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Microfluidic isolation and release of live disseminated breast tumor cells in bone marrow
Breast cancer represents a significant therapeutic challenge due to its aggressive nature and resistance to treatment. A major cause of treatment failure in breast cancer is the presence of rare, low-proliferative disseminated tumor cells (DTCs) in distant organs including the bone marrow. This study introduced a microfluidic-based approach to improve the immunodetection and isolation of these rare DTCs for downstream analysis, with an emphasis on optimizing immunocapture, release, and enrichment methods of live DTCs as compared to the standard approach for blood-borne circulating tumor cells (CTCs). EGFR (epidermal growth factor receptor) and EpCAM (epithelial cell adhesion molecule), two key cell surface markers in breast cancer, were validated as efficient cell capture targets for DTCs within microfluidic chambers. Furthermore, we demonstrated that a combination of 0.25% trypsin and impulse was the most effective for releasing captured cells, maintaining high viability, and preserving essential cellular characteristics. Using a metastatic mouse breast cancer model, we achieved a 47.9-fold enrichment of live DTCs. Analysis of blood and bone marrow samples obtained from a breast cancer patient with minimal residual disease at two timepoints revealed a reduction in CTCs and an increase in DTCs following adjuvant chemotherapy. This observation suggested a potential dynamic interplay between CTCs and DTCs in response to therapy. Our results underscore the potential of the microfluidic approach in enhancing DTC detection and shed light on the importance of monitoring both CTCs and DTCs in breast cancer prognosis and treatment response assessment.
Starvation-induced HBP metabolic reprogramming and STAM2 O-GlcNAcylation facilitate bladder cancer metastasis
A methodological framework for deriving the German food-based dietary guidelines 2024: Food groups, nutrient goals, and objective functions
Background For a growing number of food-based dietary guidelines (FBDGs), diet optimization is the tool of choice to account for the complex demands of healthy and sustainable diets. However, decisions about such optimization models’ parameters are rarely reported nor systematically studied. Objectives The objectives were to develop a framework for (i) the formulation of decision variables based on a hierarchical food classification system; (ii) the mathematical form of the objective function; and (iii) approaches to incorporate nutrient goals. Methods To answer objective (i), food groups from FoodEx2 levels 3-7 were applied as decision variables in a model using acceptability constraints (5 th and 95 th percentile for food intakes of German adults ( n = 10,419)) and minimizing the deviation from the average observed dietary intakes. Building upon, to answer objectives (ii) and (iii), twelve models were run using decision variables from FoodEx2 level 3 ( n = 255), applying either a linear or squared and a relative or absolute way to deviate from observed dietary intakes, and three different lists of nutrient goals (allNUT-DRV, incorporating all nutrient goals; modNUT-DRV excluding nutrients with limited data quality; modNUT-AR using average requirements where applicable instead of recommended intakes). Results FoodEx2 food groups proved suitable as diet optimization decision variables. Regarding deviation, the largest differences were between the four different objective function types, e.g., in the linear-relative modNUT-DRV model, 46 food groups of the observed diet were changed to reach the model’s goal, in linear-absolute 78 food groups, squared-relative 167, and squared-absolute 248. The nutrient goals were fulfilled in all models, but the number of binding nutrient constraints was highest in the linear-relative models (e.g. allNUT-DRV: 11 vs. 7 in linear-absolute). Conclusion Considering the various possibilities to operationalize dietary aspects in an optimization model, this study offers valuable contributions to a framework for developing FBDGs via diet optimization.
The application of neutron imaging to examine ethene hydrogenation over a carbon-supported palladium catalyst
Abstract The combination of a heterogeneous catalyst operating within a defined reactor comes within the domain of reaction engineering, which takes cognisance of combined roles for both the catalyst and the reactor to define the overall operational system. One technique which is demonstrating much promise in investigating reaction engineering issues is neutron imaging. The technique is skewed towards monitoring hydrogen and hydrogenous species so, with hydrogen being ubiquitous in industrial organic chemistry and the penetrating power of the neutrons, neutron imaging can monitor hydrogen concentrations distributed throughout steel reactors whilst the reaction is taking place. In this way, neutron imaging can be used to assess the homogeneity of active catalyst beds and, additionally, determine how hydrogen is being partitioned throughout the catalyst bed as a function of time-on-stream. These are important parameters in the reaction engineering of catalytic systems involving transformations of hydrogen containing species. The article commences by reviewing the handful of existing neutron imaging studies in this field, then progresses to describe the application of the neutron imaging technique to investigate ethene hydrogenation over a 5 wt% Pd/C powder catalyst at 333 K and ambient pressure in a rectangular stainless-steel reactor. Modulations of the incident gas stream are seen to lead to spatially resolvable fronts moving across the bed and illustrate the diffusion of reagents from the reactor inlet across to the reactor exit. Thus, the investigation reveals spatially and temporally resolved elementary reactions that contribute to the hydrogenation process.
