Photodynamic therapy (PDT), extensively explored as a non-invasive and spatio-temporal therapeutic modality for cancer treatment, encounters challenges related to the brief half-life and limited diffusion range of singlet oxygen. Lipid peroxides, formed through the oxidation of polyunsaturated fatty acids by singlet oxygen, exhibit prolonged half-life and potent cytotoxicity. Herein, we employed small molecule co-assembly technology to create nanoassemblies of pyropheophorbide a (PPa) and docosahexaenoic acid (DHA) to bolster PDT. DHA, an essential polyunsaturated fatty acid, co-assembled with PPa to generate nanoparticles (PPa@DHA NPs) without the need for additional excipients. To enhance the stability of these nanoassemblies, we introduced 20% DSPE-PEG as a stabilizing agent, leading to the formation of PPa@DHA PEG NPs. Upon laser irradiation, PPa-produced singlet oxygen swiftly oxidized DHA, resulting in the generation of cytotoxic lipid peroxides. This process significantly augmented the therapeutic efficiency of PDT. Consequently, tumor growth was markedly suppressed, attributed to the sensitizing and amplifying impact of DHA on PDT in a 4T1 tumor-bearing mouse model. In summary, this molecule-engineered nanoassembly introduces an innovative co-delivery approach to enhance PDT with polyunsaturated fatty acids.

A chemical investigation of , isolated from cysts of the plant parasitic nematode , affored three dactylfungin derivatives (-) and three tetralone congeners (-). Dactylfungin C (), laburnicolin (), and laburnicolenone () are previously undescribed natural products. Chemical structures of the isolated compounds were determined based on 1D and 2D NMR spectroscopic analyses together with HR-ESI-MS spectrometry and comparison with data reported in the literature. The relative configurations of compounds , , and - were determined based on their ROESY data and analysis of their coupling constants ( values). The absolute configurations of - were determined through the comparison of their measured and calculated TDDFT-ECD spectra. Compounds - were active against azole-resistant .

This study aims to explore the potential of Internet of Things (IoT) devices and explainable Artificial Intelligence (AI) techniques in predicting biomarker values associated with GDM when measured 13-16 weeks prior to diagnosis. We developed a system that forecasts biomarkers such as LDL, HDL, triglycerides, cholesterol, HbA1c, and results from the Oral Glucose Tolerance Test (OGTT) including fasting glucose, 1-hour, and 2-hour post-load glucose values. These biomarker values are predicted based on sensory measurements collected around week 12 of pregnancy, including continuous glucose levels, short physical movement recordings, and medical background information. To the best of our knowledge, this is the first study to forecast GDM-associated biomarker values 13 to 16 weeks prior to the GDM screening test, using continuous glucose monitoring devices, a wristband for activity detection, and medical background data. We applied machine learning models, specifically Decision Tree and Random Forest Regressors, along with Coupled-Matrix Tensor Factorisation (CMTF) and Elastic Net techniques, examining all possible combinations of these methods across different data modalities. The results demonstrated good performance for most biomarkers. On average, the models achieved Mean Squared Error (MSE) between 0.29 and 0.42 and Mean Absolute Error (MAE) between 0.23 and 0.45 for biomarkers like HDL, LDL, cholesterol, and HbA1c. For the OGTT glucose values, the average MSE ranged from 0.95 to 2.44, and the average MAE ranged from 0.72 to 0.91. Additionally, the utilisation of CMTF with Alternating Least Squares technique yielded slightly better results (0.16 MSE and 0.07 MAE on average) compared to the well-known Elastic Net feature selection technique. While our study was conducted with a limited cohort in South Africa, our findings offer promising indications regarding the potential for predicting biomarker values in pregnant women through the integration of wearable devices and medical background data in the analysis. Nevertheless, further validation on a larger, more diverse cohort is imperative to substantiate these encouraging results.

Pancreatic cancer fine delineation in medical images by physicians is a major challenge due to the vast volume of medical images and the variability of patients.

Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown.

The synthetic antioxidant improved the shelf life of meat products; however, consumers start to reject them for health reason. For this, the natural antioxidants like Myrtle distillate leaves (MDL) could be an interesting alternative and potential natural antioxidant given their richness in bioactive compounds. This study aimed to test the effect of myrtle distillate leaves (MDL) as natural antioxidant in premortem phase as diet of cull ewes and in postmortem phase in form of powder added to deboned legs on meat' quality. All ewes received individually 500 g of hay and 750 g of concentrate for Control (C) group; for Myrt group, the concentrate was partially replaced (400 g) by pellets containing 30% MDL and 350 g concentrate. For each ewe, both legs were used for the experiment; one leg was treated with MDL powder and the other with Control. Meat from ewes' fed MDL presented better scores for red color, aftertaste and juiciness, than control group. Meat treated with MDL powder showed the highest values of total phenolic, α-tocopherol content and redness score with lower lipid oxidation ( < .05). The microbiological quality of meat was not affected by MDL. Myrtle distillate leaves could be used in different forms, in order to obtain higher meat product quality.

