Miracle-dz/UniFAR-FTUs huggingface dataset:
Stability of Engineered Micro or Nanobubbles for Biomedical Applications

A micro/nanobubble (MNB) refers to a bubble structure sized in a micrometer or nanometer scale, in which the core is separated from the external environment and is normally made of gas. Recently, it has been confirmed that MNBs can be widely used in angiography, drug delivery, and treatment. Thus, MNBs are attracting attention as they are capable of constructing a new contrast agent or drug delivery system. Additionally, in order to effectively use an MNB, the method of securing its stability is also being studied. This review highlights the factors affecting the stability of an MNB and the stability of the MNB within the ultrasonic field. It also discusses the relationship between the stability of the bubble and its applicability in vivo.
SAXS studies of X-ray induced disulfide bond damage: Engineering high-resolution insight from a low-resolution technique

A significant problem in biological X-ray crystallography is the radiation chemistry caused by the incident X-ray beam. This produces both global and site-specific damage. Site specific damage can misdirect the biological interpretation of the structural models produced. Cryo-cooling crystals has been successful in mitigating damage but not eliminating it altogether; however, cryo-cooling can be difficult in some cases and has also been shown to limit functionally relevant protein conformations. The doses used for X-ray crystallography are typically in the kilo-gray to mega-gray range. While disulfide bonds are among the most significantly affected species in proteins in the crystalline state at both cryogenic and higher temperatures, there is limited information on their response to low X-ray doses in solution, the details of which might inform biomedical applications of X-rays. In this work we engineered a protein that dimerizes through a susceptible disulfide bond to relate the radiation damage processes seen in cryo-cooled crystals to those closer to physiologic conditions. This approach enables a low-resolution technique, small angle X-ray scattering (SAXS), to detect and monitor a residue specific process. A dose dependent fragmentation of the engineered protein was seen that can be explained by a dimer to monomer transition through disulfide bond cleavage. This supports the crystallographically derived mechanism and demonstrates that results obtained crystallographically can be usefully extrapolated to physiologic conditions. Fragmentation was influenced by pH and the conformation of the dimer, providing information on mechanism and pointing to future routes for investigation and potential mitigation. The novel engineered protein approach to generate a large-scale change through a site-specific interaction represents a promising tool for advancing radiation damage studies under solution conditions.
Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

Significance Identifying signaling pathways contributing to resistance to anti-TNF therapy in rheumatoid arthritis is crucial for the development of new therapeutic strategies for refractory rheumatoid arthritis. Th17 cells, a subset of proinflammatory CD4+ T cells, are implicated in the pathogenesis of the disease. We analyzed the gene expression profiles of Th17-enriched CD4+ T cells in anti-TNF–treated patients with rheumatoid arthritis and found that the elevated expression levels of transcription factor USF2 in anti-TNF refractory patients were associated with increased proinflammatory signaling of Th17 cells. USF2-knockdown experiments in Th17 cells revealed that USF2 promotes the pathogenicity of Th17 cells. These findings have implications for the development of new therapeutic strategies for refractory rheumatoid arthritis. IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA− CD4+ T (CCR6+ T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+ T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+ T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targeting USF2 in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.
Pre-Discharge Predictors of 1-Year Rehospitalization in Adolescents and Young Adults with Severe Mental Disorders: A Retrospective Cohort Study

Background and objectives: Readmissions of youths hospitalized for a severe mental disorder are common events and bear a remarkable human, social, and economic burden. The current study aimed at evaluating predictors of 1-year rehospitalization in a sample of adolescents and young adults with severe mental disorders. Materials and Methods: Data for ≤25-year-old inpatients with a severe mental disorder and consecutively admitted between 1 January 2016 and 30 June 2019 were collected. Subjects were retrospectively assessed over a follow-up period of one year after the index discharge to track readmissions—i.e., the primary outcome variable. Standard descriptive statistics were used. The association between variables and 1-year rehospitalization was estimated using the univariate Cox proportional hazards regression model. We then carried out a multivariable Cox regression model, also estimating the covariate-adjusted survivor function. Hazard ratios (HRs) with related 95% confidence intervals (95% CIs) were provided. Results: The final sample included 125 individuals. The multivariable Cox regression model estimated that co-occurring substance use disorders (HR = 2.14; 95% CI: 1.08 to 4.26; p = 0.029) and being admitted for a suicide attempt (HR = 2.49; 95% CI: 1.13 to 5.49; p = 0.024) were both significant predictors of 1-year rehospitalization. Conclusions: Our study showed that comorbid substance use disorders and being admitted for a suicide attempt were predictors of early readmission in youths with severe mental disorders. Although their generalizability is limited, our findings could contribute to improve the quality of young patients’ mental health care by identifying vulnerable subjects who may benefit from tailored interventions to prevent rehospitalizations.
Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties

Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of S. epidermidis was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections.
Neuroadaptive Finite-Time Control for Nonlinear MIMO Systems With Input Constraint

This article considers the problem of finite-time (FT) tracking control for a class of uncertain multi-input–multioutput (MIMO) nonlinear systems with input backlash. A modified FT command filter is designed in each step of backstepping, which ensures the output of the filter can faster approximate the derivatives of virtual signals, suppress chattering, and relax the input signal limit of the Levant differentiator. Then, the corresponding improved FT error compensation mechanism is adopted to reduce the negative impact of filtering errors. Furthermore, a neural-network-adaptive technology is proposed for MIMO systems with input backlash via FT convergence. It is shown that desired tracking performance can be implemented in finite time. The simulation example is presented to illustrate the effectiveness and advantages of the new design method.
Moving Past the Loss: A Longitudinal Qualitative Study of Health Care Staff Experiences of Disinvestment

This longitudinal qualitative study examines staff experience of disinvestment from a service they are accustomed to providing to their patients. It took place alongside a disinvestment trial that measured the impact of the removal of weekend allied health services from acute wards at two hospitals. Data were gathered from repeated interviews and focus groups with 450 health care staff. We developed a grounded theory, which explains changes in staff perceptions over time and the key modifying factors. Staff appeared to experience disinvestment as loss; a key difference to other operational changes. Early staff experiences of disinvestment were primarily negative, but evolved with time and change-management strategies such as the provision of data, clear and persistent communication approaches, and forums where the big picture context of the disinvestment was robustly discussed. These allowed the disinvestment trial to be successfully implemented at two health services, with high compliance with the research protocol.
Worldwide Epidemiology of Diabetes-Related End-Stage Renal Disease, 2000-2015.

OBJECTIVE The annual risk among patients with diabetes of reaching end-stage renal disease (ESRD) is largely unknown worldwide. This study aimed to compare the incidence of diabetes-related ESRD by creating a global atlas during 2000-2015. RESEARCH DESIGN AND METHODS The annual incidence of ESRD among patients with diabetes was calculated as the quotient of the number of incident ESRD patients with diabetes divided by the total number of patients with diabetes after subtraction of the number with existing ESRD. The estimated ESRD prevalence and annual incidence were validated with use of the data provided by Fresenius Medical Care, Germany, and previously reported data, respectively. RESULTS Data were obtained from 142 countries, covering 97.3% of the world population. The global percentage of the prevalent ESRD patients with diabetes increased from 19.0% in 2000 to 29.7% in 2015 worldwide, while the percentage of incident ESRD patients due to diabetes increased from 22.1% to 31.3%. The global annual incidence of ESRD among patients with diabetes increased from 375.8 to 1,016.0/million with diabetes during 2000-2015. The highest average rates were observed in the Western Pacific Region. Comparatively, the rates of incident ESRD among European patients with diabetes ranged from one-half (309.2 vs. 544.6) to one-third (419.4 vs. 1,245.2) of the rates of the Western Pacific population during 2000-2015. CONCLUSIONS Great and nonrandom geographic variation in the annual rates among patients with diabetes of reaching ESRD suggests that distinct health care, environmental, and/or genetic factors contribute to the progression of diabetic kidney disease. Measures to prevent and treat diabetes-related ESRD require better patient susceptibility stratification.
Ion-Conducting Thermoresponsive Films Based on Polymer-Grafted Cellulose Nanocrystals.

