Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Associated with Breakthrough Fungemia Caused by Candida, Trichosporon, or Fusarium Species in Patients with Hematological Disorders

Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. ABSTRACT Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years (P = 0.011), chronic renal failure (P = 0.0087), septic shock (P < 0.0001), steroid administration (P = 0.0085), and liposomal amphotericin B breakthrough fungemia (P = 0.0011). An absolute neutrophil count of >500/μL was significantly more common in candidemia in the multivariate analysis (P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia (P = 0.036 and P = 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia (P = 0.016 and P = 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.
Why Isn't Teleworking Working?

Since the 1970s, employers have attempted to introduce more flexible working arrangements in their quest to improve efficiency and reduce costs. More recently, when faced with more turbulent labour markets and skills shortages, employers, unions and academics have advocated a balance between organisational and employee flexibility. Besides the extensive use of traditional flexible working arrangements - for example, part-time employment and shift work - it has been anticipated that annual hours, job sharing and teleworking would become the way of the future. Perplexingly, this has rarely eventuated. This article examines teleworking, its rationale and its failure to deliver on its initial hype. Drawing on insights from recent research as well as data from the New Zealand and International Cranet surveys of human resource management practices amongst large firms, the article explores the various theoretical and practical angles associated with teleworking. In particular, the importance of traditional management and employee attitudes is stressed.
Natural Frequency of Thin Plates

Theoretical natural frequency of a thin plate having initial deflection and subjected to cylindrical bending are obtained and compared with experimental results chiefly in the buckled state. The plate is firmly clamped at both ends. In the author's experiment of the two dimensional panel flutter, the elastic property of the test panel was confirmed by the measurement of the resonant frequency and the configuration of the panel. The present paper shows the details of the theo- retical basis of this method. Two-modes approximation by the buckling modes and GALERKIN's method is used at first. It is clarified that threemodes approximation must be used in the region of large buckling deflection. Furthermore an approximate analysis by the vibration modes of the beam having no axial stress is shown as a study on the accuracy of approximation. Good agreement is seen between theory and experiment. The natural frequency is sensitive to initial deflection.
Comparison of HIV DNA decay and immune recovery between early and chronic HIV‐infected individuals 96 weeks after ART

Although antiretroviral therapy (ART) has prolonged the lives of HIV‐infected individuals, HIV reservoir remains the main stumbling block to HIV cure. Presently, early ART initiation is one of the effective measures to reduce the HIV reservoir. The effects of ART in Chinese individuals with acute and early HIV infection (AEHI) and chronic HIV infection (CHI) were analyzed in this study.
On the normative advantages of dopamine and striatal opponency for learning and choice

The basal ganglia (BG) contribute to reward-driven behavior, but it is unclear why such behavior should rely on notoriously complex circuitry involving opponent striatal pathways. Dopamine (DA) nonlinearly modulates activity and plasticity in the BG and is itself dynamically modulated across tasks. We develop the OpAL* model to assess the normative advantages of such circuitry. In OpAL*, dynamic DA modulation differentially amplifies the striatal pathway most tuned to the accumulated history of positive or negative outcomes. This efficient coding mechanism avoids a vexing explore-exploit tradeoff that plagues traditional RL models in sparse reward environments. OpAL* exhibits robust advantages over alternative models across a range of environments, particularly with sparse reward. These advantages depend on opponent and nonlinear Hebbian plasticity mechanisms previously thought to be pathological. Finally, OpAL* captures risky choice patterns arising from DA and environmental manipulations across species, suggesting that they result from a normative biological mechanism. Everybody wants the most they can possibly get For the least they can possibly do – Todd Snider, “Easy Money”
Cortical interneuron loss and seizure generation as novel clinically relevant disease phenotypes in Cln2R207X mice

Aims CLN2 disease is a fatal inherited childhood neurodegenerative disorder. Although a disease-modifying therapy now exists, a fundamental lack of understanding of disease pathogenesis has hampered development of more effective therapies. To better understand the cellular pathophysiology of CLN2 disease, we investigated the nature and progression of neuropathological and neurological changes in the recently generated Cln2R207X mouse. Methods We have detailed microglial activation, astrogliosis, cytokine and chemokine expression, and neuron loss across the forebrain and spinal cords of Cln2R207X mice, along with quantitative gait analysis. We also performed long-term electroencephalography (EEG) recordings to characterize seizure activity, a clinically-relevant phenotype yet to be defined in any CLN2 disease model. Results Histology revealed early localized microglial activation months before neuron loss in the thalamocortical system and spinal cord, which was accompanied by astrogliosis. These pathological changes were more pronounced and occurred in the cortex before the thalamus or spinal cord. There were early-onset and progressive changes in the expression of specific chemokines and cytokines including IL-33, IP-10, and MIP-1α. Gait analysis revealed impaired performance only at disease end stage. EEG recordings revealed robust and progressive epileptiform activity from disease mid-stage including spontaneous seizures, which were accompanied by a profound loss of cortical GABAergic interneurons. Conclusions Our data reveal novel phenotypes in Cln2R207X mice that differ markedly in their timing and progression through the CNS from other NCL mouse models. Our findings provide new insights on CLN2 disease pathogenesis and clinically-relevant readouts for future therapeutic studies.
Integration of multi‐omics data reveals interplay between brassinosteroid and Target of Rapamycin Complex signaling in Arabidopsis

