Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantly shorter in LOAD cases than in controls (p<0.001 for both sporadic and familial cases). Interestingly, LTL were associated to disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the patho-genesis of LOAD.

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.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

Rationale. A biomaterial is proposed for closing extensive bone defects in the maxillofacial region. The composition of the biomaterial includes high molecular weight chitosan, chondroitin sulfate, hyaluronate, heparin, alginate and inorganic nanostructured hydroxyapatite. The purpose of the study is to demonstrate morphological and histological early signs of reconstruction of a bone cavity of a critical size. Materials and methods. The studies were carried out on 84 white female rats weighing 200 g. The control group of animals consisted of 44 individuals, the study group - 40. In all animals, three-walled bone defects 0.5 cm in size were applied subperiosteally in the region of the angle of the lower jaw and filled in the experimental group with a gel mass of chitosan -alginate-hydroxyapatite (CH-SA-HA). In control animals, the bone cavities were filled with an auto-blood clot. The follow-up periods were 3.5.7 days, 2.3.4.6.8 and 10 weeks. Results. The chitosan construct after implantation actively replaced defects early with the formation of a full-fledged new bone tissue compared to control animals. Morphological analysis of the walls of the bone defect on the 7th day showed signs of the formation of spongy bone tissue, after two weeks - a pronounced increase in bone volume (P<0.01), after 6 weeks after surgery, the closure of the defect was 70-80%, after 8 weeks - 100% without disturbing bone morphology with a high degree of mineralization. Conclusion The use of modified chitosan after filling eliminates bone defects of critical size in the maxillofacial region, reveals early signs of bone neoformation, and serves as a promising material in reconstructive dentistry.

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.

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.

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.

A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease attended Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to failure of other treatments (phototherapy, oral acitretin) for psoriasis and Psoriasis Area Severity Index &lt;10. We evaluated the impact of ustekinumab, a potent immunosuppressor, on the risk of infectious diseases in this patient followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, culture of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation, absence of pathogenic variants in the genes analyzed and no clinically significant variants were detected in the whole exome. The main infections included chronic sinusitis, tonsillitis, fungal and bacterial otitis, gastroenteritis, and community-acquired pneumonia. The patient was infected with COVID-19, dengue (twice), and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence susceptibility to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease in a patient with LOCID.

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

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.

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.

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

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.

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

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

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

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

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.

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.

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.

A retrospective cohort study was performed to determine the likelihood of malignant stroke after mechanical thrombectomy via ASPECTS-PASS score(A-P score), a novel scoring system using ASPECT score and number of arterial-passes. This prediction score is designed to help clinicians take early measures. Malignant stroke is defined as a large MCA infarct with mass effect that develops during the first 5 days following presentation and is associated with approximately 80% mortality. Previous studies have shown an association of low ASPECTS and high number of passes with poor outcome.We performed a retrospective cohort analysis on 78 patients with anterior circulation stroke who underwent mechanical thrombectomy at our hospital. We analyzed the likelihood of developing malignant stroke post thrombectomy in the first 5 days following successful recanalization (TICI ≽ 2b). Malignant stroke is defined as severe symptoms secondary to edema as evidenced by midline shift, cistern engorgement, and hemorrhagic conversion with edema. Patients with ASPECTS of 0-5 were excluded. We used two variables to predict the outcome: ASPECT score and number-of-passes. We used the equation ASPECT score minus number-of-passes (A-P) to arrive at a single number to predict the risk of malignant stroke. A-P scoring scale ranged from 0-9. Our study showed a statistically significant inverse relationship of A-P score and risk of malignant stroke. Approximately 90% of patients with A-P score < 5 developed malignant stroke in our study. A-P score can help predict malignant stroke post thrombectomy even after successful recanalization. Thus, A-P score of ≤ 5 suggests very high risk. (A-P) Score can assist clinicians to take early measures, and thereby prevent worse outcomes.