Oral fluid supplementation for the prevention of post-dural puncture headache: A noninferiority randomized controlled trial
Aim(s) To investigate the impact of the absence of specific advice for oral fluid intake, compared to supplementation water intake on the occurrence of post-dural puncture headache. Design A prospective, open-label, non-inferiority, multicenter trial including hospitalized patients requiring a diagnostic lumbar puncture in seven hospitals in France. Methods Patients were randomly allocated (1:1) either to receive no specific advice on oral fluid intake (FREE-FLUID), or to be encouraged to drink 2 liters of water (CONTROL) within the 2 hours after lumbar puncture. The primary outcome was the post-dural puncture headache rate within the 5 days after lumbar puncture, with a non-inferiority margin of 10%. The secondary outcome was the time-to-post-dural puncture headache onset between Day 0 and Day 5. Results From November 2016 and July 2019, we have included 554 participants. The primary outcomes occurs in 33.1% patients in the FREE-FLUID group, versus 38.0% in the CONTROL group with adjusted difference of 3.7%. Conclusion Among patients who had lumbar puncture, our study shows the noninferiority of the absence of specific advice on water intake after a lumbar puncture, compared with advice to increase oral fluid to prevent a post-dural puncture headache. Impact The value of questioning the appropriateness of non-evidence-based nursing care may allow time to be devoted to more relational and comforting care. Reporting method The study adheres to the CONSORT reporting guidelines. Patient or public contribution No patient or public contribution. Trial Registration Clinical Trials.gov (NCT02859233, August 9, 2016).
Relative importance of soil fertility and microtopography as CO2 and CH4 exchange drivers in a northern boreal fen ecosystem
Relationship between sleep variables and interoceptive awareness in daytime workers
Interoception refers to the sensation of internal and physiological bodily states, such as heart rate, and contributes to the maintenance of bodily internal homeostasis. Some studies showed that interoceptive awareness is related to experiencing nightmares and subjective sleep quality. Similarly to the perception of heart rate variability, sleepiness is thought to be mainly evoked by homeostatic processes and is based on the awareness and recognition of internal body signals. However, the relationship between subjective excessive daytime sleepiness and interoceptive awareness has not been addressed. Therefore, this study examined the relationship between interoceptive awareness and multiple sleep variables including subjective excessive sleepiness in daytime workers. A web questionnaire survey was conducted targeting daytime workers in Japan, and data from 461 participants were used for analyses. Multiple regression analyses showed weak but significant relationships between subjective excessive daytime sleepiness, insomnia symptoms, nightmare distress, and dream frequency and the components of interoception awareness measured by the Multidimensional Assessment of Interoceptive Awareness. However, no components of interoceptive awareness were related to workday sleep loss or social jetlag of day workers. The results of this study suggest that subjective sleepiness, in addition to nightmare distress and sleep quality, is associated with interoceptive awareness. To the best of our knowledge, this study is the first to analyze the relationship between subjective daytime excessive sleepiness and interoceptive awareness. Further investigation of this relationship is expected to lead to a better understanding of sleep disorders and to elucidate individual differences in the accuracy of subjective assessments of sleepiness.
Study on the multi-wavelength variation of 3C 454.3
Abstract The variation mechanism of the blazar is still an open question. In this study, we collect the long-term multi-wavelength data of 3C 454.3 to conduct a comprehensive study. The local cross-correlation functions were computed between the $$\gamma$$ -ray and R band fluxes, as well as between B and K band fluxes. No significant time lags were found among these bands, which suggests that the optical and $$\gamma$$ -ray emissions are co-spatial. The color indices variation behavior showed a redder-when-brighter trend in the lower state, and a saturation state in the higher state. The slope of the linear correlations between the logarithms of synchrotron and inverse-Compton fluxes changed from 0.61 to 3.34 for different band pairs, which could be explained by a model of Doppler-boosted log-parabolic synchrotron emission combined with stable background contamination. The model could also reproduce the spectral energy distributions at different brightness. This study can help us to better understand the variation mechanism of blazars.
