Background: Little information exists regarding the differences in the clinical and laboratory characteristics of Kikuchi-Fujimoto disease (KFD) according to age. Objective: To evaluate the clinical and laboratory characteristics of KFD according to age. Methods: We retrospectively evaluated patients diagnosed with KFD at Pusan National University Hospital between 2010 and 2020. Results: Eighty patients (46 children and 34 adults) with a mean age of 21.5 ± 11.8 years (range, 3–49 years) were included in the study. Among children, the male sex ratio was higher, in adults, the female sex ratio was higher. Fever, tenderness in the lymph node, and skin rashes were more common in children, while myalgia and weight loss were more common in adults. In children, the recurrence rate was significantly higher among boys than among girls (15.8% vs 0.0%, P=0.001). EBV and ANA positivity rates were higher in boys than in girls. In adults, the recurrence rate was significantly higher in women than in men (18.2% vs 0.0%, P=0.005). ANA positivity rates were higher in women than in men. Conclusion: The clinical features, laboratory findings, and recurrence of KFD may differ depending on age and sex. Clinicians should be aware of this.

The aim of this work was to study age-related changes in the behaviour of adult Wistar rats using the open field (OF) and elevated plus maze (EPM) tests. Behavioural changes related to motor activity and anxiety were of particular interest. Results showed that as male and female rats progressed from 2 to 5 months of age there was a decrease in the level of motor and exploratory activities, and an increase in the level of anxiety. Age-related changes were dependent upon initial individual characteristics of behaviour. For example, animals that demonstrated high motor activity at 2 months become significantly less active by 5 months, and animals that showed a low level of anxiety at 2 months become more anxious by 5 months. Low-activity and high-anxiety rats did not show any significant age-related changes in OF and EPM tests from 2 to 5 months of age, except for a decrease in the number of rearings in EPM. Significant individual differences in the behaviour of rats in OF and EPM tests observed at 2 months were not apparent by 5 months.

A key concern in an ageing society is citizens’ mobility. As populations age, disability impairments can affect active ageing, health-related wellbeing and quality of life. In this paper, we present the on-going research project SeriousGiggle—Game-based learning for triggering active ageing. Its goal is to assess the potential of game-based learning for active ageing and contribute to a sense of wellbeing and quality of life. It also seeks to improve the mobility of older adults by creating a set of journey plans with route guidance that are rated in terms of safety, community support, environment and age-friendliness. Drawn on our field work with 33 co-designers, 40 end users and 10 semi-structured interviews with Subject Matter Experts, we identify a set of necessary design requirements to an Age-friendly Playable City. This study recommends the use of gamification and playful techniques to engage the end-users to provide information about local traffic signs, pavement conditions, wayfinding and, therefore, help to create route guidance and walking assistance that are personalized to older adults’ context in terms of location, travel fitness, mobility impairments and motivations.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

Abstract: Extensive research shows nurses’ work environment to be particularly stressful. This study develops, explores, and psychometrically tests a new profession specific ques-tionnaire identifying generalized and specific resistance resources, that make it possible to measure resources to manage work-related stress. An exploratory study design was em-ployed. The questionnaire was developed inspired by the MEASURE approach and the salutogenic theory of health. Building on the results from a literature review of nursing re-search and salutogenesis, supplemented by twelve interviews with hospital nurses, an item pool was generated. A first version was pilot tested in a group of nurses who were studying to become specialist nurses. A second version of the questionnaire was psycho-metrically tested on nurses in close patient care (n = 475), analysed using Principal Com-ponent Analysis as the extracting technique to identify the underlying structure of the questionnaire. The Principal Component Analysis revealed a four-component model of 19 items. “Manageability as a resource for handling the workload” was the strongest compo-nent, accounting for 21 % of the explained variance. “Contacts with patients as resources for nurses’ job satisfaction” (17.8 %). “Professional attitudes are labelled as resources to nursing” (15 %). “Colleagues are important resources for remaining in the nursing profes-sion” (11 %). The structure of the questionnaire indicates its usefulness in clinical practice for measuring resistance resources.

The Global Burden of Disease Study (GBD) 2019 reveals an increasing prevalence of Type 2 Diabetes Mellitus (T2DM) from 1990 to 2019. This study delves into the role of dietary risk factors across different demographic and socioeconomic groups. Utilizing data from the GBD 2019, it analyzes age-adjusted T2DM metrics—death counts, Disability-Adjusted Life Years (DALYs), and Age-Standardized Rates (ASR)—stratified by age, sex, and region. The study employed Estimated Annual Percentage Changes (EAPCs) to track trends over time. Results show that in 2019, 26.07% of T2DM mortality and 27.08% of T2DM DALYs were attributable to poor diets, particularly those low in fruits and high in red and processed meats. Geographic variations in T2DM trends were significant, with regions like Southern Sub-Saharan Africa and Central Asia experiencing the most substantial increases in Age-Standardized Mortality Rate (ASMR) and Age-Standardized DALY Rate (ASDR). A positive correlation was noted between Socio-Demographic Index (SDI) and T2DM burden due to dietary risk factors. The study concludes that targeted public health initiatives promoting dietary changes could substantially reduce the global T2DM burden.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

This study examines the capacity of a Site-Specific Fodder Management Decision Support System (SSFM-DSS) model to assist in successful cultivation of sericea lespedeza [SL; Lespedeza cuneata (Dum.-Cours.) G. Don.], with a specific focus on small-scale agricultural systems in the southeastern United States (U.S.). The study emphasizes incorporating advanced geospatial technologies, such as Geographic Information Systems (GIS), remote sensing, and Global Navigation Satellite Systems (GNSS), to improve fodder production. The research showcases the versatility of SL under varying environmental conditions, underscoring its significance in promoting sustainable livestock production. The methodology integrates empirical field data, geospatial analysis, and predictive modeling to formulate an SSFM strategy customized to address the distinct difficulties climate change presents, such as sudden and severe drought conditions. The study introduces an automated geospatial model for assessing the appropriateness of SL production throughout Alabama, Georgia, and South Carolina. The model uses many environmental criteria, including soil properties, climate fluctuations, and terrain. Furthermore, the research was instrumental in development of a WebGIS Dashboard, which offers farmers a decision assistance system to enhance the sustainable production of SL. The results highlight the significant impact that a SSFM-DSS can have on promoting sustainable agricultural practices, providing a solution to address the issues of food security and environmental concerns in agriculture.

Repurposing previously approved drugs may fast track the route to clinic for potential senotherapeutics and improves the inefficiency of the clinical drug development pipeline. We carried out a repurposing screen of 240 clinically approved molecules in human primary dermal fibroblasts for effects on CDKN2A expression. Molecules demonstrating effects on CDKN2A expression underwent secondary screening for senescence-associated beta galactosidase (SAB) activity, based on effect size, direction and/or molecule identity. Selected molecules then underwent a more detailed assessment of senescence phenotypes including proliferation, apoptosis, DNA damage, senescence-associated secretory phenotype (SASP) expression and regulators of alternative splicing. A selection of the molecules demonstrating effects on senescence were then used in a new bioinformatic structure-function screen to identify common structural motifs. 90 molecules displayed altered CDKN2A expression at one or other dose, of which 15 also displayed effects on SAB positivity in primary human dermal fibroblasts. Of these, three were associated with increased SAB activity, and 11 with reduced activity. The female synthetic sex hormones; diethylstilboestrol, ethynyl estradiol and levonorgestrel; were all associated with a reduction in aspects of the senescence phenotype in male cells, with no effects visible in female cells. Finally, we identified that the 30 compounds that decreased CDKN2A activity the most had a common substructure linked to this function. Our results suggest that several drugs licenced for other indications may warrant exploration as future senotherapies, but that different donors and potentially different sexes may respond differently to senotherapeutic compounds. This underlines the importance of consideration of donor-related characteristics when designing drug screening platforms.

Sexual selection involving female choice or female preference (‘inter-sexual’ selection) or male-male competition (‘intra-sexual’ selection) is one of the key mechanisms for evolutionary diversification and speciation. In particular, sexual selection is recently suggested to be an important mode to drive the evolution of “novel” phenotype (i. e. “evolutionary novelty”). Despite extensive studies performed on sexually selected traits or male-specific ornaments (or weapon-like structures) with respect to their evolutionary origin and history and fitness benefits, relatively little is known about the molecular genetic mechanisms underlying their developmental process. However, with advances of genomic technologies (including whole transcriptome analysis using Next Generation Sequencing [NGS] techniques; RNA-Seq), progresses have been made to unveil the genetic background underpinning diverse sexually selected traits in different animal taxa. In the present review, we compile empirical data on the genes, genetic mechanisms or regulatory pathways underlying various sexually selected traits to explore whether the “common” genetic architectures shape the development and evolution of those traits across evolutionarily distant animal lineages. We show that the recruitment of pre-existing genetic network for a new purpose (i.e. gene network “co-option”) is rather widespread in the development and evolution of sexually selected traits, indicating that particular genes or gene-sets are repeatedly involved in different sexually selected traits. Information of genes or genetic mechanisms regulating the development of sexually selected traits would be an essential piece to complete a whole picture of the origin and evolution of sexually selected traits.

According to the guidelines of the European Association of Urology (EAU), it is recommended to exclude PSA testing when the expected remaining lifespan is less than 10 years. In this study, we provide a comprehensive analysis of the impact of prostate-specific antigen (PSA) testing on the quality of life of elderly men who are frail. We conducted a comprehensive literature review to identify publications that examine the use of PSA as a screening and prognostic tool for prostatic illnesses in frail men. Our search included the following keywords: Prostate-specific antigen, Frailty, Prostate cancer screening, Hypogonadism, and Benign Prostatic Obstruction (BPO). Prostate-specific antigen (PSA) testing can be used to identify prostate cancer in its early and treatable stages in fragile men with a life expectancy of over 15 years. Additionally, PSA testing allows for the evaluation of the effectiveness of various prostate cancer treatments and the monitoring of testosterone replacement therapy for hypogonadism. PSA is also indicative of the clinical development of patients with benign prostatic obstruction (BPO). Nevertheless, PSA is being extensively provided without individualised patient assessment, contributing to the economic strain on healthcare systems. Conducting a frailty evaluation on men to determine the potential advantages of PSA tests on their quality of life will help minimise avoidable expenses.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

This study aims at the sustainable valorization of eggshells (ES) from different countries of origin in cement concrete as a cement replacement for Hong Kong. For this purpose, sixteen different eggs from different regions across the world were selected from the local market. Firstly, the extent of uniformity in the weight and mineral content of sampled eggshells were assessed by a specific gravity test and thermogravimetric analysis (TGA), respectively. It was found that specific gravity varies between 2.02 and 2.39, with an average value of 2.20 ± 0.01, whereas CaCO₃ varies between 94.65% and 97.23%, with an average value of 96.33%. These values were a bit lower than those of extra-pure limestone (LS) because of the organic part and the porous structure of eggshells. Secondly, three different eggshells were selected for cement replacement in cement concrete, both in the uncalcined and calcined states, based on having the highest, medium, and lowest CaCO₃ content, respectively. To get the calcined eggshells, the eggshells were calcined at 800^oC for three hours. It was found that the strength of eggshells varies with CaCO₃, but the variation was acceptable. The calcined eggshells showed comparatively more compressive strength and were close to the LS because of the free CaO and the absence of an organic part. In general, the variation in the basic properties of eggshells from different regions across the world is negligible and suitable to use as a cement replacement with acceptable variation in strength in Hong Kong.

