Early Stage Research Articles

Metabolomics: A Tool to Envisage Biomarkers in Clinical Interpretation of Cancer.

Cancer is amongst the most dreadful ailments of modern times, and its impact continuously worsens global health systems. Early diagnosis and suitable therapeutic agents are the prime keys to managing this disease. Metabolomics deals with the complete profiling of cells and physiological phenomena in their organelles, thus helping in keen knowledge of the pathological status of the disease. It has been proven to be one of the best strategies in the early screening of cancer. This review has covered the recent updates on the promising role of metabolomics in the identification of significant biochemical markers in cancer-prone individuals that could lead to the identification of cancer in the early stages. The literature was collected through various databases, like Scopus, PubMed, and Google Scholar, with stress laid on the last ten years' publications. It was assessed in this review that early recognition of cancerous growth could be achieved via complete metabolic profiling in association with transcriptomics and proteomics. The outcomes are rooted in various clinical studies that anticipated various biomarkers like tryptophan, phenylalanine, lactates, and different metabolic pathways associated with the Warburg effect. This metabolite imaging has been a fundamental step for the target acquisition, evaluation of predictive cancer biomarkers for early detection, and outlooks into cancer therapy along with critical evaluation. Significant efforts should be made to make this technique most reliable and easy.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype

BackgroundNearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, virus detection and characterization were not at the earliest stages of acute infection. MethodsWe identified an X4-tropic T/F HIV-1 in a participant (40700) in the RV217 acute infection cohort. Coreceptor usage was determined in TZM-bl cell line, NP-2 cell lines, and primary CD4+ T cells using pseudovirus and infectious molecular clones. CD4 subset dynamics were analyzed using flow cytometry. Viral load in each CD4 subset was quantified using cell-associated HIV RNA assay and total and integrated HIV DNA assay. FindingsParticipant 40700 was infected by an X4 tropic HIV-1 without CCR5 using ability. This participant experienced significantly faster CD4 depletion compared to R5 virus infected individuals in the same cohort. Naïve and central memory (CM) CD4 subsets declined faster than effector memory (EM) and transitional memory (TM) subsets. All CD4 subsets, including the naïve, were productively infected. Increased CD4+ T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions, while most of the R5 T/F viruses in the same cohort are sensitive to the same panel of bNAbs. InterpretationsX4-tropic HIV-1 is transmissible through mucosal route in people with wild-type CCR5 genotype. The CD4 subset tropism of HIV-1 may be an important determinant for transmissibility and virulence. FundingInstitute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

Lipidomics and Metabolomics in Infant Atopic Dermatitis: What's the Correlation with Early Nutrition?

To date, the complex picture of atopic dermatitis (AD) has not yet been fully clarified, despite the important prevalence of this disease in the pediatric population (20%) and the possibility of persistence into adulthood, with important implications for the quality of life of those affected, as well as significant social and financial costs. The most recent scientific evidence suggests a new interpretation of AD, highlighting the important role of the environment, particularly that of nutrition in the early stages of development. In fact, the new indications seem to point out the harmful effect of elimination diets, except in rare cases, the uselessness of chrono-insertions during complementary feeding and some benefits, albeit weak, of breastfeeding in those at greater risk. In this context, metabolomics and lipidomics can be necessary for a more in-depth knowledge of the complex metabolic network underlying this pathology. In fact, an alteration of the metabolic contents in children with AD has been highlighted, especially in correlation to the intestinal microbiota. While preliminary lipidomic studies showed the usefulness of a more in-depth knowledge of the alterations of the skin barrier to improve the development of baby skin care products. Therefore, investigating the response of different allergic phenotypes could be useful for better patient management and understanding, thus providing an early intervention on dysbiosis necessary to regulate the immune response from the earliest stages of development.

