Advanced Maturation Research Articles

The Intercultural Experience Project: A practical tool leveraging multiple intercultural experiences at home to foster student intercultural competence

ABSTRACT This paper reports on an Intercultural Experience Project that higher education institutions could implement to foster student intercultural competence (ICC) without the need for cross-border mobility. The project requires students to engage in multiple, direct and indirect, interpersonal and non-personal experiences with a foreign culture while keeping a journal of their interactions. It guides students in writing a cultural essay, analysing both their own and the foreign culture as well as the distance between them, then a reflective essay on their ICC learning. Analysis of student journals and essays corroborates that the project fostered student ICC attitudes, skills, knowledge, and awareness, even leading some students to advanced intercultural maturity levels. The multiplicity of intercultural interactions enhanced the meaningfulness and depth of students’ experience, emboldened them to engage in various types of interactions, and helped them develop advanced ICC skills related to comparative, critical, and systemic thinking.

TRANSCENDING BORDERS DIGITALLY: HOW REGIONAL POLICIES SUPPORTING SOCIAL ENTREPRENEURSHIP MEDIATE EXPORT RESILIENCE?

This study investigates the complex relationship between digital transformation, regional policies, and export resilience, with a specific focus on how social entrepreneurship factors into this dynamic. The research aimed to determine how these elements collectively shape a region’s adaptability and competitiveness in the global export market. Key findings indicate that digital transformation significantly enhances export resilience, as regions with advanced digital maturity exhibit greater agility and competitiveness during market disruptions. Moreover, regional policies play a pivotal mediating role by creating an environment conducive for businesses to adopt digital technologies and promote collaboration and innovation. The study also revealed that social entrepreneurship represents a valuable means of improving export resilience through digital transformation, as social enterprises can leverage technologies to expand opportunities while generating social impact. However, realizing this potential requires regional policies aimed at supporting social entrepreneurs with resources for digital skills development and technology adoption. Overall, the research underscores the need for a comprehensive strategy integrating technology adoption, supportive policies, and promotion of social entrepreneurship to reinforce a region’s capability to successfully navigate market disruptions and achieve resilient, sustainable export growth.

Ferric citrate and apo-transferrin enable erythroblast maturation with β-globin from hemogenic endothelium

Red blood cell (RBC) generation from human pluripotent stem cells (PSCs) offers potential for innovative cell therapy in regenerative medicine as well as developmental studies. Ex vivo erythropoiesis from PSCs is currently limited by the low efficiency of functional RBCs with β-globin expression in culture systems. During induction of β-globin expression, the absence of a physiological microenvironment, such as a bone marrow niche, may impair cell maturation and lineage specification. Here, we describe a simple and reproducible culture system that can be used to generate erythroblasts with β-globin expression. We prepared a two-dimensional defined culture with ferric citrate treatment based on definitive hemogenic endothelium (HE). Floating erythroblasts derived from HE cells were primarily CD45+CD71+CD235a+ cells, and their number increased remarkably upon Fe treatment. Upon maturation, the erythroblasts cultured in the presence of ferric citrate showed high transcriptional levels of β-globin and enrichment of genes associated with heme synthesis and cell cycle regulation, indicating functionality. The rapid maturation of these erythroblasts into RBCs was observed when injected in vivo, suggesting the development of RBCs that were ready to grow. Hence, induction of β-globin expression may be explained by the effects of ferric citrate that promote cell maturation by binding with soluble transferrin and entering the cells.Taken together, upon treatment with Fe, erythroblasts showed advanced maturity with a high transcription of β-globin. These findings can help devise a stable protocol for the generation of clinically applicable RBCs.

Generating fast-twitch myotubes in vitro with an optogenetic-based, quantitative contractility assay.

The composition of fiber types within skeletal muscle impacts the tissue's physiological characteristics and susceptibility to disease and ageing. In vitro systems should therefore account for fiber-type composition when modelling muscle conditions. To induce fiber specification in vitro, we designed a quantitative contractility assay based on optogenetics and particle image velocimetry. We submitted cultured myotubes to long-term intermittent light-stimulation patterns and characterized their structural and functional adaptations. After several days of in vitro exercise, myotubes contract faster and are more resistant to fatigue. The enhanced contractile functionality was accompanied by advanced maturation such as increased width and up-regulation of neuron receptor genes. We observed an up-regulation in the expression of fast myosin heavy-chain isoforms, which induced a shift towards a fast-twitch phenotype. This long-term in vitro exercise strategy can be used to study fiber specification and refine muscle disease modelling.

