Search Results (5,316)

Background/Objectives: Leukemia is associated with high recurrence rates and cancer vaccines are emerging as a promising immunotherapy against the disease. Here, we investigate the mechanism of action by which a personalized vaccine made from leukemia cells infected with an oncolytic virus (ICV) induces anti-tumor immunity. Methods: Using the L1210 murine model, leukemia cells were infected and irradiated to create the ICV. The CRISPR-Cas9 system was used to engineer knockout cells to test in treatment efficacy studies. Results: We found that pro-inflammatory interferons (IFNs) that are produced by infected vaccine cells induce the immunoproteasome (ImP), a specialized proteasome subtype that is found in immune cells. Interestingly, we show that while a vaccine using the oncolytic vesicular stomatitis virus (oVSV) completely protects against tumor challenge, the wild-type (wt) virus, which does not induce the ImP, is not as effective. To delineate the contribution of the ImP for vaccine efficacy, we generated ImP-knockout cell lines and found no differences in treatment efficacy compared to wild-type cells. Furthermore, an ICV using another murine leukemia model that expresses the ImP only when infected by an IFN gamma-encoding variant of the virus demonstrated similar efficacy as the parental virus. Conclusions: Taken together, our data show that ImP expression by vaccine cells was not required for the efficacy of leukemia ICVs. Full article

Downy mildew caused by Plasmopara viticola is an important disease in grape production, particularly in the highly susceptible, widely cultivated Vitis vinifera L. Breeding for disease resistance is an effective solution, and V. vinifera intraspecific crosses can yield progeny with both disease resistance and high quality. To assess the potential of intraspecific recurrent selection in V. vinifera (IRSV) in improving grapevine resistance to downy mildew and to analyze the pattern of disease resistance inheritance, the disease-resistant variety Ecolly was selected as one of the parents and crossed with Cabernet Sauvignon, Marselan, and Dunkelfelder, respectively, creating three reciprocal combinations, resulting in 1657 hybrid F1 progenies. The primary results are as follows: (1) significant differences in disease resistance among grape varieties and, significant differences in disease resistance between different vintages of the same variety were found; (2) the leaf downy mildew resistance levels of F1 progeny of different hybrid combinations conformed to a skewed normal distribution and showed some maternal dominance; (3) the degree of leaf bulbous elevation was negatively correlated with the level of leaf downy mildew resistance, and the correlation coefficient with the level of field resistance was higher; (4) five progenies with higher levels of both field and in vitro disease resistance were obtained. Intraspecific hybridization can improve the disease resistance of offspring through super-parent genetic effects, and Ecolly can be used as breeding material for recurrent hybridization to obtain highly resistant varieties. Full article

Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study aimed to simulate and predict the behavior of six different types of pacifiers and their functional interaction with the tongue and palate, with the goal of understanding their potential effects on orofacial growth and development. Materials and Methods: Biomechanical analysis using Finite Element Analysis (FEA) mathematical models was employed to evaluate the behavior of six different commercial pacifiers in contact with the palate and tongue. Three-dimensional solid models of the palate and tongue were based on the mathematical framework from a 2007 publication. This allowed for a detailed investigation into how various pacifier designs interact with soft and hard oral tissues, particularly the implications on dental and skeletal development. Results: The findings of this study demonstrate that pacifiers exhibit different interactions with the oral cavity depending on their geometry. Anatomical–functional pacifiers, for instance, tend to exert lateral compressions near the palatine vault, which can influence the hard palate and contribute to changes in craniofacial growth. In contrast, other pacifiers apply compressive forces primarily in the anterior region of the palate, particularly in the premaxilla area. Furthermore, the deformation of the tongue varied significantly across different pacifier types: while some pacifiers caused the tongue to flatten, others allowed it to adapt more favorably by assuming a concave shape. These variations highlight the importance of selecting a pacifier that aligns with the natural development of both soft and hard oral tissues. Conclusions: The results of this study underscore the crucial role of pacifier geometry in shaping both the palate and the tongue. These findings suggest that pacifiers have a significant influence not only on facial bone growth but also on the stimulation of oral functions such as suction and feeding. The geometry of the pacifier affects the soft tissues (tongue and muscles) and hard tissues (palate and jaw) differently, which emphasizes the need for careful selection of pacifiers during infancy. Choosing the right pacifier is essential to avoid potential negative effects on craniofacial development and to ensure that the benefits of proper oral function are maintained. Therefore, healthcare professionals and parents should consider these biomechanical factors when introducing pacifiers to newborns. Full article

