Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolutionary Responses to Acquiring a Multidrug Resistance Plasmid Are Dominated by Metabolic Functions across Diverse Escherichia coli Lineages

Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. ABSTRACT Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions. IMPORTANCE Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. Using experimental evolution with diverse E. coli lineages and a clinical multidrug resistance plasmid, we show that although plasmids drove unique evolutionary paths per lineage, there was a surprising degree of convergence in the functions targeted by mutations across lineages, dominated by metabolic functions. Remarkably, these same metabolic functions show higher evolutionary rates in MDR-lineages in nature and in some cases, like anaerobic metabolism, their expression is directly manipulated by the plasmid. Interactions with other mobile elements resident in the genomes accelerated adaptation by disrupting genes and regulatory sequences that they inserted into. Beyond their role in horizontal gene transfer, plasmids are an important selective force driving the evolution of bacterial genomes and core cellular functions.
Cortical grey matter mediates increases in model-based control and learning from positive feedback from adolescence to adulthood

Adolescents undergo maturation in cognition and brain structure. Model-based (MB) control is known to increase from childhood to young adulthood, which is mediated by cognitive abilities. Here, we asked two questions unaddressed in previous developmental studies: Firstly, what are the brain structural correlates of age-related increases in MB control? Secondly, how are age-related increases in MB control from adolescence to adulthood influenced by motivational context? A developmental sample (n=103, age: 12-42) completed structural MRI and an established task to capture MB control. The task was modified with respect to outcome valence by including (1) reward and punishment blocks to manipulate the motivational context and (2) an additional choice test to assess learning from positive vs. negative feedback. After replicating that an age-dependent increase in MB control is mediated by cognitive abilities, we demonstrate first-time evidence that grey matter density (GMD) in the parietal cortex mediates the increase of MB control with age. While motivational context did not relate to age-related changes in MB control, learning from positive feedback improved with age. Meanwhile, negative feedback learning showed no age effects. We present a first report that an age-related increase in learning from positive feedback was mediated by reduced GMD in the parietal, medial and dorsolateral prefrontal cortex. Our findings indicate that efficient brain maturation, as putatively reflected in lower GMD, in distinct and partially overlapping brain regions is a key developmental step towards age-related increases in planning and value-based choice. Significance Statement Adolescents undergo extensive maturation in cognition and brain structure. Interestingly, model-based decision-making is also known to increase from childhood to adulthood. Here, we demonstrate for the first time that grey matter density in the parietal cortex mediates an age-dependent increase in model-based control. An age-related increase in positive feedback learning was mediated by reduced grey matter density in the parietal, medial and dorsolateral prefrontal cortex. Interestingly, a manipulation of motivational context (gain reward vs. avoid punishment) did not impact age-related changes in model-based control. These findings highlight that efficient brain maturation in distinct and overlapping cortical brain regions constitutes a key developmental step towards increases in model-based planning and value-based choice.
Investigation of planing vessels motion using nonlinear strip theory – an experimental and numerical study

ABSTRACT This study is aimed to improve Zarnick’s (1978, A nonlinear mathematical model of motions of a planing boat in regular waves. David W. Taylor Naval Ship Research and Development Center, Bethesda, MD, USA) analytical model for motions of planing vessels. A nonlinear time domain mathematical model was developed for dynamic behaviour of longitudinal motion of high-speed planing crafts in regular waves. This model was based on two-dimensional strip theory method using expanding wedge theory and momentum. Due to the nonlinearity and complex dynamic behaviour of these vessels, the time-domain simulation was adopted. Total resistance, heave and pitch motions as well as acceleration were found very sensitive to hydrodynamic coefficients. Furthermore, a set of forced oscillation and seakeeping tests on a vessel were carried out for different conditions at the Marine Engineering Research Centre of Sharif University of Technology (MERC). The effect of velocity, wavelength, and hydrodynamic coefficients were investigated on vessel motions. According to the results, decreasing added mass coefficients, velocity of the model increases. The amplitude of heave and pitch motions declined due to an increase in velocity, within the tested speed range, or by reduction of λ/L ratio. Hydrodynamic coefficients of the mathematical model have been modified accordingly, and the model represented a better agreement with the experimental data obtained by Fridsma (1969. A systematic study of the rough-water performance of planing boats. Tech. Rep. Davidson Laboratory, Stevens Institute of Technology, Hoboken, NJ, USA). This model was applied to identify the nonlinear dynamics of these vessels in both semi-planing and planing phases that can be further expanded to hybrid vessels in the future.
Online Parameter Adjustment Method for Arm Voltage Estimation of the Modular Multilevel Converter

