Miracle-dz/UniFAR-FTUs huggingface dataset:
Mass Spectrometry as a Highly Sensitive Method for Specific Circulating Tumor DNA Analysis in NSCLC: A Comparison Study

Simple Summary We compared the UltraSEEK™ Lung Panel on the MassARRAY® System (Agena Bioscience) with the FDA-approved Cobas® EGFR Mutation Test v2 for the detection of EGFR mutations in liquid biopsies of NSCLC patients, accompanied with preanalytical sample assessment using the novel Liquid IQ® Panel. For the detection of relevant predictive mutations using the UltraSEEK™ Lung Panel, an input of over 10 ng showed 100% concordance with Cobas® EGFR Mutation Test v2 and detection of all tissue confirmed mutations. In case of lower ccfDNA input, the risk of missing clinically relevant mutations should be considered. The use of a preanalytical ccfDNA quality control assay such as the Liquid IQ® Panel is recommended to confidently interpret results, avoiding bias induced by non-specific genomic DNA and low input of specific tumoral ccfDNA fragments. Abstract Plasma-based tumor mutational profiling is arising as a reliable approach to detect primary and therapy-induced resistance mutations required for accurate treatment decision making. Here, we compared the FDA-approved Cobas® EGFR Mutation Test v2 with the UltraSEEK™ Lung Panel on the MassARRAY® System on detection of EGFR mutations, accompanied with preanalytical sample assessment using the novel Liquid IQ® Panel. 137 cancer patient-derived cell-free plasma samples were analyzed with the Cobas® and UltraSEEK™ tests. Liquid IQ® analysis was initially validated (n = 84) and used to determine ccfDNA input for all samples. Subsequently, Liquid IQ® results were applied to harmonize ccfDNA input for the Cobas® and UltraSEEK™ tests for 63 NSCLC patients. The overall concordance between the Cobas® and UltraSEEK™ tests was 86%. The Cobas® test detected more EGFR exon19 deletions and L858R mutations, while the UltraSEEK™ test detected more T790M mutations. A 100% concordance in both the clinical (n = 137) and harmonized (n = 63) cohorts was observed when >10 ng of ccfDNA was used as determined by the Liquid IQ® Panel. The Cobas® and UltraSEEK™ tests showed similar sensitivity in EGFR mutation detection, particularly when ccfDNA input was sufficient. It is recommended to preanalytically determine the ccfDNA concentration accurately to ensure sufficient input for reliable interpretation and treatment decision making.
Effectiveness of an Emotional Intelligence Intervention and Its Impact on Academic Performance in Spanish Pre-Adolescent Elementary Students: Results from the EDI Program

There is clear agreement about the importance of promoting emotional intelligence in school through programs integrated in the academic curriculum. The objective of this study is to analyze the impact of the EDI program on the emotional intelligence trait and on general academic performance, as well as mathematics and language performance. The participants were 5th grade elementary school students between 10 and 11 years old. A quasi-experimental repeated-measures design was used, with a comparison group and four assessment points. The results showed, on the one hand, the effectiveness of a two-year intervention in improving emotional intelligence and, on the other hand, its positive influence on academic performance in general, and specifically on mathematics and language performance. In the non-intervention group, general academic performance and language performance declined. The results are discussed, and recommendations are made for future interventions.
Distribution of the cholinergic nuclei in the brain of the weakly electric fish, Apteronotus leptorhynchus: Implications for sensory processing

