COVID-19 Pandemic and Stroke Care in Patients with Dementia Compared to Other Stroke Patients.

OBJECTIVES: The primary objective of this study was to examine the impact of the COVID-19 pandemic on the quality of stroke care for patients with preexisting dementia, compared with patients who had only stroke. The secondary aim was to investigate how the quality of stroke care changed during the pandemic and post-pandemic periods compared with the pre-pandemic period in patients with preexisting dementia. DESIGN: A registry-based, nationwide cohort study in Sweden. SETTING AND PARTICIPANTS: We included patients with a first stroke between 2019 and 2022, both with and without dementia. The study periods were defined as follows: pre-pandemic (January 1, 2019, to February 29, 2020), COVID-19 pandemic (March 1, 2020, to February 24, 2022), and post-COVID-19 pandemic period (February 25, 2022, to September 19, 2022). The outcomes examined were the following quality indicators of stroke care, suggested by the national guideline of stroke care in Sweden: stroke admission site, performance of swallowing assessment, reperfusion treatment, assessment for rehabilitation, and early supported discharge. METHODS: The associations were studied through group comparisons and binary logistic regressions. RESULTS: Of the 21,795 patients with strokes, 1357 had documented preexisting dementia, and 20,438 had stroke without a dementia diagnosis. Throughout all study periods, a significantly lower proportion of patients with stroke with preexisting dementia, compared with stroke-only patients, received reperfusion treatment, assessments for rehabilitation, and early supported discharge from stroke units. In the subgroup of stroke patients with preexisting dementia, no significant associations were found regarding the quality indicators of stroke care before, during, and after the pandemic. CONCLUSIONS AND IMPLICATIONS: Disparities in quality of stroke care were observed between stroke patients with preexisting dementia and those with only stroke during the COVID-19 pandemic. However, there were no statistically significant differences in stroke care for patients with dementia across the pandemic.

Surface-Displayed Mannanolytic and Chitinolytic Enzymes Using Peptidoglycan Binding LysM Domains.

Using Lactiplantibacillus plantarum as a food-grade carrier to create non-GMO whole-cell biocatalysts is gaining popularity. This work evaluates the immobilization yield of a chitosanase (CsnA, 30 kDa) from Bacillus subtilis and a mannanase (ManB, 40 kDa) from B. licheniformis on the surface of L. plantarum WCFS1 using either a single LysM domain derived from the extracellular transglycosylase Lp_3014 or a double LysM domain derived from the muropeptidase Lp_2162. ManB and CsnA were fused with the LysM domains of Lp_3014 or Lp_2162, produced in Escherichia coli and anchored to the cell surface of L. plantarum. The localization of the recombinant proteins on the bacterial cell surface was successfully confirmed by Western blot and flow cytometry analysis. The highest immobilization yields (44-48%) and activities of mannanase and chitosanase on the displaying cell surface (812 and 508 U/g of dry cell weight, respectively) were obtained when using the double LysM domain of Lp_2162 as an anchor. The presence of manno-oligosaccharides or chito-oligosaccharides in the reaction mixtures containing appropriate substrates and ManB or CsnA-displaying cells was determined by high-performance anion exchange chromatography. This study indicated that non-GMO Lactiplantibacillus chitosanase- and mannanase-displaying cells could be used to produce potentially prebiotic oligosaccharides.

Factors associated with hepatitis B knowledge among people of Vietnamese ethnicity in Australia.

Despite high hepatitis B (HBV) prevalence among people of Vietnamese ethnicity in Australia and elsewhere, there is limited research on levels of HBV knowledge and factors associated with such knowledge. The aim of this study was to examine HBV knowledge and associated demographic and attitudinal factors among people of Vietnamese ethnicity in Australia. People of Vietnamese ethnicity (n = 966) were recruited through community events and social media groups to complete online surveys measuring HBV knowledge, attitudes towards HBV, levels of mistrust in Western medicine, and demographic characteristics. Findings of this study indicate that levels of knowledge are mixed, with gaps in knowledge related to transmission and treatment of the virus. Those with greater knowledge of HBV tended to be older, have higher levels of formal education, have been tested for HBV, and know someone living with HBV. Those with lower levels of knowledge tended to have more negative attitudes towards the virus and greater levels of mistrust in Western medicine. Given that health literacy is connected to effective communication from health providers, we suggest that there is a need for the development of health promotion and education resources targeted at people of Vietnamese ethnicity and translated into Vietnamese. We propose that such resources be developed in consultation with Vietnamese communities and health providers to ensure that they are culturally appropriate and sensitive to people of Vietnamese ethnicity living in Australia.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Prevalence of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in Vietnam.

