Search Results (66)

The Maternal Embryonic Leucine Zipper Kinase (MELK) gene is a member of the Snf1/AMPK serine/threonine kinase family. MELK has recently attracted considerable interest in cancer biology due to its aberrant overexpression in various malignancies, including glioma, breast, lung, colorectal, gastric, and hematological cancers. It has been shown that higher MELK levels are often correlated with unfavorable prognosis, aggressive tumor manifestations, resistance to treatment, and stem-like tumor morphologies. In this review we aim to summarize the current understanding of MELK biology, including its functions in cell cycle regulation, apoptosis, oncogenic signaling pathways, and tumor stemness. We also discuss the therapeutic potential, limitations, and controversy of MELK inhibitors, and implications in cancer diagnosis and treatment. MELK may not be a universal driver oncogene; nonetheless, it is consistently linked to aggressive disease, underscoring its potential as a prognostic biomarker and a candidate for therapeutic co-targeting in combination treatments. Full article

Background/Objectives: Edwardsiella tarda is a rare Gram-negative pathogen that uncommonly infects humans. Neonatal infections are extremely rare but often severe, with a high incidence of central nervous system (CNS) complications. Case presentation: We report a term neonate born via spontaneous vaginal delivery who developed systemic signs of infection within 18 h of life. Blood and cerebrospinal fluid (CSF) cultures grew Edwardsiella tarda. CSF analysis revealed severe meningoencephalitis. Maternal stool culture was also positive for E. tarda, suggesting vertical transmission. Despite initial systemic antibiotic therapy with ampicillin, gentamicin, and ceftriaxone, neuroimaging revealed progressive multifocal brain abscesses. The infant underwent a series of neurosurgical procedures, including bilateral drainage of abscesses, Rickham reservoir placement and ventriculoperitoneal shunting. A revised antibiotic regimen, including systemic meropenem and trimethoprim-sulfamethoxazole plus intrathecal gentamicin, was administered. At six months, the infant showed mild motor delay with lower limb hypertonia and was under close neurosurgical and developmental follow-up. Methods: We conducted a literature review of 12 published neonatal E. tarda infections, including our case. Results: Most infected infants presented within 72 h of life and exhibited CNS involvement. Mortality was 25%, and 44% of survivors experienced long-term neurologic sequelae. Conclusions: Edwardsiella tarda infection in neonates is rare but potentially devastating. Early suspicion, culture confirmation, aggressive antibiotic therapy, and multidisciplinary care, including neurosurgical management, are essential for improving outcomes. Full article

To better understand the motivation underlying harassment of adult matings by infants, we studied infant harassment behaviors in a multilevel social primate, wild (provisioned) Sichuan snub-nosed monkeys (Rhinopithecus roxellana). Two harassment patterns were identified: care-seeking and sociable. Infants showed more frequent harassment in response to sexual activities of their mothers than non-mothers, with more care-seeking harassment directed to their mothers. The responses of mothers and non-mothers to infant harassment were different, with the former showing increased caretaking of their infants. Infants harassing non-mothers were more likely to receive aggression from the latter than infants harassing their own mothers. Overall, the more frequently infants harassed matings, the more care they received and the more attacks they received. We conclude that in Sichuan snub-nosed monkeys, infant harassment of their mother’s sexual activity is an effective behavioral tactic to receive more maternal care. It can therefore be interpreted as indirect support for the parent–offspring conflict hypothesis. Full article