Psychological readiness following Anterior Cruciate ligament Reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7±2.5 years old; 174.2±7.5 cm; 70.2±8.5 kg; 18.2±8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°.s-1 and 180°.s-1). Based on ACL-RSI scores, they were divided into “cases” and “controls”, deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps’ and hamstrings’ rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls cases showed significantly lower angle-specific quadriceps and hamstrings torque close to extension and lower RTD, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes’ RTS by focusing on the restoration of RTD and strength at angles close to full knee extension.

Genetic engineering technology offers opportunities to improve many important agronomic traits in crops, including insect-resistance. However, genetically modified (GM) exogenous proteins in edible tissues of transgenic crops has become an issue of intense public concern. To advance the application of GM techniques in maize, a Cre/loxP-based strategy was developed for manipulating the transgenes in green tissues while locking it in non-green tissues. In the strategy, the site-specific excision can be used to switch on or off the expression of transgenes at specific tissues. In this work, two basic transgenic maize named KEY carrying the Cre gene and LOCK containing the Vip3A gene with a blocked element, were obtained based on their separate fusion gene cassettes. The expression level and concentration of Vip3A were observed with high specific accumulation in green tissues (leaf and stem), and only a small amount in root and kernel tissues in the KEY × LOCK hybrids. The insect-resistance of transgenic maize against two common lepidopteran pests, Ostrinia furnacalis and Spodoptera frugiperda, was assessed in the laboratory and field. The results indicated that the hybrids possessed high resistance levels against the two pests, with mortality rates above 73.6% and damage scales below 2.4 compared with the control group. Our results suggested that the Cre/loxP-mediated genetic engineering approach has a competitive advantage in GM maize. Overall, findings from this study are significant for providing a feasible strategy for transgenes avoiding expression in edible parts and exploring novel techniques toward the biosafety of GM plants.

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

The length of stay (LOS) in the hospital emergency department (ED) is a crucial key performance indicator that is used to track and manage the performance of the ED as a whole. Our study had two objectives. Firstly, we aimed to evaluate the association between LOS and the most common primary ICD-10 diagnoses. To achieve this, we examined LOS in groups with specific (internal, surgical, neurological, and traumatic diseases) and non-specific diagnoses in adult ED visits at a tertiary referral hospital between 2017 and 2019 (134,675 visits in total). Our secondary objective was to measure LOS by age, day of the week, time of day, and season. The mean LOS was 254 minutes and was the shortest in the traumatic group (160 minutes), while in other groups it was significantly longer: neurological by 185 minutes, internal medicine by 158 minutes, surgical by 36 minutes, and non-specific by 24 minutes. In conclusion, non-specific diagnoses accounted for 21% of all ICD-10 primary diagnoses. In this group of patients, the percentage of hospitalizations was the highest. Other significant determinants of LOS were the patients’ age, the day of the week, the time of arrival, and repeated visits.

Pharmaceutically active compounds (PhACs) enter soil with organic substrates such as manure. Such complex substrates differently affect PhACs’ soil sorption. To elucidate the effects, batch experiments were conducted using five selected chemicals as model constituents. Urea, KH2PO4, acetic acid, phenol and nonadecanoic acid (C:19) altered the sorption strength and/or nonlinearity of sulfadiazine, caffeine and atenolol in a topsoil. The nonlinear Freundlich model best described sorption. Overall, the PhACs’ sorption coefficients increased in the sequence urea<phosphate<phenol<C:19<acetic acid. The sorption nonlinearity also increased in most cases. The effects on sulfadiazine and caffeine were rather similar, but in many cases different from atenolol. Phosphate mobilized sulfadiazine and caffeine and urea mobilized sulfadiazine, which was explained by sorption competition resulting from specific preference of similar sorption sites. Soil sorbed phenol strongly increased the sorption of all three PhACs; phenolic functional groups are preferred sorption sites of PhACs in soil. The large increase in sorption of all PhACs by acetic acid was attributed to a loosening of the soil organic matter and thus the creation of additional sorption sites. The effect of C:19 fatty acid, however, was inconsistent. These results help to better understand the sorption of PhACs in mixtures of soil and manure.

The endomembrane system in plant cells enables the cell to manage and coordinate a variety of membranous compartments so that they and their contents arrive at the right location. The secretory pathway takes part in this complex network and has its gateway at the Endoplasmic Reticulum. Therefore, alterations at the Endoplasmic reticulum level could condition how protein trafficking takes place or, at least, influence how such cargo leaves this organelle. With this work, we intended to assess how abnormalities at the Endoplasmic Reticulum would interfere with protein sorting and trafficking. Thus, we used a novel Arabidopsis mutant - leb-2 GFP-h -, presenting ER morphology alterations. Our results show that alterations in the leb-2 GFP-h mutant did not disrupt PSI A/B–mCherry transport to the vacuole but influences the expression of endogenous aspartic proteinases. Furthermore, the study of key-endomembrane genes expression revealed an upregulation of the SNAREs AtVAMP722 and AtVAMP723. As a whole, the leb-2 mutant seems not to interfere with vacuolar routes but may be implicated in secretion events.

Transgender (TG) describes individuals whose gender identity differs from the social norms. Some TG people undergo gender-affirming hormone therapy (HT) and may be considered as a sub-group of population susceptible to environmental contaminants for their targets and modes of action. Aim of the work is to set appropriate HT doses and identify specific biomarkers to implement TG animal models. Four adult rats/group/sex are subcutaneously exposed to 3 doses of HT (plus control) selected starting from available data. Demasculinizing-feminizing model (dMF): β-estradiol plus cyproterone acetate: 0.09+0.33, 0.09+0.93 and 0.18+0.33 mg, 5 times/week. Defeminizing-masculinizing model (dFM): testosterone 0.45, 0.95 and 2.05 mg, 2 times/week. Clitoral gain and sperm count, histophatological analysis of reproductive organs and liver, hormone serum levels and gene expression of sex-dimorphic CYP450 are evaluated. In dMF model, the selected doses, leading to T serum levels at the range of the corresponding cisgender, induced strong general toxicity and cannot be used in long-term studies. In dFM model, 0.45 mg of testosterone represents the correct dose. In addition, the endpoints selected are considered suitable and reliable to implement the animal model. The sex-specific CYP expression is a suita-ble biomarker to set proper (de)masculinizing/(de)feminizing HT and to implement TG animal models.

: Using line × tester analysis, the current research analyses parental genotypes and their combinations in normal conditions and identifies the genes influencing yield characteristics. In the present study, 15 diverse genotypes, including 10 lines, 5 testers, and 50 F1s hybrids, were evaluated for 13 morphological and 2 biochemical traits. A suitable location was taken to study the effect of 15 characters. The results exposed that ability mean squares were significant for all studied additive and non-additive components. In this direction, the general combining ability of PBW-343, DBW-39, K-402, K-1317, KRL-210, and K-68 were higher than the remaining parents. For morphological traits like yield, the top five crosses were described based on SCA effects, namely, HD-3086 × HD-3171, K-402 × K-9107, K-1317 × K-9107, HD-2967 × K-0307 and K-402 × K-68 in F1 generation. In addition, the high value of heritability was estimated for plant height (77.32%), spike length (32.26%), biological yield/plant (59.52%), and grain yield/plant (68.76%). However, the moderate values of heritability were estimated for days to maturity (22.78%) and phenol color reaction (18.00%). The higher genetic advance was not found for recorded characters; however, a moderate genetic advance was recorded for grain yield per plant (13.15%) and harvest index (11.72%). High heritability coupled with moderate genetic advance was recorded for two characters grain yield per plant and harvest index in F1 and F2 generations.

With a longer-term goal of addressing the comparative behavior of the aqueous halides F$^-$, Cl$^-$, Br$^-$, and I$^-$ on the basis of quasi-chemical theory (QCT), here we study structures and free energies of hydration clusters for those anions. We confirm that energetically optimal $(\mathrm{H_2O})_n\mathrm{X}$ clusters, with X = Cl$^-$, Br$^-$, and I$^-$, exhibit \emph{surface} hydration structures. Computed free energies based on optimized surface hydration structures utilizing a harmonic approximation, typically (but not always) disagree with experimental free energies. To remedy the harmonic approximation, we utilize single-point electronic structure calculations on cluster geometries sampled from an AIMD (\emph{ab initio} molecular dynamics) simulation stream. This \emph{rough-landscape} procedure is broadly satisfactory and suggests unfavorable ligand crowding as the physical effect corrected. Nevertheless, this procedure can break down when $n \gtrsim 4$, with the characteristic discrepancy resulting from a relaxed definition of clustering in the identification of $(\mathrm{H_2O})_n\mathrm{X}$ clusters, including ramified structures natural in \emph{physical cluster theories.} With ramified structures, the central equation for the present rough-landscape approach can acquire some inconsistency. Extension of these physical cluster theories in the direction of QCT should remedy that issue, and should be the next step in this research direction.

The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and in-sect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The Zinc-finger an-tiviral protein (ZAP) in vertebrate cells can bind CpG dinucleotides in viral RNA, limiting virus replication. Interestingly, the genomes of ISFs contain more CpG dinucleotides compared to VIFs. In this study, we investigated whether ZAP prevents two recently discovered lineage II ISFs, Binjari (BinJV) and Hidden Valley viruses (HVV) from replicating in vertebrate cells. BinJV protein and dsRNA replication intermediates were readily observed in human ZAP knockout cells when cultured at 34 ˚C. In ZAP expressing cells, inhibition of the interferon response via interferon response factors 3/7 did not improve BinJV protein expression, whereas treatment with kinase inhibitor C16, known to reduce ZAP’s antiviral function, did. Importantly, at 34 ˚C both BinJV and HVV successfully completed the infection cycle in human ZAP knockout cells evident from infectious progeny virus in the cell culture supernatant. Therefore, we identify vertebrate ZAP as an important barrier that protects vertebrate cells from ISF infection This provides new insights into flavivirus evolution and the mechanisms associated with host switching.