PURPOSE: Chronic obstructive pulmonary disease and obstructive sleep apnea are two common respiratory diseases. Chronic obstructive pulmonary disease patients co-morbid with obstructive sleep apnea are associated with increased cardiovascular adverse events, frequent acute exacerbations, and higher mortality. Only a few studies on obstructive sleep apnea among patients with chronic obstructive pulmonary disease are available in Vietnam. The study aims to determine the prevalence of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in Vietnam. METHODS: This is a cross-sectional study in patients with chronic obstructive pulmonary disease at multi-sites in Vietnam: the People's Hospital of Gia Dinh, Bach Mai Hospital, Phoi Viet Clinics, and Lam Dong Medical College using type 3 sleep monitoring device at sleep labs to diagnose obstructive sleep apnea in all study participants. RESULTS: Two hundred seventy-eight patients with chronic obstructive pulmonary disease were enrolled. Among the patients, 93.2% were male, with an average age of 66.9 ± 9.3 and a BMI of 21.9 ± 3.8 kg/m2; 82.0% were symptomatic including 44.6% in group B and 37.4% in group D with average post-FEV1 of 49.8 ± 18.3% predicted values. One hundred seventeen patients (42.1%) with chronic obstructive pulmonary disease presented obstructive sleep apnea defined by AHI ≥ 15 events/h. CONCLUSIONS: The prevalence of obstructive sleep apnea in patients with chronic obstructive pulmonary disease in Vietnam was 42.1% for an AHI of ≥ 15 events/h.

The Olera.care Digital Caregiving Assistance Platform for Dementia Caregivers: Preliminary Evaluation Study.

BACKGROUND: The increasing prevalence of Alzheimer disease and Alzheimer disease-related dementia in the United States has amplified the health care burden and caregiving challenges, especially for caregivers of people living with dementia. A web-based care planning tool, Olera.care, was developed to aid caregivers in managing common challenges associated with dementia care. OBJECTIVE: This study aims to preliminarily evaluate the quality and usability of the Olera.care platform and assess the preferences of using the technology and interests in learning about different older adult care services among caregivers. METHODS: For interview 1, we aim to understand caregiving needs and let the participants start engaging with the platform. After they engage with the platform, we schedule the second interview and let the participants complete the Mobile Application Rating Scale. The survey also included sociodemographic characteristics, caregiving experiences, communication preferences in technology adoption, and older adult care service use and interests. Descriptive statistics were used to describe the quality and usability of the platform and characteristics of the participants. We conducted 2-sample 2-tailed t tests to examine the differences in the Mobile Application Rating Scale evaluation scores by caregiver characteristics. RESULTS: Overall, 30 adult caregivers in Texas completed the evaluation. The majority were aged ≥50 years (25/30, 83%), women (23/30, 77%), White (25/30, 83%), and financially stable (20/30, 67%). The Olera.care platform evaluation showed high satisfaction, with an overall mean rating of 4.57 (SD 0.57) of 5, and scored well in engagement (mean 4.10, SD 0.61), functionality (mean 4.46, SD 0.44), aesthetics (mean 4.58, SD 0.53), and information quality (mean 4.76, SD 0.44) consistently across all participants. A statistically significant difference (P=.02) was observed in functionality evaluation scores by duration of caregiving, with caregivers dedicating more hours to care rating it higher than those providing less care (mean 4.6, SD 0.4 vs mean 4.2, SD 0.5). In addition, caregivers with less caregiving experience reported significantly higher evaluation scores for aesthetics (P=.04) and information quality (P=.03) compared to those with longer years of caregiving. All participants expressed a willingness to recommend the app to others, and 90% (27/30) rated the app overall positively. Most of the participants (21/30, 70%) favored anonymous interactions before receiving personalized feedback and preferred computer browsers over mobile apps. Medical home health services were the most used, with a diverse range of services being used. Caregiver support groups, medical providers, memory care, meal services, and adult day care were among the most desired services for future exploration. CONCLUSIONS: The Olera.care web-based platform is a practical, engaging, easy-to-use, visually appealing, and informative tool for dementia caregivers. Future development and research are essential to enhance the platform and comprehensively evaluate it among a broader population.

