Future Disease Research Articles

Epidemiological Characteristics and Prevention of COVID-19

At around March of 2020, the new coronavirus, now named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), spread fast across the world. The symptoms of SARS-CoV-2, such as fever, cough, difficult breathing, and pneumonia were similar to the infection of influenza virus, which mislead the public at the beginning of the virus outbreak. In addition, social issues in aspects of economy, environment, and resource distribution should be considered as factors of what lead to the global pandemic as well. This article briefly introduced the pathology of COVID-19, summarized factors that lead to the global pandemic from three aspects: the complexity and variation of the virus, the validity of the vaccine, and the action and countermeasures of the public health system. Then, this article discussed the countermeasures aim from public health system and individual at this pandemic particularly, providing some ideas for pandemic of infection diseases in future.

Evaluation of Periodontal Status and Serum C-Reactive Protein Levels in Adult Cigarette Smokers

Background: This study aimed to evaluate the periodontal status of adult smokers and assess their serum C-reactive protein (CRP) levels, hypothesizing an association between periodontal inflammation, smoking, and elevated serum CRP, a marker for cardiovascular diseases. The primary objective is to contribute to the assessment and prevention of potential cardiovascular diseases in adult smokers. Methods: This cross-sectional study was conducted at HIT Hospital and Dental Hospital HITEC-IMS Taxila Cantt over five months from October 20, 2021, to March 31, 2022, the study included 60 healthy male adult smokers and 20 healthy male non-smokers as a control. Basic periodontal examination involved the use of a periodontal probe, assessing parameters such as gingival index, bleeding on probing, oral pigmentation, presence of periodontal pockets, and gingival recession. Blood samples were collected to evaluate serum CRP levels. Results: Smokers exhibited higher rates of gingival recession (38.3%), gingival pigmentation (43.3%), and periodontal pocket formation (33.3%) compared to the nonsmokers control group, with significant p-values of 0.040 in gingival recession and 0.035 in the presence of periodontal pockets. Serum CRP levels were significantly elevated in adult smokers, with a significant p-value of 0.024. Conclusion: The study concluded that adult smokers show signs of periodontitis, and their serum CRP levels are elevated. Assessing periodontal status and serum CRP in adult smokers may aid in risk assessment and reducing the likelihood of developing future cardiovascular diseases.

Excess mortality in adults from Sao Paulo during the COVID-19 pandemic in 2020: analyses of all-cause and noncommunicable diseases mortality

In this study, we estimated the excess mortality from all-causes of death and noncommunicable diseases (NCDs) in adults living in the state of São Paulo during the COVID-19 pandemic in 2020. Number of deaths were retrieved from the Mortality Information System before (2017–2019) and during (2020) the COVID-19 pandemic, considering the following underlying causes of death: Neoplasms; Diabetes Mellitus; Circulatory System Diseases, and Respiratory System Diseases. Standardized Mortality Ratio (SMR) were calculated by dividing the mortality rates in 2020 by average mortality rates in 2017–2019, according to sex, age group, geographic location (state, capital, and Regional Health Departments). In 2020, occurred 341,704 deaths in the state of São Paulo vs 290,679 deaths in 2017–2019, representing an 18% increase in all-cause mortality (SMR 1.18) or 51,025 excess deaths during the first year of COVID-19 pandemic. The excess mortality was higher in men (186,741 deaths in 2020 vs 156,371 deaths in 2017–2019; SMR 1.18; 30,370 excess deaths) compared to women (154,963 deaths in 2020 vs 134,308 deaths in 2017–2019; SMR 1.15; 20,655 excess deaths). Regarding NCDs mortality, we observed a reduction in cancer mortality (SMR 0.98; −1,354 deaths), diseases of the circulatory system (SMR 0.95; −4,277 deaths), and respiratory system (SMR 0.88; −1,945). We found a 26% increase in Diabetes Mellitus mortality (SMR 1.26; 2885 deaths) during the pandemic year. Our findings corroborate the need to create and strengthen policies aimed at the prevention and control of NCDs, in order to mitigate the impact of future infectious disease pandemics.

Temporal trends of migraine and tension-type headache burden across the BRICS: implications from the Global Burden of Disease study 2019.