Mechanically robust, thermoresponsive, ion-conducting nanocomposite films are prepared from poly(2-phenylethyl methacrylate)-grafted cellulose nanocrystals (MxG-CNC-g-PPMA). One-component nanocomposite films of the polymer-grafted nanoparticle (PGN) MxG-CNC-g-PPMA are imbibed with 30 wt % imidazolium-based ionic liquid to produce flexible ion-conducting films. These films with 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (MxG-CNC-g-PPMA/[H]) not only display remarkable improvements in toughness (>25 times) and tensile strength (>70 times) relative to the corresponding films consisting of the ionic liquid imbibed in the two-component CNC/PPMA nanocomposite but also show higher ionic conductivity than the corresponding neat PPMA with the same weight percent of ionic liquid. Notably, the one-component film containing 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (MxG-CNC-g-PPMA/[E]) exhibits temperature-responsive ionic conduction. The ionic conductivity decreases at around 60 °C as a consequence of the lower critical solution temperature phase transition of the grafted polymer in the ionic liquid, which leads to phase separation. Moreover, holding the MxG-CNC-g-PPMA/[E] film at room temperature for 24 h returns the film to its original homogenous state. These materials exhibit properties relevant to thermal cutoff safety devices (e.g., thermal fuse) where a reduction in conductivity above a critical temperature is needed.
Bioimpedance phase angle in elite male athletes: a segmental approach

Objective: Phase angle (PA), a bioelectrical impedance analysis (BIA) parameter, has proven to be a proxy of body cell mass in athletes, but very few data are available on its segmental evaluation (upper and lower limbs). Therefore, we aimed to assess whether whole-body and segmental PA varied among elite male athletes of different sports and compared these to control groups. Additionally, we investigated its relationship with anthropometric and body composition parameters. Approach: Elite athletes practicing cycling, water polo and ballet dance aged 18–40 years underwent anthropometric and BIA measurements. PA (whole-body and upper and lower limbs) was considered as raw BIA variable. Data were also compared with healthy subjects with similar characteristics who served as control groups. Main results: Participants included three groups of male athletes: 18 cyclists (age 28.6 ± 3.4 years; weight 70.6 ± 5.4 kg; BMI 21.5 ± 1.4 kg m2), 20 water polo players (age 23.9 ± 4 years; weight 89.0 ± 5.2 kg; BMI 25.9 ± 1.9 kg m2) and 18 ballet dancers (age 19.2 ± 1.3 years; weight 63.3 ± 5.8 kg; BMI 20.8 ± 1.0 kg m2) and three groups of healthy control subjects each of which similar for general characteristics (one to one) to the previous ones. Both whole-body and limb PAs were significantly higher in athletes compared to their respective controls, whereas no differences were found among sport groups. PA was positively correlated with BMI and fat-free mass (FFM) more in athletes than in controls and FFM was the main determinant. Significance: PA may represent a useful proxy parameter of soft tissue mass quality, directly related to physical activity level. Furthermore, the direct evaluation of segmental PA among athletes practicing different sports may be useful for assessing and monitoring the differences among athletes and changes due to training.
The Perception System of Intelligent Ground Vehicles in All Weather Conditions: A Systematic Literature Review

Perception is a vital part of driving. Every year, the loss in visibility due to snow, fog, and rain causes serious accidents worldwide. Therefore, it is important to be aware of the impact of weather conditions on perception performance while driving on highways and urban traffic in all weather conditions. The goal of this paper is to provide a survey of sensing technologies used to detect the surrounding environment and obstacles during driving maneuvers in different weather conditions. Firstly, some important historical milestones are presented. Secondly, the state-of-the-art automated driving applications (adaptive cruise control, pedestrian collision avoidance, etc.) are introduced with a focus on all-weather activity. Thirdly, the most involved sensor technologies (radar, lidar, ultrasonic, camera, and far-infrared) employed by automated driving applications are studied. Furthermore, the difference between the current and expected states of performance is determined by the use of spider charts. As a result, a fusion perspective is proposed that can fill gaps and increase the robustness of the perception system.
Urban Hedgehog Behavioural Responses to Temporary Habitat Disturbance versus Permanent Fragmentation