Numerical Modelling of Carrier Transport in Organic Field Effect Transistors

Background: Organic field effect transistors (OFETs), used in the fabrication of nanosensors, are one of the most promising devices in organic electronics because of their lightweight, flexibility, and low fabrication cost. However, the optimization of such OFETs is still in an early stage due to the minimal analytical and numerical models presented in the literature. Objective: This research presses to demonstrate a numerical carrier transport model based on the finite element method (FEM) to investigate the I-V characteristic of OFETs. Methods: Two various organic semiconductor materials have been included in the study, polyaniline and pentacene, where micro-scale, as well as nano-scale models have been presented. OFETs regarding channel length, dielectric thickness, and doping level impact have been studied. We nominated the threshold voltage, the on/off current ratio, the sub-threshold swing, and the field effect mobilities as the primary output evaluating parameters. Results: The numerical model has shown the criticality of the doping effect on tuning the device flowing drain current to exceed 300 μA saturation current, along with a threshold voltage of -0.1 V under a channel length of 30 nm. Conclusion: The study highlights the effectiveness of polyaniline over pentacene as nano-channel length OFET due to the boosted conductivity of polyaniline concerning pentacene.

Comparing tooth development timing between ethnic groups, excluding nutritional and environmental influences.

The timing of dental development in ethnic Finns and Somalis, who were born and living in Finland, was compared, with efforts to minimize environmental bias. The developmental status of seven lower left permanent teeth were staged according to Demirjian et al., using panoramic radiographs from 2,100 Finnish and 808 Somali females and males, aged 2 to 23 years. For each tooth, a continuation-ratio model was constructed to analyze the allocated stages as a function of sex and ethnic origin. Several statistically significant differences in mean age of certain tooth developmental stage transitions were revealed. While Somalis generally displayed stage transitions at younger age, none of the seven teeth consistently showed earlier stage transitions in Somalis compared to Finns. Within each tooth, the lowest (or highest) mean age of stage transition varied without any discernible pattern between the two ethnic groups. Overall, the observed differences in mean age of stage transition between the groups was minimal, suggesting a low impact on clinical and forensic age assessment practice. In conclusion, the studied ethnic Finn and Somali groups with equal nutritional and /or environmental conditions exhibit similar timing in the development of all lower left permanent teeth.

Narratives of growth of formative technological innovation systems based on a knowledge perspective: the case of medical devices

Purpose This study aims to analyze the narratives of growth during the initial stages of development of the medical device technological innovation system (TIS). This paper used micro/nanofluidic-based point-of-care testing (mnPOCT), a breakthrough technology in the health-care sector. Design/methodology/approach This study presents a framework that includes measures of knowledge breadth and sharing mechanisms based on cognitive and actor-based networks. The framework integrates bibliometric, network and statistics-based approaches with a focus on the first decade of mnPOCT development. Findings In addition to the typical patterns of technological emergence, the mnPOCT sector exhibits distinctive characteristics. This paper observed significant scientific content and a high geographic concentration. Although small- and medium-sized enterprises, particularly startups, detonate knowledge development, large companies play a subtle yet impactful role as innovation mediators. Interfirm alliances are sparse, reflecting the complementarities between startups and large firms throughout the innovation value chain. These alliances show a significant correlation with SME knowledge creation. Research limitations/implications This study provides researchers and practitioners with guidelines for assessing the dynamics of the growth of technologies in the earliest stages of growth through knowledge and implications for research strategy toward the development and deployment of effective system interventions. Originality/value The study of formative TISs presents challenges because of the nascent characteristics and uncertainties surrounding emerging technologies. Current discussions on the narratives of growth of emerging TISs are limited to broad descriptions, which hinder understanding of these formative stages. This study offers a unique approach to assessing the initial stages of technological evolution. Moreover, it contributes to the existing literature by providing guidelines for managing new technologies for R&D researchers and practitioners.

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.

Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF. We included 81 patients with stage D HF (ICM, n=44; DCM, n=37) undergoing left ventricular assist device implantation (n=59) or heart transplantation (n=22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation. Patients with ICM or DCM did not differ regarding age (61.5±5.7 vs. 56.5±12.7years, P=0.164), sex (86% vs. 84% male, P=0.725), type 2 diabetes mellitus (34% vs. 18%, P=0.126) or chronic kidney disease (8% vs. 11%, P=0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6±41.4 vs. 141.9±59.9pmol/(s*mg), P=0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59±0.28 vs. 0.69±0.36pmol/(s*ml), P=0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6±164.1 vs. 503.0±198.5nmol/min/mg protein, P=0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P=0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r=-0.296, P=0.019). Fibrosis was more prevalent in ICM (20.9±21.2 vs. 7.2±5.6% of area, P=0.002), but not associated with oxidative capacity (r=-0.13, P=0.327). More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.