Acetylcholine acts as a neurotransmitter/neuromodulator of many central nervous system processes such as learning and memory, attention, motor control, and sensory processing. The present study describes the spatial distribution of cholinergic neurons throughout the brain of the weakly electric fish, Apteronotus leptorhynchus, using in situ hybridization of choline acetyltransferase mRNA. Distinct groups of cholinergic cells were observed in the telencephalon, diencephalon, mesencephalon, and hindbrain. These included cholinergic cell groups typically identified in other vertebrate brains, for example, motor neurons. Using both in vitro and ex vivo neuronal tracing methods, we identified two new cholinergic connections leading to novel hypotheses on their functional significance. Projections to the nucleus praeeminentialis (nP) arise from isthmic nuclei, possibly including the nucleus lateralis valvulae (nLV) and the isthmic nucleus (nI). The nP is a central component of all electrosensory feedback pathways to the electrosensory lateral line lobe (ELL). We have previously shown that some neurons in nP, TS, and tectum express muscarinic receptors. We hypothesize that, based on nLV/nI cell responses in other teleosts and isthmic connectivity in A. leptorhynchus, the isthmic connections to nP, TS, and tectum modulate responses to electrosensory and/or visual motion and, in particular, to looming/receding stimuli. In addition, we found that the octavolateral efferent (OE) nucleus is the likely source of cholinergic fibers innervating the ELL. In other teleosts, OE inhibits octavolateral hair cells during locomotion. In gymnotiform fish, OE may also act on the first central processing stage and, we hypothesize, implement corollary discharge modulation of electrosensory processing during locomotion.
Cone beam CT multisource configurations: evaluating image quality, scatter, and dose using phantom imaging and Monte Carlo simulations

The purpose of this study was to compare various multisource configurations applied to cone beam CT (CBCT) using phantom imaging and Monte Carlo simulations. Image quality, scatter, and dose were evaluated in both overlapping (large cone angle) and collimated (small cone angle) configurations for CBCT. Four x-ray tube configurations were considered: traditional one source, three source overlapping, six source overlapping, and six source collimated. Image quality was evaluated on a prototype breast CT system using the following five phantoms: a Defrise phantom, a previously reported CBCT QA phantom (Corgi), a polyethylene cylinder, and two anthropomorphic phantoms (hand and knee). Scatter contamination and radiation dose were evaluated using Monte Carlo simulations of a voxelized polyethylene cylinder. The modulation of the Defrise phantom disks on average was 2.7X greater for the six source collimated configuration than the six source overlapping configuration. The data lost from cone beam artifact (spatial domain) and the null cone (frequency domain) in the overlapping configuration were completely recovered using the collimated configuration. The maximum scatter-to-primary ratio (SPR) for the overlapping configuration was 0.81 and the maximum SPR for the collimated configuration was 0.26. The average dose and maximum dose was 4X less in the collimated six source configuration when compared with the overlapping configurations. The maximum dose for the overlapping configurations (one, three & six) remained constant, but the average dose for the multisource (three & six source) overlapping configurations increased 25% when compared to the one source configuration. Use of a collimated multisource x-ray tube configuration was shown to provide significant improvements in image quality throughout the cone-beam geometry field-of-view, reduction in scatter contamination, and more efficient use of dose in comparison to both the traditional CBCT geometry with a single source and the overlapping multisource configurations.
The inhibitory effect of Gualou Guizhi Decoction on post-ischemic neuroinflammation via miR-155 in MCAO rats.

BACKGROUND Gualou Guizhi Decoction (GLGZD) is commonly used to treat stroke. The present study investigated the potential roles of GLGZD on inflammation involving microRNA-155 (miR-155) in a model of ischemic stroke using middle cerebral artery occlusion (MCAO) rats. METHODS Sprague-Dawley rats were randomly divided into three groups: Sham operated group, MCAO model group, and GLGZD treatment group. The ischemic model was established by 2 h left MCAO followed by reperfusion. Neurological deficits were evaluated with a modified Ashworth scale in each group. The changes in individual paw parameters were assessed by Catwalk gait analysis. Inflammatory cytokines were measured by enzyme linked immunosorbent assay (ELISA) and protein levels and gene expression related to inflammation were detected by Western blot and quantitative reverse transcription-PCR (qRTPCR) assays, respectively. The expression of inflammatory signaling proteins was additionally detected by immunohistochemistry. RESULTS Treatment of MCAO rats with GLGZD improved neuronal defects and limb motivity. Additionally, GLGZD was able to inhibit miR-155 upregulation, resulting in down-regulation of miR155-targeted molecules in MCAO rats, including suppressor of cytokine signaling 1 (SOCS1), inhibitor of nuclear factor kappa-B kinase (IKK), mothers against decapentaplegic homolog 2 (SMAD2) and CCAAT/ enhancer binding protein beta (CEBPβ). Meanwhile, the production of anti-inflammatory cytokines was dramatically enhanced by GLGZD treatment when comparing with the MCAO model group. CONCLUSIONS In conclusion, GLGZD down-regulates miR-155, mediating subsequent neuroinflammation and resulting in neuroprotection which contributes to reduced spasticity after ischemic stroke.
The Long-Term Effect of Adapting the Vertical Position of Implants on Peri-Implant Health: A 5-Year Intra-Subject Comparison in the Edentulous Mandible Including Oral Health-Related Quality of Life

