Telecoupling, interactions between social-ecological systems across large, often global, distances, drives negative impacts from the forest-based carbon market. Yet, these negative impacts have been underreported; and therefore, likely vastly underestimated. We identify how these unintended negative impacts may occur and provide recommendations for the forest-based carbon market to better account for externalities by prioritising positive social impact, expanding comprehensive ecological outcomes and improving transparency of investments. We call for a carbon market that is designed to account for its global interconnectedness.

The development of plant-based meat analogues has become a significant challenge for the food industry in recent years due to the increasing demand for sustainable and healthier proteins in the context of a global protein transition. Plant-based meat analogues imitate the visual, textural, and chemical properties of traditional meat products and are required to closely resemble meat to appeal to consumers. In addition, consumers demand natural, clean-label, and nutritional and healthy products. To address these challenges, the food industry must develop highly healthy, nutritious, and E-number-free meat analogue products. Understanding the functionality of each ingredient and its role in the food matrix is crucial to being a key player in the innovation of the meat analogues market. This review provides updated information on the primary ingredients utilized for the development of plant-based burger meat alternatives and their functionality. The key components of meat analogue burgers are outlined, including plant proteins, binding agents, fats and oils, flavorings, colorings, preservatives, fortificants, and clean-label considerations.

The hard open problem of finding the lower bound for the Fokker Planck Kolmogorov’s time-dependent controller parameter probability density function is addressed for the first time in literature in this work. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to multi-interdisciplinary fields of human knowledge, and beyond. So, this by default adds more taste and credibility to this study. Concluding thoughts are included at the end of the work along with a difficult outstanding problem and the direction of future work.

This work is the first in literature to tackle the difficult open problem of determining the upper bound and threshold theorem for the TDCDP (time-dependent controller parameter) of the (Fokker Planck Kolmogorov) probability density function. This revolutionary exposition will put control theory and other related inter-disciplinary fields to a higher level towards contemporary control theory. Notably, based on the influential role of control theory in both engineering and industry, this paper will be of great value to all engineering and industry professionals who seek to know more about advanced trends within control theory settings. On the other remit of the spectrum, Fokker Planck Kolmogorov(FPK) equations are of high importance to physicists as well as mathematicians, based on their multiple applicability to information theory, graph theory, data science, finance, economics, and beyond. So, this by default adds more taste and credibility to this study. This leads by nature to introducing a different flavor to this ground-breaking research by highlighting the impact of Fokker Planck Kolmogorov(FPK) to revolutionize crypocurrency,which have received its name because it uses encryption to verify transactions, a new debatable digital payment system that doesn't rely on banks to verify transactions. It’s a peer-to-peer system that can enable anyone anywhere to send and receive payments. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

This study aimed to evaluate the discrepancies between genetic and visual coat color assignment in the Sarcidano Horse and to elucidate potential reasons. Individual DNA from 90 Sarcidano Horses was used for genetic assignment of coat color to explore the correspondence with individual forms containing phenotypical traits. The MC1R exon 1 and ASIP exon 3 have been genotyped and sequenced to obtain a picture of the coat color distribution in this breed. Surprisingly, once we compared the genetic results with the individual forms reporting the phenotypic data for each subject, a certain degree of non-correspondence between the phenotypic and genetic data in relation to coat color emerged. From the genetic analysis, Chestnuts (n = 58) resulted the most common Sarcidano Horse (n = 58), followed by a quite large number of Blacks (n = 28) and a very small number of Bays (n = 4), whereas phenotypic distribution resulted in 38 Chestnuts, 40 Bays, only 2 Blacks, and 10 Grays (without the possibility of recognizing the true color they carried). Chestnut resulted a very representative coat color, while many horses that visually identified as Bays were genetically Blacks. This discrepancy, that could be due to a variety of individual and external factors, including age, time of year, living situation and dietary condition, suggesting the importance of accurate coat color identification to ensure adequate features registration and reliable prediction of offspring’s coat color.

We are introducing a highly efficient 48-channel ultrasound beamforming system ideal for ultrasound endoscopy applications. The system includes a transmitter and a receiver, which allow for low-area, high-resolution imaging acquisition. The transmitter uses a charge redistribution HV (high voltage) scheme to generate three-level pulses that actuate the transducer, implemented with the standard CMOS process for optimal cost and power savings. Meanwhile, the receiver features a sub-array structure and a delay generator that reduces area usage. To achieve high-resolution ultrasound imaging acquisition with low computational power, we developed the Shift Coherence Factor (SCF) algorithm, which is hardware-friendly. This approach delivers a lateral resolution over 20% better than the conventional delay and sum (DAS) algorithm, with a contrast ratio of over 30 dB. The system was implemented in a 180 nm standard CMOS process with an area of 24.98 mm2, power consumption of 8.23 mW per channel, achieving a delay resolution of 8.33 ns, and a low-area implementation of 0.52 mm2 per channel. The system offers high-quality imaging acquisition with minimal additional area and power consumption, which has great potential for 3D imaging or catheterized ultrasound systems.

