Early Stage Research Articles

Exploring the spatial interference effects elicited by social and non-social targets: A conditional accuracy function approach.

Recent studies employing the spatial interference paradigm reveal qualitative differences in congruency effects between gaze and arrow targets. Typically, arrows produce a standard congruency effect (SCE), with faster responses when target direction aligns with its location. Conversely, gaze targets often lead to a reversed congruency effect (RCE), where responses are slower in similar conditions. We explored this dissociation using the Conditional Accuracy Function (CAF) to assess accuracy across reaction time bins. Using a hierarchical linear mixed modelling approach to compare cropped eyes, and full faces as social stimuli, and arrows as non-social stimuli, we synthesized findings from 11 studies, which led to three distinct models. The results showed that with non-social targets, incongruent trials exhibited lower accuracy rates in the first bin than in subsequent bins, while congruent trials maintained stable accuracy throughout the distribution. Conversely, social targets revealed a dissociation within the fastest responses; alongside a general reduction in accuracy for both congruency conditions, congruent trials resulted in even lower accuracy rates than incongruent ones. These results suggest with gaze targets that additional information, perhaps social, in addition to the automatic capture by the irrelevant target location, is being processed during the earlier stages of processing.

Accelerated Exosomal Metabolic Profiling Enabled by Robust On-Target Array Sintering with Metal-Organic Frameworks.

Pancreatic cancer is highly lethal, and survival chances improve only with early detection at a precancerous stage. However, there remains a significant gap in developing tools for large-scale, rapid screening. To this end, a high-throughput On-Target Array Extraction Platform (OTAEP) by direct sintering of a series of metal-organic frameworks (MOFs) for dual in situ extraction, encompassing both exosomes and their metabolic profiles, is developed. Based on the principle of geometry-dependent photothermal conversion efficiency and standard testing, the appropriate MOF functional unit is identified. This unit enables exosome enrichment within 10 min and metabolic fingerprint extraction in under 1 s of laser irradiation, with over five reuse. To further accelerate and enhance the quality of metabolic profile analysis, the application of Surrogate Variable Analysis to eliminate hidden confounding factors within the profiles is proposed, and five biomarkers demonstrated by MS/MS experiments are identified. These biomarkers enable early diagnosis, risk stratification, and staging of pancreatic cancer simultaneously, with sensitivity of 94.1%, specificity of 98.8%, and precision of 94.9%. This work represents a breakthrough for overcoming throughput challenges in large-scale testing and for addressing confounding factors in big data analysis.

From womb to wellness: early environmental exposures, cord blood DNA methylation and disease origins.

Fetal exposures can induce epigenetic modifications, particularly DNA methylation, potentially predisposing individuals to later health issues. Cord blood (CB) DNA methylation provides a unique window into the fetal epigenome, reflecting the intrauterine environment's impact. Maternal factors, including nutrition, smoking and toxin exposure, can alter CB DNA methylation patterns, associated with conditions from obesity to neurodevelopmental disorders. These epigenetic changes underscore prenatal exposures' enduring effects on health trajectories. Technical challenges include tissue specificity issues, limited coverage of current methylation arrays and confounding factors like cell composition variability. Emerging technologies, such as single-cell sequencing, promise to overcome some of these limitations. Longitudinal studies are crucial to elucidate exposure-epigenome interactions and develop prevention strategies. Future research should address these challenges, advance public health initiatives to reduce teratogen exposure and consider ethical implications of epigenetic profiling. Progress in CB epigenetics research promises personalized medicine approaches, potentially transforming our understanding of developmental programming and offering novel interventions to promote lifelong health from the earliest stages of life.

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1>2cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P=0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. In pathologic stage I (>2cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.

Updating the residual strength – damage index diagrams for hull girder collapse predictions of grounded ships

ABSTRACT A decade ago, the authors introduced the concept of residual strength-damage index diagrams to facilitate rapid predictions of buckling collapse in damaged structures. They demonstrated this approach with an example focused on predicting the collapse of hull girders. [Paik JK, Kim DK, Park DH, Kim HB, Kim MS. 2012b. A New Method for Assessing the Safety of Ships Damaged by Grounding. Int J Marit Eng. 154:A1–A20.]. This paper is a sequel to the 2012 paper by updating the grounding damage data used for the diagrams with more ships in types and sizes, where a total of 12 ships for three different types with four sizes per type are considered: oil tankers (Panamax, Aframax, Suezmax and VLCC), bulk carriers (Handysize, Supramax, Kamsarmax, Capesize), and container ships (3,500TEU, 5,000TEU, 7,500TEU and 13,000TEU). Literature reviews are also made to gain insights on the hull girder collapse of grounded ships, which can be implemented into the updated diagrams. It is confirmed that the proposed methodology can be useful in predicting the hull girder collapse of grounded ships at an earlier stage so that the best timely rescue schemes can be developed to prevent unwanted consequences after grounding, such as casualties, sinking and marine pollution.