No studies have induced maternal behavior in goats through hormonal treatment. We evaluated whether ovariectomized goats treated with estradiol benzoate (EB2; n = 7 nulliparous and 10 multiparous goats) or progesterone + estradiol benzoate (P4 + EB2; n = 7 nulliparous and 7 multiparous goats), before or after vagino-cervical stimulation (VCS), displayed maternal behavior. When all goats were measured within treatments, in the EB2 group, low-pitch bleats were more frequent, and the time spent cleaning the kids was longer after VCS (p < 0.01), while location changes were more frequent before VCS. In nulliparous goats, those in the EB2 group emitted more low-pitch bleats after VCS than before (p = 0.04). The frequency of location changes was higher before VCS than after (p = 0.05). In multiparous goats, the frequency of smelling the kids and aggression toward the kids before VCS was higher in the EB2 group than in the P4 + EB2 group (p < 0.01). Within treatments, the EB2 group emitted more low-pitch bleats after VCS than before (p = 0.01), and the duration of cleaning the kids was longer after VCS than before (p = 0.028). Within the P4 + EB2 group, the kids were smelled more frequently after VCS than before (p = 0.03). The maternal index after vagino-cervical stimulation was higher in goats with EB2 (p = 0.002). Nulliparous goats treated with P4 + EB2 had a higher maternal index compared with those treated with EB2 alone (p = 0.04). In conclusion, regardless of parity, maternal behavior induced with the EB2 treatment was better when VCS was applied. Likewise, maternal experience altered the response. In multiparous females, any of the treatments were better after VCS, while in nulliparous females, this was only evident with the EB2 treatment. Full article

Long-term breastfeeding is a modifiable, protective factor against breast cancer, particularly triple-negative breast cancer (TNBC), a highly aggressive subtype with limited therapeutic options. Recent findings suggest that the protective effects of breastfeeding are mediated not only through hormonal regulation and epithelial differentiation but also via the modulation of the breast microbiota. This review examines epidemiological data on the association between breastfeeding duration and TNBC risk reduction, highlights the composition and functions of breast microbiota in health and disease, and discusses how dysbiosis may contribute to carcinogenesis. By examining the microbiome’s role in maintaining breast health, we emphasize how breastfeeding contributes to a natural defense system against TNBC, offering a unique perspective on the intersection of maternal health, microbiology, and cancer prevention. Breastfeeding not only provides maternal and infant benefits but also emerges as a biological strategy that promotes cancer resistance through its influence on the breast microbiota. Integrating epidemiological, microbiological, and mechanistic evidence suggests that future research deliberately combining these domains will be essential to clarify causal pathways and translate findings into prevention and intervention strategies against TNBC. Full article

The review provides an overview of research concerning the assessment of cattle welfare in different housing systems. Hence, it restricts its scope to factors known to have a particular influence on the expression of their natural behaviours. It analyses the impact of housing systems on social and maternal bonds, as well as on the health and productivity of animals and on the feeding behaviour and physical activity of animals. It also pays attention to the occurrence of stereotypies, indicating the quality of the environment in which animals live, and attempts to determine the extent to which environmental enrichment improves welfare. It can be seen that welfare can vary significantly depending on the cattle rearing system. In intensive rearing environments, weaning calves and limited space often result in stress and behavioural disorders (e.g., cross-sucking). Extensive systems, offering access to pasture and longer cow–calf contact, usually provide higher levels of welfare. A freestall system allows greater freedom of movement and social contact but requires appropriate management to prevent aggression; in contrast, the tethering system limits movement, which increases the risk of stress and health problems. It has also been shown that enriching the living space of animals can significantly improve their welfare, regardless of the housing system. By balancing productivity with ensuring that the cattle are able to express their natural behaviours and maintain good health, it is possible to benefit both the animals and the agricultural sector as a whole, increasing its profitability and gaining consumer confidence. Full article

Although previous studies have shown that parental burnout is a risk factor for adolescents’ development, much remains unknown about the associations between mothers’ parental burnout and adolescents’ aggression as well as the potential mechanisms underlying this relation. To fill these gaps, the current study tested the relationship between mothers’ parental burnout and adolescents’ aggression, as well as the mediating role of maternal rejection and the moderating role of adolescent empathy and gender. A total of 578 Chinese adolescent–mother dyads (for adolescents, 52.42% girls, M_age = 15.30, SD = 1.67; for mothers, M_age = 42.71, SD = 5.49) completed questionnaires regarding mothers’ parental burnout, adolescent aggression, and perceived maternal rejection, as well as empathy. The results showed that mothers’ parental burnout was significantly and positively associated with adolescent aggression and that this relationship was partially mediated by adolescent-perceived maternal rejection. Furthermore, the moderated mediation analysis further revealed that adolescents’ cognitive empathy served as a buffer in the relationship between parental burnout and adolescents’ aggression. In addition, the relation between parental burnout and aggression as well as parental burnout and maternal rejection was stronger for boys. These findings emphasize the need to improve social cognitive abilities in aggression intervention programs. Full article