Background: Thyroid nodules are common, affecting nearly 65% of the general population. While they are widespread, it's crucial to recognize that the majority of these nodules are not cancerous and can be effectively managed through careful monitoring. Thyroid ultrasound is commonly used to evaluate thyroid nodules owing to its low cost, wide availability and technical ease of application. In sonography, it's crucial to assess characteristics and vascular flow. Yet, conventional color and power Doppler ultrasound may not always effectively capture small vessels and low velocities due to their limitations. Superior Microvascular Imaging can display the blood flow of small vessels and low-velocity blood flow, which is difficult to visualize with conventional Doppler ultrasound. Meanwhile other thyroid scans, that utilize either [99mTc] pertechnetate or (18)F-fluorodeoxyglucose, can categorize nodules as hyperactive ('hot'), exhibiting normal activity ('warm'), or having reduced/no activity ('cold'). Thus, the main goal of screening and tracking thyroid nodules is to improve the management of potentially worrisome thyroid malignancies. Methodology: The study was conducted within the structural framework of a network meta-analysis, with the index tests being - SMI, Radionuclide Scanning and Color Doppler, and the general link between them being the reference gold standard. The data collection involved searching for all pertinent literature using PubMed, Google Scholar, and the Cochrane Library databases. The essential data was extracted following the application of specific inclusion and exclusion criteria.This meta-analysis included 7 RCTs with 1,152 patients for Radionuclide Scanning, 10 RCTs with 1,847 patients for SMI and 8 RCTs with 4,480 patients for Color Doppler. They were analyzed using the QualSyst tool and the risk of bias was evaluated by using QUADAS-2 analysis.The statistical software packages MetaDiSc 1.4, RevMan (Review Manager, version 5.3), SPSS (Statistical Package for the Social Sciences, version 20) and Excel in Stata 14 were used to perform the statistical analyses. Result: According to the findings, the sensitivity for Radionuclide Scanning is calculated as 0.79 (range: 0.76 to 0.81) and specificity as 0.55 (range: 0.50 to 0.60) with a 95% confidence interval. The overall diagnostic odds ratio (DOR) for Radionuclide Scanning Is 10.54.Additionally, with a 95% confidence interval, SMI exhibits a sensitivity of 0.82 (with a range of 0.79 to 0.84) and a specificity of 0.86 (with a range of 0.84 to 0.88), while the overall DOR is approximately 25.73. Color Doppler demonstrates a calculated sensitivity of 0.71 (ranging from 0.69 to 0.74) and specificity of 0.81 (ranging from 0.79 to 0.83) with a 95% confidence interval, while its DOR is 13.48.Conclusion: As evidenced by this meta-analysis, blood flow dependent imaging techniques are superior in their abilities to be used as diagnostic tests, especially in conjunction with their use in detecting thyroid nodules. This study offers a starting point for delving deeper into the utilization of Radionuclide Imaging, Superior Microvascular Imaging and Color Doppler in diagnosing thyroid nodules in a clinical setting. Key Words: - Thyroid Nodule, Radionuclide Scanning, Superior Microvascular Imaging, Color Doppler Diagnosis, Sensitivity, Specificity, Diagnostic imaging

In New Orleans, Louisiana the population’s poor baseline health led to its establishment as an early epicenter for severe acute COVID-19. Antici-pating future outbreaks of COVID-19 and other respiratory viruses, we need to identify correlates of outcome, from real clinical experience. 89 patients were recruited into the ClinSeqSer acute COVID-19 longitudinal observational study, from the beginning of the outbreak in March to July 2020. Patients admitted for acute COVID-19 were enrolled in person. The cohort is unique as it is 68% Black, 53% female, of average age of early 60s, and prevalence of obesity and hypertension respectively of 55% and 83%. The outcomes are: 53% severe (20% fatal, 33% non-fatal) and 47% non-severe, with severe defined as death or requiring mechanical ventila-tion or high flow oxygen. Obesity and admit systolic blood pressure (SBP) >140mmHg are each associated with severe outcome and, despite respective sensitivity of 71% and 76%, specificity ~66% for both, and ac-curacy of 60% and 70% by ROC analysis, would likely provide useful predictors of outcome in critically stressed health care systems. We discuss pathophysiologic hypotheses to explain why high admit SBP is observed only in half of patients with pre-COVID hypertension and is associated with severe outcome.

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium’s dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. Aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, being the effect pronounced also when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin treated cells, which were unable to form colonies, were actually ROS+/PI–. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.

Based on the nonlinear failure criterion and modified tangential technique, the upper bound solutions of supporting pressure on the deep tunnel face were obtained under pore water pressure conditions. The influence of parameters on the supporting pressure and collapse range was investigated according to the unlimited block failure mechanism. It is found that the upper bound solutions of supporting pressure increase with the growth of the nonlinear coefficient and pore water pressure coefficient. The collapse range of the tunnel face scales out with the increase of the nonlinear coefficient and shrinks when increasing the pore water pressure coefficient. Moreover, with the increase of the nonlinear coefficient, the impact strength on supporting pressure and collapse range declines gradually. According to the calculating results, it is manifest that both the pore water pressure and nonlinear criterion factors have negative impacts on the stability of the tunnel face. Thus, more attention should be paid to these parameters to ensure face stability in deep tunnel construction.

The application of distributed fiber optic strain and temperature measurement can be utilized to address a multitude of measurement tasks across a diverse range of fields, particularly in the context of structural health monitoring in the domains of building construction, civil engineering, and special foundation engineering. However, a comprehensive understanding of the influences on the measurement method and the sensors is essential to prevent misinterpretations or measurement deviations. In this context, this study investigated the effects of moisture exposure, including various salt solutions and a high pH value, on a distributed strain measurement using Rayleigh backscattering. Three fiber optic sensors with different coating materials and one uncoated fiber were exposed to five different solutions for 24 hours. The study revealed significant discrepancies in deformation between the three coating types depending on the surrounding solution. Furthermore, in contrast to the prevailing literature, which predominantly describes swelling effects, a negative deformation was observed in a magnesium chloride solution. The findings of this study indicate that corresponding effects can impact the precision of measurement, potentially leading to misinterpretations. Conversely, these effects could be used to conduct large-scale monitoring of chemical components using distributed fiber optic sensing.

This paper presents the development and implementation of a Pan-Tilt-Zoom (PTZ) camera interfaced with a Jetson processor hosting Artificial Intelligence (AI) algorithms, designed to address the challenges of traditional biometric capture for first-time passport photos of young children. The system enhances the accuracy, efficiency, and adaptability of facial biometric capture by recognizing and accommodating the dynamic and diverse behaviors of children. Utilizing AI, the system detects faces and analyzes facial features using 68 landmark points, ensuring high-quality images that meet ISO standards. These technical specifications, implementation process, and performance evaluations of the developed system are provided in this paper, demonstrating the potential of the proposed AI Face-Capture to advance biometric identification and verification for young children.