Impact of genetic variations in the WNT family members and RUNX2 on dental and skeletal maturation: a cross-sectional study

BackgroundThis study evaluated if genetic variations in the WNT family members and RUNX2 are associated with craniofacial maturation, investigating dental and skeletal maturity in children and teenagers.MethodsRadiographs from pre-orthodontic treatment of Brazilian patients (7 to 17 years-old) were used to assess dental (panoramic radiographs) and skeletal maturity (cephalometric radiographs). The chronological age (CA) was calculated based on the date of birth and the time the radiographs were performed. For the dental maturity analysis, the Demirjian (1973) method was used and a delta [dental age - chronological age (DA-CA)] was calculated. For the skeletal maturity analysis, the Baccetti et al. (2005) method was used and the patients were classified as “delayed skeletal maturation”, “advanced skeletal maturation” or “normal skeletal maturation”. DNA isolated from buccal cells was used for genotyping of two genetic variations in WNT family genes: rs708111 (G > A) in WNT3A and rs1533767 (G > A) in WNT11; and two genetic variations in RUNX2: rs1200425 (G > A) and rs59983488 (G > T). A statistical analysis was performed and values of p < 0.05 indicated a significant difference.ResultsThere were no associations between dental maturity and genotypes (p > 0.05). In the skeletal maturity analysis, the allele A in the rs708111 (WNT3A) was statistically more frequent in patients with delayed skeletal maturation (Prevalence Ratio = 1.6; 95% Confidence Interval = 1.00 to 2.54; p-value = 0.042).ConclusionsThe rs708111 in the WNT3A gene impacts on skeletal maturation.

Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep

BackgroundTherapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions.MethodsCombined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively). Control groups received no CEMF treatment. Bone healing was evaluated radiographically, morphometrically (micro-CT), biomechanically and histologically.ResultsIn the 3-mm gap model, the CEMF group (n = 6) exhibited higher callus mineral density compared to the Control group (n = 6), two-fold higher biomechanical torsional rigidity and a histologically more advanced callus maturity (no statistically significant differences). In the 17-mm graft model, differences between the Control (n = 6) and CEMF group (n = 6) were more pronounced. The CEMF group showed a radiologically more advanced callus, a higher callus volume (p = 0.003) and a 2.6 × higher biomechanical torsional rigidity (p = 0.024), combined with a histologically more advanced callus maturity and healing.ConclusionsThis study showed that CEMF therapy notably enhanced bone healing resulting in better new bone structure, callus morphology and superior biomechanical properties. This technology could transform a standard inert orthopedic implant into an active device stimulating bone tissue for accelerated healing and regeneration.

ESTIMATION OF THE PREDICTIVE EFFECT OF BODY MASS INDEX-PERCENTILE ON SKELETAL MATURATION IN A NIGERIAN POPULATION.

Objectives: To determine the predicting the effect of BMI-index percentile on the skeletal maturation of Nigerian children. &#x0D; Design: A prospective cross-sectional study.&#x0D; Setting: This study was conducted in a tertiary health care facility in North-Central Nigeria.&#x0D; Participants: Children between the ages of 5-17 years consisting of 44 males and 30 females that presented in the Child Dental clinic over a period of eight months were recruited for the study.&#x0D; Main outcome measured: Skeletal maturation was assessed using the middle phalanx of the third finger (MP3) while the standard WHO growth chart specific for age (2-20 years) and gender was used for grading BMI-percentile. The unpaired t-test was used to compare mean chronological age of the stages of MP3 according to gender. Multinomial logistic regression used to determine the predictive effect of age, gender and BMI percentile on pubertal growth spurt.&#x0D; Results: The BMI-percentile had weak correlation with the pubertal growth spurt (r=0.089, p=0.448). Gender (p=0.004) and chronological age had significant (p&lt;0.001) predictive effect on the skeletal maturation. A one-percentile increase in the BMI-percentile decreases the likelihood of healthy children to be in the peak-pubertal by 1.504 when compared to obese children (p=0.305). &#x0D; Conclusions: This study showed that BMI-percentile is a weak predictor of skeletal maturation. However, obese children had a tendency towards advanced skeletal maturation than healthy participants. It is therefore suggested that orthodontists should consider early implementation of jaw modification treatments among obese children.

