The approach to the personal experience and previous ideas about Physical Education of future Primary Education teachers is a starting point of great interest for the teaching of the subject of Didactics of Physical Education. The study aims to investigate these prior beliefs and to verify to what extent this initial perception changes after taking the course on “Didactics of Physical Education”. A concurrent mixed-methods study was conducted, which included two data collection procedures: (1) a pre-experimental design with a single group featuring pre-test and post-test; (2) the analysis of students' autobiographical accounts of their school experience with physical education. The participants were students enrolled in the Bachelor’s degree program in Primary Education at the University of Santiago de Compostela (USC) who undertook the course last year. The results obtained reveal that after taking the subject of Didactics of Physical Education, students give greater value to more positive concepts of learning, socializing, participating, and playing, among others. Similarly, in the post-test, the assessment of concepts such as competitiveness and physical fatigue diminished. In their autobiographical memories, students associate good memories with relationships with classmates and the playful and socializing nature of the subject; and among the bad memories, they highlight the content related to physical performance, competitiveness, and lack of attention to the diversity of students and their individual characteristics.

The present study analyzed the effect of temperature, pH, retention time, pretreatment and mixing ratio on the anerobic digestion process. The parameters during the anaerobic co digestion of cow manure and food waste were then optimized using the Taguchi experimental design method. ANOVA is carried out to find the significant parameters which influence the biogas production. Experimental tests were carried out at laboratory scale reactors kept at different temperatures (28 °C, 35 °C, and 50 °C). The specific methanogenic Performance (SMP) during anerobic digestion at higher temperatures was characterized with the analysis of acetate, propionate, butyrate, hydrogen, glucose, and formate. The improvement of biogas production with different pre-treatment i.e., ultrasonic, autoclave, and microwave techniques also analysed. The results showed that reactor that maintained at 35 °C showed the highest biogas production. While the reactor that maintained at lower temperature (28 °C) produced the lower volume of biogas. As the retention time increases, the amount of biogas produced increases. Methanogenic activities of microorganisms reduced at higher temperature conditions (65 °C). Biogas production increased by 28.1%, 20.23%, and 13.27 % when the of substrates treated with ultrasonic, autoclave, and microwave, respectively, compared to the untreated substrate. The optimized condition for the highest biogas production during anaerobic co digestion of food waste and cow manure is temperature of 35 °C, pH of 7 and mixing ratio (CM: FW=1.5:0.5). ANOVA showed that temperature is the most important input parameter affecting biogas production, followed by mixing ratio.

Nuclear Magnetic Resonance (NMR) and its various forms are extensively utilized in both research and clinical settings to analyse molecules. NMR data pre-processing, while essential to NMR data analysis, can be uniquely complex. Despite the availability of software tools, understanding these processes can be challenging, complicating the selection of appropriate pre-processing steps. In this review, we elucidate pre-processing steps in the time domain from a mathematical and statistical perspective, explaining direct current offset removal, eddy current correction, shift and linear prediction, weighting, zero filling, and domain transformation using plain language and fundamental mathematical formulas. Our objective is to clarify these processes in simple terms and provide general guidance.

The aim of the study was to compare the standard baseline imaging, with extended radiological staging. To assess our hypothesis, we performed a prospective, single-centre study which included 132 participants recruited between October 2015 and March 2020. Descriptive statistics, the Friedman and chi-squared tests were performed and p < 0.05 was considered significant. Patients were grouped into two cohorts, CT scan cohort (n=87) and PET-CT cohort (n=43). In the first group the originally determined disease stage changed in 36.8 % of cases, in second group in 51.2 %. The consistency between assessment of axillary lymph nodes by imaging (cN) and the postoperative pathology report (pN) was evaluated. In most cases, clinical and pathological evaluation of involved nodes was consistent, for CT scan the result was χ2(1) = 18.98; p < 0.001, for PET-CT the result was χ2(1) = 6.41; p = 0.03. Highly customized radiation therapy defined as dose boost within the involved lymph nodes, not covered by surgeon, was applied in nine patients.

The objective of the present report is the dissemination of information acquired during the application of ISO 6579-1:2017 for the isolation of Salmonella spp. from swine samples. ISO 6579-1:2017 is the officially recommended by the EU protocol for the isolation of Salmonella spp., aiming in the harmonization of effective successful control of Salmonella infection in food producing animals. Successful control of animal salmonellosis is highly dependent on the sensitivity of the biochemical methods reliably detecting the presence of the pathogen in various stages of food production. Application of ISO 6579-1:2017 resulted in the isolation of twelve Salmonella spp. and eighteen other members of the family of Enterobacteriaceae biochemically and antigenically resembling salmonellae. The findings necessitated in the depth evaluation of the culture media xylose-lysine-desoxycholate agar (XLD), Salmonella-Shigella Agar (SS), Brilliant Green Agar (BGA), Salmonella Chromogenic Agar (SCA), Triple Sugar Iron (TSI) and modified semi-solid Rappaport–Vassiliadis (MSRV) agar. The evaluation showed that these culture selective media differed significantly in their performance regarding the isolation of Salmonella from swine samples. It was concluded that the presence of atypical Salmonella strains negatively affects the prevalence of Salmonella, thus the identification of carrier pigs, eventually affecting the efficiency of control programs. Thus, doubtful results require additional biochemical testing for confirming the accuracy of such universally recommended isolation methods.

This study leverages transformer-based models and focuses on data representation strategies in the named entity recognition task, including "single" (one sentence per vector), "merged" (multiple sentences per vector), and "context" (sentences joined with attention to context). Performance analysis reveals that models trained with a single strategy may not perform well on different data representations. A combined training procedure is proposed to address this limitation, using all three strategies to enhance the stability and adaptability of the model. The results of this approach are presented and discussed for various datasets for four languages (English, Polish, Czech, and German), demonstrating the effectiveness of the combined strategy.

Dialogue State Tracking is an essential component in multi-domain dialogue systems, aiming to accurately determine the current dialogue state based on the dialogue history. Existing research has addressed the issue of multiple mappings in dialogues by employing slot self-attention as a data-driven approach. However, learning the relationships between slots from a single sample has limitations and introduces noise. In this paper, we propose an External Slot Relation Memory-based Dialogue State Tracking model (ER-DST). By utilizing an external memory storage, we learn the relationships between slots as a dictionary of multi-domain slot relations. Additionally, we employ a small filter to discard slot information irrelevant to the current dialogue state. Experimental results on the MultiWOZ2.0 and MultiWOZ2.1 benchmarks demonstrate significant improvements while reducing the time complexity to O(n).

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

Abstract: In network science and big data, the concept of finding meaningful infrastructures in networks has emerged as a method of finding groups of entities with similar properties within very complex systems. The whole concept is generally based on finding subnetworks which have more properties (links) amongst nodes belonging to the same cluster than nodes in other groups (A concept presented by Girvan and Newman, 2002). Today meaningful infrastructure identification is applied in all types of networks from computer networks, to social networks to biological networks. In this article we will look at how meaningful infrastructure identification is applied in biological networks. This concept is important in biological networks as it helps scientist discover patterns in proteins or drugs which helps in solving many medical mysteries. This article will encompass the different algorithms that are used for meaningful infrastructure identification in biological networks. These include Genetic Algorithm, Differential Evolution, Water Cycle Algorithm (WCA), Walktrap Algorithm, Connect Intensity Iteration Algorithm (CIIA), Firefly algorithms and Overlapping Multiple Label Propagation Algorithm. These al-gorithms are compared with using performance measurement parameters such as the Mod-ularity, Normalized Mutual Information, Functional Enrichment, Recall and Precision, Re-dundancy, Purity and Surprise, which we will also discuss here.

Radio Frequency Interference (RFI) detection and characterization play a critical role to in ensuring the security of all wireless communication networks. Advances in Machine Learning (ML) have led to the deployment of many robust techniques dealing with various types of RFI. To sidestep an unavoidable complicated feature extraction step in ML, this paper proposes an efficient end-to-end method using the latest advances in deep learning to extract the appropriate features of the RFI signal. Moreover, this study utilizes the benefits of transfer learning to determine both the type of received RFI signals and their modulation types. To this end, the scalogram of the received signals is used as the input of the pre-trained convolutional neural networks (CNN), followed by a fully-connected classifier. This study considers a digital video stream as the signal of interest (SoI), transmitted in a real-time satellite-to-ground communication using DVB-S2 standards. To create the RFI dataset, the SoI is combined with three well-known jammers namely, continuous-wave interference (CWI), multi- continuous-wave interference (MCWI), and chirp interference (CI). This study investigated four well-known pre-trained CNN architectures, namely, AlexNet, VGG-16, GoogleNet, and ResNet-18, for the feature extraction to recognize the visual RFI patterns directly from pixel images with minimal preprocessing. Moreover, the robustness of the proposed classifiers is evaluated by the data generated at different signal to noise ratios (SNR).

The aim of this study was to assess if the ovine articular cartilage serine proteinase inhibitors (SPIs) were related to the Kunitz inter-α-trypsin inhibitor (ITI) family. Ovine articular cartilage was finely diced and extracted in 6M urea and SPIs isolated by sequential anion exchange, HA affinity and Sephadex G100 gel permeation chromatography. Selected samples were also subjected to chymotrypsin and concanavalin-A affinity chromatography. Eluant fractions from these isolation steps were monitored for protein and trypsin inhibitory activity and pooled fractions assessed by affinity blotting using biotinylated trypsin to detect active SPIs and by Western blotting using antibodies to α1-microglobulin, bikunin, TSG-6 and 2-B-6 (+) CS stub epitope generated by chondroitinase-ABC digestion. This identified 2-B-6 (+) positive 220-250,120, 58 and 36 kDa SPIs. The 58 kDa SPI contained α1-microglobulin, bikunin and chondroitin-4-sulphate stub epitope consistent with its identity as the α1-microglobulin-bikunin (AMBP) precursor and was also isolated by concanavalin-A lectin affinity chromatography indicating it had N-glycosylation. Kunitz protease inhibitor (KPI) species of 36, 26, 12 and 6 kDa could be autolytically generated by prolonged storage of the aforementioned 120 and 58 kDa SPIs; chymotrypsin affinity chromatography also generated the 6kDa SPI. KPI domain 1 and 2 SPIs were separated by concanavalin lectin affinity chromatography, domain 1 displayed affinity for this lectin indicating it had N-glycosylation. KPI 1 and 2 both displayed potent inhibitory activity towards trypsin, chymotrypsin, kallikrein, leucocyte elastase and cathepsin G. Localisation of versican, lubricin and HA in the surface regions of articular cartilage represented probable binding sites for the ITI SPs with likely importance in the preservation of joint function.

Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

On average, one in ten patients die because of a diagnostic error and medical errors are the third largest cause of death in the word. While LLMs have been proposed to help doctors with diagnoses, no research results have been published on comparing the diagnostic ability of many popular LLMs on an openly accessible real-patient cohort. In thus study, we compare LLMs from Google, OpenAI, Meta, Mistral, Cohere and Anthropic using our previously published evaluation methodology and explore improving their accuracy with RAG.

Perioperative dysglycemia in cardiac surgery is associated with poor outcomes. Glycemic variability rather than glucose levels are a predictor of length of ICU stay, rise in creatinine and acute kidney injury after cardiac surgery. Glycated haemoglobin (HbA1c) values correspond closely with average blood glucose levels and cut off values can be used to define diabetic and pre-diabetic status. These have been correlated with perioperative events. This narrative review discusses the role of glycated hemoglobin in cardiac surgery.

Background/Objectives: This study aimed to identify various risk factors associated with breast cancer and explore different treatment strategies based on socio-economic, hormonal, and clinical perspectives.; Methods: We analyzed socio-economic, hormonal, genetic, and clinical variables using data from 356 questionnaires obtained from breast cancer patients at Hassan II Regional Hospital in Agadir, Morocco ; Results:The study reveals that the average age of breast cancer patients is 50 ± 10.72 years, with a mode of 47 years and an age range from 29 to 94 years. Notably, women aged 38 are most frequently diagnosed with triple-negative breast cancer. Significant socio-economic trends were observed among the participants, with the majority being housewives (91%) and nearly half residing in rural areas (48.60%). High rates of illiteracy (74.72%) and financial difficulties (54.2%) pose challenges in accessing healthcare services. Psychological distress is prevalent, with 40.7% experiencing anxiety and 30.1% experiencing sadness. The use of oral contraceptives varies, with implications for breast cancer risk. Additionally, statistics on menarche and menopause suggest hormonal influences on breast cancer development. Histological analysis indicates a predominance of grade II invasive ductal carcinoma and left breast localization. Metastases are present in nearly 38.20% of cases. Notably, surgery as the primary treatment effectively treats medium-sized tumors while limiting metastasis. Furthermore, a comparison of treatment strategies reveals a preference for letrozole among postmenopausal patients and tamoxifen among premenopausal patients; Conclusions:These findings highlight the complexity of breast cancer risk factors and therapeutic approaches, emphasizing the importance of personalized care and targeted interventions.

Recent advancements in neural machine translation (NMT) offer promising potential for generating cross-language clinical natural language processing (NLP) resources. There is a pressing need to be able to foster the development of clinical NLP tools that extract key clinical entities in a comparable way for a multitude of medical application scenarios, hindered by lack of multilingual annotated data. This study explores the efficacy of using NMT and annotation projection techniques with expert in the loop validation to develop named entity recognition (NER) systems for an under resourced target language (Catalan) by leveraging Spanish clinical corpora annotated by domain experts. We employed a state-of-the-art NMT system to translate three clinical case corpora. The translated annotations were then projected onto the target language texts and subsequently validated and corrected by clinical domain experts. The efficacy of the resulting NER systems was evaluated against manually annotated test sets in the target language. Our findings indicate that this approach not only facilitates the generation of high-quality training data for the target language (Catalan) but also demonstrates the potential to extend this methodology to other languages, thereby enhancing multilingual clinical NLP resource development. The generated corpora and components are publicly accessible, providing potentially a valuable resource for further research and application in multilingual clinical settings: https://zenodo.org/doi/10.5281/zenodo.13133124.

CGP do not substantially differ between initial tumor vs tumor recurrence and recurrent thymomas vs non-recurrent thymomas. Cell-cycle control genes alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different between the cohorts, but specific clinical features varied between the cohorts. Overall severity from first to last visit increased in the younger cohort but not in the older cohort. While some specific clinical features in the older cohort were stable from the first to the last visit, others showed improvement or worsening. These data do not support the hypothesis that mild MECP2 variants or less overall severity leads to increased longevity in RTT but demonstrate that clinical features change with increasing age in adults with RTT. Additional work is needed to understand disease progression in adults with RTT.

Gastrointestinal bleeding (GIB) after heart transplantation (HT) remains a significant clinical issue. The study aimed to explore its incidence, trends, outcomes and clinical predictors of GIB in HT patients. Adult patients who underwent HT between 2015 and 2021 at Union Hospital were recruited and divided into two groups based on the presence or absence of postoperative GIB. Primary outcomes were evaluated by follow-up. Independent predictors of GIB after HT were identified by logistic regression analysis. A nomogram prediction model was constructed according to these independent variables, and the accuracy of the model was assessed using the receiver operating characteristic (ROC) curve and the calibration curve. Among 461 patients, 40 (8.7%) developed GIB post-HT. HT patients with postoperative GIB exhibited higher in-hospital, 30-day, 90-day and 1-year mortality (all P < 0.05). Multivariate analysis identified age, preoperative warfarin, postoperative continuous renal replacement therapy and postoperative nasogastric tube as independent risk factors for GIB following HT. The nomogram prediction model was performed using the 4 variables. The area under the curve (AUC) of this model was 0.852(95% CI: 0.787-0.917, P < 0.001) and the calibration curve was close to the ideal diagonal line. GIB following HT is associated with a poor clinical prognosis. The constructed nomogram, incorporating its independent risk factors, demonstrated a favorable predictive value for GIB.

Von Hippel-Lindau disease (VHL) is a multiple organ neoplastic syndrome with autosomal dominant transmission, complete penetrance, and variable expression caused by mutations in the VHL gene. Although VHL disease is hereditary in many cases, new mutations cause up to 20 % of the incidence. Mutations in VHL may cause the development of cysts and tumors in many organs, including brain and spinal cord hemangioblastoma, renal cell carcinoma (RCC), retinal heman-gioblastoma (RH), pheochromocytoma, epididymal and broad ligament cystadenomas, endo-lymphatic sac tumor, pancreatic neuroendocrine tumors, and renal and pancreatic cysts. VHL is a syndrome associated with functional inactivation of the Von Hippel–Lindau protein (pVHL). pVHL is a tumor suppressor mainly known for its role as a regulator of hypoxia-inducible factor (HIF) activity. The prevalence of VHL disease is between 1 in 39 000 and 1 in 91 000 individuals in different regional populations. Here, we review the etiology, epidemiology, pathophysiology, genetics, clinical manifestations, diagnosis, and current treatments, as well as the molecular aspects of this disease. We also discuss the animal models used to study this disease, VHL biomarkers, and current VHL clinical trials for VHL according to NIH.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

Retinitis pigmentosa (RP) is a heterogeneous inherited retinal disorder. Mutations in KIZ cause autosomal recessive (AR) RP. We aimed to characterize the genotype, expression pattern, and phenotype in a large cohort of KIZ cases. Sanger and whole exome sequencing were used to identify KIZ variants. Medical records were reviewed and analyzed. Thirty one patients with biallelic KIZ mutations were identified: 28 homozygous for c.226C>T (p.R76*), 2 compound heterozygous for p.R76* and c.3G>A (p.M1?), and one homozygous for c.247C>T (p.R83*). c.226C>T is a founder mutation among patients of Jewish descent. Clinical parameters were less severe in KIZ compared to DHDDS and FAM161A cases. RT-PCR analysis in fibroblast cells revealed the presence of four different transcripts in both WT and mutant samples with a lower percentage of the WT transcript in patients. Sequence analysis identified an exonic sequence enhancer (ESE) that includes the c.226 position which is affected by the mutation. KIZ mutations are an uncommon cause of IRD worldwide, but are not rare among Ashkenazi Jews. Our data indicate that p.R76* affect an ESE which in turn results in pronounced skipping of exon 3. Therefore, RNA-based therapies might show low efficacy since the mutant transcripts is spliced.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p

Polycystic Ovary Syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder in women of reproductive age. Diagnosis of this syndrome relies on criteria established by the Rotterdam Consensus, with PCOS phenotypes being crucial for distinguishing potential complications, treatment approaches, and timing. The aim of this study is to characterize the biodemographic, clinical, metabolic, and reproductive variables and their association with PCOS phenotypes in a population from the Ecuadorian Andes. Methodology: A cross-sectional study was conducted with a non-random consecutive sample of 92 women attending the gynecology and endocrinology outpatient clinic at the Technical University of Loja Hospital (UTPL)-Santa Inés, Loja, Ecuador, between January 2022 and July 2023.Results: The average age was 22±3.4 years, predominantly mestizo, urban, single, with higher education and a medium-high socioeconomic status. Oligo-amenorrhea and acne appear strongly associated with phenotypes A and B, while hirsutism and polycystic ovaries on ultrasound show a weaker association with these phenotypes. Alopecia is more prevalent in phenotypes C and D. Triglyceride levels and BMI have a strong association with phenotypes A and B. Total testosterone levels, 17 OH progesterone, LH, and free androgen index show a moderate association with phenotypes A and B, while other reproductive variables exhibit weak associations. Conclusions: Classical phenotypes A and B of PCOS are most common in Andean Ecuadorian women, carrying higher risks of insulin resistance, anovulation, metabolic disorders, and elevated triglycerides compared to phenotypes C and D. Ethnic diversity and sociocultural habits influence the prevalence and clinical manifestations of phenotypes.

