Different severe energy crises episodes occurred in the world in the last five decades. Energy crises lead to deterioration of international relations, economic crises, changes in monetary systems and social problems in countries. This paper aims to show the essential determinants of energy crises by developing a binary logit model which estimates the predictive ability of thirteen indicators in a sample that covers the period from January 1973 to December 2022. The empirical results show that the energy crises are mainly due to energy supply-demand imbalances (petroleum stocks, fossil energy production-consumption imbalance and changes in energy imports by country groups), energy investments (oil and natural gas drilling activities), economic and financial disruptions (inflation, dollar index, index of global real economic activity) and geopolitical risks. Additionally, the model is capable of accurately predicting the world energy crisis event months with 99% probability.

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.

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.

Samarinda City is one of the most attractive cities in Borneo Island (Indonesia) and also as a capital city of EastBorneo Province. The expansion of urban areas becomes essential due to rapid population and housing demand. Base on the statistical report, the annual population growth rate is 0.018% from the year 2016-2017 with a total population of 843446 inhabitants. Many natural disasters occur in some areas in this city, especially flooding. This natural disaster occurs almost every year, many people suffered and forced to evacuate. In 2018 there is 3 flood event with 28311 people was suffered and evacuated, and 5170 houses were flooded [1]. During the flood event, it was very possible to gain damages to their property and make traffic stuck. One common way to reducing the damages is using Early Warning Systems (EWS). Early warning is a major element for disaster risk reduction, including damages. To prevent and mitigate the impact of a disaster, many countries had taken action to build various methods of a public warning system. An effective early warning system focused on people-centered and comprises the following element, such as risk knowledge, technical monitoring and service, communication and dissemination of warnings, and community response capability [2]. Related to the existing condition which Samarinda is a Muslim-dominated city and obviously has a lot of a number of mosques. This is a good potency to develop an early warning system because every mosque has a loudspeaker for echoing Adzan (Muslim prayer-calling). With this existing condition, the loudspeaker can be utilized as a flood outdoor-voice warning announcer. The aim of this study is to briefly introduce the strategy of dissemination early warning by utilizing mosques. The hope of early warning dissemination is giving enough time to the people to evacuate their property to reduce damages and possibly to giving information to avoiding traffic stuck (in a certain location)due to flooding. The results of this study can be used as input for decision-makers to develop effective flood management strategies and policies, especially in the case of an early warning system where not well-developed in Samarinda.

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

At the beginning of 2023 the Italian former prime minister, the former health minister and 17 others including the current president of Lombardy region, were placed under investigation on suspicion of aggravated culpable epidemic in connection with the government’s response at the start of the COVID-19 pandemic. The charges revolve around the failure by authorities to take adequate measures to prevent the spread of the virus in the Bergamo area, which experienced a significant excess of deaths during the initial outbreak. The aim of this paper is to analyse pandemic data of Italy and Lombardy region in the first 10 days of the pandemic, spanning from the 24th of February 2020 to the 4th of March 2020. The objective is to determine whether the use early warning indicators could have facilitated the identification of a critical increase in infections. This identification, in turn, would have enabled the timely formulation of strategies for pandemic containment, thereby reducing the number of deaths. In conclusion, to translate our findings into practical guidelines, we propose a low-cost early warning method for infectious respiratory diseases with asymptomatic carriers.

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.

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

Flood Early Warning Systems (FEWSs) using Machine Learning (ML) has gained worldwide popularity. However, determining the most efficient ML technique is still a bottleneck. We assessed FEWSs with three river states, No-alert, Pre-alert, and Alert for flooding, for lead times between 1 to 12 hours using the most common ML techniques, such as Multi-Layer Perceptron (MLP), Logistic Regression (LR), K-Nearest Neighbors (KNN), Naive Bayes (NB), and Random Forest (RF). The Tomebamba catchment in the tropical Andes of Ecuador was selected as case study. For all lead times, MLP models achieve the highest performance followed by LR, with f1-macro (log-loss) scores of 0.82 (0.09) and 0.46 (0.20) for the 1- and 12-hour cases, respectively. The ranking was highly variable for the remaining ML techniques. According to the g-mean, LR models correctly forecast and show more stability at all states, while the MLP models perform better in the Pre-alert and Alert states. Future efforts are recommended to enhance the input data representation and develop communication applications to boost the awareness of the society for floods.

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.

Currently, Korea is experiencing localized extreme rainfall, which accounts for more than 80% of flood-related disasters, and is increasing in small river basins, where more than 60% of flood-related casualties occur. These events are caused by climate change and geological factors and their impact is becoming more severe. As a result, an effective measurement system is required to mitigate their impact, particularly in small stream basins that are especially vulnerable due to their steep slopes, small catchment areas, and lack of maintenance and management capacity. In addition, a Flood Early Warning Framework (FEWF) that forecasts discharge and depth during flood events is crucial for reducing casualties. Therefore, this research is focused on developing the FEWF using the nomograph and rating curve methods, which are established by the robust constrained nonlinear equation solver and are suitable for small streams. The FEWF is evaluated using real-time data observed over 7-years period from the Closed-circuit Television-based Automatic Discharge Measurement Technology (CADMT), and the results show that the FEWF is effective in forecasting discharge and depth during flood events. The use of CADMT technology for real-time data can develop an accurate and reliable FEWF, which can help mitigate the impacts of extreme rainfall events and reduce the number of flood-related casualties in small stream basins.

Dengue fever remains one of the most significant public health challenges globally, particularly in tropical and subtropical regions. Traditional early warning systems (EWS) for dengue outbreaks, based on retrospective epidemiological data, suffer from delays and limited predictive accuracy. Modern systems, leveraging real-time data, artificial intelligence (AI), and machine learning (ML), improve accuracy but can be costly and difficult to implement in resource-constrained settings. This paper proposes a novel hybrid model that integrates the strengths of both traditional and modern EWS, with real-world examples from Brazil, and Malaysia. The hybrid model balances accuracy, scalability, and cost-effectiveness, making it a feasible option for low- and middle-income countries.

Extreme weather events, such as heat waves and heavy precipitation, are becoming increasingly frequent due to climate change, necessitating the development of effective early warning systems (EWS) to mitigate their impacts. This study introduces an advanced EWS designed specifically for Italy, which integrates the FourCastNet global forecasting model with Elevation-integrated TEmperature and Precipitation SRGAN downscaling (E-TEPS) to enhance the spatial resolution and accuracy of climate predictions. Building on previous work that demonstrated E-TEPS's effectiveness in downscaling temperature and total precipitation variables, this research applies the integrated system to two severe weather events in Central Italy: the Emilia-Romagna floods of 2023 and the Marche floods of 2022. The system's performance was evaluated using key metrics, including Mean Absolute Error (MAE), Root Mean Square Error (RMSE), and Pearson Correlation, by comparing downscaled outputs from FourCastNet and ERA5 datasets against high-resolution ground truth data from the Euro-Mediterranean Center on Climate Change (CMCC) dataset. The results indicate that the integrated system offers improved predictive accuracy, particularly in capturing critical climate variables, with the entire EWS delivering high-resolution forecasts and final outputs in under one minute. Although potential limitations were identified due to biases in the underlying datasets, which could affect forecast reliability in regions with complex topography or extreme weather conditions, this research highlights the potential of combining machine learning models with downscaling techniques to enhance EWS precision, providing valuable insights for future climate forecasting and disaster preparedness strategies.

Objective: This study aims to construct an early risk warning model to predict the risk of treatment failure in patients undergoing sequential High-Flow Nasal Cannula (HFNC) oxygen therapy following mechanical ventilation weaning. Methods: A retrospective analysis was conducted on clinical data from 145 patients who received HFNC treatment in the Emergency Intensive Care Unit of the Third People's Hospital of Bengbu City from June 2018 to June 2023. A wide range of indicators including general information, comorbidities, laboratory test results, vital signs, disease-related scores, and oxygenation data were collected. Data analysis was performed using R software, starting with the Lasso regression to filter features related to treatment outcomes. Patients were divided into a training set (70%) and a validation set (30%) using random grouping software. The Random Forest algorithm was then employed to evaluate and rank the important features related to outcome indicators. The predictive efficiency and stability of the model were assessed through the Receiver Operating Characteristic (ROC) curve, calibration curve, and decision curve analysis, culminating in the construction of an early risk warning nomogram. Results: The study found that the Random Forest model exhibited high predictive accuracy in the training set (AUC=0.98) and good stability in the validation set (AUC=0.84). Key feature variables identified by the model, such as APACHE II score, BNP, NLR, mROX, and SOFA, were found to significantly impact the prediction of HFNC treatment failure. Based on these variables, an early warning nomogram was further developed, providing clinicians with a convenient and effective risk assessment tool. Conclusion: This study has constructed an early risk warning model based on the Random Forest algorithm, capable of effectively predicting the risk of HFNC treatment failure. The model's high predictive efficiency and stability offer strong support for clinical decision-making, contributing to personalized treatment and improved patient outcomes. Future research should aim to expand the sample size, perform multicenter validation, and explore the integration of the model into Clinical Decision Support Systems for real-time risk assessment and intervention.

Pancreatic cancer (PC) is the most lethal type of cancer, it has the lowest 5-year survival rate among all other types of cancers. More than half of PC cases are diagnosed at an advanced stage due to PC’s insidious and non-specific symptoms. Surgery remains the most efficacious treatment option currently available, but only 10-20% of PC cases are resectable upon diagnosis. As of now, the sole biomarker approved by the United States Food and Drug Administration (US-FDA) for PC is carbohydrate antigen 19-9 (CA19-9); however, its use is limited use for early diagnosis. An in-creasing number of studies have investigated a combination of biomarkers. Lately, there has been considerable interest in the application of a liquid biopsy, including the utilization of microRNAs (miRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs). Screening for PC is indicated for high-risk patients; studies on new diagnostic models combined with biomarkers for early detection have also shown promising results for the ability of these models and biomarkers to aid clinicians in deciding on whether to start screening. This review seeks to provide a concise overview of the advancements in existing biomarkers and explore novel strategies for the early detection of PC.

Pancreatic cancer is the most lethal cancer, it has lowest 5-year survival rate among other types of cancers. More than half of pancreatic cancer are diagnosed at distant stage due to its insidious and non-specific symptoms. Surgery is the most effective treatment to date, but only 10-20% are resectable upon diagnosis. Currently, the only biomarker approved by the United States Food and Drug Administration (US-FDA) for pancreatic cancer is carbohydrate antigen 19-9 (CA19-9); however, it has limited use for early diagnosis. An increasing number of studies have a combination of biomarkers. Recently, the application for liquid biopsy has drawn a lot of attention, such as the use of microRNA (miRNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTC). Screening for pancreatic cancer is indicated for high-risk patients; studies of new diagnostic models combined with biomarkers for early detection also showed promising results to aid clinicians in deciding on whether to start screening. This review aims to summarize the progress on current biomarkers and new potential strategies for early detection of pancreatic cancer.