Headache disorders have become a significant global public health issue, with a notably high prevalence observed in developing countries. However, few studies have assessed headache disorders trends in Brazil, Russia, India, China and South Africa (BRICS). This study aimed to assess the prevalence of headache disorders in individuals across the BRICS, spanning the years 1990 to 2019. We obtained headache disorders data from the Global Burden of Disease 2019 study (GBD2019). This evaluation examined incidence rates, prevalence, and disability-adjusted life-years (DALYs) for migraine and tension-type headache (TTH) across demographic factors like age, gender, year, and country. Migraine and TTH were diagnosed based on the International Classification of Headache Disorders (ICHD-3) criteria. We used disease codes from the International Classification of Diseases, 10th revision to identify migraine and TTH cases. Statistical analyzes included calculating age-standardized rates and estimated annual percentage changes. Future disease burden was projected using a log-linear age-period-cohort model. In 2019, India had the highest prevalence of migraine (213890207.93 cases) and TTH (374,453,700 cases). Brazil had the highest migraine age-standardized prevalence rate (18,331 per 100,000) and incidence rate (1,489 per 100,000). For TTH, India had the highest prevalence (26,160 per 100,000) while Russia had the highest incidence (11,512 per 100,000). From 1990 to 2019, China showed the greatest increase in migraine and TTH prevalence. India had the highest migraine (7,687,692) and TTH (741,392) DALYs in 2019. Migraine and TTH remain highly prevalent in BRICS nations, inflicting considerable disability burden. While India and China face mounting disease prevalence, Brazil contends with high incidence rates. Tailored interventions based on country-specific epidemiological profiles are warranted to mitigate the public health impact.

Vaikų profilaktiniai patikrinimai pirminėje asmens sveikatos priežiūroje: literatūros apžvalga

Summary. The purpose of the preventive health check-up of children and adolescents is to assess the harmonious development of patients, identify health disorders, and prevent the occurrence of future diseases. In Lithuania, health checks of children and adolescents are carried out periodically. Family doctors or pediatricians, who suspect health disorders in a child during a preventive health check-up, can prescribe all the necessary instrumental or laboratory tests and send the necessary specialists for consultation. In foreign countries, the culture of preventive health check-ups for children and adolescents is somewhat different, as check-ups are not carried out every year.
 A literature review was performed using PubMed and Google Scholar search engines, in the MEDLINE electronic database. The search was carried out from 01.11.2022 to 01.02.2023. The systematic review included 16 articles on the topic. After analyzing the scientific articles, it can be stated that preventive health screening of children and adolescents is carried out in many countries, but with the help of different healthcare professionals and also at different time intervals. Preventive examinations in PSP are carried out by a family doctor, a pediatrician, a nurse, an ophthalmologist, a dentist, and in some countries also a physical medicine and rehabilitation doctor and a psychologist.

EFFECTS OF ESSENTIAL CAREGIVER POLICIES ON COVID-19 AND NON-COVID-19 DEATHS IN NURSING HOMES

Abstract Balancing the safety of nursing home residents with their need for social interaction has emerged as a key challenge from the COVID-19 pandemic. Strict bans on nursing home visitation eventually led to growing concern that physical isolation may have unintended harms on nursing home residents. To address this concern, at staggered times between June 2020 and January 2021, 17 states implemented Essential Caregiver policies allowing nursing home visitation by designated family members or friends under controlled circumstances. Using the Nursing Home COVID-19 Public File and other relevant data, we analyze the effects of Essential Caregiver policies on COVID-19 and non-COVID-19 deaths for nursing home residents. To estimate plausibly causal effects, we employ recent innovations in difference-in-differences and event-study estimation. We find that on average, Essential Caregiver policies prevent 0.44 non-COVID-19 deaths, 0.42 COVID-19 deaths, and 0.86 total deaths per 1,000 residents in a two-week period, representing 8 percent, 17 percent, and 11 percent of the sample mean for the three outcomes, respectively. The effects are mainly driven by state policies that are mandatory or implemented without restrictions and are larger for high-quality facilities and highly staffed facilities. Our results suggest that nursing home residents derive substantial benefit from regular social interaction with family members and friends and from the additional care they provide. Our findings support the use and expansion of Essential Caregiver policies to balance resident safety and the need for social interaction for future infectious disease outbreaks.

