphoma (n = 1) were enrolled. All patients had high‐risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non‐haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41–54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77–100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow‐up of 55 (41–89) months, 14 patients are relapse‐free and 15 are alive, with a five‐year progression‐free survival and an overall survival of 70% (95% CI = 60–80%) and 75% (95% CI = 66–84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.
The role and molecular mechanism of FoxO1 in mediating cardiac hypertrophy

Cardiac hypertrophy can lead to heart failure and cardiovascular events and has become a research hotspot in the field of cardiovascular disease. Despite extensive and in‐depth research, the pathogenesis of cardiac hypertrophy is far from being fully understood. Increasing evidence has shown that the transcription factor forkhead box protein O 1 (FoxO1) is closely related to the occurrence and development of cardiac hypertrophy. This review summarizes the current literature on the role and molecular mechanism of FoxO1 in cardiac hypertrophy. We searched the database MEDLINE via PubMed for available evidence on the effect of FoxO1 on cardiac hypertrophy. FoxO1 has many effects on multiple diseases, including cardiovascular diseases, diabetes, cancer, aging, and stem cell activity. Recent studies have shown that FoxO1 plays a critical role in the development of cardiac hypertrophy. Evidence for this relationship includes the following. (i) FoxO1 can regulate cardiac growth/protein synthesis, calcium homeostasis, cell apoptosis, and autophagy and (ii) is controlled by several upstream signalling molecules (e.g. phosphatidylinositol 3‐kinase/Akt, AMP‐activated protein kinase, and sirtuins) and regulates many downstream transcription proteins (e.g. ubiquitin ligases muscle RING finger 1/muscle atrophy F‐box, calcineurin/nuclear factor of activated T cells, and microRNAs). In response to stress or external stimulation (e.g. low energy, oxidative stress, or growth factor signalling), FoxO1 undergoes post‐translational modification and transfers from the cytoplasm to nucleus, thus regulating the expression of a series of target genes in myocardium that are involved in cardiac growth/protein synthesis, calcium homeostasis, cell apoptosis, and autophagy. (iii) Finally, targeted regulation of FoxO1 is an effective method of intervening in myocardial hypertrophy. The information reviewed here should be significant for understanding the roles of FoxO1 in cardiac hypertrophy and should contribute to the design of further studies related to FoxO1 and the hypertrophic response. It should also shed light on a potential treatment for cardiac hypertrophy.