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by a variety of both signs and symptoms; it mainly affects women of childbearing age, with an estimated prevalence of 24/100,000 people in Europe and North America. SLE is often described as an antibodies-driven disease as its clinical manifestations are usually associated with the presence or the absence of specific antibodies. Objectives To evaluate clinical manifestations in patients with SLE and to assess the relationship with the presence of specific antibodies by using real-world data. Methods A retrospective study was performed; the 2019 EULAR/ACR Classification Criteria for Systemic Lupus Erythematosus were used to classify patients with SLE. Data concerning serological profiles (which included Antinuclear antibodies – ANA, anti dsDNA, anti-Ro/SS-A, anti-La/SS-B, anti-Sm) were gathered along with medical records of clinical manifestations. Complement levels were also tested for possible clinical correlations. χ² or Fisher's exact tests were utilized to establish associations between autoantibodies and symptoms. The odds ratios (OR) and their 95% confidence intervals (CI) were computed. No correction was made for multiple testing; only a p-value 0.01 ≤ was considered significant. Results One-hundred and twenty-seven patients (n=127, mean age 53.43 ±14.02) were enrolled in this study. Anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies showed an association with photosensitivity and pericarditis; furthermore, a strong association was found between anti-Ro antibodies and proteinuria, but only if anti-dsDNA antibodies were present as well. Patients who tested positive for anti-La/SSB antibodies correlated with a threefold increase in the risk of developing pericarditis. Lastly, anti-Smith appeared to be associated with NPSLE as well as an increased risk for both autoimmune haemolytic anemia and thrombocytopenia. Conclusions In our study, many associations confirmed those found in previous studies; however, new relationships between antibodies and clinical manifestations were found thus indicating the need for additional evaluations to assess these correlations further.

Psoriasis is a common chronic immune-mediated disease with many comorbidities and impacts on quality of life. Among the treatment options for psoriasis, phosphodiesterase-4 (PDE4) inhibi-tors are emerging with expanding options. PDE4 inhibitors play a pivotal role in the inflamma-tory cascade by degrading cyclic adenosine monophosphate (cAMP), contributing to pro-inflammatory mediator production. Apremilast, an oral PDE4 inhibitor, is an approved class for psoriasis. While effective, its adverse effects can limit its utility. Roflumilast, a topical PDE4 inhibitor, was recently also approved for psoriasis and shows promise in clinical trials. Crisaborole, approved for atopic dermatitis, has also been studied in psoriasis. This updated re-view summarizes evidence from randomized clinical trials regarding the efficacy and safety of PDE4 inhibitors in psoriasis treatment. By highlighting their potential benefits and limitations, this review provides valuable insights for clinicians and researchers aiming to optimize psoriasis therapy.

To gain insight into the real-life care of patients in the healthcare system, data from hospital information systems and insurance systems are required. Consequently, linking clinical data with claims data is necessary. To ensure their syntactic and semantic interoperability, the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) was chosen. However, there is no detailed guide that would allow researchers to follow a consistent process for data harmonization. Thus, the aim of this paper is to conceptualize a generic data harmonization process for OMOP CDM. For this purpose, we conducted a literature review focusing on publications that address the harmonization of clinical or claims data in OMOP CDM. Subsequently, the process steps used and their chronological order were extracted for each included publication. The results were then compared to derive a generic sequence of the process steps. From 23 publications included, a generic data harmonization process for OMOP CDM was conceptualized, consisting of nine process steps: dataset specification, data profiling, vocabulary identification, coverage analysis of vocabularies, semantic mapping, structural mapping, extract-transform-load-process, qualitative and quantitative data quality analysis. This process can be used as a step-by-step guide to assist other researchers in harmonizing source data in OMOP CDM.

The aim of the study was to analyze the oral etiology of patients with odontogenic sinusitis (ODS）and to compare the differences in demographic data, clinical symptoms, extent of sinus involvement, bone penetration of the maxillary sinus floor (MSF) between different etiologies. A retrospective investigation was conducted on 103 patients with ODS recruited from Beijing Tongren Hospital. All enrolled patients underwent sinus CT, nasal endoscopy, and oral examination. A comparison of the patients' clinical symptoms, extent of involvement of the sinuses, and bone resorption of the MSF according to odontogenic etiologies was conducted. Follow-up was based on symptoms, clinical examination. The most common odontogenic etiologies were endo-periodontal lesions (EPL. 49.5%), apical periodontitis (AP, 32.0%) and periodontitis (PE, 8.7%). There were statistically significant differences in age (P=0.002), sex (P=0.036), inflammation involving the ethmoid sinus (P=0.037), and bone penetration of the MSF (P<0.001) between the AP, EPL, and PE groups. There were no significant differences in sinusitis symptoms (P>0.005) among patients with different odontogenic etiologies. In conclusion, EPL is a neglected oral etiology with a destructive effect on the bone of the MSF, and Should receive more attention in diagnosis and treatment.

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions are inconclusive and conflicting. The aim of the study was to review existing literature on the effects of probiotics in gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases such as PubMed, Google Scholar, MEDLINE and Scopus databases were searched for the data. The study followed standard procedures for data extraction using PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was conducted. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn’s disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective and 1 study results were inconclusive. Meta-analysis, on the contrary, didn’t demonstrate any significant protective effects of probiotics. Having a τ² value of zero and I² of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

Advances in nanotechnology have paved the way for more effective drug delivery using particulate and non-particulate nano-based formulations across a range of applications. In the oral cavity, local delivery using mucoadhesive formulations has advantages over conventional formulations for increasing local efficacy whilst reducing unwanted adverse effects. Nano-formulations provide the opportunity for new formulations with enhanced intraoral stability, local action, and improved patient acceptability.

Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.

High-fidelity patient simulation (HFPS) is widely used in professional training to enhance students’ competence in clinical management. Problem-solving (PS) and clinical reasoning (CR) skills are essential to developing students in professional competence in safe and effective care. These two skills should be initiated at the early training. However, little is known about the effects of HFPS on developing PS and CR skills in first year undergraduate students. Therefore, this pre- and post-experimental study aimed to investigate the effects of HFPS on development of PS and CR skills in first-year nursing students. The students were required to go through four sessions, preparation, pre-briefing and orientation, simulation role-playing, and debriefing, for the HFPS. The study utilized the Problem-Solving Inventory (PSI) and the Nurses Clinical Reasoning Scale (NCRS) to measure problem-solving and clinical reasoning abilities before and after HFPS. Bivariate analysis, one-sample t-test, and independent t-test were performed to evaluate the performance of the PS and CR skills at the two study periods. One hundred eighty-nine students were recruited, with a mean age of 20.56 years, and 73% were female students. The analytic results showed that the PSI, particularly in domains of Problem-Solving Confidence (PSC) (p&lt;0.001) and overall PS (p&lt;0.001), and the CR (p&lt;0.001) had significant improvement after HFPS. The study concluded that HFPS is an effective innovative method to significantly improve students’ problem-solving and clinical reasoning abilities. Nurse educators play an important role in providing explicit learning instructions in a simulation guideline that directs and guides students to learn at each stage of HFPS. Students should take more initiative and engage in their learning through HFPS to enhance their competence in knowledge and higher intellectual skills for personal and professional developments.

The 2019 COVID-19 pandemic caused by SARS-CoV-2 has resulted in many fatalities worldwide. Despite various types of supportive care, mortality rates for patients with comorbidities remain high. To explore alternative treatment options, interferons (IFNs) have emerged as promising therapeutic drugs for SARS-CoV-2. This review aims to investigate the potential of IFNs as a drug with details on their mechanisms of action, and available data on their use with ongoing clinical trials, results, potential limitations, and challenges. Recently published research articles, which were systematically searched through online databases, have been selected and found that IFNs have colossal potential in treating SARS-CoV-2 infection by modulating the host's immune response and inhibiting viral replication and decreasing the severity of disease and hospitalization (p = 0.03, ±0.05) and (p = 0.04, ±0.05) respectively. However, due to less available data, more controlled and randomized trials are needed to confirm the efficacy and safety of IFN therapy. The optimal dosing and duration of IFN therapy also remain to be determined. Although further research is needed the wait for ongoing clinical trial results under investigation is also important for a better understanding of IFN therapy.

Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about the overall epidemiology and prognostic factors of the pathology. The purpose of this study is to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with GIST in the past decade. Methods: A total of 2,374 patients diagnosed with GIST, between 2010 and 2017, were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of GIST. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and GIST related mortality among US patients between 2010 and 2017 revealed higher overall mortality in Non-Hispanic Blacks (HR= 1.516, 95% CI 1.172-1.961, p= 0.002), age 80+ (HR= 9.783, 95% CI4.185-22.868, p= 0), followed by age 60-79 (HR= 3.408, 95% CI 1.488-7.807, p=0.004); male patients (HR= 1.795 , 95% CI 1.461-2.206, p=0); advanced disease with distant metastasis (HR= 3.865 , 95% CI 2.977-5.019, p=0), followed by regional involvement by both direct extension and lymph node involvement (HR= 3.853, 95% CI 1.551-9.57, p=0.004); and widowed patients (HR= 1.975, 95% CI 1.494-2.61, p= 0), followed by single patients (HR= 1.53, 95% CI 1.154-2.028, p=0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR= 1.687, 95% CI 1.19-2.392, p= 0.003). Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that non-Hispanic blacks, male patients, and patients older than 60 years have a higher mortality with GIST. Furthermore, patients who received chemotherapy have a higher GIST specific mortality and married patients had a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing those interactions. The results of this study may help treating clinicians to identify patient populations associated with dismal prognosis as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival, we hope to encourage clinicians to involve family members of the affected patients early in the disease course as the social support might impact the prognosis.

Our search of existing cancer databases aimed to assess the current landscape and identify key needs. We analyzed 71 databases, focusing on genomics, proteomics, lipidomics, and glycomics. We found a lack of cancer-related lipidomic and glycomic databases, indicating a need for further development in these areas. Proteomic databases dedicated to cancer research were also limited. To assess overall progress, we included human non-cancer databases in proteomics, lip-idomics, and glycomics for comparison. This provided insights into advancements in these fields over the past eight years. We also analyzed other types of cancer databases, such as clinical trial databases and web servers. Evaluating user-friendliness, we used the FAIRness principle to assess findability, accessibility, interoperability, and reusability. This ensured databases were easily accessible and usable. Our search summary highlights significant growth in cancer databases while identifying gaps and needs. These insights are valuable for researchers, clinicians, and database developers, guiding efforts to enhance accessibility, integration, and usability. Addressing these needs will support advancements in cancer research and benefit the wider cancer community.