Air pollution has recently gained much attention from the general population. Despite pollution control being an issue in both urban and rural regions, most of the available research has concentrated on urban districts. Hence, investigations into how urban-rural transition affects PM2.5 are warranted within the framework of urban-rural integration. Using the Yellow River Basin as a case study, this study employed the entropy method and Analytic Hierarchy Process (AHP) to uncover the extent of urban-rural transformation. It then used the spatial autocorrelation method to investigate the spatiotemporal features of PM2.5 and the spatial econometric model to investigate the mechanisms that influence the relationship between urban-rural transformation and PM2.5. The results are as follows: (1) Over time, there was a discernible upward tendency in the change in urban-rural areas. The development has progressed from asymmetrical north-east and south-west elevations to a more balanced pattern of north-east, middle-east, and west-west elevations. (2) The PM2.5 concentration increased steadily, then fluctuated, and finally decreased. Notably, the general pattern has not changed much, and it is high in the east and low in the west. (3) Different subsystems of the urban-rural transformation have different impacts on air pollution at different stages. The influence of industrial transformation (IT) on PM2.5 showed an inverted “N-shaped” curve of negative-positive-negative changes, and the industrial structure played a leading role in the spatiotemporal evolution of PM2.5. Currently, an inverted "U-shaped" curve forms the left side of the impact of population transition (PT) on PM2.5. Land development (LT) has a "U-shaped" curve for its effect on PM2.5. This research provides a new perspective on the topic of PM2.5 and its connection to urban-rural integration, which is crucial to understanding the dynamics of this shift. To achieve its goal of high-quality development, it supports regional initiatives to reduce PM2.5 emissions in the Yellow River Basin. Moreover, it can provide a reference for decision-makers in the world’s densely populated areas that suffer from serious air pollution.

Einstein was skeptical of part of quantum mechanics, and he believed that Heisenberg’s uncertainty principle did not reflected the full depth of reality. He famously stated, ”God does not play dice with the universe.” However, since quantum mechanics has passed so many experimental tests, most physicists today assume that Einstein was wrong. Nevertheless, we will demonstrate that Heisenberg’s uncertainty principle must be modified to unify gravity with quantum mechanics. This modification leads to the Certainty-Uncertainty principle where the certainty part is strongly linked to gravity. This means Einstein likely was right in his intuition also on this point. The key is to understand that the de Broglie wavelength is not the actual wavelength of matter but merely a derivative of the true matter wavelength, namely the Compton wavelength. Furthermore, one must understand that the gravitational constant, first introduced in 1873, is simply a composite constant needed to rectify the in- complete definition of kilogram mass introduced into Newtonian gravity in 1873.

Fragile X syndrome (FXS) is an intellectual developmental disorder characterized, inter alia, by deficits in short-term processing of neural information such as sensory processing and working memory. The primary cause of FXS is the loss of fragile X messenger ribonucleoprotein (FMRP), which is profoundly involved in synaptic function and plasticity. Short-term synaptic plasticity (STSP) may play important roles in functions that are affected by FXS. Recent evidence points to a crucial involvement of presynaptic calcium sensor synaptotagmin-7 in STSP. However, how the loss of FMRP affects STSP and synaptotagmin-7 have been insufficiently studied. Further-more, males and females are affected differently by FXS, but the underlying mechanisms remain elusive. The aim of the present study is to investigate possible changes in STSP and the expres-sion of synaptotagmin-7 along the hippocampus of adult males and females in the Fmr1 knock-out (KO) rat model of FXS. We found that paired-pulse ratio and frequency facilita-tion/depression, two forms of STSP, as well as the expression of synaptotagmin-7, are normal in adult KO males, but paired-pulse ratio is increased in the ventral hippocampus of KO females. Furthermore, we found no gender-related but robust region-dependent difference in STSP. AM-PA receptors are similarly expressed in the two hippocampal segments of the two genotypes and in both genders. Also, basal excitatory synaptic transmission is higher in males compared with females. Interestingly, we found more than twofold higher levels of synaptotagmin-7, not syn-aptotagmin-1, in the dorsal compared with the ventral hippocampus in males of both genotypes and in wild type females. These results point to the susceptibility of the female ventral hippo-campus to FMRP loss. Importantly, the different levels of synaptotagmin-7 that parallel the higher score of synaptic facilitation in the dorsal vs ventral hippocampus suggest that synapto-tagmin-7 may play a pivotal role in defining the striking difference in STSP along the long axis of the hippocampus.

The signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arose during the acute phase of COVID19 by an increased breakdown of haematocytes, to which the liver responds by reducing the production of albumin, in order to prevent a too large decrease in haematocrit.In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID. My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the intravenous administration of donor blood products, starting with albumin concentrate. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable. I suspect that most Long COVID patients will exhibit a high serum ferritin level as a result of internal haemolysis, and haematocrit and albumin values at the high and low extremes of the reference range because the liver can not keep up with the recovery of the red bone marrow.

Undoubtedly, there is a potential impact of large language models like ChatGPT in revolutionizing information retrieval and knowledge discovery, particularly in the context of the vast amount of electronic material available. On another strong note, the current work offers a first time ever mathematical approach to accurately fine tune perplexity AI, which sets a giant step ahead towards accurate next generations AI. Having started this world leading discovery, the upper and lower bounds of perplexity AI, namely , , respectively, are obtained for the first-time ever. Concluding remarks combined with emerging open problems and next research phase are provided.