Characterization of mesothelin gene expression in dogs and overexpression in canine mesotheliomas

IntroductionCanine mesotheliomas are uncommon malignant tumors typically detected late. Minimally invasive diagnostic biomarkers would facilitate diagnosis at earlier stages, thereby improving clinical outcomes. We hypothesized that mesothelin could be used as a reliable diagnostic biomarker for canine mesotheliomas since it has been used as a cancer biomarker for human mesothelioma. We aimed to explore and characterize mesothelin gene expression in dogs and assess its use as a diagnostic biomarker for canine mesotheliomas.Materials and methodsWe quantified expressed canine mesothelin transcripts via reverse transcription polymerase chain reaction (RT-PCR) and sequenced them using ribonucleic acid (RNA) extracted from a canine mesothelioma cell line. After confirming mesothelin expression, we assessed its levels in major organ tissues and compared them with those in the mesothelioma tissues using quantitative PCR (qPCR). Mesothelin overexpression in mesotheliomas was detected, and we further compared its levels using qPCR between mesotheliomas and non-mesotheliomas using tumor tissues and clinical sample effusions, confirming its significance as a diagnostic biomarker for canine mesothelioma.ResultsMesothelin complementary deoxyribonucleic acid (cDNA) was amplified via RT-PCR, yielding a single band of expected upon DNA electrophoresis. Sequence analyses confirmed it as a predicted canine mesothelin transcript from the genome sequence database. Comparative sequence analysis of the deduced amino acid sequence of the expressed canine mesothelin demonstrated molecular signature similarities with the human mesothelin. However, the pre-sequence of canine mesothelin lacks the mature megakaryocyte potentiating factor (MPF) portion, which is typically cleaved post-translationally with furin. Mesothelin expression was quantified via qPCR revealing low levels in the mesothelial and lung tissues, with negligible expression in the other major organs. Canine mesothelin exhibited significantly higher expression in the canine mesotheliomas than in the noncancerous tissues. Moreover, analysis of clinical samples using qPCR demonstrated markedly elevated mesothelin expression in canine mesotheliomas compared to non-mesothelioma cases.Discussion and conclusionCanine mesothelin exhibits molecular and biological characteristics akin to human mesothelin. It could serve as a vital biomarker for diagnosing canine mesotheliomas, applicable to both tissue- and effusion-based samples.

Layered Silicates Exhibiting MOF-Like Gate-Opening Behaviors in Liquid-Phase Adsorptions: Experimental and Theoretical Investigations.

Layered silicates, including clay minerals, can be used as liquid-phase adsorbents in many important applications. However, because their two-dimensional interlayer space is narrow and not entirely opened due to the presence of interlayer species, guest species are forced to penetrate while expanding the interlayer space, which limits their adsorption performances compared with microporous materials such as MOFs and zeolites. Herein, as reported for the adsorption of gaseous species on flexible MOFs, we report a layered silicate that exhibits gate-opening adsorption in liquid phases. This layered silicate, synthesized via dilute acid treatment of the parent sodium-type, exhibits an abrupt increase in the basal spacing (layer thickness + interlayer space) to reach a plateau even at an earlier stage of benzoic acid adsorption from acetonitrile, whereas a typical layered silicate, magadiite, exhibits a gradual increase in the basal spacing as adsorption progress under identical conditions. The layered silicate shows an excellent adsorption capacity and rate for benzoic acid uptake from acetonitrile, which is considerably higher than that of magadiite. With comprehensive adsorption tests using different adsorbates and solvents, we propose that the layered silicate has zeolite-like but distorted, flexible open microchannels within each layer, and the intralayer microchannels can effectively and rapidly accommodate the solvent (acetonitrile) molecules, which are capable of expanding the framework to initiate the adsorption of aromatic compounds. The density function theory calculation revealed the adsorption mechanism, where the layered silicate accommodates acetonitrile in the intralayer microchannel followed by the interlayer space, and the former selectively plays a role as the adsorption site of aromatic compounds via exchange with acetonitrile.