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

Cryoglobulinaemia is characterised by immunoglobulins which precipitate at temperatures be-low 37°C and redissolve on warming. Monoclonal IgM immunoglobulin may be associated with type I and II cryoglobulinaemia with underlying Waldenström macroglobulinemia, monoclonal gammopathy of undetermined significance or other non-Hodgkin lymphoma. We review the clinical characteristics, laboratory testing and suggest a management approach for monoclonal IgM associated cryoglobulinaemia. Laboratory testing is critical as even a minimal amount of measurable cryoglobulin may result in symptoms. Accurate detection of cryoglobulins may be challenging and care must be taken with preanalytical variables and repeat testing of monoclo-nal protein and cryoglobulins is indicated if clinical suspicion is high. Presentations range from asymptomatic disease to multisystem involvement so careful evaluation of the features and thorough interrogation of organ systems and the underlying clone is critical. Immediate man-agement is required for clinical red flag features. Due to their rarity, data to inform treatment decisions are scant and collaborative research is imperative to aid defining optimal treatment strategies.

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

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

Many clinical trials end uninformatively. Informativeness, in the context of clinical trials, defines whether a study’s results definitively answer its research questions with meaningful next steps. One subset of these trials are those focused on global health set in low-resource settings. Global health clinical trials benefitting people in low-resource settings are funded primarily by a limited number of large foundations, pharmaceutical firms (“industry”), and national governments. While clinical trial protocols are required to go through reviews in regulatory and ethical domains, outside of industry-funded trials, funders rarely require focused scientific design reviews. There are no documented standards and processes, or even best practices, for funders to perform scientific reviews after the funding commitment. Considering the investment in and standardization of ethical and regulatory reviews, and the prevalence of studies ending without clarity or never finishing, it may be that scientific reviews of trial designs with a focus on informativeness offer the best chance for improved outcomes and return on investments in clinical trials. A maturity model is a helpful tool for knowledge transfer to help grow capabilities in a new area, or for those looking to perform a self-assessment in an existing area. Such a model is offered for scientific design reviews of clinical trial protocols: a valuable and often-neglected governance step for funders or sponsors, among others. This maturity model includes 11 process areas and 5 maturity levels. Each of the 55 process area levels is populated with descriptions on a continuum toward an optimal state to improve trial protocols in the area of risk of failure. This tool allows for prescriptive guidance on next investments to improve attributes of post-funding reviews of trials, with a focus on informativeness.

With the growing hope that disease-modifying treatments could target the molecular basis of neurodegenerative diseases even before the onset of symptoms, there is mounting pressure to define disease entities based on pathophysiology rather than on clinical syndromes. The Alzheimer’s disease research community has recently transitioned from diagnostic criteria based on an amnestic syndrome to a purely biomarker-based disease definition, relying on the demonstration of amyloid-beta pathology, tau pathology, and neurodegeneration. In contrast, current diagnostic criteria for Parkinson’s disease still rely on the presence of the well-described clinical syndrome of parkinsonism, with the addition of characteristic motor- and non-motor signs and symptoms. However, there is now unequivocal evidence that Parkinson’s disease starts years before the onset of parkinsonism. Furthermore, neuropathologically defined Lewy body disease is clinically heterogeneous, combining a range of motor, non-motor, dopaminergic and non-dopaminergic features. Finally, clinically defined Parkinson’s disease has diverse underlying etiologies most, but not all, associated with α-synuclein positive Lewy pathology. In light of recent scientific advances, we propose a biologically based definition for the diagnosis of Parkinson's disease, initially to be used for research purposes. The criteria use a three-component ‘G-S-N’ system. The first is documentation of defined gene variants (‘G’), which cause or strongly predispose to PD as the most upstream component. The second is α-synuclein pathology (‘S’), currently defined as pathological α-synuclein deposition in tissue or positive α-synuclein seeding assays. The third is evidence of underlying neurodegeneration (‘N’), currently defined by specific neuroimaging procedures. The associated clinical syndrome (‘C’) is defined by a single high-specificity feature or multiple lower-specificity features. Initiating this transition will enable the field to fuel both basic and clinical research and move closer to the precision medicine required to develop clinically meaningful disease-modifying therapies. We acknowledge current limitations, ethical implications, and the need for prospective validation of this approach.

Background: Aluminum phosphide (AlP), also known as “rice tablet,” is widely used as an effective pesticide. However, AlP poisoning is a common cause of mortality in many countries, such as Iran. Unfortunately, there is no specific antidote for AlP toxicity to date. AlP releases phosphine gas when it is exposed to moisture and acid. Phosphine is a robust mitochondrial toxin that could significantly inhibit cellular energy metabolism. AlP poisoning is an emergency condition that needs instant and effective intervention. Dihydroxyacetone (DHA) is a simple saccharide used for several pharmacological as well as cosmetic purposes. Previously, we found that DHA could significantly prevent mitochondrial impairment induced by toxic agents such as cyanide and phosphine in various in vitro and in vivo experimental models.Methods: Hospitalized patients (n = 111) were evaluated for eligibility criteria. Among these patients, n = 35 cases were excluded due to incomplete data (n = 11) and suspicion of poisoning rather than AlP (n = 24). Meanwhile, n = 76 cases with confirmed AlP poisoning were included in the study. AlP-poisoned patients who did not receive DHA (n =18) were used as the control group.Patients (n = 58) received at least one dose of DHA (500 ml of 5% DHA solution w/v, i.v.) in addition to routine treatment of AlP poisoning. Arterial blood gas (ABG), blood pH, bicarbonate levels, and other vital signs and biochemical measurements were monitored. Moreover, the mortality rate and time of hospitalization were evaluated in both DHA-treated (n = 58) and AlP-poisoned patients without DHA administration (n = 18). Several biomarkers were assessed before (upon hospitalization) and after DHA treatment. The routine tests for AlP-poisoned patients in this study were the measurement of electrolytes (K+ and Na+), WBC, RBC, hemoglobin, INR, carbonate (HCO3), blood pH, PaCO2, and PaO2 and SGPT, SGOT, BUN, Cr. Results: Upon patients' admission, significant decreases in blood pH (acidosis), blood PaO₂, and HCO₃ levels were the hallmarks of AlP poisoning. It was found that DHA significantly alleviated biomarkers of AlP poisoning and tremendously enhanced patients’ survival rate compared to patients treated based on hospital routine AlP poisoning protocols (no DHA). No significant adverse effects were evident in DHA-treated patients in the current study.Interpretation: These data suggest that parenteral DHA is a novel and effective antidote against AlP poisoning.Trial registration: IR.SUMS.REC.1394.102

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

The overall objective of this mixed-method digital-based observational study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic. The Qualtrics Core XM platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews. Various validated mental health assessments were administered: Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Tool-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS). A total of 485 participants took part, of which 73.4% were female and 70.1% of the sample were white British. A high prevalence of anxiety, exhaustion and depression were identified across all participants. A significant mental health impact was identified among the CTU workforce where wellbeing was compromised during the course of the COVID-19 pandemic.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined as exocrine gland hypofunction resulting in dry eyes and dry mouth. Recent interest in biological therapies for pSS has been garnered, however achieving FDA-approval has been challenging due to the numerous complications in the trials. Current literature lacks insight and a molecular target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term “Primary Sjögren's syndrome”. Articles published between 2000 and 2021 in English language were included. Our findings revealed the potential targets for pSS treatment in clinical trials and the most recent advances in understand-ing of molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is overlooking the treatment of extraglandular symptoms such as fatigue, depression and anxiety which pervade most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways and immune reaction have been studied and proved the efficacy and safety. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grad-ing systems adding extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene therapy, stem cell and tissue engineering ther-apy.

The traditional nomenclature system for classifying Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), based on clinical phenotype, described Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA) and Microscopic Polyangiitis (MPA) as distinct clinical entities. This classification has proved its expedience in clinical trials and every day clinical practice, yet, a substantial overlap in clinical presentation still exists, and often causes difficulties in prompt definition and clinical distinction. Additionally, new insights into the AAV pathogenesis point out that PR3 and MPO-AAV may not represent expressions of the same disease spectrum but rather two distinct disorders, as they display significant differences. Thus, it is supported that a classification based on ANCA serotype (PR3-ANCA, MPO-ANCA or ANCA-negative), could be more accurate and also closer to the nature of the disease, instead of the phenotype-based one. This review aims to elucidate the major differences between PR3 and MPO-AAV, in terms of epidemiology, pathogenesis, histological and clinical manifestations, and response to therapeutic approaches.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

Combination treatment, i.e., the use of two or more drugs for the same condition, is frequent in medicine if monotherapy yields an insufficient therapeutic response. We here review and challenge clinical study designs and formats of reporting outcomes for the evaluation of the benefit/risk ratio of combination treatment over monotherapy. We demonstrate that benefits of combination treatment at the group level over-estimate the probability of benefit at the single patient level based on outcome simulations under almost any imaginable setting. Based on these findings we propose that studies testing combination treatment should always report on percentages of responders to monotherapy and combination treatment. We provide equations that allow calculation of the percentage of patients truly benefitting from combination (responders to both monotherapies) and that of patients exposed to risk of harm from adverse effects without a reasonable expectation of individual benefit. These considerations are explained based on real clinical data, mostly from the field of functional urology (male lower urinary tract symptoms).

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

Clinical trials for Alzheimer’s disease (AD) face multiple challenges, such as the high screen failure rate and even allocation of heterogeneous participants. Artificial intelligence (AI), which has become a potent tool of modern science with the expansion in the volume, variety, and velocity of biological data, offers promising potential to address these issues in AD clinical trials. In this review, we introduce the current status of AD clinical trials and topic of machine learning. Then, a comprehensive review is focused on the potential applications of AI in the steps of AD clinical trials, including the prediction of AD biomarkers and differential diagnosis of AD in the prescreen during eligibility assessment and the likelihood stratification of patients who will progress to AD dementia and fast cognitive decline group from the slow decline group in randomization. Finally, this review provides challenges, developments and the future outlook on the integration of AI into AD clinical trials.