Despite high success rates of dental implants, surface exposure may occur as a consequence of biologic width establishment associated with surgery. This prospective split-mouth study evaluated the effect of early implant surface exposure caused by initial bone remodeling on long-term peri-implant bone stability and peri-implant health. Additionally, Oral Health-Related Quality of Life (OHRQoL) was assessed by means of the Oral Health Impact Profile-14 (OHIP-14). Twenty-six patients received two non-splinted implants supporting an overdenture in the mandible by means of locators. One implant was installed equicrestally (control) and the second one was installed subcrestally, taking at least 3 mm soft tissue thickness into account (test). During initial bone remodeling (up to 6 months postoperatively), equicrestal placement yielded 0.68 mm additional surface exposure compared to subcrestal placement (p < 0.001). Afterwards, bone level and peri-implant health were comparable in both treatment conditions and stable up to 5 years. The implant overdenture improved OHRQoL (p < 0.01) and remained unchanged thereafter (p = 0.51). In conclusion, adapting the vertical position of the implant concerning the soft tissue thickness prevents early implant surface exposure caused by initial bone remodeling, but in a well-maintained population, this has no impact on long-term prognosis. The treatment of edentulousness with an implant mandibular overdenture improves OHRQoL.
Clock-Controlled Mitochondrial Dynamics Correlates with Cyclic Pregnenolone Synthesis

Neurosteroids are steroids synthetized in the nervous system, with the first step of steroidogenesis taking place within mitochondria with the synthesis of pregnenolone. They exert important brain-specific functions by playing a role in neurotransmission, learning and memory processes, and neuroprotection. Here, we show for the first time that mitochondrial neurosteroidogenesis follows a circadian rhythm and correlates with the rhythmic changes in mitochondrial morphology. We used synchronized human A172 glioma cells, which are steroidogenic cells with a functional core molecular clock, to show that pregnenolone levels and translocator protein (TSPO) are controlled by the clock, probably via circadian regulation of mitochondrial fusion/fission. Key findings were recapitulated in mouse brains. We also showed that genetic or pharmacological abrogation of fusion/fission activity, as well as disturbing the core molecular clock, abolished circadian rhythms of pregnenolone and TSPO. Our findings provide new insights into the crosstalk between mitochondrial function (here, neurosteroidogenesis) and circadian cycles.
Offspring Birth Weight Is Associated with Specific Preconception Maternal Food Group Intake: Data from a Linked Population-Based Birth Cohort