Comparison of Face Masks by Arduino Sensors


 
 
 The COVID-19 pandemic in early 2020 has created a health crisis around the world. There have been many precautions taken against the virus, such as social distancing and the use of personal protective equipment. Face masks are an essential part of personal protective equipment, especially for essential workers. Although the pandemic has caused a high demand for facemasks, there is limited scientific knowledge available on the various types of masks. Knowledge about the air quality inside the different facemasks could be beneficial for both the COVID-19 pandemic and future disease outbreaks, which will seemingly increase in the future. There are different types of masks, ranging from tight-fitting N95 respirator masks to looser surgical masks to homemade cloth masks. Herein, N95 respirator masks, surgical masks, cloth face masks, and surgical masks on top of N95 respirator masks were compared in terms of CO2 levels, Volatile Organic Compound levels (VOCs), temperature, humidity, and O2 concentrations. To record these measurements, Arduino-based sensors were constructed and utilized for the measurements. It was found that the N95 mask and the surgical mask on top of the N95 mask trapped the highest concentration of carbon dioxide, VOCs, temperature, humidity, and the lowest oxygen levels compared to the surgical mask and cloth mask.
 
 

Machine learning based techniques for ECG noise removal and feature extraction

Machine learning (ML) is being applied to all aspects of life with the development of artificial intelligence (AI). This paper explores the application of machine learning technology in electrocardiogram (ECG) analysis to diagnose and classify a patient's current cardiac disease, predict possible future diseases, and provide a personalised treatment plan. However, several challenges have been highlighted. First, individual ECG signals display variability, causing concern about effective diagnosis based on changing ECG data. Second, different diseases can produce similar ECG results, requiring powerful classification algorithms to accurately classify diseases. Finally, using patient information to predict the probability of future heart attacks is critical to developing appropriate prevention and treatment strategies. Overcoming these challenges could revolutionise the field of cardiology. It could enable precise and proactive medical intervention. The study highlights the potential of machine learning to improve cardiovascular care and personalised medicine and emphasises the importance of addressing key challenges to maximise its impact in clinical practice.

Amino acid catabolite markers for early prognostication of pneumonia in patients with COVID-19

Effective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages.

Influence of Physical Activity during Pregnancy on Neonatal Complications: Systematic Review and Meta-Analysis.

Newborn hospitalisations after delivery are indicators of poor neonatal health with potential risks of future diseases for children. Interventions to promote a healthy environment have been used during pregnancy, with physical activity as a principal element. A systematic review and meta-analyses were performed to evaluate the effect of physical activity during pregnancy on neonatal intensive care unit (NICU) admissions and Apgar 1 and 5 scores (Registration No.: CRD42022372493). Fifty studies (11,492 pregnant women) were included. There were significantly different rates of NICU admissions between groups (RR = 0.76, 95% CI = 0.62, 0.93; Z = 2.65, p = 0.008; I2 = 0%, and Pheterogeneity = 0.78), and significant differences in Apgar 1 (Z = 2.04; p = 0.04) (MD = 0.08, 95% CI = 0.00, 0.17, I2 = 65%, Pheterogeneity = 0.00001) and Apgar 5 (Z = 3.15; p = 0.002) (MD = 0.09, 95% CI = 0.04, 0.15, I2 = 80%, and Pheterogeneity = 0.00001), favouring intervention groups. Physical activity during pregnancy could help to reduce the risk of NICU admissions that are related to neonatal complications.

LoC-SERS platform for rapid and sensitive detection of colorectal cancer protein biomarkers

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection.

A Serendipitous Outcome of COVID-19: Modifications to ICU Management.

Nosocomial infections are common in intensive care units (ICUs) and often cause increased morbidity and mortality rates in ICU patients. With the emergence of the highly infectious COVID-19, the high prevalence of hospital-acquired infections (HAIs) in ICU has caused much more concern because patients admitted to the ICU have a more severe and prolonged form of the disease. These patients are more likely to develop HAIs than non-ICU patients. Medical communities adopted several measures to make ICU management safer during the pandemic all over the world. In this study, we re-examined the challenges faced and the changes made in ICU management during the pandemic to speculate how these changes will be relevant post-pandemic and can be permanently incorporated into the ICU to improve safety, management, and critical care and make critical care better equipped for future disease breakouts.

Perceived Quality of Life Is Related to a Healthy Lifestyle and Related Outcomes in Spanish Children and Adolescents: The Physical Activity, Sedentarism, and Obesity in Spanish Study.