The method used to calculate insertion indexes plays an important role in determining the overall performance of the modular multilevel converter. Direct voltage control, which is the simplest option, results in a large circulating current ripple because this modulation technique does not account for the arm voltage ripples. This led to the development of compensated modulation techniques that compensate for the arm voltage ripples thereby eliminating the circulating current ripple. There are two variants of compensated modulation—closed loop and open loop. The closed-loop version requires measurement of the arm voltages without distortion and delay, which is difficult to achieve in practice. The open-loop method overcomes this challenge by using estimated arm voltages. However, accurate knowledge of the system parameters is needed for effective removal of the circulating current ripples. This is a limitation because the parameters change with time and operating conditions. This paper presents a modified version of the open-loop method, which includes a scheme for correcting parameter errors online. The method estimates the parameters, arm capacitances, and time delay, by using feedback controllers acting on the circulating current ripples. Mathematical derivation of the method, together with its validation using simulation and experimental tests, is presented in detail.
Interventions to reduce the incidence of medical error and its financial burden in health care systems: A systematic review of systematic reviews

Background and aim Improving health care quality and ensuring patient safety is impossible without addressing medical errors that adversely affect patient outcomes. Therefore, it is essential to correctly estimate the incidence rates and implement the most appropriate solutions to control and reduce medical errors. We identified such interventions. Methods We conducted a systematic review of systematic reviews by searching four databases (PubMed, Scopus, Ovid Medline, and Embase) until January 2021 to elicit interventions that have the potential to decrease medical errors. Two reviewers independently conducted data extraction and analyses. Results Seventysix systematic review papers were included in the study. We identified eight types of interventions based on medical error type classification: overall medical error, medication error, diagnostic error, patients fall, healthcare-associated infections, transfusion and testing errors, surgical error, and patient suicide. Most studies focused on medication error (66%) and were conducted in hospital settings (74%). Conclusions Despite a plethora of suggested interventions, patient safety has not significantly improved. Therefore, policymakers need to focus more on the implementation considerations of selected interventions.
The importance of taking ART appropriately in children and adolescents with HIV-1 to reach the highest capacity of immune function later in life

Current antiretroviral therapy (ART) guidelines recommend treating all children with HIV-1 infection. This has changed from the broader use of ART to treat children to improve morbidity and minimise mortality. However, prior to current recommendations, not everyone with HIV-1 received timely treatment. What happens to the paediatric immune system when HIV-1 replication is not appropriately supressed remains unclear. 11 samples from adolescents with HIV-1 on ART and uninfected controls in the UK, aged 12–25 years, were examined; overall, adolescents with CD4+ counts > 500/μl and a viral load < 50 copies/ml were compared with adolescents with CD4+ counts < 500/μl and a viral load > 50 copies/ml at time of sampling. Measurements of thymic output were combined with high throughput next generation sequencing and bioinformatics to systematically organize CD4+ and CD8+ T cell receptor (TCR) repertoires. TCR repertoire diversity, clonal expansions, TCR sequence sharing, and formation of TCR clusters in HIV-1 infected adolescents with successful HIV-1 suppression were compared to adolescents with ineffective HIV-1 suppression. Thymic output and CD4+ T cell numbers were decreased in HIV-1 infected adolescents with poor HIV-1 suppression. A strong homeostatic TCR response, driven by the decreased CD4+ T cell compartment and reduced thymic output was observed in the virally uncontrolled HIV-1-infected adolescents. Formation of abundant robust TCR clusters and structurally related TCRs were found in the adolescents with effective HIV-1 suppression. Numerous CD4+ T cell numbers in the virally controlled adolescents emphasize the importance of high thymic output and formation of robust TCR clusters in the maintenance of HIV-1 suppression. While the profound capacity for immune recovery in children may allow better opportunity to deal with immunological stress, when ART is taken appropriately, this study demonstrates new insights into the unique paediatric immune system and the immunological changes when HIV-1 replication is ongoing.
Comparison of Breast Cancer Radiotherapy Techniques Regarding Secondary Cancer Risk and Normal Tissue Complication Probability – Modelling and Measurements Using a 3D-Printed Phantom