This is growing recognition of early onset gastrointestinal (GI) malignancies in young adults

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

Many countries have implemented free early childhood education to solve the affordability and accessibility problems without considering the sustainability of policy; thus, they have to discontinue the policy. The city of Nanjing, China, is no exception. This case study adopted a mixed-methods approach to understanding how and why the policy was formulated, implemented, and failed in the city, using the “policy cycle” framework. Altogether 232 kindergarten principals and teaching/research staff were randomly sampled and surveyed, and 5 kindergarten principals and 5 teaching/researcher staff were interviewed. The results indicated that there were many obstacles to the policy’s sustainability, including the conflict of interest, the inefficient policy implementation, the insufficient funding, and more social inequality issues. And the policymakers made mistakes in the five domains of the policy cycle: the context of influence, the context of policy text production, the context of practice, the context of outcomes, and the context of political strategy. Finally, the lessons for a more sustainable policy decision process are discussed.

A prospective longitudinal study of 54 patients who underwent intestinal anastomosis and were started on early enteral nutrition at the University Hospital of the Central University of Venezuela (November 2022 to September 2023), all of them fulfilled the inclusion criteria. Taking as early enteral nutrition two study groups: GROUP 1 tolerance at 24 hours and GROUP 2. Tolerance at 48 hours. Hospital stay and complications were evaluated. Of the 54 patients 40(74.1%) were operated on in emergency surgery 46(85.2%) patients were male. There was no difference in the mean ages of the two diet groups (P=0.254), the mean age was 33.9/14.8 years. There was no statistically significant difference (P=0.086) in the mean number of days of hospitalization (4.7/2.4 days) between patients according to the type of diet. Vomiting occurred in 20.37%, with no statistically significant differences between the groups of patients with diet 1 and 2. There were 2 (3.7%) cases of leakage that required reintervention, and this complication was not associated with the initiation of a particular type of diet, type of surgery, surgical time or site of injury. Early enteral nutrition is a viable option in patients undergoing intestinal anastomosis, is not associated with the incidence of dehiscence, is well tolerated by the patients, has acceptable complications, most frequently associated with vomiting, and reduces hospital stay.

Allergic diseases are becoming a major healthcare issue in many developed nations, where living environment and lifestyle are most predominantly distinct. Such differences include urbanized, industrialized living environments, overused hygiene products, antibiotics, stationary lifestyle, and fast-food based diets tend to reduce microbial diversity and lead to impared immune protection, which further increase the development of allergic diseases. In the same time, studies also showed that modulating microbiomes can ameliorate allergic symptoms. Therefore, in this paper, we aimed to review recent findings on the potential role of the human microbiome in the gastrointestinal tract, surface of skin and respiratory tract for the development of allergic diseases. Furthermore, we addressed a potential therapeutic or even preventive strategy for such allergic diseases by modulating the human microbial composition.

Landslides are natural disasters that normally cause misery over the Mount Elgon region, especially in Bududa district. A landslide early warning system was developed in collaboration with the community and this study investigated it’s effectiveness in disseminating warnings to the community. The data were collected from 82 respondents (mean age 43) and 4 focus group discussions (one per village). Majority of the respondents lost crops (35.9%); land (29.8%); lives and livestock (6.9%). The frequent occurrence of landslides is due to the changes in landuse patterns; settlement on steep slopes; and prolonged rainfall of low intensities. The study found that, 93.2% of respondents have ever received the warnings and alerts. 78.8% of those who received the warnings evacuated. The use of radios to disseminate warnings is the most efficient communication channel (44.4%) followed by using the clan members (19.5%). Only 40% of the women received the early warning through radios, an indicator that this channel puts women at a disadvantage. The main challenges regarding utilization of early warning system were: poor timing (29.9%); poor coordination (20.7%); and poor sensitization (18.4%). There is need to strengthen the community networks, and with continuous sensitization, the effectiveness of the landslides early warning will improve and this is expected to enhance the resilience of the community to landslides.

Physical literacy (PL) is increasingly recognised as essential to fostering lifelong physical activity (PA) engagement, particularly when nurtured in early childhood. However, there remains limited understanding of how key stakeholders in early years (EY) education perceive, value, and implement a PL informed approach. This exploratory study aimed to investigate a variety of EY stakeholders' knowledge and beliefs regarding PL and PA in relation to 3-5-year-olds. A concurrent mixed-methods approach was used, incorporating semi-structured expert interviews (n=11), focus groups (n=22), and a survey (n=210) to gather both qualitative and quantitative data. Thematic analysis was applied to identify key themes, and survey data was analysed to complement and triangulate qualitative findings. Findings revealed variation in stakeholders' awareness of PA recommendations, confusion over terminology, and the influence of environmental and policy constraints on practice. Stakeholders acknowledged the importance of PL but expressed uncertainty about the connection between academic theory and practical application. Resource limitations, conflicting priorities, and lack of training and policy support emerged as key barriers. Feedback on an educational PL-EY model was generally positive, emphasising its potential educational value while underscoring the need for clearer guidance and support. Given the pivotal role of EY education in shaping children’s behaviours, health, and well-being, this study highlights the necessity of a holistic approach to interventions, strong stakeholder involvement, and evidence-based practices to foster PL in EY children and raises critical questions about what effective interventions to develop PL in this age group should consider and look like.

Background: Oral hypoglycemic agents are typically the first-line treatment for type 2 diabetes mellitus (T2DM). This study examines the benefits of initiating insulin as the first-line therapy for newly diagnosed T2DM patients. Methods: A PubMed search using keywords ‘Type 2 Diabetes Mellitus’ and ‘Early STIIT’ included RCTs assessing beta cell function, insulin resistance, glycemic control, and lipid profiles. Revman 5.4.1 software was used for meta-analysis, with outcomes represented as mean difference (MD) and 95% confidence intervals (CI). Results: Significant reductions in fasting blood glucose (FBG: MD -4.75, 95% CI -7.07, -2.43), HbA1c (MD -1.84, 95% CI -3.01, -0.68), and postprandial glucose (PPG: MD -9.02, 95% CI -10.48, -7.56) were observed with early STIIT therapy compared to baseline. Beta cell function improved (HOMA-B: MD 53.70, 95% CI 27.78, 79.63) and insulin resistance decreased (HOMA-IR: MD -1.84, 95% CI -3.65, -0.04). Lipid profile improvements included reductions in total cholesterol (TC), triglycerides (TG), and LDL, with no change in HDL. BMI remained stable (MD -0.15, 95% CI -0.82, 0.51). Most patients achieved long-term remission and glycemic control without oral hypoglycemic agents. Conclusion: Early STIIT in newly diagnosed T2DM patients significantly reduces glycemic markers and maintains long-term glycemic control, preserving beta cell function. The therapy also improves lipid profiles, reducing TC, TG, and LDL. Initiating insulin as a first-line treatment shows promising results for glycemic control and overall metabolic health.

Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal’s health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in Bos indicus. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in Longissimus thoracis skeletal muscle of Bos indicus cattle. A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3’-5’-cyclic adenosine monophosphate (cAMP) signaling which present the upregulated adenylate cyclase 3 (ADCY3) gene and significatively hypomethylated in promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef.

Early marriage is a phenomenon that has an impact on various aspects of life which then affects human development. This study aims to conduct a literature review on the implications of early marriage on human development. The method used in this study is the SLR (Systematic Literature Review) method. Data collection was carried out by documenting all literature that met the research inclusion requirements. The literature obtained as many as 25 articles from the Google Scholer database with the help of Harzing's Publish or Perish application. From this literature study, it was found that the phenomenon of early marriage has implications for the human development index based on health indicators and life expectancy, education, and welfare. Another finding is that women are the most disadvantaged from the impact of early marriage. Things that can be done to deal with the phenomenon and impact of early marriage include formal and non-formal education, strengthening access to health and education services, creating empowerment programs, and strengthening regulations and legal protection.

Slow-roll inflation may simultaneously solve the horizon problem and generate a near scale-free fluctuation spectrum $P(k)$. These two processes are intimately connected via the initiation and duration of the inflationary phase. But a recent study based on the latest {\it Planck} release suggests that $P(k)$ has a hard cutoff, $k_{\rm min}\not=0$, inconsistent with this conventional picture. Here we demonstrate quantitatively that most---perhaps all---slow-roll inflationary models fail to accommodate this minimum cutoff. We show that the small parameter $\epsilon$ must be $\gtrsim 0.9$ throughout the inflationary period to comply with the data, seriously violating the slow-roll approximation. Models with such an $\epsilon$ predict extremely red spectral indices, at odds with the measured value. We also consider extensions to the basic picture (suggested by several earlier workers) by adding a kinetic-dominated or radiation-dominated phase preceding the slow-roll expansion. Our approach differs from previously published treatments principally because we require these modifications to---not only fit the measured fluctuation spectrum, but to simultaneously also---fix the horizon problem. We show, however, that even such measures preclude a joint resolution of the horizon problem and the missing correlations at large angles.

The recent measurement of a cutoff k_min in the fluctuation power spectrum P(k) of the cosmic microwave background may vitiate the possibility that slow-roll inflation can simultaneously solve the horizon problem and account for the formation of structure via the growth of quantum fluctuations in the inflaton field. Instead, we show that k_min may be interpreted more successfully in the R_h=ct cosmology, as the first mode exiting from the Planck scale into the semi-classical Universe shortly after the Big Bang. In so doing, we demonstrate that such a scenario completely avoids the well-known trans-Planckian problem plaguing standard inflationary cosmology, with some additional clues that may motivate further development of Kaluza-Klein cosmologies, string theories and supergravity.

