Exploring the contribution of proximal family risk factors on SLC6A4 DNA methylation in children with a history of maltreatment

The estimation of the Hubble constant in the past few decades has increasingly become more accurate with the advance of new techniques. But its value seems to depend on the epoch at which the measurements are made. The Planck estimate of the Hubble constant from the observations of the CMBR in the early Universe is about 67.

Introduction: People with schizophrenia have poor cardiometabolic health, with elevated 10-year cardiovascular disease risk (CVD-R) scores and poor quality of life (QOL). There is lack of understanding of these issues in early psychosis. Aims: To quantify CVD-R in people with early psychosis and profile their obesity prevalence, lifestyle behaviours and QOL. Secondary aim was to explore associations between lifestyle behaviours/treatment characteristics and CVD-R/QOL. Method:Baseline data from 81 RCT participants were used to profile cardiometabolic health risks (QRISK®3, BMI and waist circumference). Participants self-reported lifestyle behaviours and QOL. Relationships between modifiable treatment/lifestyle factors and QOL/CVD-R were explored using bivariate analyses. Results: Participants’ relative risk for CVD over 10 years was 1.93 times higher than healthy counterparts; 39% also had an obese BMI and physical QOL was poor. No significant associations were observed between CVD-R or QOL with treatment characteristics and lifestyle factors. Discussion: Despite positive lifestyle behaviours, participants had elevated CVD-R scores and poor physical health related QOL. Quantifying CVD-R with QRISK®3 may highlight the need for health promotion interventions. Implications for practice: Mental health professionals should be alert to elevated cardiometabolic health risks in early psychosis, particularly as these can occur in the context of relatively healthy lifestyle behaviours.

Digital Educational Recourses (DER) have undergone a rapid evolution and integration into the educational contexts. Teachers play a fundamental role in incorporating technology into their classrooms, so it is important to identify the value that teachers on DER and reflect on the implications for their practice. Through the qualitative methodology the necessary data is obtained with open-response inter-views with teachers. This dataset was analysed and categorised using AQUAD. The results suggest that teachers acknowledge the importance of integrating digital re-sources into their classrooms, although there was no consensus regarding the appropriate level at which to do so. Further the inter-views revealed that younger teachers tend to use more self-elaborated or selected resources. Teachers noted the benefits of using technology, especially in regard to maintaining student motivation, how-ever they also highlighted a number of extrinsic challenges and limitations. The results indicate there is a relationship between teachers’ perceptions and their practice, although this could be improved.

Increasing evidence suggests that prenatal exposure to opioids can adversely influence brain development, yet, limited data exists on the effects of opioid-exposure on preschool language development. Our study aimed to characterize the nature and prevalence of language problems in children prenatally exposed to opioids, and the factors that support or hinder language acquisition. A sample of 100 children born to pregnant women in methadone maintenance treatment and 110 randomly identified non-exposed children were studied from birth to age 4.5 years. At 4.5 years, 89 opioid-exposed and 103 non-exposed children completed the preschool version of the Clinical Evaluation of Language Fundamentals (CELF-P) as part of a comprehensive neurodevelopmental assessment. Children prenatally exposed to opioid had poorer receptive and expressive language outcomes at age 4.5 years compared to non-exposed children. After adjustment for child sex, maternal education, other pregnancy substance use, maternal pregnancy nutrition and prenatal depression, opioid exposure remained a significant independent predictor of children’s total CELF-P language score. Examination of a range of potential intervening factors showed that a composite measure of the quality of parenting and home environment at 18 months and early childhood education participation at 4.5 years were important positive mediators.

Climate information can help vulnerable populations anticipate disasters before they happen and enable communities prepare for and cope with them. A complementary log-log regression model based on quantitative study in coastal communities in Tanzania was used to assess the likelihood of the rural poor, rural non poor, urban poor, and urban non poor to receive early warning information about flood, drought and other disasters. Individuals in the urban poor category were 35% less likely to receive early warning information about flood, drought and other disasters whereas urban non-poor residents were 49% more likely to receive same. This disadvantage to the urban poor persists even when adaptive capacity, geographical location and socio-environmental factors are accounted. Nuclear households consisting of a male head and female partner who have children or not had higher likelihood of receiving early warning information on flood, drought and other disasters (OR = 1.47, p < 0.001) compared with their counterparts in female-centred households (no husband or male partner). Residents with tertiary education were more likely (OR = 1.91, p < 0.001) to report that they had received early warning information about flood, drought and other disasters compared with their counterparts without any formal education. This zero-order relationship was completed mediated by geographical location and socio-environmental factors in the multivariate model. The results underline the key role access to climate- and disaster-related information play in enhancing adaptive capacity to reduce vulnerability to natural hazards, as well as the importance of targeting the most vulnerable households in policy interventions to improve resilience in the face of a changing climate.

The aim of this article is to analyze the evidence against the effectiveness of intervention programs based on the participation of parents of children with autism. To obtain the data, a systematic search was carried out in four databases (ProQuest-PsychArticles, ProQuest-ERIC, ProQuest-PubMed, and Scopus). These documents were refined under the inclusion/exclusion criteria and a total of 51 empirical studies were selected. They were classified, first, according to the function of the intervention objective and, later, by the methodology applied (19 studies based on comprehensive interventions, 11 focused on the nuclear symptoms of ASD, 12 focused on the promotion of positive parenting and 9 interactions focused on children play). Once all the documents have been analyzed, the evidence indicates scientific efficacy in most studies, mainly in those based on child development and the application of behavioral analysis principles. Also, the positive influence of parent participation in such programs was demonstrated.

The stage of a super-early scale-invariant Universe is considered on the basis of the Poincaré–Weyl gauge theory of gravity in a Cartan–Weyl space-time. An approximate solution has been found that demonstrates an inflationary behavior of the scale factor and, at the same time, a sharp exponential decrease in the effective cosmological constant from a huge value at the beginning of the Big Bang to an extremely small (but not zero) value in the modern era, which solves the well-known “cosmological constant problem”.

In the case that ship operators may not be aware of the potential risks of environmental factors in situation of high causation probability during the initial stage of the geometric probability analysis process, it is likely that higher-grade collision accident measures will not be taken. However, if any risks is told to the ship operators, more effective and intentional measures can be taken in time. Moreover, if the causation probability corresponding to environmental factors is no less than the risk early warning critical value calculated based on historical collision accident data, there would be a high-risk level that a collision may occur. A new method is put forward based on quantitative analysis of environmental factors and previous collision statistics to provide early warning of any accident risk, and a risk early-warning critical value (REWCV) can be obtained based on this simple but highly operational and practical method. A case study of Three Gorges Reservoir in China indicates that the range of environmental factors where the probability of collision accident grows rapidly is consistent with environmental limits defined by Chinese maritime standards. In addition, the relationship between the risk early-warning critical value and the number of previous collision accident is also clarified.

Chronic myelogenous leukemia (CML) was the first malignancy for which clinical outcome was drastically improved by kinase inhibitor therapy. Kinase inhibitors targeting other well-known oncogenes have been introduced into clinical practice, but none have shown the same magnitude of clinical benefit as ABL1 inhibition in CML. We argue that early detection is an underappreciated, but critically important factor in success of ABL1 inhibitors in treatment of CML. We show that CML provides a window into how many types of cancer may look and behave at an early stage, prior to diagnosis and the development of additional genomic alterations. The remarkable clinical benefits of ABL1 inhibition is likely due to early detection of CML at a stage in which the tumor is driven by single oncogenic alteration which can be successfully controlled by the inhibitor. Thinking of CML as a prototype for effective systemic treatment based on early cancer detection may help to develop strategies for improving treatment for other types of cancer.

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social nesting, a species-typical behavior naturally occurring in standard housing conditions, for such behavioral monitoring. We provide an example of its use to evaluate social deficits and the long-term effects of neonatal sensorial stimulation in male and female adult 3xTg-AD mice for Alzheimer's disease compared to sex- and age-matched NTg counterparts with normal aging. Social nesting was sensitive to genotype (worse in 3xTg-AD mice), sex (worse in males), profile, and treatment (distinct temporal patterns, time to observe the maximum score and incidence of the perfect nest). Since social nesting can be easily included in housing routines, this neuroethological approach can be useful for animal's welfare, monitoring the disease's progress, and evaluating potential risk factors and effects of preventive/therapeutical strategies. Finally, the non-invasive, painless, simple, short time and low-cost features of this home-cage monitoring are advantages that make social nesting feasible to be successfully implemented in most animal department settings.

In Kenya, millions of children have limited access to nurturing care. With the COVID-19 pandemic, it is anticipated that vulnerable children will bear the biggest brunt of the direct and indirect impacts of the pandemic. This review aimed to deepen understanding of the effects of COVID-19 on nurturing care from conception to four years of age, a period where the care of children is often delivered through caregivers or other informal platforms. The review has drawn upon the empirical evidence from previous pandemics and epidemics, and anecdotal and emerging evidence from the ongoing COVID-19 crisis. Multifactorial impacts fall into five key domains: direct health; health and nutrition systems, economic, social and child protection, and child development and early learning. The review proposes program and policy strategies to guide the re-orientation of nurturing care, prevent the detrimental effects associated with deteriorating nurturing care environments, and support the optimal development of the youngest and most vulnerable children. These include the provision of cash transfers and essential supplies for vulnerable households, and strengthening of community-based platforms for nurturing care. Further research on COVID-19 and the ability of children’s ecology to provide nurturing care is needed, as is further testing of new ideas.

Background/Objectives: Chronic pain syndromes pose a significant global health challenge to patients and physicians with a complex relationship of biological and psychosocial factors that are only partly understood. Emerging research suggests an association between prenatal and childhood adversity and the development of somatic syndromes, particularly in females. This study aims to explore the relationship between sexual dimorphic epigenetic changes in the connectome and prenatal and early life adversity (ELA). Methods: A review of existing literature was conducted, examining studies utilising MRI to identify critical periods of environmental influence on neural phenotypes. Results: The findings indicate a significant association between prenatal and childhood adversity and the emergence of central sensitisation syndromes, particularly among females. Notably, alterations in grey matter volume and neural connectivity patterns were observed, suggesting that early adverse experiences can influence pain signalling mechanisms. Conclusions: Understanding the role of sex differences in brain circuitry is crucial for developing personalised pain management strategies. This study highlights the importance of considering both biological and psychosocial factors in addressing chronic pain, as interventions based predominantly on male subjects may be less effective for females. Further research is warranted to explore these differences and refine therapeutic approaches.

Background/Objectives: While studies suggest that young children can learn and think about sustainability, most research has focused on children aged three to five, leaving a significant gap in understanding how to engage toddlers (under three) in early childhood education for sustainability (ECEfS). This study aims to address this gap, a crucial and often overlooked area, by investigating early childhood teachers' perceptions of ECEfS and their pedagogical practices for nurturing sustainability in a toddler group in a Swedish preschool. Methods: The study employed a case study approach, incorporating observations, interviews, and document analysis for data collection. Qualitative techniques were used for data analysis. The research was conducted with a strong commitment to ethical considerations, including obtaining participants' consent, ensuring confidentiality and privacy, informing them of their right to withdraw, and maintaining anonymity. Results: The findings of this study bring hope. They indicate that teachers understand education for sustainability and can implement sustainability-related pedagogical practices in a toddler group. They can create suitable learning environments and establish connections between sustainability issues and daily life activities in the classroom, enhancing the children's overall learning experience. Conclusions: The study's findings underscore the pivotal role of educators in shaping the mindsets and behaviors of future generations, thereby supporting the long-term goals of sustainable development. By nurturing toddlers' innate curiosity and harnessing their brain's plasticity, educators can effectively engage toddlers in ECEfS and promote sustainable development from an early age. The study's implications highlight the need to prioritize ECEfS during toddlerhood to realize the full potential of this critical investment in the future of our planet.

We study the collapse of spherical cold clouds beyond black hole (BH) formation to investigate the possibility of a bounce in the in-falling matter when a critical density or pressure is reached. As a first step, we analyze the pressureless collapse in general relativity (GR), where an analytic solution exists, and demonstrate that an equivalent Newtonian solution can be derived. Such equivalence also holds for spherically symmetric perfect fluids with uniform density and non-vanishing pressure. We numerically investigate the Newtonian collapse of such clouds with masses of $5$, $20$, and $1000$ M$_\odot$ obeying a polytropic equation of state (EoS). By choosing EoS parameters inspired by typical neutron star conditions, we observe bounces at and above nuclear saturation density. Assuming approximate uniformity, we explore the equivalent GR behaviour of the matter during the bounce. Our findings are: i) A GR bounce occurs around the ground state of the matter, characterized by $P = -\rho$. ii) The GR solution significantly differs from the Newtonian result due to the presence of curvature ($k \neq 0$). iii) Both the curvature and the ground state are crucial factors in allowing a GR bounce to occur.