The energy efficiency of grinding depends on the appropriate selection of cutting conditions, grinding wheel and workpiece material. Additionally, the estimation of specific energy consumption is a good indicator to control the energy consumed during the grinding process. Consequently, this study develops a model of material removal rate to estimate the specific energy consumption based on the measurement of active power consumed in a plane surface grinding of C45K with different thermal treatments and AISI 304. This model identifies and evaluates the power dissipated by sliding, ploughing and chip formation in a industrial-scale grinding process. Furthermore, the instantaneous positions of the abrasive grains during cutting are described to study the material removal rate. The estimation of specific chip formation energy is similar to that described by other authors in laboratory scale, which allows to validate the model and experiments. Finally, the results show that the energy consumed by sliding is the main phenomenon of energy dissipation in industrial-scale grinding process, where it is denoted that sliding energy by volume unity decreases as the depth of cut and speed of workpiece increase.

The seasonally adjusted civilian labor force participation rate, the sum of employed and unemployed persons as a percentage of the civilian non-institutional population, is analysed in the general to specific modelling framework with a saturating set of step indicators from January 1977 through June 2018. The results indicate that, ceteris paribus, the rise in the ratio of women to men in the labor force in addition to positive demographic movements can largely account for the rise in the labor force participation rate up to January 2000. Subsequently, the aging population helps to explain the decline. Recessions play a transitory role.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

In the context of artificial intelligence's pervasive integration across sectors, the rigorous examination of methodologies used in constructing mathematical models is imperative. This study delves into facial recognition models, particularly in their ability to extract features such as age. We address the prevalent practice of training models with unbalanced datasets and its implications for model performance and bias introduction. Utilizing 27,305 facial images, we investigate the influence of dataset imbalance on age prediction based on ethnicity. Employing preprocessing and oversampling techniques, we equalize sample sizes across ethnicities. A Convolutional Neural Network trained on the balanced dataset serves as our baseline, while three additional models undergo training with a 50% sample size reduction for each group to assess accuracy degradation. Our findings reveal a notable decline in accuracy for ethnic groups with reduced representation. The Asian group experiences a 67.94% accuracy deterioration, followed by a 51.60% drop for the Black group, and a 38.46% decline for the White group. These results underscore the sensitivity of certain ethnic groups to underrepresentation, highlighting the nuanced impact on age prediction accuracy. While a 50% reduction in representation does not uniformly result in a 50% accuracy decline, it unquestionably influences predictive accuracy for affected groups.

INTRODUCTION: With an increase in the aging population, the application of evidence-based practice in geriatric education can strengthen knowledge, skills, and clinical experience for healthcare students caring for older adults. Age Friendly Health Systems (AFHS) is one of the frameworks founded on providing evidence-based and low-risk care centered on what matters most to older adults, their families, and caregivers. Virtual Reality (VR) platforms are gaining popularity due to their ability to provide an immersive, hands-on learning experience resembling an actual medical practice or care setting. Immersive learning enhances students’ sensory perceptions, promoting an innovative and engaging way of acquiring concepts that are difficult to teach in real life. This study aimed to design, develop, implement, and evaluate a case-based training module highlighting AFHS and educating medical students on the 4Ms approach in geriatric care (What Matters, Medication, Mentation, and Mobility). METHODOLOGY: The project was a feasibility study completed in two phases. Phase one included planning and development of a case-based scenario incorporating 4Ms of AFHS. Phase two included implementing and evaluating the VR training module into the geriatric curriculum for medical students. RESULTS: The final VR case displays a hospital and post-acute setting where an elderly patient is admitted for a hip fracture. Students learn how to triage and treat patients from admission to discharge while demonstrating their knowledge of AFHS. Approximately 10% of students completed the evaluation survey, and preliminary results indicate significant knowledge change in pre-post scenario-based training on AFHS. CONCLUSION: The VR education platform and embedded scenario promise an innovative adaptation of technology in learning the concepts of the 4Ms of AFHS. However, future studies should explore VR education with clinical assessment evaluation to ensure competence in providing Age-Friendly care.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

Keywords: Addis Ababa; dietary factors; nutritional status; school-age children

In recent years, there has been a growing interest in the prediction of facial age due to its diverse applications in fields such as security, entertainment, and healthcare. The current scourge of underaged voting in Nigeria is a problem and this research delves into the realm of facial age prediction by employing four well-known convolutional neural network (CNN) architectures, namely VGG16, ResNet50, Mobile Net, and VGG19 to predict chronological ages from facial pictures of person. The objective is to achieve precise age estimation from facial images, utilizing two datasets: UTKFace and CASIA African Facial Datasets. The results of this investigation are noteworthy. Specifically, the VGG16 model which demonstrated remarkable performance, yielding a Mean Absolute Error (MAE) of 1.76 when applied to the UTK-Face dataset. Additionally, when utilizing Mobile-Net, an unprecedented MAE of 1.10 was achieved for the Casia Africa Face Dataset. Notably, this marks the first instance of employing the dataset for facial age detection with CNNs, and this approach outperformed previous works, yielding the lowest MAE among all the studies reviewed.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS.Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm³. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume.Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS. Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm3. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: Myocardial infarction (MI) is a major cause of mortality worldwide. Its presentation as ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) is influence by atherosclerosis risk factors. Aim: To assess the patterns of presentation and predicting risk factors of acute MI in Kosovo. Methods: This is a cross sectional study from the Clinic of Cardiology of the University Clinical Center of Kosovo, which included all patients hospitalized with acute MI over a period of 7 years (January 1st, 2014 to December 31st, 2020). Data was collected using a structured questionnaire and epidemiological patterns and risk factors were analyzed. Results: Among 7353 patients admitted with acute MI (age 63 ± 12 years, 29% female), 4366 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. Patients age was not different between the two groups (p=0.077). NSTEMI patients smoked less (48.3% vs. 54%, p<0.001), but were more diabetics (37.8% vs. 33.6%, p<0.001), more hypertensives (69.6% vs. 63%, p<0.001), frequently had family history for coronary artery disease (CAD) (40% vs 38%, p=0.009), and included more females compared to STEMI patients (32% vs 27%, p<0.001). The two groups of patients, did not differ in the prevalence of significant CAD on angiography (66.8% vs. 67.8%, p = 0.396), but NSTEMI patients underwent less primary percutaneous interventions compared with STEMI patients (43.6% vs. 55.2%, p < 0.001). Conclusion: In Kosovo, STEMI is commoner than NSTEMI, who were mostly males, more likely to have diabetes, hypertension and family history for CAD compared to those with NSTEMI. Smoking and arterial hypertension proved the strongest predictors of acute MI, in Kosovo, thus highlighting the urgent need for better atherosclerosis risk control and education strategy.

Introduction: Determination of radiological bone age (BA) is a diagnostic method that consists of estimating chronological age (CA) from the bone maturation of children. Although environmental and hormonal factors can interfere with bone ossification, the process is essentially dependent on ancestral inheritance. These ethnic backgrounds are not usually considered, which can lead to biased interpretations and inadequate decision-making by pediatricians or forensic experts. The objective of this study was to determine the precision and accuracy of these radiological procedures among different ethnic groups. Methods: A qualitative systematic review carried out following MOOSE statement and previously registered in the International Prospective Registry of Systematic Reviews PROSPERO (CRD42023449512). Search was performed in MEDLINE (PubMed) (n=561), Cochrane Library (n=261), CINAHL (n=103), Web of Science (WOS) (n=181) and public institutional repositories (n=37) from inception to 31st December 2022 using Mesh as “Diagnostic Techniques and Procedures”, “Diagnostic imaging”, “Radiography”, “Age Determination by Skeleton” and free terms combining with booleans “AND” and “OR”. PEDro scale, and Risk of Bias in non-randomized Studies of Exposure (ROBINS-E) were used to assess methodological quality and risk of bias of included studies respectively. Results: 51 articles (n=19,531) were included according to the inclusion criteria previously established. There was a good to moderate methodological quality and a high to very high risk of bias. Skeletal methods for determining BA were precised in terms of intra-observer and inter-observer reliability in all ethnic groups. Regarding to accuracy of Skeletal methods in Caucasians and Hispanic children, GPA was accurate at all ages, but in youths, TW3 RUS could be a consistent alternative. In Asian and Arab, GPA and TW3 overestimated BA in adolescents near adulthood. In African youths, GPA overestimated BA while TW3 was more accurate in estimating CA. Dental and Cervical radiographic methods are equally precise but lesser accurate than Skeletal BA determination. Conclusion: Skeletal radiographic methods GPA and TW3 are both precise for BA determination among all ethnical groups, but their accuracy in estimating CA can be altered by racial bias.

Malnutrition is the main cause of child mortality in developing nations, especially in Sub-Saharan Africa and South Asian countries. This undernutrition status is predominantly higher among primitive tribal (ST) children under 5 years of age. The nutritional status of tribal children is a serious concern in India. For this, there should be intends to examine the prevalence and determinants of primitive tribal children's nutritional status. To investigate the effect of household, child’s & maternal characteristics on biological children under 5 years of age. The study aims to find out the association between some selected determinants on scheduled tribe child’s nutritional status. The study used some selected variable of scheduled tribe mothers, household characteristics and their children anthropometric indices from DHS datasets of India, which was published by the NFHS datasets of India. In this study People datasets and Children (Under 5 years of age) of interviewed women file datasets of NFHS-IV & V is taken. The datasets of West Bengal, ST mothers, and their child into consideration as per the research interest. Then to analyze the determinants of ST children (U5 age) nutritional status, some determinant factors are taken from mothers, children and household characteristics. Children’s stunting, wasting and underweight as dependent variable and the mothers, child’s and household’s characteristics as independent variable. The statistical analysis was done by using Pearson Chi square test used to analyze the association between dependent and independent variables. The study results shows that the mother’s educational status, child’s age, birth order, size of child at birth, type of residence had significant associations with stunting. Mother's anemia status and mother age had significant associations with wasting. Mother education, currently breastfeeding, child age, sex of the child, birth order, size of child at birth, type of residence, wealth, toilet facility, and cooking fuel shows a significant association with underweight. The results found that many determinant factors had a significant role among ST children's (U5 age) nutritional status. Thus, the findings will help to achieve tentative resource allocation, and utilization through various programs and policies to improve the ST children (U5 age) nutritional status. There is a need to take a multisectoral and multidimensional approach to develop for those primitive tribal children.

