Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic utility of six mutated genes for older patients with acute myeloid leukemia

Approximately 50% of older patients with acute myeloid leukemia (AML) do not obtain chromosomal abnormalities as an effective risk‐stratification, and present cytogenetically normal AML (CN‐AML). To develop a reliable prediction model for stratifying the risk of these elderly patients, we conducted a study with a discovery and validation design. As a result, we found the top 6 mutated genes in the discovery cohort of 26 case by the whole exome sequencing, and verified as recurrent mutations in the large cohort of 329 patients by Sanger sequencing. The top 6 genes were NPM1, FLT3‐ITD, DNMT3A, CEBPA double allele, IDH1 and IDH2 mutations, and the frequency of each gene in the combining cohort was 36.8%, 19.8%, 20.1%, 5.8%, 14.9% and 22.5%, respectively. In addition, clinical variables such as age, white blood cell counts, genes of IDH1 and DNMT3A mutations, European LeukemiaNet genotype (NPM1 mutations and lacking FLT3‐ITD or CEBPA double allele mutations) and treatment protocols were independent factors for predicting the probabilities of overall and event‐free survival. The prediction nomograms based on these significant factors showed accurate discrimination. In conclusion, we developed a reliable prediction model for stratifying the risk of elderly patients with CN‐AML.
Experimental determination of a double-valued drag relationship for glacier sliding

Abstract The contribution of glaciers to sea-level rise and their effects on landscape evolution depend on the poorly known relationship between sliding speed and drag at the ice/bed interface. Results from experiments with a new rotary laboratory device demonstrate empirically for the first time a double-valued drag relationship like that suggested by some sliding theories: steady drag on a rigid, sinusoidal bed increases, peaks and declines at progressively higher sliding speeds due to growth of cavities in the lee sides of bed undulations. Drag decreases with increased sliding speed if cavities extend beyond the inflection points of up-glacier facing surfaces, so that adverse bed slopes in contact with ice diminish with further cavity growth. These results indicate that shear tractions on glacier beds can potentially decrease due to increases in sliding speed driven by weather or climate variability, promoting even more rapid glacier motion by requiring greater strain rates to produce resistive stresses. Although a double-valued drag relationship has not yet been demonstrated for the complicated geometries of real glacier beds, both its potential major implications and the characteristically convex stoss surfaces of bumps on real glacier beds provide stimulus for exploring the effects of this relationship in ice-sheet models.
Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

ABSTRACT The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo. A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6Chi monocytes in vivo. These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses.
Individual differences in neural mechanisms of selective auditory attention in preschoolers from lower socioeconomic status backgrounds: an event-related potentials study.

Selective attention, the ability to enhance the processing of particular input while suppressing the information from other concurrent sources, has been postulated to be a foundational skill for learning and academic achievement. The neural mechanisms of this foundational ability are both vulnerable and enhanceable in children from lower socioeconomic status (SES) families. In the current study, we assessed individual differences in neural mechanisms of this malleable brain function in children from lower SES families. Specifically, we investigated the extent to which individual differences in neural mechanisms of selective auditory attention accounted for variability in nonverbal cognitive abilities in lower SES preschoolers. We recorded event-related potentials (ERPs) during a dichotic listening task and administered nonverbal IQ tasks to 124 lower SES children (77 females) between the ages of 40 and 67 months. The attention effect, i.e., the difference in ERP mean amplitudes elicited by identical probes embedded in stories when attended versus unattended, was significantly correlated with nonverbal IQ scores. Larger, more positive attention effects over the anterior and central electrode locations were associated with superior nonverbal IQ performance. Our findings provide initial evidence for prominent individual differences in neural indices of selective attention in lower SES children. Furthermore, our results indicate a noteworthy relationship between neural mechanisms of selective attention and nonverbal IQ performance in lower SES preschoolers. These findings provide the basis for future research to identify the factors that contribute to such individual differences in neural mechanisms of selective attention.
Visual intensity and pattern discrimination deficits after lesions of the optic lobe in pigeons.