Understanding the nature of the Dark Matter (DM) is one of the current challenges in modern astrophysics and cosmology. Knowing the properties of the DM particle would shed light on physics beyond the Standard Model and even provide us with details of the early Universe. In fact, the detection of such a relic would bring us information from the pre-Big Bang Nucleosynthesis (BBN) period, an epoch from which we have no data, and could even hint at inflationary physics. In this work, we assume that the expansion rate of the Universe after inflationary is governed by the kinetic energy of a scalar field ϕ, in the so-called “kination” model. We assume that the ϕ field decays into both radiation and DM particles, which we take to be Weakly Interacting Massive Particles (WIMPs). The present abundance of WIMPs is then fixed during the kination period through either a thermal “freeze-out” or “freeze-in” mechanism, or through a non-thermal process governed by the decay of ϕ. We explore the parameter space of this theory with the requirement that the present WIMP abundance provides the correct DM relic budget. Requiring that BBN occurs during the standard cosmological scenario sets a limit on the temperature at which the kination period ends. Using this limit and assuming the WIMP has a mass m_χ = 100 GeV, we obtain that the thermally-averaged WIMP annihilation cross section has to satisfy the constraints 3.5 × 10⁻¹⁶ GeV⁻² ≲ (σv) ≲ 1.4 × 10⁻⁵ GeV⁻² in order for having at least one of the production mechanism to yield the observed amount of DM. This result shows how the properties of the WIMP particle, if ever measured, can yield information on the pre-BBN content of the Universe.

Studies have shown that nearly half of rural toddlers in China have cognitive delays due to an absence of stimulating parenting practices, such as early childhood reading, during the critical first three years of life. However, few studies have examined the reasons behind these low levels of stimulating parenting, and no studies have sought to identify the factors that limit caregivers from providing effective early childhood reading practices (EECRP). This mixed-methods study investigates the perceptions, prevalence and correlates of EECRP in rural China, as well as associations with child cognitive development. We use quantitative survey results from 1,720 caregiver-child dyads across 100 rural villages/townships in northwestern China and field observation and interview data with 60 caregivers from these same sites. The quantitative results show significantly low rates of EECRP despite positive perceptions of early reading and positive associations between EECRP and cognitive development. Qualitative results suggest that low rates of EECRP in rural China are not due to the inability to access books, financial or time constraints, or the absence of aspirations. Rather, the low rate of book ownership and absence of reading to young children is driven by the insufficient and inaccurate knowledge of EECRP among caregivers, which leads to their delayed, misinformed reading decisions with their young children, ultimately contributing to developmental delays.

Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. 2) and NT-proBNP (<8500 vs. 8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. On multivariate analysis the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout the follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.

It is generally believed that the universe emerged from the Big Bang, before which space and time did not exist. However, Penrose proposed his theory of conformal cyclic cosmology, in which an aeon existed preceding this universe. Based on the cosmological principle, the universe is homogeneous and isotropic, expanding without center, but recently more and more deviations have been observed. By studying the fundamental particles and reactions of nature, we initiated a model that the Big Bang is the result of the collapse of a neutrino star within a black hole. We therefore re-analyze the cosmic microwave background (CMB) and find that the Center of the universe where the Big Bang occurred was at 0.66 ^+0.03 _-0.01 times the radius of the surface of last scattering away from the Local Supercluster (LS) and at Galactic coordinates (l, b) = (286^o +/- 10^o, -43^{o +7} _-6). If we look from the LS to the Center, the universe is spinning clockwise. Our findings are supported by Penrose’s conformal cyclic cosmology, low-variance circle sets in the CMB, and many other independent observational evidence of cosmic inhomogeneities, spatial anisotropies, and time variations.

We present a Quantum Space Model (QSM) of the evolution of the universe based on the theory that space consists of energy quanta from which it began. We used the Friedmann equations to trace its history and show that Dark Energy is the energy of space which caused its accelerating expansion.The universe started from a quanta of space which was triggered by quantum fluctuations that caused the Big Bang. It then expanded and cooled undergoing phase transitions to radiation, fundamental particles, and matter. Matter grew into galaxies, and was consolidated by gravity into Black Holes, ending in a Big Crunch and Deep Freeze inside a Black hole at 1.380 trillion years. Fluctuations caused a new Bang to start another cycle in its life. If the Law of Conservation of Energy is universal, then the cosmos is eternal. Our results support the theoretical predictions of a cyclic universe by Steinhardt and associates, as well as Penrose. Space and energy are equivalent as embodied in the Planck energy equation. They are the two most fundamental quantities that govern cosmic evolution. The two principal long range forces are the gravitational force and the space force,which maybe the fifth force in the universe. They provide the clockwork mechanism operating our cyclic universe.

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or programming fetal. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including Celiac Disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age at gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1-3%. It is not known what factors act to modify the risk of disease in genetically at risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD.

In a recent paper we had discussed possibility of DM at high redshifts forming primordial planets composed entirely of DM to be one of the reasons for not detecting DM (as the flux of ambient DM particles would be consequently reduced). In this paper we discuss the evolution of these DM objects as the universe expands. As universe expands there will be accretion of DM, Helium and Hydrogen layers (discussed in detail) on these objects. As they accumulate more and more mass, the layers get heated up leading to nuclear reactions which burn H and He when a critical thickness is reached. In the case of heavier masses of these DM objects, matter can be ejected explosively. It is found that the time scale of ejection is smaller than those from other compact objects like neutron stars (that lead to x-ray bursts). These flashes of energy could be a possible observational signature for these dense DM objects.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Epidemiological studies point cholesterol as a possible key factor for both prostate cancer incidence and progression. So, it could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis, remains unknown. Oncogene clonal induction in Drosophila melanogaster accessory gland allows to reproduce tumorigenesis from initiation to early progression, where tumour cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, high cholesterol diet displays limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport or metabolic response, impairs the formation of such tumors. Furthermore, in this context, high cholesterol diet suppresses this impairment. Taken together, these results reveal that during early tumorigenesis, tumour cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Altogether, these results suggest by which mechanism reduction of dietary cholesterol could lower the risk and slow down the progression of prostate cancer.

The question of whether the early visual cortex (EVC) is involved in visual mental imagery remains a topic of debate. In this paper, I propose that the inconsistency in findings can be explained by the unique challenges associated with investigating EVC activity during imagery. During perception, the EVC processes low-level features which means that activity is highly sensitive to variation in visual details. If the EVC has the same role during visual mental imagery, any change in the visual details of the mental image would lead to corresponding changes in EVC activity. Within this context, the question should not be whether EVC is ‘active’ during imagery but how its activity relates to specific imagery properties. Studies using methods that are sensitive to variation in low-level features reveal that imagery can recruit the EVC in similar ways as perception. However, not all mental images contain a high level of visual details. Therefore, I end by considering a more nuanced view which states that imagery can recruit the EVC, but that does not mean that it always does so.

The BKL singularity inside a rotating black hole would be a neutrino star. Once its mass exceeds the limit that neutrino degeneracy pressure could support (larger than 3×10²² M_⊙), the neutrino star singularity would collapse, raising the temperature to the maximum and dropping the entropy to the minimum to initiate a Big Bang. From the cosmic microwave background, we find where the Big Bang occurred at about 0.66 times the radius of the surface of last scattering away from us and at Galactic coordinates (l, b) ≃ (286°,-43°). As it expands, the clockwise spinning universe has been veering towards the ellipsoidal. These findings are consistent with independent observations of cosmic inhomogeneities, spatial anisotropies, and time variations.

Breeding early-maturing cultivars is one of the most important objectives for pear breeding. Very early-maturing pear provides an excellent parental material for crossing, while the immature embryo and low seed germination of its hybrid progenies often limit the selection and breeding of new early-maturing pear cultivars. In this study, we choose a very early maturing pear cultivar ‘Pearl Pear’ as study object, and investigate the effects of cold stratification, culture medium and seed coat on the germination and growth of early maturing pear seeds. Our results show that cold stratification (4℃) treatment could significantly improve the germination rates of early maturing pear seeds. A 100 days of low temperature pre-treatment and germination on White medium could increase the germination rate up to 84.54%. We also observe that seed coat removal could improve the germination activity of early maturing pear seeds, and middle seed coat removal (MSR) represents an optimal method with its high germination rate and low contamination. The results of our study established an improved protocol for seed germination of early-maturing pear seeds, which will greatly facilitate the breeding of new very early-maturing pear cultivars.

Lung cancer remains the leading cause of cancer-related death worldwide. The involvement of lymph nodes by the tumor has a strong impact on survival of patients. For this reason, lymphadenectomy plays a crucial role in the staging and prognosis of NSCLC, to define the most appropriate therapeutic strategies concerning the stage of the disease. To date, the benefit, in terms of survival, of the different extents of lymphadenectomy remains controversial in the scientific community. It is recognized that metastatic involvement of mediastinal lymph nodes in lung cancer is one of the most significant prognostic factors, in terms of survival, and it is therefore mandatory to identify patients with lymph node metastases who may benefit from adjuvant therapies, to prevent distant disease and local recurrences. The purpose of this review is to evaluate, the role of lymphadenectomy in early-stage NSCLC in terms of efficacy and accuracy, comparing systematic, sampling and lobe-specific lymph node dissection and analyzing the existing critical issue, through a search of the most relevant articles published in the last decades.

The AUC-ROC is a widespread measure to assess the performance of a binary classification model across various discrimination thresholds. Yet, it is not apt for unbalanced class problems and is misleading for early retrieval. For instance, link prediction in complex networks is an unbalanced early retrieval problem, whose goal is to offer a ranking of the nonobserved network links, prioritizing a small cohort of positive links (for which we are sure the labels are reliable) on top of a list largely populated by unlabeled links (for which the labels are uncertain). Differently from binary classification, here the evaluation focuses on how the predictor prioritizes the positive class, because the negative class does not exist and is replaced by an unlabeled class. For decades, scholars have been investigating the necessity to correct and to generalize the AUC-ROC to work for both unbalanced classification and early retrieval evaluation, this is requested in many applied domains of computational science. Here we propose the area under the magnified ROC (AUC-mROC), a new measure that adjusts the standard AUC-ROC to work for unbalanced early retrieval problems such as link prediction. Finally, we introduce the area under the generalized ROC (AUC-gROC), which unifies both AUC-mROC and AUC-ROC to provide a universal and reliable evaluation measure that can work for both classification and early retrieval problems, regardless of class proportion.This discovery represents a critical achievement, culminating in success after decades of contentious research. Its solution promises to significantly impact various domains within applied computational science.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Many children have suspected delayed language development and need extensive support from parents and the health care team. This study aimed to investigate suspected delayed language development and factors associated with suspected delayed language development among early childhood in Southern Thailand. Children aged 24 to 60 months were recruited as study samples using stratified random sampling conducted in 23 districts and simple randomized seven sections (425 children). Instruments comprised demographic data of the children and families, The preschool temperament questionnaire, and the Language Development Screening questionnaire using developmental surveillance and promotion manual. I was collecting data from July 2020 to January 2021. Data analysis used descriptive statistics and logistic regression. The results showed that 40.9 percent suspected delayed development. Daily screen time exceeding 2 hours per day (A.O.R. = 17.30, 95% CI: 7.35-40.72), and regarding a child's temperament, moderate-to-difficult temperament (A.O.R. = 9.56, 95% CI: 5.12-17.85) were significantly associated with a suspected delay of language development. The study suggested two-way communication and appropriate responses will help develop children's language.

