Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH.

BACKGROUND Ultra-high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue, however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon. PURPOSE This work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half-maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue. METHODS We developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic-linear model and the radiosensitivity related parameters were adjusted in 1 Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles. RESULTS The results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose dependent response trends, if the g value is identical in both tumor and normal tissue. CONCLUSIONS The therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue dependent. For breast cancer, FLASH is beneficial in a minority of cases, however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia. This article is protected by copyright. All rights reserved.
Autocorrelation and regularization of query-based information retrieval scores

Query-based information retrieval refers to the process of scoring documents given a short natural language query. Query-based information retrieval systems have been developed to support searching diverse collections such as the world wide web, personal email archives, news corpora, and legal collections. This thesis is motivated by one of the tenets of information retrieval: the cluster hypothesis. We define a design principle based on the cluster hypothesis which states that retrieval scores should be locally consistent. We refer to this design principle as score autocorrelation. Our experiments show that the degree to which retrieval scores satisfy this design principle correlates positively with system performance. We use this result to define a general, black box method for improving the local consistency of a set of retrieval scores. We refer to this process as local score regularization. We demonstrate that regularization consistently and significantly improves retrieval performance for a wide variety of baseline algorithms. Regularization is closely related to classic techniques such as pseudo-relevance feedback and cluster-based retrieval. We demonstrate that the effectiveness of these techniques may be explained by their regularizing behavior. We argue that regularization should be adopted either as a generic post-processing step or as a fundamental design principle for retrieval models.
Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes

Introduction Gene therapy is a promising approach to be applied in cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies. However, cardiomyocytes are crucial cell types that are considered hard-to-transfect. The entrapment of nucleic acids in non-viral vectors, such as lipid nanoparticles (LNPs), is an attractive approach for safe and effective delivery. Methods Here, a mini-library of engineered LNPs was developed for pDNA delivery in cardiomyocytes. LNPs were characterized and screened for pDNA delivery in cardiomyocytes and identified a lead LNP formulation with enhanced transfection efficiency. Results By varying lipid molar ratios, the LNP formulation was optimized to deliver pDNA in cardiomyocytes with enhanced gene expression in vitro and in vivo, with negligible toxicity. In vitro, our lead LNP was able to reach a gene expression greater than 80%. The in vivo treatment with lead LNPs induced a twofold increase in GFP expression in heart tissue compared to control. In addition, levels of circulating myeloid cells and inflammatory cytokines remained without significant changes in the heart after LNP treatment. It was also demonstrated that cardiac cell function was not affected after LNP treatment. Conclusion Collectively, our results highlight the potential of LNPs as an efficient delivery vector for pDNA to cardiomyocytes. This study suggests that LNPs hold promise to improve gene therapy for treatment of cardiovascular disease.
Analysis of Diabetes Clinical Data Based on Recurrent Neural Networks

At present, diabetes is one of the most important chronic noncommunicable diseases, that have threatened human health. By 2020, the number of diabetic patients worldwide has reached 425 million. This amazing number has attracted the great attention of various countries. With the progress of computing technology, many mathematical models and intelligent algorithms have been applied in different fields of health care. 822 subjects were selected in this paper. They were divided into 389 diabetic patients and 423 nondiabetic patients. Each of the subjects included 41 indicators. Too many indicator variables would increase the computational effort and there could be a strong correlation and data redundancy between the data. Therefore, the sample features were first dimensionally reduced to generate seven new features in the new space, retaining up to 99.9% of the valid information from the original data. A diagnostic and classification model for diabetes clinical data based on recurrent neural networks were constructed, and particle swarm optimization (PSO) was introduced to optimise recurrent neural network's hyperparameters to achieve effective diagnosis and classification of diabetes.
Influence of an energy deficient and low carbohydrate acute dietary manipulation on iron regulation in young females

