Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide screening identified SEC61A1 as an essential factor for mycolactone-dependent apoptosis in human premonocytic THP-1 cells

Buruli ulcer is a chronic skin disease caused by a toxic lipid mycolactone produced by Mycobacterium ulcerans, which induces local skin tissue destruction and analgesia. However, the cytotoxicity pathway induced by mycolactone remains largely unknown. Here we investigated the mycolactone-induced cell death pathway by screening host factors using a genome-scale lenti-CRISPR mutagenesis assay in human premonocytic THP-1 cells. As a result, 884 genes were identified as candidates causing mycolactone-induced cell death, among which SEC61A1, the α-subunit of the Sec61 translocon complex, was the highest scoring. CRISPR/Cas9 genome editing of SEC61A1 in THP-1 cells suppressed mycolactone-induced endoplasmic reticulum stress, especially eIF2α phosphorylation, and caspase-dependent apoptosis. Although previous studies have reported that mycolactone targets SEC61A1 based on mutation screening and structural analysis in several cell lines, we have reconfirmed that SEC61A1 is a mycolactone target by genome-wide screening in THP-1 cells. These results shed light on the cytotoxicity of mycolactone and suggest that the inhibition of mycolactone activity or SEC61A1 downstream cascades will be a novel therapeutic modality to eliminate the harmful effects of mycolactone in addition to the 8-week antibiotic regimen of rifampicin and clarithromycin.
Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients

Background Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. Methods In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. Results Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p = .013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min (p = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline (p < .01). Conclusions In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an “activated” electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.
Evidence of co-exposure with Brucella spp, Coxiella burnetii, and Rift Valley fever virus among various species of wildlife in Kenya

Background Co-infection, especially with pathogens of dissimilar genetic makeup, may result in a more devastating impact on the host. Investigations on co-infection with neglected zoonotic pathogens in wildlife are necessary to inform appropriate prevention and control strategies to reduce disease burden in wildlife and the potential transmission of these pathogens between wildlife, livestock and humans. This study assessed co-exposure of various Kenyan wildflife species with Brucella spp, Coxiella burnetii and Rift Valley fever virus (RVFV). Methodology A total of 363 sera from 16 different wildlife species, most of them (92.6%) herbivores, were analysed by Enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against Brucella spp, C. burnetii and RVFV. Further, 280 of these were tested by PCR to identify Brucella species. Results Of the 16 wildlife species tested, 15 (93.8%) were seropositive for at least one of the pathogens. Mean seropositivities were 18.9% (95% CI: 15.0–23.3) for RVFV, 13.7% (95% CI: 10.3–17.7) for Brucella spp and 9.1% (95% CI: 6.3–12.5) for C. burnetii. Buffaloes (n = 269) had higher seropositivity for Brucella spp. (17.1%, 95% CI: 13.0–21.7%) and RVFV (23.4%, 95% CI: 18.6–28.6%), while giraffes (n = 36) had the highest seropositivity for C. burnetii (44.4%, 95% CI: 27.9–61.9%). Importantly, 23 of the 93 (24.7%) animals positive for at least one pathogen were co-exposed, with 25.4% (18/71) of the positive buffaloes positive for brucellosis and RVFV. On molecular analysis, Brucella DNA was detected in 46 (19.5%, CI: 14.9–24.7) samples, with 4 (8.6%, 95% CI: 2.2–15.8) being identified as B. melitensis. The Fisher’s Exact test indicated that seropositivity varied significantly within the different animal families, with Brucella (p = 0.013), C. burnetii (p = <0.001) and RVFV (p = 0.007). Location was also significantly associated (p = <0.001) with Brucella spp. and C. burnetii seropositivities. Conclusion Of ~20% of Kenyan wildlife that are seropositive for Brucella spp, C. burnetii and RVFV, almost 25% indicate co-infections with the three pathogens, particularly with Brucella spp and RVFV.
Making use of scenarios. Supporting scenario use in product design

The discipline of Scenario-Based Product Design (SBPD) guides the use of scenarios in a product design process. As concrete narratives, scenarios could facilitate making explicit how users would use the designed product in their activities, allowing usability studies to be an integrated part of the design process early on and not as a detached post-design testing. The early framework for scenario use was in the design of computer applications with the rise of Information Technology in the 1980s. The later works are often tailored to each new domain, even to some extent to each specific case, making the developed approaches not directly applicable to other domains. Within the context of consumer product design, the prior work is incomplete in that it has not fully addressed the particular characteristics of this domain. This thesis complements the understanding on SBPD from the theoretical perspective with an application of this knowledge to support the practice of product design. Through collaboration with industry, a tool is developed to provide a practical guidance for applying SBPD in design practice. The contribution of this research is a practice-based approach to create, use and manage scenarios in a product design process. The effort to create and maintain scenarios is considered justified as long as the scenario use is sustainable, and there is good interfacing with other activities in the design process. Future work could use the tool design and the recommendations provided in this thesis as the basis for making the support tool available to the design industry at large.
Prognosis and risk factors of chronic kidney disease progression in patients with diabetic kidney disease and non-diabetic kidney disease: a prospective cohort CKD-ROUTE study

