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

The aim of this study was to develop and validate a predictive early tooth loss multivariable model for periodontitis patients before periodontal treatment. A total of 544 patients seeking periodontal care at a university dental hospital were enrolled in the study. Teeth extracted after periodontal diagnosis and due to periodontal reasons were recorded. Clinical and sociodemographic variables were analyzed, considering the risk of short-term tooth loss. This study followed the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines for development and validation, with two cohorts considered as follows: 455 patients in the development phase and 99 in the validation phase. As a result, it was possible to compute a predictive model based on tooth type and clinical attachment loss. The model explained 25.3% of the total variability and correctly ranked 98.9% of the cases. The final reduced model area under the curve (AUC) was 0.809 (95% Confidence Interval (95% CI): 0.629 - 0.989) for the validation sample and 0.920 (95% CI: 0.891 - 0.950) for the development cohort. The established model presented adequate prediction potential of early tooth loss due to periodontitis. This model may have clinical and epidemiologic relevance towards the prediction of tooth loss burden.

Objectives: To develop a multivariate model for risk factors specific to early onset preeclampsia (EOP) and late onset preeclampsia (LOP) in our entire population (singleton and twin pregnancies). Material and methods: 20 year-observational population-based historical cohort study (2001-2020). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion’s maternity. A standardized validated epidemiological perinatal data base. Results: During the 20-year period, there were 81,834 pregnancies and 83,555 infants born, 1232 dichorionic and 350 monochorionic twin pregnancies. There were 2120 cases of preeclampsia, of which 2001preeclamptic singleton pregnancies and 119 twin pregnancies (incidence 7.5% in twin pregnancies vs 2.5% singletons, OR 3.0, p<0.001). Independent risk factors for EOP and LOP in a multivariate model (controlling for the two major confounders: namely maternal ages -both risks for EOP and LOP- and maternal pre-pregnancy BMI – specific risk factor for LOP) were: history of preeclampsia (aOR 11.7 for EOP, 7.8 for LOP, p < 0.0001), chronic hypertension (aOR 7.3 for EOP, 3.9 for LOP, p < 0.0001), history of perinatal death (aOR 2.2 for EOP, p < 0.0001 and 1.48 for LOP, p= 0.007), primipaternity (aOR 3.0 for EOP and 3.6 for LOP, p = 0.001), dizygotic twin pregnancies (aOR 3.7 for EOP, p < 0.0001 and 2.1 for LOP, p = 0.003), monozygotic twin pregnancies (aOR 3.98 for EOP, p = 0.003 and NS for LOP), ovulation induction (aOR 5.6 for EOP, p = 0.004 and NS for LOP), and in vitro fertilization (aOR 2.8 for EOP, p = 0.05 and NS for LOP). Specific to LOP and NS for EOP: renal diseases (aOR for LOP 2.9, p= 0.007) and gestational diabetes mellitus (aOR 1.2, p= 0.04). Conclusions: Maternal ages over 35 years, chronic hypertension , history of preeclampsia, ovulation induction, in vitro fertilizations, history of perinatal deaths and twin pregnancy (in our experience, especially mono zygotic twin pregnancies) are significant risk factors for EOP. New paternity is an independent factor for both EOP and LOP.

Rapid spread of African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries world-wide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, alternative transmission routes for ASFV have yet to be assessed. Here, we demonstrate that ASFV can efficiently be transferred from infected boars to naïve recipient gilts through artificial insemination (AI). In modern pig production, semen from boar studs often supplies many sow herds. Thus, the infection of a boar stud presents the risk of rapidly and widely distributing ASFV within or between countries. Daily blood and semen collection from four boars after intramuscular inoculation with ASFV strain ‘Estonia 2014’ resulted in detection of ASFV genomes in the semen as early as 2 dpi, in blood at 1 dpi while semen quality remained largely unaffected. Ultimately, after insemination with extended semen, 7 of 14 gilts were ASFV positive by 7 days post insemination, and all gilts were ASFV positive by 35 days post insemi-nation. Twelve out of 13 gilts aborted at the onset of fever. A proportion of fetuses originating from the remaining gilt showed both abnormalities and replication of ASFV in fetal tissues. Thus, we present evidence for the efficient transmission of ASFV to gilts via AI and also to im-planted embryos. These results underline the critical role that boar semen could play in ASFV transmission.

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.

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.

The recent COVID-19 pandemic has caused tremendous damage to social economy and people’s health. Some major issues fighting COVID-19 include early and accurate diagnosis and the shortage of ventilator machines for critical patients. In this work, we propose a closed-loop solution to deal with COVID-19: portable biosensing and wearable photoacoustic imaging for early and accurate diagnosis of infection and magnetically neuromodulation or minimally invasive electrical stimulation to replace the traditional ventilation. Proposed technique can guarantee ubiquitous and onsite detection, and electrical hypoglossal stimulator can be more effective in helping severe patients as well as reducing complications caused by ventilators.

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: The manifestations, severity, and mortality of COVID-19 are considered to be associated with the changes in various hematological parameters and in immunity. Associations of immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status with cardiac function and hematological and biochemical parameters in apparently health subjects are poorly understood. Methods: The present cross-sectional study included 307 healthy volunteers (24-69 years of age; 44.8±8.6 years; 80.4% men) and was initiated in 2019 before the COVID-19 pandemic. COVID-19 episodes were confirmed by detection of IgG-SARS against SARS-CoV-2 S1 RBD to reveal 70 IgG-SARS-positive and 237 negative participants. Numerous ultrasound characteristics were assessed by echocardiography, and 15 hematological and biochemical parameters were assayed in the blood. Descriptive and comparative analysis was based on the IgG-SARS status of the participants. Results: The left ventricular mass index, mitral ratio of peak early to late diastolic filling velocity or flow velocity across the mitral valve, and deceleration time of early mitral inflow were decreased (P<0.05) in IgG-SARS-positive participants versus those in IgG-SARS-negative participants according to multivariate logistic regression analysis. Erythrocyte sedimentation rate and platelet count were slightly increased, and blood hemoglobin was decreased in IgG-SARS-positive participants compared with those in IgG-SARS-negative participants. Conclusions: LV filling, inflammation, blood coagulation, and hemoglobin appear to be influenced by COVID-19 infection in healthy participants. These observations contribute to the development of a population recovery strategy after the episodes of COVID-19.