Objective: To analyze and investigate the impact of early rehabilitation training based on developmental sequencing on the growth and development of late preterm infants. Methods: This study focused on preterm infants admitted to our hospital from June 2021 to November 2021. Strict screening was applied to select 54 cases for inclusion. Clinical data were collected for all study subjects, and based on different intervention plans, they were divided into a control group and an experimental group, with 27 cases in each group. The experimental group received intervention based on a developmental sequencing early rehabilitation model in addition to routine care, while the control group only received routine care intervention. The growth and development of the two groups of preterm infants were compared during the study, including physical indicators, intellectual-motor skills, neurobehavioral assessments, and developmental monitoring. Results: The clinical data of the two groups of preterm infants were comparable, with no significant differences (P>0.05). The experimental group exhibited significantly higher values in physical indicators such as weight, head circumference, and height compared to the control group (P<0.05). Intellectual-motor scores (MDI and PDI) of the experimental group were higher than those of the control group (P<0.05). The NBNA scale scores for various dimensions were higher in the experimental group compared to the control group (P<0.05). The DQ values of the experimental group were higher than those of the control group (P<0.05). Conclusion: Early rehabilitation training based on developmental sequencing has a positive impact on the growth and development of late preterm infants. Through systematic and sequenced rehabilitation interventions, various aspects of development in late preterm infants can be promoted effectively. This approach not only improves physical development but also enhances intellectual-motor skills, neurobehavioral development, and overall developmental levels. The results are significant, indicating the worthiness of widespread application and promotion.

Background: Post-operative pancreatic fistula (POPF) is a common complication associated with pancreatic resections. Early identification of this adverse event could avoid otherwise prolonged hospital stay due to clinical management and treatment of symptoms created by POPF. This retrospective study investigated the prevalence of pancreatic fistula among patients who underwent oncological pancreatic resection between August 2018 and December 2023 at Bnai-Zion Medical Center. Elevated C-reactive protein levels have been utilized as an early postoperative marker indicating the presence of inflammation due to tissue injury complication. Objective: The aim of the current study was to evaluate the prediction potential of elevated C-reactive protein levels in detecting the risk for infection created by pancreatic fistula. Methods: Demographic and clinical data was collected from medical records files of ninety-four pancreatic cancer patients’ cohort who were subjected to resection. Results: A significant increase in C-reactive protein levels was found on day three following surgery at the group of forty-six patients having developed pancreatic fistula compared to patients without pancreatic fistula (p=0.002). There was no statistical difference among the groups in any demographic characteristics (such as age, gender, BMI, smoking status, etc.) and any other clinical features (e.g. serum albumin levels, chemotherapy protocol, surgical technique, hospitalization time, lymph node involvement). Conclusions: The results of the study suggest that C-reactive protein could serve as an early biomarker for pancreatic fistula formation in patients undergoing pancreatic resection for cancer.

Early Endosomes represent first line sorting compartments or even organelles for internalized molecules. They enable the transport of molecules or ligands to other compartments of the cell, such as lysosomes for degradation or recycle them back to the membrane by various mechanisms. Moreover, early endosomes function as signaling and scaffolding platform to initiate or prolong distinct signaling pathways. Accordingly, early endosomes have to be recognized as either part of a degradation or recycling pathway. The physical proximity of many ligand-binding receptors with other membrane bound proteins or complexes such as NADPH oxidases may result in an interaction of second messengers like reactive oxygen species (ROS) and early endosomes that promote correct recognition of individual early endosomes. In fact, redoxosomes comprise an endosomal subsection of signaling endosomes. One example of such potential interaction is epidermal growth factor receptor (EGFR) signaling. Here we summarize recent findings on EGFR signaling as a well-studied example for receptor trafficking and trans-activation and illustrating the interplay between cellular and endosomal ROS.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

Castanopsis hystrix, a precious tree species in Southeast Asia, has the advantages of rapid growth and high-quality wood materials. However, there are problems such as long breeding cycle, time-consuming and low efficiency, which greatly restricts the industrial development of C. hystrix. To perform the genome selection (GS) for growth and wood traits and the early selection of superior progeny have great significance for the rapid breeding of new superior varieties of C. hystrix. The 226 clones in the main distribution and 479 progenies within 23 half-sib families were used as experimental materials in this study. Genotyping datasets were obtained by high-throughput re-sequencing technology, and GS studies were conducted on the growth (tree height (H), diameter at breast height (DBH)) and wood (wood density (WD), fiber length (FL), and fiber length-width ratio (LWR)) traits. The coefficient of variation (CV) of five phenotypic traits ranged from 10.1% to 22.73%, the average CV of growth traits was 19.93%, and the average CV of wood traits was 9.72%. The Pearson correlation coefficients between the five traits were almost significantly positive. Based on the Genomic Best Linear Unbiased Prediction (GBLUP) model, the broad-sense heritabilities of growth traits were higher than those of wood quality traits, and the different number of SNPs had little effect on the heritability estimation. GS prediction accuracy first increased and then reached a plateau around 3K SNPs for all five traits. The broad-sense heritability of these five traits was significantly positively correlated with their GS predictive ability (r=0.564, P

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

The early Church had an incredible encounter with the resurrected Christ. Being living witnesses, Christ’s followers spread the Gospel in the world through the power of the Holy Spirit. This piece argued that the Bible contains methodologies used by the Apostles who laid down their lives for the sake of the message of the Cross. Furthermore, it has been contested in this study that the emphasis today has shifted to personal theological agendas of reading the Bible for intellectual preferences. As a result of Christianity’s current emphasis on dogmatic beliefs, various unbiblical approaches to reading the Bible have emerged that ignore the ethical reading of the Bible. This study has reinvestigated the reasons to apply this approach in our modern era to live the Bible rather than any other approach. And one among them is the Enlightenment era which distorted the relationship between ethics and theology (Perry 46). Apart from the above, this study also revealed that many Bible believers have twisted biblical truths because they focus on their convictions. As a result, many strategies fail to provide sound biblical teachings to understand any particular event in the light of the original message of the Bible to reflect upon our situation today. Therefore, in light of the above, on the one hand, the approach of the early Church Fathers is used to reimagine contemporary challenges from this perspective. On the other hand, even though thousands of books have been written on various methodologies to study the Bible, the core concern to critique these current approaches is not personal or denominational, religion-based but rather 'invitational and servational' to live with these biblical beliefs to reorient an ethical approach towards cross-cultural reading in our local and global contexts addressing the problems (injustice and marginalization) and responding to the contemporary challenges.

We present the use of interconnected optical mesh networks for early earthquake detection and localization, exploiting existing terrestrial fiber infrastructure. Employing a Waveplate model, we integrate real ground displacement data from seven earthquakes, magnitudes ranging from four to six, to simulate the strains within fiber cables and collect large set of light’s polarization evolution data. These simulations help to enhance a Machine-Learning model that is trained and validated to detect Primary waves arrivals that precede earthquakes’ destructive Surface waves. The validation results show that the model achieves over 95% accuracy. The Machine-Learning model is then tested against an M4.3 earthquake, exploiting three interconnected mesh networks as a smart sensing grid. Each network is equipped with a sensing fiber placed to correspond with three distinct seismic stations. The objective is to confirm earthquake detection across the interconnected networks, localize the epicenter coordinates by a triangulation method and calculate fibers to epicenter distance. This setup allows early warning generation to municipalities close to epicenter location, and progressing to those further away. The model testing shows 98% of accuracy in detecting primary wave and one-second of detection time, affording nearby areas 21-seconds to take countermeasures, and an extended 57-seconds in more distant areas.

This research investigates the perceptions of parents belonging to the Sidama ethnic group re-garding the significance of technology in early childhood education. The study aims to elucidate how parents perceive the role of technology, such as digital devices and educational applications, in the education and development of their young children. Through qualitative interviews con-ducted with 30 parents and thematic analysis, the study uncovers diverse perspectives, shedding light on cultural, socioeconomic, and educational factors influencing parental attitudes towards technology in early childhood education among the Sidama people. Findings indicate a spectrum of views ranging from enthusiastic embracement to cautious reservation, revealing nuanced considerations that inform parental decisions regarding technology integration in their children's learning experiences.

Triclopyr is an auxin-like herbicide extensively employed to manage weeds in food crops and pastures. Triclopyr has been detected in environmental matrices, with a notable presence within aquatic ecosystems. Given the limited understanding of its fate in the environment, potential implications for environmental and human health, and the lack of adequate monitoring in various environmental compartments, triclopyr is now considered a contaminant of emerging concern (CEC). The present study was undertaken to investigate the impact of triclopyr on zebrafish development, with a specific focus on assessing its embryotoxic, behavioral, and neurotoxic effects at environmentally realistic concentrations ranging from 0.5 to 50 µM on zebrafish embryos. Our results revealed that triclopyr caused sublethal effects on zebrafish embryos, such as delayed hatchability at 50 µM, yolk sac retention at 0.5, 1, 5, and 10 µM, and uninflated swim bladder at 50 µM concentration of triclopyr. Moreover, a subtle alteration in the swimming activity of larvae was observed in the 10 µM triclopyr after 144 hours of exposure. However, the activity of acetylcholinesterase, remained unchanged after triclopyr exposure. Taken together, these comprehensive findings suggest that triclopyr can induce adverse effects on the early development of zebrafish, even at concentrations detected in aquatic environments.

IIt is important that Master’s Degree students in psychology, regardless of their future specialisa-tion, know about Attention Deficit Hyperactivity Disorder (ADHD). The aim is evaluate and an-alyse the ADHD-related knowledge held by students of Early Childhood Education and Primary Education. The findings that were obtained in this study (on the chronicity of the disorder, changes in manifestations throughout the life cycle, and the importance of early and multidisci-plinary intervention) have clear implications in relation to the specific training in ADHD for fu-ture teachers. It is essential to broaden the specific training in relation to ADHD in studies for the Master’s Degrees in Early Childhood Education and Primary Education and through contin-uous training.

It is essential to consider the factors that affect early childhood development because doing so can help identify potential risks and window of opportunity for intervention to improve outcomes for children. However, identifying risk and protective factors in early childhood requires careful consideration of several challenges and an integrated approach that recognises the complex and dynamic nature of development. The purpose of this study was to identify and describe the prevalent psychosocial risk and protective factors in the early childhood development phase, using an ecological perspective. The study employed a quantitative cross-sectional study using a random sampling technique. The final sample consisted of 505 caregivers of children aged 5 years old and younger. This study revealed that the most prevalent protective factors include child self-regulation, parent-child warmth, family management and collective efficacy but more importantly social support. While risk factors may exist this is mitigated by social support as it moderates and buffers against the effects of risk factors, as indicated by the various research studies cited.

Malaria remains a primary public health challenge in Africa, and there is growing interest in leveraging artificial intelligence (AI) to raise malaria interventions. This research examines the possible influence, challenges, and recommendations for implementing AI-based personalized malaria interventions in Africa. AI offers several opportunities in malaria management, including early detection and prediction of outbreaks, improved diagnosis, personalized interventions, optimal treatment recommendations, surveillance and response, resource optimization, and research innovation. However, the implementation of AI in malaria interventions faces various challenges. These include data availability and quality, infrastructure and resource constraints, contextual relevance and generalizability, ethical and privacy considerations, integration into healthcare workflows, and the need to build trust and acceptance among stakeholders. To address these challenges, it is recommended to strengthen data infrastructure, build local capacity in AI technologies, contextualize AI models to local settings, address ethical considerations, establish monitoring and evaluation frameworks, promote collaboration and knowledge sharing, and secure sustainable funding and long-term commitment. By considering these recommendations, stakeholders can work towards implementing AI-based personalized malaria interventions in Africa that can contribute to improving malaria control outcomes, reducing the weight of the disease, and advancing public health in the region.

