Miracle-dz/UniFAR-FTUs huggingface dataset:
A New RF Heating Strategy for Thermal Treatment of Atherosclerosis

Objectives: Restenosis remains a challenge for the treatment of atherosclerosis due to the damage of the endothelial layer and induced proliferation of the smooth muscle cell. Methods: A new RF heating strategy was proposed to selectively ablate the atherosclerosis plaque, and to thermally inhibit the proliferation of smooth muscle cells, while keeping the endothelial cells intact. To achieve the goal, an internal cooling agent and distributed electrodes have been integrated in the new designed balloon catheter to focus the shape conformal energy onto the plaque shape. A three-dimensional (3-D) model with experimentally fitted parameters has been established to demonstrate the heating ability of the design and evaluate the microelectrodes configurations for different plaque geometries. Results: The 3-D shape of the lesions resulting from different electrodes settings is obtained. It is found that by individual control of the micro-electrodes, special shapes of the lesions can be formed, which can match the eccentric crescent plaques. Besides, through changing of the polarity of the electrodes, separate lesions can be reached. This suggests the possibility for treatment of disconnected plaques in situ. Conclusion: By the control of RF heating and convection coefficient of the internal cooling agent, a targeted heating region away from the inner surface of the blood vessel can be realized. Significance: This study has illustrated the possibility of achieving a precision thermal treatment of atherosclerosis in favor of inhibiting further restenosis.
Are we listening to everything the PARK genes are telling us?

The cardinal motor symptoms that define Parkinson's disease (PD) clinically have been recognized for over 200 years. That these symptoms arise following the loss of dopamine neurons in the substantia nigra has been known for the last 50. These long‐established facts have fueled a broadly held expectation that degenerating dopaminergic neurons alone hold the key to understanding and curing PD. This prevalent expectation is at odds with the observation that many nonmotor symptoms, including depression and cognitive inflexibility among others, can appear years earlier than the overt dopaminergic neuron degeneration that drives motor abnormalities and are not improved by levodopa treatment. Thus, preserving or rescuing dopamine neuron health and function is of paramount importance, but this alone fails to capture the underlying neurobiology of earlier‐appearing nonmotor symptoms. Insight into the complete landscape of disease‐related abnormalities and the context in which they arise can be gleaned from a more comprehensive consideration of the PARK genes that are known to cause PD. Here, we make the case that a full incorporation of research showing when and where PARK genes are expressed as well as the impact of gene mutation on function throughout life, in tandem with research studying how dopaminergic neuron degeneration begins, is essential for a full understanding of the multi‐dimensional etiology of PD. A broad view may also reveal something about long‐term adjustments cells and systems make in response to gene mutation and help to identify mechanisms conferring the resilience or susceptibility of some cells and systems over others.
Differences in clinical characteristics, muscle mass, and physical performance among different frailty levels in Chinese older men

The study was conducted in accordance with the To the Editor: Frailty is defined as a vulnerable state that places older adults at increased risk for adverse health Declaration of Helsinki and was approved by the Ethical outcomes, and can explain substantial heterogeneity of health status. Previous studies have demonstrated the utility of the frailty phenotype scale and frailty index (FI) in identifying frail older people in China. Several experimental and clinical studies on frailty have been published using the above methods in recent years, but influential factors for discriminating frailty levels in Chinese older adults have not yet been determined. Elucidating this issue is of importance, because early detection of frailty-related factors and subsequent intervention are essential for safeguarding functionality and preventing the occurrence of adverse consequences among older people.
The Preclinical and Clinical Progress of Bacteriophages and Their Lytic Enzymes: The Parts are Easier than the Whole