Here we mathematically model black holes and the early universe following dynamics similar to RLC electrical models, focusing on their similarities at the singularity. We use this mathematically modelling to hypothesize the evolution of an expanding universe as the result of a black hole collapse followed by its evaporation. Or model consists of several steps defined by: (1) the formation of a black hole following general relativity equations; (2) growth of the black hole modelled as a resistance-capacitance-like electrical circuit; (3) expansion of space-time following the disintegration of the black hole, modelled by RLC-like dynamics. In updating this article, version 2, we will expand by presenting three additional examples related to the theory of the generalization Boltzmann's constant in curved space-time and the theory of general and especial relativity. We will calculate the critical mass to produce a black hole in the LHC, the existence of a high temperature Bose-Einstein condensate and finally we will demonstrate the existence of a tangential force to the repulsion force in the disintegration of subatomic particles. In the update of this article, version 3, we will expand to develop two examples. First, we will present the relationship between M-theory, extra dimensions with the theory of the generalization of Boltzmann's constant in curved space-time. Secondly, we will propose the idea of ​​updating the Lambda-CDM model, considering the primordial gravitational waves to correctly describe the evolution of the universe.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

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

This study examined the status of Education for Sustainable Development (ESD) practices and the understanding of Sustainable Development (SD) among Saudi kindergarten teachers in a specific governorate. Two hundred twenty-seven kindergarten teachers participated, and data was collected through a questionnaire. The results indicated that most kindergarten teachers (89.9%) were unaware of SD. The overall status of ESD practices among the participating teachers was weak, with an average score of 2.60 out of 4. Among the different dimensions, values (2.74), competencies (2.69), and practice (2.65) obtained relatively higher scores, while the content dimension (2.49) received the lowest score. Significant differences were found in the mean scores of ESD practices based on teachers’ qualifications and the type of school. However, no differences were observed based on experience. The lack of awareness regarding SD emerged as the primary barrier to implementing ESD in kindergarten institutions. Expanding teacher training was identified as the most crucial step in promoting ESD in kindergartens. The findings highlight the importance of raising awareness among Saudi kindergarten teachers about SD, providing professional development opportunities to enhance ESD implementation in classrooms, and creating teaching materials aligned with ESD principles.

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.

The physiological response to a psychological stressor broadly impacts energy metabolism. In-versely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA) and sympathetic nervous system activation. Glu-cocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of ener-gy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physi-ological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunc-tion, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, the most prominent are early-life adversity, or exposure to traumatic stress. We hypothe-sise that when the HPA axis is so disturbed after early-life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

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

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

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

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a 2-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 hours of blood culture incubation (range 7.5-20 hours), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which of Streptococcus epidermidis in neonates with LOS and one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.

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

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms toward the foreign material silicone. The aim of this work was to enlighten the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome, and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intra-individual absolute quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to profile wound proteome formed around SMI the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation and adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

Through an investigation of recently discovered Incantation of Wish-Fulfillment amulets from the Silla kingdom, this paper reveals that early Korea had more diverse forms of dhāraṇī practices than previously assumed. This paper’s analysis of these amulets from Korea contributes toward filling the gap in our current understanding of the material practice pertaining to the Incantation of Wish-Fulfillment widely practiced in medieval East Asia. Based on an interdisciplinary analysis of the two amulet sheets of the Incantation of Wish-Fulfillment from Silla, this paper explored hitherto unknown aspects of early Korean dhāraṇī practice. Previously, the only material dhāraṇī practice in early Korea was thought to be the enshrinement of textual relics in pagodas based on the Pure Light Incantation, which has little connection to contemporaneous Chinese dhāraṇī practice. However, the newly discovered Incantation of Wish-Fulfillment amulets, whose date this paper inferred to be between the eighth and ninth century, show that the Unified Silla also had a dhāraṇī practice closely linked to the Chinese practice. However, unlike the Chinese Incantation of Wish-Fulfillment amulets that were buried in tombs, the Silla amulets were likely enshrined in one of the pagodas erected on Mount Nam, Gyeongju. At the same time, the Silla epigraph from Myogilsang Pagoda at Haeinsa shows that the Incantation of Wish-Fulfillment was placed in the pagoda so as to wish for good afterlives of the soldiers who died at the battle, suggesting that placing the Incantation of Wish-Fulfillment in a pagoda had a function similar to that of burying the Chinese amulet in the tomb.

Background: Early rehabilitation is an important strategy for the treatment of severe diseases. The study aimed to assess the efficacy of early rehabilitation of patients with mild-to-moderate COVID-19. Methods: The retrospective single-center study with propensity score matching. Results: 180 patients (54 (44 - 62.3) yo) divided into three equal groups: 1 - physical exercises; 2 - physical exercises and chest massage in an electrostatic field; 3 - no rehabilitation. The length of stay (LOS) in the hospital in group 1 was 14 (11-15) days, group 2 - 13 (11-15) days, group 3 - 15 (13-18) days, p=0.0026. Physical exercises for patients with CT-1 improved the quality of life, assessed by the EQ-5D questionnaire, by reducing the level of anxiety and depression. The Hazard Ratio (HR) for desaturation (<93%) was 2.34 (95% Confidence Interval (CI) 1.18-4.63) for group 2, p=0.001. The HR for C-reactive protein level above 50 mg/l in patients with CT-2 was 2.33 (95% CI 1.56-3.47), p=0.0001. Conclusions: Rehabilitation programs are safe for СOVID-19-patients; reduce hospital LOS; improve the quality of life. Continuous monitoring of a patient's condition during rehabilitation is essential. ClinicalTrials.gov ID: NCT0580836

Malignancy is a fatal disease with an increasing incidence with each passing year, and the early diagnosis of malignancy can significantly improve the cure rate of patients, which has profound implications for saving patients' lives. The changes of miRNA are closely related to the occurrence of malignant tumors. The expression of miRNA in many malignant tumors is obviously different and unique from that in normal tissues. In this study, a strategy for amplifying microRNA (miRNA) signal was designed using duplex specific nuclease (DSN), which was then combined with Peptide nucleic acid (PNA) probe hybridization technology to prepare a sensitive and efficient paper-based lateral flow biosensor (LFB) for the detection of pancreatic cancer (PC) associated microRNA-10b. The performance evaluation results of the LFB showed that the detection limit of miR-NA-10b is 5 nM/mL, and carries demonstrated well specificity, stability, reproducibility. The biosensor prepared in this paper can provide accurate and rapid detection of miRNA-10b. The detection results play a guiding role in the early diagnosis of PC. Meeting the clinical need for largescale screening of individuals at high risk of PC. Providing new avenues to achieve early mass screening in individuals at high risk of PC.