The causal relationship of DTI phenotypes and epilepsy: A two sample mendelian randomization study.

Clinical studies indicated a link between DTI imaging characteristics and epilepsy, but the causality of this connection had not been established. Therefore, we employed the Mendelian randomization analysis method to determine the causal relationship between DTI imaging characteristics and epilepsy. We used Mendelian randomization analysis to identify the causal relationship between brain structure and the risk of epilepsy. GWAS data of DTI phenotypes, focal epilepsy, and genetic generalized epilepsy (GGE) were utilized in the analysis. Our study found that DTI imaging phenotypes had a causal risk relationship with epilepsy. These phenotypes had a statistical impact on the risk of epilepsy seizures. There were differences in DTI phenotype causality between GGE and focal epilepsy, which were associated with the clinical phenotype differences of the two types of epilepsy. Our study demonstrated that the diagnosis of subtypes could be assisted by comparing the differences in DTI phenotypes of specific brain regions. This meant that by studying the changes in brain regions before the onset of epilepsy, we might be able to intervene in epilepsy at an earlier stage. Our study used Mendelian randomization to explore the causal relationship between brain structure, as seen in DTI imaging, and epilepsy. We found that specific DTI phenotypes are linked to an increased risk of epilepsy seizures, with notable differences between genetic generalized epilepsy and focal epilepsy. This suggested that analyzing DTI phenotypes could help in diagnosing and potentially intervening in epilepsy earlier by finding brain changes before seizures begin.

Polyclonal-to-monoclonal transition in colorectal precancerous evolution.

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited1-3. Here we used a base editor-enabled DNA barcoding system4 to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent celllineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer.

Prevalence and Clinical Significance of Skin Manifestations in Parkinson Disease Patients

Background: Parkinson's disease (PD) is primarily characterized by motor symptoms, but non-motor symptoms, including skin manifestations, are increasingly recognized. These remain underexplored despite their potential impact on quality of life. Objectives: This study aimed to evaluate the prevalence and clinical features of skin findings in PD patients, with a focus on identifying potential pathogenetic links between dermatological conditions and PD. Methods: A total of 215 PD patients were included. Comprehensive dermatological examinations were performed, and demographic and clinical data were collected. Statistical analysis was conducted using SPSS 23.0, with significance set at P < 0.05. Results: Skin conditions were found in 92.1% of PD patients. Xerosis, seborrheic dermatitis, and hyperhidrosis were the most common findings. Pre-PD xerosis was associated with an earlier stage of PD (P = 0.001). Use of PD medications, such as levodopa/carbidopa/entacapone, was linked to a lower incidence of seborrheic dermatitis (P = 0.040). A significant correlation was also noted between rosacea and cherry angioma (P = 0.01). Conclusion: Dermatological conditions are prevalent in PD and may precede its motor symptoms. Skin assessments could aid early diagnosis and management of PD, highlighting the need for further research on their pathogenetic mechanisms.

Keeping Community During a Pandemic

The purpose of this qualitative exploratory study was to better understand how LGBTQ+ senior centers created virtual communities and implemented organizational adaptation in the earliest stages of the pandemic. Three focus groups (n=22) were conducted with program facilitators and senior center employees to better understand how these key stakeholders contributed to the transition from in person senior center to virtual senior center programming in March of 2020. The experiences of LGBTQ+ program facilitators and senior center staff varied based on the nature of their assigned roles. Latent pattern content analysis of the focus groups unveiled both shared and divergent categories and themes from the two cohorts. Themes identified for program facilitators included: adaptation, interconnectedness, some not served, and virtual preference. Themes identified for senior center staff included: communication, the blurring of the personal/professional, urgent needs, and future planning.