During the last few years, several approaches have been proposed to improve early warning systems for reducing rock-fall risk. In this regard, this paper introduces a Deep learning-and (IoT) based Framework for Rock-fall Early Warning, devoted to reducing the rock-fall risk with high accuracy. In this framework, the prediction accuracy was augmented by eliminating the uncertainties and confusion plaguing the prediction model. In order to achieve augmented prediction accuracy, this framework fused the prediction model-based deep learning with a detection model-based Internet of Things. In order to determine the framework’s performance, this study adopted parameters, namely overall prediction performance measures, based on a confusion matrix and the ability to reduce the risk. The result indicates an increase in prediction model accuracy from 86% to 98.8%. In addition, a framework reduced the risk probability from (1.51 ×10-3) to (8.57 ×10-9). Our results indicate the framework’s high prediction accuracy; it also provides a robust decision-making process for delivering early warning and lowering the rock-fall risk probability.

Blood-based circulating cell free DNA(cfDNA) detection offers a non-invasive and easily accessible way for early cancer detection. Despite the extensive utility of cfDNA, there are still many challenges to develop the clinical biomarkers. For example, cfDNA with genetic alterations often compose a small portion of the DNA circulating in plasma, which can be confounded by cfDNA contributed by normal cells. Therefore, filtering out the potential false-positive cfDNA mutations from health population will be important for the cancer-based biomarkers. Additionally, many low-frequency genetic alterations are easily overlooked in small amount of cfDNA-based cancer test. We hypothesize that, the combination of diverse types of cancer studies on cfDNA can provide us a new insight to identify low-frequency genetic variant across cancer types for early clinical detection of cancers. By building a standardized computational pipeline for 1358 cfDNA samples across seven cancer types, we prioritize 129 shard genetic variants in the major cancer types. Further functional analysis of the 129 variants found that they are mainly enriched in ribosome pathways such as cotranslational protein targeting to membrane, some of which are tumor suppressor, oncogene and related to cancer initiation. In summary, our integrative analysis revealed the important roles of ribosome proteins as the common biomarkers in early cancer diagnosis.

Digital wellbeing concerns the balance and health we may experience in digital use, and the existing studies have focused on adolescents and adults. However, young children are more vulnerable to digital overuse and addiction than adults; thus, their digital wellbeing deserves empirical exploration. This scoping review synthesized and evaluated 35 collected studies on young children’s digital use and their wellbeing that were published until October of 2022 to understand the definitions, measurements, contributors, and interventions. The synthesis of evidence revealed that: (1) there was no consensus about its definition; (2) there were no effective measurements of young children’s digital wellbeing; (3) both child factors (duration and place of digital use, child demographic characteristics) and parent factors (digital use, parental perception, and mediation) contribute to young children’s wellbeing; and (4) there were some effective applications and interventions. This review contributes to the theoretical development by mapping the existing work on young children's digital wellbeing, proposing a model, and identifying the research gaps for future studies.

This study examined the relationship among the three domains of executive function (EF; cognitive shifting, inhibitory control, and working memory) to test the applicability of the unity-diversity model in preschoolers using both behavioral and fNIRS approaches. Altogether 58 Chinese preschoolers (34 boys, 24 girls, Mage = 5.86 years, SD = 0.53, Age range = 4.83-6.67 years) were administered the Dimensional Card Change Sort (DCCS), go/no-go, and missing scan task. Their brain activations in the prefrontal cortex during the tasks were examined using fNIRS. First, the behavioral results indicated that the missing scan task scores (working memory) correlated with the DCCS (cognitive shifting) and go/no-go tasks (inhibitory control). But the latter two did not correlate with each other. Second, the fNIRS results demonstrated that the prefrontal activations during the working memory task correlated with those in the same regions during the cognitive shifting and inhibitory control tasks. Still, the latter two did not correlate. The behavioral and neuroimaging evidence jointly indicates that the unity-diversity model of EF does apply to Chinese preschoolers.

Early detection of wildfires has been limited using the sun-synchronous orbit satellites due to their low temporal resolution and wildfires’ fast spread in the early stage. NOAA’s geostationary weather satellites GOES-R can acquire images every 15 minutes at 2km spatial resolution, and have been used for early fire detection. However, advanced processing algorithms are needed to provide timely and reliable detection of wildfires. In this research, a deep learning framework, based on Gated Recurrent Units (GRU), is proposed to detect wildfires at early stage using GOES-R dense time series data. GRU model maintains good performance on temporal modelling while keep a simple architecture, makes it suitable to efficiently process time-series data. 36 different wildfires in North and South America under the coverage of GOES-R satellites are selected to assess the effectiveness of the GRU method. The detection times based on GOES-R are compared with VIIRS active fire products at 375m resolution in NASA’s Fire Information for Resource Management System (FIRMS). The results show that GRU-based GOES-R detections of the wildfires are earlier than that of the VIIRS active fire products in most of the study areas. Also, results from proposed method offer more precise location on the active fire at early stage than GOES-R Active Fire Product in mid-latitude and low-latitude regions.

Groundwater degradation is a global problem linked to irrigation agriculture and aggravated by climate change. In drylands, where aquifer recharge is low, irrigation has emerged as an engine of economic growth. This problem falls under the paradigm of desertification, as it fits the definition of this complex problem in that the degradation of drylands is due to climatic variations and inappropriate human activities. Land Degradation Neutrality (LDN), the response of the United Nations Convention to Combat Desertification to the lack of progress in tackling desertification, is integrated into Sustainable Development Goal 15.3 and provides the adequate framework for implementing effective solutions. LDN prioritizes prevention strategies, and early warning systems coupled to integrated simulation models is a sound approach. We analyze the dynamics of a coastal aquifer in southern Spain, a “desertification landscape” according to the Spanish National Action Plan to Combat Desertification. For this purpose, we have (i) adapted a generic desertification model that considers socio-ecological systems as a particular case of predator-prey systems; and (ii) coupled to this model a risk analysis to calculate the probabilities of groundwater salinization under the current scenario of water resources use, driven by the expansion of greenhouse agriculture supported by external water transfer. The risk of desertification is close to 100%: groundwater salinity is 40 dS m-1 (well above tomato tolerance, 3.5 dS m-1), and 2.4 Mm3 yr–1 water transfer is needed to support the 631 ha of greenhouses. This worrying result suggests that complimentary solutions should be promoted to deactivate the ongoing process of desertification. Among them, we propose reclaimed water, diversifying the economy, or promoting crops adapted to aridity. This simulation framework shows how to explore the future of a socio-ecosystem under current scenarios and others that consider climate change, the energy crisis, or the impact of alternative solutions.

Crop-type mapping is an important intermediate step for cost-effective crop management at the field level, as an overview of all fields with a particular crop type can be used for monitoring or yield forecasting, for instance. Our study used a data set with 2400 fields and corresponding satellite observations from the federal state of Bavaria, Germany. The study classified corn, winter wheat, winter barley, sugar beet, potato, and winter rapeseed as the main crops grown in Upper Bavaria. We additionally experimented with a rejection class "Other", which summarised further crop types. Corresponding Sentinel-2 data included the normalised difference vegetation index (NDVI) and raw bands from 2016 to 2018 for each selected field. The influence of raw bands compared to NDVI was analysed and the classification algorithms, i.e. support vector machine (SVM) and random forest (RF), were compared. The study showed that the use of an index should be critically questioned and that raw bands provided a wider spectral bandwidth, which significantly improved the mapping of crop types. The results underline the use of RF with raw bands and achieved overall accuracies (OA) of up to 92%. We also predicted crop types in an unknown year with significantly different weather conditions and several months before the end of the growing season. Thus, the influence of climate anomalies and the accuracy depending on the time of prediction were assessed. The crop types of a test site and year without labels could be determined with an OA of up to 86%. The results demonstrate the usefulness of the proof-of-concept and its readiness for use in real applications.

The movement direction of propagating convective systems originating from both inland and offshore over the north coast of West Java in Indonesia is determined primarily by the prevailing wind. However, the role of a land-sea contrast and a rugged topography over southern West Java is also expected to affect propagating convective systems by increasing land-sea breezes and enhancing upward motion. These hypotheses are tested using a weather prediction model incorporating convection (up to 3 km height) to simulate the heavy rainfall event during 26–29 January associated with the 2002 Jakarta flood. First, we addressed the influence of land-sea contrast and topography on the local circulation, particularly in the area surrounding Jakarta, by replacing the inland topography over western Indonesia (96°–119°E, 17°S–0°) with a water body with an altitude of 0 m. We then compared the results of model simulations with and without topography. The results show that the main role of the topography here is enhancing the upward motion and generating a deep convective cloud in response to the land-based convective system during 26–27 January 2002, which then continuously and rapidly propagates offshore due to the cold pool mechanism. Furthermore, the land-sea contrast has a significant role in increasing sea breeze under the rapidness of the landward propagation system during 28–29 January 2002, which was strengthened by the gravity waves and resulted in early morning convection over coastal regions.

The evolutionary origin of the genome remains elusive. Here, I hypothesize that its first iteration, the protogenome, was a multi-ribozyme RNA. It evolved, likely within liposomes (the protocells) forming in dry-wet cycling environments, through the random fusion of ribozymes by a ligase and was amplified by a polymerase. The protogenome thereby linked, in one molecule, the information required to seed the protometabolism (a combination of RNA-based autocatalytic sets) in newly forming protocells. If this combination of autocatalytic sets was evolutionarily advantageous, the protogenome would have amplified in a population of multiplying protocells. It likely was a quasispecies with redundant information, e.g., multiple copies of one ribozyme. As such, new functionalities could evolve, including a genetic code. Once one or more components of the protometabolism were templated by the protogenome (e.g., when a ribozyme was replaced by a protein enzyme), and/or addiction modules evolved, the protometabolism became dependent on the protogenome. Along with increasing fidelity of the RNA polymerase, the protogenome could grow, e.g., by incorporating additional ribozyme domains. Finally, the protogenome could have evolved into a DNA genome with increased stability and storage capacity. I will provide suggestions for experiments to test some aspects of this hypothesis.

The effect of aqueous extracts of the biomass of the adult Ulomoides dermestoides beetle on the delayed effects of the defoliant paraquat causing parkinsonism in experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP⁺. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.

Timely diagnosis of Alzheimer's diseases(AD) is crucial to obtain more practical treatments. In this paper, a novel approach Based on Multi-Level Fuzzy Neural Networks (MLFNN) for early detection of AD is proposed. The focus of study was on the problem of diagnosing AD and MCI patients from healthy people using MLFNN and selecting the best feature(s) and most compatible classification algorithm. In this way, we achieve an excellent performance using only a single feature i.e. MMSE score, by fitting the optimum algorithm to the best area using optimum possible feature(s) namely one feature for a real life problem. It can be said, the proposed method is a discovery that help patients and healthy people get rid of painful and time consuming experiments. Experiments shows the effectiveness of proposed method in current research for diagnosis of AD with one of the highest performance (accuracy rates of 96.6%), ever reported in the literature.

Recent analyses of cosmic microwave background (CMB) maps have been interpreted as demonstrating that the Universe was born without an initial rotation. However, these analyses are based on unrealistic models and do not contain essential ingredients such as quantum effects, the strong, weak and gravitational interactions between the components, their intrinsic spins and magnetic moments, as well as primordial black holes. If the Universe was born spinning these effects would distribute the initial spin angular momentum among its components long before the CMB forms at recombination. A primordial spin would now appear as a nonzero total angular momentum of its components along the direction of the original spin, and a primordial large-scale rotation would no longer be apparent. The existence of a special axis or direction would break a fundamental symmetry assumed in general relativity, cosmic isotropy, and a net angular momentum implies a cosmic parity violation.