The preconception period has been recognized as one of the earliest sensitive windows for human development. Maternal dietary intake during this period may influence the oocyte quality, as well as placenta and early embryonic development during the first trimester of pregnancy. Previous studies have found associations between macronutrient intake during preconception and pregnancy outcomes. However, as food products consist of multiple macro- and micronutrients, it is difficult to relate this to dietary intake behavior. Therefore, the aim of this study was to investigate the association between intake of specific food groups during the preconception period with birth weight, using data from the Perined-Lifelines linked birth cohort. The Perined-Lifelines birth cohort consists of women who delivered a live-born infant at term after being enrolled in a large population-based cohort study (The Lifelines Cohort). Information on birth outcome was obtained by linkage to the Dutch perinatal registry (Perined). In total, we included 1698 women with data available on birth weight of the offspring and reliable detailed information on dietary intake using a semi-quantitative food frequency questionnaire obtained before pregnancy. Based on the 2015 Dutch Dietary Guidelines and recent literature 22 food groups were formulated. Birth weight was converted into gestational age-adjusted z-scores. Multivariable linear regression was performed, adjusted for intake of other food groups and covariates (maternal BMI, maternal age, smoking, alcohol, education level, urbanization level, parity, sex of newborn, ethnicity). Linear regression analysis, adjusted for covariates and intake of energy (in kcal) (adjusted z score [95% CI], P) showed that intake of food groups “artificially sweetened products” and “vegetables” was associated with increased birth weight (resp. (β = 0.001 [95% CI 0.000 to 0.001, p = 0.002]), (β = 0.002 [95% CI 0.000 to 0.003, p = 0.03])). Intake of food group “eggs” was associated with decreased birth weight (β = −0.093 [95% CI −0.174 to −0.013, p = 0.02]). Intake in food groups was expressed in 10 g per 1000 kcal to be able to draw conclusions on clinical relevance given the bigger portion size of the food groups. In particular, preconception intake of “artificially sweetened products” was shown to be associated with increased birth weight. Artificial sweeteners were introduced into our diets with the intention to reduce caloric intake and normalize blood glucose levels, without compromising on the preference for sweet food products. Our findings highlight the need to better understand how artificial sweeteners may affect the metabolism of the mother and her offspring already from preconception onwards.
Ocular blood flow and choroidal thickness changes after carotid artery stenting.

PURPOSES To evaluate changes in ocular blood flow and subfoveal choroidal thickness in patients with symptomatic carotid artery stenosis after carotid artery stenting. METHODS We included 15 men (mean age, 63.6 ± 9.1 years) with symptomatic carotid artery stenosis and 18 healthy volunteers (all men; mean age, 63.7 ± 5.3 years). All participants underwent detailed ophthalmologic examinations including choroidal thickness measurement using enhanced depth-imaging optic coherence tomography. The patients also underwent posterior ciliary artery blood flow measurements using color Doppler ultrasonography before and after carotid artery stenting. RESULTS Patients lacked ocular ischemic symptoms. Their peak systolic and end-diastolic velocities increased to 10.1 ± 13.1 (p=0.005) and 3.9 ± 6.3 (p=0.064) cm/s, respectively, after the procedure. Subfoveal choroidal thicknesses were significantly thinner in patients with carotid artery stenosis than those in the healthy controls (p=0.01). But during the first week post-procedure, the subfoveal choroidal thicknesses increased significantly (p=0.04). The peak systolic velocities of the posterior ciliary arteries increased significantly after carotid artery stenting (p=0.005). We found a significant negative correlation between the mean increase in peak systolic velocity values after treatment and the mean preprocedural subfoveal choroidal thickness in the study group (p=0.025, r=-0.617). CONCLUSIONS In patients with carotid artery stenosis, the subfoveal choroid is thinner than that in healthy controls. The subfoveal choroidal thickness increases after carotid artery stenting. Carotid artery stenting treatment increases the blood flow to the posterior ciliary artery, and the preprocedural subfoveal choroidal thickness may be a good predictor of the postprocedural peak systolic velocity of the posterior ciliary artery.
Influence of PVA Molecular Weight and Concentration on Electrospinnability of Birch Bark Extract-Loaded Nanofibrous Scaffolds Intended for Enhanced Wound Healing

Triterpenes from the outer bark of birch (TE) are known for various pharmacological effects including enhanced wound healing. Apart from an already authorized oleogel, electrospun nanofiber mats containing these triterpenes in a polyvinyl alcohol (PVA) matrix appear to be an advantageous application form. The effects of PVA molecular weight and concentration on the fiber morphology have been investigated. Three different molecular weights of PVA ranging from 67 to 186 kDa were used. The concentration of PVA was varied from 5 to 20 wt%. Polymer solutions were blended with colloidal dispersions of birch bark extract at a weight ratio of 60:40 (wt.%). The estimated viscosity of polymer solutions was directly linked to their concentration and molecular weight. In addition, both pure and blended solutions showed viscoelastic properties with a dominant viscous response in the bulk. Fiber morphology was confirmed using scanning electron microscopy (SEM). Both polymer concentration and molecular weight were found to be significant factors affecting the diameter of the fibers. Fiber diameter increased with a higher molecular weight and polymer concentration as more uniform fibers were obtained using PVA of higher molecular weight (146–186 kDa). In vitro drug release and ex vivo permeation studies indicated a faster drug release of betulin from electrospun scaffolds with lower PVA molecular weight. Our research suggests that the fabricated TE-loaded PVA electrospun dressings represent potential delivery systems of TE for wound care applications.
Application of Industry 4.0 Concept to Health Care