Deficiencies of vitamin B12 (B12) and folate (FA) are of particular interest due to their pleiotropic role in 1-carbon metabolism. In addition to adverse birth outcomes, deficiencies of B12 and FA, or an imbalance in FA/B12 status, are linked to metabolic disorders. Indian diets that are predominantly plant food-based could be deficient in these vitamins, but there are no national estimates of the prevalence of B12 and FA deficiency in Indian children and adolescents, nor of their associations with age, sex, and growth indicators. The recent Comprehensive National Nutrition Survey (CNNS-2016-18) provided estimates of the prevalence of B12 and FA deficiency at the national and state level among preschool (1-4y: 9,976 and 11,004 children respectively), school-age children (5-9y: 12,156 and 14,125) and adolescents (10-19y: 11,748 and 13,621). Serum B12 and erythrocyte FA were measured by the direct chemiluminescence method and their deficiency was defined using WHO cut-offs. The prevalence of B12 and FA deficiency was high among adolescents (31.0%, CI: 28.7-33.5 and 35.6%, CI: 33.1-8.2), compared to school-age (17.3%, CI: 15.4-19.3 and 27.6%, CI: 25.5-29.9) and preschool children (13.8%, CI: 11.7-16.2 and 22.8%, CI: 20.5-25.2, respectively). The prevalence of both B12 and FA deficiency was significantly higher by 8 and 5% points respectively, in adolescent boys compared to girls. The prevalence of B12 deficiency was higher in moderately stunted school children (by 18.9% points) than in normal children, but no such difference was observed for FA deficiency. There was wide regional variation in the prevalence of B12 and FA deficiency, but no rural-urban differences were observed across all age groups. The national prevalence of B12 deficiency among preschool or school-age children was <20% (the cut-off that indicates a public health problem). However, FA deficiency in these age groups and both FA and B12 deficiencies in adolescents were >20%, which warrants further investigation.

: Background: The thymus gland is the first lymphoid organ formed to regulate a newborn's immunity. It reaches its maximum size during puberty, after which it undergoes an atrophic procedure called involution, but its ability to grow again in response to some stresses, such as infections, neoplasia, surgeries, chemotherapy, and radiotherapy is maintained. There is not any comprehensive study on computed tomographic features of thymus gland in dogs. So, the goal of the present study is to achieve some information about thymus gland using computed tomography as a non-invasive method. Methods: One hundred and fifty dogs classified in 5 age groups and 2 breed groups were entered to this study and the thymus gland was evaluated using 2-slice computed tomography machine. The inclusion criteria for the present study were having normal complete blood count, plain and post-contrast CT scan examination of thoracic region and no history of neoplasia, chemotherapy or radiotherapy. The visibility, density, enhancement, grade, size, volume, shape, borders and lateralization of the thymus were evaluated and statistical analysis were performed. The effect of obesity on thymic grade and volume were also investigated. Results: The visibility, density, dorsal length, volume and grade decreased with increasing age. The thymic shape and lateralization were mostly wedge-shaped and left sided respectively. The borders became concave with aging and increasing body fat content caused to increase fatty degeneration of thymus. Conclusions: Declining of thymic density, grade, size and volume with aging was related to thymic involution and fatty degeneration was accelerated by increasing body fat content. Females and Males were different only in thymic shape and small and large breeds were different only in thymic volume. The thymus was visible in some geriatric dogs with no underlying disease. We hope that the present work can be used by radiologists in reading thoracic computed tomography but investigation of thymic characteristics in dogs with neoplasia and history of chemotherapy, radiotherapy and thoracic surgeries can complete this study.

Background. We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients’ age on the CM self-report was investigated. Methods. This retrospective, cross-sectional study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. The CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). Results. Three hundred thirty five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between the increasing patients’ age and a decreasing burden of CM. Conclusion. Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support the routine CM assessment in psychiatric clinical practice.

Cervical cancer is a public health issue with high disease burden and mortality in Brazil. The objectives of the present study were analyzing age, period, and cohort effects on cervical cancer mortality in women 20 years old or older from 1980 to 2019 in the North, South, and Southeast Regions of Brazil; and evaluating whether the implementation of a national screening program and the expansion of access to public health services caused impacts over the examined period and reduced the risk of death over the past years and among younger cohorts. The effects were estimated by applying Poisson regression models with estimable functions. The highest mortality rate by 100,000 women was found in Amazonas (24.13), and the lowest in São Paulo (10.56). A positive gradient was obtained for death rates as women’s age increased. The states in the most developed regions (South and Southeast) showed a reduction in the risk of death in the period that followed the implementation of the screening program and in cohort from the 1960s onwards. The North Region showed a decreased risk of death only in Amapá (2000–2004) and Tocantins (1995–2004; 2010–2019). The findings indicated that health inequities remain in Brazil and suggested that the health system has limitations regarding decreasing mortality associated with this type of cancer in regions with lower socioeconomic development.

Conclusions: Molecular classification could provide reliable supplementary information for evaluating prognostic and contribute to treatment option decision-making in EEC patients. Fertility-sparing treatment is not recommended for EEC patients with CNH and MSI-H. Furthermore, fertility-sparing treatment can be attempted in EEC patients with CHL, but regular follow-up should be carried out to early detection of EC relapse and prevention of disease progression.

This study used structural equation modelling (SEM) to evaluate the direct effect of sex and age on stroke types and outcomes in Tertiary Health Facilities in Rives State, Nigeria. The study was a cross-sectional retrospective hospital-based research that utilized specific stroke patients’ information between 2015-2019. The study obtained the sex and age, stroke type (ischemic/hemorrhagic), and outcomes (No disability/disability/death) from the records. The retrieved data was Microsoft Excel (2016), then analyzed using SPSS (version 21, Amos) and STATGRAPHICS centurion (Stat Point Tech., Inc.). From the result, out of the recorded 1916 stroke patients, 1229 (64.1%) were female, while 687 (35.9%) were males. The older adults (>55 years) had more recorded cases (n=1289) than young adults (ages 18–35 years; n=77) and middle-aged adults (ages 36–55 years, n=550). The SEM results showed that age was significantly associated with stroke type (P<0.001) and outcomes (P=0.038), while sex was significantly associated with stroke outcomes (P<0.001). The likelihood of death was 1.3 times higher in hemorrhagic stroke than ischemic stroke. In conclusion, age and sex had direct effects on stroke type, while age had a direct effect on stroke outcome. Hemorrhagic stroke was more likely to cause death than ischemic stroke in the studied population.

When in doubt, asking a peer can be very helpful. Students learn a lot of social strategies from peers. However, stated preference studies [Newman, 1993] have found that for elementary school students with math questions they prefer to ask the teacher. In this paper, we study revealed preferences instead of stated preferences. We analyze the behavior of fourth-grade students seeking face-to-face assistance while working on an online math platform. Students start by working independently on the platform before the teacher selects two or three tutors from among those who have answered 10 questions correctly. Each student is then able to choose between the teacher or one of these tutors when requesting assistance. We study the students’ preferences over 3 years, involving 88 fourth-grade classes, 2,700 students, 1,209 sessions with classmate tutors, and a total of 16,485 requests for help when there was an option to choose between a teacher or a classmate. We found that students prefer asking classmates for help 3 times more than asking their teachers when given the choice. Furthermore, this gap increases from the first to the second semester. We also found that students prefer to request help from classmates of the same sex and of higher academic performance. In this sense, students from the two highest tertiles sought help from classmates in the same two tertiles, and students from the medium tertile prefer to seek help from students of the highest tertile. However, students in the two lowest tertiles do not prefer asking for help from students from the top tertile more than from their own tertiles.

Objectives: To determine the prevalence of controlled systemic hypertension and its associated risk factors among the hypertensive patients who attended the clinic at Mbeya Zonal Referral Hospital in Tanzania. Methods: A descriptive cross-sectional quantitative study was used determine the prevalence of co to 252 hypertensive patients were recruited during clinic visit from September to November 2020 and participant was randomly selected interviews using structured self-administered questionnaires. Data was analyzed using chi square test to find the risk factors associated with controlled hypertension. Results: Among 252 participants, 94(39.7%) individuals with controlled hypertension giving the prevalence of controlled hypertension. The proportion of females with controlled hypertension was slightly higher than male (49 females to 45 males). The prevalence of uncontrolled hypertension was 152(60.3%) participants. The prevalence of controlled hypertension was higher among patients who have regular clinic visit (p< .05) and have daily adherence to their anti-hypertensive medication. A similar trend was observed among participants without financial challenges to attend clinic, short duration of illness, higher level of education and there was no association between age, sex, marital status, smoking, alcohol consumption, having health insurance and having chronic illness. Conclusion: Prevalence of controlled hypertension is higher among patients who have regular clinic visit and have daily adherence to their anti-hypertensive medication. Also, it is higher among participants without financial challenges to attend clinic so they can have regular clinic visit and checkup. Reinforcement on regular drug intake and clinic visit, good nutrition and reduced salt intake and modifying lifestyles of patient with hypertension is important.

Acute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discorvered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.

Shales are well known for their strong anisotrophic properties. The classical Athy’s model on the exponential porosity reduction with the depth commonly uses based on localities only. Shale compaction curve affects the results of the basin modeling as it is important input data, thus the standard compaction curve of shales needs to be established. This study provided a new data and complies available data of Thailand shales to propose the new empirical relationship among porosity, burial depth, and geological age. The numerical data of the geological time were estimated by the application from the relationship of velocity and depth in each geological ages. The variation of the Thailand shale data due to the different geological ages was found in this study. Finally, the standard curve of shale compaction proposed by Puttiwongrak et al. [9] was examined and confirmed by this research findings.

The hypothesis posed was whether participation in LaLiga Genuine Santander (competitive football) influenced the quality of life (QL) of the people who participated in it, since their perception of themselves is enhanced by all the aformentioned factors (self-determination, social inclusion, emotional well-being, physical well-being, material well-being, rights, personal development, interpersonal relationships). The objective was to evaluate the QL of people with Down's Syndrome (DS) using their self-perception (n=39) and the perception of the informants (family members, teachers) (n=39). The KidsLife-Down Scale, with a few modifications was used. In general, differences of opinion between the subgroups of participants with DS and informants showed that results were higher in terms of perception for participants in the DS subgroup. Scores for all variables were higher for those participants with DS who said they did engage in practicing competitive football. Despite the perception of informants provides a great deal of information regarding the QL of participants with DS, the latter should be involved in the evaluation process and their self perceptions taken into account. Our research shows that participation in the league modifies the perceptions of the participants with Down's Syndrome regarding their quality of life. However, these perceptions are not shared by the informants.

Distinguishable annual growth rings produce in Pinus roxburghii are an asset to find out the age of individual tree. This paper aimed to determine the age of P. roxburghii through coring samples and test the relationship with forest production. The biomass estimated, girths measured at two different sections and heights measured which allowed to determine the rate of tapering of the stand. The regression analysis was performed to test the relationship between various variables. The mean age of the P. roxburghii stand was found to be 23.97 (~24 years). The result showed the significant (p<0.05) positive correlation coefficient has been seen between age with girth at breast height, biomass, volume and carbon stock. However, no significant (p>0.05) correlation (r = 0.08) was found between age and height of the stand. In contrast, a correlation between diameter at breast height (DBH) was significant (p<0.05) and positive with volume, biomass, but no significant (p>0.05) correlation (r = 0.14) found between DBH and height of the stand. However, height has a significant (p<0.05) positive correlation with biomass. The mean biomass was 375 kg and mean annual increment (MAI) was 15 kg per tree. Rate of tapering of the studied stand predicted to be 3 cm diameter decreased with trunk height running at 100 cm from base to upward of P. roxburghii stand and vice versa. Result suggests that height-age relation is very weak whereas age, DBH, biomass and carbon has a significant correlation signifies that time-based forests' production and potential production estimation can be obtained in a relatively accurate way by utilizing the age of stand. The time-based forest production analysis is pioneer work in Nepal. The study affirms the tree ring count in P. roxburghii would be a credible and accurate method to determine the age of standing trees.