Intestinal parasitic infections pose a significant public health challenge in Northern Nigeria, with prevalence rates ranging from 20% to 70%. Traditional diagnostic methods, primarily microscopic examination of stool samples, face limitations such as low sensitivity and high costs. This research addresses these challenges by proposing an Artificial Intelligence (AI)-based platform for the identification and counting of intestinal parasites. A total of 651 samples were collected from the 7 Northern State of Nigeria along with questionnaire collecting data on demographic, socio-economic, hygiene habits and environmental factors. Leveraging the You Only Look Once (YOLO) V8 model, trained on a dataset of 360 pre-processed and 467 annotated images, the AI model demonstrated promising performance metrics. Information-Theory-Based approaches including (CIFE, CMIM, DISR and ICAP) were used on various machine learning models (Naïve Bayes, Random Forest, Support Vector Machine and Decision Tree) to analyse the risk factors associated with the parasitic disease. The precision-recall curve, average precision, mean average precision, and F1 score indicated reliable detection and classification across various parasite classes. The accuracy (97%) and AUC (99%) scores shows that CIFE with Random Forest has the best performance indicating the significant risk factors associated with the parasitic diseases. The model exhibited a well-balanced trade-off between precision and recall, showcasing its potential as a cost-effective and accessible tool for improving the diagnosis and treatment of intestinal parasitic infections in resource-limited settings.

This research challenges the traditional perspective on consumer behavior, which focuses on external factors shaping the sequential stages of decision-making. Instead, it proposes a paradigm shift by treating the decision-making process itself as an independent variable, exploring its impact on various outcomes like purchasing behavior, brand loyalty, and post-purchase satisfaction. This novel approach offers deeper insights into the intricacies of consumer behavior, particularly in the digital age. By uncovering the reciprocal relationships between the decision-making process and other variables, the research provides a more nuanced understanding of how consumers navigate today's complex landscape. It further delves into how variations in the decision-making process across diverse consumer groups influence various outcomes, recognizing the unique characteristics and needs of different demographics. The research also acknowledges the interplay of psychological, social, and contextual factors that shape both the decision-making process and its downstream effects, offering a comprehensive understanding of the multifaceted influences on consumer behavior. Ultimately, by studying the decision-making process as an independent variable, this research aims to equip businesses and researchers with valuable insights, enabling them to better navigate the ever-evolving world of consumer behavior.

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

Remediation of IT issues encoded into domain-specific or user-defined alerts occurring in cloud environments and customer ecosystems in a vast majority of cases suffers from accurate recommendations which could be timely supplied for recovery of performance degradations. That, of course, is hard to realize through furnishing those abnormality definitions with an appropriate expert knowledge which varies from one environment to another. At the same time, in a large proportion of support cases, the reported problems under Global Support Services (GSS) or Site Reliability Engineering (SRE) treatment ultimately go down to the product teams making them waste costly development hours on investigating self-monitoring metrics of our solutions. Therefore, the mean-time-to-resolution (MTTR) rates of problems/alerts are significantly impacted from lack of a systematic approach towards adopting AI Ops. That would imply building, maintaining, and continuously improving/annotating a data store of insights that ML models are trained and generalized across the whole customer base and corporate cloud services. Our ongoing study is in line with such a vision and validates an approach that learns the alert resolution patterns in such a global setting and explains them using interpretable AI methodologies. The knowledge store of causative rules is then applied in predicting potential sources of the application degradation reflected in an active alert instance. In this communication, we share our experiences with a prototype solution and up to date analysis demonstrating how root conditions are discovered with a high accuracy for a specific type of problem. It is validated against the historical data of resolutions performed by heavy manual development efforts. We also offer a Dempster-Shafer theory-based rule verification framework for experts as a what-if analysis tool to test their hypotheses about underlying environment.

Both cementless and cemented stems have exhibited favorable long-term outcomes in total hip arthroplasty. Nonetheless, in elderly patients, cemented hips offer an advantage because of their reduced risk of periprosthetic fractures. The present study aimed to assess the initial outcomes of 28 patients who underwent unilateral cemented total hip arthroplasty utilizing the calcar-guided A2 stem (Artiqo GmbH, Lüdinghausen, Germany). Various types of antibiotic-loaded cement were employed. Demographic data, comorbidities, and standardized clinical assessment tools, including the Harris Hip Score, were utilized during the follow-up. Radiographic assessments included preoperative, postoperative, and follow-up imaging to evaluate subsidence, osteolysis, and bone resorption. The results indicated that among the 28 patients, 5 withdrew consent, and 2 patients passed away from unrelated causes. Additionally, one prosthesis was explanted because of undersizing of the cement stopper, resulting in an inadequate cement mantle. As a result, 20 patients underwent a 1-year follow-up, revealing noteworthy enhancements in clinical scores, with no instances of radiolucent lines or osteolysis. In summary, our short-term experience with this particular cemented short-stem design yielded promising results, exhibiting excellent functional outcomes and no aseptic loosening attributable to the stem. Further clinical studies and registry data are essential to corroborate these findings.

This retrospective study aimed to assess coronary artery calcium (CAC) progression in serial computed tomography measurements according to risk factor changes. In 448 asymptomatic adults who underwent CAC measurements with more than one-year intervals, CAC progression was assessed according to age, sex, variable traditional risk factors (diabetes mellitus, hypertension, hyperlipidemia, and smoking), and initial CAC score (0, 0.1–100, and >100). Univariate and multivariate logistic regression analyses were assessed for independent predictors of rapid CAC progression (△CAC/year>20). During the 3.5-year follow-up, coronary artery calcifications occurred in 43 (12.8%) of 336 individuals with an initial CAC score of zero. Of 112 individuals with initial CAC presence, 60 (53.6%) had △CAC/year>20. Age, male sex, body mass index, and all risk factors were significantly associated with △CAC/year>20, but recently diagnosed hypertension (odds ratio [OR], 11.3) and initial CAC score (OR, 1.05) were significant independent predictors in multivariate regression analyses. CAC progression was affected by demographic and traditional risk factors, but adjusting for these factors, recently diagnosed hypertension and initial CAC score were the most influential factors for rapid CAC progression. These findings suggest that patients with higher initial CAC scores may benefit from more frequent follow-up scans and checks regarding risk factor changes.