A description of variant transthyretin amyloidosis (ATTRv) stage 1 patients and asymptomatic carriers in Spain: the EMPATIa study

BackgroundVariant transthyretin amyloidosis (ATTRv) is a rare multisystemic disorder caused by mutations in the transthyretin (TTR) gene. The aim of the present work was to describe the clinical profile of asymptomatic carriers (AC) and Coutinho stage 1 ATTRv patients in Spain.MethodsNational, multicentre, cross-sectional study that included 86 AC and 19 patients diagnosed in the previous 12 months to enrolment. Clinical and demographical data, TTR gene mutations, red flags anamnesis, neurological and cardiological assessments were collected.ResultsThe mean age of patients was 56.8 years at onset and 58.6 years at diagnosis; 53% of patients and 51% of AC were from non-endemic areas. Val50Met was the most frequent mutation in both groups. Neuropathy impairment score data (mean 17.7 ± 20.5) and small-fibre function in lower limbs assessed with SUDOSCAN revealed that patients were diagnosed at early stages of neurological impairment. Peripheral polyneuropathy (84.2%), autonomic neuropathy (73.7%), cardiac (63.2%) and gastrointestinal (47.4%) alterations were the most common symptoms in patients. Autonomic neuropathy, gastrointestinal impairment, carpal tunnel syndrome, cardiac and ocular alterations were potentially related to ATTRv in the AC group.ConclusionsThe EMPATIa study provides a detailed description of AC and Coutinho stage 1 ATTRv patients across Spain, confirming the multisystemic clinical profile of the disease. This study reveals a diagnosis delay around 1.8 years, highlighting the importance of a profound disease awareness to reach a diagnose in earlier stages of neurological impairment.

Accelerated Severity of Illness Score Enhances Prediction of Complicated Acute Hematogenous Osteomyelitis in Children.

Severity of illness determination for children with acute hematogenous osteomyelitis should be accomplished during the earliest stages of evaluation to guide treatment and establish prognosis. This study objectively defines an outcome of complicated osteomyelitis and explores an illness severity-based model with an improved ability to predict this outcome as soon and accurately as possible, comparing it to existing models. Children with Staphylococcus aureus acute hematogenous osteomyelitis (n = 438) were retrospectively studied to identify adverse events and predictors of severity. The outcome of complicated osteomyelitis was ultimately defined as the occurrence of any major or at least 3 minor adverse events, which occurred in 52 children. Twenty-four clinical and laboratory predictors were evaluated through univariate and stacked multivariable regression analyses of chronologically distinct groups of variables. Receiver operating characteristic curve analyses were conducted to compare models. Accelerated Severity of Illness Score included: triage tachycardia [odds ratio: 10.2 (95% confidence interval: 3.48-32.3], triage tachypnea [6.0 (2.4-15.2)], C-reactive proteininitial ≥17.2 mg/dL [4.5 (1.8-11.8)], white blood cell count band percentageinitial >3.8% [4.6 (2.0-11.0)], hemoglobininitial ≤10.4 g/dL [6.0 (2.6-14.7)], methicillin-resistant S. aureus [3.0 (1.2-8.5)], septic arthritis [4.5 (1.8-12.3)] and platelet nadir [7.2 (2.7-20.4)]. The receiver operating characteristic curve of Accelerated Severity of Illness Score [area under the curve = 0.96 (0.941-0.980)] were superior to those of Modified Severity of Illness Score = 0.903 (0.859-0.947), Acute Score for Complications of Osteomyelitis Risk Evaluation = 0.878 (0.830-0.926) and Chronic Score for Complications of Osteomyelitis Risk Evaluation = 0.858 (0.811-0.904). Successive receiver operating characteristic curve analyses established an exponentially increasing risk of complicated osteomyelitis for children with mild (0/285 or 0%), moderate (4/63 or 6.3%), severe (15/50 or 30.0%) and hyper-severe (33/40 or 82.5%) acute hematogenous osteomyelitis (P<0.0001). This study improves upon previous severity of illness models by identifying early predictors of a rigorously defined outcome of complicated osteomyelitis.

Simulation Training Is an Effective Tool for Implementing the Practice of a Screening Nurse in Viamedis Clinics

Screening is a vital part of practical healthcare in the Republic of Kazakhstan. Screening is a process of mass examination or testing of a group of people to identify potential diseases or conditions at an early stage, before obvious symptoms appear. The purpose of screening is early detection of health problems, which allows for treatment or prevention to begin at an earlier stage and improve the effectiveness of medical intervention.