Background/Objectives: Children with severe physical and communication disabilities face many challenges. They have very limited opportunities for upright, hands-free, self-initiated mobility. Current findings in neuroscience and theories on child development suggest that self-initiated mobility can have positive cascading effects on various developmental areas, including language and communication. This study was conducted to examine the current use of hands-free support walkers with children who have severe physical and communication disabilities and use augmentative and alternative communication and to identify the benefits and problems perceived by their parents and professionals from different disciplines. Methods: Online surveys were utilized to collect information from 127 participants, including 31 parents and 96 professionals or paraprofessionals. Results: The participants reported that these children could perform various motor activities in the hands-free support walkers to achieve different goals. Benefits identified by both parents and professionals included providing a way to exercise and stay active, improving motor control, enhancing independence, and bringing enjoyment. Professionals also observed positive impacts on communication, vocalization, use of eye contact, and problem solving. Conclusions: Results suggest that children with severe physical and communication disabilities can benefit from the upright, hands-free, self-initiated mobility provided by hands-free support walkers. Clinical implications and needs for future research are discussed. Full article

Background/Objectives: Variations in hair length are observed in many dog breeds, as determined by the canine FGF5 gene. Long-haired Akitas, which are disqualified under breeding standards of Akitas, are sometimes born to short-haired parents and may have been subjected to treatments compromising animal welfare. Here, we aimed to identify an FGF5 variant associated with hair coat variations in Akitas in Japan, and to assess how welfare of this breed can be improved by carefully planned breeding. Methods: DNA samples were obtained from 60 Akitas in 2021 (modern Akitas) and 73 Akitas in the 1970s and the 1980s (classic Akitas). Sanger sequencing was performed on all exons and exon–intron junctions of the FGF5 gene to determine the causative variant of long hair in Akitas. A real-time PCR assay was developed to genotype FGF5:c.578C>T in modern and classic Akitas. Using 54 dogs from modern Akitas, scores (1 to 10) of hair length were compared among the three genotypes (C/C, C/T, and T/T). Results: Sanger sequencing revealed that the canine FGF5:c.578C>T variant was associated with long hair in Akitas in Japan. Genotyping revealed that the frequency of the mutant T allele was 0.350 in modern Akitas, which was significantly higher (p < 0.001) than in classic Akitas (0.212). The three genotypes were not in Hardy–Weinberg equilibrium (HWE) in modern Akitas but were in HWE in classic Akitas. There were significant differences in hair length scores among the three genotypes (p < 0.001) and between the C/C and C/T genotypes (p < 0.005). There was no significant difference in the scores between male and female dogs. Conclusions: This study revealed that a causative variant that determines the long hair trait of Akitas in Japan was the FGF5:c.578C>T variant, which was inherited in an incompletely dominant manner. Akita dog breeders were more likely to select heterozygous C/T dogs based on the appearance of the hair coat for breeding dogs with an ideal fluffy hair coat. This might result in a high mutant T allele frequency and the production of undesired long-haired Akitas with T/T, which may create welfare problems. Genetic testing for this variant is necessary to improve welfare and conserve the Akita breed. Full article