Social isolation and loneliness are major public health concerns and are associated with morbidity and mortality. As this is an increasing issue in older adults, guidance for healthcare providers is a priority. The Canadian Coalition for Senior’s Mental Health (CCSMH) has de-veloped the first Canadian social isolation and loneliness guidelines to help providers recog-nize, assess, and manage social isolation and loneliness among older adults. We review and summarize these guidelines to support healthcare to apply best practices and evidence based care for older adults experiencing social isolation and loneliness.

With increasing electronic medical data and the development of artificial intelligence, Clinical Decision Support Systems (CDSSs) assist clinicians in diagnosis and prescription. Traditional knowledge-based CDSSs follow an accumulated medical knowledgebase and a predefined rule system, which clarifies the decision-making process; however, maintenance cost issues exist in the medical data quality control and standardization process. Non-knowledge-based CDSSs utilize vast amounts of data and algorithms to effectively decide; however, the deep learning black-box problem causes unreliable results. EXplainable Artificial Intelligence (XAI)-based CDSS provides a valid rationale and explainable results. It ensures trustworthiness and transparency by showing the recommendation and prediction results process through explainable techniques. However, existing systems have limitations, such as the scope of data utilization and the lack of explanatory power of AI models. This study proposes a new XAI-based CDSS framework to address these issues; introduce resources, datasets, and models that can be utilized; and provides a foundation model to support decision-making in various disease domains. Finally, we propose future directions for CDSS technology and highlight societal issues that need to be addressed to emphasize the potential of CDSS in the future.

The Roma population constitutes the largest ethnic minority in Europe, however, data regarding the prevalence of non- communicable diseases are still scarce in the medical literature. The aim of this study was to assess the clinical and metabolic particularities of a Roma population with diabetes, in comparison with a group of Romanian Caucasians. We conducted an observational, transversal study and evaluated 808 adult patients with diabetes mellitus, from a tertiary hospital providing diabetes care, aged between 18 and 89 years old, of whom the majority were men (52.84%). Most of them had type 2 diabetes mellitus (T2DM), reaching 95.1% the Caucasian group and 87.8% among the Roma patients. 81.1% of the Caucasian patients had hypertension, approximately 15% higher than the Roma group, while more than half of the patients in both groups had obesity. There were no differences concerning myocardial infarction, however, the number of patients with history of stroke was 2.1 times higher in the Roma group compared to Caucasians. Chronic kidney disease was present in 22.1% of the Roma patients, 33.25% had retinopathy, and 72.7% presented polyneuropathy. The prevalence of cardiovascular risk factors, cardiovascular disease and microvascular complications among the study Roma population are quite significant, underscoring the importance of ethnic disparities in approaching healthcare management strategies.

The artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopaedic-specific problems. One particular area of investigation focuses on the shoulder pathology, which is a range of disorders or abnormalities of shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate the current AI applications in the shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI are also discussed.

Aging is the results of several complex and multifactorial processes, where several agents contribute to increase intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms, finely regulated and strictly interconnected, initiating or contributing to biological changes anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic affects. Vitamin D (VitD) is known to have positive impact not only on muscle and bone health, but also on several extra-skeletal districts, due to the widespread presence of VDRs (VDR). VitD and VDR could be molecules potentially targeting the hallmark of aging network. To date, evidence about the potential effect of VitD on the hallmark of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seems to confirm the modulatory effect of VitD on some hallmarks aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Background: Takayasu’s arteritis is a rare type of vasculitis, with severe complications like stroke, ischemic heart disease, pulmonary hypertension, secondary hypertension, aneurysms. Diagnosis is conducted by clinical and angiographic criteria. Treatment is medical and surgical, but unfortunately, the outcome is reserved. Case presentation: A 34- year- old Caucasian women had an ischemic stroke (2009). She was diagnosed with Takayasu’s arteritis and she received treatment with methotrexate, prednisolone, antiplatelet agents, with a mild improvement of clinical state. After 5 years (2014) she associated ascending aorta aneurysm, pulmonary hypertension, mild aortic regurgitation. The surgical treatment solved both ascending aorta aneurysm and left carotid artery stenosis (ultrasound in 2009 and computed tomography angiogram in 2014). Morphopathology revealed typical appearance for Takayasu’s arteritis. Tumor necrosis factor inhibitors (TNF-inhibitors) were associated to methotrexate. At 48 years (2023) she developed coronary heart disease (angina, electrocardiogram); echocardiography revealed severe pulmonary hypertension; angiography described normal coronary arteries, abdominal aorta pseudoaneurysm and arterial-venous fistula, with origin in right coronary artery and drainage on medium pulmonary artery. The patient refused surgical/ interventional treatment; she received again TNF- inhibitors, methotrexate, antiplatelet agents, statins. Conclusions: This case report presents us a severe form of Takayasu’s arteritis. We consider that morphopathology had a great importance in revealing to clinicians the typical appearance and the stadialization of inflammatory arterial process: acute or chronic. The verdict of morphopathologist was chronic phase, with acute relapses, so we decided that immunosuppressive treatment was still necessary.

ozone-based chemiluminescence detection (CLD) has been widely applied for determining nitric oxide (NO) and its derived species in many different fields, such as environmental monitoring and biomedical research. In humans CLD was applied to determine exhaled NO and NO metabolites in biological samples. The main advantages of CLD are high sensitivity and selectivity for quantitative analysis in a wide dynamic range. Combining CLD with analytical separation techniques like gas or liquid chromatography allows the analytes to be quantified with less disturbance from matrix components or impurities. Sampling techniques like microdialysis and flow injection analysis may be coupled to CLD with the possibility of real-time monitoring of NO. However, details and precautions in experimental practice need to be addressed and clarified to avoid wrongly estimating. Therefore, using CLD as a detection tool requires a deep understanding of sample preparation procedure and chemical reactions used for liberating NO from its derived species. In this review, we discuss the advantages and pitfalls of CLD for determining NO species, the different applications and combinations with other analytical techniques, and provide general practical notes for sample preparation. These guidelines should help other researchers understand CLD data and select the best procedure for detecting NO species.