Clinical and histological similarities between sarcoidosis and tuberculosis have driven repeated investigations looking for a mycobacterial cause of sarcoidosis. Over 50 years ago “anonymous mycobacteria” were suggested to have a role in the etiology of sarcoidosis. Both tuberculosis and sarcoidosis have a predilection for lung involvement though each can be found in any area of the body. A key histopathologic feature of both sarcoidosis and tuberculosis is the granuloma – while the tuberculous caseating granuloma has an area of caseous necrosis with a cheesy consistency; the non-caseating granuloma of sarcoidosis does not have this feature. This article reviews and reiterates the complicity of the infectious agent, Mycobacterium avium ss. paratuberculosis (MAP) as a cause of sarcoidosis. MAP is involved in a parallel story as the putative cause of Crohn’s disease, another disease featuring noncaseating granulomas. MAP is a zoonotic agent infecting ruminant animals and is found in dairy products and in environmental contamination of water and air. Despite increasing evidence tying MAP to several human diseases, there is a continued resistance to embracing its pleiotropic roles. "Who Moved My Cheese" is a simple yet powerful book that explores the ways in which individuals react to change. Extending the metaphor, the “non-cheesy” granuloma of sarcoidosis actually contains the difficult-to-detect “cheese”, MAP; MAP did not move, it was there all along.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

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

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.

Early-season crop-type data are required for a variety of agricultural monitoring and decision-making applications. The early season in this study referred to the prophase and middle of a growth season. Early-season detection of crop types remains challenging because of limited discriminative features, especially for landscapes that are characterized by complex cropping patterns. In fact, different remote-sensing satellites can increase the frequency of data acquisition, which can provide more information in the early season. Moreover, optical and radar sensors have different degrees of sensitivity to crop parameters. Therefore, the integration and application of two types of multitemporal data are of great significance to improve the accuracy and timeliness of crop type detection.In deep learning (DL), convolutional neural network (CNN) and recurrent neural network (RNN) models have great potential for temporal feature extraction. Compared with RNNs, CNNs usually have fewer parameters and are more conducive to determining early-season detection dates of different crop types, which requires a lot of training because of the need to model on different dates. Nevertheless, revisit dates and temporal intervals of different satellites are usually different, resulting in different data acquisition time series; these data cannot be directly used as input for the same convolutional layer. To address this challenge, a Dual-1DCNN was bulit based on the CNN model in this study. Moreover, an incremental training method was used to attain the network on each data acquisition date and obtained the best detection date for each crop type in the early season. A case study for Hengshui City in China was conducted using time series of Sentinel-1A (S1A) and Sentinel-2 (S2). To verify this method, classical methods support vector machine (SVM) and random forest (RF) were implemented. The results demonstrated the following: (1) the Dual-1DCNN extracted discriminative features from S1A and S2 time series at the early season by producing the highest overall accuracy (OA: 87.23%); (2) for summer maize, cotton, and common yam rhizome, the Dual-1DCNN achieved F1 values of 92.39%, 87.71%, and 84.38%, respectively, at the early season (moreover, the early seasons were almost 40, 70, and 80 days before the end of the growth seasons, respectively). These findings suggested that the Dual-1DCNN is promising for the accurate and timely detection of crop types.

Breast cancer prevention is very important for a woman's health worldwide. We have demonstrated a correlation between mammography and ultrasound with diagnoses using passive microwave radiometry (MWR) and a miRNA oncopanel. While mammography screening dynamics could be completed in 3-6 months, MWR will provide us with a prediction in a matter of weeks or even days with the potential for complementary miRNA diagnostics. An early breast cancer diagnosis may be accomplished using either one of these novel techniques alone or in conjunction with more established techniques

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.

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

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 official recommendations to manage COVID-19 in the outpatient setting focus on high-cost drugs (remdesivir, nirmatrelvir-ritonavir, molnupiravir), suffering from many problems. Therefore, one may consider also other treatments meeting these criteria: • promising effectiveness, based on favorable randomized controlled trials (RCTs) of sufficient validity. Even without definitive evidence, physicians and informed patients can consider them if they are also: • safe, to the state of knowledge • with a very favorable opportunity cost • biologically plausible/not implausible • accessible • without major commercial sponsors in the trials promoting them, and with researchers without major conflicts of interests. The main focus is on a limited group of functional foods and some their active ingredients, with further mention of other substances of different origin, yet fully meeting all the aforementioned criteria. The functional foods and substances described and discussed certainly do not cover all the known effective therapies for COVID-19 (in one case also for Long-COVID), but the only therapies proposed in this paper currently satisfy all the above criteria. The supporting scientific evidence will favor meta-analyses of RCTs that include the most definitive outcome: all-cause mortality, i.e. the outcome that most fully informed people tend to prioritize. Furthermore, the reported evidence favors clinical studies of the most valid design, i.e. RCTs.

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 (&lt;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 &lt;2cm, showing that state-of-the-art deep learning can detect small PDAC and benefits from anatomy information.

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

Canistel (Pouteria campechiana (Kunth) Baehni) (yellow sapote, canistel). Originally from Mexico, the fruit is edible, and the tree is used as an ornamental and medicinal plant. Descriptive studies were carried out with the objective of morphologically characterizing the fruits and leaves of trees located in different regions of Mexico to select outstanding specimens and propose their massive reproduction. The trees were selected in three zones. In zone 2 from flower anthesis to harvest 11 months, fruits with 3 seeds, greater weight (180 to 330 g) and quantity of pulp (198.88 g), subglobose shape, total soluble solids 33 %. The fruits of zone 1 at harvest 8 months and zone 3 took 9 months to be harvested, in the rest of the characteristics evaluated were exceeded by the fruits of zone 2. To characterize the canistel (P. campechiana) leaf and identify accessions or cultivars, the three main variables, according to the principal component analysis were: leaf area, perimeter, and minor diameter. The three zones where canistel fruits and leaves were characterized are important and can be recommended for propagation in zones with favorable climatic conditions for fruiting in tropical and subtropical regions of Mexico.

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.