Exposure to chronic stress has detrimental effects on cognitive and emotional processing. Also, the neuroprotective influences of environmental enrichment (EE) and royal jelly (RJ) have been indicated in previous studies.

Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biomarkers associated with resistance and toxicity are limited. In this study, single-cell proteomic profiling of circulating CAR T cells in 32 patients treated with CD19-CAR identified that CD4Helios CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity. Deep profiling demonstrated that this population is non-clonal and manifests hallmark features of T regulatory (T) cells. Validation cohort analysis upheld the link between higher CAR T cells with clinical progression and less severe neurotoxicity. A model combining expansion of this subset with lactate dehydrogenase levels, as a surrogate for tumor burden, was superior for predicting durable clinical response compared to models relying on each feature alone. These data credential CAR T cell expansion as a novel biomarker of response and toxicity after CAR T cell therapy and raise the prospect that this subset may regulate CAR T cell responses in humans.

Acute peritonitis has remained a fatal disease despite of recent advances in care and treatment, including antibiotic and anticoagulant treatments. The cause of death is mostly sepsis-induced multiple organ failure. Oxidative stress can play an important role in this situation, but antioxidant therapy to capture any excessive reactive oxygen species has not yet been fully established.

This study investigates the association between participation in four domains of physical activity, social activities, and global life satisfaction among 2344 community-dwelling older adults (72.3 ± 5.5 years; 65.6% female) in Brazil. Comparison analyses were performed on the frequencies, and statistical analysis also included univariate and hierarchical logistic regression analysis. Of all the physical activity domains analyzed, only leisure-time physical activity was found to be associated with global life satisfaction. There was also a positive association between global life satisfaction and social activity participation. We conclude that the specific domain in which activity is performed interferes with one's perception of his or her life.

Cancer survivorship is frequently associated with severe late effects. However, research into pediatric cancer survivors on late effects in motor ability, physical self-concept and their relationship to quality of life is limited.

Measuring time-activity budgets over the complete individual life span is now possible for many animals with the recent advances of life-long individual monitoring devices. Although analyses of changes in the patterns of time-activity budgets have revealed ontogenetic shifts in birds or mammals, no such technique has been applied to date on insects. We tested an automated breakpoint-based procedure to detect, assess and quantify shifts in the temporal pattern of the flight activities in honeybees. We assumed that the learning and foraging stages of honeybees will differ in several respects, to detect the age at onset of foraging (AOF). Using an extensive dataset covering the life-long monitoring of 1,167 individuals, we compared the AOF outputs with the more conventional approaches based on arbitrary thresholds. We further evaluated the robustness of the different methods comparing the foraging time-activity budget allocations between the presumed foragers and confirmed foragers. We revealed a clear-cut learning-foraging ontogenetic shift that differs in duration, frequency and time of occurrence of flights. Although AOF appeared to be highly plastic among bees, the breakpoint-based procedure seems better capable to detect it than arbitrary threshold-based methods that are unable to deal with inter-individual variation. We developed the aof r-package including a broad range of examples with both simulated and empirical datasets to illustrate the simplicity of use of the procedure. This simple procedure is generic enough to be derived from any individual life-long monitoring devices recording the time-activity budgets, and could propose new ecological applications of bio-logging to detect ontogenetic shifts in the behaviour of central-place foragers.

Using Brownian molecular dynamics simulations, we examine the internal dynamics and biomechanical response of von Willebrand factor (vWF) multimers subject to shear flow. The coarse grain multimer description employed here is based on a monomer model in which the A2 domain of vWF is explicitly represented by a nonlinear elastic spring whose mechanical response was fit to experimental force/extension data from vWF monomers. This permits examination of the dynamic behavior of hydrodynamic forces acting on A2 domains as a function of shear rate and multimer length, as well as position of an A2 domain along the multimer contour. Force/position data reveal that collapsed multimers exhibit a force distribution with two peaks, one near each end of the chain; unraveled multimers, however, show a single peak in A2 domain force near the center of multimers. Guided further by experimental data, significant excursions of force acting on a domain are associated with an increasing probability for A2 domain unfolding. Our results suggest that the threshold shear rate required to induce A2 domain unfolding is inversely proportional to multimer length. By examining data for the duration and location of significant force excursions, convincing evidence is advanced that unfolding of A2 domains, and therefore scission of vWF multimers by the size-regulating blood enzyme ADAMTS13, happen preferentially near the center of unraveled multimers.