Background: Resistance to antimalarial drugs often used in emerging countries, including combination therapies, has forced scientists to search for and develop drugs with novel mechanisms of action, especially resistance to Plasmodium falciparum and Plasmodium vivax, which are highly prevalent in Southeast Asia, Africa, and South America. Objective: evaluate whether there is a relationship between urinalysis and resistance to in-hospital treatment of malaria in Angola. Methodology: This was a cross-sectional, prospective study with a quantitative approach. Results: of the 214 patients, the resistance rate was 24.1%, men (53.6%), between 21 and 40 years old (72.7%), employees (46.4%), from peri-urban regions (77.7%), treated with artemether (90.9), with high parasitemia (57.7%) and after 5 days of treatment, remained hospitalized (61.4%). Was a significant relationship between resistance in unemployed individuals [OR: 0.03 (95% CI: 0.01-0.29), p =0.003] and high levels of parasitemia [OR: 1.09 (95% CI: 1.09-3.95), p=0.040], remained hospitalized for more than 5 days [OR: 5.28 (95% CI: 0.65-43.1), p=0.121] and death [OR: 2.59 (95% CI: 0.32-20.9), p=0.371] when compared with other subgroups. Was a significant relationship between resistance to clear urine [OR: 5.55 (95% CI: 0.72-42.7), p =0.016], few urinary crystals [OR: 11.3 (95% CI: 5.07-25.3), p <0.001] and who presented some microorganisms that were not bacteria or fungi [OR: 3.02 (95% CI: 1 .32-6.90), p=0.009]. Conclusion: urine results, especially the appearance of cloudy urine, the presence of few crystals, and the presence of other microorganisms that are not bacteria or fungi, may be clear signs of resistance to hospital treatment with injectable antimalarials.

Semantic interoperability is a foundational concept in modern healthcare, enabling seamless communication and meaningful data exchange across diverse EHR systems. At the heart of this concept lies archetype clinical information models, which serve as standardized templates to structure and encode clinical data, ensuring consistency and shared understanding among various healthcare stakeholders. This review paper delves into the intricacies of Electronic Health Records (EHRs) within the context of semantic interoperability and the pivotal role played by archetype clinical information models. Drawing from a wealth of recent research, this review paper examines the theoretical underpinnings of semantic interoperability. By surveying the literature, it synthesizes the diverse approaches and methods employed to achieve semantic interoperability within EHR systems. Furthermore, this review does not shy away from addressing the significant challenges that persist in this arena. These challenges encompass issues related to data quality, governance, resistance to change, and the scalability and integration hurdles that healthcare organizations encounter in their quest for interoperable EHR systems. Through a comprehensive review of relevant research papers from esteemed sources including PubMed, ScienceDirect, and Taylor & Francis, the paper offers a comprehensive understanding of the approaches and methods employed in this domain. This analysis encompasses a time frame ranging from 2015 to 2023, ensuring an up-to-date assessment of the field. By presenting a well-rounded picture of the field, this review paper offers valuable insights for healthcare stakeholders, researchers, and practitioners. It underscores the enduring importance of semantic interoperability in EHR systems, not only in advancing patient care, clinical decision support, and healthcare operations but also in driving data-driven innovations in the dynamic and ever-evolving medical healthcare sector. This comprehensive examination sets the stage for future advancements in the pursuit of truly interoperable and data-driven healthcare systems.

The primary focus of this review is to explore the application and significance of coping strategies within the domains of clinical psychology and neuropsychology. These strategies consist of a variety of techniques, behaviors, and cognitive interventions, and their critical role in reinforcing resilience and facilitating adaptive responses to stressors has been highlighted. At the core of this exploration, the intricate neuropsychological relationship between brain stress pathways and the application of coping mechanisms has been analyzed. The neural aspects of stress, and how they can be influenced by adaptive strategies, are detailed, illustrating the profound impact these coping mechanisms have at a neurobiological level. Delving into the neuropsychological underpinnings, this review will shed light on how stress response pathways in the brain interact with, and can be modulated by, various coping strategies. These mechanisms are particularly salient when addressing the multifaceted challenges faced by individuals with neuropsychological or mental health issues. While these strategies span a broad spectrum, from introspection and cognitive reframing to behavioral activation and social support seeking, their integration and application remain diverse within clinical contexts. This review endeavors to elucidate the theoretical underpinnings of these strategies, their empirical support, and their practical implications within therapeutic interventions. Furthermore, the intricate interplay between individualized coping techniques and structured therapeutic methodologies will be examined, emphasizing the potential for a holistic treatment paradigm, thereby enhancing therapeutic outcomes and fostering individual resilience.

We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP) and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted to statistical analysis (α=0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD and CAL, which were statistically significant at 90 and 180 days (p&lt;0.0001). Importantly, NSPT significantly reduced the blood level of CRP (p&lt;0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.

Effective healthcare relies on accurate and timely diagnosis; however, obtaining large amounts of training data while maintaining patient privacy remains challenging. This study introduces a novel approach utilizing federated learning (FL) and a cross-device multi-modal model for clin-ical event classification using vital signs data. Our architecture leverages FL to train machine learning models, including Random Forest, AdaBoost, and SGD ensemble model, on vital signs data from a diverse clientele at a Boston hospital (MIMIC-IV dataset). The FL structure preserves patient privacy by training directly on each client's device without transferring sensitive data. The study demonstrates the potential of FL in privacy-preserving clinical event classification, achieving an impressive accuracy of 98.9%. These findings underscore the significance of FL and cross-device ensemble technology in healthcare applications, enabling the analysis of large amounts of sensitive patient data while safeguarding privacy.

Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (irAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the irAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of irAEs with an aim to develop standardized, randomized controlled trial-based management algorithms for ICI-related toxicities.