Maintaining a healthy lifestyle is crucial for safeguarding the well-being and quality of life perception, appropriate growth, and development of children and adolescents, while also mitigating the risk of future adult-onset diseases. To assess associations between perceived quality of life and healthy lifestyle and related outcomes in Spanish children and adolescents. Cross-sectional analysis of 8-16-year-old children and adolescents (n = 3534) were included in the nationwide study of Physical Activity, Sedentarism, and Obesity in Spanish Youth (PASOS). Data were collected through (1) questionnaires on health-related quality of life (HRQoL), healthy lifestyle outcomes (dietary intake, physical fitness, sleep, and screen time), and (2) anthropometric measurements for weight status assessment. Data were analysed by logistic regression, using the health-related quality of life (HRQoL) as the grouping variable. Participants with a lower HRQoL were those with a lower adherence to the MedDiet and lower achievement of the recommended daily intake of fruit and vegetables. They were also less likely to follow the recommendations for screen time and sleep (with the exception of the weekend) compared to participants with a higher HRQoL. Participants with a lower HRQoL showed a lower healthy weight status and poorer physical fitness than those with a higher HRQoL. Healthy eating habits, healthy weight status (normal weight), appropriate sleep time, physical fitness, and limited screen time play a crucial role in the perceived quality of life in children and adolescents.

Lipidomics identified novel cholesterol-independent predictors for risk of incident coronary heart disease: Mediation of risk from diabetes and aggravation of risk by ambient air pollution

IntroductionPrevious lipidomics studies have identified various lipid predictors for cardiovascular risk, however, with limited predictive increment, sometimes using too many predictor variables at the expense of practical efficiency. ObjectivesTo search for lipid predictors of future coronary heart disease (CHD) with stronger predictive power and efficiency to guide primary intervention. MethodsWe conducted a prospective nested case-control study involving 1,621 incident CHD cases and 1:1 matched controls. Lipid profiling of 161 lipid species for baseline fasting plasma was performed by liquid chromatography-mass spectrometry. ResultsIn search of CHD predictors, seven lipids were selected by elastic-net regression during over 90% of 1000 cross-validation repetitions, and the derived composite lipid score showed an adjusted odds ratio of 3.75 (95% confidence interval: 3.15, 4.46) per standard deviation increase. Addition of the lipid score into traditional risk model increased c-statistic to 0.736 by an increment of 0.077 (0.063, 0.092). From the seven lipids, we found mediation of CHD risk from baseline diabetes through sphingomyelin (SM) 41:1b with a considerable mediation proportion of 36.97% (P < 0.05). We further found that the positive associations of phosphatidylcholine (PC) 36:0a, SM 41:1b, lysophosphatidylcholine (LPC) 18:0 and LPC 20:3 were more pronounced among participants with higher exposure to fine particulate matter or its certain components, also to ozone for LPC 18:0 and LPC 20:3, while the negative association of cholesteryl ester (CE) 18:2 was attenuated with higher black carbon exposure (P < 0.05). ConclusionWe identified seven lipid species with greatest predictive increment so-far achieved for incident CHD, and also found novel biomarkers for CHD risk stratification among individuals with diabetes or heavy air pollution exposure.

Hepatitis C virus modified sE2F442NYT as an antigen in candidate vaccine facilitates human immune cell activation.

The rational selection of hepatitis C virus (HCV) vaccine antigen will aid in the prevention of future chronic liver disease burden and associated healthcare costs. We have previously shown that HCV E2 glycoprotein is not highly immunogenic, and the modification of E2 reduced CD81 binding and displayed altered cytokine and protective immune responses in vitro and in a surrogate mouse model. Here, we compared the influence of a parental and a modified sE2F442NYT glycoprotein region from HCV genotype 1a for the activation of peripheral blood mononuclear cell (PBMC)-derived dendritic cells (DCs), CD4+T cells, and B cells. Modified sE2F442NYT, when incubated with DCs, induced a higher number of CD86-positive cells. The sE2F442NYT or parental sE2 encapsulated as mRNA-lipid nanoparticle (sE2F442NYT mRNA-LNP) primed DCs co-cultured with autologous CD4+T cells did not induce CD25 or forkhead box P3 expression. PBMC-derived CD4+T cells treated with sE2F442NYT exhibited enhanced signal transducer and activator of transcription (Stat)1/Stat4 phosphorylation in response to anti-CD3/CD28 stimulation in comparison to parental sE2 treatment and facilitated isotype switching in B cells, leading to the generation of a broader subclass of antibodies. Cells treated with modified sE2F442NYT displayed an increase in activated Stat3 and extracellular signal-regulated kinase (ERK). Likewise, PBMC-derived naïve B cells upon in vitro stimulation with sE2F442NYT induced an increased proliferation, Stat3 and ERK activation, and protein kinase B (Akt) suppression. Thus, the modified sE2F442NYT antigen from HCV facilitates improved DC, CD4+T, and B cell activation compared to parental sE2 to better induce a robust protective immune response, supporting its selection as an HCV candidate vaccine antigen for preclinical and clinical HCV vaccine trials.IMPORTANCEThe nature of an enhanced immune response induced by sE2F442NYT will help in the selection of a broad cross-protective antigen from hepatitis C virus genotypes, and the inclusion of relatively conserved sE1 with sE2F442NYT may further strengthen the efficacy of the candidate vaccine in evaluating it for human use.