Abstract Diabetic kidney disease (DKD) is emerging rapidly as the leading cause of chronic kidney disease (CKD) worldwide. In this 3-year prospective, multicenter cohort study, a total of 1138 pre-dialysis CKD patients were recruited. Patients were categorized into two groups according to the etiologies of DKD and non-diabetic kidney disease (NDKD). Propensity score matching was performed to adjust for confounding factors, resulting in 197 patients being assigned to DKD and NDKD groups, respectively. The primary endpoints were 50% estimated glomerular filtration rate (eGFR) decline and initiation of kidney replacement therapy (KRT). The secondary endpoints were all-cause death and the development of cardiovascular disease (CVD) events. We found that DKD patients have a higher risk to develop 50% eGFR decline endpoint (HR:2.30, 95%CI [1.48–3.58], p < 0.001) and KRT endpoint (HR:1.64, 95%CI [1.13–2.37], p < 0.05) than NDKD patients. The 3-year cumulative incidence of 50% eGFR decline and KRT endpoint was significantly higher in DKD patients (26.90% vs.13.71% and 35.03% vs. 22.34%, respectively). The Cox regression analyses showed that the increased systolic blood pressure (SBP), DKD, decreased serum albumin (Alb), and higher CKD stages were risk factors for the 50% eGFR decline endpoint; the increased SBP, DKD, decreased serum Alb, serum creatinine (Scr), higher CKD stages, presence of proteinuria and CVD were risk factors for KRT endpoint; the increased age, decreased hemoglobin (Hb), decreased serum Alb were risk factors for all-cause death endpoint; the increased age, decreased serum Alb were risk factors for CVD events endpoint. Appropriate preventive or therapeutic interventions should be taken to control these predictive factors to delay the development of CKD complications, thereby improving the prognosis and reducing the disease burden of the high-risk populations.
Characteristics of T Cell Receptor Beta Repertoires Associated With Behçet’s Syndrome Patients With Major Organ Involvements

T lymphocytes are one of the major components of the adaptive immunity in Behçet’s syndrome (BS) pathology. To further understand of the role of T cells in Behçet’s syndrome (BS), we explore disease related T cell receptor (TCR) repertoires. Methods We performed a bulk sequencing of the TCR beta chain (TRB) of peripheral T-cells collected from 45 BS patients with panuveitis, intestinal involvement, and cardiovascular lesions and 10 cases of healthy controls (HC). Data analysis included peptide sequences, diversity analysis, variable (V)-joining (J) gene usage and K-nearest neighbor algorithm. TCR repertoire signatures, by high-throughput TCR beta chain (TRB) sequencing of peripheral blood samples from BS patients with major organ involvement.
Complex Network Evolution Model Based on Turing Pattern Dynamics

Complex network models are helpful to explain the evolution rules of network structures, and also are the foundations of understanding and controlling complex networks. The existing studies (e.g., scale-free model, small-world model) are insufficient to uncover the internal mechanisms of the emergence and evolution of communities in networks. To overcome the above limitation, in consideration of the fact that a network can be regarded as a pattern composed of communities, we introduce Turing pattern dynamic as theory support to construct the network evolution model. Specifically, we develop a Reaction-Diffusion model according to Q-Learning technology (RDQL), in which each node regarded as an intelligent agent makes a behavior choice to update its relationships, based on the utility and behavioral strategy at every time step. Extensive experiments indicate that our model not only reveals how communities form and evolve, but also can generate networks with the properties of scale-free, small-world and assortativity. The effectiveness of the RDQL model has also been verified by its application in real networks. Furthermore, the depth analysis of the RDQL model provides a conclusion that the proportion of exploration and exploitation behaviors of nodes is the only factor affecting the formation of communities. The proposed RDQL model has potential to be the basic theoretical tool for studying network stability and dynamics.
Combination of paeoniflorin and calycosin-7-glucoside alleviates ischaemic stroke injury via the PI3K/AKT signalling pathway