Chronic non-cancer pain is a highly debilitating condition affecting approximately 20% of the global population. Chronic pain may lead to significant physical disability, emotional distress, social isolation and financial burden. Whilst^. pharmacological therapies remain the cornerstone of pain management in non-cancerous chronic pain, factors including the current opioid epidemic have led to non-pharmacological techniques becoming a more attractive proposition. We explored the prevalence of medical device use and their treatment efficacy in non-cancer pain management. A systematic methodology was developed, peer reviewed and published in PROSPERO (CRD42021235384). Key words of medical device, pain management devices, chronic pain, lower back pain, back pain, leg pain and chronic pelvic pain using Science direct, PubMed, Web of Science, PROSPERO, MEDLINE, EMBASE, PorQuest and ClinicalTrials.gov. All clinical trials, epidemiology and mixed methods studies that reported the use of medical devices for non-cancer chronic pain management published between the 1^st of January 1990 and the 30^th of April 2022 were included. 13 studies were included in systematic review, of these 6 were used in the meta-analysis with 173 participants. Our meta-analysis for pain reduction in each study showed that transcutaneous electrical nerve stimulation combined with instrument-assisted soft tissue mobilization treatment and pulsed electromagnetic therapy produced significant treatment on chronic lower back pain patients. Pooled evidence revealed the use of medical device related interventions resulted in 0.7 degree of pain reduction under a 0-10 scale. Significant improvement in disability scores, with a 7.44 degree reduction in disability level compared to a placebo using a 50 score range was also seen. The application of medical devices in patients with chronic pain has gained popularity due to increasingly cost effective techniques, minimally invasiveness and greater awareness of risks associated with pharmacological management. Our analysis has shown that the optimal use of medical devices in a sustainable manner requires further extensive research, needing larger cohort studies with greater gender parity, in a more diverse range of geographical locations.

This paper aims to list the current challenges in the study of Sports Medicine in Brazil based on a review of the literature and the author's experience as a member of a transdisciplinary team in this field, as well as to discuss methods for establishing an appropriate and organized course of health activities in this context. The authors identified four significant contemporary difficulties in the field of sports medicine in Brazil that, while minor, are complicated. There is a need to publish a greater number of national studies, generate integrated knowledge through transdisciplinary research, propose sports and movement as a tool for the prevention of degenerative conditions, and research and develop better therapeutic options through transdisciplinary research. It is expected that a transdisciplinary approach will reduce divergences between the real world and science, putting an end to dogmatism, prejudice, and theoretical thinking, increasing the scientificity of sports, bringing competitive advantages, improving training, performance, and athlete health management, and contributing to the advancement of sports medicine.

Simulation-Based Medical Education that uses Virtual Patients has become increasingly important during the COVID-19 pandemic. With the need for social distancing and minimizing contact, medical simulation technology has provided a valuable tool for healthcare professionals to practice and improve their skills without the need for face-to-face interactions. MedSIM is a medically accurate simulation platform with Virtual Patients designed for undergraduate medical education. Our study involved two groups of students. The PreCOVID group, before the pandemic, underwent conventional teaching methods. The COVID group, during the pandemic, had students exposed to conventions skills taught earlier and were taught again with MedSIM. Students indicated high satisfaction with the clinical skills demonstrated by the Virtual Patients. More than half agreed that MedSIM had enabled them to perform all kinds of procedures on patients (PreCOVID group 68.8%, COVID group 71.3%), showed cues and consequences much like those in natural clinical environments (PreCOVID 68.4%, COVID 71.3%). Also, MedSIM allowed them to have a repetitive practice that helps in critical skills transfer to actual patients (PreCOVID 72.7%, COVID 74.7%). MedSIM met the expectations of most of the students. Students from both groups rated the online performance of the MedSIM simulator as "Very good." Analysis from a customized word cloud indicated that most students found MedSIM to be good and of educational value. MedSIM platform enhances healthcare professionals' skills and knowledge, leading to better patient outcomes and increased access to healthcare, supporting SDG 3 (Good Health and Well-being). It also provides a safe and controlled environment for healthcare professionals to learn and practice essential skills, supporting SDG 4 (Quality Education).

Background. It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. Methods. We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cut-off points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. Results. Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95%CI 0.10-0.54, p=0.001). Conclusion. PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.

Students' knowledge of the concept of patient safety in infection prevention and control and treatment safety is still low. Real-life problem-based learning approaches in the area of ​​clinical education assist in patient safety education. This study was designed to identify, evaluate and summarize available evidence on the effectiveness of clinical education on student achievement of patient safety competencies. The Methode that use in this study is systematic review. Search for articles in research journals obtained from Sciencedirect, Ebscohost, Garuda, Proquest and Scopus. As many as 228 articles were obtained consisting of nursing journals and health journals with the keywords clinical education, competence, and patient safety. After that, the screening process was carried out based on the inclusion criteria and obtained 25 articles that met the criteria. The result of this study are the contribution of educational institutions in the achievement of patient safety competencies for nursing students is still low and the achievement of patient safety competencies for students at the professional level is better than for students who are still learning theory in educational institutions. The conclusion of this study is clinical education carried out by educational institutions is considered ineffective in achieving the competence of patient safety for nursing students. Therefore, it is necessary to develop a patient safety model or curriculum that is attached to clinical education in nursing education institutions

Background: The treatment plan of prosthetic restorations supported by dental implants require comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A systematic review of the literature was conducted with a PICO question: "For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?". A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS* OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%) or prospective evaluations of prosthesis with various kinds of events (18%). But also narrative reviews of literature (14%) and in vitro/animal studies (16%) were found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.

The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread more than 200 countries as a global health pandemic. There are more 3 million confirmed cases and around 207,000 fatalities. The primary manifestation is respiratory and cardiac but neurological manifestations are being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.