Background Radiotherapy after breast-conserving therapy is a standard postoperative treatment of breast cancer, which can be carried out with a variety of irradiation techniques. The treatment planning must take into consideration detrimental effects on the neighbouring organs at risk—the lung, the heart, and the contralateral breast, which can include both short- and long-term effects represented by the normal tissue complication probability and secondary cancer risk. Patients and Methods In this planning study, we investigate intensity-modulated (IMRT) and three-dimensional conformal (3D-CRT) radiotherapy techniques including sequential or simultaneously integrated boosts as well as interstitial multicatheter brachytherapy boost techniques of 38 patients with breast-conserving surgery retrospectively. We furthermore develop a 3D-printed breast phantom add-on to allow for catheter placement and to measure the out-of-field dose using thermoluminescent dosimeters placed inside an anthropomorphic phantom. Finally, we estimate normal tissue complication probabilities using the Lyman–Kutcher–Burman model and secondary cancer risks using the linear non-threshold model (out-of-field) and the model by Schneider et al. (in-field). Results The results depend on the combination of primary whole-breast irradiation and boost technique. The normal tissue complication probabilities for various endpoints are of the following order: 1%–2% (symptomatic pneumonitis, ipsilateral lung), 2%–3% (symptomatic pneumonitis, whole lung), and 1%–2% (radiation pneumonitis grade ≥ 2, whole lung). The additional relative risk of ischemic heart disease ranges from +25% to +35%. In-field secondary cancer risk of the ipsilateral lung in left-sided treatment is around 50 per 10,000 person-years for 20 years after exposure at age 55. Out-of-field estimation of secondary cancer risk results in approximately 5 per 10,000 person-years each for the contralateral lung and breast. Conclusions In general, 3D-CRT shows the best risk reduction in contrast to IMRT. Regarding the boost concepts, brachytherapy is the most effective method in order to minimise normal tissue complication probability and secondary cancer risk compared to teletherapy boost concepts. Hence, the 3D-CRT technique in combination with an interstitial multicatheter brachytherapy boost is most suitable in terms of risk avoidance for treating breast cancer with techniques including boost concepts.
Logometro®: The psychometric properties of a norm-referenced digital battery for language assessment of Greek-speaking 4–7 years old children

In educational and clinical settings, few norm-referenced tests have been utilized until now usually focusing on a single or a few language subcomponents, along with very few language rating scales for parents and educators. The need for a comprehensive language assessment tool for preschool and early school years children which could form the basis for valid and reliable screening and diagnostic decisions, led to the development of a new norm-referenced digital tool called Logometro®. The aim of the present study is to describe Logometro® as well as its psychometric characteristics. Logometro® evaluates an array of oral language skills across the different language domains such as phonological awareness, listening comprehension, vocabulary knowledge (receptive and expressive), narrative speech, morphological awareness, pragmatics, as well emergent literacy skills (letter sound knowledge and invented writing) in Greek-speaking 4–7 years old children. More specifically, Logometro® has been designed in order to: (a) map individual language development paths as well as difficulties, (b) provide a descriptive profile of children’s oral language and emergent literacy skills, and (c) assist in the identification of children who are at risk for Developmental Language Disorder (DLD) or Specific Learning Disabilities (SLD). The sample consisted of 926 children aged from 4 to 7 years, which were recruited from diverse geographical provinces and represented a variety of socioeconomic backgrounds in Greece. Eight hundred participants were typically developing children (Nboys = 384 and Ngirls = 416), 126 children (NSLI = 44 and NSLD = 82) represented children with Special Educational Needs, and 126 children were typically developing peers matched for gender and age with the clinical groups. The administration lasted 90 min, depending on the participant’s age and competence. Validity (construct, criterion, convergent, discriminant, and predictive) as well as internal consistency and test–retest reliability were assessed. Results indicated that Logometro® is characterized by good psychometric properties and can constitute a norm-referenced battery of oral language and emergent literacy skills. It could be used to inform the professionals as well as the researchers about a child’s language strengths and weaknesses and form the basis on which they can design an appropriate individualized intervention if needed.
The influence of technostress, work–family conflict, and perceived organisational support on workplace flourishing amidst COVID-19