Fluorescence-Based Monitoring of Early-Stage Aggregation of Amyloid-β, Amylin Peptide, Tau, and α-Synuclein Proteins.

Early-stage aggregates of amyloid-forming proteins, specifically soluble oligomers, are implicated in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Protein aggregation is typically monitored by fluorescence using the amyloid-binding fluorophore thioflavin T (ThT). Thioflavin T interacts, however, preferentially with fibrillar amyloid structures rather than with soluble, early-stage aggregates. In contrast, the two fluorophores, aminonaphthalene 2-cyanoacrylate-spiropyran (AN-SP) and triazole-containing boron-dipyrromethene (taBODIPY), were reported to bind preferentially to early-stage aggregates of amyloidogenic proteins. The present study compares ThT with AN-SP and taBODIPY with regard to their ability to monitor early stages of aggregation of four different amyloid-forming proteins, including amyloid-β (Aβ), tau protein, amylin, and α-synuclein. The results show that the three fluorophores vary in their suitability to monitor the early aggregation of different amyloid-forming proteins. For instance, in the presence of Aβ and amylin, the fluorescence intensity of AN-SP increased at an earlier stage of aggregation than the fluorescence of ThT, albeit with only a small fluorescence increase in the case of AN-SP. In contrast, in the presence of tau and amylin, the fluorescence intensity of taBODIPY increased at an earlier stage of aggregation than the fluorescence of ThT. Finally, α-synuclein aggregation could only be monitored by ThT fluorescence; neither AN-SP nor taBODIPY showed a significant increase in fluorescence over the course of aggregation of α-synuclein. These results demonstrate the ability of AN-SP and taBODIPY to monitor the formation of early-stage aggregates from specific amyloid-forming proteins at an early stage of aggregation, although moderate increases in fluorescence intensity, relatively large uncertainties in fluorescence values, and limited solubility of both fluorophores limit their usefulness for some amyloid proteins. The capability to monitor early aggregation of some amyloid proteins, such as amylin, might accelerate the discovery of aggregation inhibitors to minimize the formation of toxic oligomeric species for potential therapeutic use.

Prostate-specific antigen testing patterns and prostate cancer stage at diagnosis in older Ohio cancer patients.

Prostate cancer (PCa) screening recommendations do not support prostate-specific antigen (PSA) screening for older men. Such screening often occurs, however. It is, therefore, important to understand how frequently and among which subgroups screening occurs, and the extent of distant stage PCa diagnoses among screened older men. Using the 2014-2016 linked Ohio Cancer Incidence Surveillance System (OCISS) and Medicare administrative database, we identified men 68 and older diagnosed with PCa and categorized their PSA testing in the three years preceding diagnosis as screening or diagnostic. We conducted multivariable logistic regression analysis to identify correlates of screening PSA and to determine whether screening PSA is independently associated with distant stage disease. Our study population included 3034 patients (median age: 73years). 62.1% of PCa patients underwent at least one screening-based PSA in the three years preceding diagnosis. Older age (75-84years: aOR [95% CI]: 0.84 [0.71, 0.99], ≥ 85: aOR: 0.27 [0.19, 0.38]), and frailty (aOR: 0.51 [0.37, 0.71]) were associated with lower screening. Screening was associated with decreased odds of distant stage disease (aOR: 0.55 [0.42, 0.71]). However, older age (75-84years: aOR: 2.43 [1.82, 3.25], ≥ 85: aOR: 10.57 [7.05, 15.85]), frailty (aOR: 5.00 [2.78, 9.31]), and being separated or divorced (aOR: 1.64 [1.01, 2.60]) were associated with increased distant stage PCa. PSA screening in older men is common, though providers appear to curtail PSA screening as age and frailty increase. Screened older men are diagnosed at earlier stages, but the harms of screening cannot be assessed.

Unmet Need in Early-Onset Parkinson's Disease: Deep Brain Stimulation and Pregnancy.

Pregnancy in women with early-onset Parkinson's disease (PD) is likely to have a higher frequency given the trend toward increasing maternal age, thus resulting in a greater overlap time between childbearing age and PD risk. Deep brain stimulation (DBS) therapy is nowadays offered to PD patients at earlier stage of the disease, when women can still be pre-menopausal. However, few data are available about DBS safety during pregnancy. From a review of the available literature, only one article was published on this topic so far. Therefore, we have developed a clinical consensus on the safety of DBS during pregnancy in PD patients.