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

The work is devoted to the search for effective solutions to the applied problem of early diagnostics of plant stress in the conditions of smart farming and based on modern explicable artificial intelligence (XAI). The study mostly oriented on the theory and practice of XAI, focused on the use of hyperspectral imagery (HSI) and Thermal Infra-Red (TIR) sensor data at the input of a neural network. The first our goal is to build an XAI neural network, explainable due to its structure, the input of which is a datascientist oriented HSI 'explanator', and the output is a biologist oriented TIR 'explanator'. In the middle is SLP-regressor which solves the universal problem of training HSI pixels to temperatures of plants, needed for early plant stress diagnostic. The result can be considered as prototype of a special XAI explanator which is assigned to transform explanator specialized on area 1 onto explanator specialized on area 2. Using this HSI-TIR explanator we ensured the follows: extend HSI data by TIR attribute; providing TIR data for early diagnostic of plant stress; reducing dimensionality HSI needed for TIR training 25 times (from 204 to 8) preserving the same accuracy of temperature prediction (RMSE=0.2-0.3C). This reducing was achieved without using PCA methods. The constructed model is computationally efficient in training: the average training time is significantly less then 1 min (Intel Core i3-8130U, 2.2 GHz, 4 cores, 4 GB). One of the 8 channels, 820 nm, is the leader in correlation with TIR, what allows building local linear temperature prediction functions.

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

Exposure to extreme heat is a known risk factor that is associated with increased heat-related illness (HRI) outcomes. The relevance of heat wave definitions could change across the health conditions and geographies due to the heterogenous climate profile. This study compared the sensitivity of 28 heat wave definitions associated with HRI emergency department visits over five summer seasons (2011-2016), stratified by two physiographic regions (Coastal and Piedmont) in North Carolina. The HRI rate ratios associated with heat waves were estimated using the generalized linear regression framework assuming a negative binomial distribution. We compared the Akaike Information Criterion (AIC) values across the heat wave definitions to identify an optimal heat wave definition. In the Coastal region, heat wave definition based on daily maximum temperature with a threshold >90^th percentile for two or more consecutive days had the optimal model fit. In the Piedmont region, heat wave definition based on the daily minimum temperature with a threshold value >90^th percentile for two or more consecutive days was optimal. Additionally, we observed that the optimal heat wave definitions from this study captured moderate and frequent heat episodes than the national weather service (NWS) heat products that worked best for extreme heat episodes. This study compared the HRI morbidity risk associated with epidemiologic-based heat wave definitions and with NWS heat products. Our findings could be used for public health education and suggest recalibrating NWS heat products.

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.

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.

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help in defining patients’ prognosis and stratification. Beyond neurofilaments, chitinases are a promising family of possible biomarker, which correlate with neuroinflammatory status. We evaluated plasmatic levels of CHI3L1 in MNDs, MND mimics and healthy controls (HCs); (2) Methods: We used Sandwich ELISA to quantify CHI3L1 in plasma samples from 44 MNDs, 7 HSP, 9 MND mimics and 19 HCs. We collect also ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, neuropsychological evaluation; (3) Results: Plasma levels of CHI3L1 resulted to be different among groups (p= 0.005). Particularly, MND mimics showed higher CHI3L1 levels compared to MNDs and HCs. CHI3LI levels did not differ among PMA, PLS and ALS and we do not find correlation among CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, red blood cells count and haemoglobin correlated with CHI3L1 levels (respectively, p&lt;0.001, r=0.63; p= 0.022, r=0.52); (4) Conclusions: CHI3L1 plasma levels resulted to be increased in the MND mimics cohort when compared to MNDs. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that CHI3L1 plasma levels did not differentiate between ALS and HCs and nor correlate with neuropsychological impairment.

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and precursor lesions at young ages, mainly at the oral cavity. As patients have defects in DNA repair mechanisms, standard-of-care treatments to OSCC such as radiotherapy and chemotherapy give rise to severe toxicities. New methods for early diagnosis are urgently necessary to allow treatments in early disease stages and achieve better clinical outcomes. We have conducted a prospective, longitudinal study whereby liquid biopsies from sixteen lesion/tumor-free patients were analyzed for the presence of mutations in cancer genes. DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evolution followed during a median time of around 2 years. In 9/16 FA patients we detected mutations in cancer genes (mainly TP53) with molecular allele frequencies (MAF) down to 0.07 %. Importantly, all patients having mutations and clinical follow-up data after mutation detection (n=6) developed oral precursor lesions or OSCC. Lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations display significantly lower risk of developing precursor lesions or OSCC. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow closer surveillance for OSCC or precursor lesions.

The rescue, digitisation, quality control, preservation and utilization of long and high quality meteorological and climate records, particularly related to historical marine data, are crucial for advancing our understanding of the Earth's climate system. In combination with land and air measurements, the historical marine records serve as foundational pillars in linking present and past weather and climate information, offering essential insights into natural climate variability, extreme events in marine areas, baseline data for assessing current changes, and inputs for en-hancing predictive climate models and reanalyses. This paper provides an overview of marine data rescue activities covering the past centuries, presents and highlights several ongoing projects across the world and how the data are used in an integrative and international framework. Current and future continuous efforts in data rescue, digitisation, quality control and the de-velopment of temporally high resolution meteorological and climatological observations from the Sea, will greatly help to further complete our understanding and knowledge of the Earth system including extremes, as well as improving the quality of reanalysis.

Introduction: Some of the practices in medicine are carried out of habit without proven benefits. This is the case of premature babies from 30 to 34 weeks of gestation who are always given parenteral fluids, even though this practice has been associated with an increase incidence of infection. At the end of 2017, we started a protocol of rationalization in the use of parenteral fluid. To administer nutrition/fluids, we used oral fluids by suction if this was possible or otherwise by oral/nasogastric tube at volumes of 70-80 mL/Kg/day divided every 3 hours, with 5 mL increments every 12-24 hours until 200 mL/K/day was achieved, always using breast milk when possible. Material and methods: The present study sought to compare results before and after this new policy. For this work, we review all premature babies between 30-34 weeks of gestation in two time periods, the first from 01/01/2010 to 12/31/2017 and the second from 01/01/2018 to 08/15/2022. The number of cases with and without parenteral fluids (PF), the incidence of infection, the weight at admission and discharge, and the change in the weight Z score between birth and discharge were compared. Both the anthropometric and outcome variables were compared using the different statistical methods according to each variable. Results: were found 920 cases with the described characteristics. The groups before and after the intervention did not show significant differences in their general demographic characteristics. We observed a decrease use of PF in the second period, from 425 cases (82.0%) before to 297 (26.2%) after implementation, p <0.0001 and fewer days of use (4.1 days/average before vs 1.3 after, p <0.0001) of PF. The weight at discharge and the change in weight Z-score were the same in both groups. Infections went from nine cases before to two cases after but it was not statistically significant. There were no complications due to less use of PF. Discussion: This study showed that the use of PF is not associated with significant changes in outcomes of interest, which reinforces that its use does not generate any benefit for the patient. Larger number of cases is required to detect differences in low incidence events such as infections.