The therapeutic potential of phages has been considered since their first identification more than a century ago. The evident concept of using a natural predator to treat bacterial infections has, however, since then been challenged considerably. Initially, the vast success of antibiotics almost eliminated the study of phages for therapy. Upon the renaissance of phage therapy research, the most provocative and unique properties of phages such as high specificity, self-replication and co-evolution prohibited a rapid preclinical and clinical development. On the one hand, the typical trajectory followed by small molecule antibiotics could not be simply translated into the preclinical analysis of phages, exemplified by the need for complex broad spectrum or personalized phage cocktails of high purity and the more complex pharmacokinetics. On the other hand, there was no fitting regulatory framework to deal with flexible and sustainable phage therapy approaches, including the setup and approval of adequate clinical trials. While significant advances are incrementally made to eliminate these hurdles, phage-inspired antibacterials have progressed in the slipstream of phage therapy, benefiting from the lack of hurdles that are typically associated with phage therapy. Most advanced are phage lytic enzymes that kill bacteria through peptidoglycan degradation and osmotic lysis. Both phages and their lytic enzymes are now widely considered as safe and have now progressed to clinical phase II to show clinical efficacy as pharmaceutical. Yet, more initiatives are needed to fill the clinical pipeline to beat the typical attrition rates of clinical evaluation and to come to a true evaluation of phages and phage lytic enzymes in the clinic.
Dermatology and anatomy laboratory: comparing three formats of integration.

BACKGROUND Medical schools rarely offer exposure to clinical dermatology in the first-year curriculum. OBJECTIVE We describe and report student satisfaction results of three novel teaching methods for integrating basic dermatology concepts into gross anatomy laboratory. METHODS During the first year of the intervention, 180 students attended an hour-long anatomy laboratory session during which skin lesions were examined. One attending and three resident dermatologists spent time at all tables of students, then circulated to answer questions. During the second year, 189 students participated in the same teaching session preceded by a 30-minute in-class lecture. During the third year, 172 students were given the option to view a supplemental online video module before or after the teaching session. Each year following the teaching session, students were sent an optional online survey regarding the impact of the teaching session on their understanding of skin lesions and their cadaver experience. RESULTS Overall, students felt the intervention helped them develop a better understanding and appreciation for dermatology. Preceding the laboratory session with a lecture or educational video yielded higher satisfaction scores. CONCLUSIONS This brief teaching intervention illustrates an approach to introducing dermatologic entities within the foundational science curriculum of the first year of medical school.
Molecularly imprinted solid-phase extraction method for the gas chromatographic analysis of organochlorine fungicides in ginseng.

A highly selective molecularly imprinted solid-phase extraction coupled with gas chromatography method was developed for the simultaneous isolation and determination of four organochlorine fungicides (pentachloronitrobenzene, pentachloroaniline, methylpentachlorophenyl sulfide, and hexachlorobenzene) in ginseng samples. A novel molecularly imprinted polymer with pentachloronitrobenzene as template was synthesized by precipitation polymerization employing butanone/n-heptane (6.5:3.5, v/v) solution as porogen. The limit of detection of the method was 0.001 mg/kg, and the limit of quantification was 0.002 mg/kg. The different spiked levels of ginseng samples were 0.05, 0.5, 2.0 for pentachloronitrobenzene and pentachloroaniline, and 0.01, 0.1, 1.0 for methylpentachlorophenyl sulfide and hexachlorobenzene. The average recoveries of four organochlorine fungicides were 87.6-92.3% of pentachloronitrobenzene, 79.3-95.2% of pentachloroaniline, 80.3-90.4% of methylpentachlorophenyl sulfide, and 83.5-91.7% of hexachlorobenzene, respectively. This new method could be applied to direct determination of four organochlorine fungicides in ginseng samples.
Towards the use of ion mobility mass spectrometry derived collision cross section as a screening approach for unambiguous identification of targeted pesticides in food.