Abstract Context Paeoniflorin (PF) and calycosin-7-glucoside (CG, Paeonia lactiflora Pall. extract) have demonstrated protective effects in ischaemic stroke. Objective To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury in vivo and in vitro. Materials and methods Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the in vivo experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed in vivo. Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO2 for 6 h. SOD, MDA, ROS, LDH and protein levels were measured in vitro. Results PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression in vivo and in vitro, and reduced GSK-3β (10.5%, 9.6%) expression. In vitro, PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively). Conclusions PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.
Quantifying congestion with player tracking data in Australian football

With 36 players on the field, congestion in Australian football is an important consideration in identifying passing capacity, assessing fan enjoyment, and evaluating the effect of rule changes. However, no current method of objectively measuring congestion has been reported. This study developed two methods to measure congestion in Australian football. The first continuously determined the number of players situated within various regions of density at successive time intervals during a match using density-based clustering to group players as ‘primary’, ‘secondary’, or ‘outside’. The second method aimed to classify the level of congestion a player experiences (high, nearby, or low) when disposing of the ball using the Random Forest algorithm. Both approaches were developed using data from the 2019 and 2021 Australian Football League (AFL) regular seasons, considering contextual variables, such as field position and quarter. Player tracking data and match event data from professional male players were collected from 56 matches performed at a single stadium. The random forest model correctly classified disposals in high congestion (0.89 precision, 0.86 recall, 0.96 AUC) and low congestion (0.98 precision, 0.86 recall, 0.96 AUC) at a higher rate compared to disposals nearby congestion (0.72 precision, 0.88 recall, 0.88 AUC). Overall, both approaches enable a more efficient method to quantify the characteristics of congestion more effectively, thereby eliminating manual input from human coders and allowing for a future comparison between additional contextual variables, such as, seasons, rounds, and teams.
Impédance de paroi des matériaux à réaction localisée

Ce travail traite du developpement de conditions aux limites (CL) pour prendre en compte des materiaux absorbants dans les codes CAA. L'approche temporelle est necessaire pour reproduire la propagation d'un bruit large bande par un seul calcul. La traduction de la relation d'impedance vers le domaine temporel est premierement realisee par une transformee de Fourier discrete tres couteuse en stockage de donnees. Des simulations de tube d'impedance montrent que la prise en compte du cisaillement de l'ecoulement est necessaire suivant le nombre de Mach. On s'attache ensuite a reduire ce stockage en utilisant les proprietees de la transformee en z. En vue de sa generalisation, la formulation de la relation d'impedance est rendue 1D suivant la normale a la paroi en chaque point de maillage. Ce traitement curviligne base sur les metriques du code de calcul permet une application locale non generatrice de frequences parasites. Des simulations de diffraction et de propagation en presence d'absorbant montrent un cout de stockage faible et un temps CPU identique au traitement d'une paroi rigide. Enfin une etude de l'absorption acoustique dans les resonateurs est effectuee en vue d'une extension des CL a des niveaux acoustiques plus eleves.
The Metabolic Adaptation in Response to Nitrate Is Critical for Actinobacillus pleuropneumoniae Growth and Pathogenicity under the Regulation of NarQ/P

Nitrate metabolism is an adaptation mechanism used by many bacteria for survival in anaerobic environments. As a by-product of inflammation, nitrate is used by the intestinal bacterial pathogens to enable gut infection. ABSTRACT Nitrate metabolism is an adaptation mechanism used by many bacteria for survival in anaerobic environments. As a by-product of inflammation, nitrate is used by the intestinal bacterial pathogens to enable gut infection. However, the responses of bacterial respiratory pathogens to nitrate are less well understood. Actinobacillus pleuropneumoniae is an important bacterial respiratory pathogen of swine. Previous studies have suggested that adaptation of A. pleuropneumoniae to anaerobiosis is important for infection. In this work, A. pleuropneumoniae growth and pathogenesis in response to the nitrate were investigated. Nitrate significantly promoted A. pleuropneumoniae growth under anaerobic conditions in vitro and lethality in mice. By using narQ and narP deletion mutants and single-residue-mutated complementary strains of ΔnarQ, the two-component system NarQ/P was confirmed to be critical for nitrate-induced growth, with Arg50 in NarQ as an essential functional residue. Transcriptome analysis showed that nitrate upregulated multiple energy-generating pathways, including nitrate metabolism, mannose and pentose metabolism, and glycerolipid metabolism via the regulation of NarQ/P. Furthermore, narQ, narP, and its target gene encoding the nitrate reductase Nap contributed to the pathogenicity of A. pleuropneumoniae. The Nap inhibitor tungstate significantly reduced the survival of A. pleuropneumoniae in vivo, suggesting that Nap is a potential drug target. These results give new insights into how the respiratory pathogen A. pleuropneumoniae utilizes the alternative electron acceptor nitrate to overcome the hypoxia microenvironment, which can occur in the inflammatory or necrotic infected tissues.
Constrained Systems in a Coarse-Grained Scenario