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients.

BACKGROUND: Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.

Comparison of Machine Learning Algorithms for Heartbeat Detection Based on Accelerometric Signals Produced by a Smart Bed.

This work aims to compare the performance of Machine Learning (ML) and Deep Learning (DL) algorithms in detecting users' heartbeats on a smart bed. Targeting non-intrusive, continuous heart monitoring during sleep time, the smart bed is equipped with a 3D solid-state accelerometer. Acceleration signals are processed through an STM 32-bit microcontroller board and transmitted to a PC for recording. A photoplethysmographic sensor is simultaneously checked for ground truth reference. A dataset has been built, by acquiring measures in a real-world set-up: 10 participants were involved, resulting in 120 min of acceleration traces which were utilized to train and evaluate various Artificial Intelligence (AI) algorithms. The experimental analysis utilizes K-fold cross-validation to ensure robust model testing across different subsets of the dataset. Various ML and DL algorithms are compared, each being trained and tested using the collected data. The Random Forest algorithm exhibited the highest accuracy among all compared models. While it requires longer training time compared to some ML models such as Naïve Bayes, Linear Discrimination Analysis, and K-Nearest Neighbour Classification, it keeps substantially faster than Support Vector Machine and Deep Learning models. The Random Forest model demonstrated robust performance metrics, including recall, precision, F1-scores, macro average, weighted average, and overall accuracy well above 90%. The study highlights the better performance of the Random Forest algorithm for the specific use case, achieving superior accuracy and performance metrics in detecting user heartbeats in comparison to other ML and DL models tested. The drawback of longer training times is not too relevant in the long-term monitoring target scenario, so the Random Forest model stands out as a viable solution for real-time ballistocardiographic heartbeat detection, showcasing potential for healthcare and wellness monitoring applications.

CinNapht AIE(E)gens for selective imaging of lipid droplets.

This article describes the synthesis and photophysical properties of Aggregation-Induced Emission (enhancement) luminogens derivated from CinNaphts dyes. These fluorophores can be obtained in good yields in a single SNAr step of a fluorinated CinNapht derivative by incorporating hindered aromatic amines. They exhibit AIE(E) behavior associated with solid-state fluorescence covering an emission range from 563 to 722 nm. One carbazole derivative demonstrates a remarkable efficiency in imaging lipid droplets in living cells through an original photophysical mechanism.

Cyclopropanation of Alkenes with Halodiazirines as Halocarbene Precursors in Continuous Flow.

The cyclopropanation reaction of alkenes with photolytically-generated chlorocarbenes from chlorodiazirines is reported as an effective way to prepare substituted 3-chloro-3-aryl-cyclopropanes. This practical and efficient approach allows the synthesis of various 3-chloro-3-aryl-cyclopropanes (32 examples) in continuous flow in 5-minute residence time under light-emitting diode (LED) irradiation. The conditions using 380 nm LED irradiation were successfully extended to the synthesis of substituted 3-bromo-3-aryl-cyclopropanes (3 examples).

Hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia.