Body morphology and bone age in obese and non-obese girls aged 8 to 15 years old

Introduction: childhood obesity is one of the main public health problems worldwide, leading to health status repercussions and growth and maturation process implications in both children and adolescents. Objective: the aim of this study was to verify body morphology and bone age variations in girls with obesity and without obesity. Methodology: this comprises a cross-sectional study conducted with 140 girls aged 8 to 15 years old, 70 with obesity and 70 without obesity. Hip and waist circumferences, body mass, height and and Body Mass Index (BMI) were determined. For maturation status determinations, bone ages were determined by a left wrist and hand radiography employing the Fels method. Results: the findigs indicate significant correlations between nutritional and maturation statuses (r=0.80; p˂0.01). Girls with obesity presented higher weight and BMI values, larger waist and hip circumferences and more advanced bone age compared to girls without obesity (p˂0.01). The same significant differences ​​(p˂0.01) were noted in the contrasting maturational group analysis, where girls presenting advanced maturation always exhibited the highest parameter values. Conclusion: nutritional status is associated to maturation status, and girls with obesity exhibit more advanced bone age than girls without obesity.

What Variables Allow the Differentiation between More and Less Successful Adolescent Volleyball Players?

Kinanthropometric and physical fitness variables have been habitually used for the detection of sports talent in adolescent populations. Considering these variables, players who obtained better scores than their peers in kinanthropometric and physical fitness variables have been traditionally selected for promotion in their teams, without taking into account the possible effect of the maturation process. The aim of the present study was to analyse the differences between adolescent volleyball players in terms of success assessment and the age category, as well as to identify variables that may predict success in volleyball. A total of 101 volleyball players in the U14 age category (28 boys and 73 girls; age = 13.28 ± 0.49 years) and 99 players in the U16 age category (20 boys and 79 girls; age = 15.24 ± 0.59 years) participated in the study. Significant differences were observed in biological maturation in male groups (p < 0.001-0.041), kinanthropometric variables related to bone structure and muscle mass in male groups (p < 0.001-0.048), in variables related to adipose tissue in the U16 female group (p = 0.012-0.032) and in physical fitness tests related to muscle strength and power (p < 0.001-0.049), indicating that more successful (MS) players showed a more advanced biological maturation process, higher values of kinanthropometric variables related to bone structure and muscle mass, and lower values in variables related to adipose tissue, as well as higher levels of physical fitness. The difference in biological maturation and its relationship with structural and muscular anthropometric variables in boys, and physical fitness tests related to muscle strength and power in both boys and girls, are of great importance in the selection process of sports talent in volleyball. These findings should be considered by clubs and coaches, who could be discarding players who could improve their sports performance in later stages when their maturational development is equalised.

Environmental and Genetic (vgll3) Effects on the Prevalence of Male Maturation Phenotypes in Domesticated Atlantic Salmon

Pre-harvest male maturation is problematic for Atlantic salmon (Salmo salar) farmers and is regulated by the environment and genetics (e.g., vgll3). Five families of all-male salmon parr (produced using YY males crossed with XX females) with different vgll3 genotypes were split between three environmental regimes in January 2018. The “advanced maturation” regime used elevated temperature (16 °C) and continuous light from January 2018 with post-smolt maturation assessed in March 2018. The “extended freshwater” regime used ambient freshwater (1–16 °C) and simulated natural photoperiod (SNP) with post-smolt maturation assessed in November 2018. The “sea transfer” regime used ambient temperatures (1–14 °C) and SNP in freshwater until May 2018 when they were transferred to 9 °C seawater with natural photoperiod for 2.5 years (final mean weight of circa. 14 kg) and assessed for post-smolt maturation, 1 sea-winter (1 SW) maturation, and 2 sea-winter (2 SW) maturation in the autumn (November/December) of 2018, 2019, and 2020, respectively. Post-smolt maturation was highest in the advanced maturation and extended freshwater regimes (39–99% depending on family) and lowest in the sea transfer regime (0–95% depending on family). In the sea transfer regime, maturity incidence increased over time (0–95% post-smolt maturation, 1–100% 1 SW, and 50–90% 2 SW maturation, depending on family). In all regimes, those homozygous for the pre-designated vgll3 “early” maturing allele had the highest incidences of maturation whilst those homozygous for the “late” allele had the lowest. A low percentage of 2 SW phenotypic and genetic females were found (0–5% depending on family), one of which was successfully crossed with an XY male resulting in progeny with an approx. 50/50 sex ratio. These results show (i) post-smolt maturation varies dramatically depending on environment although genetic regulation by vgll3 was as expected, and (ii) crossing YY sperm with XX eggs can result in XX progeny which can themselves produce viable progeny with an equal sex ratio when crossed with an XY male.