Many governments particularly in Europe are designing social interventions for the first post COVID-19 emergency phase. Definition of a ‘best practice’ for restriction release is urgent. Although data uncertainty generate difficulties, we believe near term analysis must shift from attempting to understand the numerous ‘unknowns’ to the clarification and interpretation of the few ‘knowns’, to create stepping stones towards rapid evidence-based decision making.Here, open access data on COVID-19 severity in three European countries were analyzed. Spain’s data were more comprehensive than those from Italy and Germany. Overall, COVID-19 severity shows a remarkable nonlinear growth with age that is significantly higher in adult males. Hence, age-adaptive and gender-balanced social interventions might represent efficient repopulation options for public health policymakers. Furthermore, we urge wider governmental effort for open access to relevant data. Their analysis will allow consolidation of existing trends, validation of key observations and thus facilitation of timely decisions.

In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

Kidney transplantation is the treatment of choice for patients with end-stage disease. To expand the donor reserve, it is necessary to use marginal/sub optimal donors that provide marginal organs. We retrospectively evaluated the short and long-term outcome of elderly kidney transplantation using allografts with vascular abnormalities. Between January 1999 and December 2018, 740 transplants from cadaveric donors were performed. Thirty-four elderly patients received a kidney transplantation with vascular anatomical variants (Group 1) were compared with 34 patients who received a kidney transplantation with single renal artery (SRA) (Grroup2) pair-matched by age, dialysis age, donor age, comorbidity. All participants completed the Long Form International Physical Activity Questionnaire (IPAQ) at baseline and after 4, 8, and 12 weeks after transplantation. The overall rate of surgical complications was 17.6% in Group 1 and 20.6% in Group 2, indicating that kidney with vascular anatomical variant might be successfully transplanted. Our data also emphasizes the importance of individualized physical activity in kidney transplantation with multiple arteries. Physical activity should be considered as an essential part of the medical care for renal-transplanted recipients.

We examined the causality between growth opportunities and earnings quality of the emerging economies. We develop an argument that growth opportunities should lead to high-quality earnings of the developing economies against the prior studies from developed economies which posit that growth opportunities result in a lower quality of earnings. The findings revealed that Growth Opportunities had a positive significant effect on Earnings Quality (EQ). Thus, the study concluded that growth opportunities are useful in determining the earnings quality of firms. The study recommends that managers should take advantage of their firms' growth opportunities to provide quality accounting information which will directly provide expanded opportunities for business growth. Though literature confirms that generally, earnings management might not be necessarily bad in business operational practice, managers are advised to avoid extreme aggressiveness in managing earnings as this may culminate in the negative manipulation of accounting information.

The role of the submission was to find out what changes people think they need to make in their home because of getting older. At advanced age, the likelihood of different limitations such as vision impairment, hearing impairment or physical inability is increased. Currently, tenants are often forced to leave their long-term living space, as these spaces cannot serve “new” individual needs. This transition from the privacy of their home to the new environment often appears to be a painful change. They will not have a well-known environment because their homes cannot be adapted to their new needs. The aim is a comprehensive approach to the design of such an exterior and interior space which could serve people at all stages of their life, including the terms of mobility. This means that even if there is an unexpected situation and changes in movement abilities and physiological limitations of man, not only by natural aging, but according to accidents or disabilities we can adapt the living space to the given conditions. The survey results are presented in Germany and Slovakia. In the survey, respondents expressed their opinion on what they considered important in creating an adaptive environment considering various life changes. Results are processed graphically with explanation. The results could be of an interest to architects and designers of the environment. Based on the results of the questionnaire survey, studies of possible modifications of flats and houses were developed. The contribution brought these results to three age groups of respondents; people aged 35, 50 and over 50.

Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (p&lt;0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). CONCLUSION: Compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Salt stress is one of the most severe environmental stresses limiting the productivity of crops, including rice. However, there is a lack of information on how salt-stress sensitivity varies across different developmental stages in rice. In view of this, a comparative evaluation of contrasting rice varieties CSR36 (salt tolerant) and Jaya (salt sensitive) was conducted, wherein NaCl stress (50 mM) was independently given either at seedling (S-stage), tillering (T-stage), flowering (F-stage), seed-setting (SS-stage) or throughout the plant growth, from seedling till maturity. Except for S-stage, CSR36 exhibited improved NaCl stress tolerance than Jaya, at all other tested stages. Principal component analysis (PCA) revealed that the improved NaCl stress tolerance in CSR36 coincided with enhanced activities/levels of enzymatic/non-enzymatic antioxidants (root ascorbate peroxidase for T- and S+T stages and root catalase for F-, S+T and S+T+F-stages) and higher accumulation of osmolytes (shoot proline for F-stage and S+T+F-stage), indicating better antioxidant capacitance and osmotic adjustment, respectively. In contrast, higher shoot accumulation of Na+ and consequent increase in Na+/K+, Na+/Ca+2 and Na+/Mg+2 ratio in root and shoot, were identified as major variables associated with NaCl stress induced growth reduction in Jaya. In addition, CSR36 exhibited higher levels of Fe3+, Mn2+ and Co3+ and lower Cl- and SO42-, suggesting its potential to discriminate essential and non-essential nutrients, which might contribute to NaCl stress tolerance. Taken together, the findings provided the frame-work for stage-specific salinity responses in rice, which will facilitate crop-improvement programs for specific ecological niches including the coastal regions. Rice, salt stress, stage-specific salinity, antioxidant defense, ionic homeostasis, salt tolerance

Cellular therapies have started an important new therapeutic direction for Autistic Spectrum Disease (ASD), and the ample diversity of ASD pathophysiology and the different types of cell therapies need an equally ample effort for studying the applicable ASD causes and the specific benefits of cell therapies via clinical studies.CORDUS Clinical Study is a crossover study in which autologous cord blood was administered intravenously to 56 patients between January 2019 and July 2023, and has compared its efficacy versus an individualized combination of supplements; both treatments were administered in a different sequence to all participants. Treatment efficacy was evaluated pre- and post- treatments by an independent psychotherapist with ATEC, Q-CHAT and a 16-item comparative table score, after interviews with the children’s parents and therapists.Cord blood was beneficial in the group of 3–7-year-old children (n=28; 3 out of 4 children – 78.57% - improved scores), but was much less effective in kids older than 8 years or with body weight of more than 35 kg (n=28; 1 out of 10 children improved scores). Individualized supplements were more efficacious than cord blood in 5 cases out of 28, while in 23 kids cord blood brought more improvement than supplements; 6 kids registered minor or no improvement. Statistically significant improvements were seen after cord blood infusion on areas such as verbalization and social interaction, but not on irritability or aggressive behavior; also ample individual differences were noted. No serious adverse reactions were noted during and after cord blood or supplement administration.

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

Background: The high prevalence of learning disabilities among children confirm that learning disabilities are surprisingly common. In absence of routine screening, many children still go undetected with a huge individual and family burden, while at the same time existing interventions are conflicting. The purpose of the study is to report on the design, implementation and evaluation of an innovative pilot intervention aiming to improve the quality of life of the family of students with specific learning disabilities. Method: For the purposes of this study, we used an experimental research design, using two groups (intervention and control). The intervention included four meetings with parents of children from the intervention group. To assess the quality of life of the students' family and the parenting style, the following measuring tools were used. They conducted at times and locations convenient to each participant. The instruments used to measure outcomes were two standard weighted questionnaires, the parenting style questionnaire and the family quality of life questionnaire. Findings: The results showed that the intervention program had significantly positive effects on both parenting style and children’s quality of life. Specifically, a decrease in parental authoritarianism and an increase in parental support were observed. Also, an increase in child-parent interaction, emotional and general well-being was found. Conclusion: The intervention program did improve the quality of life of the children by increasing all the variables related to the measurement of their quality of life.

Contrary to the long-held belief that the effects of vaccines are specific for the disease they were created; compelling evidence has demonstrated that vaccines can exert positive or deleterious non-specific effects (NSEs). In this review, we compiled research reports from the last 40 years, showing that live vaccines induce positive NSEs, whereas non-live vaccines induce several negative NSEs, including increased female mortality associated with enhanced susceptibility to other infectious diseases, especially in developing countries. These negative NSEs are determined by the vaccination sequence, the antigen concentration in vaccines, the type of vaccine used (live vs. non-live), and also by repeated vaccination. We do not recommend stopping using non-live vaccines, as they have demonstrated to protect against their target disease, so the suggestion is that their detrimental NSEs can be minimized simply by changing the current vaccination sequence. High IgG4 antibody levels generated in response to repeated inoculation with mRNA COVID-19 vaccines could be associated with a higher mortality rate from unrelated diseases and infections by suppressing the immune system. Since most COVID-19 vaccinated countries are reporting high percentages of excess mortality not directly attributable to deaths from such disease, the NSEs of mRNA vaccines on overall mortality should be studied in depth.

Rare-earth tetraborides RB4 are of great interest due to the occurrence of geometric magnetic frustration and corresponding unusual magnetic properties. While the Gd3+ spins in GdB4 align along the ab plane, Er3+ spins in the isomorphic ErB4 are confined to the c–axis. The magnetization in the latter exhibits a plateau at the midpoint of the saturation magnetization. Therefore, solid solutions of (Gd, Er)B4 provide an excellent playground for exploring the intricate magnetic behavior in these compounds. Single crystals of Gd(1-x)Erx B4 (x = 0, 0.2, and 0.4) were grown in aluminum flux. X-ray diffraction scans revealed single phase materials, and a drop in the unit cell volume with increasing Er content, suggesting the partial substitution of Er at the Gd sites. Heat capacity measurements indicated a systematic decrease of the Néel temperature (TN) with increasing Er content. The effective magnetic moment determined from the magnetization measurement agreed with the calculated free-ion values for Gd3+ and Er3+, providing further evidence for the successful substitution of Er for Gd. The partial substitution resulted in an anomalous ferromagnetic phase below TN, exhibiting significant anisotropy, predominantly along the c-axis. This intriguing behavior merits further studies of the magnetism in the Gd(1-x)ErxB4 borides.