Research has shown that there are significant gaps in hepatitis B knowledge among migrant communities who are at risk of hepatitis B, such as Chinese and Vietnamese communities. Many students studying within Australia come from countries with high prevalence of hepatitis B. However, there is very little research examining hepatitis B knowledge, screening, or vaccination among university students in Australia or worldwide. The aim of this paper was to measure both levels of and demographic differences in hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia. Online surveys were completed by 112 Chinese- and 95 Vietnamese-identifying students in Australia, measuring knowledge of hepatitis B, engagement in screening and vaccination, and demographic characteristics. Results show that although engagement in screening and vaccination for hepatitis B was high, there were significant gaps in knowledge around transmission of hepatitis B. There were also some key demographic differences in screening and knowledge. For instance, those born in Australia were more likely to have been screened compared to those born Mainland China, Hong Kong, or Vietnam. Chinese students born in Australia had lower levels of knowledge compared to those born in Mainland China or Hong Kong. Among both samples, knowing someone living with hepatitis B was associated with higher levels of knowledge. Findings underscore the need for education-based interventions to address the significant gaps that exist in knowledge around hepatitis B, with a specific need for culturally appropriate resources in a range of languages to cater to the diverse communities who may be at risk of hepatitis B.

RNA therapeutics for ß-thalassemia.

ß-thalassemia is an autosomal recessive disease, caused by one or more mutations in the ß-globin gene that reduces or abolishes ß-globin chain synthesis causing an imbalance in the ratio of α- and ß-globin chain. Therefore, the ability to target mutations will provide a good result in the treatment of ß-thalassemia. RNA therapeutics represents a promising class of drugs inclusive antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and APTAMER have investigated in clinical trials for treatment of human diseases as ß-thalassemia; Especially, ASO therapeutics can completely treat ß-thalassemia patients by the way of making ASO infiltrating through erythrocyte progenitor cells, migrating to the nucleus and hybridizing with abnormal splicing sites to suppress an abnormal splicing pattern of ß-globin pre-mRNA. As a result, the exactly splicing process is restored to increase the expression of ß-globin which increases the amount of mature hemoglobin of red blood cells of ß-thalassemia patients. Furthermore, current study demonstrates that RNA-based therapeutics get lots of good results for ß-thalassemia patients. Then, this chapter focuses on current advances of RNA-based therapeutics and addresses current challenges with their development and application for treatment of ß-thalassemia patients.

A novel sonoelectrochemical approach for preparing of ZnO nanoparticles.

A novel, rapid, and facile method for one-step sonoelectrochemical synthesis of zinc oxide nanoparticles (UEZ) was introduced in this study. The optimum operating parameters have been selected at a voltage of 7.5 V, KCl concentration of 0.5 M, and the reaction time of 60 min. The as-prepared UEZ were characterized by XRD, SEM, and HRTEM. It was found that the UEZ has a hexagonal wurtzite structure with high crystalline quality, good purity, a size range of 30-100 nm, and good photocatalytic degradation of methylene blue. This work provides a facile route for large-scale synthesizing ZnO nanoparticles via anodization.

A systematic review on the direct approach to elicit the demand-side cost-effectiveness threshold: Implications for low- and middle-income countries.

Several literature review studies have been conducted on cost-effectiveness threshold values. However, only a few are systematic literature reviews, and most did not investigate the different methods, especially in-depth reviews of directly eliciting WTP per QALY. Our study aimed to 1) describe the different direct approach methods to elicit WTP/QALY; 2) investigate factors that contribute the most to the level of WTP/QALY value; and 3) investigate the relation between the value of WTP/QALY and GDP per capita and give some recommendations on feasible methods for eliciting WTP/QALY in low- and middle-income countries (LMICs). A systematic review concerning select studies estimating WTP/QALY from a direct approach was carried out in seven databases, with a cut off date of 03/2022. The conversion of monetary values into 2021 international dollars (i$) was performed via CPI and PPP indexes. The influential factors were evaluated with Bayesian model averaging. Criteria for recommendation for feasible methods in LMICs are made based on empirical evidence from the systematic review and given the resource limitation in LMICs. A total of 12,196 records were identified; 64 articles were included for full-text review. The WTP/QALY method and values varied widely across countries with a median WTP/QALY value of i$16,647.6 and WTP/QALY per GDP per capita of 0.53. A total of 11 factors were most influential, in which the discrete-choice experiment method had a posterior probability of 100%. Methods for deriving WTP/QALY vary largely across studies. Eleven influential factors contribute most to the level of values of WTP/QALY, in which the discrete-choice experiment method was the greatest affected. We also found that in most countries, values for WTP/QALY were below 1 x GDP per capita. Some important principles are addressed related to what LMICs may be concerned with when conducting studies to estimate WTP/QALY.