Simple Summary Wildlife is exposed to environmental disturbances. Some are limited to a short period and pass by, others are of a permanent nature. Often these two kinds of disturbances occur simultaneously. This makes it difficult to disentangle the specific behavioural response to each disturbance. As species may respond to different disturbances in different ways, it is important to know the species-specific and disturbance-specific responses to develop effective species conservation action. We investigated the behavioural responses of European hedgehogs (Erinaceus europaeus) in Berlin to temporary disturbance (in the form of an open-air music festival) and permanent disturbance (in the form of habitat fragmentation). We show that a music festival is a major stressor that strongly influences all investigated behaviours. Urban hedgehogs in a highly fragmented area showed subtle behavioural changes compared to those in low-fragmented areas, suggesting that fragmentation was a moderate challenge which they could cope with. Thus, the temporary disturbance by a music festival had a more serious impact on hedgehog behaviour than permanent disturbance caused by fragmentation. Moreover, we show that males responded stronger to the transient disturbance and females responded stronger to habitat fragmentation. Abstract Anthropogenic activities can result in both transient and permanent changes in the environment. We studied spatial and temporal behavioural responses of European hedgehogs (Erinaceus europaeus) to a transient (open-air music festival) and a permanent (highly fragmented area) disturbance in the city of Berlin, Germany. Activity, foraging and movement patterns were observed in two distinct areas in 2016 and 2017 using a “Before & After“ and “Control & Impact“ study design. Confronted with a music festival, hedgehogs substantially changed their movement behaviour and nesting patterns and decreased the rhythmic synchronization (DFC) of their activity patterns with the environment. These findings suggest that a music festival is a substantial stressor influencing the trade-off between foraging and risk avoidance. Hedgehogs in a highly fragmented area used larger home ranges and moved faster than in low-fragmented and low-disturbed areas. They also showed behaviours and high DFCs similar to individuals in low-fragmented, low disturbed environment, suggesting that fragmentation posed a moderate challenge which they could accommodate. The acute but transient disturbance of a music festival, therefore, had more substantial and severe behavioural effects than the permanent disturbance through fragmentation. Our results are relevant for the welfare and conservation measure of urban wildlife and highlight the importance of allowing wildlife to avoid urban music festivals by facilitating avoidance behaviours.
Chloroplast immunity illuminated.

The chloroplast has recently emerged as pivotal to co-ordinating plant defence responses and as a target of plant pathogens. Beyond its central position in oxygenic photosynthesis and primary metabolism - key targets in the complex virulence strategies of diverse pathogens - the chloroplast integrates, decodes and responds to environmental signals. The capacity of chloroplasts to synthesize phytohormones and a diverse range of secondary metabolites, combined with retrograde and reactive oxygen signaling, provides exquisite flexibility to both perceive and respond to biotic stresses. These processes also represent a plethora of opportunities for pathogens to evolve strategies to directly or indirectly target "chloroplast immunity". This review covers the contribution of the chloroplast to Pathogen Associated Molecular Pattern and Effector Triggered Immunity as well as Systemic Acquired Immunity. We address phytohormone modulation of immunity and surmise how chloroplast-derived reactive oxygen species underpin chloroplast immunity through indirect evidence inferred from genetic modification of core chloroplast components and direct pathogen targeting of the chloroplast. We assess the impact of transcriptional reprogramming of nuclear encoded chloroplast genes during disease and defence and look at future research challenges.
Antioxidant and Antibacterial Activity of Caprylic Acid Vanillyl Ester Produced by Lipase-Mediated Transesterification

Vanillyl alcohol (VA), which is abundant in Vanilla bean, has strong antioxidant activity. However, the use of VA in the food and cosmetics industries is limited, due to its low solubility in emulsion or organic solvents. Meanwhile, medium chain fatty acids and medium chain monoglycerides have antibacterial activity. We synthesized butyric acid vanillyl ester (BAVE) or caprylic acid vanillyl ester (CAVE) from VA with tributyrin or tricaprylin through transesterification reaction using immobilized lipases. BAVE and CAVE scavenged 2,2-diphenyl-1-picrylhydrazyl radicals in organic solvents. In addition, BAVE and CAVE decreased the production rate of conjugated diene and triene in the menhaden oil-in-water emulsion system. While BAVE showed no antibacterial activity, CAVE showed antibacterial activity against food spoilage bacteria, including Bacillus coagulans. In this study, the antibacterial activity of vanillyl ester with medium chain fatty acid was first revealed. Zeta potential measurements confirmed that BAVE and CAVE were inserted into B. coagulans membrane. In addition, the propidium iodide uptake assay and fluorescent microscopy showed that CAVE increased B. coagulans membrane permeability. Therefore, CAVE is expected to play an important role in the food and cosmetics industries as a bi-functional material with both antioxidant and antibacterial activities.