(1) Background: Adolescent well-being is a multifaceted construct embedded in family, school, and peer socialization contexts. By adopting a social-psychological perspective we test the association between three sources of support (parents, teachers, peers) and specific components of subjective well-being (cognitive, affective, global-and-domain-specific) to determine whether there is a functional specialization of the role that these crucial socialization agents play for adolescents to attain well-being in specific life domains. (2) Methods: Cross-sectional Albanian data from Wave 3 of the Children’s Worlds International Survey (www.isciweb.org) were used, including 2,339 adolescents (age range 9-13; girls = 49.3%). A structural equation model (SEM) was employed to explore associations between supportive relationships with parents, teachers, and peers and adolescent well-being. (3) Results: Findings support a functional specialization hypothesis as parental support was significantly related to global cognitive and affective well-being; teacher support was significantly related with school satisfaction; and significant relations were found between peer support and almost all well-being variables (context-free, domain-based life satisfaction and affective subjective well-being). (4) Conclusions: Findings contribute to a more nuanced understanding of the role of supportive relationships with adults and peers in adolescents’ proximal socialization contexts (family, school, peer groups) and specific components of subjective well-being.

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.

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.

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

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

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

Based on a reflection on the tensions between play, education, and learning in early childhood, this article aims to identify and analyze the factors that limit or negatively condition the possibilities for play at school during the transition between Early Childhood Education and Primary Education in Chile. The study was conducted in four Chilean schools, with the Transition Levels of Chilean Early Childhood Education (children aged 4 and 5) and the first two levels of Primary Education (children aged 6 and 7). Based on an ethnographic approach, we combined 22 ethnographic observation days spread over two consecutive years and 59 interviews of various types with children, educators, and parents. The results show structural-material limitations on school play that mainly affect children in Primary Education. Beyond, factors associated with routines, indications, and statements governing functioning and participation in this level tend to limit or prevent play, often considered a "non-legitimate" activity. Conclusions highlight the potentialities that children's restricted or resisted play can present in terms of learning.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

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

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

A distinction is made between data rescue (i.e., copying, digitizing and archiving) and data recovery that implies deciphering, interpreting and transforming early instrumental readings and their metadata to obtain high-quality datasets in modern units. This requires a multidisciplinary approach that includes: palaeography and knowledge of Latin and other languages to read the handwritten logs and additional documents; history of science to interpret the original text, data e metadata within the cultural frame of the 17th, 18th and early 19th century; physics and technology to recognize bias of early instruments or calibrations, or to correct for observational bias; astronomy to calculate and transform the original time in canonical hours that started from twilight. The liquid-in-glass thermometer was invented in 1641 and the earliest temperature records started in 1654. Since then, different types of thermometers were invented, based on the thermal expansion of air or selected thermometric liquids with deviation from linearity. Reference points, thermometric scales, calibration methodologies were not comparable, and not always adequately described. Thermometers had various locations and exposures, e.g., indoor, outdoor, on windows, gardens or roofs, facing different directions. Readings were made only one or a few times a day, not necessarily respecting a precise time schedule: this bias is analysed for the most popular combinations of reading times. The time was based on sundials and local Sun, but the hours were counted starting from twilight. In 1789-90 Italy changed system and all cities counted hours from their lower culmination (i.e., local midnight), so that every city had its local time; in 1866, all the Italian cities followed the local time of Rome; in 1893, the whole Italy adopted the present-day system, based on the Coordinated Universal Time and the time zones. In 1873, when the International Meteorological Committee (IMO) was founded, later transformed in World Meteorological Organization (WMO), a standardization of instruments and observational protocols was established, and all data became fully comparable. In the early instrumental period, from 1654 to 1873, the comparison, correction and homogenization of records is quite difficult, mainly because of the scarcity or even absence of metadata. This paper deals about this confused situation, discussing the main problems, but also the methodologies to recognize missing metadata, distinguish indoor from outdoor readings; correct and transform early datasets in unknown or arbitrary units into modern units; finally, in which cases it is possible to reach the quality level required by WMO. The focus is to explain the methodology needed to recover early instrumental records, i.e., the operations that should be performed to interpret, correct, and transform the original raw data into a high-quality dataset of temperature, usable for climate studies.

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.

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

The first 1000 days of life is a critical period that contributes significantly to the programming of an individual's future health. Among the many changes that occur during this period, there is growing evidence that the establishment of a healthy gut microbiota early in life plays an important role in the prevention of both short- and long-term health problems. Numerous publications suggest that the quality of gut microbiota colonization depends on several dietary factors, including breastfeeding. In this respect, a relationship between breastfeeding and the risk of inflammatory bowel disease (IBD) has been suggested. IBD are chronic intestinal diseases in which perinatal factors may be partly responsible for its onset. We propose to review the existence of links between breastfeeding and IBD, based on experimental and clinical studies. Overall, despite encouraging experimental data in rodents, the association between breastfeeding and the development of IBD remains controversial in humans, partly due to considerable heterogeneity between clinical studies. The duration of exclusive breastfeeding is probably decisive for its lasting effect on IBD. Thus, specific improvements in our knowledge could support dietary interventions targeting the gut microbiome, such as the early use of prebiotics, probiotics or postbiotics in order to prevent the disease.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called ‘Hallstatt calibration plateau’ (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7^th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Twin pregnancies are highly undesirable in dairy cattle; they compromise the health and wellbeing of a cow, and its incidence dramatically impairs the farm economy. Recently, a genomic prediction for twin pregnancies has been developed. The objective of this study was to assess cow, environmental and management risk factors affecting the incidence of twin pregnancies in high-producing dairy cows in their first lactation, with special emphasis placed on the genomic prediction values for twin pregnancy. Our study population of primiparous cows proved valuable in identifying factors other than genomic predictive values influencing the twin pregnancy rate. The odds ratio for twin pregnancy was 0.85 (p &lt;0.0001) for each unit of a prediction value increase, 3.5 (p = 0.023) for cows becoming pregnant during the negative photoperiod, and 0.33 (p = 0.016) for cows producing ≥42 kg of milk at AI, compared to the remaining cows producing &lt;42kg of milk. As a general conclusion, the practical implication of our findings is that genomic prediction values can identify the risk of twin pregnancy at herd level. Given the cumulative effect of genomic selection, selecting for animals with reduced genetic risk of twin pregnancies can contribute to reduce its incidence in dairy herds.