RNA therapeutics history and future perspectives.

Ribonucleic acid (RNA) therapeutics have significantly used RNA-based drugs to the prevention and treatment of diseases as effective messenger RNA-based vaccines in response to the COVID-19 pandemic. The RNA therapeutics with five classes including antisense oligonucleotide, small interfering RNA, microRNA, APTAMER and messenger RNAs are being quickly developed to treat various human diseases as neurological disease, cardiovascular disease, genetic and rare disease, cancer disease, coronavirus disease… which cannot be treated by other conventional drugs as small molecule-based drugs and antibodies. Therefore, the discovery of these RNA therapeutics created a new avenue for treatment of various human diseases. This chapter demonstrates the history of important discoveries in RNA biology and their impact on key developments in RNA therapeutics as well as the advantages of RNA therapeutics; RNA therapeutics describes the action mechanisms and examples of RNA-based drugs approved for treatment of various disease; and RNA therapeutics discusses delivery methods for RNA therapeutics to target organs and cells. In conclusion, this chapter is designed to offer an updated important development and advance of RNA therapeutics for the prevention and treatment of various human diseases.

Malocclusion among children in Vietnam: Prevalence and associations with different habits.

Background: This study aimed to measure the prevalence of malocclusion and identify associated factors among elementary school students in Vietnam. Method: A cross-sectional study was conducted from March to December 2022 at six primary schools located in the province of Thai Binh, Vietnam. A total of 873 students were recruited for research purposes. Students were classified into normal, malocclusion classes I, II and III. Bad habits were examined. Multivariate logistic regression was used to detect associations. Results: The prevalence of malocclusion was 60.7 %; 19.0 % had Class I, 31.0 % had Class II and 10.7 % had Class III. Having finger sucking habit was associated with Class I malocclusion (OR: 3.28), and Class II malocclusion (OR: 3.22). Having lip biting habit was related to a higher odds of having Class II malocclusion (OR = 4.37) Class III malocclusion (OR = 6.83). Having tongue thrusting habit was associated with higher odds of having Class I (OR: 5.25), and Class II malocclusion (OR: 6.42). Mouth breathing was related to a higher likelihood of having Class II malocclusion (OR = 2.71). Having early loss of deciduous teeth was associated with a higher odds of having Class III malocclusion (OR = 3.83). Conclusion: Findings showed high prevalence of malocclusion, mostly class II, in elementary students in Vietnam. Bad habits such as finger sucking, biting the lower lip, tongue thrusting, mouth breathing, and early loss of deciduous teeth play important roles in developing malocclusion, which should be considered in the development of interventions.

Assessment of different continence definitions in the context of the randomized multicenter prospective LAP-01 trial-Does the best definition change over time?

BACKGROUND: A uniform definition of continence is urgently needed to allow the comparison of study results and to estimate patient outcomes after radical prostatectomy (RP). To identify a practical definition that includes both objective and subjective aspects in a tangible way, we assessed different continence definitions and evaluated which best reflects the patients' subjective perception of continence. METHODS: Our analyses included 718 patients that underwent either robot-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) in a multicenter randomized patient-blinded trial. Continence was assessed through patient questionnaires prior to and at 3, 6 and 12 months after surgery which included the number of pads used per day, the ICIQ-SF and the question "Do you suffer from incontinence? (yes/no)" to assess subjective continence. We used Krippendorff's Alpha to calculate the agreement of different continence definitions with the subjective perception. RESULTS: At 3 months, the "0/safety pad" definition shows the highest agreement by alpha = 0.70 (vs. 0.63 for "0 pads" and 0.37 for "0-1 pad"). At 6 and 12 months "0 pads" is the better match, with alpha values of 0.69 (vs. 0.62 and 0.31) after 6 months and 0.70 (vs. 0.65 and 0.32) after 12 months. The ICIQ-SF score shows good correlation with the subjective continence at 3 months (alpha = - 0.79), the coefficient then decreasing to - 0.69 and - 0.59 at 6 and 12 months. CONCLUSION: The best continence definition according to the patients' perspective changes over time, "0 pads" being the superior criterion in the long-term. We recommend using the 0-pad definition for standardized continence reporting, as it is simple yet as accurate as possible given the inevitably high subjectivity of continence perception. Trial registration The LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138.