Isotope‐Tracing for Conceptual Model Formation During the Holocene of Eletsky Palsa, Bolshezemelskaya Tundra

ABSTRACTStudies of permafrost agradation within peat mires leading to palsa growth and palsa dynamics during the Holocene are important for predicting the future of permafrost in a changing climate. The radiocarbon age of peat cover and stable isotope composition of the ice cores of palsas near Eletsky settlement, north‐east of the European part of Russia, were studied. Palsa growth was the most active between 8 and 5 cal ka BP. The main sources for ice core formation were precipitation‐fed surface and suprapermafrost waters. It is assumed that the isotope composition of the initial water was isotopically depleted compared with modern surface waters, which may be explained by general climate cooling during earlier stages of palsa growth (response to the 8.2 ka cooling event). The ice cores of the studied palsas were formed during the freezing of water in semi‐closed conditions, mainly by the segregation mechanism during permafrost agradation, thickness of the ice lenses and ice volume could depend on freezing rates and water supply. The upper part of the palsa ice core experienced deep thawing and could be saturated with meteoric water; repeated freezing of this part of the ice core likely occurred in closed system conditions.

Cognitive States Classification Analysis

Alzheimer's disease is a chronic, prolonged, and irreversible neurodegenerative disease of unknown cause. In recent years growing research interest assumes that by processing data of essential factors effective models can be defined for recognizing and predicting the disease development. The present article aims to propose classification models for the diagnosis of Alzheimer's disease cognitive states. For this aim medical data of biomarkers and cognitive assessment data are used. The novelty of the paper is to explore both the Amyloid/TAU/ Neurodegeneration framework and the biologically determined process of delay between the brain impairment and visibility of its appearances by incorporating these concepts in the model development procedure. The study explores the ability of three classifiers – Random Forest, Extreme Gradient Boosting, and Logistic Regression. Conclusion results have been done by comparison of the grouping abilities in different data spaces. The practical result of the study is helping to determine medical examinations that give accurate results for the diagnosis and prediction of the progression of the disease in possible earlier stages of the disease development.

An Improved Adaptive Neuro-fuzzy Inference Framework for Lung Cancer Detection and Prediction on Internet of Medical Things Platform

It has become increasingly difficult for medical practitioners to recognize illness in recent years due to the emergence of new diseases from their myriad causes on a daily basis. Due in large part to inadequate diagnostic and monitoring infrastructure, a substantial amount of illness and death are associated with lung cancer (LC). The aim of the paper is to find lung cancer early and help patients receive curative treatment. Quitting smoking or never starting is the best way to mitigate the potential for disease-related death. As a result, cutting-edge detection and monitoring technologies must be developed to enable rapid, accurate, and timely diagnosis. Fuzzy logic (FL) is one of the best approaches to modeling complex and uncertain systems; therefore, it helps us deal with these challenges. Fuzzy expert system for lung cancer [FES-LC] detection and prediction on Internet of medical things (IoMT) is employed to overcome the challenges. Hence, an enhanced adaptive neuro-fuzzy inference framework [ANF-IF] is proposed in the current research. The cloud-based application of an adaptive neuro-fuzzy inference system yields four risk categories: not at risk, slightly at risk, moderately at risk, and severely at risk. New methods and theoretical frameworks have made it possible to diagnose LC in its earliest stages with the help of magnetic nanoparticles (MNPs), which allow researchers to overcome the limitations of conventionally slow diagnostic efficiency. The proposed system exhibits a precision of 93.4%, accuracy of 95.1%, specificity of 90.6%, sensitivity of 92.8%, false positive rate of 0.22%, false negative ratio of 0.18%, and classification accuracy of 98.2%. The proposed method outperforms all methods and provides better lung cancer detection accuracy than others.