Pigeons were trained to discriminate stimuli that differed in luminance or geometric pattern. Following discrimination training, bilateral stereotaxic lesions were made in the optic tectum and in the associated nuclei isthmi, located within the depth of optic lobe. In some cases the nuclei isthmi were destroyed with only minimal injury to the tectal strata. After recovery from surgery, the discrimination performance of the birds was again tested. Cases with massive destruction of the optic tectum and either direct or indirect damage to the nuclei isthmi showed extremely severe postoperative deficits in visual discrimination performance. Some cases were unable to reliably discriminate gross stimulus differences even after extensive postoperative retraining. Others eventually were able to perform the simpler discrimination tasks, but failed to recover their preoperative performance capabilities on the more difficult discrimination tasks. Cases with injury confined principally to the nuclei isthmi had less impairment of performance than the ones with injury to the tectum and the isthmic nuclei. In general, the results of this study suggested that lesions of the optic tectum in pigeons produced more severe and intractable deficits of visual discrimination performance than did lesions of structures more rostral in the tectofugal pathway (i.e. nucleus rotundus or ectostriatum). The data further suggest a separate role of the nuclei isthmi in the processing of visual information. The implications of the results for the understanding of the evolution of the vertebrate visual system are discussed.
Gene transfers from diverse bacteria compensate for reductive genome evolution in the chromatophore of Paulinella chromatophora

Significance Eukaryotic photosynthetic organelles (plastids) originated >1 billion y ago via the endosymbiosis of a β-cyanobacterium. The resulting proliferation of primary producers fundamentally changed our planet’s history, allowing for the establishment of human populations. Early stages of plastid integration, however, remain poorly understood, including the role of horizontal gene transfer from nonendosymbiotic bacteria. Rules governing organellogenesis are difficult, if not impossible, to evaluate using the highly derived algal and plant systems. Insights into this issue are provided by the amoeba Paulinella chromatophora, which contains more recently established photosynthetic organelles of α-cyanobacterial origin. Here we show that the impact of Muller’s ratchet that leads to endosymbiont genome reduction seems to drive the fixation of horizontally acquired “compensatory” bacterial genes in the host nuclear genome. Plastids, the photosynthetic organelles, originated >1 billion y ago via the endosymbiosis of a cyanobacterium. The resulting proliferation of primary producers fundamentally changed global ecology. Endosymbiotic gene transfer (EGT) from the intracellular cyanobacterium to the nucleus is widely recognized as a critical factor in the evolution of photosynthetic eukaryotes. The contribution of horizontal gene transfers (HGTs) from other bacteria to plastid establishment remains more controversial. A novel perspective on this issue is provided by the amoeba Paulinella chromatophora, which contains photosynthetic organelles (chromatophores) that are only 60–200 million years old. Chromatophore genome reduction entailed the loss of many biosynthetic pathways including those for numerous amino acids and cofactors. How the host cell compensates for these losses remains unknown, because the presence of bacteria in all available P. chromatophora cultures excluded elucidation of the full metabolic capacity and occurrence of HGT in this species. Here we generated a high-quality transcriptome and draft genome assembly from the first bacteria-free P. chromatophora culture to deduce rules that govern organelle integration into cellular metabolism. Our analyses revealed that nuclear and chromatophore gene inventories provide highly complementary functions. At least 229 nuclear genes were acquired via HGT from various bacteria, of which only 25% putatively arose through EGT from the chromatophore genome. Many HGT-derived bacterial genes encode proteins that fill gaps in critical chromatophore pathways/processes. Our results demonstrate a dominant role for HGT in compensating for organelle genome reduction and suggest that phagotrophy may be a major driver of HGT.
Perception of Gait Asymmetry During Split-Belt Walking

Optimization of gait rehabilitation using split-belt treadmills critically depends on our understanding of the roles of somatosensory perception and sensorimotor recalibration in perceiving gait asymmetry and adapting to split-belt walking. Recent evidence justifies the hypothesis that perception of gait asymmetry is based mainly on detection of temporal mismatches between afferent inputs at the spinal level.
Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy

Abstract. Existing dosimetric quantities do not fully account for the dynamic interactions between the key components of photodynamic therapy (PDT) or the varying PDT oxygen consumption rates for different fluence rates. Using a macroscopic model, reacted singlet oxygen ([O21]rx) was calculated and evaluated for its effectiveness as a dosimetric metric for PDT outcome. Mice bearing radiation-induced fibrosarcoma tumors were treated with benzoporphyrin derivative monoacid ring A (BPD) at a drug-light interval of 3 h with various in-air fluences (30 to 350 J/cm2) and in-air fluence rates (50 to 150 mW/cm2). Explicit measurements of BPD concentration and tissue optical properties were performed and used to calculate [O21]rx, photobleaching ratio, and PDT dose. For four mice, in situ measurements of O23 and BPD concentration were monitored in real time and used to validate the in-vivo photochemical parameters. Changes in tumor volume following treatment were used to determine the cure index, CI=1−k/kctr, where k and kctr are the tumor regrowth rates with PDT and without PDT, respectively. The correlation between CI and the dose metrics showed that the calculated [O21]rx at 3 mm is an effective dosimetric quantity for predicting treatment outcome and a clinically relevant tumor regrowth endpoint.
Impact of gender, organized athletics, and video gaming on driving skills in novice drivers

Given that novice drivers tend to be young, and teenagers and young adult drivers are involved in the greatest number of accidents, it is important that we understand what factors impact the driving skills of this population of drivers. The primary aim of the present study was to understand the impact of gender, organized athletics, and video gaming on driving skills of novice drivers under real-world driving conditions. Novice driving students having less than five hours driving experience previous to a normal driving lesson were evaluated on their self-confidence (self-reported) prior to the lesson and driving skill evaluated by their instructor during the course of the lesson. Information was collected about gender, age, whether or not the students were involved in organized athletics, and the extent of their video game playing. There was no impact of gender or extent of video game playing on driving skills. Females were significantly less self-confident with driving than males, but this did not translate to gender differences in driving skills. Being involved in organized athletics—either currently or in the past—significantly enhanced driving skills in both females and males. Finally, novice drivers’ age was negatively correlated with driving skills. That is, younger novice drivers (especially males) had better driving skills than older novice drivers. This is counter to popular belief that young drivers lack technical driving skills because they have less experience behind the wheel. Based on the results of the current study, we hypothesize that the relatively high accident rate of younger drivers (especially male drivers) is most likely due to inattention to safety considerations rather than lack of technical driving ability.
Management of acute coronary syndromes: special considerations in women

### Learning objectives Since 1984, more women than men have died annually in the USA from cardiovascular disease (CVD). 1 Women with coronary artery disease (CAD) have worse outcomes when no adjustments are made for other characteristics and co-morbidities.2 Acute coronary syndrome (ACS) is a subset of CAD, characterised by an abrupt onset of signs and symptoms of myocardial ischaemia. It is associated with rupture or erosion of an atherosclerotic plaque that results in either the partial or complete occlusion of the infarct-related artery. ACS requires rapid assessment, diagnosis and treatment to achieve optimal outcomes. Enormous advances have been made in ACS management; however, significant sex-related disparities persist resulting in suboptimal treatment of women. This inconsistency continues to be significant even when education, income and site of care are taken into consideration.3 Although many reasons have been elucidated to explain this disparity, much remains unclear. Differences could be explained in part by the pathophysiology of CAD in men and women. For example, women with ACS are less likely to have significant obstructive CAD but are more likely to have thrombus formation and plaque erosion when compared with men with similar symptoms.4 5 Additionally, differences exist regarding treatment and management leading to deferment of evidence-based therapies in women. Women continue to be under-represented in cardiovascular trials and on average comprise only 25% of clinical investigations in ACS.6 Fortunately, as awareness of this important issue increases, more research is being done to reveal sex-specific aspects of care. The goal of this review is to highlight differences in therapy and …
Mindfulness-based cognitive therapy for anxiety symptoms in older adults in residential care