Are labor epidural catheters after a combined spinal epidural (CSE) technique more reliable than after a traditional epidural? A retrospective review of 9153 labor epidural catheters.

The combined spinal epidural (CSE) technique may associate with a lower failure rate of epidural catheters compared to traditional epidural catheters. This may be significant for the parturients as failure of neuraxial analgesia has been associated with a negative impact on birth experience. In this one-year retrospective study, the failure rate of epidural catheters was compared between 3201 and 5952 epidural catheters after initiation of neuraxial analgesia by the CSE or traditional epidural technique, respectively. Parturient background information, labor parameters, and neuraxial interventions were collected from 9153 parturients. Failure was defined as replacement of a used epidural catheter by new regional analgesia procedures or general anesthesia during intrapartum cesarean delivery. The primary outcome was the failure rate of epidural catheters. The secondary outcome was the time from the initial analgesia intervention to the epidural catheter replacement and progression of labor during this time. The CSE method was used at an earlier stage of labor, and the parturients were more often primiparous and undergoing induced labor. Earlier onset of analgesia, obesity, induced labor, anesthesiologist experience, and cesarean delivery were found to be significant cofactors for catheter failure. The unadjusted failure rate was 168/3201 (5.2%) and 223/5952 (3.7%) (OR 1.42 [1.16-1.75]) after initiation of analgesia by CSE or traditional epidural method. After controlling for the stage of labor, body mass index, induction of labor, and anesthesiologist's experience level, the adjusted OR for epidural catheter replacement was 1.04 (0.83-1.29) p = .736. The mean (SD) time until epidural catheter failure was 6.3 (4.4) and 4.0 (4.1) hours following initiation of analgesia by CSE or traditional epidural technique, respectively (p < .001). Cervical dilatation progressed from 4.3 (1.4) to 6.4 (2.1) cm and 5.1 (1.5) to 6.7 (1.7) cm between primary neuraxial analgesia and epidural catheter replacement. CSE technique was not associated with a better survival rate of epidural catheters for provision of analgesia or epidural top-up anesthesia for intrapartum CD. In addition, the time to replacement of the catheter was significantly longer when analgesia was initiated with the CSE technique. Maternal satisfaction scores were lower if catheters required replacement.

Patient journey from the appearance of red flags to the diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in Japan: a nationwide retrospective study using a medical claims database

Abstract Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of common cardiovascular conditions in the elderly, with relatively high rates among patients diagnosed with heart failure (HF) with preserved ejection fraction. In addition to cardiac symptoms such as HF, extracardiac symptoms such as carpal tunnel syndrome (CTS) and lumbar spinal stenosis (LSS) are also red flags for ATTR-CM. Tafamidis is currently the only disease-modifying therapy approved for the treatment of patients with ATTR-CM and is likely to be more effective in the earlier stage. Patients with ATTR-CM often undergo a long and difficult diagnostic journey because of the nonspecificity of clinical manifestations, resulting in delays in establishing the correct diagnosis. Purpose To identify the timing of appearance of comorbidities in patients with ATTR-CM during diagnosis. Methods In this retrospective, non-interventional, observational study using a claims database (dataset period: April 1, 2014–August 31, 2021), adult patients with a diagnosis of ATTR-CM or prescription for tafamidis 80 mg were included. The index date was defined as the first date of recording ATTR-CM diagnosis or the prescription of tafamidis 80 mg, whichever was earlier. The baseline period was defined as the period between the index date and 6 months before the index date. The onset date was defined as the first date of recording diagnosis of the first red-flags that was suspicious for ATTR-CM. Results Of 11,101,578 patients in the database, 246 patients with ATTR-CM met the inclusion criteria. A total of 239 patients were included, of whom 139 had received tafamidis 80 mg. The median (range) age at the index date was 79.0 (46.0–95.0) years, and 79.9% (191/239) were male. The most frequently reported comorbidity defined as onset of ATTR-CM was conduction disorders (88.7%) followed by atrial fibrillation/atrial flutter (50.6%), hypertensive heart disease (19.7%), aortic stenosis (15.9%), and hypertrophic cardiomyopathy (11.7%), with the median (interquartile range [IQR]) time to the index date being 15.5 (5.0–24.5), 14.0 (5.0–22.0), 9.0 (2.0–18.0), 5.0 (2.0–16.0), and 12.0 (6.5–21.5) months, respectively (Fig. 1). LSS (23.9%), neuropathy (13.0%), and CTS (7.5%) were frequently observed as extracardiac symptoms at baseline, and the median (IQR) time from appearance to the index date was 19 (9.0–28.0), 5.0 (1.0–16.0), and 18.0 (14.0–25.0) months, respectively (Fig. 2). Conclusions This study elucidated the time lag between the appearance of cardiac and extracardiac complications of ATTR-CM and its diagnosis in real-world clinical settings. These novel findings highlight the potential for earlier detection of ATTR-CM.