RATIONALE Mass spectrometry (MS) is the reference method for the screening of ultra-trace residues of pesticides in food because MS offers the required selectivity/sensitivity to gather information and enable the analyst to make informed decisions during the identification process. Here we present and discuss the use of collision cross section (CCS) values in addition to mass accuracy and retention times in a pesticide screening method that integrates all the features offered by coupling ultra-performance liquid chromatography (UPLC) with ion mobility mass spectrometry (IMS-MS). METHODS All experiments were carried out using UHPLC coupled to a travelling wave ion mobility mass spectrometer equipped with an electrospray ionization (ESI) source working in positive mode. An in-house library containing 200 pesticides was built using standard solutions and used as reference for a TWCCS calibration study. Matrix extracts were analyzed to evaluate the performance of different screening workflows based on TWCCS, mass accuracy and retention times. RESULTS The results proved that TWCCS values are very consistent, as the measured values do not differ more than 1% from the in-house reference data library and emphasized the importance of the first low m/z mobility calibration point to guarantee full independence from instrument parameters and calibrant. The screening procedure was simplified to a single step by fully exploiting the content of ion mobility without generating any false detections, either positive or negative, from spiked samples and a previous proficiency test. CONCLUSIONS The screening approach proposed in this study is unconventional and based on large mass accuracy (20 ppm) and retention time windows (0.5 min) to capture, in a first step, a maximum of detected compounds. Compounds of interest are then identified by comparing measured collision cross sections with the measured reference library collision cross sections (with relative error tolerance lower than 2%).
Influence of Steel Plates and Studs on Shrinkage Behavior and Cracking Potential of High-Performance Concrete

To help designers develop solutions to overcome the cracking problem in steel-plate-reinforced concrete composite shear walls due to the concrete shrinkage, the influence of steel plates and studs on the shrinkage behavior of high-performance concrete (HPC), including restrained shrinkage strain, shrinkage strain gradient, and cracking potential, were theoretically and experimentally investigated in this study. A model for theoretical analysis was used to research the shrinkage performance of concrete that was restrained by steel plates and studs. The major parameters involved in the experiments include the thickness and material elastic modulus of the steel plate, in addition to the diameter, height, and number of studs. It was found that the shrinkage of HPC decreases and its potential cracking increases with the increase of thickness and elastic modulus of the steel plate, and the diameter, height, and number of studs. The restraining effect of the steel plate and stud on the HPC shrinkage decreases with the distance of their respective locations. It demonstrates that the HPC near a steel plate and stud is prone to crack compared with that far away from the steel plate and stud. This potential could be reduced by uniformly restraining the HPC.
The growth ring concept: seeking a broader and unambiguous approach covering tropical species

The concept of growth rings is little discussed in the literature and their treatment remains somewhat confusing in terms of the diversity of structures described. This situation has a major impact on the study of growth rings in tropical species, in which variations and complexity are greater and accuracy of identification less good. The rigid conceptual delimitations used by dendrochronologists and wood anatomists of temperate regions cannot be applied to the study of growth rings in most tropical species, which has led to neglect of this subject. With the objective of discussing the concept of growth rings, the present study consists of a survey of anatomical, periodicity, causal and evolutionary aspects of the treatment of these structures as evidenced in previous studies, and the evaluation of their application and limitations to the development of this concept. Anatomical aspects arise through radial integrity, or the presence of early and late wood; the degree of distinction of the rings, which may vary from well to poorly defined; and tangential continuity, meaning that rings may form a complete circle in the transverse section of the trunk, or instead be tangentially discontinuous, lens‐shaped or in wedges. In addition there are a diversity of anatomical markers which enable us to recognize growth rings. Regarding periodicity, the rings may be annual, infra‐annual or supra‐annual. Causal aspects include genetic, endogenous and environmental components. Evolutionary aspects continue to be insufficiently investigated, and although most comparative studies treat growth rings recognized by different markers as though they were a single character, it remains questionable whether they can be regarded as homologous or the result of homoplasy. We conclude that the elaboration of a robust but broad definition which can include all the variation observed in growth rings of tropical species is a complex task, which is only possible by overcoming the restrictions adopted by dendrochronologists and wood anatomists of temperate regions for whom growth rings are essentially annual, strongly demarcated, tangentially continuous and restricted to the most pronounced markers.
Optimization of cyclopropane fatty acids production in Yarrowia lipolytica