Magnetic nanoparticles (MNPs) have attracted a great interest in nanomedical research. MNPs exhibit many important properties, particularly, magnetic hyperthermia for selective killing of cancer cells is one of them. In hyperthermia treatment, MNPs act as nano-heaters when they are under the influence of an alternating magnetic field (AMF). In this work, micromagnetic simulations have been used to investigate the magnetization dynamics of a single-domain nanoparticle of magnetite in an external AMF. Special attention is paid to the circumstances dealing with a dynamic phase transition (DPT). Besides, we focus on the influence of the orientation of the magnetic easy-axis of the MNP on the dynamic magnetic properties. For amplitudes of the external AMF above certain critical value, the system is not able to follow the magnetic field and it is found in a dynamically ordered phase; whereas for larger amplitudes, the state corresponds to a dynamically disordered phase and the magnetization follows the external AMF. Our results suggest that the way how the order-disorder DPT takes place, and both the metastable lifetime as well as the specific loss power (SLP), are strongly dependent on the interplay between the orientation of the magnetic easy-axis and the amplitude of the external AMF.

To create normative scores for all CrossFit® Open (CFO) workouts and compare male and female performances, official scores were collected from the official competition leaderboard for all competitors of the 2011-2022 CFO competitions. Percentiles were calculated in athletes (18 – 54 years) who completed all workouts within a single year ‘as prescribed’ and met minimum scoring thresholds. Independent t-tests revealed significant (p &lt; 0.05) sex differences for 56 of 60 workouts. In workouts scored by repetitions completed, men completed more repetitions in 18 workouts by small-to-large differences (d = 0.22-0.81), whereas women completed more repetitions in 6 workouts by small-to-medium differences (d = 0.36-0.77). When workouts were scored by time-to-completion, men were faster in 10 workouts by small-to-large differences (d = 0.23-1.12), while women were faster in three workouts by small differences (d = 0.46). In three workouts scored by load lifted, men lifted more weight by large differences (d = 2.00-2.98). All other differences were either trivial or not significant. Despite adjusted programming for men and women, the persistence of performances differences across all CFO workouts suggest resultant challenges are not the same. These normative values may be useful to training and research in male and female CrossFit® athletes.

SLI and SLD constitute two autonomous neurodevelopmental disorders, which frequently cause challenges in the diagnosis process, especially due to their nature, which has caused disagreement among clinicians regarding their recognition as separate or overlapping disorders. The objective of the study was to enlighten the path of valid diagnosis and intervention during adolescence when the two disorders change their manifestation and overlap. 200 Greek adolescents (140 boys and 60 girls), 124 already diagnosed with SLD and 76 diagnosed with SLI, 12-16 years old, participated in the study. All participants were assessed in reading, oral and written language and mathematics (mathematical operations and mathematical reasoning) along with IQ testing. In order to determine statistically significant differences, the chi-square test, independent samples t-test, odd ratios and their 95 per cent confidence intervals were implemented. The results revealed that the SLI group presented significantly greater difficulties than SLD in their overall cognitive-mental profile and in most language and mathematical measurements (number concept, executive-procedural part of solving operations and mathematical reasoning). The similarity of the two groups was mainly detected in their deficient metacognitive, metalinguistic and metamnemonic strategies. The research concludes that SLD adolescents managed to overcome their difficulties to a significant degree, while adolescents with SLI still struggle with many learning areas.

(1) Background: The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. (2) Methods: One hundred twelve 15-mer peptides covering the entire sequence of DTx protein were prepared by Spot-synthesis. Membrane-bound peptides immunoreactivity with sera from mice immunized with triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, MAPs synthesis, and ELISA development. (3) Results: Twenty epitopes were identified, being 2 in the signal peptide, 5 in the CD, 7 in the HBFT domain, and 5 in the RBD. Two 17-mer (CB/Tx-2/12 and CB/DTx-4-13) derived bi-epitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccined sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) either for huVS and miVS and when compared with a commercial ELISA test, demonstrate high performance. (4) Conclusions: Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated the specificity and eligibility to enter phase IIB studies of some epitopes to develop new and fast diagnostic assays.

Background The purpose of this study was to evaluate the prevalence of velamentous cord insertion (VCI) and the actual association between pathologically confirmed VCI and perinatal outcomes in twins based on the chorionicity. Methods All twin pregnancies who received prenatal care at a specialty clinic for multiple pregnancies, from less than 12weeks of gestation until delivery in a single institution between 2015 and 2018 were included in this retrospective cohort study. Results A total of the 941 twins were included in the study. The prevalence of VCI in dichorionic (DC) twins and monochorionic diamniotic (MCDA) twins was 5.8% and 7.8%, respectively (p=0.251). In all study population, the prevalence of vasa previa and placenta accreta were higher in VCI group compared to that of non-VCI group (p=0.008 and 0.022). In MCDA twins with VCI, birth weight, 1 and 5-minute Apgar score were lower compared to DC twins with VCI (p=0.010, 0.002 and 0.000). There was no significant association between VCI and selective fetal growth restriction (p=0.708), twin-to-twin transfusion syndrome (p=0.400) and birth-weight discordance (>20% and >25%) (p= 0.378 and 0.161) in MCDA twins. Conclusion VCI in twins was not a risk factor for adverse perinatal outcomes and twin-specific complications.

According the JKR theory of adhesive contact, changes of the contact configuration after formation of the adhesive neck and before detaching are completely reversible. This means, that after formation of the initial contact, the force-distance dependencies should coincide, independently on the direction of the process (indentation or pull-off). In the majority of real systems, this invariance is not observed. The reasons for this may be either plastic deformation in the contacting bodies or surface roughness. One further mechanism of irreversibility (and corresponding energy dissipation) may be chemical heterogeneity of the contact interface leading to the spatial dependence of the specific work of adhesion. In the present paper, this "chemical" mechanism is analyzed on a simple example of an axisymmetric contact (with axisymmetric heterogeneity). It is shown that in the asymptotic case of a "microscopic heterogeneity", the system follows, during both indentation and pull-off, JKR curves, however, corresponding to different specific surface energies. After the turning point of the movement, the contact area first does not change and the transition from one JKR curve to the other occurs via a linear dependency of the force on indentation depth. The macroscopic behavior is not sensitive to the absolute and relative widths of the regions with different surface energy but depends mainly on the values of the specific surface energy.

The cytokinins play important roles in plant growth and development by regulating gene expression at genome wide level. DNA methylation is responsive to the external environment, but whether DNA methylation changes in response to cytokinin treatment to regulate gene expression is still unclear. Here, we used bisulfite sequencing and RNA sequencing to examine genome-wide DNA methylation and gene expression patterns in poplar (Populus tomentosa) after treatment with the synthetic cytokinin 6-benzylaminopurine (6-BA). We identified 566 significantly differentially methylated regions (DMRs) in response to 6-BA treatment. Transcriptome analysis showed that 501 protein-coding genes, 262 long non-coding RNAs, and 15,793 24-nt small interfering RNAs were differentially expressed under 6-BA treatment. Among these, 79% were differentially expressed between alleles in P. tomentosa. Combined DNA methylation and gene expression analysis demonstrated that DNA methylation plays an important role in regulating allele-specific gene expression. To further investigate the relationship between these 6-BA-responsive genes and phenotypic variation, we performed SNP analysis of 507 6-BA-responsive DMRs via re-sequencing using a natural population of P. tomentosa and identified 206 SNPs that were significantly associated with growth and wood properties. Association analysis indicated that 53% of loci with allele-specific expression had primarily dominant effects on poplar traits. Our comprehensive analyses of P. tomentosa DNA methylation and the regulation of allele-specific gene expression suggest that DNA methylation is an important regulator of imbalanced expression between allelic loci.

As of today, there is not any direct report yet of the degree to which missing residues exist for experimentally determined membrane protein (MP) structures, which constitute more than half of current drug targets. With a chain- and position-specific visualisation and a statistical analysis of all MP structures inside PDB (as of September 25, 2019), this article argues that the experimentally uncharted territories (EUTs, i.e., consisting of missing residues) within PDB are pluggable and should be plugged with an experimental data-driven hybrid approach, and calls for continued development of MP structural determination with less and less EUTs, in light of MPs' crucial role in biological and biomedical research, both fundamental and pharmaceutical.

Bowlby’s (1969/1982) attachment theory has been employed as a broad and integrative framework to explore human wellness across a range of disciplines. Attachment theory has even been labelled one of the last surviving “grand theories” not to have been completely dismissed, replaced, or extensively reworked (e.g., Carr, 2012; Mercer, 2011). However, despite the ubiquitous nature of some of the theory’s fundamental tenets, there are always possibilities for new conceptual development, extension, and revision. In this paper, we critically explore the idea of “context-specific” attachment within parent-child relationships. We briefly outline critical assumptions and key areas of attachment and articulate potential rationale, conceptualisation, and relevance of contextual attachment.

This study aims to determine the optimal configuration (position and operation duration) for wall mounted mechanical mixers based on the comparison of three-dimensional computational fluid dynamics (CFD) modelling results and physical data collected from the treatment plant. A three-dimensional model of anoxic zone 1, 2 and 3 of Northern Wastewater Treatment Plant (WWTP) located at Cairns Regional Council, Cairns, Queensland, Australia was developed and validated. The model was used to simulate the flow pattern of the WWTP and the simulation results are in good agreement with the physical data varying between 0% to 15% in key locations. The anoxic zones were subject to velocities less than the desired 0.3 metres per second however results for suspended solids concentration indicate that good mixing is being achieved. Results for suspended solids concentrations suggest that the anoxic zones are towards the upper limits recommended by literature for specific power dissipation. The duration for operation of mechanical mixers was investigated and identified that the duration could be reduced from 900 seconds down to 150 seconds. Alternative mixer positioning was also investigated and identified positioning which would increase the average flow velocity with decreased duration (150 seconds). The study identified that Council may achieve savings of $24,000 per year through optimisation of the mechanical mixers.

Abstract: Presence in a recipient of antibodies directed against donor specific antigens represent a major obstacle in transplanting such patients. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques and old and new drugs are to date used to desensitize these patients. Desensitization may occur before transplantation or at the time of transplantation or after transplantation according whether physicians deal with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivity and specificity, different advantages and disadvantages. The target of the drugs used to desensitize are B cells, Plasma cells, the antibodies themselves and finally, the complement that is the final actor causing tissue disruption. If B cells are relatively easy to be targeted, more difficult are the plasma cell. Indeed, several new drugs are used in randomized trials also to defeat plasma cells. Antibodies may be removed rather easily, but often their removal is followed by a rebound. Complement is not easy to be defeated and new drugs are to date used to be successful in this action. However is to date possible to desensitize many patients and to obtain successful transplantation.