Early detection improves prognosis in pancreatic ductal adenocarcinoma (PDAC) but is challenging as lesions are often small and poorly defined on contrast-enhanced computed tomography scans (CE-CT). Deep learning can facilitate PDAC diagnosis, however current models still fail to identify small (<2cm) lesions. In this study, state-of-the-art deep learning models were used to develop an automatic framework for PDAC detection, focusing on small lesions. Additionally, the impact of integrating surrounding anatomy was investigated. CE-CT scans from a cohort of 119 pathology-proven PDAC patients and a cohort of 123 patients without PDAC were used to train a nnUnet for automatic lesion detection and segmentation (nnUnet_T). Two additional nnUnets were trained to investigate the impact of anatomy integration: (1) segmenting the pancreas and tumor (nnUnet_TP), (2) segmenting the pancreas, tumor, and multiple surrounding anatomical structures (nnUnet_MS). An external, publicly available test set was used to compare the performance of the three networks. The nnUnet_MS achieved the best performance, with an area under the receiver operating characteristic curve of 0.91 for the whole test set and 0.88 for tumors <2cm, showing that state-of-the-art deep learning can detect small PDAC and benefits from anatomy information.

Background: The incidence of fracture and surgery of the hip and lower extremities is still high. Long postoperative bed rest has the potential to increase the incidence of various complications that may increase the morbidity and mortality rate of patients after hip and lower extremities surgery. Aim: This literature review aimed to identify the effects of early mobilization in hip and lower extremity postoperative. Method: Search for articles on several databases such as ProQuest, ScienceDirect, CINAHL, Medline, Wiley Online and Scopus, using the Boolean operator by combining several keywords according to the literature review topic, with inclusion criteria are published in the last 3 years (2019-2021), used a quantitative design, written in English and full text articles. A total of 435 articles were obtained, then screened and reviewed, so that there were 16 (sixteen) eligible articles.Result: There were 11 (eleven) effects of early mobilization, i.e. reducing length of stay, reducing the risk of deep vein thrombosis (DVT), reducing pulmonary infections (pneumonia), reducing urinary tract infections, reducing the risk of wound infection, improving extremity function and ability to walk, reducing postoperative pain, reducing the risk of pressure sores, reducing postoperative delirium, reducing readmission and lowering hospitalization costs. Conclusion: This literature review showed that early mobilization is safe and effective in postoperative patients to reduce the risk of complications and adverse events. Nurses and health workers who care for patients could implement early mobilization and motivate patients to be cooperative in undergoing early mobilization.

Traditional applications of Interferometric Synthetic Aperture Radar (InSAR) data involved inverting an interferogram stack to determine the average displacement velocity. While this approach has useful applications in continuously deforming regions, much information is lost by simply fitting a line through the time series. Thanks to regular acquisitions across most of the the world by the ESA Sentinel-1 satellite constellation, we are now in a position to explore opportunities for near-real time deformation monitoring. In this paper we present a simple statistical approach for detecting offsets and gradient changes in InSAR time series. Our key assumption is that 5 years of Sentinel-1 data is sufficient to calculate the population standard deviation of the detection variables. Our offset detector identifies statistically significant peaks in the first, second and third difference series. The gradient change detector identifies statistically significant movements in the second derivative series. We exploit the high spatial resolution of Sentinel-1 data and the spatial continuity of geophysical deformation signals to filter out false positive detections that arise due to signal noise. When combined with near-real time processing of InSAR data these detectors, particularly the gradient change, could be used to detect incipient ground deformation associated with geophysical phenomena, for example from landslides or volcanic eruptions.

Background and Aims: Screening and assessment of cognitive changes in adults with Intellectual Disabilities, mainly Down Syndrome (DS), is crucial to offer appropriate services to their needs. We present a systematic review of the existing instruments assessing dementia, aiming to support researchers and clinicians’ best practice. Methods: Searches were carried out in the databases Web of Science; PubMed; PsycINFO in March 2019 and updated in May 2020. Studies were selected and examined if they: (1) focused on assessing age-related cognitive changes in person with ID; (2) included adults and/or older adults; (3) included scales and batteries for cognitive assessment. Results: Forty-eight cross-sectional studies and twenty-six longitudinal studies were selected representing a total sample of 5,851 participants (4,089 DS and 1,801 with other ID). In those studies, we found 38 scales, questionnaires, and inventories, and 14 batteries for assessing cognitive and behavioural changes in adults with DS and other ID. Conclusion: The most used instrument completed by an informant or carer was the Dementia Questionnaire for Learning Disabilities (DLD), and its previous versions. We discuss the strengths and limitations of the instruments and outline recommendations for future use.

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Purpose/Objective: Frequent consumption of fermented carbohydrates and bottle feeding contribute to the development of early childhood caries (ECC). There are no substantial findings on the effects of breastfeeding patterns on oral health conditions in children in the United States. We aimed to assess the nexus between exclusive breastfeeding during the first 6 months and oral health disorders, namely toothache, decayed teeth, or unfilled cavities in early childhood. Materials and Methods: Design: Cross-sectional epidemiologic design of nationally representative data collected via telephone surveys in the United States was utilized. Setting: National Survey of Children’s Health, 2012 Participants: Population-based random sample of parents/guardians of 24,655 children aged 6 months to 5 years. Main Outcome and Measure: Parent-reported oral health condition including toothache, decayed teeth or unfilled cavity in the past 12 months. Results: A total of 2,392 (9.7%) children aged 6 months to 5 years experienced an oral health disorder, mainly toothache, decayed teeth, or unfilled cavity in the previous 12 months. Relative to non-Hispanic White children (7.7%), a greater proportion of non-Hispanic Black (12.9%) and multi-racial children (12.6%) experienced oral health disorders (OHD). In the univariable model, relative to children who never breastfed, those who were breastfed exclusively for 6 months were 28% less likely to present with OHD, Odds Ratio (OR) = 0.72, 95% CI, 0.52-0.98. After adjustment, the protective nature of exclusive breastfeeding against OHD did not remain, adjusted OR (aOR) =1.11, 99% CI 0.79-1.57. Children of mothers with fair/poor health were almost twice as likely to have poor OHD compared with children of mothers with excellent/very good health (aOR = 1.79, 99% CI 1.08-2.69). Conclusions and Relevance: Exclusive breastfeeding for the first six months of life improved pediatric OHD and remains mutually beneficial for mothers and children. These findings suggest the importance of exclusive breastfeeding and maternal health in relation to dental hygiene in children.

The young adolescents’ sexual behaviors are under-investigated. In this quantitative descriptive study, we examined the 2019 Middle School Youth Risk Behavior Survey data of 66,366 young adolescents ages 10-14 from 10 states to determine the prevalence of early sexual debut among young adolescents. Complex sampling design was used to produce descriptive statistics and cross-tabulations to describe young adolescents' sexual behaviors. Early sexual debut was reported at nearly 8%, and 4% of those reporting the age of first sex had their first sexual intercourse before 13 years. Compared to the Whites, Black/African Americans (13.2% vs 5.1%, OR=4.51, 95% CI: 2.78-7.31) and Hispanic young adolescents (8.3 % vs 5.1 %, OR=1.44, 95% CI=1.13-1,84) were more likely to report having early sexual intercourse. Males were more likely to report having multiple sexual partners than females (48.1% vs 36.5%, OR = 1.68, 95% CI = 1.22-2.29) and were more likely to report using condoms during the last sex compared to their female counterparts (59.7% vs 50.8%, OR = 1.43, 95% CI = 1.06-1.94). This study suggests the need for more research on young adolescents’ sexual behaviors and develop sexual health interventions that target preadolescence.

Adenomyosis, a benign gynecological condition characterized by the infiltration of endometrial tissue into the myometrium, poses significant challenges to women's reproductive health. Recently, the landscape of adenomyosis diagnosis transformed significantly, thanks to advancements in imaging technologies such as transvaginal ultrasound and magnetic resonance imaging. This lead to a noticeable shift in the demographic profile of patients diagnosed with adenomyosis, including younger women of reproductive age who frequently present with a diverse array of symptoms. Approximately 20% of women are affected by adenomyosis. Adenomyosis manifests with various subtypes, distinct epidemiological profiles, symptomatology, and treatment responses, necessitating tailored approaches for optimal management. Despite its clinical significance, adenomyosis remains understudied, resulting in a significant disparity in research and literature compared to other gynecological conditions. The severity of adenomyosis is compounded when coexisting with endometriosis, particularly deep infiltrating endometriosis (DIE), leading to exacerbated fertility issues and severe symptomatology. The wide range of symptoms, including adverse pregnancy outcomes such as pre-eclampsia, highlights its wider impact and emphasizes the need for increased awareness of the condition. Furthermore, Adenomyosis is frequently associated with treatment failure in endometriosis, contributing to dienogest resistance, elevated discontinuation rates, and persistent pain post endometriosis surgery. Additionally, the lack of specific treatments tailored to adenomyosis poses a considerable challenge in clinical management.

This critical review delves into the often-overlooked aspect of early childhood language development: the potential impact of exposure to foreign languages. While multilingualism is widely celebrated for its cognitive and cultural benefits, emerging research suggests that early exposure to foreign languages may pose challenges for young children's linguistic development. The review synthesizes findings from 17 studies to explore the complexities surrounding this issue, including linguistic confusion, language delay, reduced vocabulary growth, impaired language processing, and socio-emotional implications. Additionally, mitigating factors and future directions for research and intervention are discussed. By shedding light on this topic, the review aims to inform educators, parents, and policymakers about the nuances of bilingual language acquisition and the importance of providing tailored support to optimize early childhood language development in multilingual contexts.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early-stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early-stage NSCLC. Inclusion criteria prioritized but were not limited to, clinical trials and meta-analyses on surgical approaches to early-stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection have emerged as treatments for early-stage NSCLC. Ground-glass opacities (GGOs) hve shown prognostic significance, especially when analyzing the consolidation-tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusion: The management of early-stage NSCLC requires further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

Definitive surgical resection is the preferred treatment for early-stage non-small-cell lung cancer (NSCLC). Research into genetic alterations, including epidermal growth factor receptor (EGFR) mutation, in early stage NSCLC remains insufficient. Here, we investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutation and recurrence after complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resection at a single regional cancer center were recruited. We compared the clinical and pathological data between the recurrence and non-recurrence groups. Multivariate logistic regression was used to predict the risk factors for recurrence. Among the 659 enrolled cases, the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutation was 43% (194/451). Among them, L858R point mutation and exon 19 deletion was 52.3% and 42%, respectively. ALK rearrangement was found at 5.7% (26/453), and ROS1 fusion was found at 1.6% (7/441). The recurrence rate of the entire population was 19.7%. In multivariate analysis, the presence of EGFR mutation, stage II or III (vs. stage I), and pathologic subtype (presence of solid type) were associated with recurrence. Among the recurred group, 86.5% of the patients with EGFR mutation experienced distant recurrence compared to only 66.7% of wild-type (p = 0.016), with no significant difference in median disease-free survival (p = 0.983). In conclusion, the prevalence of EGFR mutation, ALK rearrangement, and ROS1 fusion was 43.0%, 5.7%, and 1.6%, respectively in patients with early-stage NSCLC who underwent curative resection. Along with stage II/III and solid pathologic subtype, EGFR mutation was an independent risk factor for recurrence. In the recurrence group, the rate of distant metastasis was higher in patients with EGFR mutation than in those with wild-type.