Background: Self-report physical activity (PA) scales, accelerometry, and heart rate (HR) monitoring are reliable tools for PA measurement for children with cerebral palsy (CP); however, there are limitations for those who are primary wheelchair users. The purpose of our study was to evaluate face and construct validity of the PROMIS^® Pediatric PA parent proxy short form 8a in measuring PA amount and intensity in children with CP who are non-ambulatory. Methods: Face validity: Semi-structured interviews with parents and pediatric physical therapists (PTs) were conducted about the appropriateness of each item on the PROMIS^® Pediatric PA short form. Construct validity: Children with CP who were non-ambulatory participated in a one-week observational study. PA amount and intensity were examined using PA monitors (Actigraph GT9X) and HR monitors (Fitbit Charge 4). Activity counts and time in sedentary and non-sedentary intensity zones were derived and compared to the PROMIS^® T-scaled score. Results: Twenty-two physical therapists (PTs) and fifteen parents participated in the interviews, and ten children completed 1-week PA observation. Eight and seven participants completed sufficient time of uninterrupted PA and HR monitor wear, respectively. Parents and PTs agreed that several questions were not appropriate for children with CP who were non-ambulatory. PA intensity via activity counts derived from wrist worn monitors showed a strong positive correlation with the PROMIS^® PA measure. Conclusions: Construct validity in our small sample was established between PROMIS^® scores and accelerometry activity counts when documenting PA amount and intensity; however, there were some differences on PROMIS^® face validity per parent and PT respondents. Despite some concerns regarding face validity, the PROMIS^® Pediatric PA parent proxy short form 8a shows promise as a valid measure of physical activity amount and intensity in non-ambulatory children with CP, warranting further investigation and refinement. Full article

Background: Preterm infants and their families face a challenging experience during their stay in the neonatal intensive care unit (NICU). Family-centered care emphasizes the importance of welcoming parents, involving them in their baby’s daily care, and supporting the development of parenting skills. NICU staff should support parents in understanding their baby’s needs and in strengthening the parent–infant bond. Although many tools outline what parents should learn, there is a limited structured framework to monitor their involvement in the infant’s care. Tracking parental participation in daily caregiving activities could support professionals in effectively guiding families, ensuring a smoother transition to discharge. Aims: The aim of this study was to evaluate the adherence to and effectiveness of a structured tool for parental involvement in the NICU. This tool serves several key purposes: to track the progression and timing of parents’ autonomy in caring for their baby, to support parents in building caregiving competencies before discharge, and to standardize the approach of NICU professionals in promoting both infant care and family engagement. Methods: A structured template form for documenting parental involvement (“together TO-CARE template”, TTCT) was integrated into the computerized chart adopted in the NICU of Modena. Nurses were asked to complete the TTCT at each shift. The template included the following assessment items: parental presence; type of contact with the baby (touch; voice; skin-to-skin); parental involvement in care activities (diaper changing; gavage feeding; bottle feeding; breast feeding); and level of autonomy in care (observer; supported by nurse; autonomous). We evaluated TTCT uploaded data for very low birth weight (VLBW) preterm infants admitted in the Modena NICU between 1 January 2023 and 31 December 2024. Staff compliance in filling out the TTCT was assessed. The timing at which parents achieved autonomy in different care tasks was also measured. Results: The TTCT was completed with an average of one entry per day, during the NICU stay. Parents reached full autonomy in diaper changing at a mean of 21.1 ± 15.3 days and in bottle feeding at a mean of 48.0 ± 22.4 days after admission. The mean length of hospitalization was 53 ± 38 days. Conclusions: The adoption of the TTCT in the NICU is feasible and should become a central component of care for preterm infants. It promotes family-centered care by addressing the needs of both the baby and the family. Encouraging early and progressive parental involvement enhances parenting skills, builds confidence, and may help reduce post-discharge complications and readmissions. Furthermore, the use of a standardized template aims to foster consistency among NICU staff, reduce disparities in care delivery, and strengthen the support provided to families of preterm infants. Full article