Interplay between microglia and environmental risk factors in Alzheimer's disease.

Alzheimer's disease, among the most common neurodegenerative disorders, is characterized by progressive cognitive impairment. At present, the Alzheimer's disease main risk remains genetic risks, but major environmental factors are increasingly shown to impact Alzheimer's disease development and progression. Microglia, the most important brain immune cells, play a central role in Alzheimer's disease pathogenesis and are considered environmental and lifestyle "sensors." Factors like environmental pollution and modern lifestyles (e.g., chronic stress, poor dietary habits, sleep, and circadian rhythm disorders) can cause neuroinflammatory responses that lead to cognitive impairment via microglial functioning and phenotypic regulation. However, the specific mechanisms underlying interactions among these factors and microglia in Alzheimer's disease are unclear. Herein, we: discuss the biological effects of air pollution, chronic stress, gut microbiota, sleep patterns, physical exercise, cigarette smoking, and caffeine consumption on microglia; consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer's disease; and present the neuroprotective effects of a healthy lifestyle. Toward intervening and controlling these environmental risk factors at an early Alzheimer's disease stage, understanding the role of microglia in Alzheimer's disease development, and targeting strategies to target microglia, could be essential to future Alzheimer's disease treatments.

Relationship between vaginal microbiota and chorioamnionitis: A prospective cohort study

ObjectiveThis study aimed to determine the association between vaginal microbiota and chorioamnionitis and its predictive value. MethodsThirty pregnant women in their third trimester were prospectively recruited. The participants were categorized into three groups based on their clinical manifestations and placental pathology: the clinical chorioamnionitis group (IP group), the asymptomatic histological chorioamnionitis group (CP group), and the healthy control group (CN group). Basic data and medical history were collected from each participant. Vaginal samples were collected before delivery and analyzed using microbial diversity sequencing. ResultsNo significant differences were observed in age, body mass index, and education among the groups (P > 0.05). However, the IP group exhibited higher rates of low birth weight (60 % vs 20 % vs 0 %, P = 0.008) and respiratory distress syndrome (50 % vs 20 % vs 0 %, P = 0.003) compared with the CP and CN groups. The Shannon index [2.09 (1.16–3.86) vs 0.84 (0.19–1.11) vs 0.44 (0.25–0.85), P = 0.009] and Simpson index [0.70 (0.41–0.81) vs 0.26 (0.04–0.39) vs 0.11 (0.05–0.29), P = 0.010] in the IP group were higher than those in the CN and CP groups. β diversity analysis indicated that the microbial community structure differed among the three groups, with a 14.1 % variation associated with group differences (P = 0.002). At the genus level, the random forest model revealed that Lactobacillus, Dialister, Prevotella, Ligilactobacillus, and Anaerococcus had Gini indexes higher than 1. Further, linear discriminant analysis (LDA) demonstrated that the abundance of Lactobacillus crispatus in the IP group was lower than in the CN group (LDA >4.0, mean relative abundance 9.19 % vs 54.40 %, P = 0.031). The logistic regression analysis indicated that a decreased abundance of L. crispatus was associated with an increased risk of clinical chorioamnionitis. ConclusionsThe reduction of L. crispatus and increasing trend of specific anaerobic groups are associated with the onset of chorioamnionitis, suggesting their potential value in chorioamnionitis identification. The vaginal microbiota could serve as a useful biomarker for predicting future disease and tailoring surveillance efforts. Additionally, it may present a viable target for developing prevention and therapeutic strategies.