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

Background. Until now, cost of allergy treatment in insured public health care system and non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. Objective. To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in non-insured self-financing private health care system. Methods. A retrospective cohort study conducted from 2015 until 2020, compared clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1,098 subjects Results. Decrease of sp-HDM-IgE level (kU/ml) from 20.5 + 8.75 kU/ml to 12.1 + 3.07 kU/ml had been observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT it costs IDR 21,753,062.7 per child, for non SCIT it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT it costs Rp. 17,024,138.8 while with non SCIT it costs Rp. 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT it costs IDR 9,550,126.6, while with non SCIT it costs IDR 52,073,938.9. Conclusion. In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

Direct and indirect anthropogenic factors play a massive role in driving wildlife species towards extinction. Longitudinal retrospective studies identify key ‘factors’ responsible for the decline in numbers of wildlife, however, lack the reasoning behind the events leading to mortality. The overarching aim of this study was to categorize these ‘factors’ into different stressor categories faced by reptiles to understand its impact on an individual, and to compare how each stressor category influences the survival of an individual. The results from this study indicated that almost half of the number of reptiles being hospitalized were due to exposure to preliminary stressors such as lawn mowing incidents and pet attack. Primary and secondary admissions were fairly equal in number, however the mortality rate for secondary admissions was drastically high (~80%). The discussion integrates species’ ecology and stress physiology which can prove to have multi-faceted benefits across the fields of ecology and animal welfare. Ecologists can use the results from this study to comprehend species’ activity patterns to better plan reptilian conservation programs, whereas, for wildlife clinicians and rehabilitators, assignment of stressor categories could be a beneficial tool for bolstering the welfare monitoring program for small native reptiles in clinical settings.

A cross-sectional study was carried out to determine the prevalence of subclinical mastitis (SCM) among medium to large scale household dairy farms in southwestern district, Jhenaidah, Bangladesh during July to December 2019. A total of 78 (n=100) lactating cows from household dairy farms (N=32) having three or more dairy cows were selected randomly as sampled populations. Milk samples were screened for SCM by using Surf Field Mastitis Test (SFMT). The prevalence of SCM varied among farm level [71.9% (95% CI: 53.3-86.3)], individual animal level [67.9% (95% CI: 56.4-86.3)] and quarter level [29.5% (95% CI: 24.5-34.9)]. Descriptive statistics represented the farmers and farm demography, characteristics of the sampled population, and overall management feature. Random Effect Logistic Regression identified, Body Condition Score (BCS) [OR=3.8 and 2.9, at cows level and quarter level respectively (BCS-2 vs. BCS-≥3)], and breed [OR=5.1 and 2.9, at cows level and quarter level respectively (HF× Sahiwal vs. HF × Local)] as potential risk factors. This study shows that SCM is highly prevalent in the study area, which is a major threat to the dairy industry's production performance. Regular screening by SFMT, proper hygiene, improve the management system, and farmer’s awareness is required to control the disease.

Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-May 5, 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). A total of 6,997 hypertensive patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.

Objective: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. Methods: Subjects (3x10³ ≤ peripheral blood leukocyte levels < 8x10³ cells/μl) who met the inclusion criteria were recruited for this study. Enrolled subjects (n=120) were randomly assigned to either the PTE group (n=60) who were given 2.5 g/day of PTE (as Porphyra tenera extract) in capsule form or the placebo group (n=60) who were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed by measuring natural killer cell (NK-cell) activity, cytokines, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. Results: Compared to baseline, NK cell activity (%) increased for all effector cell to target cell ratios in the PTE group after 8 weeks, but there were no changes in the placebo group (p<0.1). Subgroup analysis of 101 subjects without an URI revealed that NK-cell activity in the PTE group tended to be increased for all E:T ratios (E:T=12.5:1 p=0.068; E:T=25:1 p=0.036; E:T=50:1 p=0.081) compared to the placebo group. There was a significant difference between these two groups for the E:T=25:1 ratio, which increased from 20.3±12.0% at baseline to 23.2±12.4% after 8 weeks in the PTE group (p=0.036). There was no significant difference in levels of cytokines between these two groups. Conclusions: PTE supplementation appears to enhance immune function by improving NK-cell activity without adverse effects in healthy adults.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

The use of machine learning (ML) approaches to target clinical problems is called to revolutionize clinical decision-making. The success of these tools is subjected to the understanding of the intrinsic processes being used during the classical pathway by which clinicians make decisions. In a parallelism with this pathway, ML can have an impact at four levels: for data acquisition, predominantly by extracting standardized, high-quality information with the smallest possible learning curve; for feature extraction, by discharging healthcare practitioners from performing tedious measurements on raw data; for interpretation, by digesting complex, heterogeneous data in order to augment the understanding of the patient status; and for decision support, by leveraging the previous step to predict clinical outcomes, response to treatment or to recommend a specific intervention. This paper discusses the state-of-the-art, as well as the current clinical status and challenges associated with each of these tasks, together with the challenges related to the learning process, the auditability/traceability, the system infrastructure and the integration within clinical processes.

Background: Effectiveness of Anastrozole and levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. Methods: Randomized clinical trial. Elegibility criteria: Endometriomas >3×4 cm, CA-125>35 U/mL and symptoms suggestive of endometriosis. Thirty-one women were randomized to anastrozole+Mirena®+Conservative Surgery(CS) (n=8), anastrozole+Mirena®+transvaginal ultrasound-guided puncture-aspiration(TUGPA) (n=7), Mirena®+CS (n=9), or Mirena®+TUGPA (n=7). Interventions: Anastrozole 1 mg/day and/or only Mirena® for 6 months. CS or TUGPA one month after starting medical treatment. Results: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients treated with anastrozole. For CA-125, the most significant decrease was observed without anastrozole. After CS for endometriosis, a reduction of findings of endometriomas and long-term recurrences occurred, with or without anastrozole, although anastrozole seems to delay recurrences. At 4,2±1,7 years, 88% of the patients who underwent CS were asymptomatic, compared to only 21% if TUGPA was performed, with or without anastrozole (p=0.019). Conclusion: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces more significantly the painful symptoms and delays recurrences, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time.

High throughput multiplex serological systems enable the small developer to set up tests at small cost, for microbes for which there are no commercial tests, and for aspects which have not been addressed by them. An example is testing for Zika and Tick Borne Encephalitis virus antibodies, where antigenic cross-reactions make diagnosis problematic. Our technique variant, Suspension Multiplex Immunoassay (SMIA) allows many samples to be tested for antibodies to many antigens in a short time. Computational compensation for cross-reactions is possible if a SMIA panel contains most of the potentially cross-reacting antigens. Using antibody avidity and pattern of reactivity to whole virus and nonstructural protein, antibodies due to vaccination and infection, respectively, as well as probable degree of protection, can be determined with high throughput. These multiplex techniques hold great promise for future diagnostic development. Theoretically, even large scale serological monitoring, like blood donor pathogen testing, could be done inexpensively and rationally with multiplex serology developed in house. However, the quality control demands are steep and in most cases out of scope for a single laboratory. There remain however a number of clinical applications where in house multiplex serology can be performed with adequate quality control under high throughput conditions.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Sentiment analysis is a pivotal tool for gauging the public’s perception and understanding of human communication across digital social media platforms. However, due to linguistic complexities and limited resources, sentiment analysis is not well-represented in many African languages. While benchmark Africa-Centric Pre-trained Language Models (PLMs) have been developed for various Natural Language Processing (NLP) tasks, their applications in eXplainable Artificial Intelligence (XAI) remain unexplored. In this study, we introduce a novel approach that combines Africa-centric PLMs with XAI techniques for sentiment analysis. We demonstrate that applying attention mechanisms and visualisation techniques improves the transformer-based model’s transparency, trustworthiness, and decision-making abilities when making sentiment predictions. We then employ the SAfriSenti—a multilingual sentiment corpus for South African under-resourced languages. We use the corpus to perform various sentiment analysis experiments and also enable comprehensive evaluations, comparing the performance of Africa-centric models against mainstream PLMs. The Afro-XLMR model outperformed all models and achieved an average F1-score performance of 71.04% across the five tested languages and the lowest error rate among the evaluated models. Additionally, we incorporated techniques like Local Interpretive Model-Agnostic Interpretation (LIME) and Shapley Additive Interpretation (SHAP) in the sentiment classifier’s output to enhance the Afro-XLMR model’s interpretability and explainability. As a result, the use of XAI strategies ensures that sentiment predictions are not only accurate and interpretable but also understandable, fostering trust and reliability in the decision-making of AI-driven NLP technologies, particularly in the context of African languages.

Frailty is a common condition in older adults that negatively impacts health and quality of life. This study evaluated a comprehensive, personalized, and coordinated intervention under the Value-Based Care approach to address frailty's multidimensional nature in older people. It em-ployed a pre-post randomized controlled design, involving frail individuals over 65 years in Valencia, Spain. Assessments were conducted at baseline, 12 months (immediately post-intervention), and 18 months. The intervention included a personalized care plan supported by technology, with monthly motivational follow-ups and plan updates by health professionals and participants. Outcomes were measured using an assessment questionnaire that included the International Consortium for Health Outcomes Measurement dataset for the older population: physical health, physical functioning, general mental health, satisfaction with social activities and relationships, ability to carry out usual social roles and activities, pain, general quality of life, loneliness, physical frailty, psychological frailty and social frailty. The study found signifi-cant improvements in physical frailty, quality of life, reduced health resource use and hospitali-zations, and lower levels of pain and depression/anxiety compared to baseline. The findings suggest further research into value-based care approaches, emphasizing the development and activation of personalized, comprehensive programs for older individuals with frailty.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improve the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical-dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

Over the last decade, highly pathogenic avian influenza (HPAI) has severely affected poultry production systems across the globe. In particular, massive pre-emptive depopulation of all poultry within the certain distance has raised concerns regarding animal welfare and food security. Thus, alternative approaches to reducing unnecessary depopulation, such as risk-based depopulation, are highly demanded. This paper proposes a data-driven method to generate a rule table and risk score for each farm to identify preventive measures against HPAI. To evaluate the proposed method, 105 cases of HPAI occurring in a total of 381 farms in Jeollanam-do from 2014 to 2023 were evaluated. The accuracy of preventive measure identification was assessed for each case using both the conventional culling method and the proposed data-driven method. The evaluation showed that the proposed method achieved an accuracy of 84.19%, significantly surpassing the previous 10.37%. The result was attributed to the proposed method reducing the false-positive rate by 83.61% compared with the conventional method, thereby enhancing the reliability of identification. The proposed method is expected to be utilized in selecting farms for monitoring and management of HPAI.