Background: This study investigated the relationship between problematic media use (PMU) and working memory in preschoolers. Methods: Parents of children aged 3 to 7 (260 boys, 257 girls; M_age = 5.57, SD = 0.73) in Jinan, China, completed questionnaires assessing children’s PMU and working memory. Subsequently, High (n_high = 32, M_age = 4.53, SD = 0.67) and Low (n_low = 30, M_age = 4.67, SD = 0.66) PMU groups, based on the survey data, complete a dual 1-back task during functional near-infrared spectroscopy (fNIRS) recording. Results: Behavioral accuracy and reaction time showed no significant group differences. However, a significant interaction between the PMU group and gender on prefrontal activation was observed, F(1, 60) = 5.88–7.59, ps < 0.05, ηp² = 0.09–0.12. High-PMU boys exhibited greater left prefrontal activation than low-PMU boys, while low-PMU girls showed greater activation in these same areas compared to low-PMU boys. A three-way interaction of group, task condition, and gender on prefrontal activation was also found, F(2, 60) = 5.81–6.42, p < 0.01, ηp² = 0.10–0.19, suggesting that neural responses varied by task and participant characteristics. Conclusions: These findings indicate that PMU may be associated with altered prefrontal activation during working memory tasks in preschoolers, with gender playing a moderating role. Full article

Cultivated land quality is a key factor in ensuring sustainable agricultural development. Exploring differences in cultivated land quality under distinct cropping systems is essential for developing targeted improvement strategies. This study takes place in Shenyang City—located in the typical black soil region of Northeast China—as a case area to construct a cultivated land quality evaluation system comprising 13 indicators, including organic matter, effective soil layer thickness, and texture configuration. A minimum data set (MDS) was separately extracted for paddy and upland fields using principal component analysis (PCA) to conduct a comprehensive evaluation of cultivated land quality. Additionally, an obstacle degree model was employed to identify the limiting factors and quantify their impact. The results indicated the following. (1) Both MDSs consisted of seven indicators, among which five were common: ≥10 °C accumulated temperature, available phosphorus, arable layer thickness, irrigation capacity, and organic matter. Parent material and effective soil layer thickness were unique to paddy fields, while landform type and soil texture were unique to upland fields. (2) The cultivated land quality index (CQI) values at the sampling point level showed no significant difference between paddy (0.603) and upland (0.608) fields. However, their spatial distributions diverged significantly; paddy fields were dominated by high-grade land (Grades I and II) clustered in southern areas, whereas uplands were primarily of medium quality (Grades III and IV), with broader spatial coverage. (3) Major constraint factors for paddy fields were effective soil layer thickness (21.07%) and arable layer thickness (22.29%). For upland fields, the dominant constraints were arable layer thickness (27.57%), organic matter (25.40%), and ≥10 °C accumulated temperature (23.28%). Available phosphorus and ≥10 °C accumulated temperature were identified as shared constraint factors affecting quality classification in both systems. In summary, cultivated land quality under different cropping systems is influenced by distinct limiting factors. The construction of cropping-system-specific MDSs effectively improves the efficiency and accuracy of cultivated land quality assessment, offering theoretical and methodological support for land resource management in the black soil regions of China. Full article

This study addresses fairness in machine learning for student academic performance prediction using the UCI Student Performance dataset. We comparatively evaluate logistic regression, Random Forest, and XGBoost, integrating the Synthetic Minority Oversampling Technique (SMOTE) to address class imbalance and 5-fold cross-validation for robust model training. A comprehensive fairness analysis is conducted, considering sensitive attributes such as gender, school type, and socioeconomic factors, including parental education (Medu and Fedu), cohabitation status (Pstatus), and family size (famsize). Using the AIF360 library, we compute the demographic parity difference (DP) and Equalized Odds Difference (EO) to assess model biases across diverse subgroups. Our results demonstrate that XGBoost achieves high predictive performance (accuracy: 0.789; F1 score: 0.803) while maintaining low bias for socioeconomic attributes, offering a balanced approach to fairness and performance. A sensitivity analysis of bias mitigation strategies further enhances the study, advancing equitable artificial intelligence in education by incorporating socially relevant factors. Full article