This research paper is mainly aimed to elaborate the initial risk management and measures which government of Pakistan took towards Novel Corona Virus (COVID-2019). This initial response and planning was devised after the early outbreak of COVID-2019 in Wuhan, China in early time of January 2020. Pakistan devised a comprehensive plan that not to evacuate their student from Wuhan, China. The government of Pakistan in compliance with the National Institute of Health (NIH) devised and documented comprehensive plans such as the flight operations postponed related to Umerah pilgrims, which were intended to go to sacred places of KSA (The Kingdom of Saudi Arabia). The process of visa, immigration policy totally changed and the government of Pakistan notified it officially that, no new visas of visit, student, and business would be issued in due course of uncertainty due to COVID-2019. The government of Pakistan also announced medical emergency and notified through the country’s provinces the process of testing and treatment of COVID-2019. The government of Pakistan also allocated funds for medical supplies and named out the particular country’s best laboratories. The government of Pakistan also locked down all the cities with the emergency announcement that people should stay inside the home in quarantine or self-isolation. NIH (The National Institute of Health) played a vital role in executing the planning to cope with COVID – 2019). The National Institute of Health responded as “The Centre for Disease Control”. In aid to the government, the national army of Pakistan responded in a proactive manner towards planed execution. The medical corps of Pakistan army dedicated themselves to treat the suspected patients of COVID – 2019. Due to plans, policies being documented, implemented in such a way productive way that from February 28, 2020 to till date there is not much critical situation and issues are not present. There are much productive results as there is not much boom in a rise of COVID-2019 patients. This lockdown under the authority of the provinces resulted in fruitful outcomes. Background: On January 02, 2020, authorities of the People Republic of China elaborated that they have encountered with a novel type of infectious viral disease 2019. Later on January 12, the authorities from China elaborated the related sequence of Corona Virus diseases 2019 names as COVID – 2019. When COVID-2019 being identified in Wuhan, Hubei China, as an early response the Government of Pakistan in support of the National Institute of Health (Field Epidemiology & Disease Surveillance Division) published a health advisory about novel coronavirus. Methods: According to Global Health Security Index, Pakistan is ranked as 105th country among 195 countries in GHS index. Overall Score of Pakistan is 35.5. The score of Early Detection and Reporting for Epidemics of Potential International Concern is 41.7. A Graphical depiction of the COVID-19 cases placed until April 10, 2020 as well as a graph trend line of recovered as well as death rate is also depicted. According to the graphical facts of Government of Pakistan and World meters, the recovery rate of COVID-19 is about 98 percent and 2.1 percent death rate is reported against the total cases. Trend analysis with line graph was drawn based on available data from official dashboard web portal of the government of Pakistan and worldometers.info. Data figures were incorporated from March to August 18, 2020 in MS Excel and then subsequently deployed to draw trend analysis from managing risk to recovery. Results: The line graph showed a slowdown in the COVID-19 cases and high rate of recoveries from COVID-19 in Pakistan. On March 11, 2020, there were 20 confirmed cases of coronavirus reported in Pakistan. No death was recorded in very first seven days, on March 18, 2020 only two deaths were reported. On August 18, 2020, there were 272128 recoveries, 6201 deaths, total confirmed cases 290445, and total test were 2340072 in Pakistan. As a results, we can report that due to early measures taken by government of Pakistan no mass scale destruction in terms of death and cases been recorded in Pakistan. Conclusions: To till date, the government of Pakistan tried its level best to minimize the coronavirus cases as much as they can. However, the ending of the potential attack of an outbreak would depend upon the well organized and coordinated approach at all levels such as true directed decisions, fully preparedness, as well implementation and evaluation of continuous decisions. As the recovery rate of the cases is 98 percent and merely death rate is 2.1 percent, concluded that in future it would be a good sign to stop the potential outbreak. Also, lock down as well as precautionary measurement taken by the provincial governments resulted a decline number of COVID-19 cases in the country. Another good sign is that merely 4 percent population of Pakistan is of more than 60 years of old it can be concluded that there are less chances of mass death due to outbreak of COVID-19.

Young women with breast cancer represent 15% of cancer cases in Latin America. Genomic studies have found that early-onset breast-cancer cases exhibit a higher genetic susceptibility and a specific genomic signature as compared to their older counterparts. The aim of this study was to describe clinically relevant germline mutations in a cohort of young women with breast cancer. To achieve this, we analyzed hereditary-cancer genes from whole-exome sequencing data in 108 unrelated women with an extreme phenotype of breast cancer (≤40 years of age), diagnosed and treated at the National Cancer Institute of Mexico; 11% of the patients carried a pathogenic variant. BRCA2 comprised 46% of the mutations, followed by BRCA1 with 23%; PALB2 with 15%; and TP53 and RAD51C with 8 % each. This article describes a novel pathogenic mutation in RAD51C c.519dupT. The median age at diagnosis was 35 years overall; however, it was six years younger in patients with mutations. Age at diagnosis (OR=0.82, CI 95% 0.71-0.94; P= 0.008) and first-degree family history of cancer (OR=8.26, CI95% 1.35-50; P= 0.022) were the only epidemiological variables associated with mutational status. We found no differences in disease-free survival (p=0.403) or overall survival (p=0.735) among mutational status subgroups.

Changes in curricula, publication policy and information technology, notably in China have led to concentrations in the role of STEM (science, technology, engineering and mathematics) education in early childhood and applauded to proliferations of imported up-to-date reading materials and mobile apps in English. This paper proposes a longitude study of a Chinese toddler learning STEM by reading picture books and playing with tablet and suggests new horizons in parenting and in STEM education during children's early years. The present study carried out from 2016, when the participant reached one year old, eligible to learn to speak and to concentrate on the picture books read by parents who had filled a language background questionnaire with information on themselves and the participant. Tablet playing brought about for the two-year-old toddler and collections of STEM books in English was added for the second year. Data collection lasted for two years with an iLab video camera, capturing utterances and motions for five minutes per week transcribed by VoiceScript software. Tests were given quarterly at private home by tapping in mobile app "Bilingual Child Learning" which consists of 20 basic STEM themes before scores were collected. Findings indicate that (1) it is accessible for children of very early years to be engaged in English STEM resources, (2) kids' limited English dominance does not impede learning STEM, (3) and to think in English in early STEM contributes to children's English.

The purpose of interdisciplinary communication during the early architectural design stage is to achieve the early integration of knowledge in different professional fields, which can help architects to choose correct design development strategies during the early architectural design stage. However, because there is too little information at the early design stage, and design solutions are still rapidly changing and developing, the uncertainties at this stage make it difficult for consultants in other disciplines to provide their views and analysis. In spite of this situation, the emergence of generative modeling is changing design procedures and methods of communication and cooperation for architectural teams, and has brought about a shift in the way architects transmit design information from "what" (declarative information) to "how" (procedural information). Generative modeling is like an aircraft's dashboard: It can provide a basis for interdisciplinary communication, provide interdisciplinary knowledge packages, and bring about a shift in interdisciplinary communication that will reduce the architectural team's communication needs and cost. This study uses a real design case to show the feasibility of generative modeling. Employing generative modeling as a basis, architects can enhance the efficiency of design change and multi-disciplinary communication during the early design stage, integrate specialized knowledge in relevant fields, use this knowledge to formulate design criteria for the next stage, and effectively transmit design decisions. As a consequence, the changes to the cost structure of design revisions and communication between different disciplines has initiated a paradigm shift toward multi-disciplinary communication in architectural design.

To help reduce the impact of geohazards, an innovative landslide early-warning technology based on an energy demodulation-based fiber optic sensing (FOS-LW for short) technology, is introduced in this paper. FOS-LW measures the energy change in a sensing fiber at the segment of micro-bending, which can be caused by landslide movements, and automatically raises an alarm as soon as the measured signal intensity in the fiber reaches a pre-set threshold. Based on the sensing of micro-bending losses in the fiber optics, a two-event sensing algorithm has been developed for the landslide early-warning. The feasibility of the FOS-LW technology is verified through laboratory simulation and field tests. The result shows that FOS-LW has some unique features such as the graded alarm, real-time responses, remote monitoring, low cost and passive optical network, and can be applied in the early-warning of landslides.

In the recent concrete industry, high fluidity concrete is being widely used for the pouring of dense reinforced concrete. Normally, in the case of high fluidity concrete, it includes high binder contents, so it is necessary to replace part of the cement through admixtures such as fly ash to procure economic feasibility and durability. This study shows the mechanical properties and field applicability of high fluidity concrete that using mass of fly ash as alternative materials of cement. The high fluidity concrete mixed with 50% fly ash was measured to manufacture concrete that applies low water/binder ratio to measure the mechanical characteristics as compressive strength and elastic modulus. Also, in order to evaluate the field applicability, high fluidity concrete containing high volume fly ash was evaluated that fluidity, compressive strength, heat of hydration and drying shrinkage of concrete.

Background: Despite tremendous advances in medicine, infective endocarditis (IE) continues to be a challenge for physicians due to increasing morbidity and unchanged high mortality. Objectives: Our aim was to evaluate clinical outcomes in patients with IE and to identify predictors of in-hospital mortality. Material and methods: The study was retrospective, single-centered, and included 270 patients diagnosed with IE, for the period 2005-2021 (median age 65 (51–74), man 177 (65.6%). Results: Native IE (NVIE) was found in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%) and cardiac device-related IE (CDRIE) in 2 (0.7%), significantly more in the non-survivors group. Healthcare associated IE (HAIE) was 72 (26.7%), the most common pathogen were Staphylococci and the proportion of Gram-negative bacteria (GNB) non-HACEK were significantly higher in non-survivor’s vs survivors (11 (15%) vs 9 (4.5%), p=0.004). Overall, early surgery was performed in 54 (20%) patients, with a significant difference between deceased/alive (3 (4.5%) vs 51 (25.1%, p=0.000). The all-cause in-hospital mortality rate was 24.8% (67). The risk factors identified that increased the risk of death were septic shock (OR – 83 1; 95% CI (17.0-405.2), p=0.000) and acute heart failure (OR –24.6; 95% CI (9.2-65.0), p=0.000). Early surgery (OR – 0.03, 95% CI (0.01-0.16), p=0.000) and low Charlson comorbidity index (OR – 0.85, 95% CI (0.74-0.98, p=0.026) in turn reduce this risk. Conclusion: We found that acute heart failure and septic shock are independent predictors of in-hospital mortality. Low Charlson comorbidity index and early surgery increased survival. Knowing the predictors of death would change the therapeutic approach to a more aggressive one and improve the near and long-term prognosis of patients with IE.

This study introduces an advanced method for climate downscaling using a Super-Resolution Generative Adversarial Network (SRGAN), referred to as Elevation-integrated TEmperature and Precipitation SRGAN downscaling (E-TEPS), to enhance the spatial resolution of climate data, specifically 2m-temperature above the surface and total precipitation, from the high-resolution Euro-Mediterranean Center on Climate Change (CMCC) dataset over Italy. Traditional Numerical weather prediction (NWP) as well as global climate models (GCMs) generally lack the resolution required for local applications, and this research addresses that gap by refining GCM outputs to provide detailed local climate insights. E-TEPS incorporates elevation maps as auxiliary inputs, significantly improving the accuracy of downscaled temperature and precipitation data. Utilizing Google Cloud's computational resources, the model processes large climate datasets and runs complex training operations efficiently. The system is exceptionally fast, delivering all results in under 10 seconds. The model demonstrates superior performance over two interpolation methods (bicubic and linear), used as traditional downscaling methods, achieving lower Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE), higher Pearson Correlation for temperature, and higher agreement values for the precipitation. Visual comparisons confirm that E-TEPS generated high-resolution outputs exhibit fewer artifacts and better detail preservation, particularly in regions with complex terrain and variable climatic conditions. These findings underscore the potential of our model in delivering precise, high-resolution climate predictions, thereby enhancing the performance of early-warning systems and supporting more effective climate-related decision-making. This paper is the first part of a two-part series; the second part will demonstrate the integration of this downscaling method with the FourCastNet global forecasting model to enhance climate predictions at a regional level, particularly focusing on high-resolution forecasts for Italy.

Early childhood may be a stressful period for families with a significant impact on parents’ mental health and the child’s healthy development. The goal of the SKKIPPI cohort study was to assess the occurrence and determinants of psychosocial stress and mental health disorders in parents as well as in their offspring in early childhood in three German regions. Based on random samples from three residents' registration offices, parents with infants up to 12 months of age at the time of sampling, were invited to participate in the study. A screening online questionnaire was newly developed, available in four languages, to assess common psy-chosocial stressors and mental health problems of parents with small children. The study enrolled 4,984 mothers and 962 fathers. The most common potential psychosocial stressors at baseline were professional problems (mothers 22%, fathers 33%), lack of social sup-port (20%, 14%), and severe, negative experiences in childhood (22%, 16%). Obses-sive-compulsive thoughts (21%, 16%), depressive (9%, 9%) and anxiety symptoms (11%, 7%) were the most frequently reported mental health problems by both parents. Regulatory prob-lems of the child were reported by between 1.5% and 5.1% of parents. The SKKIPPI study showed that a substantial proportion of parents are burdened by psychoso-cial problems and suffer from mental health problems in the first years after birth. Early pre-ventive and low-threshold support measures should be available in the health and social care system. The newly developed questionnaire can be used to screen in the relevant populations in order to avoid disturbances in the mother-child attachment.