Immigration and access to dementia diagnostics and treatment: A nationwide study in Sweden.

•Compared to Swedish-born people, foreign-born people were less likely to receive dementia diagnostic tests.•Being born in Africa or Europe was associated with lower chance of receiving cholinesterase inhibitors.•Asian-born people had higher chance of receiving cholinesterase inhibitors, but were less likely to receive memantine.•Disparities existed in dementia diagnostics and treatment between Swedish-born and foreign-born people, but were not consistent after adjusting for MMSE scores.

The Correlation Between Glycation Gap and Renal Complications in Patients with Type 2 Diabetes Mellitus.

Purpose: The aim of this study was to investigate the correlations between the glycation gap (GG) and renal complications such as urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus patients. Materials and Methods: A cross-sectional study was conducted on 104 individuals (52 males and 52 females), aged 36-93 years old. Fasting blood glucose (FBG), HbA1c, and serum fructosamine were measured simultaneously. GG was calculated as the difference between the measured and fructosamine-based predicted HbA1c levels (FHbA1c). Results: There was a moderately positive correlation between HbA1c and fructosamine concentration (r = 0.488; p < 0.001). GG was positively correlated with UACR (r = 0.3275; p = 0.0007), negatively correlated with eGFR (r = -0.3400; p = 0.0004). HbA1c was positively correlated with UACR (r = 0.2437; p = 0.0127) but not correlated with eGFR (r = -0.444; p = 0.6542). Fructosamine has a positive correlation with eGFR (r = 0.2426; p = 0.0131) but not with UACR (r = -0.1021; p = 0.3025). Conclusion: GG was positively correlated with UACR and inversely correlated with eGFR in type 2 Diabetes mellitus patients. This suggests that GG is a valuable index for predicting kidney complications due to diabetes.

mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors.

BACKGROUND: Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically "cold" tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines. mRNA-based immunotherapeutics have also garnered widespread interest for their potential to revolutionize cancer treatment. In this study, we developed a novel and scalable approach for the production of personalized mRNA-based therapeutics that target multiple tumor rejection antigens in a single therapy for the treatment of refractory brain tumors. METHODS: Tumor-specific neoantigens and aberrantly overexpressed tumor-associated antigens were identified for glioblastoma and medulloblastoma tumors using our cancer immunogenomics pipeline called Open Reading Frame Antigen Network (O.R.A.N). Personalized tumor antigen-specific mRNA vaccine was developed for each individual tumor model using selective gene capture and enrichment strategy. The immunogenicity and efficacy of the personalized mRNA vaccines was evaluated in combination with anti-PD-1 immune checkpoint blockade therapy or adoptive cellular therapy with ex vivo expanded tumor antigen-specific lymphocytes in highly aggressive murine GBM models. RESULTS: Our results demonstrate the effectiveness of the antigen-specific mRNA vaccines in eliciting robust anti-tumor immune responses in GBM hosts. Our findings substantiate an increase in tumor-infiltrating lymphocytes characterized by enhanced effector function, both intratumorally and systemically, after antigen-specific mRNA-directed immunotherapy, resulting in a favorable shift in the tumor microenvironment from immunologically cold to hot. Capacity to generate personalized mRNA vaccines targeting human GBM antigens was also demonstrated. CONCLUSIONS: We have established a personalized and customizable mRNA-therapeutic approach that effectively targets a plurality of tumor antigens and demonstrated potent anti-tumor response in preclinical brain tumor models. This platform mRNA technology uniquely addresses the challenge of tumor heterogeneity and low antigen burden, two key deficiencies in targeting the classically immunotherapy-resistant CNS malignancies, and possibly other cold tumor types.