Background/Objectives: Pseudohypoparathyroidism (PHP) is a group of genetic disorders characterized by end-organ resistance to multiple hormones, short stature, brachydactyly, subcutaneous ossifications, obesity, and developmental delays. The tissue specific imprinting of GNAS in the hypothalamus may lead to different eating behavior phenotypes in maternally inherited (PHP1A, PHP1B) vs. paternally inherited (PPHP) variants. In this exploratory study, we aimed to evaluate differences in eating behaviors in a cohort of patients with PHP1A, PPHP and PHP1B. Methods: Assessments included caregiver-reported measures (hyperphagia questionnaire, children’s eating behavior questionnaire, child feeding questionnaire) and self-reported measures (three factor eating behavior questionnaire). Results: A total of 58 patients with PHP1A, 13 patients with PPHP and 10 patients with PHP1B contributed data, along with 124 obese pediatric controls. An increased risk of obesity was found in PHP1A vs. PPHP (adult body mass index (BMI) 39.8 ± 8.7 vs. 30.2 ± 7.4 kg/m², p = 0.03). Parents reported significantly earlier onset of interest in food in children with PHP1A (2.0 ± 2.3 years) and PHP1B (1.1 ± 1.3 years) compared with controls (5.2 ± 3.2 years, p < 0.001). Measures of hyperphagia, satiety and other feeding behaviors were all similar to controls. The highest hyperphagia questionnaire scores were seen prior to adolescence. In a multi-year, longitudinal assessment of 11 pediatric patients with PHP1A, hyperphagia scores were stable and 25% showed an improvement in symptoms. Conclusion: Patients with PHP1A/1B may have hyperphagia symptoms from a young age but they do not worsen over time. Patients may overeat when allowed access to food, but do not usually have disruptive food seeking behaviors. Early diagnosis can give clinicians the opportunity to provide anticipatory diagnosis on the increased risk of obesity in PHP1A/1B and need for scheduled meals and controlled portions. Further studies with larger cohorts are needed to confirm these findings. Full article

Background: The diagnosis of a disability in a child may significantly impact the entire family system. While existing literature has primarily focused on parental reaction to the diagnosis, little is known about how typically developing siblings process this event. Methods: This exploratory study presented the preliminary psychometric properties of the Reaction to Diagnosis Questionnaire—Sibling Version, adapted from an instrument originally designed to assess parental reaction to the child’s diagnosis. Following a back-translation and adaptation process, a cross-sectional study was conducted on 623 typically developing siblings (M = 24.6 years, SD = 5.76) of individuals with neurodevelopmental disorders or physical disabilities. Results: Exploratory factor analyses supported a refined 32-item questionnaire with two factors—lack of resolution versus resolution, both showing excellent internal reliability. No significant differences were found based on typically developing sibling sex, age, or type of disability of the brother/sister, while correlational analyses indicated that greater disability severity was associated with lower resolution and higher lack of resolution. Conclusions: Results suggested that the Reaction to Diagnosis Questionnaire—Sibling Version is a promising tool for assessing the reaction to the brother/sister diagnosis on behalf of the typically developing siblings. Further research is needed to confirm these results and inform intervention programs promoting well-being and adaptive family functioning. Full article