The remote working environment is characterised by excessive use of new technology and work activities that extend to personal time. It is expected of each employee to balance multiple roles whilst maintaining maximum performance and individual wellbeing; however, without adequate support from an organisation, employees languish instead of flourish. The current study applied a model to investigate the combined effect of technostress, work–family conflict, and perceived organisational support on workplace flourishing for higher education employees. The study followed a cross-sectional quantitative research framework. Data were collected from a sample of 227 academic and support staff employees from a selected residential University in South Africa. The results indicated that technostress through perceived organisational support and through work–family conflict influences workplace flourishing. No direct significant effect was reported between technostress and workplace flourishing. Technostress, work–family conflict, and perceived organisational support combined explained 47% variance in workplace flourishing. Perceived organisational support displayed the strongest direct effect on workplace flourishing, and technostress is a strong determinant of work–family conflict, which then mediates the relationship between technostress and workplace flourishing. The study concluded that providing organisational support and creating policies favourable to work–life balance assist employees in managing techno-overload, techno-invasion, and techno-complexity (technostress) better and enhance workplace flourishing. Although employees struggle in the remote working context with demands imposed by techno-overload, techno-invasion, and techno-complexity, the results indicate that perceived organisational support and balanced work life act as job resources that enhance emotional, psychological, and subjective wellbeing (workplace flourishing).
Molecular characterization of thioester-containing proteins in Biomphalaria glabrata and their differential gene expression upon Schistosoma mansoni exposure

Schistosomiasis is a disease caused by trematode parasites of the genus Schistosoma that affects approximately 200 million people worldwide. Schistosomiasis has been a persistent problem in endemic areas as there is no vaccine available, currently used anti-helmintic medications do not prevent reinfection, and most concerning, drug resistance has been documented in laboratory and field isolates. Thus, alternative approaches to curtail this human disease are warranted. Understanding the immunobiology of the obligate intermediate host of these parasites, which include the freshwater snail Biomphalaria glabrata, may facilitate the development of novel methods to stop or reduce transmission to humans. Molecules from the thioester-containing protein (TEP) superfamily have been shown to be involved in immunological functions in many animals including corals and humans. In this study we identified, characterized, and compared TEP transcripts and their expression upon S. mansoni exposure in resistant and susceptible strains of B. glabrata snails. Results showed the expression of 11 unique TEPs in B. glabrata snails. These transcripts present high sequence identity at the nucleotide and putative amino acid levels between susceptible and resistant strains. Further analysis revealed differences in several TEPs’ constitutive expression levels between resistant and susceptible snail strains, with C3-1, C3-3, and CD109 having higher constitutive expression levels in the resistant (BS90) strain, whereas C3-2 and TEP-1 showed higher constitutive expression levels in the susceptible (NMRI) strain. Furthermore, TEP-specific response to S. mansoni miracidia exposure reiterated their differential expression, with resistant snails upregulating the expression of both TEP-4 and TEP-3 at 2 h and 48 h post-exposure, respectively. Further understanding the diverse TEP genes and their functions in invertebrate animal vectors will not only expand our knowledge in regard to this ancient family of immune proteins, but also offer the opportunity to identify novel molecular targets that could aid in the efforts to develop control methods to reduce schistosomiasis transmission.
Examining the Effect of Transcranial Electrical Stimulation and Cognitive Training on Processing Speed in Pediatric Attention Deficit Hyperactivity Disorder: A Pilot Study

Objective Processing Speed (PS), the ability to perceive and react fast to stimuli in the environment, has been shown to be impaired in children with attention deficit hyperactivity disorder (ADHD). However, it is unclear whether PS can be improved following targeted treatments for ADHD. Here we examined potential changes in PS following application of transcranial electric stimulation (tES) combined with cognitive training (CT) in children with ADHD. Specifically, we examined changes in PS in the presence of different conditions of mental fatigue. Methods We used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD. Participants received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or transcranial random noise stimulation (tRNS), while completing CT, and the administration order was counterbalanced. PS was assessed before and after treatment using the MOXO-CPT, which measures PS in the presence of various conditions of mental fatigue and cognitive load. Results tRNS combined with CT yielded larger improvements in PS compared to tDCS combined with CT, mainly under condition of increased mental fatigue. Further improvements in PS were also seen in a 1-week follow up testing. Conclusion This study provides initial support for the efficacy of tRNS combined with CT in improving PS in the presence of mental fatigue in pediatric ADHD.