Abstract: The marketing of Sugar-Sweetened Beverages (SSBs) within grocers is an obesogenic factor that negatively impacts children’s nutritional behavior, specifically regarding people from racial and ethnic minority groups. We aimed to develop and employ a methodology that more precisely assesses the availability, price, and promotion of SSBs to young immigrant children within independently owned grocery stores. A case comparison design was used to explore the differences in the grocery store landscape of SSB marketing by conducting an enhanced Nutrition Environment Measures Survey-SSB (NEMS-SSB) within 30 grocery stores in the Hispanic and Latino enclaves in Southwest Detroit, in the Arab and Chaldean enclaves in North-central Detroit, and in Warren, Hamtramck, and Dearborn, in comparison with 48 grocers in Metro Detroit. Organic, plant-based, and unsweetened toddler and infant beverages, as well as questions about marketing, were added to the original NEMS-S to capture the promotion tactics used in marketing SSBs. NEMS-SSB scores revealed in the immigrant enclaves there was a significantly higher availability of SSBs in grocery stores (−2.38), and they had lower prices than those in the comparison group (−0.52). Availability of unsweetened and organic beverages was zero in 97% of all participating grocery stores. Signage featuring cartoon characters was the most frequent in-store SSB marketing tactic. Widespread SSB marketing towards toddlers within the grocery stores in immigrant enclaves could be linked with the higher childhood obesity prevalence among this population. Our findings can assist local and national organizations in developing and implementing healthy eating interventions. This study can be repeated in other states to provide comparable results.

(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.

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.

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.

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.

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.

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.

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

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

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.

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.

Forestry workers play a crucial role in implementing forest management programs, but their outdoor work exposes them to rising temperatures caused by global climate change, which poses potential health risks related to heat. This study focuses on Indonesian forestry workers and examines the relationship between their knowledge of heat-related issues, risk perception, and precautionary behavior in dealing with increasing workplace heat exposure. Developing effective precautionary behavior is essential for preventing heat-related health disorders and promoting health protection programs. To facilitate a comprehensive comparison of the three variables, interviews were conducted with two groups of outdoor workers, comprising 210 forestry workers and 215 paddy farmers. The findings indicate that increasing knowledge about heat-related issues promotes precautionary behavior, and risk perception acts as a mediator between knowledge and behavior. Additionally, the study highlights that the emotion of "dread" intensifies perceived risk and predicts positive behavior change. To enhance heat-related knowledge, exploring the potential use of a "fear" tone is important. In conclusion, comprehensive strategies need to be implemented to promote precautionary behavior among vulnerable forestry workers, particularly manual laborers.

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.

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.

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.

Existing studies provide evidence that buildings and the construction sector are the largest consumers of natural resources and carry the greatest responsibility for greenhouse gas emissions. In order to reverse this situation, future challenges involve utilising the least resources possible. To this end, building refurbishment becomes a crucial strategy given its potential to improve operational energy efficiency and to extend the life span of existing building stock, thereby reducing the environmental impact while also providing social and economic benefits to our cities. Life Cycle Sustainability Assessment (LCSA) has become one of the scientific community’s most widely recognised methodologies for the evaluation of the social, economic, and environmental dimensions (Triple Bottom Line), since it assesses sustainability using quantitative metrics. However, the implementation of this methodology to support the refurbishment process at the project stage in building design tools, such as BIM, remains scarce. One of the main obstacles lies in the difficulties of accessing the building information, given that the system boundaries only cover new materials and products. Hence, this study proposes a BIM plug-in development to support the multi-dimensional building material selection in the early design steps based on the LCSA of a building during the refurbishment stage and validates its application in a case study. The results show the viability of using this tool during the early design stages and demonstrate the consistency of the results to evaluate various material and product alternatives for the refurbishment of the envelope system of a multi-family residential building. This study contributes towards the integration of decision-making by providing real-time assessment of the building envelope.

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

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.

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.