Gut microbiota maturity mediates the protective effect of siblings on food allergy

The mechanisms underlying the protective effect of older siblings on allergic disease remain unclear but may relate to the infant gut microbiota. We sought to investigate whether having older siblings decreases the risk of IgE-mediated food allergy by accelerating the maturation of the infant gut microbiota. In a birth cohort assembled using an unselected antenatal sampling frame (n= 1074), fecal samples were collected at 1 month, 6 months, and 1 year, and food allergy status at 1 year was determined by skin prick test and in-hospital food challenge. We used 16S rRNA gene amplicon sequencing to derive amplicon sequence variants. Among a random subcohort (n= 323), microbiota-by-age z scores at each time point were calculated using fecal amplicon sequence variants to represent the gut microbiota maturation over the first year of life. A greater number of siblings was associated with a higher microbiota-by-age z score at age 1 year (β = 0.15 per an additional sibling; 95% CI, 0.05-0.24; P= .003), which was in turn associated with decreased odds of food allergy (odds ratio, 0.45; 95% CI, 0.33-0.61; P< .001). Microbiota-by-age z scores mediated 63% of the protective effect of siblings. Analogous associations were not observed at younger ages. The protective effect of older siblings on the risk of developing IgE-mediated food allergy during infancy is substantially mediated by advanced maturation of the gut microbiota at age 1 year.

Review: Early and late determinants of puberty in ruminants and the role of nutrition.

This article reviews the scientific literature on puberty with a focus on ruminants and draws inference, where appropriate, from recent findings in transgenic mouse models and human pathology. Early genetic determinants of puberty have been discovered in humans suffering from hypogonadotropic hypogonadism or central precocious puberty. Transgenic mouse models selected on the basis of the causative defective genes helped in discovering the cellular and molecular mechanisms involved. Most of the genes found are involved in the development of neuroendocrine networks during embryo development and early postnatal life. Notwithstanding that the development of neuroendocrine networks takes place early in puberty, a delay or acceleration in the development of Gonadotropin Releasing Hormone (GnRH) neurons has an impact on puberty onset inducing a delay or an advance, respectively. Among the genes discovered in humans and laboratory models, only a few of them displayed polymorphisms associated with advanced sexual maturity, but also marbling, growth traits and callipygian conformation. This could be related to the fact that rather than puberty onset, most research monitored sexual maturity. Sexual maturity occurs after puberty onset and involves factors regulating the maturation of gonads and in the expression of sexual behaviour. The association with growth and metabolic traits is not surprising since nutrition is the major environmental factor that will act on late genetic determinants of puberty onset. However, a recent hypothesis emerged suggesting that it is the postnatal activation of the GnRH neuronal network that induces the acceleration of growth and weight gain. Hence, nutritional factors need the activation of GnRH neurons first before acting on late genetic determinants. Moreover, nutritional factors can also affect the epigenetic landscape of parental gamete's genome with the consequence of specific methylation of genes involved in GnRH neuron development in the embryo. Season is another important regulator of puberty onset in seasonal small ruminants and appears to involve the same mechanisms that are involved in seasonal transition in adults. The social environment is also an underestimated factor affecting puberty onset in domestic ruminants, most research studies focused on olfactory cues, but the genetic basis has not heretofore been adequately tackled by the scientific community. Additionally, there is some evidence to suggest transgenerational effects exist, in that nutritional and social cues to which parents were exposed, could affect the epigenetic landscape of parental gametes resulting in the epigenetic regulation of early genetic determinants of puberty onset in their offspring.

Growth and maturity status of young elite and sub-elite tennis players

The purposes of this study were to determine the growth and maturity status of young competitive tennis players and to examine their associations with national rankings. The participants were 36 male and 34 female players who competed in the U14 national team selection tournament in 2022. They were divided into three groups according to their results and entries as national players (n = 8), main draw players (n = 31), and qualifying players (n = 31). Ages at peak height velocity and growth status were calculated. Regardless of gender, the mean height and body mass percentiles of players were above the 60th centile. In girls, the results indicated that both national and main draw players were significantly more advanced in maturation (p&lt; 0.05) and had higher body mass indexes (p&lt; 0.05) than qualifying players. In boys, no significant differences were observed among the three groups for all variables. Correlation results showed that maturity status was the most correlated (p&lt; 0.01) variable in girls. No significant relationships between rankings and other variables were obtained for boys. These results suggest that physical size and advanced maturity should be taken into consideration in the selection and identification of youth elite female tennis players.