ABSTRACT Objectives: Anxiety in older people is under-diagnosed and poorly treated despite significant impairments that arise from anxiety. Mindfulness-based cognitive therapy (MBCT) has been shown to be a promising treatment for anxiety. The aim of this study was to determine the effect of an MBCT program on anxiety symptoms in older people living in residential care. Method: Fifty-two participants (34 females) were randomly allocated into therapy and control groups using a 2 × 3 mixed design. The average age of participants was 83 years. Results: The group effect showed significant improvements on all measures at the end of the seven-week program in the therapy group, while the control group did not show significant changes. Conclusion: This study represents one of the first studies of the effectiveness of an MBCT program on anxiety symptoms for older people using a randomized controlled trial. The study has implications for future research that include the effectiveness of MBCT for the treatment of anxiety symptoms in older people, the utility of group therapy programs in residential care and the benefits of using specialized instruments for older populations.
Evolutionary time drives global tetrapod diversity

Global variation in species richness is widely recognized, but the explanation for what drives it continues to be debated. Previous efforts have focused on a subset of potential drivers, including evolutionary rate, evolutionary time (maximum clade age of species restricted to a region), dispersal (migration from one region to another), ecological factors and climatic stability. However, no study has evaluated these competing hypotheses simultaneously at a broad spatial scale. Here, we examine their relative contribution in determining the richness of the most comprehensive dataset of tetrapods to our knowledge (84% of the described species), distinguishing between the direct influences of evolutionary rate, evolutionary time and dispersal, and the indirect influences of ecological factors and climatic stability through their effect on direct factors. We found that evolutionary time exerted a primary influence on species richness, with evolutionary rate being of secondary importance. By contrast, dispersal did not significantly affect richness patterns. Ecological and climatic stability factors influenced species richness indirectly by modifying evolutionary time (i.e. persistence time) and rate. Overall, our findings suggest that global heterogeneity in tetrapod richness is explained primarily by the length of time species have had to diversify.
Phototrophic pigment diversity and picophytoplankton abundance in permafrost thaw lakes

24 November 2015 Dr. Jorien E. Vonk, Guest Editor, Biogeosciences, Email: j.e. vonk@uu.nl Dear Dr. Vonk, Phototrophic pigment diversity and picophytoplankton abundance in permafrost thaw lakes by A. Przytulska, S. Crevecoeur, C. Lovejoy, J. Comte and W.F. Vincent Thank you for your continuing help and for requesting that we now upload our manuscript. This has been fully revised in response to the two sets of referee comments, as per our response letter that we sent you previously and as further detailed and updated below. Thank you for your ongoing consideration and editorial handling of this manuscript. Sincerely,
An improved Akt reporter reveals intra- and inter-cellular heterogeneity and oscillations in signal transduction

ABSTRACT Akt is a key node in a range of signal transduction cascades and play a critical role in diseases such as cancer and diabetes. Fluorescently-tagged Akt reporters have been used to discern Akt localisation, yet it has not been clear how well these tools recapitulate the behaviour of endogenous Akt proteins. Here, we observed that fusion of eGFP to Akt2 impaired both its insulin-stimulated plasma membrane recruitment and its phosphorylation. Endogenous-like responses were restored by replacing eGFP with TagRFP-T. The improved response magnitude and sensitivity afforded by TagRFP-T–Akt2 over eGFP–Akt2 enabled monitoring of signalling outcomes in single cells at physiological doses of insulin with subcellular resolution and revealed two previously unreported features of Akt biology. In 3T3-L1 adipocytes, stimulation with insulin resulted in recruitment of Akt2 to the plasma membrane in a polarised fashion. Additionally, we observed oscillations in plasma membrane localised Akt2 in the presence of insulin with a consistent periodicity of 2 min. Our studies highlight the importance of fluorophore choice when generating reporter constructs and shed light on new Akt signalling responses that may encode complex signalling information. This article has an associated First Person interview with the first author of the paper. Highlighted Article: Plasma membrane recruitment of full-length Akt2 in 3T3-L1 adipocytes displays both polarity and oscillations in membrane association following insulin stimuli, as revealed by using an improved Akt2–TagRFP-T fusion protein.