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.

Schizophrenia patients with an earlier age of onset have been found to have more serious negative symptoms and cognitive deficits. Oxidative stress is thought to be implicated in cognitive impair-ment in schizophrenia. Total antioxidant capacity (TAOC) is an essential indicator of oxidative stress. However, the association between age of onset, TAOC, and cognitive performance in schizophrenia is still unexplored. In this study, 201 patients (age: 26.5±9.6 years, male: 53.2%) with drug naïve schizophrenia were recruited. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma TAOC levels were an-alyzed using established procedures. Results showed that early-onset (EO) patients had higher TAOC levels, more severe negative symptoms and performed worse on Visuospatial/Constructional, Language and RBANS total score compared with non-EO patients. After Bonferroni correction, only non-EO patients showed a significant inverse relationship between TAOC levels and RBANS language, attention, and total scores. Our findings suggest that early /late age of onset may be correlated with psychopathological symptoms, cognitive impairment and oxidative responses in schizophrenia. Furthermore, the age of onset may moderate the relationship between TAOC and cognitive function in patients with schizophrenia. These findings suggest that improving oxidative stress status in non-EO schizophrenia patients may enhance their cognitive function.

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.

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.

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.

One in 12 babies is born with a rare genetic disease. Sadly, most cases are undetected until later age, missing time for early treatment and opportunity to prevent complications. Humanity has entered a new era where Big Data collected by governments, including 2D and 3D facial scans, are available. Many rare genetic diseases can be identified by artificial intelligence (AI) analysis of the facial photo. Phenotyping AI utilizations facilitate comprehensive and accurate genetic evaluations. AI processing of this Big Data to identify rare genetic diseases could bring unimaginable benefits to healthcare, although this would be a questionable step in terms of citizen privacy and could lead to future "Orwellian" ramifications with government abuse. Going forward, a balance must be found between protecting the privacy of citizens and the enticing use of AI for their health risks and cost savings through prevention. The unimaginable potential of AI early diagnostics from facial photos also raises various ethical and legal concerns. This paper presents concept, protentional methods and legal and other limitations within EU legal framework in contrast with potential benefits. This paper is focused on AI utilization to early diagnostic of rare genetic diseases. Shift of paradigm in the screening for rare genetic diseases in population with AI face analysis is expected to have a significant impact. The potential of AI algorithms utilizations similar to face2gene app in general population or systematically on Big governmental datasets recording facial traits changes in time can have significant impact on public health but at the same time give raise to profound concern as violation of one’s privacy.

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.

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

Introduction: Unlike cigarette smoking, secondhand smoke (SHS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. We systematically reviewed the association between SHS and the risk of onset and/or progression of MS.Methods: We systematically screened MEDLINE/PUBMED, Science Direct, LILACs, and SCIELO searching for publications between January 1st , 2010, and July 5, 2021 with the following keywords: “multiple sclerosis and smoking”; “multiple sclerosis and passive smoking”; “multiple sclerosis and secondhand smoking”. An 11-year filter was applied from 2010 to 2021. Results: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of SHS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between SHS and MS development, and one study that did not find a significant association between SHS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between SHS and MS. Seven observational studies reported higher odds of MS onset when associated with SHS. Four observational studies did not show a relationship between SHS and MS onset or progression.Discussion: Most articles showed a positive association between SHS exposure and the risk of developing MS. On the other hand, an association between SHS and a higher risk for MS progression could not be established.

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.

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.

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

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.

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.

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.

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 $K$.

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.

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.

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.

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.

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.

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.