It is currently recognized that an injudicious strategy in the last decades has been not only focusing of research typically on caries in children, but also the narrow focusing on fluoride, because despite sufficient availability of fluoride in water and oral healthcare products, caries levels escalate steadily as people get older and caries remain a main public health issue to be settled. In the last two decades the scientific community intensified efforts of exploring other products for caries prevention, herbal products being one of these approaches. Because preliminary evidence indicated that clinical trials for caries prevention with herbal products are heterogeneous in design, quality and products evaluated, we performed a scoping review intended to explore the main characteristics of such clinical trials. From an initial collection of 1986 unique papers from different literature databases, 56 articles satisfied the inclusion and exclusion criteria. The species investigated, dosage forms, study designs, duration of intervention, controls, endpoints, quality of reporting and risk of bias are discussed. 85.71% of the trials reviewed here reported positive results but given the methodological flaws and biases affecting them, it is difficult to conclude on the efficacy of those products based on the studies published thus far.

Managing blood cholesterol levels is important for the treatment and prevention of diabetes, cardiovascular disease, and obesity. An easy-to-use, portable cholesterol blood test will accelerate more frequent testing by patients and at-risk populations. We aim to evaluate the performance of smartphone-based point-of-care cholesterol blood tests as compared to that of hospital-grade laboratory tests. We used smartphone systems that are already familiar to many people. Because smartphone systems can be carried around everywhere, blood can be measured easily and frequently. We compared the results of cholesterol tests with those of existing clinical diagnostic laboratory methods. We found that smartphone-based point-of-care lipid blood tests are as accurate as hospital-grade laboratory tests (N=116, R>0.97, P<0.001 for all 3 cholesterol blood tests: total cholesterol, high density lipoprotein, and triglyceride). Our system will be useful for those who need to manage blood cholesterol levels to motivate them to track and control their behavior.

This paper presents a methodology for the integration of Building Information Modeling (BIM) and Life Cycle Cost Analysis (LCCA) to assess the economic implications of designing aging-in-place (AIP) homes at the conceptual stage. With the global increase in the aging population, there is an increased demand for housing solutions tailored to the needs of elderly individuals. Focusing on the importance of the early phase of design, this study aims to improve the process of making efficient decisions by providing a comprehensive assessment of the life cycle costs associated with AIP homes. The study introduces a semi-automated model for the economic evaluation of AIP homes, enabling the estimation of costs throughout the houses’ entire life cycle, from design and construction to operation, maintenance, and eventual renovation or disposal. The said model facilitates the exploration of the long-term economic feasibility of design’s related decisions with an emphasis on the importance of considering the life cycle costs early during the design process to optimize the functionality and economic viability. By investing in accessible and universal design features upfront, the initial costs for modifications can lead to long-term savings by reducing the need for extensive retrofits. The model can easily do comparison between different design alternatives in terms of their lifecycle costs, allowing designers to assess the financial impact of using important features in their design such as wider doorways, accessible bathrooms, and elevators. Overall, this study provides valuable insights for designers and homeowners about the economic aspects of designing AIP homes as a support for efficient decision-making during the early stages of the design process.

In order to solve the problem of large eddy current loss and high temperature rise caused by large amount of permanent magnet, a new type of combined magnetic pole permanent magnet motor is proposed in this paper. The sinusoidal distribution subdomain model of non-uniform air gap rotor is established by using Laplace equation, and the analytical expression of eddy current loss of rotor in uniform air-gap and non-uniform air-gap is derived. The effect of rotor eccentricity on eddy current loss is obtained. According to the characteristics of distributed winding of non-uniform air gap combined pole permanent magnet motor, equivalent treatment is performed to obtain the equivalent thermal conductivity, so as to establish equivalent thermal network model of motor, calculate the temperature value of each component of the motor, and verify the correctness of the thermal network model through the method of magnetothermal bidirectional coupling. Finally, an experimental platform is set up to carry out temperature rise experiments on the two prototypes respectively. Experimental results show that the non-uniform air-gap rotor structure can effectively reduce the rotor eddy current loss and motor temperature rise, and also verify the accuracy of the analytical model calculation results.

Soccer is the leading cause of all sports-related ocular injuries in Europe and Israel and leads to blindness at a disproportionately high rate, especially among children (Thompson et al., 2019). With soccer being the most popular sport in the world, it is surprising the only solution to ocular injuries are sports glasses which can cause direct damage to the eye and impair peripheral vision by 15%, calling for an alternative (Smith & Jones, 2020). This work, based on an imported facial model, focuses on both the qualitative and quantitative aspects of building a personalized, low-cost (through optimizing material needed), superior apparatus to conventional sports glasses. The quantitative side examines a modified and model-validated (through a SRS of thirty unique extrapolated points) multivariate linear regression equation, based on horizontal and vertical rotation angles (n=60) trained with residual and computer simulation data, that can accurately extrapolate and quantify ocular impact from all horizontal and vertical rotation angles and a modified Hertzian Contact Stress Equation to determine the thickness of the apparatus using the elasticity modulus, impact force, and geometrical facial and soccer-ball features. The qualitative side examines where firstly, ocular impact is most prevalent, and secondly, where most impact is seen from rotating the ball horizontally and vertically through analysis of Pearson’s Correlation Coefficient at the supraorbital, medial canthus, infraorbital, and lateral canthus regions from both regression equations as well as a cost-benefit analysis for comparison with conventional sports glasses. The findings discovered in this work lay the groundwork for future research to build a customized low-cost ocular injury prevention device which can simultaneously ensure complete ocular safety while enhancing athletic performance for over 250,000,000 players (Johnson & Garcia, 2022).

The continuous flowing spacetime forms a spacetime group G, one of its fundamental groups is the Poincare group PO(1,3), and the matter and interaction fields are representations of its intrinsic spacetime group. As a kind of quantized space-time unit, space-time group elements generate both space-time manifolds and matter. Matter and fields are aggregates of the quantum space-time within them and determine their type: the Lorentz group SO(1,3) represents a rotating spacetime corresponding to visible matter and the translation group P^1,3 represents a translational spacetime corresponding to dark matter and dark energy. The aggregation mode of space-time degrees of freedom in matter reveals that charge conjugation symmetry is the inverse symmetry of internal time of charged particles, and the external parity breaking of neutrinos is also due to their internal spatial aggregation mode.

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.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

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.