Ensuring sustainable impact of the national report on climate change and health in Germany 2023

Abstract Issue/problem The Robert Koch Institute recently coordinated a status report on climate change and health for Germany, detailing the current and future impact of climate change on health through 14 chapters. Description of the problem A central aim was to ensure the report’s long-term impact and public health value. Essential areas of focus have therefore been stakeholder-specific communication and establishing a network of experts for continued scientific exchange. Results The publication of the report as peer-reviewed articles has served to reach the scientific community. Another target group are public health practitioners and decision makers at subnational levels, who can contribute towards climate change mitigation and adaptation measures relevant to health, as recommended in the report. This latter group was reached through various methods and formats of science communication, including conferences aimed at the public health sector, through target-group oriented podcasts, social media engagement and digital town hall discussions. Following publication, the experts involved in writing, reviewing and using the report were invited to establish a network in order to support long-term scientific exchange and collaborations and in turn ensure the report’s sustainable impact and value. Lessons Through follow-up evaluations, the reception of the report and the further communication needs of this target group were analysed. A major lesson was to include the insights of public health practitioners more systematically and at an earlier stage in any future reports. As for the establishment of a network, a survey amongst the authors and other experts showed what this group considers the goals of this network: creating synergies and connections with existing initiatives and providing a platform for further exchange, especially amongst researchers addressing similar questions, such as the efficacy of mitigation and adaptation measures, from different angles. Key messages • Local public health practitioners are important stakeholders for climate change and health for ensuring public health impact. • The expertise in the network will support continued scientific exchange on climate change and health and thus ensure the national report’s sustainability.

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and &amp;gt;60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was &amp;lt;0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

ADGRU: Adaptive DenseNet with gated recurrent unit for automatic diagnosis of periodontal bone loss and stage periodontitis with tooth segmentation mechanism.

Periodontics and gingivitis are two of the most widely prevalent illnesses that affect people nowadays. The sixth most common disease in the world is periodontitis, and detecting periodontal bone loss is essential in the earlier condition and is crucial for the development of the proper diagnosis. Early bone loss detection can be assisted by using computer-assisted radiography examination. Understanding disease progression helps to select the most effective treatment action. An effective deep model is suggested to detect periodontal bone loss at an earlier stage for preventing the progression of Periodontics bone loss. This work is intimated by collecting images from online resources. Further, the images gathered from the dataset are preceded by the tooth segmentation which is done using DenseUNet + + . Further, the segmented images are given to the Adaptive DenseNet with Gated Recurrent Unit (AD-GRU) for detecting periodontal bone loss and this diagnosis is used for the periodontitis stage, where the ADGRU performance is augmented by optimizing the attributes using the Refined Red Kite Optimization Algorithm (RRKOA). The offered approach attained an accuracy of 94.45% which is higher than the88.63%, 90.58%, 89.54%, and 92.96% attained by the LSTM, DenseNet, GRU, DenseNet-GRU. The findings of the simulation proved the designed framework outperformed the traditional model with high accuracy. The developed effectual deep model-based periodontal bone loss and stage periodontitis diagnosis structure is used in healthcare applications.