Purpose: Early glottic cancer is a highly curable malignancy. Disease control is achieved by resec-tion or external beam radiation with similar long-term results according survival. Surgery is predominantly performed by transoral endoscopic approach, due to reduced complication rates when compared to open cordectomy. Open cordectomy might still be warranted in cases of inad-equate surgical accessibility. Aim of the present study was to compare endoscopic versus open approach in relation to complications and outcome in an up-to-date patient group. Methods: 219 patients underwent primary tumor resection in early glottic cancer (UICC stages I-II). 168 opera-tions were performed endoscopically, 51 operations were open transcervical cordectomies. We compared survival data with non-parametric methods and functional outcome according to need of tracheostomy, feeding tube and voice functional outcome following ELS protocol. Results: There were no significant differences in overall survival (OS). 2 years OS after endoscopic surgery was 90.5% vs 95.3% after transcervical resection. As expected, OS in T1b and T2 tumors was worse than in T1a tumors. We found a statistically significant difference in disease free survival (DFS) within the T1a and T1b/T2 group (Log rank test: p=0.006) but no relevant difference be-tween the two surgical modalities, even when the data was stratified by T-categories performing a Cox regression (hazard ratio 1.21, p=0.712). Patients who underwent open surgery had a sig-nificantly worse peri- and postoperative course with longer hospital stay, higher frequency of tracheotomies and longer need for nasogastric tubes. Functional results were comparable within the two patient groups while higher tumor size / stage was an unfavorable predictor for voice re-habilitation. Conclusion: Open cordectomy leads to more complications but offers comparable oncological and functional outcome when compared to transoral endoscopic approach in early glottic cancer. Open surgery therefore continues to be a valid treatment option when endoscopic resection is not possible.

Early-life adversity can profoundly impact individual development, yet some demonstrate resilience. Longitudinal studies tracking individuals over extended periods have aided our understanding of resilience and growth following adverse childhood experiences. This paper reviews insights from influential studies like the Kauai Longitudinal Study, the Adverse Childhood Experiences (ACE) Study, and the Dunedin Study. It explores key findings on risk and protective factors, adaptation trajectories, and long-term outcomes associated with resilience. Theoretical frameworks and methodological considerations are discussed. The paper examines how this research informs interventions, policies, and support systems for fostering resilience. It highlights the need for diverse samples, integrating biological and environmental factors, and investigating intergenerational impacts. By synthesizing longitudinal research, this paper elucidates complex pathways to resilience and positive development despite early adversity, offering insights for research and supporting vulnerable populations.

Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring’s liver microRNAs. Mouse offspring of WD-fed mothers were given daily a placebo (controls) or BC during suckling. The liver miRNAome was analyzed in recently weaned animals by microarray hybridization. BC impacted the liver miRNAome differently in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet.

High seismic activity in the Himalayas and the increasing urbanization of its surrounding areas in the northern Indian region pose significant threats to both lives and properties. To mitigate the risk of seismic events, an earthquake early warning system can be used in the region. This system would be particularly beneficial to cities and towns in the mountainous and foothill regions that are located near earthquake sources. The government and the science and engineering community have re-sponded to this call by establishing the Uttarakhand State Earthquake Early Warning System (UEEWS). The system became fully operational on August 4, 2021, after being launched by the government of Uttarakhand. The UEEWS includes 170 accelerometers in the seismogenic part of the Uttarakhand region of the Himalayas. Ground motion data is transmitted to a central server through a dedicated private telecommunication network 24 hours a day, seven days a week.The system is designed to issue warnings for moderate to high-magnitude earthquakes via a mobile application installed on users' devices and sirens installed in government-owned public buildings. The UEEWS has successfully issued alerts for light earthquakes that occurred in the instrumented region and warnings for moderate earthquakes that occurred in the vicinity of the instrumented area. This paper provides an overview of the design of the UEEWS, details of the instrumentation, adaptation of attributes and their relation to earthquake parameters, the operational flow of the system, and information about the dissemination of warnings

Keywords: early childhood; education; quality; measurement; monitoring; majority world; Item Response Theory; psychometrics

The Standard Model (SM) of particle physics successfully describes electromagnetic, weak, and strong forces but omits gravity. We introduce the Kinematrix Field Theory (KFT), integrating gravity into this fundamental force framework through a novel particle, the kinematon. This gauge boson, existing in both massless and massive forms, advances the SM's scope to address enigmas like dark matter and neutrino masses. We detail the mathematical structure of the KFT and establish Feynman rules for kinematon interactions with fermions and gauge bosons. The KFT, synergizing with the Higgs mechanism and general relativity, aspires to a unified quantum theory of gravity. We explore the kinematon's phenomenological implications and potential experimental signatures, forecasting significant advancements in fundamental physics and setting a course for future explorations in the SM.

Over recent years, the swine industry has witnessed the withdrawal of antibiotics and continuous regulation of zinc and copper oxides in the early-life nutrition of piglets. Due to this development, alternative ingredients or additives from plant sources have been tremendously explored. Therefore, this study's objective was to evaluate the effect of dietary supplementation with tannins on weaned piglets’ growth performance, serum antioxidant capacity, and immune status using a meta-analysis approach. With only the inclusion of non-challenged weaned piglets, a total of 16 studies with parameters of interest were deemed eligible after a two-step screening process following a comprehensive literature search in the scientific databases of Web of Science, Scopus, ScienceDirect, PubMed, and Google Scholar. Two main categories of data, including the study’s characteristics and response variables (growth performance, serum antioxidant, and immune indices), were extracted. Applying the random-effects models, Hedges’ g effect size of supplementation with tannins was calculated using the R software to determine the standardized mean difference (SMD) at a 95% confidence interval. Sub-group analysis and meta-regression further explored heterogeneity (PSMD 0.05, I2 50%, n ≥10). Supplementation with tannin reduced average daily gain (p = 0.20) and feed conversion ratio (p 0.01); however, it increased average daily feed intake (p = 0.07) and final body weight (p 0.01). Meta-regression models indicated that tannin dosage and supplementation duration were directly associated with tannins' effectiveness on productive performance. In the serum, the concentration of glutathione peroxidase, superoxide dismutase, and total antioxidant capacity were elevated (p 0.01) in response to tannins supplementation, while malondialdehydes was reduced (p 0.01). Likewise, decreased immunoglobin A (p = 0.47) and increased immunoglobin M and G levels (p 0.01) were detected. In conclusion, dietary supplementation with tannins, particularly with chestnut and grape seed proanthocyanidins, increases the productivity of weaned piglets. At the same time, it is a possible nutritional strategy to mitigate oxidative stress and stimulate gut health. Thus, supplementing chestnut and grape seed proanthocyanidin tannins in the early phase of swine production could be used to alleviate the incidence of diarrhea.

Background: Neonatal sepsis associated with severe morbidity and mortality defines the systemic condition arising from the bacterial, viral, fungal origin associated with hemodynamic and clinical alterations. Symptomatology can be different, from subclinical to severe, focal or systemic disease. The causal agent comes from maternal flora or can be of community/hospital origin. Material and method: Our retrospective study evaluated 121 newborns (both preterm and term), divided into three groups: early onset sepsis (35), late onset sepsis (39), and control group (47), from 0 to 28 days old. Blood samples and cultures were collected at admission, after 24 hours, and 72 hours. Results: The two-sample Wilcoxon signed rank test revealed a statistically significant difference between the initial and final measures of lactate dehydrogenase (LDH) and ferritin within the early onset sepsis (EOS) and late onset sepsis (LOS) groups. No significant differences were observed for those two variables within the control group. There were significant differences for first and last measurements of C-Reactive Protein (CRP) (p = 0.029), leukocyte count (p = 0.002), and platelets (TR) (p = 0.00001). Conclusions: Ferritin is a potential biomarker that can be associated with systemic response and sepsis in both cases of early and late onset sepsis.

This study develops a 7-layer Long Short-Term Memory (LSTM) model to enhance early diabetes detection in Oman, aligning with the theme of 'Artificial Intelligence in Healthcare'. The model focuses on addressing the increasing prevalence of Type 2 diabetes, projected to impact 23.8% of Oman's population by 2050. It employs LSTM neural networks to manage factors contributing to this rise, including obesity and genetic predispositions, and aims to bridge the gap in public health awareness and prevention. The model's performance is evaluated through various metrics. It achieves an accuracy of 99.40%, specificity and sensitivity of 100% for positive cases, a recall of 99.34% for negative cases, an F1 score of 96.24%, and an AUC score of 94.51%. These metrics indicate the model's capability in diabetes detection. The implementation of this LSTM model in Oman's healthcare system is proposed to enhance early detection and prevention of diabetes. This approach reflects an application of AI in addressing a significant health concern, with potential implications for similar healthcare challenges globally.st diagnostic capabilities, representing a significant leap forward in healthcare technology in Oman.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM), and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided in two groups: group A, with PROM ≥ 18 hours and group B, with PROM < 18 hours. Both groups were further split into subgroups: proven sepsis, probable sepsis and no sepsis. Descriptive statistics, ANOVA analysis, and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cells count from the first (p = 0.005) and third day (p = 0.028), and high CRP values from the first day (p = 0.004). Procalcitonin (area under the curve - AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early onset neonatal sepsis. (4) Conclusions: Further studies are needed to explore other bi-omarkers of sepsis in both pregnant women and newborns to better predict EOS.

Correlations between the Neoproterozoic belts surrounding the West African Craton and northern Brazilian cratons have long been a subject of interest and controversies. Due to the splitting of African and South American continents by the Atlantic oceanic domains, no direct links are preserved, requiring relying on various geological or geophysical characteristics to propose such correlations. In addition to the opening of the Atlantic oceanic domains, another difficulty arises from the covering of northern Brazilian belts by upper Paleozoic and Mesozoic basins, making these correlations speculative. Recently, four orogens have been evidenced in the Neoproterozoic belts of the western margin of the West Africa Craton, while the belts on the eastern side underwent only one orogeny. Similarities with the Pan-African I (900-650 Ma) and with the Pan-African II (650-480 Ma) orogenic events have been evidence in the western Brazilian belts (Araguay and Paraguay). The two first orogens on the western margin (Pan-African I and Pan-African II) can thus be extended to the western Brazilian belts and can be considered as parts of a single geodynamic system running from the Mauritania to the Paraguay including the “Gurupi rift” as an aulacogen connected to the NNW-SSE Panafrican I and II oceanic domains. Consequently, the eastern Brazilian belt should rather be linked the Eastern Trans-Saharan belts.

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk for neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 11.1% respectively. Specificity, negative and positive predictive values between methods showed no significant variance, though multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it can not be recommended for this indication.

Background. This study aimed to establish a prognostic nomogram for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with early-onset endometrial cancer (EOEC). Methods. Patients diagnosed with EOEC during 2004-2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were performed to ascertain the independent factors impacting the prognosis of EOEC patients, while a prognostic nomogram was established. Its performance was verified by the receiver operating characteristic (ROC) curves, and calibration plots. The prediction accuracy and clinical net benefit between the model, TNM stage and SEER stage were further compared by the concordance index (C-index) and decision curve analysis (DCA). Results. A total of 4415 eligible patients with EOEC were identified and enrolled in this study. Independent prognostic factors for OS and CSS were confirmed by multivariate Cox regression, which were further incorporated to constructed a nomogram. ROC curves and calibration curves indicated an optimal accuracy of the nomogram. Meanwhile, the C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Conclusions. Nomogram based on risk factors was developed as an individualized tool to predict OS and CSS for EOEC patients. The novel tool will assist in patient counseling and selection of appropriate therapeutic regimens.

Our comprehension of fundamental cosmological principles hinges on a thorough understanding of the early universe. The Lambda Cold Dark Matter (ΛCDM) model has emerged as a valuable framework for elucidating various cosmic phenomena, uniting a cosmological constant (Λ) with cold dark matter (CDM). Nevertheless, recent observations, particularly data from the Planck, WMAP, and DES missions that probe the early universe, alongside local measurements of the Hubble constant, have unveiled significant inconsistencies. These inconsistencies have magnified the perplexing issue known as the Hubble Tension, thereby challenging our current understanding of the universe. To address this conundrum, we adopt a comprehensive approach encompassing a review of cosmological fundamentals, an exploration of the ΛCDM model, an examination of the cosmic microwave background (CMB), power spectrum, and perturbation theory, a thorough review of existing research, and finally, an investigation of real data. By undertaking these early universe processes, we aim to understand more about Hubble constant and its consequence in ΛCDM model.