Objective: To analyze the clinical efficacy and safety of monotherapy and dual therapy in patients with early ischemic stroke. Methods: The study was conducted from August 2020 to August 2021, and 80 patients with early ischemic stroke who received treatment at our hospital during this period were selected as the study population. They were randomly divided into a control group and an observation group, with 40 patients in each group. The control group received conventional monotherapy, while the observation group received conventional dual therapy. The efficacy and safety indicators of the two groups were compared.Results: The treatment efficacy, functional recovery, blood indicators, and inflammation markers in the observation group were all superior to those in the control group (all, P<0.05); there was no significant difference in the drug safety profile between the two groups (P>0.05).Conclusion: The dual antiplatelet therapy is more ideal than monotherapy for treating patients with early ischemic stroke. It can further promote the recovery of neurological and cognitive function, improve hematological and inflammatory response indicators in patients, and the safety of this regimen is comparable to monotherapy.

The Süttő 21 site is a fissure fill of the freshwater limestone of the Gazda quarry in Süttő. The material was collected between 2017 and 2019, the results are summarised in this article, with a special focus on the small vertebrate fauna of the site and its stratigraphic and paleoecological significance. The fissure fill can be placed around the early/middle Pleistocene boundary (ca. 1.1 and 0.77 Ma). The paleoecological analysis of the herpeto- and mammal fauna of the sequence indicates the proximity of a permanent water body. The lower part of the sequence is dominated by open habitat indicator taxa indicating a cool, dry climate. Towards the upper part of the sequence, the climate remained cool but became wetter, and the vegetation gradually changed to forest-steppe/open forest. The fauna of the Süttő 21 site can be compared with the material of sites, which are of similar age, thus revealing taxonomic and paleoecological differences between different areas of the country. While a warm, dry climate and open vegetation can be reconstructed in the Villány Hills around the early/middle Pleistocene boundary, the northern Hungarian areas had a cooler, wetter climate, and slightly more closed (grove, forest-steppe) vegetation during this period.

Estimation of the potential consequences from events occurring downstream of a dam are part of the risk assessment needed during the installation phase of a new dam. In case of specific Natural or Man Made ongoing or prospected events, it may be also important to carry out fast computations that can provide information on the areas at risk either because the original design analyses are not available or because the parameters needed are different. This study is aimed to develop a procedure that strongly facilitates the preparation of the input deck and the derivation of the output quantities to allow a fast analysis of a dam break event using a shallow water model, NAMI DANCE, as the analysis tool.

Background: In healthy children, the frequency of anomalous persistence of primitive reflexes (PRs) and craniosacral blocks (CBs) are unknown, as well as their impact on neurodevelopment, behaviour disorders and related consequences. We aim to know the prevalence of anomalous PRs and CBs in apparently healthy children and its relationships with behavior and neurodevelopment anomalies. Methods: Participants (n=120) were evaluated through physical examination to detect PRs and CBs, an ad hoc parent survey to collect perinatal events, and children behavior assessment by teachers using Battelle score. Results: PRs were present in 89.5%. Moro (70.8%), cervical asymmetric (78.3%) and cervical symmetric PRs (67.5%) were the most frequent observed PRs. CBs were found in 83.2%, and the most frequent CBs were dura mater (77.5%) and sphenoid bone (70%) blocks. Moro, cervical asymmetric and cervical symmetric active primitive reflexes are significantly associated to cranial blocks of dura mater, parietal zones, and sphenoid bone sway. Gestational disorders or perinatal complications were associated to a higher frequency of PRs and CBs. The presence of PRs and CBs were associated with abnormal Battelle scores and neurobehavioral problems. Conclusion: Presence of PRs and CBs in children without diagnosed diseases are frequent and related with disturbances in childhood neurodevelopment.

This study aimed to investigate how transplanting date affects the agronomic and grain quality traits of two early maturing rice varieties. The experiment was conducted in the rice research field of Chungnam Agricultural Research and Extension Services, South Korea and rice materials were transplanted at intervals of approximately 15 days from April 16 to July 16 in 2019 and 2020. Results showed that agronomic and grain quality traits varied according to the transplanting date, and earlier transplanting resulted in the longer period of days from transplanting to heading (DTH). The spikelet number m-2 was highly correlated with the milled rice yield (r = 0.963** for Jinbuol, r = 0.909** for Yeoreumi) and it significantly decreased as the transplanting date was delayed, which was leading to lower yield. Environmental factors, the mean temperature during the grain filling stage, had a negative correlation with head rice rate (r2 = 0.825** for Jinbuol, r2 = 0.803** for Yeoreumi), and the number of days from transplanting to heading showed negative correlation with protein content (r2 = 0.777** for Jinbuol, r2 = 0.833** for Yeoreumi). Therefore, increasing the number of days from transplanting to heading date can lead to higher milled rice yield and lower protein content, and avoiding heading dates on July 17 can improve the appearance traits. As a results, it is suggested that early transplanting is advantageous to increase the milled rice yield and grain quality of early maturing rice.

In this paper, we have investigated the impact of an early learning assessment on students' motivation for improving their performance throughout the semester. An observation analysis was conducted on an entry level mechanical engineering course in which students are enrolled in during their first semester of engineering work. This study analyzes the effect that a first exam, with an average below a passing grade, has on student's outcome in the course. It was hypothesized that students were motivated to achieve their desired grade outcomes following inadequate performance on the first exam. This was investigated by diving into the results of the course and referencing initial performance to the remaining exam and assessment outcomes. Students were placed into grade bands ranging from 0 to 100 in 20% increments. Their results were tracked and it was shown that for the second mechanics exam, averages jumped 43.333%, 35.35%, and 30.055% for grade bands of 0 to 20, 20 to 40, and 40 to 60 respectively. Assessment grades increased as well with the remaining assessments being averaged to a score of 91.095%. Variables contributing to student performance came from both with-in and outside the classroom. Learning communities, material differentiation, and student and professor adaptation all contributed to the rise in performance. It was concluded that the internal and external variables acted in combination with one another to increase student dedication to achieve success.

Rangelands are a key resource present all over the world as it covers half of emerged lands. They are even more important in drylands, where they cover 48% of the total area. Intensification and the additional pressure added by climate change push these systems towards desertification. Over the last two decades, we have developed and applied System Dynamics (SD) models for the study of Mediterranean grasslands. In addition, we have developed procedures and analysis tools, such as global sensitivity analysis, stability analysis condition, or risk analysis, in order to detect the main drivers of these socio-ecological systems and provide indicators about their long-term sustainability. This paper reviews these works, their scientific background, and the most relevant conclusions, including purely technical and rangeland-related ones as well as our experience as systemic modelers in a world driven by field specialists.

The aim of the current study was to determine the relation between subclinical mastitis and rumination behavior registered with an online sensor system. According to the results of the general clinical examination of 650 milking cows, 10 cows with subclinical mastitis (SCM) and 10 clinical healthy cows (HG) were selected (without clinical signs of any diseases). Rumination behavior biomarkers were registered with RumiWatch noseband sensor (RWS; ITIN + HOCH GmbH, Fütterungstechnik, Liestal, Switzerland). Sensors were implanted on the first day after calving. Data from the RWS from 13th days before the diagnosis and 13 days after diagnosis of SCM were used to compare with HG data during the same period. The healthy cows were monitored during the same days as the SCM cows.

Although the presence of dark energy is well established from various observations, its true nature is still not well understood. The cosmological constant term seems to be the preferred candidate. In earlier work we had a constant cosmological constant term to limit the sizes of large-scale structures at lower redshifts. In this work, we extend this to large scale structures at higher redshifts. Here we invoke a time varying cosmological constant to set constraints on sizes of galaxies at high redshifts and see that they are consistent with their observed sizes. The time-varying cosmological constant also provides a possible solution to the puzzle of structure formation of large disk galaxies (like the Wolfe disk) observed at very early stages of the Universe. Future observations of galaxies at even higher redshifts could support our approach.

Significant challenges exist globally regarding literacy teaching and learning, particularly in poor socio-economic settings in countries of the Global South. In this paper we argue that to address these challenges, major features of how the brain works that are currently ignored in the educational literature should be taken into account. First, perception is an active process based in detection of errors in hierarchical predictions of sensory data and action outcomes. Reading is a particular case. Second, emotions play a key role in underlying cognitive functioning. Innate affective systems underlie and shape all brain functioning, including oral and written forms of language and sign. Third, there is not the fundamental difference between listening/speaking and reading/writing often alleged on the basis of evolutionary arguments. Both are socio-cultural practices driven and learnt by the communication imperative of the social brain. Fourth, like listening, reading is not a linear, bottom-up process. Both are non-linear contextually shaped psycho-social processes of understanding, shaped by current knowledge and cultural contexts and practices. Reductionist neuroscience studies which focus on decontextualized parts of reading cannot access all the relevant processes. An integrated view of brain function reflecting this non-linear nature implies that an ongoing focus on personal meaning and understanding provides positive conditions for all aspects of literacy learning. Assessment of literacy teaching at all its stages should include indicators that take into account these foundational features relating reading and writing to neuroscience.

Osteosarcoma is the most common subtype of primary bone cancers, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein-protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events such as MMP2 and MMP9 and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we could identify well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.