The concept and policies of multiple early cancer detection (MCED) have gained significant attention from governments worldwide in recent years. In the era of burgeoning artificial intelligence (AI) technology, the integration of MCED with AI has become a prevailing trend, giving rise to a plethora of MCED AI products. However, due to the heterogeneity of both the detection targets and the AI technologies, the overall diversity of MCED AI products remains considerable. The types of detection targets encompass protein biomarkers, cell-free DNA, or combinations of these biomarkers. In the development of AI models, different model training approaches are employed, including datasets of case-control researches or real-world cancer screening datasets. Various validation techniques, such as cross-validation, location-wise validation, and time-wise validation are used. All of the factors show significant impacts on the predictive efficacy of MCED AIs. After the completion of AI model development, deploying the MCED AIs in clinical practice presents numerous challenges, including presenting the predictive reports, identifying the potential locations and types of tumor, and addressing cancer-related information such as clinical follow-up and treatment. This study reviews several mature MCED AI products currently available in the market, detecting their composing factors from serum biomarkers detection, MCED AIs training/validation, and the clinical application. The review illuminates the challenges encountered by existing MCED AI products across these stages, offering insights into the continued development and obstacles within the field of MCED AI.

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

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

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

Aim: To improve risk stratification in early-stage endometrial cancer (EC), we performed mo-lecular classification, and L1CAM immunohistochemistry (IHC) for additional risk assessment. Method: We analyzed archival tumor tissue from 247 early-stage EC patients. POLE mutations were detected using a Droplet digital polymerase chain reaction assay and Sanger sequencing, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI test. Additionally, we conducted IHC of p53 and L1CAM. Results: The 247 ECs were categorized into four subgroups: POLE-mutated (13.0%), MMR-deficient (27.9%), p53-abnormal (8.5%), and non-specific molecular profile (NSMP, 50.6%). We further subcategorized NSMP subgroup into NSMP-L1CAMneg (44.9%) and NSMP-L1CAMpos (5.7%), which we refer to as the molecu-lar-L1CAM classification. The molecular-L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p <0.001, each). Similarly, the simplified L1CAM-p53 categorization, for practical use, remained an independent prognostic factor for RFS and OS (p <0.001, p =0.003, respectively). Conclusion: Integrating the molecu-lar-L1CAM classification or the simplified L1CAM/p53 categorization can enhance risk stratifi-cation in early-stage EC, providing valuable prognostic information to guide treatment deci-sions and improve patient outcomes.

B and T lymphocytes demonstrate important alterations in patients with Systemic Lupus Erythematous (SLE), with significant up-regulation of Double Negative (DN) B cells. Aim of this study was to evaluate correlation of T cell immunity changes with the distinct B cell-pattern SLE. In the present study, Flow cytometry was performed in 30 patients with SLE, on remission, and 31 healthy controls, to detect DN B cells (CD19+IgD-CD27-) and a wide range of T lymphocyte subpopulations, based on the presence of CD45RA, CCR7, CD31, CD28, CD57, defined as naive, memory and advanced differentiated/senescent T cells. Both B and T lymphocytes were significantly reduced in SLE patients. However, the percentage of DN B cells were increased, compared to HC, 12.9(2.3-74.2) vs. 8(1.7-35), p=0.04. Distribution of CD4 and CD8 lymphocytes demonstrated a shift to advanced differentiated subsets. The population of DN B cells had significant positive correlation with most of early differentiated T lymphocytes, CD4CD31+, CD4CD45RA+CD28+, CD4CD45RA+CD57-, CD4CD45RA-CD57-, CD4CD28+CD57-, CD4CD28+CD57+, CD4 CM, CD8 CD31+, CD8 NAÏVE, CD8CD45RA-CD57-, CD8CD28+CD57-, CD8CD28+CD57+. Multiple Regression analysis revealed CD4CD31+, CD8CD45RA-CD57- and CD8CD28+CD57- cells as independent parameters contributing to DN B cells, adjusted R2=0.534, p<0.0001. The predominance of DN B cells in patients with SLE is closely associated with early differentiated T lymphocyte subsets, indicating a potential causality role of DN B cells in T lymphocyte activation.

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

Here we will electrically-quantum model the neutron and proton as a three-phase alternating current electric generator, for this, we will use the theory of three-phase electric generators and vector or phasor diagrams. We will use this model to hypothesize how the quarks that form neutrons and protons with a combined mass of 10 MeV/c², can generate, through quarks-antiquarks-gluon interactions, a mass of 939.56 MeV/c² for the neutron and a mass of 938.27 MeV/c² for the proton. Using quantum mechanics and the theory of the generalization of the Boltzmann constant in curved space-time we will calculate the number of quarks-antiquarks-gluons and gravitons inside a neutron. We will also analyse βˉ decay using vector diagrams, we will calculate the tension of the string T₀ and the length of the string ℓs between quarks-antiquark and finally, we will model a black hole using a neutron equivalent model. In version 2 of this article, we will update the vector diagrams of the βˉ decay and theoretically calculate the energy of the W⁻ boson, the Z⁰ boson, and the Θ angle, Θ = arc cos (W⁻/Z⁰). We will demonstrate, through vector diagrams, that quarks-antiquarks-gluon interactions are the cause of the origin of the W⁻ boson and the Z⁰ boson. We will also demonstrate how the fine structure constant α originates. It is important to make clear, in future updates, we will describe the relationship that exists between the theory described in this paper and the Isospin theory, flavour and colour theory

Successful implementation of antibiotic stewardship programs (ASP) requires a well-structured approach involving all stakeholders. Despite embracing key responsibilities, nurses’ role remains poorly defined, preventing consistent engagement. We conducted a scoping survey to assess knowledge, attitude and perception of nurses towards nurse-led initial sepsis risk evaluation using the sepsis risk calculator (SRC) of newborns admitted to the mother-baby unit. Single-center, cross-sectional study. Study link was sent to all full-time nurses in mother-baby unit. Survey centered around knowledge of unit’s ASP and attitude and perception towards nurse-led initial sepsis risk evaluation. 89% response rate. 100% agreed that SRC reduced antibiotic use and 66% felt nurse-led sepsis risk evaluation will enhance nurse involvement, but this was offset by extra burden of work (66%) and low confidence in differentiating stable from clinically unstable infants (46%). Other facilitating factors included greater nurse/patient ratio (100%), targeted education (89%) and incorporation of the SRC into EMR (78%). Only 11% were willing to serve as champions for it. There was no significant correlation to age or experience however, greater number of fresh grads were interested in championing this effort. Our study identifies a need for strong foundation of knowledge and greater nurse/patient ratio as two main factors for improving nurse-led use of the SRC. Multi-site studies scoping barriers to nursing involvement for successful implementation of ASPs are necessary.