Ship pilots and maritime safety administration have an urgent need for more accurate and earlier warnings on strong wind gusts. This study firstly investigates the “Oriental Star” cruise ship cap-sizing event in 2015, one of the deadliest shipwreck events in recent years, and explores all related hydro-meteorological components in a global mesoscale model. It is found that, rather than the missing signal in raw surface wind prediction, the cumulus precipitation variable (CP) increases dramatically during the accident occurrence, which significantly corresponds to the sub-grid strong wind gust. The effective lead-time can be extended from 24hr (deterministic model) to 48hr (en-semble model). This finding is then verified in another two recent deadly cruise boat accidents. The introduction of the new variable is bearing the hope of improvement to the current maritime safeguard system, on predicting sub-grid strong wind gusts for small-size cruise boats in offshore and inland rivers. Finally, an automatic-response system is developed to provide economical con-vection prediction via Inmarsat email communication, aiming to explore operational severe con-vective gust early-warning and appropriate numerical mesoscale model application.

This study aimed to describe the injury profiles of young Korean baseball players according to position and age as the proportion and distribution of injuries based on playing position and age remains unclear. A total of 271 elite youth baseball players aged 8 to 16 years were divided into two groups: elementary school (ES) (n=135) and middle school (MS) (n=136). The participants' basic, baseball practice, and injury information were collected. Injuries in the MS group were not limited to the elbow and shoulder, and the injury prevalence varied by age group and baseball position. The most injured body region in the ES group was the elbow joint, regardless of the position. In contrast, the most injured body region in the MS group was the lower back, except for infielders whose elbows were the most injured. Additionally, the MS group was more likely to experience injuries of the lower back (OR=4.27, 95% CI=2.47–7.40), shoulder (OR=1.93, 95% CI=1.08–3.43; P=0.024), and knee (OR=2.15, 95% CI=1.17–3.94; P=0.012). Our findings indicate that excessive practice and lack of rest during MS (growth spurt period) can significantly increase the risk of lower back problems in young baseball players.

Introduction: The choice of Cardiac Preservation Solution (CPS) for myocardial protection at the time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm Heart Transplantation (HTx) outcomes. Thus, we retrospectively analyzed our adult HTx performed with two different CPS, during a period of 12 years, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. Methods: From January 2009 to December 2020, 154 adult HT were performed in our hospital. Patients were divided in two groups according to the CPS used: St. Thomas (n=75, group P 1) and HTK-Custodiol (n=79, group P 2). The choice of CPS was related to an institutional policy; from 2009 to 2015, St. Thomas solution was exclusively used, and after that, HTK-Custodiol alone. Results: There was no significant difference between the two groups in terms of preoperative and intraoperative features. Postoperatively, the Custodiol group showed significantly lower inotropic score (p&lt;0.0001), mean rejection score (p= 0.036) and 30 days mortality (p=0.0068). The use of HTK-Custodiol was the only variable that improved midterm survival (HTK-Custodiol vs St Thomas, HR= 0.20 (95% CI: 0.069 -0.6) p=0.0039). Conclusion: In our single center experience, using HTK-Custodiol as myocardial protection during heart procurement leads to improved outcomes after HTx, including postoperative inotropic score, rejection score, 30-days mortality and midterm survival.

Through an ambitious development blueprint called Agenda 2063, Africa is on a mission to creating the ‘Africa We Want’ by the year 2063, centred on science, technology, and innovation. While the 2063 development agenda portends attainment of socio-economic development and prosperity in Africa, it brings with it an enormous need for strategic investment in research to ensure that no one is left behind. This paper presents insights from the African Research Initiative for Scientific Excellence (ARISE) programme on inclusive research capacity strengthening investment in Africa. The insights are drawn from a comprehensive candidate selection process for ARISE, from which 45 researchers (from a pool of 929 applicants) are recruited for ARISE Fellowships. The 45 early-to-mid-career researchers, 37% of which are women, are hosted in 45 institutions of higher learning located in 38 countries across Africa, conducting 5-year research fellowships with grants of up to €500,000 each. The insights from the ARISE programme contribute to the debate on effective approaches to programme scoping, design, and delivery, underscoring the need for consideration of scientific excellence in the context of diversity in research support capacity and investments across Africa.

Global and human development and freedoms increasingly thrive on robust and policy-oriented research and related activities. Yet, the African research landscape faces a myriad of challenges, resulting in a very unequal continent in terms of research and research capacity. The prevailing research inequities and challenges in Africa are even more pronounced in the social sciences, humanities, arts, and related fields (SSHA). Here, the strengths and impact of scholarship in SSHA fields are often overshadowed by deficits and apparent preferential investment in research in science, technology, engineering, and mathematics-related fields. In response, the African Academy of Sciences commissioned a study in 2020 to generate evidence on the SSHA research support landscape in Africa. This paper summarizes findings from the literature review, key informant interviews, a bibliometric analysis, a survey with a sample of 670 respondents from SSHA communities in Africa, and a series of focus group discussions. We highlight key messages and make recommendations focussing on lessons learnt opportunities, and priorities for intervention to enhance significant SSHA research leadership capacity strengthening and, ultimately, minimize research inequalities in Africa.

The article is devoted to solving the problem of searching for universal explainable features that can remain explainable for a wide class of objects and phenomena and become an integral part of Explainable AI (XAI). The study is implemented on the example of an applied problem of early diagnostics of plant stress, using Thermal IR (TIR) and HSI, presented by 8 vegetation indices/channels. Each such index was presented by 5 statistical values. A Single-Layer-Perceptron classifier was used as the main instrument. TIR turned out to be the best of the indices in terms of efficiency in the field and sufficient to detect all 7 key days with 100% accuracy. Our study shows also that there are a number of indices, inluding NDVI, and usual color channels Red, Green, Blue, which are close to TIR possibilities in early plant stress detection with 100% accurasy or near, and can be used for wide class of plants and in different conditions their treatment. The stability of the stress classification in our study was maintained when the training set was reduced up to 10% of the dataset volume. The entropy-like feature of (max-min) for any indices/channels have determined as a leadersheep universal high-level explainable feature for the plant stress detection, which used in interaction with some of other statistical features.

In this study, we discuss the properties of absolute vacuum space and how these properties can play a vital role in creating a mechanism in which the very first particle gets created simultaneously everywhere and we find the limit in which when the absolute vacuum volume reaches will lead to the collapse that leads to the creation of the first particle. This discussion is made following to the elementary dimensions theory study that was peer-reviewed at the end of 2020, everything in the universe is made from four elementary dimensions, these dimensions are the three spatial dimensions (X, Y, and Z) and the Vacuum resistant as the factor of change among the four, time itself wasn’t considered as the fourth dimension, rather time corresponds to a factor of change, and during the research it was found out that the Vacuum resistant is the factor of change in the Absolute Vacuum space, where time is a hypothetical concept, that represents changes during certain events compared to a constant change rate event.Therefore, time does exist, but as a factor of change, and as the Vacuum resistant in the absolute vacuum space, Time= factor of change= Vacuum resistant. In the study, the internal and external vacuum resistant volume equivalent is found, External Vacuum resistant=3.2857602*10^15 *mass. This equation is used to identify the amount of Free external vacuum resistant created during nuclear fission and fusion: Initial mass of the excited nucleuses mass of the created new nucleuses+ 3.2857602*10^15 * the lost Mass. In elementary dimensions, the energy created during nuclear reactions is equivalent to the free External vacuum resistant created through nuclear reactions, and mass is equivalent to the internal Vacuum resistant.

Complete pathologic response (pCR) predicts the long-term outcome of neoadjuvant treated (NAC) breast cancer (BC) but is reached in <10% of hormone-receptor-positive patients. Biomarkers able to guide adjustment or interruption of an ineffective therapy are desired. Here, we evaluated whether shifts in the serum concentration of thymidine kinase 1 (sTK1) during NAC could be utilized as a biomarker. In the PROMIX trial, women with localized HER2- BC received neoadjuvant epirubicin/docetaxel in six cycles. sTK1 was measured with an ELISA in 54 patients at cycles 1-4 and in a total of 131 patients before and 48h after cycle 1. The prognostic significance of the results was evaluated by log-rank tests of Kaplan–Meier estimates. Treatment resulted in a 2-fold increase of sTK1 before and 3-fold increase 48h after the cycles, except for the first cycle, where half of patients reacted with a decrease (post/pre sTK1- ratio <1.12) and the other half reacted with an increase (ratio >1.12). OS rates in ER+ patients with ratios of >1.12 and <1.12 were 97.7% and 78% (p=0.005), respectively, and DFS rates were 90.7% and 68% (p=0.006), respectively. Thus, response of sTK1 at the first cycle of chemotherapy could be used both as an early biomarker for guidance of chemotherapy and for the study of inherent tumor chemo-sensitivity, which could predict long-term outcome prior to therapy.

This study explored father involvement as a social determinant of child health within the context of macro-environmental changes in Mongolia. Using data for children aged 3-4 from UNICEF’s Multiple Indicator Cluster Surveys, this cross-sectional analysis examined the association between father presence and engagement with child health and educational outcomes. Multivariate regression modeling was employed to identify associations between father presence, engagement, and child outcomes including fever, respiratory illness, diarrhea and preschool attendance. In unadjusted analyses, father engagement was associated with higher odds of pre-school attendance (OR=1.12; 95% CI 1.04-1.20) but not with child illness (OR=1.04; 95% CI 0.95-1.14). Father engagement was no longer associated with pre-school attendance after controlling for potentially confounding variables (ORadj = 0.95; 95% CI 0.88-1.03). Unadjusted and adjusted analyses showed that father presence was not associated with acute illness or preschool attendance. Results also suggest that a larger proportion of children were engaged in activities by their mother compared to their father or other adults. Data indicate that father presence and engagement were not associated with child illness or pre-school attendance. Factors such as maternal education, household wealth, and region of residence are stronger predictors of preschool attendance and should continue to be considered for promoting child health and development in Mongolia.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

Natural circulation loop (NCL) systems are buoyancy-driven heat exchangers that are used in various industrial applications. The concept of passive heat exchange in NCL systems is attractive, because there is no need for an externally driven equipment (e.g., a pump) to maintain the fluid circulation. However, relying on buoyancy as the sole driving force may lead to several potential difficulties, one of which is generation of (possibly) time-varying nonlinearities in the dynamical system, where a difference in the time scales of heat transfer and fluid flow causes the flow to change from a steady-state regime to either an oscillatory regime or a flow-reversal regime, both of which are undesirable. In this paper, tools of symbolic time series analysis (e.g., probabilistic finite state automata (PFSA)) are proposed to identify selected regimes of operation in NCL systems, where the underlying principle is built upon the concept of pattern classification from measurements of fluid-flow dynamics. The proposed method is shown to be capable of identifying the current regime of operation from the initial time response under a given set of operational parameters. The efficacy of regime classification is demonstrated by testing on two data sets, generated from numerical simulation of a MATLAB SimuLink model that has previously been validated with experimental data. The results of the proposed PFSA-based classification are compared with those of a hidden Markov model (HMM) that serves as the baseline.

Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together. Background: Clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia," "side effects," "agranulocytosis," "TRS," or "bipolar affective disorder (BAF)" for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: We selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: We considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) Clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.

There is a major clinical need for accurate biomarkers for prostate cancer prognosis, to better inform treatment strategies and disease monitoring. Current clinically recognised prognostic factors, including prostate-specific antigen (PSA) levels, lack sensitivity and specificity in distinguishing aggressive from indolent disease, particularly in patients with localised intermediate grade prostate cancer. There has therefore been a major focus on identifying molecular biomarkers that can add prognostic value to existing markers, including investigation of DNA methylation, which has a known role in tumorigenesis. In this review, we will provide a comprehensive overview of the current state of DNA methylation biomarker studies in prostate cancer prognosis, and highlight the advances that have been made in this field. We cover the numerous studies into well-established candidate genes, and explore the technological transition that has enabled hypothesis-free genome-wide studies and the subsequent discovery of novel prognostic genes.