This study introduces a novel approach to optimal Service Level Agreement (SLA) tier selection in online services by incorporating client-side obsolescence factors into effective SLA planning. We analyze a comprehensive dataset of 600 million records collected over four years, focusing on the lifecycle patterns of browsers published into the iPhone and Samsung ecosystems. Using Gaussian Process Regression with a Matérn kernel and exponential decay models, we model browser version adoption and decline rates, accounting for data sparsity and noise. Our methodology includes a centroid-based filtering technique and a quadratic decay term to mitigate bot-related anomalies. Results indicate distinct browser delivery refresh cycles for both ecosystems, with iPhone browsers showing peaks at 22 and 42 days, while Samsung devices exhibit peaks at 44 and 70 days. We quantify the support duration required to achieve various SLA tiers as follows: for 99.9% coverage, iPhone and Samsung browsers require 254 and 255 days of support, respectively; for 99.99%, 360 and 556 days; and for 99.999%, 471 and 672 days. These findings enable more accurate and effective SLA calculations, facilitating cost-efficient service planning considering the full service delivery and consumption pipeline. Our approach provides a data-driven framework for balancing aggressive upgrade requirements against generous legacy support, optimizing both security and performance within given cost boundaries. Full article

Aggressive behaviour in pigs poses significant challenges to animal welfare, production efficiency, and economic performance in the pork industry. This review explores the multifaceted causes of pig aggression, focusing on genetic, environmental, and physiological factors. Aggression in pigs is categorized into social, maternal, fear-induced, play, and redirected aggression, with early-life hierarchies and environmental stressors playing critical roles. Physiological markers, such as elevated cortisol and reduced serotonin levels, are closely linked to aggressive behaviour, while dietary interventions, including tryptophan supplementation, have shown promise in mitigating aggression. Environmental factors, such as overcrowding, noise, and heat stress, exacerbate aggressive tendencies, whereas enrichment strategies, like music and improved housing conditions, can reduce stress and aggression. Genome-wide analyses have pinpointed specific polymorphisms in neurotransmitter genes (DRD2, SLC6A4, MAOA) and stress-response loci (RYR1) as significant predictors of porcine aggression. Advances in genomic technologies, including genome-wide association studies (GWASs) and transcriptomic analyses, have further elucidated the genetic and epigenetic underpinnings of aggressive behaviour. Practical application in breeding programmes remains challenging due to aggression polygenic nature and industry hesitancy toward genomic approaches. Future research should focus on integrating genetic markers into breeding programmes, developing multitrait selection indices, and exploring epigenetic modifications to improve animal welfare and production efficiency. By addressing these challenges, the pork industry can enhance both the well-being of pigs and the sustainability of production systems. Full article

Adolescent externalizing problems are commonly linked to maternal psychological distress and family functioning, but these associations remain underexplored in the Greek sociocultural context. This study examined how maternal symptoms of depression, anxiety, and stress, along with adolescent-perceived family functioning, predict externalizing behaviors in Greek adolescents. A total of 563 adolescent–mother dyads (63.4% girls; M_age = 15.03 and SD = 0.83) participated. Mothers completed the Child Behavior Checklist (CBCL), the Depression Anxiety Stress Scales (DASS-21), and the Family Assessment Device (FAD–GF), while adolescents completed the Youth Self-Report (YSR) and FAD–GF. Hierarchical regression analysis showed that adolescent-perceived family functioning was the strongest predictor of externalizing behavior (β = 0.24 and p < 0.001), even after accounting for demographic and maternal mental health variables. The final model explained 18% of the variance in adolescent externalizing problems. Mediation analysis confirmed that family functioning partially mediated the relationship between maternal depression and adolescent externalizing problems, with a significant indirect effect (a × b = 0.088, Sobel z = 2.90, and p = 0.004). Gender differences were found for self-reported aggressive behavior (t = −2.40, p = 0.017, and d = 0.20), with girls scoring higher than boys. These findings highlight the indirect impact of maternal depression through family dynamics and underscore the importance of culturally sensitive, family-centered interventions to reduce adolescent externalizing problems. Full article