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

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: The National Lung Screening Trial (ILST) and the NELSON study showed that lung cancer-specific mortality can be reduced by 20-24% using low-dose computed tomography (LDCT) screening in high-risk populations, due to an increase in early-stage diagnoses. RESEARCH QUESTION: How much lung cancer-related direct costs may be reduced using a LDCT screening programme based on the ILST protocol in a public healthcare system?STUDY DESIGN AND METHODS: Cost analysis of lung cancer screening (LCS) vs. usual care in the framework of the retail price of the Catalan public healthcare system. The LCS group included costs of screening (ILST protocol), treatment cost according to weighted average distribution of TNM staging in the NLST and NELSON trials, lung cancer detection rate (CDR) and smoking cessation intervention. The usual care group included treatment costs based on distribution of TNM staging registered in the Spanish index hospital. RESULTS: In the usual care group, treatment costs were €91,959. In the 5-year duration of the LCS programme, the average expected costs per subject were €1,342 (range €1,054-1,832 depending on malignancy in detected nodules) for screening and €32,431 for treatment, with an expected reduction of €952 based on an average CDR of 1.6%. The decrease in cost resulting from stage shift offsets 70.6% of the costs of the screening programme. INTERPRETATION: Baseline 5-year LCS costs are low according to the ILST protocol. In the Catalan public healthcare system, the expense reduction from the stage shift due to the LCS programme compensates a substantial part of its costs.

(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.

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

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

The 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.

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

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

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.

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.

Background: Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery in conventional extracorporeal circulation (CECC), with an incidence of 15-50%. The POAF pathophysiology is not known, and no blood biomarkers exist. However, an association between increased ferritin levels and increased AF risk, has been demonstrated. Based on such evidence, here, we evaluated the effectiveness of ferritin and other haemato-chemical parameters as a POAF onset biomarker in subjected to cardiac surgery. Materials and Methods: We enrolled 90 patients (mean age= 66.9±2.8 years; 40 men and 20 females) with diverse heart pathologies and subjected to cardiothoracic surgery. Their blood samples were collected and used to determine haemato-chemical parameters. The tree test approach was used to detect the best data-driven ferritin cuff-off value (=141 ng/ml) to predict POAF risk. Results: The data obtained demonstrated significant higher concentrations, absolute values, and percentages, of ferritin, RDW, PLTs, in POAF patients. However, the ferritin resulted to be the independent factor associated with the onset POAF risk. Thus, we detected the ferritin cut-off value, which, when ≥ 141 ng/ml identifies the subjects at the highest POAF risk. Conclusions: Ferritin values≥ 141 ng/ml might be used as predictive POAF biomarker.

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

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.

Link prediction is an unbalanced early retrieval problem, whose goal is to prioritize a small cohort of positive links on top of a list largely populated by unlabelled links. Differently from binary classification, here the evaluation focuses on how the predictor prioritizes the positive class because, in practice, a negative class does not exist. Previous studies explained that AUC-ROC is not apt for unbalanced class problems and is misleading for early retrieval problems, therefore standard AUC-ROC is not appropriate for evaluation of link prediction. However, some scholars argue that an AUC-ROC like evaluation accounting for the relative positioning of the few positive links among the vastness of unlabelled links remains a valid concept to pursue. Here we propose the area under the magnified ROC (AUC-mROC), a new measure that adjusts the standard AUC-ROC to work also for unbalanced early retrieval problems such as link prediction.

Mesozoic-Palaeozoic marine carbonate rocks are important hydrocarbon reservoirs in the Central Uplift area of the South Yellow Sea Basin (SYSB). Due to the lack of boreholes and the great heterogeneity of carbonate reservoirs, the distribution of porous carbonate reservoirs and their related key controlling factors remain unclear. Based on seismic inversion and isotope analysis, this study explores the factors affecting the distribution of porous Carboniferous-Early Permian carbonate reservoirs in the SYSB. In this study, the log-seismic characteristics of porous carbonate reservoirs, sensitive lithology parameters, and physical property parameters are extracted and analyzed. The pre-stack simultaneous inversion technique is applied to predict the lithology properties and physical properties of the porous carbonate reservoirs. Moreover, the sedimentary of carbonate is analyzed using isotopes of carbon, oxygen, and strontium. The results indicate that porous carbonate reservoirs with porosities of 3%~5% mainly occur at the paleo-highland (Huanglong Formation and Chuanshan Formation) and the slope of paleo-highland (Hezhou Formation). The porous carbonate reservoirs of the Qixia Formation are only locally developed. In addition, the study area was dominated by a warm and humid tropical climate from the Carboniferous to Early Permian, with four sea-level eustatic fluctuation indicated by the negative and positive δ13C excursions. When the sea level fell, the study area was exposed and denuded, and the supply of terrigenous detrital was dominated, which significantly influenced the carbonate deposit and diagenesis. This study highlights that sedimentation was a key factor in controlling the quality of Carboniferous-Early Permian carbonate reservoirs. The methods proposed in this study can be used in other carbonate-dominated strata worldwide.