Hepcidin is a liver‐derived hormone that regulates iron metabolism. Recent studies suggest that an energy‐deficient diet or low carbohydrate (CHO) availability may increase hepcidin in the absence of inflammation. The purpose of the present study was to examine the impact of either an energy‐deficient diet or an ED diet with low CHO intake during three consecutive days on hepcidin responses, hematological variables, and energy metabolism in young Japanese women. Twenty‐two young females were divided into two different groups, either an energy‐deficient with low CHO intake group (ED + LCHO; 2.0 ± 0.3 g/kg/day CHO, 39%CHO, 1123 kcal/day) or an energy deficient with moderate CHO intake group (ED; 3.4 ± 0.3 g/kg/day CHO, 63%CHO, 1162 kcal/day). During the three consecutive days of the dietary intervention program, participants consumed only the prescribed diet and maintained their habitual physical activity levels. Body composition, substrate oxidation, iron metabolism, and inflammation were evaluated pre‐ and post‐intervention. Serum iron and ferritin levels were significantly elevated following the intervention (p < 0.001, p = 0.003, respectively). Plasma interleukin‐6 (IL‐6) levels did not change following the intervention. Serum hepcidin levels significantly increased after the intervention (p = 0.002). Relative change in hepcidin levels was significantly higher in the ED + LCHO (264.3 ± 87.2%) than in the ED group (68.9 ± 22.1%, p = 0.048). Three consecutive days of an energy‐deficient diet increased fasting hepcidin levels. Moreover, elevated hepcidin levels were further augmented when an energy‐deficient diet was combined with a lower CHO intake.
PGE2‐EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase

Brown adipose tissue (BAT) functions as a thermogenic organ and is negatively associated with cardiometabolic diseases. N6‐methyladenosine (m6A) modulation regulates the fate of stem cells. Here, we show that the prostaglandin E2 (PGE2)–E‐prostanoid receptor 3 (EP3) axis was activated during mouse interscapular BAT development. Disruption of EP3 impaired the browning process during adipocyte differentiation from pre‐adipocytes. Brown adipocyte‐specific depletion of EP3 compromised interscapular BAT formation and aggravated high‐fat diet‐induced obesity and insulin resistance in vivo. Mechanistically, activation of EP3 stabilized the Zfp410 mRNA via WTAP‐mediated m6A modification, while knockdown of Zfp410 abolished the EP3‐induced enhancement of brown adipogenesis. EP3 prevented ubiquitin‐mediated degradation of WTAP by eliminating PKA‐mediated ERK1/2 inhibition during brown adipocyte differentiation. Ablation of WTAP in brown adipocytes abrogated the protective effect of EP3 overexpression in high‐fat diet‐fed mice. Inhibition of EP3 also retarded human embryonic stem cell differentiation into mature brown adipocytes by reducing the WTAP levels. Thus, a conserved PGE2‐EP3 axis promotes BAT development by stabilizing WTAP/Zfp410 signaling in a PKA/ERK1/2‐dependent manner.
Bio-inspired Superwettable Surface for the Detection of Cancer Biomarker: A Mini Review

Inspired by nature, superwettable material-based biosensors have aroused wide interests due to their potential in cancer biomarker detection. This mini review mainly summarized the superwettable materials as novel biosensing substrates for the development of evaporation-induced enrichment-based signal amplification and visual biosensing method. Biosensing applications based on the superhydrophobic surfaces, superwettable micropatterned surfaces, and slippery lubricant-infused porous surfaces for various cancer biomarker detections were described in detail. Finally, an insight of remaining challenges and perspectives of superwettable biosensor is proposed.
Reassessing acetyl‐CoA supply and NADPH availability for mevalonate biosynthesis from glycerol in Escherichia coli

Mevalonate is an important platform compound for the biosynthesis of isoprenoids. It can be synthesized from acetyl‐CoA in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) by the introduced mvaES operon in Escherichia coli. The influences of E. coli hosts, acetyl‐CoA supply, and NADPH availability were assessed and engineered to improve the production titer and yield of mevalonate from glycerol. As a result, E. coli DH5α was found to be the best host with high specific capability and titer of mevalonate from glycerol. Through the engineering of phosphoketolase‐phosphotransacetylase (xPK‐PTA) bypass and NADPH availability, a final titer of 7.21 g/L with a specific capability of 1.36 g/g dry cell weight was gained in flask culture. Our work could offer new information to metabolically engineer the mevalonate pathway for the efficient production of isoprenoids.
Cell repertoire and proliferation of germinative cells of the model cestode Mesocestoides corti