AgW materials exhibit excellent properties and are widely used as contact materials in low- and medium-voltage switches. In this study, a pre-sintering and infiltration method was employed to pre-sinter W powder with Cu, Ni, and (Cu+Ni) addition in the low temperature range of 950–1050 °C. The low-temperature sintering behaviours of W skeletons with different additives were investigated. Subsequently, AgW70, AgW75, AgW80, and AgW85 materials were prepared through infiltration at 1050 °C. The microstructure morphology and physical properties of high-W contact materials were investigated using a metallographic microscope and scanning electron microscope. The mechanism of low-temperature sintering-infiltration of high-W contact materials was elucidated. The results indicated that pure W and 1% Cu-added W skeletons experience minimal linear shrinkage within the temperature range of 950–1050 °C. The linear shrinkage curves of W skeletons with different additives coincided under the conditions of 950–1000 °C/90 min. At 1050 °C, after sintering for 150 min, the particle boundaries in the W skeleton were fully spheroidised, with a dihedral angle of 120°. At 1050 °C and after 150 min of infiltration, cross-sectional micrographs of the AgW material revealed the presence of irregular Ni layers, where Ni spatially enveloped/encapsulated Ag. With an increase in the W content, the electrical conductivity and relative density of AgW(70–85) materials decreased, whereas the hardness of the materials increased.

The disruptive application of ChatGPT (GPT-3.5, GPT-4) to a variety of domains has become a topic of much discussion in the scientific community and society at large. Large Language Models (LLMs), e.g., BERT, Bard, Generative Pre-trained Transformers (GPTs), LLaMA, etc., have the ability to take instructions, or prompts, from users and generate answers and solutions based on very large volumes of text-based training data. This paper assesses the impact and potential impact of ChatGPT on the field of digital forensics, specifically looking at its latest pre-trained LLM, GPT-4. A series of experiments are conducted to assess its capability across several digital forensic use cases including artefact understanding, evidence searching, code generation, anomaly detection, incident response, and education. Across these topics, its strengths and risks are outlined and a number of general conclusions are drawn. Overall this paper concludes that while there are some potential low-risk applications of ChatGPT within digital forensics, many are either unsuitable at present, since the evidence would need to be uploaded to the service, or they require sufficient knowledge of the topic being asked of the tool to identify incorrect assumptions, inaccuracies, and mistakes. However, to an appropriately knowledgeable user, it could act as a useful supporting tool in some circumstances.

Bone metastasis detection and quantification on bone scintigraphy is challenging and clinical important for treatment and patient’s life quality. To develop a CNN based diagnostic system for automated segmentation on bone metastasis regions is non-trivial, especially for a small dataset. A dataset in house comprising 100 breast cancer patients and 100 prostate cancer patients is utilized for this research. The Double U-Net model is adapted through the integration of background removal, adding negative samples, and transfer learning methods for bone metastasis detection. The performance is investigated via 10-fold cross-validation and computed in pixel-wise scale. The best model we achieved has precision of 63.08%, sensitivity of 70.82%, and F1-score of 66.72%. The developed system has the potential to provide pre-diagnostic reports for physicians in final decisions and the calculation of the bone scan index (BSI) with the combination with bone skeleton segmentation.

Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, it is important to have early diagnosis and appropriate treatment. Objectives. The aim of the study was to know the evolution of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material or pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia and 50 had pre-emptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with pre-emptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Pre-emptive therapy avoided progression to meningitis in patients with CrAg LFA-positive patients. Pre-emptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.

This research investigates the effect of pre-soaking treatment on plant-based aggregate using a wet grout binder to formulate a high-strength lightweight concrete (HSLWC). The surface modification utilising a novel grout soaking technique with various water-to-cement (w/c) ratios indicated a new method of approach for the recent development of lightweight plant-based aggregate (LWPA). In this experiment, the fresh and hardened properties of modified LWPA lightweight concrete were assessed by verifying their workability, densities, compressive and split tensile strengths towards the modulus of elasticity. The results showed that pre-soaking plant-based lightweight aggregate (w/c: 0.6, 0.8, 1.0, and 1.2) slightly increased the density of the samples compared to untreated LWPA. The oven-dry density of treated and untreated LWPA is controlled in the range of HSLWC. The outcomes indicated that the workability of the surface- modified LWPA has significant improvement up to 40% in 6 min for (TDS)/0.6 sample compared to the original LWPA. The mechanical properties of the LWPA concrete with surface modification method exhibit substantial increment of compressive strength, split tensile strength, and modulus of elasticity were recorded at 22%, 26%, and 34%, respectively. Significantly, the findings from this scientific method revealed that the pre-soaking treatment method on LWPA has shown to be a highly recommended technique in improving interfacial bonding while performing as one of the most promising solutions to improve the properties of lightweight concrete.

The implementation of green roofs as sustainable urban drainage systems provides benefits for stormwater control and the environment and is always more encouraged. In this paper, the estimation of the probability of vegetation survival without irrigation has been proposed as a guide to choose the proper values for the design parameters; in particular the growing medium thickness has been related to the average return interval of the water content at the end of the dry period. Moreover the study represents an improvement of the analytical probabilistic approach since a chain of consecutive rainfall events has been considered, in order to take into account the possibility that the storage capacity is not completely available at the beginning of each event because of the pre-filling from more than one previous rainfall as typically happens for green roofs. Finally, developed equations have been validated by means of their application to two case studies, respectively in northern and southern Italy.

Purpose The gradual increase in geriatric issues and global imbalance of the ratio between patients and healthcare professionals has created a demand for intelligent systems with the least error-prone diagnosis results to be used by less medically trained persons and save clinical time. This paper aims at investigating the development of an image-based colourimetric analysis. The purpose of recognising such tests is to support wider users to begin a colourimetric test to be used at homecare settings, telepathology, etc. Design/methodology/approach The concept of an automatic colourimetric assay detection is delivered by utilising two cases. Training Deep Learning (DL) models on thousands of images of these tests using transfer learning, this paper i) classifies the type of the assay, and ii) classifies the colourimetric results. Findings This paper demonstrated that the assay type can be recognised using DL techniques with 100% accuracy within a fraction of a second. Some of the advantages of the pre-trained model over the calibration-based approach are robustness, readiness and suitability to deploy for similar applications within a shorter period of time. Originality/value To the best of our knowledge, this is the first attempt to provide Colourimetric Assay Type Classification (CATC) using DL. Humans are capable to learn thousands of visual classifications in their life. Object recognition may be a trivial task for humans, due to photometric and geometric variabilities along with the high degree of intra-class variabilities it can be a challenging task for machines. However, transforming visual knowledge into machines, as proposed, can support non-experts to better manage their health and reduce some of the burdens on experts.

Kersting’s groundnut is an important source of protein and essential nutrients that contribute to food security in West Africa. However, the crop is still underexploited by the populations and under-researched by the scientific community. This study aimed to investigate the genetic diversity and population structure of 217 Kersting’s groundnut accessions from five origins using 886 DArTseq markers. Gene diversity was low and ranged from 0.049 to 0.064. The number of private alleles greatly varied among populations (42–192) and morphotypes (40–339). Moderate to very high levels of selfing and inbreeding were observed among populations (s=56–85%, F_IS=0.389–0.736) and morphotypes (s=57–82%, F_IS=0.400–0.691). Moreover, little to very high genetic differentiations were observed among populations (0.006≤F_IS≤0.371) and morphotypes (0.029≤F_IS≤0.307). Analysis of molecular variance partitioned 38.5% of the genetic variation among and 48.7% within populations (P<0.001). Significant isolations by distance were detected between populations (R²=0.612, P=0.011) and accessions (R²=0.499, P<0.001). Discriminant analysis of principal components and neighbour joining consistently distinguished eight distinct clusters. These data provide a global picture of the existing genetic diversity for Kersting’s groundnut and will guide the choice of breeding strategies to increase production.

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

Calibrating ecological models or making decisions with them is an optimisation problem with challenging methodological issues. Depending on the optimisation formulation, there may be a large variety of optimisation configurations (e.g. multiple objectives, constraints, stochastic criteria) and finding a single acceptable solution may be difficult. The challenges are exacerbated by the high computational cost and the non linear or elusive mathematical properties that increased with the complexity of numerical models. From the feedbacks of practitioners, the need for a guideline for conducting optimisation of complex models has emerged. In this context, we propose a practical guide for the complex model optimisation process, covering both calibration and decision-making. The guide sets out the workflow with recommendations for each step based on existing tools and methods usually scattered throughout the literature. This guide is accompanied with an ODDO template (Overview, Design, Details of Optimisation) to standardise the published description of model-based optimisation and suggests research directions.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

This paper presents our approaches for the SMM4H’24 Shared Task 5 on the binary classification of English tweets reporting children’s medical disorders. Our first approach involves fine-tuning a single RoBERTa-large model, while the second approach entails ensembling the results of three fine-tuned BERTweet-large models. We demonstrate that although both approaches exhibit identical performance on validation data, the BERTweet-large ensemble excels on test data. Our best-performing system achieves an F1-score of 0.938 on test data, outperforming the benchmark classifier by 1.18%.

Motivation is essential in education, with highly motivated learners engaging more deeply with content and more ably transferring knowledge to new contexts. However, the validity of scales to measure motivation has been underexplored in pre-clerkship medical education. This study evaluates the validity of the Situational Motivation Scale (SIMS) for measuring motivation among pre-clerkship medical students in post-situational and short-term contexts. Using a sample of n = 156 students from the Frank H. Netter MD School of Medicine at Quinnipiac University, SIMS was tested for construct validity with attention paid to content, response process, internal structure, relationships to other variables, and consequences of use evidence. Small modifications from present to past tense in English were made for clarity following focus group feedback, and content validity was ensured via expert consultation. SIMS demonstrated strong internal consistency with a satisfactory Cronbach’s alpha for all subscales and anticipated patterns of correlations. Factor analysis confirmed appropriate factor loadings, with a stronger model fit for the short-term context, and no observed adverse effects on student engagement. These findings support the robustness of SIMS in capturing intrinsic, extrinsic, and amotivation in pre-clerkship medical students, highlighting its applicability for short-term and situational motivational assessment.