We investigated the impact of perinatal dioxin exposure (indicated by dioxin levels in maternal breast milk) on clock gene mRNA expression in buccal cells of 9-year-old children from the Da Nang birth cohort in Vietnam using reverse transcription polymerase chain reaction. Of the 56 boys and 34 girls (67% detection rate) in whom PER1 was detected, BMAL1 was detected in only 16 boys and 15 girls. Dioxin levels were significantly higher in girls with BMAL1 detection than in girls without detection. In girls, higher relative BMAL1 expression levels were associated with greater levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and toxic equivalents of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. Moreover, BMAL1 expression levels were correlated with shorter night sleep duration on weekdays, greater sleep duration on holidays, and higher hyperactivity scores. After adjusting for maternal parity, relative PER1 expression levels were higher in boys with higher toxic equivalents of polychlorinated dibenzofuran than those in girls. Although higher PER1 expression levels were correlated with greater verbal aggression and hostility scores in girls, no such associations were found in boys. These findings suggest the possible existence of sex-specific effects of perinatal dioxin exposure on circadian rhythms regulated by clock genes, particularly BMAL1, leading to sleep and behavioral problems in later life. Full article

Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis and lacks actionable molecular targets for treatment. Maternal embryonic leucine zipper kinase (MELK) is highly expressed in TNBC and has been implicated in poor clinical outcomes, though its mechanistic role in the aggressive biology of TNBC is poorly understood. Here, we demonstrate a role of MELK in TNBC progression and metastasis. Analysis of publicly available datasets revealed that high MELK expression correlates with worse overall survival, recurrence-free survival, and distant metastasis-free survival, and MELK is co-expressed with metastasis-related genes. Functional studies demonstrated that MELK inhibition, using genomic or pharmacologic inhibition, reduces mammosphere formation, migration, and invasion in high-MELK-expressing TNBC cell lines. Conversely, MELK overexpression in low-MELK-expressing cell lines significantly increased invasive capacity in vitro and metastatic potential in vivo, as evidenced by enhanced metastasis to the liver and lungs in a chorioallantoic membrane assay. These findings highlight MELK as a key regulator of TNBC aggressiveness and support its potential as a therapeutic target to mitigate metastasis and improve patient outcomes. Full article

Objective: Intrauterine resuscitation (IR) may be employed during labor to reduce emergency deliveries with concerns for fetal wellbeing emanating mostly from increased uterine contraction frequency and/or intensity. However, there is no standard definition of what constitutes IR, and how its impact is assessed. Here, we have created two measures of relative IR effectiveness, determined over a two-hour time frame after Pitocin was first initiated, and asked how fetal risk severity at the time of its initiation impacted IR effectiveness and the clinical decisions made. Methods: We analyzed 118 patients receiving Pitocin who underwent IR at least once during labor. Retrospectively, we assessed risk levels using our Fetal Reserve Index version 2 (FRI v2) scores that were calculated in 20 min timeframes. FRIv2 scores include various maternal, obstetric, and fetal risk factors, uterine contraction frequency, and FHR baseline rate, variability, accelerations, and decelerations. We define 3 IR scenarios to assess relative IR effectiveness. (1) No reduction in PIT infusion rates (PITSAME), (2) decreased PIT infusion rates (DPIT), or (3) PIT turned off (PIT OFF). Maternal repositioning and oxygen administration are nearly universal across all types and, therefore, are not considered in groupings. We then created two measures of IR effectiveness by classifying changes in FRI v2 scores over six 20 min windows coincident with and following IR use as (1) “Improvement” (improvement relative to the FRIv2 score at IR initiation) and (2) “Stabilization” (no further decrease in FRI score relative to the FRIv2 score in the sixth 20 min epoch after IR initiation). We evaluated the relative effectiveness of the three PIT options, and to test whether the level of fetal risk at the time of IR initiation affected its short-term effectiveness, FRI v2 risk scores were assigned to one of three groups (Green [1.00–0.625]; Yellow [0.50–0.25]; Red 0.25–0.0]). Higher scores indicate lower risk. Statistical analysis was performed with ANOVA and t- tests. Results: Overall, the first and/or the only initiation of IR resulted in improvement in 71% of cases and stabilization in 78% of cases. The remaining 22% were failures, meaning that the FRIv2 score in the 6th 20 min period was lower than the score at the time of initiation. There were modest, but not statistically significant, differences in effectiveness (improvement or stabilization) by type of IR. There was a trend toward lower IR effectiveness of PIT OFF during IR initiation when compared to PIT continuation or decreased groups. Conclusions: IR initiation or type did not vary significantly by retrospectively calculated levels of fetal risk, showing that wide variation in clinician practices, not necessarily correlated with what we believe actual risk was, determine how IR was used. The FRI provides contextualization of FHR elements by adding maternal, fetal, and obstetric risk factors, and increased uterine activity enables a more rigorous and reproducible approach to analysis of emerging fetal compromise and IR effectiveness. As practice has shifted from the over-aggressiveness of PIT use to now premature discontinuations with any tracing variation, we need better metrics. FRIv2 further improves its physiologic underpinnings. Thus, we propose a new approach to the overall assessment of IR practice. Full article