Background: Malignant pleural mesothelioma (MPM) is an atypical, belligerent tumor that matures into cancer in the pleura, a stratum of tissue bordering the lungs. Pleural mesothelioma is a common type of mesothelioma that accounts for about 75 percent of all mesothelioma diagnosed yearly in the United States. Diagnosis of mesothelioma takes several months and is expensive. Given the difficulty of diagnosing MPM, early identification is crucial for patient survival. Our study implements artificial intelligence and recommends the best fit model for early diagnosis and prognosis of MPM. Method: We retrospectively retrieved patient’s medical reports generated by Dicle University, Turkey and implemented multi-layered perceptron (MLP), voted perceptron (VP), Clojure classifier (CC), kernel logistic regression (KLR), stochastic gradient decent SGD), adaptive boosting (AdaBoost), Hoeffding tree (VFDT), and primal estimated sub-gradient solver for support vector machine (s-Pegasos). We evaluated the models, compared and tested using paired T-test (corrected) at 0.05 significance based on their respective classification accuracy, f-measure, precision, recall, root mean squared error, receivers characteristic curve (ROC), and precision-recall curve (PRC). Results: In phase-1 SGD, AdaBoost.M1, KLR, MLP, VFDT generates optimal results with the highest possible performance measures. In phase-2, AdaBoost with a classification accuracy of 71.29% outperformed all other algorithms. C-reactive protein, platelet count, duration of symptoms, gender, and pleural protein were found to be the most relevant predictors that can prognosticate mesothelioma. Conclusion: This study confirms that data obtained from biopsy and imagining tests are strong predictors of mesothelioma but are associated with high cost, however, can identify mesothelioma with optimal accuracy. Predictive analytics without using biopsy results can diagnose mesothelioma with acceptable accuracy. Implementation of phase-2 followed by phase-1 can address diagnosis expenses and maximize disease prognosis. Additionally, results indicate improved MPM diagnosis using AI methods dependent upon the specific application.

Background: This study aims to compare the impact of early and late post-discharge cardiopulmonary rehabilitation on the outcomes of intensive care unit (ICU) survivors. Methods: The retrospective, cohort study used a sub-database of the Taiwan National Health Insurance Research Database (NHIRD) that contains information of all patients had ICU admission between 2000 and 2012. Early group was defined if patients had received cardiopulmonary rehabilitation within 30 days after ICU discharge, and late group was define as if patients had received cardiopulmonary rehabilitation between 30 days and one year after ICU discharge. The end points were mortality and re-admission during the 3-year follow-up. Results: Among 2136 patients received cardiopulmonary rehabilitation after ICU discharge, 994 was classified early group and other 1142 patients were classified as late group. Overall, early group had a lower mortality rate (6.64% vs 10.86%, p = 0.0006), and a lower ICU readmission rate (47.8% vs 57.97%, p < 0.0001) than late group after 3-year follow-up. Kaplan-Meier analysis showed that early group had significantly lower mortality (p=0.0009) and readmission rate (p<0.0001) than late group. In multivariate analysis, the risk of ICU readmission was found to be independently associated with late group (HR, 1.28; 95% CI, 1.13-1.47). Conclusions: Early post-discharge cardiopulmonary rehabilitation among ICU survivors has the long-term survival benefit and significantly decreases the readmission rate.

While it is generally accepted that food habits established during infancy will track into later childhood, longitudinal analysis of children’s food preferences is rare. This paper examines whether maternal-reported child food preferences at five years of age are the same as that reported at two years; and identifies any patterns of change from two- to five- years. Mothers in the Australian NOURISH trial reported child food preferences at two and five years of age. A four point scale was utilised - ‘like’, ‘neither like or dislike’, ‘dislike’, ‘never tried’. The proportion of children having the same preference at the two time points was calculated (95%CI) for 48 foods (cereals, 4; vegetables, 20; fruit, 14; meat/alternatives, 6; dairy, 4). For foods where ≤50% children had consistent preferences, the pattern of food preference change was determined. For 40/48 foods, more than half of the children were reported to have the same preference at two years of age, and three years later, at age five. Foods for which ≤50% children had the same preference at both ages were high-sugar breakfast cereals, zucchini, mushrooms, eggplant, spinach, lettuce, cabbage and celery. Findings reinforce the importance of promoting a consistent message regarding early and frequent exposure to a variety of healthy foods, particularly during the first 2 years of life, as the preferences established in these early years are likely to be maintained over time.

Recent analyses of cosmic microwave background surveys have revealed hints that there may be a non-trivial running of the running of the spectral index. If future experiments were to confirm these hints, it would prove a powerful discriminator of inflationary models, ruling out simple single field models. We discuss how isocurvature perturbations in multi-field models can be invoked to generate large runnings in a non-standard hierarchy, and find that a minimal model capable of practically realising this would be a two-field model with a non-canonical kinetic structure. We also consider alternative scenarios such as variable speed of light models and canonical quantum gravity effects and their implications for runnings of the spectral index.

The survival rates of women with stage 0 or 1 breast cancer stands at almost 100% and around 93% for stage 2. As the disease advances with decreasing survival, the rate detoriates to 72% for stage 3 and about 22% for stage 4 (ACS, 2018). Undoubtedly, earlier presentation is synonymous with better prognosis and survival. In fact data indicates that early stage breast cancer diagnoses has 90% survival rate as compared to 27% for the advanced states (ACS, 2018). In this regard, governmental and non-governmental agencies are working tirelessly towards the realization of improved breast cancer care and survival through early presentation and detection. For instance, the Sustainable Development Goal (SDG) Target 3.4 seeks to reduce by one third, premature mortality from cancers and other non-communicable diseases through prevention and treatment. Clearly, early presentation, diagnoses and treatment will assist in the realization of the SDG target 3.4 goal. To achieve this, research must be focused on early presentation among women with breast cancer.. However, current studies have focused mainly on advanced breast cancer regarding treatment, symptoms experience (emotional and psychological), coping and support systems, and the reasons for delayed diagnoses and treatment. Objective In this review, it is argued that, rather than focusing on advanced breast cancer which has been adequately explored, the attention has to be on what measures or approaches promote early presentations among Ghanaian women. Methods The review included all primary studies that provided answers to the phenomenon of interest. It included both quantitative and qualitative studies. Search scope encompassed studies within the last ten years; thus from 2010 to 2020 irrespective of the country of study.Studies were included if: The paper is of a primary study; the study population included women with early BC or BC symptoms; the study outcome is the association between early stage breast cancer and earlier presentation; the study has a comprehensive data analysis protocol; the results of the studies are unique.A thorough literature search was conducted using the following electronic database: Google scholar and Pubmed. Google scholar alert on new studies was subscribed. This gave update on newly published papers for appraisal and possible inclusion.Manual identified of other potentially eligible publications by searching the reference lists of retrieved studies was also done. After a thorough search, this review included studies from several countries around the Globe such as Ireland, London, Turkey, Iran, Ghana, Kenya, Ethiopia etc Data Collection The title and or abstract of all retrieved papers were independently scanned through to establish which studies should be further evaluated. The full texts of these potential articles were then assessed. Extraction The Cochrane extraction form for data extraction was resorted to. From each eligible article, the following study identifiers/information were extracted: author(s), first author, year, title, objective, article type, location, setting, study design and method, sample size, instruments used, and results. Results Prompt help seekers mainly self-discovered their BC, and this occurred through accidental touch, after menstruation, through breastfeeding, during grooming, and while taking their bath.Notably, women who were termed prompt help seekers had higher seriousness perception of their symptoms. This was likened to their level of understanding and awareness, as well as periodic examination and comparison. Similarly, women who knew they were at risk for breast on account of family history, and increased incidence of BC in their localities, labeled their initial symptoms as requiring prompt attention.Following interpretation and labeling of symptoms, the participants generally resorted to symptom monitoring until the onset of additional and or intense symptoms. Though most women thought of benign growths, a few feared it could be malignant. These emotional reactions led the women to purposively seek clarification by selectively consulting others. Further, participants opened up to social acquaintances such as family relationships, people with prior experience of breast disease, and in some few instances health professionals. Some women also resorted to media items to better their understanding. Remarkably, prompt help seekers sort for help within one month. Last but not least, some women first communed with their creator after discovery and labeling based on their spiritual affiliations.Also, researchers should consider conducting surveys to assess the BC risks for specific smaller groups. This would help tailor specific educational interventions to promote earlier presentation and treatment among the vulnerable.

Cymbidium faberi Rolfe is one of the traditional Chinese orchids with important ornamental value, and the cultivation of Cymbidium faberi Rolfe mutant strains with different appearances is essential to increase its economic value, but at present, the acquisition of Cymbidium faberi Rolfe mutant strains basically relies on natural mutation.The objectives of this research were to mutagenize Cymbidium faberi Rolfe protocorm-like bodies (PLBs) and shoots in vitro using sodium azide (NaN3), and to screen and evaluate mutants in mutagenized Cymbidium faberi Rolfe seedlings using morphological characteristics.Cymbidium faberi Rolfe PLBs and shoots were used as mutagenic materials, and co-cultivated in induced shoots growth medium with the addition of 0.0 (control), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 mg/L and 0.0 (control), 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10.0 mg/L NaN3 to induce the mutations, and the mortality rates of the PLBs and shoots were increased with the increase of the NaN3 concentration.At 14 d of co-cultivation, PLBs and shoots were most efficiently mutagenized with 1.5 mg/L and 4.0 mg/L NaN3, respectively.After the explants were cultured for 3 months, changes in leaf and flower morphology were observed in some mutants: shorter and thicker leaves, shorter node length, reduced height, and mid-translucent leaves compared with controls; and some Cymbidium faberi Rolfe bloomed prematurely, with single flowers with large, thick petal sepals and small inflorescences, and colours include light green throughout, and a few with purple stamens.This suggests that NaN3 can effectively mutagenise Cymbidium faberi Rolfe PLBs and shoots to satisfy people's demand for Cymbidium faberi Rolfe's ornamental properties while increasing its economic value.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. The study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had a significantly higher cytoplasmic E-cadherin score (P=0.043), they were significantly less differentiated (P=0.007), more advanced (P=0.005), and predominately affected right colon (P=0.030) in comparison to non-mucinous tumors. Epithelial tumors were significantly better differentiated (P=0.034) and with less prominent tumor budding (P < 0.001) than mesenchymal tumors. The process of EMT appears to be more prominent in tumors of younger patients regardless of mucinous histology. EMT status may represent a useful prognostic tool in early-onset CRC.