Exercise or physical activity are recommended options within stepped-care treatment models for depression. However, few physicians present these options to patients, in part because of the impression that the supporting evidence is weak or inconsistent. We speculate that the coocurrence of "counter-messaging" and deficient critical appraisal may lead to such impressions. We focus on TREAD-UK (ISRCTN16900744), the largest trial to investigate "whether physical activity can be an effective treatment for depression within primary care". In media statements, researchers declared that exercise was ineffective in lowering depression. We examined (a) the results of the trial, critiques, and rejoinders, (b) the impact on internet searches, and (c) whether TREAD-UK was critically appraised, as reflected in citing articles. We show that the results of TREAD-UK were misrepresented. The media campaign resulted in a fourfold increase in relevant internet searches. Of articles characterising the results, 57% adopted the interpretation that exercise failed to lower depression, whereas only 17% were critiques. We identify similarities to media portrayals of the OPERA (ISRCTN43769277), DEMO (NCT00103415), and DEMO-II trials (NCT00695552). We note a disconcerting trend of media campaigns that misrepresent the effects of exercise on depression and call for increased scrutiny in peer reviewing both pre- and post-publication.

To explore why adherence to vital sign observations scheduled by an early warning score protocol reduces at night.

This paper considers the position-based consensus in a network of agents with double-integrator dynamics and directed topology. Two types of distributed observer algorithms are proposed to solve the consensus problem by utilizing continuous and intermittent position measurements, respectively, where each observer does not interact with any other observers. For the case of continuous communication between network agents, some convergence conditions are derived for reaching consensus in the network with a single constant delay or multiple time-varying delays on the basis of the eigenvalue analysis and the descriptor method. When the network agents can only obtain intermittent position data from local neighbors at discrete time instants, the consensus in the network without time delay or with nonuniform delays is investigated by using the Wirtinger's inequality and the delayed-input approach. Numerical examples are given to illustrate the theoretical analysis.

At meiosis, hundreds of programmed DNA double-strand breaks (DSBs) form and are repaired by homologous recombination. From this large number of DSBs, only a subset yields crossovers (COs), with a minimum of one CO per chromosome pair. All DSBs must be repaired and every recombination intermediate must be resolved to avoid subsequent entanglement and chromosome breakage. The conserved BLM-TOP3α-RMI1 (BTR) complex acts on early and late meiotic recombination intermediates to both limit CO outcome and promote chromosome integrity. In Arabidopsis, the BLM homologues RECQ4A and RECQ4B act redundantly to prevent meiotic extra COs, but recombination intermediates are fully resolved in their absence. In contrast, TOP3α is needed for both processes. Here we show through the characterization of specific mutants that RMI1 is a major anti-CO factor, in addition to being essential to prevent chromosome breakage and entanglement. Further, our findings suggest a specific role of the C-terminal domains of RMI1 and TOP3α, that respectively contain an Oligo Binding domain (OB2) and ZINC finger motifs, in preventing extra-CO. We propose that these domains of TOP3α and RMI1 define a sub-domain of the BTR complex which is dispensable for the resolution of recombination intermediates but crucial to limit extra-COs.

In this paper, we propose a new interim connection space (ICS) called LabLab, which is an updated version of LabPQR, to overcome the drawback that the last three dimensions of LabPQR have no definite colorimetric meanings. We extended and improved the method by which the first three dimensions of LabPQR are deduced to obtain an ICS consisting of two sets of CIELAB values under different illuminants, and the reconstructed spectra from LabLab were obtained by minimizing colorimetric errors by means of the computational formula of the CIE-XYZ tristimulus values combined with least-squares best fit. The improvement obtained from the proposed method was tested to compress and reconstruct the reflectance spectra of the 1950 Natural Color System color chips and more than 50,000 ISO SOCS color patches as well as six multispectral images acquired by multispectral image acquisition systems using 1600 glossy Munsell color chips as training samples. The performance was evaluated by the mean values of color differences between the original and reconstructed spectra under the CIE 1931 standard colorimetric observer and the CIE standard illuminants D50, D55, D65, D75, F2, F7, F11, and A as well as five multichip white LED light sources. The mean and maximum values of the root mean square errors between the original and reconstructed spectra were also calculated. The experimental results show that the proposed three LabLab interim connection spaces significantly outperform principal component analysis, LabPQR, XYZLMS, Fairman-Brill, and LabRGB in colorimetric reconstruction accuracy at the cost of slight reduction of spectral reconstruction accuracy and illuminant independence of color differences of the suggested LabLab interim connection spaces outperform other interim connection spaces. In addition, the presented LabLab interim connection spaces could be quite compatible with the extensively used colorimetric management system since each dimension has definite colorimetric meanings and is perceptually uniform.