Callovian source rock modelling as encountered in the Chotts Basin and the Gulf of Gabes: Generation and maturity distribution

The Callovian series are considered as proven to have sourced the reservoirs of the Ezzaouia and El Bibene fields of south-eastern Tunisia. However, its potential is still subject of debate associated with its paleogeographic distribution along with its burial and thermal histories. In this study, 17 wells drilled in the southern Chotts Basin and the Gulf of Gabes were used to model the burial and maturity histories of the Callovian series and estimate volumes of generated and expelled hydrocarbons.The Callovian organic material is generally marked by type II-III with low to moderate contents (up to 1%). The Callovian successions located in the north-eastern part of the Chotts Basin bear low total organic carbon (TOC) contents averaging 0.25%.TOC content and petroleum potential maps were generated with the Callovian series showing a source potential, southwards of the study area.Modelling results show variable burial and thermal histories depending on the location of selected wells. The series with source rock potential in wells located south of the Chotts Basin are in a an early to mid-mature stage with substantial amounts of generated oil. The Callovian series in the Gulf of Gabes are marked by advanced thermal maturity with gas generation being initiated since 10My. A maturity map is proposed for the Callovian series underlying four different stages of maturity.

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities

Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.

Multiple factors affecting occurrence of soft scald and fungal decay in apple during storage

Some apple cultivars are highly susceptible to soft scald, a physiological disorder that can lead to large losses. The effect of harvest time, gradual cooling regimes and storage conditions on soft scald and fungal decay was investigated in two common apple cultivars, ‘Aroma’ and ‘Frida’ in a three year trial 2018–2020. Further, possible relationships between weather conditions during the growing season and 28 d before harvest and soft scald incidence along with fungal decay after storage were studied. The year with the highest rainfall had the highest incidence of soft scald and fungal decay. Our results suggest that the relative humidity during a period of 28 d before harvest was important for later development of soft scald in ‘Frida’, and together the results from ‘Frida’ and ‘Aroma’ showed a moderate correlation between relative humidity and soft scald. Gradual cooling showed conflicting results, and no treatment consistently lowered soft scald incidence. Gradual cooling led to inconclusive results, and storage in ambient air led to higher incidence of soft scald as compared to some investigated ULO storage conditions. Advanced maturity was associated with soft scald development and more fungal decay in one out of three years in ‘Aroma’, but did not affect incidence in ‘Frida’. The etiology of soft scald seems to be dependent of multiple factors.

Uptake and Translocation of Foliar-Applied L-Proline in Sweet Cherry (Prunus avium L.)

Foliar application of nitrogen (N) may supplement soil-applied N in sweet cherry orchards. The proteinogenic amino acid L-proline is a potential source of organic N. However, little is understood about its uptake and effects on fruit quality. In this study, 15N-labelled L-proline was spray-applied to branches of the cultivar ‘Lapins’ either pre- or post-harvest. Leaves, fruit, and whole branches were sampled to investigate the uptake and allocation of foliar-applied N. Both treatments resulted in elevated 15N levels in leaves, with N derived from proline (%NDP) comprising 0.22% and 0.45% after pre- and post-harvest applications, respectively. The fruit was a sink for pre-harvest L-proline, with the highest %NDP in the pedicel (0.21%), followed by the skin (0.17%) and flesh (0.12%). Quality outcomes of smaller, darker fruit with lower stem retention indicate advanced maturity following L-proline application. Both pre- and post-harvest treatments resulted in the recovery of 15N in branches at late dormancy, with %NDP in bark (0.12%), buds (0.15%), and wood (0.02%) of the post-harvest treatment twice as high compared with those from the pre-harvest treatment. This study demonstrates proof of concept of the uptake of L-proline into the leaves of sweet cherry plants and translocation into the fruit and storage organs of the branch.