The objective is to describe infant feeding practices and the nutritional status of infants under six months among Syrian refugees in Greater Beirut, Lebanon. A cross-sectional study was conducted among Syrian refugee mothers with children under five years (July-October 2018), mothers with infants under six months were included in the analysis (n=114). Additionally, eleven focus groups discussions were conducted to explore supportive factors and barriers associated with early breastfeeding practices. The prevalence of pre-lacteal feeding was high (62.5%), whereas early initiation of breastfeeding (EIBF) was low (31%), and exclusive breastfeeding (EBF) very low (24.6%). About one-fifth of the infants were suffering from anemia (20.5%) and 9.6% were wasted. Supporting factors of adequate infant feeding practices comprised knowledge on maternal nutrition and EBF, in addition to receiving support from healthcare professionals and family members. Identified barriers included preterm delivery, pre-lacteal feeding, an at-risk waist circumference and moderate to severe depression among mothers, bottle feeding, early introduction of food, maternal health reasons, breastmilk substitutes’ distribution, and misinformation offered by mothers-in-law. To address sub-optimal feeding practices documented among Syrian refugees in our study, existing infant and young child feeding policies and programs need to be strengthened and revised to tackle the identified gaps.

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.

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

Introduction: Pediatric-Onset Multiple Sclerosis (POMS) is characterized by high inflammatory disease activ-ity. Our aim was to describe the treatment sequencing and report the impact Highly Effective Disease Modifying Treatment (HET) had on disease activity. Materials and Methods: 2/5 consecutive POMS were administered HET as initial therapy after diagnosis. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. Results: Our patients had an average age of 13.8 years (range 9-17) at di-agnosis and 13.4 years (range 9-16) at disease onset, 2/5 (40%) POMS were female. The pre-treatment aver-age annualized relapse rate was 1.6 (range 0.8-2.8) and the average follow-up length was 5 years (range 3-7). A total of 2/5 (40%) patients were stable on HET at initial therapy, 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2-5). Conclusion: it has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.

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.

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.

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.

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.

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

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.

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.

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

Real-world evidence (RWE) is increasingly involved in the early benefit assessment of medicinal drugs. It is expected that RWE will help to speed up approval processes comparable to RWE developments in vaccine research during the COVID-19 pandemic. Definitions of RWE are diverse marking the highly fluid status in this field. So far, RWE comprises information produced from data routinely collected on patient’s health status and/or delivery of health care from various sources other than traditional clinical trials. These sources can include electronic health records, claims, patient-generated data including in home-use settings, data from mobile devices as well as patient, product and disease registries. The aim of the present update was to review the current RWE developments and guidelines mainly in the U.S., the UK, Europe and Germany field during the last decade. RWE has already been included in various approval procedures of regulatory authorities reflecting its actual acceptance and growing importance in evaluating and accelerating new therapies. However, since the RWE research is still in a transition process and since a number of gaps in this field have been explored, more guidance and a consented definition are necessary to increase the implementation of real-world data.