Graphene quantum dots (GQDs) obtained by microwave-induced pyrolysis of glutamic acid and triethylenetetramine (trien) are fairly stable, emissive, water-soluble, and positively charged nano-systems able to interact with negatively charged meso-tetrakis(4-sulfonatophenyl) porphyrin (TPPS₄). The stoichiometric control during the preparation affords a supramolecular adduct, GQDs@TPPS₄, that exhibits a double fluorescence emission from both the GQDs and the TPPS₄ fluorophores. These supramolecular aggregates have an overall negative charge that is responsible for the condensation of cations in the nearby aqueous layer, and a three-fold acceleration of the metalation rates of Cu²⁺ ions has been observed with respect to the parent porphyrin. Addition of various metal ions leads to some changes in the UV/Vis spectra and has a different impact on the fluorescence emission of GQDs and TPPS₄. The quenching efficiency of the TPPS₄ emission follows the order Cu²⁺ > Hg²⁺ > Cd²⁺ > Pb²⁺ ~ Zn²⁺ ~ Co²⁺ ~ Ni²⁺ > Mn²⁺ ~ Cr³⁺ >> Mg²⁺ ~ Ca²⁺ ~ Ba²⁺, and it has been related to literature data and to the sitting-atop mechanism that large transition metal ions (e.g., Hg²⁺ and Cd²⁺) exhibit in their interaction with the macrocyclic nitrogen atoms of the porphyrin, inducing distortion and accelerating the insertion of smaller metal ions, such as Zn²⁺. For the most relevant metal ions, emission quenching of the porphyrin evidences a linear behavior in the micromolar range, with the emission of the GQDs being moderately affected through a filter effect. Deliberate pollution of the samples with Zn²⁺ reveals the ability of the GQDs@TPPS₄ adduct to detect sensitively Cu²⁺, Hg^2+, and Cd²⁺ ions. Full article

Background: Very preterm infants are at increased risk of impairment. The objective was to explore the effect of immediate parent–infant skin-to-skin contact at very preterm birth on cognition, motor, social, and language development during the two first years. Methods: The Immediate Parent-Infant Skin-To-Skin Study (IPISTOSS) was a clinical trial with inclusions between April 2018 to June 2021, in three Scandinavian neonatal intensive care units. Infants were randomised at gestational age 28 + 0 to 32 + 6 weeks plus days, to immediate and continuous skin-to-skin contact at birth or conventional care, during the first six hours of life. Results: At three months, 42 infants underwent a General Movement Assessment. At four and 12 months, 69 and 62 infants, respectively, were assessed with the Alberta Motor Infant Scale. At 24 months, language and cognition were tested in 62 infants with the Bayley Scales of Infant and Toddler Development, third edition. Parents completed the Modified Checklist for Autism in Toddlers for 57 infants. There were no significant differences in motor development, cognition, or autism spectrum disorders. A significant difference in language scores in favour of immediate skin-to-skin contact, was found, when adjusted for fathers’ education, mothers’ education, and infants’ sex, Beta (95% CI): 32.00 (7.57, 56.43) p = 0.01, 11.51 (8.94, 55.06) p = 0.007, and 32.00 (7.85, 56.15) p = 0.01, respectively. Conclusions: Skin-to-skin contact immediately at birth did not enhance cognition, motor, or social development during the first two years of life but may have been important for language skills. Our findings support the World Health Organisation guidelines recommending iSSC for preterm born infants in all settings. Full article

Medicinal plants have been used in traditional medicines all over the world to treat human diseases throughout human history. Many of the medicinal plants have frequently become food and nutrition plants. A more sophisticated investigation resulted in discovering numbers of biologically important secondary metabolites of plants. Pentacyclic triterpenoids represent an important group of the plant secondary metabolites that have emerged as having top biological importance. While the most widespread plant triterpenoids and a majority of their semisynthetic derivatives have been reviewed quite often, other plant pentacyclic triterpenoids and their derivatives have so far been less frequently studied. Therefore, attention has been focused on selected pentacyclic triterpenoids, namely on arjunolic acid, asiatic acid, α- and β-boswellic acids, corosolic acid, maslinic acid, morolic acid, moronic acid, and the friedelane triterpenoids, and on different derivatives of the selected triterpenoids in this review article. A literature search was made in the Web of Science for the given keywords, covering the required area of secondary plant metabolites and their semisynthetic derivatives starting in 2023 and ending in February 2025. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and the biological activity of their relevant derivatives have been summarized therein. Even if cytotoxicity of the compounds has mainly been reviewed, other biological effects are mentioned if they appeared in the original articles in connection with the selected triterpenoids and their derivatives, listed above. A comparison of the effects of the parent plant products and their derivatives has also been made. Full article