Cholesteric nanostructure biosensors on flexible paper fibres for disease detection through label-free techniques and image analysis

ABSTRACT We have achieved a successful synthesis of a label-free, flexible, portable, and colour-indicating biosensor using cholesteric nanostructure liquid crystals (LCs), commonly referred to as cholesteric LCs (CLCs), on paper fibres. This innovative approach holds significant promise for rapid screening in precision medicine and other applications. We incorporated optically active nematic LCs in various configurations within CLCs, allowing them to rotate along different axes. When exposed to light, these LCs reflected light at specific wavelengths. By employing polarised optical microscopy and a charged couple device (CCD), we conducted titration experiments with bovine serum albumin (BSA) on the paper substrate and quantified protein concentrations based on the observed colour shifts. Utilising internal Python pixel analysis software, we evaluated the red, green, and blue colour components, which served as biomarkers for different BSA concentrations. Our results demonstrated a linear correlation between BSA concentration and colour variations. This CLC-based paper-substrate biosensor exhibits the potential to efficiently screen a large number of samples, thereby enhancing the diagnostic accuracy in clinical settings. Combining the colour-indicating and quantifiable attributes of CLCs with the affordability and portability of paper substrates, we have developed a versatile biosensor. Its ease of use, rapid response, and high sensitivity make it a promising tool for future disease detection endeavours.

Engineering a highly selective leucine aminopeptidase near-infrared fluorescence probe for early diagnosis of diabetic nephropathy

Diabetic nephropathy (DN) is one of the most serious and general complications of diabetes, while schedules for prevention and treatment are unsatisfactory. Leucine aminopeptidase (LAP) as one of the biomarkers of DN is associated with glomerular and/or tubular injury. Imaging of LAP activity in DN disease model in vivo is thus beneficial for early diagnosis and prevention of DN, but such a strategy is still lacking. Herein, an enzyme-activated probe HD-LAP with a NIR fluorescence emission for specific detection of LAP activity in the DN model is designed and synthesized. HD-LAP has a significant fluorescence enhancement after reacted with LAP and shows a NIR fluorescence emission at 704 nm based on intramolecular charge transfer mechanism. Moreover, HD-LAP can be employed to image LAP activity in HK-2 and HepG2 cells. More importantly, HD-LAP is the first example to real-time image LAP in DN mice and clinical serum samples. These results demonstrated that HD-LAP is promising as a powerful tool for the research on LAP associated diabetic diseases in future.

Longitudinal clustering of Life's Essential 8 health metrics: application of a novel unsupervised learning method in the CARDIA study.

Changes in cardiovascular health (CVH) during the life course are associated with future cardiovascular disease (CVD). Longitudinal clustering analysis using subgraph augmented non-negative matrix factorization (SANMF) could create phenotypic risk profiles of clustered CVH metrics. Life's Essential 8 (LE8) variables, demographics, and CVD events were queried over 15ears in 5060 CARDIA participants with 18years of subsequent follow-up. LE8 subgraphs were mined and a SANMF algorithm was applied to cluster frequently occurring subgraphs. K-fold cross-validation and diagnostics were performed to determine cluster assignment. Cox proportional hazard models were fit for future CV event risk and logistic regression was performed for cluster phenotyping. The cohort (54.6% female, 48.7% White) produced 3 clusters of CVH metrics: Healthy & Late Obesity (HLO) (29.0%), Healthy & Intermediate Sleep (HIS) (43.2%), and Unhealthy (27.8%). HLO had 5 ideal LE8 metrics between ages 18 and 39years, until BMI increased at 40. HIS had 7 ideal LE8 metrics, except sleep. Unhealthy had poor levels of sleep, smoking, and diet but ideal glucose. Race and employment were significantly different by cluster (P < .001) but not sex (P = .734). For 301 incident CV events, multivariable hazard ratios (HRs) for HIS and Unhealthy were 0.73 (0.53-1.00, P = .052) and 2.00 (1.50-2.68, P < .001), respectively versus HLO. A 15-year event survival was 97.0% (HIS), 96.3% (HLO), and 90.4% (Unhealthy, P < .001). SANMF of LE8 metrics identified 3 unique clusters of CVH behavior patterns. Clustering of longitudinal LE8 variables via SANMF is a robust tool for phenotypic risk assessment for future adverse cardiovascular events.