Early and accurate mapping of winter canola planting areas provides critical support for sustainable cropland management. Although some methods have been proposed to map the winter canola at the flowering or later stage, mapping winter canola planting areas at the early stage is still challenging, due to the insufficient understanding of the multi-source remote sensing features sensitive for winter canola mapping. This study proposed an early-stage winter canola area mapping method by using the combination of optical and synthetic aperture radar (SAR) data. We analyzed the spectral features, backscatter coefficients, and textural features of winter canola based on Sentinel-2 and Sentinel-1 images. Random forest (RF) and Support Vector Machine (SVM) classification models were built to map winter canola based on early-stage images and field samples in 2017 and then apply the best model to corresponding satellite data in 2018-2022. Results showed that: (1) The red edge and near-infrared-related spectral features were most important for the mapping of early-stage winter canola, followed by VV, DVI and GOSAVI, which also showed greater differences than the other features; (2) Based on Sentinel-1 and Sentinel-2 data, winter canola could be earliest mapped around 130 days prior to ripening (i.e., early overwinter stage) with the F-score over 0.85 and the OA over 81%; (3) Adding Sentinel-1 could improve the OA by about 2%-4% and the F-score by about 1% -2% in winter canola mapping. (4) The F-score of winter canola mapping based on the classifier transfer approach in 2018-2022 varied between 0.75 and 0.97, and the OA ranged from 79% to 86%. This study demonstrates the potential of early-stage winter canola mapping using the combination of Sentinel-2 and Sentinel-1 images, which could provide valuable and timely information for stakeholders and decision makers.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Introduction: Physiotherapy exercises administered to preterm infants in the NICU can enhance motor skills and expedite the discharge process for infants born before 30 weeks of gestational age. The research delves into the influence of physiotherapy programs on these preterm infants' activity and participation levels. Methods: The intervention group received a one-month physiotherapy program including massage around the mouth, mobilization and weight-bearing exercises, and massage therapy for the extremities, while the control group did not. The motor skills were evaluated by the Test of Infant Motor Performance (TIMP), Dubowitz Neurological examination, and Preterm Oral Feeding Readiness Scales (POFRAS). Results: There was a significant difference in The TIMP, Dubowitz Optimal Score, Type of Non-Invasive Ventilation, TIMP Range, and POFRAS scores in the physiotherapy group rather than the control group (p<0.05). There were no differences in the length of stay in the NICU, respiration rate, heart rate, body temperature, oxygen saturation, body weight on the evaluation day, body weight at discharge, head circumference at discharge between the groups (p>0.05) Discussion: We conclude that physiotherapy in NICU improves the motor outcomes, activity and participation in preterm infants rather than the body functions and structure like vital signs and infants’ body weight.

Lung cancer remains the leading cause of cancer-related mortality worldwide. The main issue is the absence of a screening test available in clinical practice; the identification of non-invasive biomarkers is thus an urgent clinical necessity. Currently, low-dose computed tomography (LD-CT) demonstrates a 20% reduction of lung cancer mortality. However, it is not particularly suitable for clinical practice because of the costs, radiation, and the false positive rate. Several studies have therefore focused on research into biomarkers in body fluids. Despite the power of certain molecules to distinguish lung cancer patients from healthy subjects, no biomarker has yet been shown to significantly and reliably influence clinical decisions or to be translated from the laboratory to clinical practice. We performed an overview of the peer-reviewed biomedical literature published in the last 10 years on the research regarding biomarkers for the early diagnosis of lung cancer via a comprehensive analysis of the reviews published this past year. Our main aim was to bring to light the limitations and strengths of the research already conducted. Furthermore, future prospectives have been explored, bearing in mind the management of clinical trials and their integration into clinical practice.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR=11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycemia. Plant-based therapies are characterized by low bioavailability in ocular tissues. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR, were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Fundus of retinal arterioles, retina histopathology and lens transmission electron microscopy (TEM), were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fiber disorganization. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately edematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA formation and increased antioxidant capacity. Retinal edema and disorganization in lens fibers were still present.

Purpose: This study evaluates the performance of the Early Intervention Physiotherapist Framework (EIPF) for injured workers. This study provides a proper follow-up period (3 years) to examine the impacts of the EIPF program on injury outcomes such as return to work (RTW) and time to RTW. This study also identifies the factors influencing the outcomes. Methods: The study was conducted on data collected from compensation claims of people who were injured at work in Victoria, Australia. Injured workers who commenced their compensation claims after the first of January 2010 and had their initial physiotherapy consultation after the first of August 2014 are included. To conduct the comparison, we divided the injured workers into two groups: physiotherapy services provided by EIPF-trained physiotherapists (EP) and regular physiotherapists (RP) over the three-year intervention period. We used three different statistical analysis methods to evaluate the performance of the EIPF program. We used descriptive statistics to compare two groups based on physiotherapy services and injury outcomes. We also completed survival analysis using Kaplan-Meier curves in terms of time to RTW. We developed univariate and multivariate regression models to investigate whether the difference in outcomes achieved after adjusting for significantly associated variables. Results: The results showed that physiotherapists in the EP group on average dealt with more claims (over twice as many) than those in the RP group. Time to RTW for the injured workers treated by the EP group was significantly lower than for those who were treated by the RP group, indicated by descriptive, survival and regression analyses. Earlier intervention by physiotherapists led to earlier RTW. Conclusion: This evaluation showed that the EIPF program achieved successful injury outcomes three years after implementation. Motivating physiotherapists to intervene earlier in the recovery process of injured workers by initial consultation helps to improve injury outcomes.

Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between April 1, 2013, and March 31, 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angi-ography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, P = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.

It has been suggested that primordial planets could have formed in the early Universe and the missing baryons in the Universe could be explained by primordial free-floating planets of solid hydrogen. Many such planets were recently discovered around the old and metal poor stars and such planets could have formed at early epochs. Another possibility for missing baryons in the Universe could be that these baryons are admixed with DM particles inside the primordial planets. Here we discuss the possibility of admixture of baryons to the DM primordial planets discussed earlier. We consider gravitationally bound DM objects with the DM particles constituting them varying in mass from 20 to100GeV. Different fractions of DM particles mixed with baryonic matter in forming the primordial planets are discussed. For the different mass range of DM particles forming DM planets, we have estimated the radius and density of these planets with different fractions of DM and baryonic particles. It is found that for heavier mass DM particles with the admixture of certain fractions of baryonic particles, the mass of the planet increases and can reach or even substantially exceed Jupiter-mass. The energy released during the process of merger of such primordial planets is discussed. Also the energy required for the tidal breakup of such an object in the vicinity of a black hole is also discussed.

Epigenetic alterations are heritable and enduring modifications in gene expression that play a pivotal role in immune evasion. These include alterations to noncoding RNA, DNA methylation, and histone modifications. DNA methylation plays a crucial role in normal cell growth and development but alterations in methylation patterns such as hypermethylation or hypomethylation can enable tumor and viral cells to evade host immune responses. Histone modifications can also inhibit immune responses by promoting the expression of genes involved in suppressing normal immune function. In the case of T-cell lymphoma, adult T-cell Lymphomas (ALT) also undergo immune evasion through the exceptional function of its accessory and regulatory genes. Epigenetic therapies are emerging as a promising adjunct to traditional immunotherapy and chemotherapy regimens. Clinical trials are currently investigating the use of epigenetic therapies in combination with immunotherapies and chemotherapies for more effective treatment of ATL and other cancers. This review highlights epigenetic alterations that are widely found in T cell malignancies.

Antibiotic therapy is a cornerstone of modern medicine, yet the development of antibiotic re-sistance threatens to render these therapies ineffective. The gut microbiota, a complex ecosystem of microorganisms residing in the gastrointestinal tract, plays a critical role in modulating anti-biotic efficacy and resistance. This review delves into the intricate relationship between gut mi-crobiota, antibiotic therapy, and resistance, and discusses the potential applications of gut mi-crobiota research in guiding personalized antibiotic therapy and resistance mitigation strategies. Recent advancements in metagenomics, metatranscriptomics, and metabolomics have demon-strated the potential for tailored antibiotic regimens that minimize collateral damage to com-mensal bacteria and reduce the risk of resistance. Adjuvant therapies such as probiotics, prebi-otics, and synbiotics have shown promise in restoring gut microbial balance and mitigating the adverse effects of antibiotic therapy. We address the challenges associated with this emerging field including the need for standardized methodologies, ethical considerations, and interdisci-plinary collaboration. With continued interdisciplinary collaboration and the implementation of standardized methodologies, gut microbiota research can contribute to the global fight against antibiotic resistance and improve patient outcomes.

The application of movement-detection sensors is crucial for understanding surface movement and tectonic activities. The development of modern sensors has been instrumental in earthquake monitoring, prediction, early warning, emergency commanding and communication, search and rescue, and life detection. There are numerous sensors currently being utilized in earthquake engineering and science. It is essential to review their mechanisms and working principles thoroughly. Hence, we have attempted to review the development and application of these sensors by classifying them based on the timeline of earthquakes, physical or chemical mechanisms of sensors, and location of sensor platforms. In this study, we analyzed all available sensor platforms that have been widely used in recent years, with satellites and UAVs being among the most used. The findings of our study will be useful for future earthquake response and relief efforts, as well as research aimed at reducing earthquake disaster risks.

Background: Implant surface topography is a key element in achieving osseointegration. Nanostructured surfaces have shown promising results in accelerating and improving bone healing around dental implants. The main objective of the present clinical and histological study is to compare, at 4 and 6 weeks, (w) bone-to-implant contact in implants having either machined surface (MAC), SLA medium roughness surface or a Nanostructured Calcium-Incorporated sur-face (XPEED®). Methods: 35 mini-implants with 3 different surface treatments (XPEED® (n=16) – SLA (n=13) – Machined (n=6), were placed in the posterior maxilla of 11 patients then, retrieved at either 4 or 6w in a randomized split-mouth study design. Results: The BIC rate measured at 4 and 6w respectively, was: 16.8 % (±5.0) and 29.0 % (±3.1) for MAC surface; 18.5 % (±2.3) and 33.7 % (±3.3) for SLA surface; 22.4 % (±1.3) and 38.6 % (±3.2) for XPEED® surface. In all types of in-vestigated surfaces, the time factor appeared to significantly increase the BIC rate (p < .05). XPEED® surface showed a significantly higher values when compared to both SLA and MAC values at 4w (p < .05). Also, at 6w, both roughened surfaces (SLA and XPEED® ) showed signifi-cantly higher values (p < .05) than turned surface (MAC). Conclusion: Nanostructured Calcium titanate coating is able to enhance bone deposition around implants at early healing stages.