Cyclopropane fatty acids, which can be simply converted to methylated fatty acids, are good unusual fatty acid candidates for long‐term resistance to oxidization and low‐temperature fluidity useful for oleochemistry and biofuels. Cyclopropane fatty acids are present in low amounts in plants or bacteria. In order to develop a process for large‐scale biolipid production, we expressed 10 cyclopropane fatty acid synthases from various organisms in the oleaginous yeast Yarrowia lipolytica, a model yeast for lipid metabolism and naturally capable of producing large amounts of lipids.
The ezh2(sa1199) mutant zebrafish display no distinct phenotype

Polycomb group (PcG) proteins are essential regulators of epigenetic gene silencing and development. The PcG protein enhancer of zeste homolog 2 (Ezh2) is a key component of the Polycomb Repressive Complex 2 and is responsible for placing the histone H3 lysine 27 trimethylation (H3K27me3) repressive mark on the genome through its methyltransferase domain. Ezh2 is highly conserved in vertebrates. We studied the role of ezh2 during development of zebrafish with the use of a mutant allele (ezh2(sa1199), R18STOP), which has a stop mutation in the second exon of the ezh2 gene. Two versions of the same line were used during this study. The first and original version of zygotic ezh2(sa1199) mutants unexpectedly retained ezh2 expression in brain, gut, branchial arches, and eyes at 3 days post-fertilization (dpf), as revealed by in-situ hybridization. Moreover, the expression pattern in homozygous mutants was identical to that of wild types, indicating that mutant ezh2 mRNA is not subject to nonsense mediated decay (NMD) as predicted. Both wild type and ezh2 mutant embryos presented edemas at 2 and 3 dpf. The line was renewed by selective breeding to counter select the non-specific phenotypes and survival was assessed. In contrast to earlier studies on ezh2 mutant zebrafish, ezh2(sa1199) mutants survived until adulthood. Interestingly, the ezh2 mRNA and Ezh2 protein were present during adulthood (70 dpf) in both wild type and ezh2(sa1199) mutant zebrafish. We conclude that the ezh2(sa1199) allele does not exhibit an ezh2 loss-of-function phenotype.
Characteristics of School-Associated Youth Homicides — United States, 1994–2018

To understand trends and characteristics in school-associated homicides involving youths, data from CDC's School-Associated Violent Death Surveillance System were analyzed for 393 single-victim incidents that occurred during July 1994-June 2016 and 38 multiple-victim incidents (resulting in 121 youth homicides) during July 1994-June 2018. School-associated homicides consistently represent <2% of all youth homicides in the United States (1,2). The overall 22-year trend for single-victim homicide rates did not change significantly. However, multiple-victim incidence rates increased significantly from July 2009 to June 2018. Many school-associated homicides, particularly single-victim incidents, are similar to youth homicides unrelated to schools, often involving male, racial/ethnic minority youth victims, and occurring in urban settings. The majority of both single-victim (62.8%) and multiple-victim (95.0%) homicides were from a firearm-related injury. A comprehensive approach to violence prevention is needed to reduce risk for violence on and off school grounds.
Changes in area and number of nature reserves in China