Brassinosteroids (BR) and Target of Rapamycin Complex (TORC) are two major actors coordinating plant growth and stress responses. BRs function through a signaling pathway to extensively regulate gene expression and TORC is known to regulate translation and autophagy. Recent studies revealed that these two pathways crosstalk, but a system-wide view of their interplay is still missing. Thus, we quantified the level of 23,975 transcripts, 11,183 proteins, and 27,887 phosphorylation sites in wild-type Arabidopsis and in mutants with altered levels of either BRASSINOSTEROID INSENSITIVE 2 (BIN2) or REGULATORY ASSOCIATED PROTEIN OF TOR 1B (RAPTOR1B), two key players in BR and TORC signaling, respectively. We found that perturbation of BIN2 or RAPTOR1B levels affects a common set of gene-products involved in growth and stress responses. Furthermore, we used the multi-omic data to reconstruct an integrated signaling network. We screened 41 candidate genes identified from the reconstructed network and found that loss of function mutants of many of these proteins led to an altered BR response and/or modulated autophagy activity. Altogether, these results establish a predictive network that defines different layers of molecular interactions between BR-or TORC-regulated growth and autophagy.
RF4Del: A Random Forest approach for accurate deletion detection

Efficiently detecting genomic structural variants (SVs) is a key step to grasp the “missing heritability” underlying complex traits involved in major evolutionary processes such as speciation, phenotypic plasticity, and adaptive responses. Yet, the SV-based genotype/trait association studies are still largely overlooked mainly due to the lack of reliable detection methods. Here, we present a random forest (RF) method for accurate deletion identification: RF4Del. By relying on the analysis of the mapping profiles, data already available in most sequencing projects, RF4Del can easily and quickly call deletions. Several classic and ensemble learning strategies were carefully evaluated using proper benchmark data. RF4Del was trained and tested on simulated data from the model species Drosophila melanogaster to detect deletions. The model consists of 13 features extracted from a mapping file. We show that RF4Del outperforms established SV callers (DELLY, Pindel) with higher overall performance (F1-score > 0.75; 6x-12x sequence coverage) and is less affected by low sequencing coverage and deletion size variations. RF4Del could learn from a compilation of sequence patterns linked to a given SV. Such models can then be combined to form a learning system able to detect all types of SVs in a given genome, beyond the one used in our study. https://github.com/alvesrcoo/eletric-scheep
Predation increases prey fitness via transgenerational priming

Preparing your offspring for future challenges via priming can directly enhance its fitness. However, evidence for transgenerational priming has been limited to eukaryotic organisms. Here we test the hypothesis that predation primes bacteria such that their future generations respond with a more effective defence induction. In an evolution experiment, Escherichia coli was cultivated either in monoculture or in coculture with the predatory ciliate Tetrahymena thermophila. After 18 days, fitness and defensive clustering capabilities of derived bacterial populations were determined. Our results reveal that (i) predation can prime E.coli to induce their defensive cluster formation across generations and that (ii) three days of predation are sufficient to increase the fitness of predator-exposed over that of predator-free populations. Thus, our study shows that predation can have priming effects in bacterial populations that operate across generations, which concurs with the emerging perception that bacteria feature mechanisms to actively shape their evolutionary fate.
Co-release of histamine and GABA in prefrontal cortex excites fast-spiking interneurons and causes divisive gain change in pyramidal cells; an effect that is enhanced in older mice