Early diagnosis of malaria and treatment seeking behavior play key role in controlling and preventing further complication related to malaria disease. Aim of this study was to determine the responses on early malaria diagnosis and treatment seeking behavior among outpatient clients attending at Sekou toure regional referral hospital in Mwanza, Tanzania. Methods: A cross-sectional study was conducted among outpatient client at Sekou-Touré regional referral hospital, convenient simple random sampling used and self-administered questionnaire were used to collect data and data was entered into Microsoft excel and then exported to SPSS version 25.0 for further analysis and presented on the percentages and table. The analysis of strength of relationships between categorical variables was conducted using the Chi-square test. A p-value of ≤ 0.05 was considered to be statistically significant. Results: A total of 192 respondents completed the study with a response rate of 97.6%. The study revealed that Most of the respondents about 90.6% stated they would seek treatment from health facility when symptoms appear. However, only 6.3% seek treatment within 24 hours of onset of illness (p= 0.017). Half of respondents (50.5%) experienced malaria symptoms in the past six months and only 30% seek for treatment at health facility. Preference of health facility, (51%) respondents were going direct to pharmacy to buy medicine for self-treatment. Overall, cost of service, time consumed and distance of health facility especially health center shows significant with such delay. Conclusion: A low proportion of malaria-suspected patients sought treatment within 24 h of fever onset compared to the national target. Distance from the health facility, cost of service and time consumed were found to be predictors of early treatment-seeking behavior for malaria. Strengthening strategies tailored to increasing awareness for communities about malaria, importance of going hospital and early treatment-seeking behavior is essential.

The incidence and prevalence of food allergy (FA) are increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants particularly in those at high or low risk of atopy are still unclear. This 1-year study evaluated the safety of early introduction of single foods (milk, egg, or peanut), vs. two foods (milk/egg, egg/peanut, milk/peanut), vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/fish/soy at low, medium, or high doses) vs no early introduction in infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity with standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixture was 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least 6 months of age. Results demonstrate that infants at either high or low risk for atopy were able to tolerate early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that early introduction of foods, particularly simultaneous mixtures of many allergenic foods is efficacious for preventing FA and can occur safely.

Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm was stably reduced at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated Odds Ratios (95% Confidence Intervals) for Disease Free Survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with ORs approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) forDFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.

Background: Early-stage interventions in a potential pandemic are important tounderstand as they can make the difference between runaway exponential growththat is hard to turn back and stopping the spread before it gets that far. COVID-19 is an interesting case study because there have been very different outcomesin different localities. These variations are best studied after the fact if precisionis the goal; while a pandemic is still unfolding less precise analysis is of value inattempting to guide localities in the early stages to learn lessons of those that pre-ceded them. Methods: I examine three factors that could differentiate strategy: asymptomaticspread, differences in use of the Bacillus Calmette-Guerin (BCG) tuberculosis vac-cine and cloth face masks.Results:Differences in disease progression as well as the possibility of alternativestrategies to prevent COVID-19 from entering the runaway phase or damping itdown later can be elucidated by a study of asymptomatic infection. A study todemonstrate not only what fraction are asymptomatic but how contagious they arewill also inform policy on universal mask wearing. Conclusions: While a COVID-19 outbreak is at a level that makes accurate trace-and test possible, investigation of asymptomatic transmission is viable and shouldbe attempted to enhance understanding of spread and variability in the disease aswell as policy options for slowing the spread.

Antecedents. EFs (EFs) are the basis for establishing a goal and working towards that goal by coordinating thoughts and actions. EFs are fundamental to several aspects of daily life, specifically for academic performance. Aim. To analyze and compare the development of EFs in the transition period between the first and second cycles of Early Childhood Education. Methodology. Non-experimental methodology, ex post facto design, descriptive, cross-sectional evolution study. Participants. Preschoolers of different educational levels (first and second cycle of Infant Education). In this study the participants have been evaluated by different informants: 54.42% by parents and 45.58% by teachers. In relation to gender, 52.65% were male and 47.35% were female. In relation to age, 37.54% had a range of 2-3 years and 62.46% had a range of 4-5 years. Measurement. Instrument development of EFs were evaluated using BRIEF-P by key informants. Results. Preschoolers in the first cycle show significantly higher scores than preschoolers in the second cycle in BRIEP-P. Conclusions. The development of EF is key in these first key moments, having a special impact on later development and academic performance. It is necessary to work on EFs from the first cycle of Early Childhood Education, considering the evolutionary development of EFs.

This study investigates the impact of AI-generated contexts on preservice teachers' computational thinking (CT) skills and their acceptance of educational robotics. This article presents a methodology for teaching robotics based on AI-generated contexts aimed at enhancing CT. An experience was conducted with 122 undergraduate students enrolled in an Early Childhood Education program, aged 18-19 years, who were training in a Computer Science and Digital Competence course. The experimental group utilized a methodology involving AI-generated practical assignments designed by their lecturers to learn educational robotics, while the control group engaged with traditional teaching methods. The research addressed five key questions: the effectiveness of AI-generated contexts in improving CT skills, the specific domains of CT that showed significant improvement, the perception of student teachers regarding their ability to teach with educational robots, the enhancement of perceived knowledge about educational robots, and the overall impact of these methodologies on teaching practices. Findings revealed that the experimental group exhibited higher engagement and understanding of CT concepts, with notable improvements in problem-solving and algorithmic thinking. Participants in the AI-generated context group reported increased confidence in their ability to teach with educational robots and a more positive attitude towards technology integration in education. The results underscore the importance of context and support in fostering both confidence and acceptance of educational technologies among future educators. This research contributes to the growing body of literature at the intersection of AI, robotics, and education, advocating for the integration of AI and robotics into teacher training curricula. Future research should explore the long-term effects of these methodologies on CT skills and teaching practices across diverse educational settings.

Transcriptomes from stem-inoculated Scots pine saplings were analyzed to identify unique and enriched H. annosum transcripts in the early stages of infection. Comparing different time points since inoculation identified 131 differentially expressed H. annosum gene with p values ≤ 0.01. Our research supports the results of previous studies on the Norway spruce – Heterobasidion annosum s.l. pathosystem, indicating the role of carbohydrate- and lignin degradation genes in pathogenesis at different timepoints post inoculation and the role of lipid metabolism genes (including but not limited to the delta-12 fatty acid desaturase gene previously reported to be an important factor). The results of this study indicate that malic enzyme could be a potential gene of interest in the context of H. annosum virulence.

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. This study investigates whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted at the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant group based on the bacteria’s susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from peak to end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 hours (p = 0.0057); and 0%, 29 vs. 54 hours (p = 0.0475). Conclusions: In septic shock with bacteraemia, faster catecholamine dose reduction indicates bacterial susceptibility to initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of appropriate initial empiric therapy.

Phytophthora cinnamomi is a devastating soil-borne plant pathogen. The primary source of P. cinnamomi infection is the soil, where the pathogen can persist for long periods. Effective prevention and management of this pathogen in tree crops require an early and reliable detection method. In this study, we develop a simple, fast, reliable, and sensitive method based on real-time quantitative PCR (qPCR) for P. cinnamomi detection and quantification directly in plant or soil samples. Primers were developed targeting the nuclear single-copy ras-related protein gene Ypt1, suitable for Phytophthora-specific PCR. The specificity of the assay was confirmed by testing it against genomic DNA from 50 isolates across 8 different Phytophthora clades, including very similar P. parvispora. The efficiency and reliability of the qPCR protocol were evaluated on challenging environmental samples, such as plant tissue of different host trees (walnut, chestnut, oak) and naturally infected soils in walnut orchards. The main outcome was the development of a qPCR method for the specific identification and quantification of P. cinnamomi in natural soil samples. Additionally, this study established a systematic and repeatable soil sampling method and developed an efficient soil DNA extraction technique to apply the developed qPCR in naturally infested soils of walnut orchards.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a single stranded RNA virus which has resulted in the Coronavirus Disease 2019 (COVID-19) pandemic and has infected millions of people all over the world. SARS-CoV-2 has been mutating rapidly resulting in the emergence of multiple variants to escape the host immune system mainly by mutations in its receptor binding domain (RBD) of the spike protein. This rapid evolution of the SARS-CoV-2 posed a great challenge regarding the efficacy and effectiveness of the current SARS-CoV-2 vaccines. The RBD and full-length spike of SARS-CoV-2 is the main target of the neutralizing antibodies. Many SARS-CoV-2 variants are considered to have the potential to escape from the host immune system. In this study, the RBD of Alpha, Beta, Gamma, Kappa and Omicron and the full-length spike of BA.1, BA.2, BA.3, BA.4/5, BQ.1.1 and XBB.1.5 Omicron variants were used as coating antigens in Enzyme Linked Immuno-Sorbent Assay (ELISA) to check the neutralization capability of COVID-19 convalescent sera from patients of first wave of infection occurring in Wuhan. Our results show that the currently circulating Omicron BQ.1.1, XBB.1.5 and previous Omicron BA.1, BA.2 and BA.4/5 do not show significant reduction in neutralization, while Omicron BA.3 and previous variants Alpha, Beta, Gamma, Kappa, and Omicron showed a significantly reduced neutralization when compared to the wild-type Wuhan strain. These results indicate patients recovering from natural infection of early original Wuhan strain may have the potential to resist infection of current circulating variants and the vaccines using the prototype antigen may still working for newly emerged variants.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

Aim: This analytical cross-sectional study aimed to examine whether there is a correlation between tumor differentiation and certain biomarkers in patients with hepatocellular carcinoma (HCC). Methods: Poorly differentiated (n=443), moderately differentiated (n=379), and well-differentiated (n=272) tumors were separated from the research population, along with a control group (n=364). Biopsies were used to establish the presence of HCC, and biomarker levels were analyzed using chemiluminescence immunoassays in both infected and uninfected individuals. Results: The correlation between age and tumor size was shown to be statistically significant (p0.05) across all subgroups using both descriptive and inferential statistics. Patients with hepatitis C virus and non-A, non-B hepatitis had more advanced tumors than those with other types of poorly differentiated liver cancer. Similarly, individuals with HBsAg and moderate differentiation had bigger tumors, although there was no correlation between hepatitis C and non-A, non-B. Patients with HBsAg or hepatitis C had bigger tumors in the well-differentiated group, albeit the hepatitis C connection was not statistically significant. In addition, the study stressed that tumor size increases with age and that farmers were the most commonly diagnosed profession category. Conclusions: It is clear that early detection in infected populations is crucial for improving HCC outcomes and that chemiluminescence immunoassay has the potential to be a helpful platform for biomarker research. However, the study is limited by its small sample size and its emphasis on only three tumor markers, indicating that more biomarker research is required to improve the accuracy of HCC diagnosis and prognosis.