UNESCO highlights socio-emotional, cognitive, and behavioral learning as critical for advancing sustainability. As major events, sports generate significant social, economic, and environmental impacts. This study analyzed how academic background, gender, age, sport type, and modality influenced elite Colombian Olympic and Paralympic athletes' socio-emotional competencies. Methods: Colombian elite athletes who were members of the “Support to the Excellence Coldeportes Athlete” participated in the study. The total population studied included 334 Colombian elite athletes: mean age 27.10 ± 6.57 years old with 13.66 ± 6.37 years practicing his/her sports modality. The socio-emotional competencies of the participants were assessed using the Socio-emotional Competencies Scale (SECS). Results: Men scored higher in interpersonal regulation, self-awareness, conflict resolution, and emotional regulation. Younger athletes (≤25 years) had higher self-consciousness. Individual versus team sports did not differ. Paralympians showed higher motivation, self-awareness, teamwork, and emotional regulation. University educated athletes scored higher in motivation, self-awareness, teamwork, and empathy. All competencies positively correlated. Conclusion: Individualized interventions targeting improved socio-emotional performance are vital for sustainability and should account for differences across gender, age, education, and disability status.

Abstract: Sarcopenia poses a significant challenge to public health and can severely impact the quality of life of aging populations. Despite extensive efforts to study muscle degeneration using traditional animal models, there is still a lack of effective diagnostic tools, precise biomarkers, and treatments for sarcopenia. Zebrafish models have emerged as powerful tools in biomedical research, providing unique insights into age-related muscle disorders like sarcopenia. The advantages of using zebrafish models include their rapid growth outside of the embryo, optical transparency during early developmental stages, high reproductive potential, ease of husbandry, compact size, and genetic tractability. By deepening our understanding of the molecular processes underlying sarcopenia, we may develop novel diagnostic tools and effective treatments that can improve the lives of aging individuals affected by this condition. This review aims to explore the unique advantages of zebrafish as a model for sarcopenia research, highlight recent breakthroughs, outline potential avenues for future investigations, and emphasize the distinctive contributions that zebrafish models offer. Our research endeavors to contribute significantly to addressing the urgent need for practical solutions to the impact of sarcopenia on aging populations, ultimately striving to enhance the quality of life for individuals affected by this condition.

Treating clubfoot in walking age children is debated, despite studies showing that using Ponseti casting principles can correct the mid-foot effectively. We aimed to explore techniques and approaches for management of older children with clubfoot and identify areas of management consensus. A mixed-methods cross-sectional electronic survey on delayed presenting clubfoot (DPC) was sent to 88 clubfoot practitioners (response rate 56.8%). We collected data on decision-making, casting, imaging, orthotics, surgery, re-currence, rehabilitation, multidisciplinary care and contextual factors. The quantitative data were analysed using descriptive statistics and the qualitative data were analysed using conventional content analysis. Many respondents used the Pirani score and some used the PAVER score to aid deformity severity assessment and correctability [1,2]. Ponseti casting principles were consistently applied with a stepwise approach. Con-textual factors influenced the timing of the treatment, the decision to treat a bilateral deformity simultaneously, and casting intervals. Differences were seen around orthotic usage and use of tibialis anterior tendon transfer following full correction. The survey identified consensus areas in overall principles of management for delayed presenting clubfoot and implementation of Ponseti principles, indicating these principles are well recognized as a multidisciplinary approach for older children with clubfoot. Some dif-ferences in approach may reflect different economic or social contexts. The principles can be adapted well for different geographical and healthcare contexts.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness world-wide. We recently reported that polyethylene glycol (PEG) can activate the alternative pathway of the complement system and induce choroidal neovascularization (CNV) in mice. Currently, no other investigator has demonstrated CNV after PEG injection in the mouse eye. The aim of this article is twofold: we review the histologic changes in mouse retina and retinal pigmented epithelium (RPE) after treatment with PEG, and we summarize a model of wet and dry AMD pathogenesis in mice through subretinal PEG treatment of RPE cells and retinal layers. We injected (subretinal) male C57BL/6 mice with 2 μL of solution containing 0.5 mg and 1.0 mg of PEG or PBS in control groups. Eyes were harvested at day 1, 3 and 5 after injection and processed for analysis. Sections were immunohistochemically stained for complement component C3, mem-brane attack complex (MAC), and cytokeratin 18. Light and laser confocal microscopy was used for image capturing. PEG increased deposition of C3 and MAC on RPE cells and on all retinal layers after 1.0 mg injection. PEG induced loss of cellular contacts between RPE cells and migration of RPE cells in the subretinal space at day 1 after PEG injection. After 0.5 mg PEG injection, increased size of RPE cells was detected at day 3 and 5. Apoptotic bodies were observed in outer nuclear layer at day 3 and 5 after 0.5 mg PEG treatment. RPE cells with dark cytoplasm and condensed chromatin were observed. Higher doses of PEG induce CNV, encouraged RPE cell proliferation and death, and damage photoreceptors in mice. This simple and fast model may be useful to explore the pathogenesis of both dry and wet AMD.

Accurately estimating a person's age is crucial for identity verification at all critical checkpoints, including airports, land borders, and seaports. Human gait may be used as a biometric identifier and indicator of age, among other things. This study aims to develop methods for estimating a person's age by observing their walk. In this paper, a novel technique for preprocessing the proposed gait dataset has been used by utilizing a combination of the gait energy image (GEI), the accumulated frame difference energy image (AFDEI), and the invariant moment of the image. The proposed technique outperformed state-of-the-art methods in terms of accuracy. The proposed method was tested and evaluated using a convolutional neural network (CNN), and it achieved an average accuracy of 90.35% across 14 different view angles within 5 K-Fold, the proposed method resulted in 94.68% and 94.54% in 30º and 75º view degree respectively. concluding that the approach is effective and promising for estimating age using human gait.

(1) Background: Breast cancer is the second leading cause of cancer death among women. The accurate prediction of survival intervals will help physicians make informed decisions on treatment strategies or the use of palliative care for patients; (2) Methods: The gene expression is predictive and correlates to patient prognosis. To establish a reliable prediction tool, we collected the RNA-seq data of breast cancer patients, a total of 1187 RNA-seq data (median age 58 years), in FPKM format from the TCGA database. Among them, 144 RNA-seq data with date of death information was selected to establish the SaBrcada-AD dataset. We first normalized the SaBrcada-AD dataset to transcripts per million (TPM) to build survival prediction model SaBrcada. After normalization and dimension raising, the differential gene expression data were used for testing eight different deep learning architectures. Among them, GoogLeNet performed the best. Considering the effect of age on prognosis, we examined all ages between the lower and upper quartiles of patient age for a stratified random sampling test; (3) Results: Stratifying by age based on a cut-off of 61 years of age improved the accuracy of SaBrcada compared to previous findings, resulting in an accuracy of 0.798. We also built a free website tool to provide 5 kinds of predicted survival period information for clinician reference; (4) Conclusions: We established a breast cancer survival analysis prediction model, SaBrcada, and a website tool with the same name. Through this highly reliable survival analysis model and website tool, information on survival intervals will be provided for clinicians as part of precision medicine.

In this paper, using the discrete time model, we consider the average age of all files for a cached-files-updating system where a server generates N files and transmits them to a local cache. In order that the cached files are fresh, in each time slot the server updates files with certain probabilities. The age of one file or its age of information (AoI) is defined as the time the file stays in cache since it was last time sent to cache. Assume that each file in cache has corresponding request popularity. In this paper, we obtain the distribution function of the popularity-weighted average age over all files, which gives a complete description of this average age. For the random age of single file, both the mean and its distribution have been derived before by establishing a simple Markov chain. Using the same idea, we show that an N dimensional stochastic process can be constituted to characterize the changes of N file ages simultaneously. By solving the steady-state of the resulting process, we obtain the explicit expression of stationary probability for an arbitrary state-vector. Then, the distribution function of the popularity-weighted average age can be derived by mergering a proper set of stationary probabilities. For the possible applications, the distribution function can be utilized to calculate the probability that the average age violates certain statistical guarantee.

Introduction: Osteoarthritis (OA) and age-related degeneration (ARD) are stimulants for the development of the fabella in the knee joint. This meta-analysis updates previous studies and reviews on the prevalence of the fabella in OA or ARD knee joints. In addition, it provides a quantitative estimation of the fabellar prevalence in knees having OA and ARD. Methodology: Twenty studies comprising of data from 11,056 knee joints were included in the analysis, consisting of 6,819 Knees of OA subjects (including those with age more than 40 years) and 4,237 knees of non-OA subjects (including less than 40years) knees, respectively. 2,434 knees had fabellae present in OA subjects (including more than 40years), and 844 fabellae were present in non-OA subjects (including less than 40years). The Odds and Risk Ratios were calculated. Sensitivity analysis and cumulative analysis were conducted to assess the robustness of the findings. Results: Prevalence of fabella was found to be higher in OA knees, where the Risk Ratio of developing fabella was 2.50 (2.07-3.01). Compared with this, the Risk Ratio for the incidence of fabella in OA with ARD knee was 1.84 (1.66-2.03). The bilateral occurrence of fabella was more common than unilateral. The risk of developing fabella in individuals aged less than forty-year was 63% less than individuals aged more than forty years. Conclusion: OA and ARD would increase the prevalence of fabella by 84%, thus acting as stimulants and risk factors for ossified fabella.

Purpose: Perceptual learning and production practice are basic mechanisms that children depend on to acquire adult levels of speech accuracy. In this study, we examined perceptual learning and production practice as they contributed to changes in speech accuracy in three- and four-year-old children. Our primary focus was manipulating the order of perceptual learning and baseline production practice to better understand when and how these learning mechanisms interact. Method: Sixty-five typically-developing children between the ages of three and four were included in the study. Children were asked to produce CVCCVC nonwords like /bozjəm/ and /tʌvtʃəp/ that were described as the names of make-believe animals. All children completed two separate experimental blocks: a baseline block in which participants heard each nonword once and repeated it, and a test block in which the perceptual input frequency of each nonword varied between 1 and 10. Half of the participants completed a baseline-test order; half completed a test-baseline order. Results: Greater accuracy was observed for nonwords produced in the second experimental block, reflecting a production practice effect. Perceptual learning resulted in greater accuracy during the test for nonwords that participants heard 3 or more times. However, perceptual learning did not carry over to baseline productions in the test-baseline design, suggesting that it reflects a kind of temporary priming. Finally, a post hoc analysis suggested that the size of the production practice effect depended on the age of acquisition of the consonants that comprised the nonwords. Conclusions: The study provides new details about how perceptual learning and production practice interact with each other and with phonological aspects of the nonwords, resulting in complex effects on speech accuracy and learning of form-referent pairs. These findings may ultimately help speech-language pathologists maximize their clients’ improvement in therapy.