Evaluation of the patients after the surgical correction of idiopathic scoliosis in long-term follow-up with the clinical neurophysiology methods has not been presented in detail. This study aimed to compare the results of the neurophysiological studies in 45 girls with scoliosis of Lenke 1-3 types performed pre- (T0), postoperatively (T1, one week after surgery), and 6 months after the surgery (T2). Parameters of surface electromyography during the attempt of maximal contraction (mcsEMG) and transcranially evoked motor evoked potentials (MEP) recorded from anterior tibial muscles, as well as the electroneurography (ENG) of peripheral transmission in the peroneal nerve motor fibers were compared. The results indicate that efferent neural conduction function both centrally and peripherally as well as TA muscle function improve immediately after surgical correction of scoliosis (at p=0.05) and further normalization appears after six months in long-term follow-up (at p=0.03). It has been found in sEMG recordings, that the TA muscle motor unit recruitment function after half a year from surgical treatment in IS patients is comparable to the normal condition. ENG recordings results indicated the gradual retreat of the motor fibers injury symptoms mainly of the axonal type in peroneal nerves, the surgeries improved also the lumbar ventral roots’ neural transmission to the functional status considered as normal. MEP amplitude parameters recorded after the surgical scoliosis correction in T1 indicated a slight improvement in the efferent transmission of neural impulses within the fibers of the spinal tracts; in long-lasting T2 observation, they reached values comparable to those recorded in healthy volunteers bilaterally. Preoperatively (T0) the results of all neurophysiological study parameters in IS patients were asymmetrical at p=0.036-0.05 and recorded as worse on the concave side, suggesting the lateralization of neurological motor deficits. One week postoperatively (T1), this asymmetry was recorded as gradually reduced, showing almost no difference between the right and left sides six months later (T2). The presented algorithm of the diagnostic proceeding pre-, early post-, and long-lasting postoperatively using mcsEMG, MEP, and ENG neurophysiological examinations can be significant not only in making the final decision regarding surgical treatment and its personalization but also helps in precise ascertaining its effects as well as in predicting the final result of IS treatment.

A community-level nutrition intervention was implemented among tribal children (3 to 6 years) in Telangana, India. The one-year intervention involved six nutrient-rich formulations of millet-pulse-groundnut based products, suited to local taste preferences. Anthropometric measurements of height, weight and Mid-Upper-Arm -Circumference (MUAC) along with haemoglobin (Hb) levels were monitored at baseline and endline. The treatment group showed considerable gain in height (3.2 cm), weight (1.68 kg) and MUAC (0.33 cm), over the control group. Paired t-test indicated significant differences (p<.01) between pre- and post-intervention anthropometric measurements. Positive shifts were observed in wasting (WHZ; -1.2 ±1.3 to -0.9± 1), stunting (HAZ; -1.8±1.6 to -0.3±1.3) and underweight (WAZ; -1.9±1.2 to -0.7±1) among treatment group. Hb levels in the treatment group also improved significantly from 9.70 ± 0.14 g/dl (moderately-anaemic) to 11.08 ± 0.13 g/dl (non-anaemic). Post-intervention Focus Group Discussions (FGDs) involving mothers and teachers confirmed the positive impact. Thus, nutritional intervention formulated using climate resilient millets, pulses and groundnut, promotes dietary diversity and improves the nutrition & health status of children.

Empowering teachers with Critical Thinking and understanding of sustainability is vital for guiding students’ informed decisions and actions in today’s world. Higher education needs innovative, student-centered methods like case-based teaching in order to promote Critical Thinking and the principles of Education for Sustainable Development. The aim of the study was to explore and evaluate pre-service teachers' Critical Thinking when engaged with case studies in a practicum preparation course centered on Education for Sustainable Development. Nine undergraduate students in Teacher Education participated in the study and answered four case studies. The case studies’ responses were analyzed through a bottom-up content analysis revealing eight higher-order categories. While approaching the case studies, student-teachers followed thinking processes similar to the processes proposed by the iterative models of Critical Thinking as perceived by Garrison (1991) and/or Brookfield (1987). Nevertheless, in some cases, pre-service teachers’ disengagement was evident. The rubric assessment highlighted that the responses fell under three profiles, namely the “Deficient Critical Thinker”, the “Emerging Critical Thinker” and the “Competent Critical Thinker”. The findings emphasize the need for targeted and individualized teaching interventions in teacher higher education programs aiming at Education for Sustainable Development complying with the learning needs of student-teachers’ Critical Thinking profiles.

Agriculture is one of the indispensable fields for the survival of mankind. Potatoes also have a significant role in the field of agriculture. The quality and quantity of potatoes are significantly impacted by several diseases, such as early blight and late blight, and manual interpretation of these leaf diseases is time-consuming and inconvenient. Fortunately, leaf appearance is used to detect diseases in potato plants. Productivity will considerably rise if the infections are detected early. Different types of image processing methods and machine learning methods are used for early recognition of those diseases from leaf images so that the product losses are decreased significantly. For the incredible and marvelous performance of CNN, it is the most popular deep learning method that is used immensely for the recognition of leaf diseases from images. Several pretrained deep learning models, such as VGG16, ResNet50, InceptionV3, MobileNetV2, Xception, and a deep learning model developed using CNN, are employed for potato leaf disease classification and recognition on the same dataset. The transfer learning technique is applied to the pretrained model and the data augmentation technique is applied to the Proposed CNN model for potato disease classification from leaf samples. Compared to pretrained models, the proposed CNN model offers the lowest loss and highest accuracy for potato leaf disease detection while using fewer parameters and layers. It achieves the best performance with a test accuracy of 99.33% compared to other Pretrained models used in the diagnosis of potato leaf disease.

Body Expression (BE) has been defined in the past decades as a discipline within Physical Education (PE) with very particular characteristics and a strong emotional component. In this study, a programme of this discipline was applied to university Physical Activity and Sports Sciences (PASS) students from six consecutive academic years: three prior to and three during the pandemic. A pre-post design was used to determine how the BE programme affected the university students' self-concept (SC). To do so, a questionnaire with a multidimensional approach to this construct was administered, whose dimensions were closely related to the BE programme's characteristics. The results revealed significant improvements in the final SC, compared to the initial SC. Men reported lower SC values than women before the programme implementation, but higher at the end. Therefore, the change was larger in men, so the programme may have had an equalising effect between groups. It was also verified that the pandemic had particularly affected women.

Passive and forced drinking harm was prevalent but less recognized in Chinese adolescents. We educated adolescents on such harm to reduce their intention to drink. Students (n=1244) from 7 secondary schools in Hong Kong participated in a video-based health talk on passive and forced drinking harm. Paired t-test was used to assess their change in knowledge of passive and forced drinking, health and social harm of drinking after the health talk. McNemar's chi-squared test and adjusted multivariable logistic regression (AOR) were used to assess their change in intention to drink and intention to quit. Students were less likely to drink (OR 0.29, 95% CI 0.19-0.42) and more likely to quit drinking (OR 3.50, 1.10-14.6) after the health talk. Increased knowledge of passive drinking was associated with less intention to drink (AOR 0.93, 0.90-0.97), increased knowledge of health harm (adjusted b 0.06, 0.05-0.08), and social harm of drinking (adjusted b 0.12, 0.10-0.16). Similar associations were observed in forced drinking (intention to drink: AOR 0.87, 0.79-0.96; health harm: adjusted b 0.16, 0.12-0.19; social harm: adjusted b 0.36, 0.28-0.43). We showed preliminary evidence that the health talk on passive and forced drinking reduced the intention to drink in adolescents.

The likelihood of pre-hypertensive young adults developing hypertension has been steadily increasing over the past few years. Despite the fact that aerobic exercise training (AET) has demonstrated positive results in lowering high blood pressure, the efficacy of different types of AET among pre-hypertensive young adults has not been well-established. The objective of this study was to evaluate the effectiveness of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) on blood pressure (BP) of physically inactive pre-hypertensive young adults. 32 adults (age 20.0±1.1 years and BMI 21.5±1.8) were randomly assigned into 3 groups: HIIT, CMT and control (CON). HIIT and CMT groups participated in 5 weeks of AET; while the CON group followed a DASH diet plan only. The HIIT protocol consisted of 1:4 minute work to rest ratio of participants 80%-85% heart rate reserve (HR-reserve) and 40%-60% HR-reserve respectively for 20-minutes, CMT group exercised at 40%-60% of HR-reserve continuously for 20-minutes. In both HIIT and CMT groups, systolic blood pressure (SBP) (3.8±2.8 mmHg, P=0.002 VS 1.6±1.5 mmHg, P=0.011) was significantly reduced. While, significant reductions in the diastolic blood pressure (DBP) (2.9±2.2 mmHg, P=0.002) and mean arterial pressure (MAP) (3.1±1.6mmHg, P<0.0005) were noted only in the HIIT group. No significant differences in SBP (-0.4±3.7 mmHg, P=0.718), DBP (0.4±3.4 mmHg, P=0.714), or MAP (0.1±2.5mmHg, P= 0.892) were observed in the CON group. Both HIIT and CMT decreased the BP in physically inactive pre-hypertensive young adults; however, HIIT yielded more beneficial results in terms of reducing the SPB, DBP and MAP.

The novel coronavirus (COVID-19) was first reported in the U.S. on December 29, 2019 and has spread rapidly throughout the country, affecting individuals with varying severity due to their risk status. According to the Centers for Disease Control and Prevention, it is estimated that 45.4% of US adults are at higher risk for complications from coronavirus disease because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. In this study, we developed a mathematical model to assess the impact of a COVID-19 vaccine among low and high risk groups. Numerical simulations shows vaccinating both low and high risk groups simultaneously, rather than prioritizing the vaccine on high risk group only, further reduces the daily mortality. The result supports the need for an aggressive vaccination program, regardless of whether individuals are within the low or high risk population.

The basic principles of geological risk calculation through Probability of Success (PoS) are mostly applied for numerical estimation of additional hydrocarbon existence in proven reservoirs or potential hydrocarbon discoveries in selected geological regional subsurface volume. It can be tailored and validated for a comprehensive input dataset collected in the selected petroleum province, adapted by dividing up geological events into several probability categories and classes. The most applied categories are (existence of) reservoir rocks, traps and isolators, source rocks, migration pathways and preservation conditions for hydrocarbons The methodology results in unique probability values as multiplication of independent statistical events, which can also be applied in the assessment of a potential hydrocarbon discovery of desired minimal volume and its value in any virtual currency like risk-neutral dollars. Such methodology has been extensively developed in the last decades in the Croatian subsurface, mostly in the Croatian part of the Pannonian Basin System (CPBS). Through the adaptation of geological categories, it was also applied in hybrid, i.e., stochastical, models developed in the CPBS (Drava Depression). Stochastically estimation of porosity was already applied. As the robustness of this methodology is very high, it was also modified to estimate the influence of water-flooding in increasing oil recovery in some proven Neogene sandstone reservoirs in the CPBS (Sava Depression). This new modification is being presented to be applied to geological risk calculation, intending to assess the safety of geological environment in deep wells, where depleted radioactive fuel would be disposed, a subject of great importance. The case study encompassed the magmatic and metamorphic rocks in the pre-Neogene basement of the CPBS. For disposal purpose, these are regionally lithologies considered as to be the safest ones considering petrophysical values, water saturation, recent weathering and tectonic activity.