Effect of the COVID-19 pandemic on the well-being of middle-aged and older Europeans

The COVID-19 pandemic has been associated with a general decline in well-being. However, there is limited evidence on the effect of the pandemic on the general population, and especially among the ageing population. We assessed the overall impact of the pandemic on the well-being of middle-aged and older adults residing in 27 European countries, focusing on the time-period before summer 2021. We used a sample of 46,209 respondents from the two population-based longitudinal Corona Surveys collected during summer 2020 and summer 2021. To test our hypotheses, we used latent change score models. All analyses were stratified by sex. The COVID-19 pandemic affected middle-aged and older Europeans’ well-being irrespective of their sex. Being infected by the COVID-19 virus at the start of the pandemic had a negative impact on well-being. As expected, adults with Long COVID experienced the most pronounced decline in well-being. A novel finding was the decline in the level of well-being among adults not infected by the COVID-19 virus. Support should be provided at community levels with specific attention towards individuals with Long COVID symptoms and those infected with COVID-19 at earlier stages of the pandemic.

Strengthening ecosystems

Abstract The mission of THCS activities with respect to strengthening ecosystems is based on the understanding that the actual transformation of health and care systems is dependent on the ability of numerous actors to align their goals and actions so that they are complementary. At the same time, it is also true that the transformation takes place at national, regional and local levels, making activities and support at these levels essential for the success of THCS. Therefore, the focus lies on connecting and supporting the broad community and other stakeholders in developing ecosystem-wide approaches and creating awareness and urgency among ecosystem layers and components, thus serving as a platform for transformation. One strand of activities for strengthening ecosystems aims at identifying, analysing, describing and disseminating key learnings from successful transformative ecosystems (TE’s). TE’s are broad constellations of interacting organisations and people who are committed, and through aligned actions, able to reach joint, explicitly defined goals in long-term. Making not only the most successful TE’s but also the dynamics explaining their achievements visible, value is being added through three main routes. Firstly, the experiences are distributed widely on European arenas and platforms as well as through national, regional and local channels to inspire ecosystem building processes in earlier stages of maturity. Secondly, collaboration between identified forerunner ecosystems is supported to enable mutual peer-learning. Thirdly, the examples are used to give guidance and inspiration to consortia that are applying for or receiving THCS project funding. As strategic partners of the ecosystem strengthening activities, other work packages of the THCS programme as well as the THCS National Mirror Groups are of great importance.

Future of Uremic Toxin Management

During the progression of chronic kidney disease (CKD), the retention of uremic toxins plays a key role in the development of uremic syndrome. Knowledge about the nature and biological impact of uremic toxins has grown exponentially over the past decades. However, the science on reducing the concentration and effects of uremic toxins has not advanced in parallel. Additionally, the focus has remained for too long on dialysis strategies, which only benefit the small fraction of people with CKD who suffer from advanced kidney disease, whereas uremic toxicity effects are only partially prevented. This article reviews recent research on alternative methods to counteract uremic toxicity, emphasizing options that are also beneficial in the earlier stages of CKD, with a focus on both established methods and approaches which are still under investigation or at the experimental stage. We will consequently discuss the preservation of kidney function, the prevention of cardiovascular damage, gastro-intestinal interventions, including diet and biotics, and pharmacologic interventions. In the final part, we also review alternative options for extracorporeal uremic toxin removal. The future will reveal which of these options are valid for further development and evidence-based assessment, hopefully leading to a more sustainable treatment model for CKD than the current one.

Inter-brain synchrony is associated with greater shared identity within naturalistic conversational pairs.

Inter-brain synchrony occurs between individuals who feel connected socially, but how synchrony relates to felt connectedness under naturalistic social interaction has remained enigmatic. We hypothesized that inter-brain synchrony between naturally interacting individuals might be associated with the internalization of a social identity, a link between an individual's personal identity and the social group to which the individual belongs. A convenience sample of sixty participants were split into dyads and interacted naturalistically on a social task. Through mapping EEG oscillatory waveforms onto a conceptual model categorizing the formation of a social identity within a naturalistic conversation, greater inter-brain synchrony was observed in the emergent stage within the formation of a social identity compared to earlier stages, where a social identity was not present. We provide evidence for greater neural synchrony related to higher socio-psychological connectedness during the development of social identity under naturalistic social interaction.