(1) Background: It is unclear whether the reported presenting clinical features of coronavirus disease 2019 (COVID-19) are useful in identifying high-risk patients for early testing and isolation in the emergency department (ED). We aimed to compare the exposure history, clinical, laboratory, and radiographic features of ED patients who tested positive and negative for COVID-19; (2) Methods: We conducted a case-control study in seven EDs during the first five weeks of the COVID-19 outbreak in Hong Kong. Thirty-seven laboratory-confirmed COVID-19 patients were compared with 111 age- and gender-matched controls; (3) Results: There were no significant differences in patient characteristics and reported symptoms between the groups, except patient-reported fever. A positive travel history or contact history was the most significant predictor for COVID-19 infection. After adjustment for age and presumed location of acquiring the infection in Wuhan/Hubei, patient-reported fever (OR 2.6, 95% CI 1.1 to 6.3), delayed presentation (OR 5.0, 95% CI 2.0 to 12.5), having medical consultation before ED presentation (OR 7.4, 95% 2.9 to19.1), thrombocytopenia (OR 4.0, 95% CI 1.6 to 9.7), raised lactate dehydrogenase (OR 5.9, 95% CI 1.9 to 18.5), haziness, consolidation or ground-glass opacity on chest radiography (OR 5.6, 95% CI 2.0 to 16.0), and bilateral changes on chest radiography (OR 13.2, 95% CI 4.7 to 37.4) were associated with a higher odds of COVID-19 separately while neutrophilia was associated with a lower odds (OR 0.3, 95% CI 0.1-0.8); and (4) Conclusions: This study highlights several features that may be useful in identifying high-risk patients for early testing and isolation while waiting for test result. Further studies are warranted to verify the findings.

The first reports of the acute and often fatal illness known as the “English Sweat” are from 1485 and its last known outbreak was in 1551. During this period, the Sweat produced only five epidemic waves. Except for one outbreak which spread to the northern part of the continent of Europe in 1529, the Sweat was confined almost exclusively to England, with only anecdotal reports of isolated infections in other parts of the British Isles. The Sweat was thus only a minor component in the panorama of infectious disease affecting mediaeval and early modern Europe. Nevertheless, it continues to fascinate both medical historians and modern infectious disease biologists – the latter group now often engaged in competing exercises in retrospective diagnosis. This paper seeks to explore the reasons for such enduring interest, using the Early English Books Online (EEBO) text corpus to analyse the various contexts in which the Sweat was discussed up to 1700. EEBO shows that references to the Sweat occur repeatedly in astrological and religious discourses, especially from the mid-17^th century onwards. Four salient examples are examined in detail. It is proposed that the cultural memory of the Sweat, in the 150 years following its disappearance, was kept disproportionately alive not so much by accounts of its alarming symptoms but more due to its metaphorical and illustrative utility in non-medical discourse.

Visual examination of nails can reflect the human health status. Diseases such as nutritive imbalances and skin diseases can be identified by looking the colors around the plate part of the nails. We present the AI-based NAILS method to detect fingernails through segmentation and labeling. We built a generalized model to identify single fingers, their fingernail plates and retrieve their color data. A pre-trained deep learning Neural Network algorithm containing different images of fingernails as reference frames is used to identify different fingernails edges and the color areas around them in real-time. The novel aspect of our NAILS sensor model is that it allows to analyze –via a GUI and the use of a HD webcam, the tiniest dynamical signals from changes in fingernail colors. This feature could be used to self-extract primary signs of diseases in humans.

In 1935, Einstein and Rosen (ER), in their seminal paper "Particle Problem in General Relativity" proposed that "a particle in the physical Universe has to be described by mathematical bridges connecting two sheets of spacetime" in order to achieve a consistent understanding of quantum fields in curved spacetime. We discuss similar conclusions independently arrived at by Schr\"{o}dinger in 1956 and 't Hooft in 2016 in the context of cosmological and black hole spacetimes. Quantum effects at gravitational horizons involve inverse harmonic oscillators. We demonstrate that an analogous ER proposal of a mathematical bridge is envisioned by Berry and Keating for the description of a quantum inverse harmonic oscillator that has horizons in its phase space. Recently proposed direct-sum quantum theory reconciles the ER's vision by expressing a single quantum state in the physical space as a direct-sum of two components in the parity conjugate regions with opposite arrows of time. We discuss the implications of this framework for offering a new understanding of the ER bridges, promising a unitarity description of quantum fields in curved spacetime along with observer complementarity. Furthermore, we present compelling evidence for our new understanding of ER bridges in the form of large-scale parity asymmetric features in the cosmic microwave background. We finally discuss the implications of this new understanding for our endeavors in combining gravity and quantum mechanics.

During the COVID-19 pandemic, wastewater surveillance was used to monitor community transmission of SARS-CoV-2. As new genetic variants emerged, the need for timely identification of these variants in wastewater became an important focus. In response to increased reports of Omicron transmission across the United States, the Oklahoma Wastewater Surveillance team utilized allele-specific RT-qPCR assays to detect and differentiate variants, such as Omicron, from other variants found in wastewater in Oklahoma. The PCR assays showed presence of the Omicron variant in Oklahoma on average two weeks before official reports, which was confirmed through genomic sequencing of selected wastewater samples. Through continued surveillance from November 2021 to January 2022, we also demonstrated the transition from prevalence of the Delta variant to prevalence of the Omicron variant in local communities. We further assessed how this transition correlated with certain demographic factors characterizing each community. Our results highlight RT-qPCR assays as a rapid, simple and cost-effective method for monitoring community spread of SARS-CoV-2 genetic variants in wastewater. Additionally, they demonstrate that specific demographic factors such as ethnic composition and household income can correlate with the timing of SARS-CoV-2 variant introduction and spread.

It is not plausible to predict disasters; however, still the least that may be done is to get ready for that. In disaster circumstances, nowadays, the existing internet of things (IoT) technology is rather developed and capable of being highly beneficial. For many countries, the early warning system for natural catastrophes is a crucial challenge, especially for high seismic hazard countries. Primary function of an early warning system is to assist individuals and authorities to save lives and reduce secondary damage once a disaster occurs. Even though such systems have been defined for the earthquake on the basis of IoT, the least attention has been focused on the post decisions for substructure monitoring systems which can control the gas and electric lifelines given the critical time. Combination of Fuzzy system with IoT can improve the decision making process after the disasters occur. This program minimizes costs and destruction in cities. Tehran is a high seismic hazard area which contains an expanded network of the gas transmission system. Hence, a major seismic event may cause serious loss directly and indirectly owing to the damage to the gas and electric transmission network. The proposed early warning system contains a grid of strong ground motion stations. Each station contains five sensors to collect accurate data and send the data to the cloud server, then the server executes relevant scenarios.

From the various perspectives of Machine Learning (ML) and the multiple models used in this discipline, there is an approach aimed at training models for the Early Detection (ED) of anoma-lies. The early detection of anomalies is crucial in multiple areas of knowledge since identifying and classifying them allows for early decision-making and provides a better response to mitigate the negative effects caused by late detection in any system. This article presents a literature review to examine which machine learning models (MLM) operate with a focus on ED in a multidisci-plinary manner and specifically how these models work in the field of fraud detection. A variety of models were found, including Logistic Regression (LR), Support Vector Machines (SVM), De-cision Trees (DT), Random Forests (RF), Naive Bayesian Classifier (NB), K-Nearest Neighbors (KNN), Artificial Neural Networks (ANN), Extreme Gradient Boosting (XGB), among others. It was identified that MLMs operate as isolated models, categorized in this article as Single Base Models (SBM) and Stacking Ensemble Models (SEM). It was identified that MLMs for ED in multiple areas under SBM and SEM implementation achieved accuracies greater than 80% and 90%, respectively. n fraud detection, accuracies greater than 90% were reported by the authors. The article concludes that MLMs for ED in multiple applications, including fraud, offer a viable way to identify and classify anomalies robustly, with a high degree of accuracy and precision. MLMs for ED in fraud are useful as they can quickly process large amounts of data to detect and classify suspicious transactions or activities, helping to prevent financial losses.

Agriculture is an industry that heavily relies on the environment. The increasing frequency of ex-treme disasters attributable to climate change has adversely affected agricultural land and dis-rupted the stability of the supply of agricultural products. Therefore, we implemented a research program focused on current strategies for adapting to agricultural meteorological disasters. The primary goal was to actively promote disaster prevention information and techniques through information platforms and applications and to provide refined forecasting and an early warning system to enhance preparedness for and recovery from agricultural disasters. This initiative can transform passive mitigation into dynamic action by disseminating crucial information to farmers. We integrated meteorological data and crop characteristics to develop disaster prevention strate-gies for the predisaster, during-disaster, and postdisaster stages to empower farmers to implement autonomous disaster prevention, ensuring their profitability and minimizing the impact of disas-ters. This paper presents an agricultural disaster prevention system involving cross-disciplinary collaboration to establish an early warning system for crop disasters. However, the effectiveness of the early warning system relies on the availability of complete meteorological and crop infor-mation, necessitating high-density agricultural meteorological stations, refined weather forecast services, historical crop damage data, and ongoing research and development on disaster preven-tion technology. In the system, a diversified social media interface is used to provide local farmers with weather forecast information. When impending disasters are identified, the platform acti-vates disaster prevention measures to reduce agricultural losses. This article paper introduces Taiwan’s agricultural disaster prevention system as a complete disaster prevention strategy.

Multiple sclerosis is a chronic, autoimmune disease that mainly affects the central nervous system, including the brain, spinal cord, and optic nerve. This disease can cause clinical symptoms such as cognitive decline, muscle weakness, spasms, and fatigue in patients, and the onset tends to be younger. Current medication can only prevent or alleviate symptoms, so early diagnosis of this disease can increase patients' chances of treatment. Although the use of nuclear magnetic resonance detection can improve the efficiency of early auxiliary diagnosis, it still requires experienced doctors to spend too much time and energy on comprehensive judgment. To reduce the time cost and improve the efficiency of multiple sclerosis diagnosis, this article proposes a detection and recognition algorithm for multiple sclerosis based on wavelet entropy and self-adaptive particle swarm optimization. Firstly, a triple discrete wavelet transform is performed on the brain image of multiple sclerosis, and then 10 wavelet entropies are extracted from the decomposed wavelet subbands, which can reduce the feature dimensions of the image; Then, the algorithm of self-adaptive particle swarm optimization is used to optimize the feedforward neural network, in order to obtain the optimal connection weights and thresholds during the training process. The result of the model is with an average sensitivity of 92.29±1.89, specificity of 92.54±0.67, precision of 92.48±0.59, accuracy of 92.42±0.88, and F1 score of 84.85±1.74, Matthews correlation coefficient of 92.37±0.96, and Fowlkes223 Mallows Index of 92.38±0.96. The experimental results indicate that this algorithm has a very important data support role in detecting multiple sclerosis.

This article reviews the introduction of Alzheimer's Disease (AD), neural networks, training and learning of neural networks, applications of neural networks in early diagnosis of AD, applications of neural networks in AD drug discovery, other brain diseases, and challenges faced by AD. First, the paper introduces the background and characteristics of AD. AD is a degenerative neurological disorder characterized by impaired memory, decreased cognitive function, and loss of neurons. These characteristics place a huge burden on the lives and families of patients. Next, the basic principle and structure of neural network are discussed. A neural network is a computational model made up of multiple neurons that can perform tasks by learning and adapting to input data. In particular, the key concepts of neural network hierarchy, activation function and weight adjustment are discussed. Then, the training and learning methods of neural networks are discussed. Common techniques such as backpropagation algorithm and gradient descent optimizer are introduced in detail, as well as the importance of data preprocessing and model evaluation. Next, the paper focuses on the application of neural network in early diagnosis of AD. By extracting features from brain image data, neural networks can automatically identify differences between AD patients and healthy subjects, enabling early diagnosis and intervention. In addition, the application of neural networks in AD drug discovery is also discussed. By analyzing and predicting a database of known drugs, neural networks can help discover potential treatments for AD and speed up the drug discovery process. The paper further explores the application of neural networks in other brain diseases and highlights the challenges faced by AD, such as the lack of reliable biomarkers, complex pathological mechanisms, etc. In summary, this paper presents a systematic overview of AD, neural networks, training and learning of neural networks, applications of neural networks in early diagnosis of AD and drug discovery, and other brain diseases and challenges associated with AD.

The brief paper utilises Zimbabwe as a case study to discuss the effects of El Nino in Southern Africa. It offers potential adaptation and mitigation measures for farmers to prepare for the forecasted El Nino-influenced rainy season 2023/24 and the future. To reduce climate and weather hazards connected with El Nino, the brief report suggests anticipatory action methods be applied in southern Africa, using Zimbabwe as a case study. To protect farmers' livelihoods and enhance drought readiness for the forthcoming agricultural seasons, the paper suggests a degree of strategic, tactical, and operational decision-making that the agriculture industry should adhere to. It emphasised the significance of providing farmers with knowledge and advice regarding drought and heat stress, including cultivating crop varieties and livestock and sufficient fire safety precautions. The brief paper calls to advocate for anticipatory action to avert El Nino in Southern Africa.