Early seedling development and survival of seagrasses Posidonia australis and P. sinuosa using different seed‐based restoration methods

Seagrass seed‐based restoration has been developed in several places worldwide, but disturbance at the vulnerable initial stages of seedling recruitment has proved to be a major bottleneck to successful restoration. A detailed investigation of seagrass seedling survival and growth at the earliest stages of seedling development is an important contribution to developing techniques to improve seedling establishment and survival. Here, we investigated the early seedling development of Posidonia australis and P. sinuosa as well as quantifying the variation in seedling survival and development under different seed‐based restoration methods. Early seedling development was documented in indoor aquaria during the first month after fruit dehiscence. In the second ex situ experiment, we determined the effects of three different restoration methods (surface sowing, seedling planting, and planting inside a hessian bag) on seedling survival and development over the first 2 months of life. In the first experiment, a primary root with the first root hairs developed after 7 days. After 1 month, roots were 20–60 mm in length, firmly establishing the seedling into the sediment. Compared to surface sowing, seedling planting and hessian bag restoration treatments did not significantly affect survival for P. australis but increased seedling mortality in P. sinuosa, although growth was greater (shoot and root lengths were approximately 50 and 40% longer, respectively). These aquarium‐scale experiments suggest that planting methods would enhance seedling establishment at larger scales in some species, promoting restoration of damaged seagrass habitats.

Health policies and guidelines to promote, protect and support early childhood development: A narrative review

ABSTRACT This comprehensive review examines the pivotal role of health policies and guidelines in promoting, protecting, and supporting early childhood development (ECD). Recognizing the multifaceted nature of ECD, the study explores key elements commonly found in policies that span health, education, social services, and community support. The focus is on creating an integrated approach that ensures the optimal well-being and growth of children during their formative years. The review highlights the significance of maternal and child health care, emphasizing contact toward prenatal and postnatal care for pregnant women and newborns. Nutritional policies center around supporting breastfeeding and ensuring access to nutritious food, laying the foundation for a healthy start in life. Early childhood education programs and parental education initiatives are crucial components, emphasizing cognitive, social, and emotional development from the earliest stages. The review underscores the importance of a holistic perspective, urging the integration of services across sectors to provide a comprehensive framework for ECD. Research-based policies, continuous monitoring, and evaluation mechanisms ensure evidence-driven decision-making and ongoing refinement of strategies. Additionally, the role of legislation and advocacy is highlighted in protecting the rights and well-being of children and advocating for ECD at various levels. In the end, this review highlights the importance of ECD guidelines and health policies as investments that not only help individual children but also enhance societal productivity and general well-being. By prioritizing the early years, policymakers can lay a strong foundation for future health, learning, and success.

Early Identification and Management of Patients with Rash on Apalutamide.

Apalutamide is a selective androgen receptor signalling inhibitor that is used in the treatment of prostate cancer. Skin rash is one of the most common adverse events with apalutamide. Although the majority of rash events are grade 1 and 2, the appearance of skin rash during treatment can lead to dose reduction, a pause in treatment or even treatment discontinuation, especially if patients present late when the rash has become severe. This in turn can result in a significant delay or even a permanent discontinuation in the patient's treatment of prostate cancer. As apalutamide is a generally well tolerated and an effective treatment for many men with advanced prostate cancer, it is extremely important to make attempts to prevent skin problems or to manage them at the earliest stage possible. We therefore have developed practical guidance for the management of apalutamide-related rash, including an infographic with recommendations for rash management by grade. Central to this approach is patient education and awareness. Encouraging patients to proactively care for their skin from the start of treatment and informing them of the risk of rash with apalutamide therapy are essential. If the patient observes any skin changes, they should be advised to report it straight away to their cancer care team. Adopting this simple, proactive approach of patient education and increased vigilance from the care team is expected to lead to early identification of rash and subsequent intervention to allow for quicker resolution and enable patients to continue their cancer treatment with a drug that can delay disease progression and increase survival in patients with prostate cancer.

749. GENDER DIFFERENCE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract In Japan, esophageal cancer is often more common in men, with a lower incidence in women than in men, accounting for 12% of the total number of cancers. In Japan and the West, SCC is involved in alcohol and tobacco. These habits are characteristically more common among men. Women are more likely to be diagnosed at an earlier stage than men. Therefore, we examined the prognosis, stage, and pathology of 145 men and 30 women who underwent radical surgery for esophageal cancer over the past 5 years. (Result) p stage is male: stage 0:7(5%), stage 1:35(25%), stage II: 58(40%), stage III:35(25%), stage IV:10(7%) female: Stage 0: 2 (7%), Stage 1: 12 (40%), Stage II: 6 (20%), Stage III: 9 (30%), Stage IV: 1 (3%). Significantly more men had advanced cancer. No difference was observed regarding Ly and V. Although there were no differences in location and histology, depth of invasion and lympho node metastasis were significantly enhanced in males. (table 1) Kaplanmier survival rate after 5 years was significantly better for women than for men. (Fig 1).(Conclusion) Compared to men, women had less advanced cancer at the time of discovery and a better 5-year survival rate.