We studied how co-release of histamine/GABA from axons originating from the hypothalamic tuberomammillary nucleus (TMN) and projecting to the prefrontal cortex (PFC) influences circuit processing. We opto-stimulated histamine/GABA co-release from genetically defined TMN axons that express the histidine decarboxylase gene (TMNHDC axons). Whole-cell recordings were used to monitor excitability of visually identified PFC neurons in layer 2/3 of prelimbic (PL), anterior cingulate (AC) and infralimbic (IL) regions before and after opto-stimulated histamine/GABA release. We found that histamine-GABA co-release influences the PFC through actions on distinct neuronal types: histamine stimulates fast-spiking interneurons; and co-released GABA enhances tonic (extrasynaptic) inhibition on pyramidal cells (PyrNs). For fast spiking non-accommodating interneurons, opto-stimulation increased excitability, an effect blocked by histamine H1 and H2 receptor antagonists. The excitability of other interneuron types in the PFC was not altered. In contrast, the combined action of histamine and GABA co-release from TMNHDC axons produced predominantly divisive gain changes in PyrNs, increasing their resting input conductance, and decreasing the slope of the input-output relationship. The direct inhibitory effect of TMNHDC axon activation on PyrNs was not blocked by histamine receptor antagonists but was blocked by GABAA receptor antagonists. Across the adult lifespan (from 3 months to over 2 years of age), stimulation of TMNHDC axons in the PFC inhibited PyrN excitability significantly more in older mice. For individuals that maintain cognitive performance into later life, increases in TMNHDC modulation of PyrNs could enhance information processing and be an adaptive mechanism to buttress cognition.
Treatment of Preschool Children With Autism Spectrum Disorder: A Trial to Evaluate a Learning Style Profile Intervention Program in China

Objective To investigate whether the provision of learning style profile (LSP) training improves development in preschool children with autism spectrum disorder (ASD) in China and to describe the characteristics of children who benefit from the intervention. Methods Eighty-one children aged 36 to 72 months who were diagnosed with ASD for the first time were recruited for the intervention group. All of them received 24 weeks of LSP training, consisting of hospital- and home-based training. Twenty-one children with ASD of the same age in the control group had never received any intervention after diagnosis but underwent an assessment. Assessments were conducted at baseline and 24 weeks later. Differences in the developmental level and severity of ASD symptoms over time and between groups were analyzed by repeated standardized measures. Secondary analyses examined age effects among the 36– 48-, 48– 60-, and 60–72-month age groups. Results Within-group comparison of the intervention group revealed significant treatment effects after the intervention, according to: language, social and adaptive developmental quotients (DQs) of the China Developmental Scale; total Childhood Autism Rating Scale (CARS) score; and hyperactivity, peer problems, total difficulties, and prosocial behavior scores of the Strengths and Difficulties Questionnaire (SDQ). Similar gains were observed in gross and fine motor DQs of the China Developmental Scale and emotional symptoms and conduct problems scores of the SDQ; however, the differences between these pre- and postintervention scores did not reach statistical significance. Comparisons among the three age groups in the intervention groups demonstrated a significant age effect on adaptive DQs of the China Developmental Scale; total CARS score; hyperactivity, peer problems and total difficulties scores of the SDQ. Comparison between the intervention and control groups revealed significant treatment effects on language, social and adaptive DQs of the China Developmental Scale; total CARS score; and emotional symptoms, conduct problems, hyperactivity, peer problems, total difficulties, and prosocial behavior scores of the SDQ after the intervention. Similar gains were observed in gross and fine motor DQs of the China Developmental Scale, although differences between the two groups did not reach statistical significance. Conclusion Our findings suggest that LSP training can effectively improve social behavior and reduce the severity of ASD symptoms in children with ASD. Our data also highlight the importance of early intervention.
1α,25-Dihydroxyvitamin D3 Promotes Angiogenesis After Cerebral Ischemia Injury in Rats by Upregulating the TGF-β/Smad2/3 Signaling Pathway

Stroke is a disease with high morbidity, disability and mortality, which seriously endangers the life span and quality of life of people worldwide. Angiogenesis and neuroprotection are the key to the functional recovery of penumbra function after acute cerebral infarction. In this study, we used the middle cerebral artery occlusion (MCAO) model to investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25-D3) on transforming growth factor-β (TGF-β)/Smad2/3 signaling pathway. Cerebral infarct volume was measured by TTC staining. A laser speckle flow imaging system was used to measure cerebral blood flow (CBF) around the ischemic cortex of the infarction, followed by platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and isolectin-B4 (IB4) immunofluorescence. The expression of vitamin D receptor (VDR), TGF-β, Smad2/3, p-Smad2, p-Smad3, and vascular endothelial growth factor (VEGF) was analyzed by western blot and RT-qPCR. Results showed that compared with the sham group, the cerebral infarction volume was significantly increased while the CBF was reduced remarkably in the MCAO group. 1,25-D3 reduced cerebral infarction volume, increased the recovery of CBF and expressions of VDR, TGF-β, p-Smad2, p-Smad3, and VEGF, significantly increased IB4+ tip cells and CD31+ vascular length in the peri-infarct area compared with the DMSO group. The VDR antagonist pyridoxal-5-phosphate (P5P) partially reversed the neuroprotective effects of 1,25-D3 described above. In summary, 1,25-D3 plays a neuroprotective role in stroke by activating VDR and promoting the activation of TGF-β, which in turn up-regulates the TGF-β/Smad2/3 signaling pathway, increases the release of VEGF and thus promotes angiogenesis, suggesting that this signaling pathway may be an effective target for ischemic stroke treatment. 1,25-D3 is considered to be a neuroprotective agent and is expected to be an effective drug for the treatment of ischemic stroke and related diseases.
Buoyancy Versus Local Stress Field Control on the Velocity of Magma Propagation: Insight From Analog and Numerical Modelling