Fragility scales are intended to help in therapeutic decisions. Here we asked if the fragility as-sessment in MM patients ≥75 years old qualified for treatment by the local physician correlates with the choice of treatment: a 2- or 3-drug regimen. Between 7/2018 to 12/2019 we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in com-pletely dependent. Patients with more than 3 comorbidities were 26.9% (53 patients). Thus, ac-cording to the Palumbo calculator, 43 patients were in the intermediate-fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received 3-drug regimens and 20.3% (40) received 2-drug regimens. In each ECOG group, more than 3/4 of patients received 3-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received 3-drug regimens. Out of 53 pa-tients with at least 4 comorbidities, 71.7% received 3-drug regimens, and the rest 2-drug regi-mens. Three-drugs regimens received 34 patients from the intermediate-fit group (79.0%), and 123 (79.9%) from the frail group. Early mortality occurred in 25 patients (12.7%). No one discon-tinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with tri-ple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations which questions the clinical utility of current fragility scales in everyday practice.

Diabetes mellitus and dental caries (tooth decay) are not only common Non Communicable Diseases (NCDs) contributing to high burden of diseases but costly diseases to manage. Diabetes mellitus is a leading cause of mortality and reduced life expectancy across the globe. Early child hood dental caries (ECC) denotes a common chronic childhood disease and cariogenic dietary patterns dominated by refined sugar is one of the main causative factors. Thus, high burden of ECC could be a proxy indicator of excessive refined sugar consumption of a child. If such unhealthy dietary patterns are continued through to adolescent to adulthood, there is a high probability of an individual becoming a diabetic. Therefore, it is rational to argue high ECC burden in a country could be an indicator of future burden of diabetes. Moreover, ECC provides a critical period and a window of opportunity across life-course perspective, to intervene with cariogenic dietary patterns underpinned by common risk factor approach. This could be achieved by tailored dietary counseling for parental care givers of children with ECC. A healthy dietary pattern fostered in the childhood, most probably would continue to adulthood which may become beneficial in reducing the incidence of diabetes. Against this backdrop, we provide a perspective from Sri Lanka: a lower-middle-income country (LMIC) which records the highest prevalence of diabetes and pre-diabetes in south Asia. Our perspective will provide novel insights and innovative ideas into prevention and control of diabetes burden in LMICs, harnessing the potential of preventive dentistry.

The effects of global warming combined with the progressive expansion of urbanization have considerably increased exposure to urban flooding and runoff widespread erosion risk, also causing shallow landslides and mud flows, respectively in urbanized areas of lowland and hill/foothill environments. Increasing urban flooding resilience has become a priority at virtually all levels of governance. The analysis of a different hazard scenarios, in which various hydro-meteorological conditions and management alternatives are examined, should act as the basis for the effective design and evaluation of interventions to improve urban flooding resilience. Turin Metropolitan Area (TMA), located in north-western Italy, represents a unique case due to its complex orography, with a mountainous sector in the west side and a flat or hilly part in the east side. During the warm season, these environmental conditions make the urban area prone to severe atmospheric convection causing frequent hailstorms and rainstorms of high intensity that may impact on urban infrastructures (i.e., drainage system and road network), thus requiring an adequate management as a key factor to reducing risk and losses. The urban areas of TMA are monitored by polarimetric Doppler weather radars and by a dense rain gauges network. Analyzing several case studies of urban flooding, this research work assesses the feasibility of a meteorological radar early warning system based on the identification of rainfall thresholds that characterize urban flooding, occurring in the lowlands, and the runoff erosion phenomena affecting the urbanized hills and foothills.

Growth-preserving instrumentation techniques are utilized in early-onset scoliosis (EOS) cases requiring surgical intervention. Shilla technique corrects the deformity and may reduce the need for surgical treatment with its growth-directing effect. As with other techniques, various prob-lems can be encountered following the administration of the Shilla technique. The aim of this study was to examine the effect of complications encountered with Shilla treatment on correction and growth. Sixteen patients with a follow-up period of at least 1 year who received Shilla growth guidance for EOS were included in the study. No complications occurred in 50% cases and no unplanned surgery was required. Of the remaining 8 patients with postoperative im-plant-related complications (50%), 6 (37.5%) required unplanned surgery; this consequently caused implant failure in the proximal region in 5 cases (31.25%) and deep tissue infection around the implant in 1 case (6.25%). Deformity correction, spine length, and quality-of-life scores significantly improved in EOS through Shilla growth guidance. Although implant-related com-plications were observed and related unplanned surgeries were required with Shilla growth guidance in our patients, these complications did not have a significant negative effect on correc-tion and spine growth.

Children’s health, development and education cannot be handled separated; they form one process and are profoundly interrelated. This article considers how to ensure children’s physical and mental fitness for school and maintain it once they are there. Rwanda Is a case study of health and development issues which render children unreceptive to education. This is not news to Rwanda’s government, but until recently the donor community was not interested in supporting implementation. The story of Rwanda illustrates the need to think about changes of policy and practice in their context of structures and culture – how they interact and how they are facilitated or constrained by structures and by cultural understandings. To grasp what is going on and for successful implementation of policy, it is necessary to look at situations as a whole and consider human and governmental agency as real influences rather than just consequences of causal mechanisms.

After surgery, oral cavity healing occurs in a hostile environment and requires proper oral care and hygiene to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of chlorhexidine based (CHX) mouth rinse and a novel bone bioactive liquid (BBL) mouth rinse on oral healing within seven days application post-surgery. A randomized, double blind clinical trial conducted in 81 patients. The mouth rinses were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to measure pain index. Early wound healing score (EHI) was determined in evaluate the oral cavity healing progress. No adverse effects were observed using the mouth washes, but CHX resulted in teeth staining. CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS stating day 4. Relative to CHX group, the EHI scores were significantly higher in the BBL group, independent from the tooth location. No gender differences were observed in both VAS and EHI scores. Relative to the commercially available CHX, BBL mouth rinse reduced pain and accelerated oral cavity healing. Suggesting an improvements of oral cavity microenvironment at the wound site that mediates soft tissue regeneration.

Molecular autism research is evolving towards a biopsychosocial framework that is more informed by autistic experiences. In this context, research aims are moving away from correcting external autistic behaviors and towards alleviating internal distress. Autism Spectrum Conditions (ASCs) are associated with high rates of depression, suicidality and other comorbid psychopathologies, but this relationship is poorly understood. Here, we integrate emerging characterizations of internal autistic experiences within a molecular framework to yield insight into the prevalence of psychopathology in ASC. We demonstrate that descriptions of social camouflaging and autistic burnout resonate closely with the accepted definitions for early life stress (ELS) and chronic adolescent stress (CAS). We propose that social camouflaging could be considered a distinct form of CAS that contributes to allostatic overload, culminating in a pathophysiological state that is experienced as autistic burnout. Autistic burnout is thought to contribute to psychopathology via psychological and physiological mechanisms, but these remain largely unexplored by molecular researchers. Building on converging fields in molecular neuroscience, we discuss the substantial evidence implicating mitochondrial dysfunction in ASC to propose a novel role for mitochondrial allostatic load in the relationship between autism and psychopathology. An interplay between mitochondrial, neuroimmune and neuroendocrine signaling is increasingly implicated in stress-related psychopathologies, and these molecular players are also associated with neurodevelopmental, neurophysiological and neurochemical aspects of ASC etiology. Together, this suggests an increased exposure and underlying molecular susceptibility to ELS that increases the risk of psychopathology in ASC. This article describes an integrative framework shaped by autistic experiences that highlights novel avenues for molecular research into mechanisms that directly affect the quality of life and well-being of autistic individuals. Moreover, this framework emphasizes the need for increased access to diagnoses, accommodations, and resources to improve mental health outcomes in autism.

Seemingly normal tissues progressively become populated by mutant clones over time. Most of these clones bear mutations in well-known cancer genes but only rarely do they transform into cancer. This poses questions on what triggers cancer initiation and what implications somatic variation has for cancer early detection. We analysed recent mutational screens of healthy and cancer-free diseased tissues to compare somatic drivers and the causes of somatic variation across tissues. We then reviewed the mechanisms of clonal expansion and their relationships with age and diseases other than cancer. We finally discussed the relevance of somatic variation for cancer initiation and how it can help or hinder cancer detection and prevention. The extent of somatic variation is highly variable across tissues and depends on intrinsic features, such as tissue architecture and turnover, as well as the exposure to endogenous and exogenous insults. Most somatic mutations driving clone expansion are tissue-specific and inactivate tumour suppressor genes involved in chromatin modification and cell growth signalling. Some of these genes are more frequently mutated in normal tissues than cancer, indicating a context-dependent cancer promoting or protective role. Mutant clones can persist over a long time or disappear rapidly, suggesting that their fitness depends on the dynamic equilibrium with the environment. The disruption of this equilibrium is likely responsible for their transformation into malignant clones and knowing what triggers this process is key for cancer prevention and early detection. Somatic variation should be considered in liquid biopsy, where it may contribute cancer-independent mutations, and in the identification of cancer drivers, since not all mutated genes favouring clonal expansion also drive tumourigenesis. Somatic variation and the factors governing homeostasis of normal tissues should be taken into account when devising strategies for cancer prevention and early detection.

Along most of the European littoral, oysters were appreciated as a wholesome and palatable food since the Stone Age, yet were transported much further from their natural habitats when long-distance trade in marine foodstuffs began in medieval times. The brackish waters of the Baltic Sea are not considered a suitable environment for this mussel, and therefore all archaeological oyster shell finds are the result of import to the eastern Baltic. In this study, over 1000 shells found in different medieval and early modern archaeological contexts in Estonia were analysed and the obtained data recorded in a data repository. Some conclusions are set out, based on shell size and shape, and breakage traces, but more detailed taphonomic studies are left for the future. The study identifies the earliest imports of oysters recorded by archaeological material and written sources. Both show records not much earlier than the 16th century AD. Although no information is preserved about the exact origin of oysters imported to Estonia, the oyster beds most probably exploited are those in the central eastern North Sea, i.e. the Wadden Sea.

The presented research faces the problem of early detection of sepsis for patients in the Intensive Care Unit. The PhysioNet/Computing in Cardiology Challenge 2019 facilitated the development of automated, open-source algorithms for the early detection of sepsis from clinical data. A labeled clinical records dataset for training and verification of the algorithms was provided by the challenge organizers. However, a relatively small number of records with sepsis, supported by Sepsis-3 clinical criteria, led to highly unbalanced dataset (only 2% records with sepsis label). A high number of unbalanced data records is a great challenge for machine learning model training and is not suitable for training classical classifiers. To address these issues, a number of various models were investigated. A solution including feature selection and data balancing techniques was proposed in this paper. In addition, several performance metrics were investigated. Results show, that for successful prediction, a particular model having few or more predictors based on the length of stay in the Intensive Care Unit should be applied.

Glaucoma is a disease associated with retina of eye. Presently, millions of human being is suffering from this disease. Early detection of these diseases can save the people from blindness. Therefore, various methods have been developed for its detection. In this paper, we have studied the reported methods and summarized their performance in terms of accuracy of detection.

Purpose: Despite significant improvements in early detection of breast cancer, some patients still require mastectomy. One clinical problem currently being analyzed is the possibility of preserving the areola-nipple complex (NAC). The aim of this study was to evaluate the treatment results of breast cancer patients who underwent mastectomy with immediate breast reconstruction with sparing of the NAC. Methods: 335 patients who underwent mastectomy with breast reconstruction – with sparing (group I: 300 patients) or removal of NAC (group II: 35 patients), treated in the period 07.2014-06.2020. In the study groups, the length of overall survival (OS) and recurrence-free survival (RFS) were determined – up to 24 months after the end of treatment (short-term results) and up to 80 months (long-term results). The mean follow-up time of patients was 55.6 ± 19.7 months. Results: In 50 patients (14.9%), recurrence of neoplastic disease was observed (in group I: 14.7%, in group II: 17.1%; p=0.6972). It was most often a recurrence of cancer in the scar after mastectomy – in 25 patients (respectively: 7.7% vs 5.7%; p=0.6775) or distant metastases – in 16 patients (4.0% vs 11.4%; p=0.051). A total of 10 deaths were observed (6 – 2.0% vs 4 – 11.4%; p=0.0019). A total of 37 patients (10.7% vs 14.3%) required removal of their implant, mainly due to symptoms of infection – in 24 cases (7.3% vs 5.7%). Conclusion: Preserving the NAC is a safe therapeutic procedure in patients undergoing mastectomy with the option of reconstructive treatment. In both groups of patients, similar early and late treatment results were obtained.