The impact of canine-assisted intervention on stress reduction among university students in Thailand
Stress negatively impacts university students, leading to adverse outcomes. While canine-assisted intervention (CAI) has been shown to reduce self-reported stress, no studies have investigated stress levels and associated biomarkers in dogs and students simultaneously. This study examined salivary cortisol, blood pressure, and pulse rate in 122 university students experiencing self-reported moderate to high stress before an encounter with a dog (T1), immediately before meeting a dog (T2), and after spending 15 minutes interacting with a dog (T3). Participants assessed their stress level using a visual analog scale, and blood pressure and pulse rate were measured at three time points. Salivary cortisol was also measured at T1 and T3. Six privately owned dogs, all in good health and comfortable with strangers, participated in the intervention sessions. Salivary and fecal cortisol samples from the dogs were collected in the morning before commencing activities, at noon, and in the evening after human interactions ended. The results showed that the expectation of interacting with dogs reduces self-reported stress, pulse rate, and salivary cortisol, which remained significantly lower after the interaction. Salivary cortisol concentrations in dogs did not differ throughout the day. By contrast, fecal glucocorticoid metabolite concentrations during the week dogs interacted with students were higher (P = 0.0012) than those during the week post-experiment, which, based on behavior, appeared to indicate positive stimulation. These findings highlight the potential of integrating CAI into university stress management programs. Future research could explore extending these benefits to community dogs, long-term effects, and enhancing accessibility to this form of stress relief.
The development of specific emotion comprehension components in 1285 preschool children
The impact of work-family conflict on job burnout among community social workers in China
In China, for community social workers, work-family conflict has become a common phenomenon that may harm their well-being. Based on the analysis of a survey of community social workers in four cities in China, this study demonstrated that community workers’ work-family conflict significantly affects burnout, role overload mediates the relation between work-family conflict and burnout, and cognitive crafting negatively moderates the relation between role overload and burnout. The conclusions validate the job crafting theory and enrich the research on job burnout under the JD-R model. The practical significance of the study is that on the one hand, community and individual workers can effectively alleviate burnout by clarifying their roles. On the other hand, it also reminds managers that they should pay attention to the physical and mental health of social workers to enable them to develop healthily.
LCD-AHP-TRIZ methodology enhances low-carbon principles in smart product design
Deciphering the structural consequences of R83 and R152 methylation on DNA polymerase β using molecular modeling
DNA polymerase β, a member of the X-family of DNA polymerases, undergoes complex regulations both in vitro and in vivo through various posttranslational modifications, including phosphorylation and methylation. The impact of these modifications varies depending on the specific amino acid undergoing alterations. In vitro, methylation of DNA polymerase β with the enzyme protein arginine methyltransferase 6 (PRMT6) at R83 and R152 enhances polymerase activity by improving DNA binding and processivity. Although these studies have shown that methylation improves DNA binding, the underlying mechanism of enhancement of polymerase activity in terms of structure and dynamics remains poorly understood. To address this gap, we modeled the methylated enzyme/DNA complex and conducted a microsecond-long simulation in the presence of Mg ions. Our results revealed significant structural changes induced by methylating both R83 and R152 sites in the enzyme. Specifically, these changes caused the DNA fragment to move closer to the C- and N-subdomains, forming additional hydrogen bonds. Furthermore, the cross-correlation map demonstrated that methylation enhanced long-range correlations within the domains/subdomains of DNA polymerase β, along with an increase in the linear mutual information value between the domains/subdomains and DNA fragments. The graph connectivity network also illustrated that methylation modulates the information pathway and identifies residues exhibiting long-distance coupling with the methylated sites. Our results provide an atomic-level understanding of the structural transition induced by methylation, shedding light on the mechanisms underlying the methylation-induced enhancement of activity in DNA polymerase β.