Abstract Abstract The phylum Platyhelminthes shares a unique population of undifferentiated cells responsible for the proliferation capacity needed for cell renewal, growth, tissue repair and regeneration. These cells have been extensively studied in free-living flatworms, whereas in cestodes the presence of a set of undifferentiated cells, known as germinative cells, has been demonstrated in classical morphology studies, but poorly characterized with molecular biology approaches. Furthermore, several genes have been identified as neoblast markers in free-living flatworms that deserve study in cestode models. Here, different cell types of the model cestode Mesocestoides corti were characterized, identifying differentiated and germinative cells. Muscle cells, tegumental cells, calcareous corpuscle precursor cells and excretory system cells were identified, all of which are non-proliferative, differentiated cell types. Besides those, germinative cells were identified as a population of small cells with proliferative capacity in vivo. Primary cell culture experiments in Dulbecco's Modified Eagle Medium (DMEM), Echinococcus hydatid fluid and hepatocyte conditioned media in non-reductive or reductive conditions confirmed that the germinative cells were the only ones with proliferative capacity. Since several genes have been identified as markers of undifferentiated neoblast cells in free-living flatworms, the expression of pumilio and pL10 genes was analysed by qPCR and in situ hybridization, showing that the expression of these genes was stronger in germinative cells but not restricted to this cell type. This study provides the first tools to analyse and further characterise undifferentiated cells in a model cestode.
Epinephrine evokes shortening of human airway smooth muscle cells following β2 adrenergic receptor desensitization

Epinephrine (EPI), an endogenous catecholamine involved in the body’s fight-or-flight responses to stress, activates α1-adrenergic receptors (α1ARs) expressed on various organs to evoke a wide range of physiological functions, including vasoconstriction. In the smooth muscle of human bronchi, however, the functional role of EPI on α1ARs remains controversial. Classically, evidence suggests that EPI promotes bronchodilation by stimulating β2-adrenergic receptors (β2ARs). Conventionally, the selective β2AR agonism of EPI was thought to be, in part, due to a predominance of β2ARs and/or a sparse, or lack of α1AR activity in human airway smooth muscle (HASM) cells. Surprisingly, we find that HASM cells express a high abundance of ADRA1B (the α1AR subtype B) and identify a spontaneous “switch-like” activation of α1ARs that evokes intracellular calcium, myosin light chain phosphorylation, and HASM cell shortening. The switch-like responses, and related EPI-induced biochemical and mechanical signals, emerged upon pharmacological inhibition of β2ARs and/or under experimental conditions that induce β2AR tachyphylaxis. EPI-induced procontractile effects were abrogated by an α1AR antagonist, doxazosin mesylate (DM). These data collectively uncover a previously unrecognized feed-forward mechanism driving bronchospasm via two distinct classes of G protein-coupled receptors (GPCRs) and provide a basis for reexamining α1AR inhibition for the management of stress/exercise-induced asthma and/or β2-agonist insensitivity in patients with difficult-to-control, disease subtypes.
Smart home technology to support older people's quality of life: A longitudinal pilot study

Abstract Aim This pilot study aimed to explore the impact of Smart Home technology to support older people’s quality of life, particularly for those who live alone. Background There has been an increased interest in using innovative technologies and artificial intelligence to enable Smart Home technology to support older people to age independently in their own homes. Methods This study used a pre‐and post‐test design. The seven item Personal Wellbeing Index was used to measure participants’ subjective quality of life across seven quality of life domains. Participants (n = 60) aged between 68 and 90 years (M = 80.10, SD = 5.56) completed a 12‐week personalised Smart Home technology program. Results Approximately half of the participants lived alone (48.3%). Participants’ quality of life significantly increased (p = 0.010) after Smart Home use. Two domains, “achieving in life” (p = 0.026) and “future security” (p = 0.004), were also significantly improved after participating in the Smart Home technology program. Improvements in quality of life did not vary as a function of living arrangement (all ps > .152, all ηp2 > .00). Conclusion The current study provides preliminary evidence for the role of Smart Home technology in supporting older people’s quality of life, particularly their sense of achieving in life and future security.
Spruce giga-genomes: structurally similar yet distinctive with differentially expanding gene families and rapidly evolving genes.