The incidence of cancer in organ transplant patients is higher than in the non-transplanted population. The incidence increases with increasing age. The use of Fludeoxyglucose positron emission tomography/CT (PET/CT) is sensitive and specific to detect PTLD LD compared with conventional CT imaging. We analyzed the medical data of 127 patients aged over 60 years, who underwent heart transplantation in the above period, who have been practicing early CT-PET for diagnostic purposes between February 2007 and October 2018. Of 127 consecutive patients who underwent CT-PET, SUVs up than 4, were found in 84 patients of which 20 were affected by PTLDs, seven patients were affected by chronic non neoplastic inflammatory diseases, the remainder were affected by other neoplasms. The favorable effect of physical activity programs on cardiorespiratory and psychomotor function occur in all patients. In conclusion, CT-PET at the first doubts about the possibility of the development of neoplasms has allowed a diagnosis and then a treatment more quickly. Education in behavioral norms that improve the patient's quality of life is necessary.

Pomegranate peel is a natural source of phenolics, claimed to possess healing properties, among which antioxidant and antidiabetic. In line with this evidence, the ethyl acetate PGE extract, obtained by Soxhlet from the peel of Dente di cavallo DC2 variety and characterized by a 4% amount of ellagic acid, has been studied for its hypoglycemic, antiglycation and antioxidative cytoprotective properties, in order to support a possible further nutraceutical interest. The α-amylase and α-glucosidase enzyme inhibition, interference with advanced glycation end-products (AGE) formation and metal chelating abilities were evaluated as hypoglycemic mechanisms. Also, considering that oxidative stress is associated with hyperglycemia complications, PGE antioxidant cytoprotective properties under hyperglycemic conditions were assayed. Phenolic profile was characterized by integrated chromatographic and spectrophotometric methods. Under our experimental conditions, PGE strongly inhibited the tested enzymes, especially α-glucosidase, and exerted chelating and antiglycation properties. Also, it reduced both ROS and GSH levels under hyperglycemic conditions, thus suggesting its ability to support cell functions by counteracting intracellular oxidative stress. Along with ellagic acid, rutin was the major identified flavonoid (about 4 %) of PGE. Present results suggest PGE to be a possible remedy for hyperglycemia management and encourage further studies to exploit its promising properties.

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

In some cases, the human impact on ancient landscapes has been so profound that local soils still remain significantly affected even after hundreds and thousands of years after ending impact. We studied the Late Bronze Age Muradymovo settlement located in Urals, Russia, aiming to estimate the consequences of the ancient people activity for environment. Despite the present humid climate, the modern soils inside the cultural layer of the study site contain more than 27% of gypsum at a depth of just 10 cm from the surface, and a microrelief of the study site is typical of a gypsum desert. The nearby background Chernozems are gypsum-free to a depth of 2 meters. According to the archaeological data, the ancient people belonged to the ‘Srubno-Alakul’ archaeological culture (1750–1350 yrs BC cal) and had a tradition of building their houses from gypsum rocks. At the present time, this area is still unsuitable for human settlement. The properties of modern soils inside the cultural layer of the study site are directly affected by the Late Bronze Age human activities. It has been identified on soil morphology, micromorphology and chemical properties of soils developed inside the cultural layer of the settlement.

Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Cathinone is a natural stimulant found in Catha edulis and commonly used in new psychoactive substances. The objective of this study was to examine the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathine and cathinone concentrations were identified and quantified using ion trap liquid chromatography (LC-IT/MS), while the metabolic profile was determined using the quadrupole time of flight UPLC-QTOF/MS method in the serum, brain, lung, liver, kidney, and heart over a period of 0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours. The findings revealed a dynamic interplay between the pharmacokinetics of cathinone and its impact on organ-specific biomarkers. The distribution of cathinone and cathine was determined in serum, brain, heart, lung, kidney, and liver. The highest concentration of cathinone was found in the kidney at 1438.6 ug/L. It gradually decreased to 1.97 within 48 hours and disappeared after 72 hours. Within half an hour, cathinone levels in the lungs, liver, and heart were found to be 859, 798.9, and 385.8 ug/L, respectively. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 ug/L and kept decreasing until they became undetectable after 24 hours. The concentration of cathinone in the rat brain reduces quickly, dropping to undetectable levels within six hours, with levels decreasing from 712.7 ug/L after just 30 minutes. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours. This indicates that the conversion of cathinone to cathine is slower in the brain and serum. The study found that cathinone's pharmacokinetics have a significant impact on organ-specific biomarkers. After administering the cathinone, there was a sharp change in biomarker levels, particularly in the liver and brain, during the initial hours. It is essential to investigate the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine. The results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. In conclusion, this comprehensive analysis of cathinone's impact on organ-specific biomarkers provides a basis for informed decision-making in medical practices and further research into the cathinone's pharmacological properties.

Background: We aimed to evaluate the impact of two different phytotherapeutic agents on the decision making regarding prostate biopsy in patients with higher-than-normal prostate-specific antigen (PSA) levels. Methods: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B), for 3 months. At the follow-up visit after 3 months all patients underwent PSA test and multiparametric magnetic resonance imaging (mpMRI). Results: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction of total PSA compared to 49 in Group B (64.4%) (p<0.001). Twenty-eight patients had PI-RADS III or higher at mpMRI: 12 in Group A and 14 in Group B. Twenty-three patients (34.8%) in Group A underwent prostate biopsy based on mpMRI findings and PSA values and 59 (77.6%) in Group B (p<0.001). Three patients in Group A showed a significant reduction of total PSA value while having positive findings at mpMRI (6%) compared with 9 in Group B (19.5%) (p<0.001). On the contrary, 7 patients in Group A did not show a significant reduction of total PSA value and had negative findings at mpMRI (43%) compared to 22 in Group B (81.4%) (p&lt;0.001). Conclusions: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster, and Urtica dioica seems an interesting tool to avoid unnecessary prostate biopsies in men with higher-than-normal PSA levels.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), 21% septal reduction therapy. Sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3) and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63 and FLNC; thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p=0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; family studies on some rare variants enriched the worldwide knowledge in HCM.

Sedimentation processes have negative socioeconomic and environmental consequences, ranging from eutrophication phenomena, loss of water quality in surface water bodies, effects on the potential for hydroelectric generation, etc. Frequently, anthropic activity is the main cause that enhances these processes through changes in land use that can lead to landscape modifications. Therefore, it is relevant to evaluate this phenomenon and to be able to discriminate the influence of different land uses on the contributions to sediment loads at different scales. The novel Compound Specific Stable Isotopes technique allows the evaluation of sediment inputs associated with different land use changes in a study region. In the present work this technique was used in the Alhajuela Lake sub-basin, within the Panama Canal Watershed. The contribution levels of three (3) representative land uses (forest, pasture and sediment) in the study area were evaluated for the sediments present in sixteen (16) selected mixing points. The main contributions of the sources to the sediments present in the main rivers and tributaries flowing into Alhajuela Lake, in the sub-basin of the same name, were identified. The results obtained are consistent with observations and measurements of sedimentation in the study area.

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that they are less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age, and the potential problems that the development of clause complexity can cause in school-age children.

Kidney fibrosis is a complex polyetiological progressive disease manifesting as an intraorgan proliferation of the connective tissue with the appearance of cicatricial changes. However, pathogenetic mechanisms of renal fibrosis remain poorly understood. The paper highlights features of the protease phenotype and histotopography of mast cells (MCs) found in the kidney, as the key players in extracellular matrix remodeling in nephrofibrosis, detected in a patient diagnosed with "nephrosclerosis with the non-functioning upper pole of the duplex right kidney in the junction of refluxing megaureter of the upper pole of the duplex right kidney". The highest content of MCs was found in the kidney areas with fibrotic changes. MCs were actively involved in the development of inflammatory and fibrotic changes in limited loci of the specific tissue microenvironment of the kidney through targeted secretion of tryptase, chymase, and carboxypeptidase A3 to the vascular endothelium, nephron epithelium, interstitium cells, and components of the intercellular substance. The formation of a profibrotic environment in the kidney interstitium was facilitated by epigenetic effects of tryptase promoting epithelial-mesenchymal transition (EMT) of the nephron epithelium. A selectively increased number and targeted secretory activity of MCs in limited loci of the kidney parenchyma without visible pathological changes evidence a trigger pathogenetic role of specific proteases in the formation of a local microenvironment with a profibrogenic metabolic profile. Thus, MCs are actively involved in the mechanisms of formation and evolution of fibrogenic niches in the kidney; this fact can be used to develop new strategies for therapeutic options of tubulointerstitial fibrosis resulted from chronic kidney injury. Further study of the molecular phenotype of mast cells reveals new fundamental mechanisms of fibrosis pathogenesis being a significant tool for personalized therapy in nephrology.

Laboratory experiments and natural phenomena investigations in this research series experimentally revealed the existence of gravitational repulsion force dependent on thermal energy content, pervading our surroundings both microscopically and macroscopically. This paper presents an alternative mathematical model of both gravitational repulsion and attraction forces between two gaseous molecules, validated by experimental data. The model is self-standing and independent of existing models built on idealistic assumptions. While existing models considered gravitational interaction as a single force, the presented experimental model considers it the resultant of two distinct forces: gravitational repulsion and attraction. When established experimental data on nitrogen, hydrogen, oxygen, water vapor, carbon monoxide and carbon dioxide were applied, the model performed, both analytically and experimentally: (1) confirming the existence of both gravitational repulsion and attraction forces among gas molecules, (2) demonstrating that the two forces follow Inverse-Cube relationship with the distance between molecules, (3) revealing that repulsion force is linearly proportional to the absolute temperature, thus filling the critical gap between energy and fundamental forces. Orders of magnitude of gravitational repulsion and attraction forces are very large compared to the gravitational force between gas molecules calculated according to the classical theory, enabling manipulation to achieve hitherto unknown outcomes and developments.

Background: The currently advised follow-up scheme of PSA-testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. Methods: All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had &lt;1 year of PSA follow-up. Postoperative PSA-values were collected. Biochemical persistence (BCP) was defined as PSA-level &gt;0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA-level &gt;0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time-points after surgery. Results: Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥0.2 ng/mL. BCR further developed in 51 (4.7%), and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA-level at 0-4 months after RARP also had unmeasurable PSA-level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Conclusions: Patients with an unmeasurable PSA-level at 3-4 months after RARP may not need to be retested until 12 months of follow-up as almost 100% of patients will not have biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA-testing substantially at the costs of hardly any missed patients with recurrent disease.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial to mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is up-regulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating the involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in malignant progression of tumor and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.

The current study investigated whether a domain-specific intervention targeting maths and executive functions of primary school children with a Roma background would be effective in improving their scholastic performance and executive functioning. In total, 122 students attending Grade 4 of elementary school took part in the project. The study concerned a pretest-intervention-training experimental design with three conditions: the experimental condition, an active and a passive control group. The results suggested that both maths performance and executive functions improved over time, with no significant differences between the three conditions. An additional correlational analysis indicated that pretest performance was not related to posttest performance for the children in the experimental and active control group.

Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.