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.

Natural systems of units $\{U_i\}$ need to be overhauled to include the dimensionless coupling constants $\{\upalpha_{U_i}\}$ of the natural forces. Otherwise, they cannot quantify all forces of nature in a unified manner. Thus, each force must furnish a system of units with at least one dimensional and one dimensionless constant. We revisit three natural systems of units (atomic, cosmological, and Planck). The Planck system is easier to rectify, and we do so in this work. The atomic system discounts $\{ G, \upalpha_G \}$, thus it cannot account for gravitation. The cosmological system discounts $\{ \slashed{h}, \upalpha_\slashed{h} \}$, thus it cannot account for quantum physics. Here, the symbols have their usual meanings; in particular, $\upalpha_G$ is the gravitational coupling constant and $\upalpha_\slashed{h}$ is Dirac's fine-structure constant. The speed of light $c$ and the impedance of free space $Z_0$ are resistive properties imposed by the vacuum itself, thus they must be present in all systems of units. The upgraded Planck system with fundamental units $${\rm UPS} \,:=\,\{ c, Z_0, G, \upalpha_G, \slashed{h}, \upalpha_\slashed{h}, \,\dots\,\!\},$$ describes all physical scales in the universe---it is nature's system of units. As such, it reveals a number of properties, most of which have been encountered previously in seemingly disjoint parts of physics, and some of which have been designated as mere coincidences. Based on the UPS results, that relate (sub)atomic scales to the Planck scale and the fine-structure constant to the Higgs field, we can state with confidence that no observed/measured physical properties are coincidental in this universe. Furthermore, we derive from first principles Koide's $K=2/3$ enigmatic constant and additional analogous quark and vector boson constants. These are formal mathematical proofs that justify a posteriori the use of geometric means in deriving the quark/boson mass ladder. This ladder allows us to also calculate the Higgs couplings to the vector bosons and the Weinberg angle in terms of only $K$.

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.

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.

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

This 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.

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

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.

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

This work analyzes a new indoor laboratory data set looking at early fire indicators in controlled and realistic experiments representing different incipient fire scenarios. The experiments were performed within the confines of an indoor laboratory setting using multiple distributed sensor nodes on different room positions. Each sensor node collected data of particulate matter (PM), volatile organic compounds (VOC), CO, CO2, H2, UV, air temperature and humidity in terms of a multivariate time series. These data hold immense value for researchers within the machine learning and data science communities who are keen on exploring innovative advanced statistical and machine learning techniques. They serve as a valuable resource for the development of early fire detection systems. The analysis of the collected data was carried out in dependence of the manhattan distance between the fire source and the sensor node. We found that especially larger particles (&gt; 0.5 μm) and VOCs show a significant dependency with respect to the intensity as a function of the manhattan distance to the source. Moreover, we observed differences in the propagation behavior of VOCs, PM, and CO, which are particularly relevant in incipient fire scenarios due to the presence of strand popagation effects.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

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

Non-suicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

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.

Hepatitis B virus (HBV) remains a dominant cause of hepatocellular carcinoma (HCC). Recently it was shown that HBV and woodchuck hepatitis virus (WHV) integrate into hepatocyte genome minutes after invasion. Retrotransposons and transposable sequences were frequent sites of the initial insertions suggesting a mechanism for spontaneous HBV DNA disperse throughout hepatocyte genome. Several somatic genes were also identified as early insertional targets in infected hepatocytes and woodchuck livers. Head-to-tail joints (HTJs) dominated amongst fusions indicating their creation by non-homologous-end-joining (NHEJ). Their formation coincided with robust oxidative damage of hepatocyte DNA. This was associated with activation of the poly(ADP-ribose) polymerase 1 (PARP1)-mediated dsDNA repair as reflected by augmented transcription of PARP1 and XRCC1, the PARP1 binding partner, OGG1, a responder to oxidative DNA damage, and by increased activity of NAD+, a marker of PARP1 activation, and HO1, an indicator of cell oxidative stress. The engagement of the PARP1-mediated NHEJ repair pathway explains HTJ format of the initial merges. The findings showed that HBV and WHV are immediate inducers of oxidative DNA damage, hijack dsDNA repair to integrate into hepatocyte genome and by this may initiate pro-oncogenic process. Tracking initial integrations may uncover early markers of HCC and help to explain HBV-associated oncogenesis.

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.

Neurodevelopmental disorders are characterized by an amalgam of genetic and epigenetic faults implicating neuronal protein-related loss-of-function and gain-of-function respectively, hence their inclusion into the category of complex diseases. Neurodevelopmental disorders are regarded as autism spectrum disorder due to this reason; that the risk factors and phenotype constitute a spectrum of faults and protein overactivity. One example of an epigenetic factor leading to the onset of neurodevelopmental delays constitutes a set of immune response-based dysregulations, as well as the excessive growth of the adaptive immune memory of the fetus or the baby following significant infectious disease during pregnancy, as well as in babies aged 0-2, given the existence of profound links between developmental immunity and developmental neurology. Given that genetic information very likely represents a form of energy, the intake of excessive pathogen-related information may transiently overload the adaptive immune memory similarly to the manner functional pathogens do whilst inducing significant illness, and if events as such occur during important stages of neuro-immunological development, then there could often be irreversible effects upon the rate of development in neurological networks that normally have a major importance in the modulation of the related cognitive and behavioral phenotype. The full extent of evidence may only be obtained via a thorough study of the applications of physical laws into biology and medicine, given the foundational role of the physical matter in the development and maintenance of life. A common misconception is that neurodevelopmental delays are characterized solely by an accumulation of protein loss-of-function incidences in the central nervous system area, rather than a disruption of neuronal region developmental rates. For example, an overexpression of neuronal proteins related to cognition factors that is accompanied by an underexpression of proteins related to social behavior is phenotypically manifested in people with sharper rational thinking and poorer communication skills, with an impact on the abilities of decision-making as well, and this tends to be regarded as a classical example of the clinical manifestation of neurodevelopmental delays. More severe forms of autism spectrum disorder tend to implicate a more generalistic impact upon the developmental rates of key human behaviors, including those related with the development and maintenance of social and intimate relationships. Likewise, more severe implications upon regular developmental rates tend to bring a major impact upon the healthy function of related functions. As a result, lower functioning forms of neurodevelopmental delays bring fresh concerns with regards to a possible uncanny increase of incidences of deviated sexuality during years of adulthood, and in the worst cases, such deviations may lead to the planning and development of criminal activity, particularly in individuals who are or become prone to breaking the moral code that established the civilized society. What holds the concerns valid is the exponential increase in the number of lower functioning autism cases throughout the world and the major signs that such an increase will continue with a full force. One major solution to this potential future problem would be a much higher investment into awareness of the exact genetic and environmental factors that directly or indirectly result in the onset of lower-functioning autism and of the current research efforts to develop the matching support for people found in situations as such. The most important aim of future research with regards to such a scenario would be a separation of disease and disability with choices made to step into more severe forms of disease and into areas that are outside of the established moral circle.