Spruces (Picea spp.) are coniferous trees widespread in boreal and mountainous forests of the northern hemisphere, with large economic significance and enormous contributions to global carbon sequestration. Spruces harbor very large genomes with high repetitiveness, hampering their comparative analysis. Here, we present and compare the genomes of four different North American spruces: the genome assemblies for Engelmann spruce (Picea engelmannii) and Sitka spruce (P. sitchensis) together with improved and more contiguous genome assemblies for white spruce (P. glauca) and for a naturally occurring introgress of these three species known as interior spruce (P. engelmannii × glauca × sitchensis). The genomes were structurally similar, and a large part of scaffolds could be anchored to a genetic map. The composition of the interior spruce genome indicated asymmetric contributions from the three ancestral genomes. Phylogenetic analysis of the nuclear and organelle genomes revealed a topology indicative of ancient reticulation. Different patterns of expansion of gene families among genomes were observed and related with presumed diversifying ecological adaptations. We identified rapidly evolving genes that harbored high rates of nonsynonymous polymorphisms relative to synonymous ones, indicative of positive selection and its hitchhiking effects. These gene sets were mostly distinct between the genomes of ecologically contrasted species, and signatures of convergent balancing selection were detected. Stress and stimulus response was identified as the most frequent function assigned to expanding gene families and rapidly evolving genes. These two aspects of genomic evolution were complementary in their contribution to divergent evolution of presumed adaptive nature. These more contiguous spruce giga-genome sequences should strengthen our understanding of conifer genome structure and evolution, as their comparison offers clues into the genetic basis of adaptation and ecology of conifers at the genomic level. They will also provide tools to better monitor natural genetic diversity and improve the management of conifer forests.
Nickel hyperaccumulation, elemental profiles and agromining potential of three species of Odontarrhena from the ultramafics of Western Iran

Abstract The profiles of trace and major elements in three Odontarrhena species from the ultramafics of Western Iran (O. callichroa, O. penjwinensis and O. inflata) were evaluated to provide detailed information on their soil-plant relationships and potentials for agromining. The mean concentrations of Ni in leaf dry matter of these three species were 877, 3,270 and 2,720 mg kg−1, respectively. The mean concentrations of total soil Ni at sites Mazi Ban, Kamyaran and Ghala Ga were 1,470, 2,480, 1,030 mg kg−1, respectively. The Bioconcentration Factor (BCF) for Ni was >1 in O. penjwinensis and O. inflata, but not in O. callichroa. A positive relationship between shoot Ni and soil pH was found for all three species. They display Ni hyperaccumulation in the leaves, but with pronounced variation in the Ni concentrations attained. Odontarrhena penjwinensis emerged as the most promising potential candidate for future Ni agromining. The progress made in this study will enable further consideration of the three Odontarrhena species, especially O. penjwinensis, for any future commercial Ni agromining of the serpentinic ultramafic soils in Western Iran. NOVELTY STATEMENT This pioneering study in a remote part of Western Iran is the first to evaluate nickel hyperaccumulating species of Odontarrhena (Alyssum) in relation to their soil-plant relationships and potential for agromining.
The Effects of Disaster Nursing Education Program on Beliefs in General Disaster Preparedness, Disaster Response Self-Efficacy, and Psychological Resilience in Nursing Students: A Single-Blind, Randomized Controlled Study

Abstract AIM This study was conducted to evaluate the effects of a disaster nursing and management education program on beliefs in general disaster preparedness, disaster response self-efficacy, and psychological resilience in nursing students. METHOD The sample consisted of nursing students receiving undergraduate education in Istanbul, Turkey. Participants were randomly divided into the intervention (n = 65) and control (n = 66) groups. The intervention group was given an eight-module education program with theoretical and applied components. Data were collected using the Belief in General Disaster Preparedness Scale, the Disaster Response Self-Efficacy Scale, and the Brief Resilience Scale. RESULTS The mean Belief in General Disaster Preparedness Scale, Disaster Response Self-Efficacy Scale, and Brief Resilience Scale scores of the intervention group were higher than those of the control group. CONCLUSION The disaster nursing and management education program provided to nursing students was determined to increase beliefs in general disaster preparedness, disaster response self-efficacy, and psychological resilience.
Genomic map of candidate human imprint control regions: the imprintome

ABSTRACT Imprinted genes – critical for growth, metabolism, and neuronal function – are expressed from one parental allele. Parent-of-origin-dependent CpG methylation regulates this expression at imprint control regions (ICRs). Since ICRs are established before tissue specification, these methylation marks are similar across cell types. Thus, they are attractive for investigating the developmental origins of adult diseases using accessible tissues, but remain unknown. We determined genome-wide candidate ICRs in humans by performing whole-genome bisulphite sequencing (WGBS) of DNA derived from the three germ layers and from gametes. We identified 1,488 hemi-methylated candidate ICRs, including 19 of 25 previously characterized ICRs (https://humanicr.org/). Gamete methylation approached 0% or 100% in 332 ICRs (178 paternally and 154 maternally methylated), supporting parent-of-origin-specific methylation, and 65% were in well-described CTCF-binding or DNaseI hypersensitive regions. This draft of the human imprintome will allow for the systematic determination of the role of early-acquired imprinting dysregulation in the pathogenesis of human diseases and developmental and behavioural disorders.