The paper describes the concept of the Industry 4.0 and its reflection in health care. Industry 4.0 connects intelligent production concepts with external factors, including those linked with the production and those linked more with human, as for example intelligent homes or social web systems. Communication, data and information play an important role in the whole system. After explaining basic characteristics of the Industry 4.0 concept and its main parts, we show how they can be utilized in the health care sector and what their advantages are. Key technologies and techniques include Internet of Things, big data, artificial intelligence, data integration, robotization, virtual reality, and 3D printing. Finally, we identify the main challenges and research directions. Among the most important ones are interoperability, standardization, reliability, security and privacy, ethical and legal issues.
Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications?

Curcumin, the main polyphenol contained in turmeric root (Curcuma longa), has played a significant role in medicine for centuries. The growing interest in plant-derived substances has led to increased consumption of them also in pregnancy. The pleiotropic and multi-targeting actions of curcumin have made it very attractive as a health-promoting compound. In spite of the beneficial effects observed in various chronic diseases in humans, limited and fragmentary information is currently available about curcumin’s effects on pregnancy and pregnancy-related complications. It is known that immune-metabolic alterations occurring during pregnancy have consequences on both maternal and fetal tissues, leading to short- and long-term complications. The reported anti-inflammatory, antioxidant, antitoxicant, neuroprotective, immunomodulatory, antiapoptotic, antiangiogenic, anti-hypertensive, and antidiabetic properties of curcumin appear to be encouraging, not only for the management of pregnancy-related disorders, including gestational diabetes mellitus (GDM), preeclampsia (PE), depression, preterm birth, and fetal growth disorders but also to contrast damage induced by natural and chemical toxic agents. The current review summarizes the latest data, mostly obtained from animal models and in vitro studies, on the impact of curcumin on the molecular mechanisms involved in pregnancy pathophysiology, with the aim to shed light on the possible beneficial and/or adverse effects of curcumin on pregnancy outcomes.
Latent Profiles of Health Behaviors in Rural Children with Overweight and Obesity.

OBJECTIVE The objectives were to identify profiles of school-age children with overweight and obesity (OW/OB) from rural counties based on patterns of diet, activity, and sleep, to examine demographic predictors, and to examine whether profiles were differentially associated with psychosocial functioning. METHODS Participants included 163 children (Mage = 9.8) and parents. Children wore accelerometers to assess physical activity and sleep duration. Consumption of fruits and vegetables (F/V) and sugar-sweetened beverages (SSB) was assessed with a food frequency questionnaire. Self-report of emotional, social, and academic health-related quality of life (HRQOL), peer victimization, social skills, and social problem behaviors was collected, as well as parent-report of HRQOL. Latent variable mixture modeling (LVMM) was conducted. RESULTS Sleep did not significantly contribute to profile differentiation and was removed. Four profiles emerged: (a) Low F/V + Low SSB + Low activity, (b) Low F/V + Low SSB + Moderate activity, (c) High F/V + High SSB + Low activity, and (d) Moderate F/V + Moderate SSB + High activity. Older children were more likely to be in profile 1. After controlling for child age, parents of children in profile 1 reported significantly lower child social HRQOL than parents of children in profiles 2 and 4. Children in profile 4 reported experiencing significantly lower victimization than those in profile 3. CONCLUSIONS There are subgroups of rural children with OW/OB that engage in various combinations of healthy and unhealthy behaviors. LVMM has the potential to inform future interventions and identify needs of groups of children with OW/OB.