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.

Background and Objectives: The purpose of this study was to assess the bleeding that occurs during the first weeks of gestation and its implications throughout pregnancy. Secondarily, we studied the associated complications that appeared and tried to identify possible risk factors that could serve to select women at a greater risk of adverse outcomes that could benefit from an early diagnosis and improved monitoring. Materials and Methods: We selected all the women who consulted for first trimester metrorrhagia in the Emergency Department of the Hospital QuirónSalud in Malaga over the year 2015. We refer to first trimester metrorrhagia as that which occurs until week 12+6. Once the pregnant women were identified, we studied certain risk factors already present prior to the gestation and others associated with the gestation and its evolution. Results: After reviewing the visits to the obstetrics and gynecology emergency department, we selected those patients that met the inclusion criteria, resulting in a sample of 696 patients that we followed up. The average age of our patients was 34.1 years, with an average number of visits to the hospital of 1.67, most of them between the 5th and 8th weeks of pregnancy. 45.3% of these pregnancies resulted in a first trimester miscarriage, mainly between weeks 6 and 8. We tried to establish associations in order to identify possible risk factors, finding a relationship between increased maternal age and a higher risk of first trimester pregnancy loss, which rises as maternal age increases (33,37 4,316 years vs 35,01 4,740 years). This increase in risk is proportional to the increase in age. We made subgroups of women over 35 and over 40 and confirmed that increased age led to worse outcomes. We also studied several gestational complications and concluded that they appeared more frequently among older women. These complications include prematurity (33.11 vs 34.48 years), gestational diabetes (33.11 vs 36.06 years) and preeclampsia (33.25 vs 35 years). We reviewed the obstetric history of pregnant women whose gestation resulted in miscarriage and found that 50.5% of them had previously had another loss. Conclusions: Comparing the results with data from the general population, we found that the rate of first trimester miscarriage is up to 3 times higher among women who present bleeding during the first weeks of gestation compared to those who do not develop this complication. Maternal age is a risk factor for first trimester pregnancy loss and for the development of complications associated with pregnancy.

The catastrophic failure of two dams in Libya in the night of 10th and 11th September 2023, resulted in a significant amount of water and debris destroying a large part of the city of Derna, which is located downstream of the two dams. The flood caused more than 6000 fatalities and the dis-placement of thousands of people from the city. The dams failed due to heavy rainfall caused by the Medicane Daniel, resulting in intense precipitation and the dams overspilling after reaching full capacity. This paper analyses the consequences of the dam breach by modelling the flow discharge and the flooding of the city of Derna. The analysis compares the computed quantities with the findings of the post-event satellite image analysis from UNOSAT and Copernicus, the field reports, and information gathered from the social media through AI detection. The results allows to better understand the dynamics of the dam breach, its initial parameters and an assessment of the accu-racy of the results.

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

The impact of early maternal age on several outcomes (e.g. mental health issues, delinquency, aggression, impulsivity, victimization and interpersonal difficulties) has been studied since the late 1980s. Research has demonstrated links between exposure to adverse childhood experiences (ACEs) and trauma related outcomes such as substance abuse, interpersonal and self-directed violence, and sexual risk-taking, to name a few. The current study analyzed the incidence of ACE exposure and mental health outcomes (e.g. suicidal behaviors or self-harm, psychiatric hospitalizations, and substance use) as related to early maternal age in youth known to have experienced trafficking or sexual abuse. General demographics and incidence of various experiences and clinical presentations (e.g. ACE exposure, age of mother at birth of youth and age at first birth), and history of self-harm, substance use and psychiatric hospitalization were examined in a sample of 225 youth referred for services subsequent to experiences of sex trafficking or exploitation. Relationships between ACE exposure and maternal age related to mental health outcomes was also examined. Trafficked and exploited youth reported rates of ACE exposure and poor mental health outcomes at far greater rates than the general population. Significant findings were related to early maternal age and engaging in self-harm or suicidal behaviors. Previously anticipated mediational analyses were not conducted due to the sample size and lack of correlations. Findings highlight the significant ACE exposure and high needs of exploited, trafficked and abused youth and related mental health outcomes, emphasizing the need for early and comprehensive preventive and therapeutic interventions.

Exploiting the existing optical fiber network’s terrestrial infrastructure offers unexpected solutions to global challenges. We aim to expand the current network by incorporating a streaming telemetry system to integrate earthquake early detection. The purpose is to analyze and interpret alteration of light’s polarization induced by seismic events, particularly Primary earthquake waves that precede destructive Surface waves. This analysis facilitates the development of an early warning system and implementation of earthquakes countermeasures to mitigate humanitarian and economic impact. Consequently, we have developed a Python-based Waveplate Model designed to monitor light’s polarization changes within optical fibers buried underground. The model incorporates real ground displacement data from a 4.9 magnitude earthquake that struck in Marradi region, central Italy. We propose a novel approach of a smart sensing grid of optical network empowered by machine learning, trained on a large number of polarization evolution extracted from two distinct sensing fibers to identify the pattern of polarization change occurring during Marradi earthquake. Test Results demonstrate that this method can detect Primary waves within one second time-frame, achieving an accuracy rate of 99.5%. This system therefore affords nearby regions 52 seconds to take emergency response, and an extended margin of 62 seconds in more distant areas.

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.

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.