The amending potential of vermicompost, compost and digestate from urban biowaste: Evaluation using biochemical, Rock-Eval® thermal analyses and transmission electronic microscopy

Organic fraction of municipal solid waste can be recovered using a variety of processes including composting, anaerobic digestion and vermicomposting. The impact of these products was evaluated using an innovative approach combining quantitative and qualitative analyses. Chemical analysis showed that the organic matter content of dry compost, digestate and vermicompost was 76 %, 67.2 % and 41.7 %, respectively. Index of Recalcitrant Organic Carbon (IROC) was higher for vermicompost (87.2 %) than for compost (77.9 %) or digestate (66.9 %). The Rock-Eval® approach was correlated to the IROC with its R-index (R2 = 0.97). Transmission electron microscopy was used to describe the microbial activity, the decomposition state and we observed more advanced maturity from vermicompost, compost to digestate. Finally, the digestate is predicted to have a fertilizing effect whereas the compost should have more an amending effect in the medium/long term. Due to a higher degree of stability, the vermicompost could have both a fertilizing and amending effect.

CAPItello-280: A phase III study of capivasertib and docetaxel versus placebo and docetaxel in metastatic castration-resistant prostate cancer.

TPS287 Background: Docetaxel is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed on an androgen receptor-targeted agent (ARTA; typically, abiraterone, enzalutamide, apalutamide, or darolutamide). However, most patients develop chemotherapy resistance, and median overall survival (OS) remains under 3 years. Preclinical studies have associated phosphoinositide 3-kinase (PI3K)/protein kinase (AKT)/phosphatase and tensin homolog (PTEN) pathway signaling with the development of mCRPC and with resistance to taxane chemotherapy. The ProCAID Phase II trial (NCT02121639) examined whether adding capivasertib, a potent, selective inhibitor of all three AKT isoforms (AKT1/2/3), to docetaxel chemotherapy improved clinical outcomes. Although no difference in the primary endpoint (composite progression-free survival [PFS]) was detected, OS, a secondary endpoint, was extended in the capivasertib plus docetaxel treatment group. A subsequent follow-up analysis at advanced maturity suggested that the OS benefit in ProCAID was restricted to patients who had received prior treatment with an ARTA. Methods: CAPItello-280 is a Phase III study to confirm the efficacy and safety of capivasertib in combination with docetaxel compared with placebo and docetaxel in patients with mCRPC who have not previously received chemotherapy for mCRPC, but whose disease has progressed despite treatment with an ARTA in any setting. Approximately 790 patients will be randomized 1:1 to receive either capivasertib or matching placebo (320 mg orally, twice daily [BD], 4 days on, 3 days off) plus docetaxel (75 mg/m2 on day 1 of each 21-day cycle for 6–10 cycles, with prednisone or prednisolone 5 mg BD or 10 mg once daily) with a background of continued androgen deprivation therapy until disease progression, unacceptable toxicity, death, or withdrawal of consent. The primary endpoint is OS; secondary endpoints include radiographic PFS, time to pain progression, symptomatic skeletal events, safety, and tolerability. Recruitment began in March 2022 and is planned at 207 study sites in 20 countries, including the USA, Canada, Europe, South America, and Asia-Pacific. Clinical trial information: NCT05348577 .

Towards the Control of the Reproduction of the Yellow Clam Amarilladesma mactroides (Reeve, 1854) in Captivity: Effects of Different Stimuli on the Spawning of Laboratory-Conditioned and Unconditioned Breeders

The effects of temperature manipulation, addition of sperm solution, and exposure to alkalized pH and/or hydrogen peroxide (H2O2) as possible spawning inducers in laboratory-conditioned and unconditioned adults of the yellow clam (Amarilladesma mactroides) were evaluated. In three trials, clams were laboratory-conditioned for 14 days and exposed to thermal shocks (from 20 °C to 23–29 °C), while clams from three additional trials were not conditioned but acclimatized for 45 min before spawning induction. Although conditioning advanced gonad maturity and increased the condition factor, none of the thermal treatments triggered spawning in these first trials. Histological analysis indicated that the gonads of conditioned clams were not mature. Alternatively, unfertilized and fertilized eggs, and larvae were observed after unconditioned clams were induced to spawn. The gonads of unconditioned clams were in an advanced stage of maturity. Exposure to temperature shocks, alone or in combination with the addition of sperm solution and with H2O2, resulted in spawning. Clams exposed to H2O2 kept their valves closed and had a high mortality rate. Temperature manipulation is the most promising stimulus to induce spawning in A. mactroides. As the success of conditioning depends on the stage of gonadal development at the time of capture in the wild, a period longer than 14 days may be necessary.