Nature reserves (NR) are the cornerstone of biodiversity conservation. Over the past 60 years, the rapid expansion of NRs in China, one of the world's megadiverse countries, has played a critical role in slowing biodiversity loss. We examined the changes in the number and area of China's NRs from 1956 to 2014 and analyzed the effect of economic development on the expansion of China's NRs from 2005 to 2014 with linear models. Despite a continuing increase in the number of NRs, the total area of China's NRs decreased by 3% from 2007 to 2014. This loss resulted from downsizing and degazettement of existing NRs and a slowdown in the establishment of new ones. Nature reserves in regions with rapid economic development exhibited a greater decrease in area, suggesting that downsizing and degazettement of NRs are closely related to the intensifying competition between economic growth and conservation. For example, boundary adjustments to national NRs, the most strictly protected NRs, along the coast of China's Yellow Sea, a global biodiversity hotspot with a fast‐growing economy, resulted in the loss of one‐third of the total area. One of the most important ecosystems in these NRs, tidal wetlands, decreased by 27.8% because of boundary adjustments and by 25.2% because of land reclamation. Our results suggest conservation achievement, in terms of both area and quality, are declining at least in some regions in the Chinese NR estate. Although the designation of protected areas that are primarily managed for sustainable use has increased rapidly in recent years in China, we propose that NRs with biodiversity conservation as their main function should not be replaced or weakened.
Electroporation-Induced Stress Response and Its Effect on Gene Electrotransfer Efficacy: In Vivo Imaging and Numerical Modeling

Objective: Skin is an attractive target tissue for gene transfer due to its size, accessibility, and its immune competence. One of the promising delivery methods is gene delivery by means of electroporation (EP), i.e., gene electrotransfer (GET). To assess the importance of different effects of electroporation for successful GET we investigated: stress response and transfection efficacy upon different pulse protocols. Moreover, numerical modeling was used to explain experimental results and to test the agreement of experimental results with current knowledge about GET. Methods: Double transgenic mice Hspa1b-LucF (+/+) Hspa1b-mPlum (+/+) were used to determine the level of stress sensed by the cell in the tissue in vivo that was exposed to EP. The effect of five different pulse protocols on stress levels sensed by the exposed cells and their efficacy for gene electrotransfer for two plasmids pEGFP-C1 (EGFP) and pCMV-tdTomato was tested. Results: Quantification of the bioluminescence signal intensity shows that EP, regardless of the electric pulse parameters used, increased mean bioluminescence compared to the baseline bioluminescence signal of the non-exposed skin. The results of numerical modeling indicate that thermal stress alone is not sufficient to explain the measured bioluminescence signal. Of the tested pulse protocols, the highest expression of EGFP and tdTomato was achieved with HV-MV (high voltage – medium voltage) protocols, which agrees also with numerical model. Significance: Although EP is widely used as a method for gene delivery, we show that the field could benefit from the use of mathematical modeling by introducing additional parameters such as EP induced stress and electrophoretic movement of plasmids.
A Human Skin Model Recapitulates Systemic Sclerosis Dermal Fibrosis and Identifies COL22A1 as a TGFβ Early Response Gene that Mediates Fibroblast to Myofibroblast Transition

Systemic sclerosis (SSc) is a complex multi-system autoimmune disease characterized by immune dysregulation, vasculopathy, and organ fibrosis. Skin fibrosis causes high morbidity and impaired quality of life in affected individuals. Animal models do not fully recapitulate the human disease. Thus, there is a critical need to identify ex vivo models for the dermal fibrosis characteristic of SSc. We identified genes regulated by the pro-fibrotic factor TGFβ in human skin maintained in organ culture. The molecular signature of human skin overlapped with that which was identified in SSc patient biopsies, suggesting that this model recapitulates the dermal fibrosis characteristic of the human disease. We further characterized the regulation and functional impact of a previously unreported gene in the setting of dermal fibrosis, COL22A1, and show that silencing COL22A1 significantly reduced TGFβ-induced ACTA2 expression. COL22A1 expression was significantly increased in dermal fibroblasts from patients with SSc. In summary, we identified the molecular fingerprint of TGFβ in human skin and demonstrated that COL22A1 is associated with the pathogenesis of fibrosis in SSc as an early response gene that may have important implications for fibroblast activation. Further, this model will provide a critical tool with direct relevance to human disease to facilitate the assessment of potential therapies for fibrosis.