The objective of this study was to evaluate the effect of maternal experience on behavior, progesterone and estradiol concentrations, weight and body condition in goats in the peripartum period, as well as the behavior and weight of the kids in the first hours after birth. Twenty multiparous and 10 primiparous dairy goats were enrolled. Behaviors such as walking, isolation, aggression, eating, inactivity and rumination were recorded in females during the last three days prior to the day of delivery, as well as the behaviors of the dam and her progeny in the first 2 h postpartum and the ability of the mother to discriminate between own kid and the alien one (selectivity test) at 2 h postpartum. Gestational and postpartum plasma progesterone and estradiol concentrations were determined. In the prepartum period there was a higher percentage of primiparous goats that were eating and remained less inactive compared to multiparous goats (p < 0.05). During the postpartum period, the lick latency to the kid was shorter in multiparous than in primiparous goats (p = 0.015). There was a greater proportion of kids born from multiparous (67%) than from primiparous (27%) that stood up in the first 30 min postpartum (p < 0.0001). Therefore, the proportion of multiparous kids (33%) than primiparous kids (9%) that were nursed within the first hour after birth was also higher (p < 0.0001). Progesterone and estradiol concentrations were not affected by maternal experience, neither in the prepartum nor the postpartum. In conclusion, maternal experience affected some behaviors at peripartum of the dam and vitality in the kid; however, the differences in behavior were not accompanied by differences in the variations in circulating estradiol and progesterone levels in the dam. Full article

Background: This study evaluated the effectiveness of an online intervention designed to improve parent–child interactions and address disordered eating behaviors in children. Using remote video-feedback sessions based on observations of mother–child feeding interactions, the intervention offers a cost-effective and environmentally friendly alternative to traditional in-person methods. Aims: The study aimed to assess the impact of online intervention on the quality of mother–child interactions during feeding and its effectiveness in reducing psychopathological symptoms in both mothers and children. Methods: The intervention was conducted entirely online, with improvements measured using SVIA scores for mother–child interactions and the SCL-90/R Global Severity Index (GSI) for maternal psychopathological symptoms, alongside evaluations of children’s emotional and behavioral functioning, particularly anxiety, depression, and aggression. Results: The intervention significantly improved the quality of mother–child interactions across all SVIA subscales and led to reductions in maternal symptoms of depression and anxiety, as well as decreases in children’s emotional and behavioral symptoms. Conclusions: These findings suggest that online video-feedback interventions can effectively enhance mother–child relationships and reduce psychopathological symptoms in both mothers and children, although further research with larger sample sizes and more robust statistical analyses is needed to confirm these results. Full article