This study was aimed at investigating the protective effects of glass ionomer cement (GIC) and surface pre-reacted glass ionomer (S-PRG) fillers used as dental restorative materials on demineralization of bovine enamel. GlasIonomer FX ULTRA (FXU), Fuji IX GP Extra (FIXE), CAREDYNE RESTORE (CDR) were used as GICs. PRG Barrier Coat (BC) was used as the S-PRG filler. They were incubated in a lactic acid solution (pH = 4.0) for 6 d at a temperature of 37 °C. The mineral was etched from the enamel surface, and a large number of Ca and P ions were detected in solution. The Al, F, Na, Sr, and Sr ions were released in GICs and S-RPG fillers. The Zn ion was released only in CDR and the B ion was released only in BC. The presence of apparent enamel prism peripheries was observed after 6 d of treatment for the group containing only enamel blocks. pH values for the FXU, FIXE, CDR, BC, and enamel block groups after 6 d were 6.5, 6.6, 6.7, 5.9, and 5.1, respectively. Therefore, the observed pH neutralization effect suppressed progression of caries due to the release of several ions from the restoratives.

Prestress loss evaluation in prestressed strand is essential for prestressed structures. However, the sensors installed outside the duct can only measure the total prestress loss. The sensors attached on strand inside the duct also have several problems, such as inadequate durability in an aggressive environment, vulnerable damage at tensioning and so on. This paper proposes a new installation method for long-gauge fiber Bragg grating (LFBG) sensor to prevent accidental damage. Then the itemized prestress losses were determined in each stage of the pre-tensioning and post-tensioning according to the LFBG measurements. We verified the applicability of the LFBG sensors for prestress monitoring and the accuracy of the proposed prestress loss calculation method during pre-tensioning and post-tensioning. In the pre-tensioning case, the calculated prestress losses had less deviation from the true losses than those obtained from foil-strain gauges, and the durability of the LFBG sensors was better than foil-strain gauges, whereas in post-tensioning case, the calculated prestress losses were close to those derived from theoretical predictions. Finally, we monitored prestress variation in the strand for 90 days. The itemized prestress losses at each stages of post-tensioning were obtained by the proposed calculation method to show the prospect of the LFBG sensors in practical evaluation.

We propose a notion of $(q,\sigma,\tau)$-differential graded algebra, which generalizes the notions of $(\sigma,\tau)$-differential graded algebra and $q$-differential graded algebra. We construct two examples of $(q,\sigma,\tau)$-differential graded algebra, where the first one is constructed by means of generalized Clifford algebra with two generators (reduced quantum plane), where we use a $(\sigma,\tau)$-twisted graded $q$-commutator. In order to construct the second example, we introduce a notion of $(\sigma,\tau)$-pre-cosimplicial algebra.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

(1) Background: Eosinophils importance as T2 inflammation markers is known to be fundamental in asthma, chronic sinusitis, vasculitis. In cancer, despite their potential antiproliferative effect, their role remains unclear. Our purpose was to describe the relation between baseline blood eosinophil count (EOS) and overall survival in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We have analyzed retrospectively the data of 137 adult patients, who underwent surgical treatment of PDAC between years 2012-2019 with no history of systemic steroid use directly before surgical treatment and no metastases found intraoperatively. (3) Results: EOS&lt;0,1 G/l (vs. ≥0,1 G/l) was an independent prognostic factor for OS both the uni- and multivariate Cox regression (respectively: HR=1,48, p=0,035 and HR=1,57, p=0,021). According to EOS and PDAC stage, median OS were: in stage I-III, EOS ≥0,1 G/l group: 14,5 months, in stage I-III, EOS &lt;0,1 G/l group: 8,0 months, in stage IV, EOS ≥0,1 G/l group: 7,0 months, in stage IV, EOS &lt;0,1 G/l group: 5,0 months. (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that T2 inflammation may be the factor directly or indirectly lengthening survival of PDAC patients.

Liver injury caused by various factors significantly impacts human health. Stem cell transplantation has potential for enhancing liver functionality, but safety concerns such as immune rejection, tumorigenesis, and the formation of emboli in the lungs remain. Recent studies have shown that stem cells primarily exert their effects through the secretion of extracellular vesicles (EVs). EVs have been shown to play crucial roles in reducing inflammation, preventing cell death, and promoting liver cell proliferation. Additionally, they can function as carriers to deliver targeted drugs to the liver, thereby exerting specific physiological effects. EVs possess several advantages, including structural stability, low immunogenicity, minimal tumorigenicity targeting capabilities, and convenient collection,. Consequently, these factors have garnered significant attention from researchers and are expected to become alternative therapeutic agents to stem cell therapy. This article provides a comprehensive review of the current research progress on the use of stem cell-derived EVs in the treatment of liver injury.

Mass spectrometry (MS) has revolutionized clinical chemistry, offering unparalleled capabilities for biomolecule analysis. This review explores the growing significance of MS, particularly when coupled with liquid chromatography (LC-MS), in identifying disease biomarkers and quantifying biomolecules for diagnostic and prognostic purposes. The unique advantages of MS in accurately identifying and quantifying diverse molecules have positioned it as a cornerstone in personalized medicine advancement. MS-based technologies have transformed precision medicine, enabling comprehensive understanding of disease mechanisms and patient-specific treatment responses. LC-MS has shown exceptional utility in analyzing complex biological matrices, while high-resolution MS has expanded analytical capabilities, allowing detection of low-abundance molecules and elucidation of complex biological pathways. The integration of MS with other techniques, such as ion mobility spectrometry, has opened new avenues for biomarker discovery and validation. As we progress towards precision medicine, MS-based technologies will be crucial in addressing the challenges of individualized patient care, driving innovations in disease diagnosis, prognosis, and treatment strategies.

In July 2017, a family of three members; a 46-year-old male, a 45-year-old female and their 8-year-old daughter, returned to South Africa from Thailand. They presented symptoms consistent with mosquito-borne diseases, including fever, headaches, severe body aches and nausea. Mosquito bites in all family members suggested recent exposure to arthropod-borne viruses. Dengue virus 1 (Genus Orthoflavivirus) was isolated (isolate no. SA397) from the serum of the 45-year-old female via intracerebral injection in neonatal mice and subsequent passage in VeroE6 cells. Phylogenetic analysis of this strain indicated close genetic identity with cosmopolitan genotype 1 DENV1 strains from Southeast Asia, assigned to major lineage K, minor lineage 1 (DENV1I_K.1), such as GZ8H (99.92%) collected in November 2018 from China and DV1I-TM19-74 isolate (99.72%) identified in Bangkok, Thailand, in 2019. Serum samples from the 46-year-old male yielded a virus isolate that could not be confirmed as DENV1, prompting unbiased metagenomic sequencing for virus identification and characterization. Illumina sequencing identified multiple segments of a Mammalian orthoreovirus (MRV), designated Human/SA395/SA/2017. Genomic and phylogenetic analysis classified Human/SA395/SA/2017 as MRV-3 and assigned a tentative genotype MRV-3d based on the S1 segment. Genomic analyses suggested Human/SA395/SA/2017 may have originated from reassortments of segments among swine, bat, and human MRVs. The closest identity of the viral attachment protein σ1 (S1) was related to a human isolate identified from Tahiti, French Polynesia, in 1960. This indicates ongoing circulation and cocirculation of Southeast Asian and Polynesian strains, but detailed knowledge is hampered by limited availability of genomic surveillance. This case represents a rare concurrent importation of two distinct viruses with different transmission routes in the same family with similar clinical presentations. It highlights the complexities of diagnosing diseases with similar sequelae in travellers returning from tropical areas.

Type 2 diabetes mellitus (T2DM) poses a significant economic and clinical burden. Clinical inertia is defined as the failure of healthcare providers to modify therapy in the presence of clear indications. This study aimed to identify patient opinions on insulin to understand the barriers preventing type 2 diabetes patients from initiating insulin treatment when recommended by their physician. This cross-sectional observational study included 671 individuals with poorly controlled T2DM and HbA1c levels exceeding 10%. These patients required either the initiation or escalation of their existing insulin therapy. The participants were referred to Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) for consultation between January 2022 and July 2022.Results: During discussions between the researcher (clinician) and the inadequately controlled T2DM patients, the primary reasons for refusing insulin therapy were identified. These reasons included fear of injections, the belief that insulin induces dependence and is a last resort, concerns about hypoglycemia and complications, cost, difficulty in computing doses, social stigma, inconvenience and disruption to life and work, storage challenges, fear of weight gain, dependence on others, and lack of confidence.The study concludes that the clinical barriers faced by individuals who refuse the initiation of insulin therapy are diverse. The most common belief among the patients was that insulin leads to dependence (38%), while the smallest percentage cited a lack of confidence in insulin as an effective treatment for lowering hyperglycemia.

Clinical academics experience dual workplaces; the clinical and the research environment. However, working in two workplaces leads to difficulty in forming an integrated identity, and hence affects a person’s work environment and well-being. The aim was to explore how clinical academics experience the psychosocial work environment and their suggestions for improving and changing work well-being. A multicenter qualitative approach with group interviews inspired by participatory action de-sign was used. A purposeful criterion sampling strategy was used, selecting researchers affiliat-ed with the university's research network (n=12). Data were analyzed by thematic analysis and the consolidated criteria for reporting qualitative research was applied. The main finding “lack of integration of research in clinical practice”, revealed how clinical academics balanced between the two practices, how their need for belonging in both work environments were established by fellowship, and how motivational factors and role models could be enhanced through a joint commitment of responsibility in research units and clinical practice. This study provides a contemporary understanding of the challenges that clinical academics en-counter and what solutions they would offer. This study adds to knowledge on psychological work well-being and provides solutions on how clinical academics can achieve integration of research in clinical practice.