Proteomics was used in the calanoid copepod Eurytemora affinis for screening of protein expression modifications induced by organic contaminants. The copepods were exposed in a continuous flow-through system for 86 h to environmentally relevant concentrations of contaminants representative of the pollution in the Seine Estuary (Haute-Normandie, France; diuron, 500 ng L(-1) ; alkylphenol mixture, 1000 ng L(-1) ). Proteome analysis of whole-body copepod extracts by 2-dimensional gel electrophoresis revealed that the contaminants induced modifications in protein expression, with the highest quantitative variations occurring after diuron exposure. Specifically, 88 and 41 proteins were differentially expressed after diuron and alkylphenol treatments, respectively. After mass spectrometry analysis, 51 (diuron exposure) and 15 (alkylphenol exposure) proteins were identified. The identified proteins were potentially related to energy metabolism, cell growth, nervous signal conductivity, excitotoxicity, oxidative stress response, and antioxidant defense. The data suggest a massive general disturbance of physiological functions of E. affinis after diuron exposure, whereas alkylphenols induced an alteration of a few targeted physiological functions. The protein expression signatures identified after contaminant exposure deserve further investigation in terms of the development of novel potential biomarkers for water quality assessment. Environ Toxicol Chem 2016;35:1860-1871. © 2015 SETAC.

This investigation is a secondary analysis of data from a randomized control trial of the PLAY Home Consultation Intervention Program which was conducted with 112 preschool children with Autism Spectrum Disorders and their parents (Solomon et al. in J Dev Behav Pediatr 35:475-485, 2014). Subjects were randomly assigned to either a community standard (CS) treatment group or to the PLAY Project plus CS Treatment (PLAY). PLAY subjects received monthly parent-child intervention sessions for 1 year during which parents learned how to use the rationale and interactive strategies of the Developmental, Individual-differences, Relationship-based (DIR) intervention model (Greenspan and Weider in The child with special needs: encouraging intellectual and emotional growth. DeCapo Press, Cambridge, MA, 1998) to engage in more responsive, affective and less directive interactions with their children. This investigation examined whether PLAY intervention effects on parents' style of interacting with their children as well as on children's social engagement mediated the effects of PLAY on children's autism severity as measured by ADOS calibrated severity scores. Regression procedures were used to test for mediation. There were two main findings. First the effects of PLAY on children's social engagement were mediated by the increases in parental responsiveness and affect that were promoted by PLAY. Second, the effects of PLAY on the severity children's Social Affect disorders were mediated by changes in parental responsiveness and affect; however, the effects of Responsive/Affect were mediated by the impact these variables had on children's social engagement. Results are discussed in terms of contemporary models of developmental change including the developmental change model that is the foundation for DIR.

There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics). This paper is one in a series of articles on the data curation process in nanoinformatics (nanocuration). Other articles in this series discuss key aspects of nanocuration (temporal metadata, data completeness, database integration), while the focus of this article is on the nanocuration workflow, or the process of identifying, inputting, and reviewing nanomaterial data in a data repository. In particular, the article discusses: 1) the rationale and importance of a defined workflow in nanocuration, 2) the influence of organizational goals or purpose on the workflow, 3) established workflow practices in other fields, 4) current workflow practices in nanocuration, 5) key challenges for workflows in emerging fields like nanomaterials, 6) examples to make these challenges more tangible, and 7) recommendations to address the identified challenges. Throughout the article, there is an emphasis on illustrating key concepts and current practices in the field. Data on current practices in the field are from a group of stakeholders active in nanocuration. In general, the development of workflows for nanocuration is nascent, with few individuals formally trained in data curation or utilizing available nanocuration resources (e.g., ISA-TAB-Nano). Additional emphasis on the potential benefits of cultivating nanomaterial data via nanocuration processes (e.g., capability to analyze data from across research groups) and providing nanocuration resources (e.g., training) will likely prove crucial for the wider application of nanocuration workflows in the scientific community.