Comparative analysis of organoid, air-liquid interface, and direct infection models for studying pathogen–host interactions in endometrial tissue
Measuring real-time violence exposure and its impact on intimate partner violence perpetration among adolescents
Background Intimate partner violence (IPV) has dire health consequences. To intervene, it is critical we first understand why young men perpetrate IPV. One theory is that men who experience violence are more likely to perpetrate violence. We used real time data to examine how daily and repeat experiences of violence affect IPV behaviors. Methods We enrolled 498 males aged 15-19 years in Soweto, South Africa during 2020-2022. We collected data through weekly mobile phone surveys (n = 12,603) delivered over a year. Generalized linear mixed effect models were used to fit IPV perpetration as a function of past-24-hour violence victimization; models included indicators for between-person and within-person components of victimization. Findings In at least one survey submitted, 13% of boys reported perpetrating physical IPV and 5% perpetrating sexual IPV. Any victimization in the past 24-hours significantly increased the odds of physical (OR 4.00) and sexual violence perpetration (OR 2.45). When examined individually, sexual violence victimization had the strongest association (OR of 7.96 for physical and 4.88 sexual IPV perpetration). We also examined the between-person influence of victimization. Boys who experienced more violence on average (a higher person-centered mean exposure) were substantially more likely to perpetrate both physical IPV and sexual IPV as compared to boys with overall low levels of victimization. Conclusion Adolescent boys who experience violence are more likely to use violence against their partners that same day. To break this cycle, it will be critical to understand the mechanisms by which proximal victimization triggers onward violence perpetration. Both the current findings and the next steps highlight the importance of real-time, repeated data collection.
Illuminating ecology and distribution of the rare fungus Phellinidium pouzarii in the Bavarian Forest National Park
Abstract Due to their cryptic lifestyle, hidden diversity and a lack of ecological knowledge, conservation of wood-inhabiting fungi continues to be a niche interest. Molecular methods are able to provide deeper insights into the ecology of rare fungal species. We investigated the occurrence of the rare wood-inhabiting fungus Phellinidium pouzarii across the Bavarian Forest National Park in Germany using a fruit body survey, amplicon sequencing and qPCR. Additionally, we sequenced the genome of P. pouzarii and characterized the chemical substances responsible for its distinctive scent. Our approach gave matching results between amplicon sequencing and qPCRs, however, we found no evidence that P. pouzarii is more abundant in the National Park than we can assume based on fruit body inventories, underlining the species’ critically endangered status. Genomics revealed P. pouzarii’s repertoire of ligninolytic enzymes, pointing towards a white rot lifestyle. Two main components of P. pouzarii’s distinct odour we identified (2-phenylethanol, methyl p-anisate) are known to act as insect attractants and/or to possess antimicrobial properties.
Correction: Neuroprotective effect of Kaempferol Glycosides against brain injury and Neuroinflammation by inhibiting the activation of NF-κB and STAT3 in transient focal stroke
Comparing ISO 4049 and Fourier-transform infrared spectroscopy for assessing ambient light sensitivity in dental resin composites
Impact of a three-week full leg cast immobilization on infant crawling kinetics and spatiotemporal parameters
Despite its importance in the development of mobility in infants, there is a general lack of quantified data on infant crawling, and a specific lack of understanding of crawling kinetics, which includes the relative weightbearing and force generation among the four limbs. Moreover, because of the difficulty of measurement and study design, there is no longitudinal quantification of the impact of a perturbation to typical development, such as limb immobilization. This study measured kinetic and spatiotemporal outcomes in a typically developing infant prior to a fracture that necessitated a long-leg cast that immobilized the left knee and ankle, while crawling with the cast, and again one day after cast removal, and two weeks post. The study utilized a pressure-sensing mat to generate outcomes. Crawling in the cast resulted in a 37% decrease in speed, a shift of weight toward the arms (toward the right arm in particular), and a shift from double and quadruple limb support toward triple limb support. Upon removal of the cast, the unweighting and limb support patterns persisted, while speed recovered and actually exceeded baseline. Triple limb support was 12% at baseline, 28% in the cast, and 32% immediately following cast removal. Two weeks later, the value had dropped back to 17%, while speed continued to increase following a linear trend vs. age. These data provide insight into an infant’s ability to reorganize crawling kinematics, and the persistence of that reorganization following remobilization.