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow (BM) microenvironment. Despite the progress made in treatment, some MM patients still die within the first year of diagnosis. Numerous studies investigating microRNA (miRNA) expression patterns suggest they may be good prognostic markers. The primary aim of this study was to analyze the expression of selected miRNAs in the serum of MM patients subsequently treated with bortezomib-based regimens and determine their potential to predict early mortality. The study was conducted in 69 prospectively-recruited patients with newly-diagnosed MM admitted to the Department of Hematology of the Copernicus Memorial Hospital, Lodz (Poland) between 2017 and 2021. Among them, 17 patients experienced death within 12 months of diagnosis. The expression of 31 selected miRNAs was determined using miRCURY LNA miRNA Custom PCR Panel. The obtained clinical data included patient characteristics on diagnosis, treatment regimen, response to treatment, and follow-up. Differential expression analysis found two miRNAs to be significantly downregulated in the early mortality group: hsa-miR-328-3p (fold change- FC: 0.72, p=0.0342) and hsa-miR-409-3p (FC: 0.49, p=0.0357). Univariate and multivariate logistic regression analyses were performed to assess the early mortality rate. The final model consisted of hsa-miR-409-3p, hsa-miR-328-3p, age and R-ISS 3. It yielded an area under the curve (AUC) of 0.863 (95%CI: 0.761-0.965) with 88.2% sensitivity and 77.5% specificity. Further external validation of our model is necessary to confirm its clinical value.

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.

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.

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.

Carcinoembriogenic antigen (CEA) is a routine marker for follow-up of colo-rectal cancers. We aimed to determine whether a CEA increase within the normal range can be linked to a recurrence risk. We included 78 consecutive patients with colo-rectal cancer, who underwent curative surgical treatment with or without chemo- or radiotherapy. As reference, we used the smallest value of the CEA during follow-up. A total of 34/78 patients (43.6%) had fluctuations of CEA of at least 1.1 ng/ml, with or without increases above 5 ng/ml. In 27/34 patients (79.4%) increases of CEA were explained either by recurrence (15/34 patients, 44.1%), adjuvant chemotherapy (7/34 patients, 20.6%) or benign pathology (5/34 patients, 14.7%). In 5 of 22 recurrences (23%) a CEA increase of at least 1.1 ng/ml, but below 5 ng/ml preceded the clinical relapse by a median of 8 months (range 3-22 months). The 4-year disease-free survival was 89% in patients with postoperative CEA <2.5 ng/ml, and 55% in patients with CEA >2.5 ng/ml. CEA increase by at least 1.1 ng/ml within the normal range, after curative treatment of colorectal cancer can be either an early sign of relapse or can be usually explained by other pathological processes.

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the 1^st human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the 4^th post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19^th century but did not receive much recognition by embryologists.

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

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

Eating Disorders (ED) constitute a serious public health issue affecting predominantly women and appearing typically in adolescence or early adulthood. EDs are extremely difficult to treat as these disorders are ego-syntonic and many patients do not seek treatment. It is vital to focus on the development of successful early-intervention programs for individuals presenting at-risk and are on a trajectory towards developing EDs. This study is a randomized controlled trial evalu-ating an innovative digital gamified Acceptance and Commitment early-intervention program (AcceptME) for young females showing signs and symptoms of an ED and at high-risk for an ED. Participants (N=92; Mage=15.30 years, SD=2.15) received either AcceptME (N=62) or a waitlist control (N=30). Analyses indicated that the AcceptME program effectively reduced weight and shape concerns, with large effects when compared to waitlist controls. Most participants scored below the at-risk cut-off (WCS score<52) in the AcceptME at end-of-intervention (57.1%) com-pared to controls (7.1%) with odds of falling into the at-risk group being 14.5 times higher for participants in the control group. At follow-up, 72% of completers reported scores below the at-risk cut-off in the AcceptME group. The intervention also resulted in a decrease in ED symp-tomatology and increased body image flexibility. Overall, results suggest that the AcceptME program holds promise for early-intervention of young women at-risk for developing an ED.