A number of new approaches based on fractional calculus have been presented and discussed in the literature over the past years. Their purpose is to find out different perspectives and describe particular phenomena in connection with field theory and gravity at a more fundamental level. On the other hand, procedures related to canonical quantization are really essential in field theory. More recently, the investigation of a wide category of new classical field-theoretic models and their respective quantized counterparts have been pursued which yield a very rich scenario that enables us to connect different areas of physics. For instance, it is not fairly well-known how to deal with dissipative or nonlinear systems; there are many paths of investigation in the literature; none of them presents a systematic and general procedure to tackle the problem. However, it is widely accepted today that the fractional formalism may be viewed as a powerful alternative to study dissipative systems. In our present contribution, we propose a pragmatic and detailed way of addressing the question. Adopting a particular approach to fractional calculus, this paper sets out to build up a consistent extension of the Faddeev-Jackiw (or Symplectic) algorithm to carry out the quantization procedure of nonconservative models in the standard canonical way. In our treatment, we shall choose the so-called Modified Riemman Liouville (MRL) approach, where the chain rule is as workable as it is in the standard differential calculus. We believe that, by adopting the extended version of Fractional Symplectic Quantization procedure, it shall be possible to carry out a deeper analysis of gauge theories implemented in a coarse-grained scenario.
A systematic review of randomized controlled trials on efficacy and safety of transcranial direct current stimulation in major neurodevelopmental disorders: ADHD, autism, and dyslexia

Among the target groups in child and adolescent psychiatry, transcranial direct current stimulation (tDCS) has been more applied in neurodevelopmental disorders specifically, attention‐deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and dyslexia. This systematic review aims to provide the latest update on published randomized‐controlled trials applying tDCS in these disorders for evaluating its efficacy and safety.
Small is Beautiful: Compressing Deep Neural Networks for Partial Domain Adaptation

Domain adaptation is a promising way to ease the costly data labeling process in the era of deep learning (DL). A practical situation is partial domain adaptation (PDA), where the label space of the target domain is a subset of that in the source domain. Although existing methods yield appealing performance in PDA tasks, it is highly presumable that computation overhead exists in deep PDA models since the target is only a subtask of the original problem. In this work, PDA and model compression are seamlessly integrated into a unified training process. The cross-domain distribution divergence is reduced by minimizing a soft-weighted maximum mean discrepancy (SWMMD), which is differentiable and functions as regularization during network training. We use gradient statistics to compress the overparameterized model to identify and prune redundant channels based on the corresponding scaling factors in batch normalization (BN) layers. The experimental results demonstrate that our method can achieve comparable classification performance to state-of-the-art methods on various PDA tasks, with a significant reduction in model size and computation overhead.
Delegation and consultation on operational and tactical issues: Any difference in their potentialities for a healthier psychosocial work environment?

Abstract Background Despite the growing number of studies on direct participation labor‐management practices, little is known about the role of their different discretionary degrees (delegation or consultation) and topics in their relationship with the psychosocial work environment by occupational groups. Methods Cross‐sectional study on the relationship between direct participation and work‐related psychosocial risks (using COPSOQ‐ISTAS21 v3) on a representative sample of the salaried and wage‐earning employees in Spain (n = 1807). Prevalence ratios were calculated using adjusted Poisson regression models, controlling for 10 other labor‐management practices, sex, and age, and stratified by occupational group. Results The use of direct participation was either associated consistently with a healthier psychosocial work environment (mostly in manual occupations, which presented twice as many positive associations as nonmanual occupations, and of greater strength, mostly in the control and social support dimensions) or there were no significant associations (mostly among nonmanual occupations and in relation to work pace). More frequent and stronger associations were observed when consultation and delegation were used in combination. If used separately, consultation achieved better results among manual occupations and delegation among nonmanual occupations. Direct participation topics were not important for results in manual occupations whereas results were better on tactical (vs. operational) issues in nonmanual occupations. Conclusions Direct participation does not change power structure, but it may be a useful intervention at the company level to reduce work‐related psychosocial exposures and associated diseases among workers in manual occupations, and consequently for decreasing occupational exposures and health inequalities.