Magmatic dykes interact with heterogeneous crustal stress. As a result, their propagation towards the surface can be tortuous and their propagation velocity may vary. While the deflection of dykes in response to the local stress field has been addressed by several studies, less has been done about the effect on their propagation velocity. Understanding under which conditions an intrusion may accelerate or decelerate due to crustal stress heterogeneities has obvious important implications in terms of forecasting the timing of the onset of the eruption. Here we analyse the velocity of fluid-filled crack propagation in a gelatin block characterized by a heterogenous stress field considering the case study of a load applied at the surface. We find that a crack deflected towards the load and its underlying compressive stress field is decelerated. By comparing experimental results with numerical solutions, we evidence the potential complementary role played by stress field variations and changes in trajectory orientation, controling the buoyancy, on the velocity of magma propagation. We also show that the energy release estimated along the crack path by simplified numerical models appears to be a good proxy for the velocity. We conclude that numerical models allowing for magma path estimations could also be used to infer magma velocity variations. In addition, 1D numerical models solving for the fluid flow along a prescribed path, provide velocity variation as a function of the surrounding stress field and the magma driving pressure.
Exploring the Impact of the “RUEU?” Game on Greek Students’ Perceptions of and Attitudes to European Identity

European identity is a complex, multi-faced and inherently imprecise concept relating to a range of socio-political and psychological factors. Addressing this topic in educational practice, particularly with respect to Higher Education students, constitutes a complex and open problem for research. This paper reports on an experimental study designed to explore the effectiveness of the educational game “RUEU? ” in supporting university students in understanding the key socio-political issues regarding European identity. Quantitative data regarding Greek university students’ (N = 92) attitudes to European identity, before and after playing the game, were collected. Students’ performance of the game group (N = 46) was compared with that of a control group (N = 46) who explored the same issues about European identity through a tutor-guided discussion. The findings showed that both instructional interventions were effective but in different ways. The participants in the game-based group appeared more attached to the EU after the intervention and moved toward a more balanced description of their Greek and European identity. On the other hand, the students in the control group rated higher what “European identity” and being EU citizen means to them. The findings indicated the potential of game-based interventions to deliver not only academic content but also to promote students’ reflection and influence them at an attitudinal and emotional level.
Knowledge, Attitudes, and Practices About COVID-19 Among Healthcare Workers in Iran During the First Wave of the Pandemic

Background and Objective Investigating the knowledge, attitudes, and practices about the coronavirus disease 2019 (COVID-19) among healthcare workers (HCWs) could be an early step toward identifying their potential educational needs and possible factors involved in misinformation. The objective of this study was to investigate the knowledge, attitudes, and practices about COVID-19 among healthcare workers in Iran during the first wave of the pandemic. Materials and Methods The current descriptive-correlational study was conducted during the 1st days of the COVID-19 epidemic in Iran from March 24th to April 3rd, 2020. Participants included all healthcare workers at hospitals, including physicians, dentists, pharmacists, nurses, midwives, laboratory and radiology assistants, and other hospital professionals during the study period. Data were collected through an online self-administrative questionnaire. Results The responses of 1,310 participants were analyzed, of which 900 (68.7%) were female. The mean (SD) knowledge score was 25.4 (3.3), 84.7% out of 30. More than 90% of participants correctly recognized the main symptoms, transmission route, and preventive measures for COVID-19. The mean (SD) attitude score was 16.9 (1.1), 93.9% out of 18. Most participants agreed with keeping safe physical distancing, self-isolation upon symptom onset, and city lockdowns. The mean (SD) score for general practices about COVID-19 was 20.8 (2.0), 86.7% of 24. Conclusion The knowledge and practice of HCWs were appropriate, and their attitudes were mainly positive. However, there is still room for improvement regarding concerning misinformation and quackeries about COVID-19.